Investigating the association between educational attainment and allostatic load with risk of cancer mortality among African American women.

BACKGROUND: African American (AA) women navigate the world with multiple intersecting marginalized identities. Accordingly, AA women have higher cumulative stress burden or allostatic load (AL) compared to other women. Studies suggest that AA women with a college degree or higher have lower AL than AA women with less than a high school diploma. We examined the joint effect of educational attainment and AL status with long-term risk of cancer mortality, and whether education moderated the association between AL and cancer mortality. METHODS: We performed a retrospective analysis among 4,677 AA women within the National Health and Nutrition Examination Survey (NHANES) from 1988 to 2010 with follow-up data through December 31, 2019. We fit weighted Cox proportional hazards models to estimate adjusted hazard ratios (aHRs) of cancer death between educational attainment/AL (adjusted for age, income, and smoking status). RESULTS: AA women with less than a high school diploma living with high AL had nearly a 3-fold increased risk (unadjusted HR: 2.98; 95%C CI: 1.24-7.15) of cancer death compared to AA college graduates living with low AL. However, after adjusting for age, this effect attenuated (age-adjusted HR: 1.11; 95% CI: 0.45-2.74). AA women with high AL had 2.3-fold increased risk of cancer death (fully adjusted HR: 2.26; 95% CI: 1.10-4.57) when compared to AA with low AL, specifically among women with high school diploma or equivalent and without history of cancer. CONCLUSIONS: Our findings suggest that high allostatic load is associated with a higher risk of cancer mortality among AA women with lower educational attainment, while no such association was observed among AA women with higher educational attainment. Thus, educational attainment plays a modifying role in the relationship between allostatic load and the risk of cancer death for AA women. Higher education can bring several benefits, including improved access to medical care and enhanced medical literacy, which in turn may help mitigate the adverse impact of AL and the heightened risk of cancer mortality among AA women.

Investigating the Association between Educational Attainment and Allostatic Load with Risk of Cancer Mortality among African American Women.

Background African American (AA) women navigate the world with multiple intersecting marginalized identities. Accordingly, AA women have higher cumulative stress burden or allostatic load (AL) compared to other women. AL correlates with poorer health outcomes and increased risk of cancer death. However, research indicates AA women with a college degree or higher have lower AL than AA women with less than a high school diploma. We examined whether educational attainment differences and AL status in AA women are associated with long-term risk of cancer mortality. Methods We performed a retrospective analysis among 4,677 AA women respondents using National Health and Nutrition Examination Survey (NHANES) data from 1988 through 2010 with follow up data through December 31, 2019. We fit Cox proportional hazards models to estimate adjusted hazard ratios (aHRs) of cancer death between educational attainment/AL (adjusted for age, sociodemographic, and health factors). Results AA women with less than a high school diploma living with high AL had nearly a 3-fold increased risk (unadjusted HR: 2.98; 95%C CI: 1.24â€"7.15) of cancer death compared to AA college graduates living with low AL. However, after adjusting for age, the increased risk of cancer death in those with less than a high school diploma and high AL attenuated (age-adjusted HR: 1.11; 95% CI: .45-2.74). Conclusions Differences in educational attainment and AL in AA women were not associated with increased risk of cancer mortality when adjusted for age. Previous studies have shown that increased allostatic load is associated with increased risk of cancer death. However, for African American women, higher educational attainment does not modify the risk of cancer mortality. The benefits that may come along with higher education such as increased access to medical care and better medical literacy do not change the risk of cancer mortality in AA women.

AHA Life's essential 8 and ideal cardiovascular health among young adults.

Objective: This study assessed cardiovascular health (CVH) in young adults using the 2022 AHA Life's Essential 8 (LE8) score and compared it with the Life's Simple 7 (LS7) score. Methods: Individuals aged 18 to 44 years without a history of cardiovascular disease in the National Health and Nutrition Examination Survey (NHANES) cycles were included. Data from 2007-2008 to 2017-2018 were combined to create 3 groups (2007-2010, 2011-2014, and 2015-2018) for analysis. The LE8 score and its components were computed in the overall population and stratified by sex and race/ethnicity. Trends for the LE8 score were analyzed using adjusted linear regression models. Results: Among 12,197 young adults, representing an estimated 89.4 million individuals, from the NHANES 2007-2018, the CVH in the overall population and across all subgroups was stable (Ptrend >0.05). The blood lipid score improved across all subgroups (Ptrend:<0.05). The mean LE8 score was 69.2±0.3. Females (71.4±0.4) had better CVH compared with males (67.2±0.4). Non-Hispanic Black individuals (65.1± 0.3) had the lowest CVH compared with Non-Hispanic White individuals (69.9±0.5), Mexican American individuals (67.3±0.3), and other race individuals (71.2±0.4). Of the 46.1 million individuals categorized as intermediate CVH by the LS7 score, 8.1 million (17.6%) and 2.3 million (5.0%) were reclassified to poor and ideal CVH by the LE8 score, respectively. Of the 40.1 million individuals categorized as ideal CVH by the LS7 score, 18.9 million (47.1%) and 0.1 million (0.2%) were reclassified to poor CVH and intermediate CVH by the LE8 score, respectively. Conclusion: Among US young adults, there has been no improvement in CVH over the last decade with notable sex and race/ethnicity-associated differences in the LE8 score. Nearly 1 in 4 young adults had ideal CVH using the LE8 score compared with 1 in 2 individuals using the LS7 score.

Adherence patterns in naïve and prevalent use of infliximab and its biosimilar.

INTRODUCTION: Although short-term clinical trials have demonstrated that switching from infliximab (INF) bio-originator to its biosimilar is safe with no significant loss of efficacy, there are limited real-world data comparing their patterns of use and adherence. METHODS: Using 2015-2018 IBM Marketscan data, we established 4 cohorts of patients with at least one administration or pharmacy claim for INF bio-originator or biosimilar in 2017, including INF naïve biosimilar users, INF prevalent biosimilar users, INF naïve bio-originator users, and INF prevalent bio-originator users, defined according to their prior use of INF from 2015 to their first INF administration in 2017. The proportion of days covered (PDC) was calculated for patients with at least 6, 12, or 18 months of follow-up time. Factors associated with optimal adherence (PDC > 80%) were evaluated using log-binomial models. RESULTS: We identified 96 INF naïve biosimilar users, 223 INF prevalent biosimilar users, 2,149 INF naïve bio-originator users, and 10,970 INF prevalent bio-originator users. At the end of 18 months of follow-up, 64% of INF prevalent bio-originators, 48% of INF naïve biosimilars, 41% of INF naïve bio-originators, and 36% of INF prevalent biosimilars had optimal adherence. Depression, previous hospitalization, and greater use of prior biologics were negatively associated with adherence, whereas IBD diagnoses (referent to RA) and age 55-64 (referent to < 35) were positively associated with high adherence. CONCLUSION: INF prevalent users had higher adherence in our analyses than INF naïve users. However, further studies with larger sample size are needed to evaluate INF biosimilar users' adherence.

Gel-electrophoresis based method for biomolecular interaction.

Electrophoresis is one of the most important analytical technologies for characterization of macromolecules and their interactions. Among them, native gel electrophoresis is used to analyze the macromolecules in the native structure. It differs in principle and information from those obtained by sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) or blue native polyacrylamide gel electrophoresis (BN-PAGE). SDS-PAGE is carried out in the presence of strong denaturant, SDS, while BN-PAGE is done in the presence of negatively charged dye, e.g., Coomassie brilliant blue, G-250. Here, we describe native gel electrophoresis using agarose gel and a buffer at pH 6.1 composed of histidine and 2-(N-morpholino) ethanesulfonic acid. First, a protocol for vertical and horizontal formats of agarose native gel electrophoresis is described followed by different staining procedures. Then, various examples obtained using the developed procedure will be shown to demonstrate how the technology can be applied to specific cases and the advantages or caveats of the present technology.

Advancing Behavioral Intervention and Theory Development for Mobile Health: The HeartSteps II Protocol.

Background: Recent advances in mobile and wearable technologies have led to new forms of interventions, called "Just-in-Time Adaptive Interventions" (JITAI). JITAIs interact with the individual at the most appropriate time and provide the most appropriate support depending on the continuously acquired Intensive Longitudinal Data (ILD) on participant physiology, behavior, and contexts. These advances raise an important question: How do we model these data to better understand and intervene on health behaviors? The HeartSteps II study, described here, is a Micro-Randomized Trial (MRT) intended to advance both intervention development and theory-building enabled by the new generation of mobile and wearable technology. Methods: The study involves a year-long deployment of HeartSteps, a JITAI for physical activity and sedentary behavior, with 96 sedentary, overweight, but otherwise healthy adults. The central purpose is twofold: (1) to support the development of modeling approaches for operationalizing dynamic, mathematically rigorous theories of health behavior; and (2) to serve as a testbed for the development of learning algorithms that JITAIs can use to individualize intervention provision in real time at multiple timescales. Discussion and Conclusions: We outline an innovative modeling paradigm to model and use ILD in real- or near-time to individually tailor JITIAs.

Inpatient Diagnosis of Delirium and Encephalopathy: Coding Trends in 2011-2018.

BACKGROUND: Ten medical societies have called for scientific literature to integrate research on delirium and encephalopathy, while physicians continually debate how to accurately document diagnoses of acute confusional states. OBJECTIVE: To promote this integration, we evaluated trends in diagnoses of delirium and encephalopathy among hospitalized adults and physician specialties, incorporating transitions to the Diagnostic and Statistical Manual of Mental Disorders-5 and the International Classification of Disease, tenth edition. METHODS: Using the 2011-2018 IBM MarketScan datasets, we identified delirium/encephalopathy patients aged ≥18 years using International Classification of Disease 9/10 codes among hospitalized patients. We identified physician specialties associated with the hospitalization and comorbidities within one year before the diagnosis of delirium or encephalopathy. Log-binomial models were used to evaluate diagnostic trends, adjusting for age, gender, insurance, and comorbidities. RESULTS: We identified 10,509 hospitalized patients with a diagnosis of delirium and 94,438 with encephalopathy between 2011 and 2018. Although the number of patients with either diagnosis increased over time, the use of delirium diagnosis was less than it was for encephalopathy compared with 2011 after adjusting for covariates (adjusted risk ratio 0.45; 95% confidence interval 0.43 to 0.48). During the 8 years, neurologists and internists increased their use of both diagnoses, whereas only psychiatrists increased their use of delirium. Family practice physicians and nurse practitioners presented no significant change in either diagnosis for this timeframe. CONCLUSIONS: Our results suggest that refined diagnostic codes and criteria may alter trends among clinicians in diagnosing delirium and/or encephalopathy. Additional diagnostic clarity may be necessary to support refined diagnoses among family practice physicians and nurse practitioners.

Correlates of COVID-19 Vaccine Hesitancy among a Community Sample of African Americans Living in the Southern United States.

In the United States, African Americans (AAs) have been disproportionately affected by COVID-19 mortality. However, AAs are more likely to be hesitant in receiving COVID-19 vaccinations when compared to non-Hispanic Whites. We examined factors associated with vaccine hesitancy among a predominant AA community sample. We performed a cross-sectional analysis on data collected from a convenience sample of 257 community-dwelling participants in the Central Savannah River Area from 5 December 2020, through 17 April 2021. Vaccine hesitancy was categorized as resistant, hesitant, and acceptant. We estimated relative odds of vaccine resistance and vaccine hesitancy using polytomous logistic regression models. Nearly one-third of the participants were either hesitant (n = 40, 15.6%) or resistant (n = 42, 16.3%) to receiving a COVID-19 vaccination. Vaccine-resistant participants were more likely to be younger and were more likely to have experienced housing insecurity due to COVID-19 when compared to both acceptant and hesitant participants, respectively. Age accounted for nearly 25% of the variation in vaccine resistance, with 21-fold increased odds (OR: 21.93, 95% CI: 8.97-5.26-91.43) of vaccine resistance in participants aged 18 to 29 compared to 50 and older adults. Housing insecurity accounted for 8% of the variation in vaccine resistance and was associated with 7-fold increased odds of vaccine resistance (AOR: 7.35, 95% CI: 1.99-27.10). In this sample, AAs under the age of 30 and those experiencing housing insecurity because of the COVID-19 pandemic were more likely to be resistant to receiving a free COVID-19 vaccination.

B Cells in Atherosclerosis: Mechanisms and Potential Clinical Applications.

Because atherosclerotic cardiovascular disease is a leading cause of death worldwide, understanding inflammatory processes underpinning its pathology is critical. B cells have been implicated as a key immune cell type in regulating atherosclerosis. B-cell effects, mediated by antibodies and cytokines, are subset specific. In this review, we focus on elaborating mechanisms underlying subtype-specific roles of B cells in atherosclerosis and discuss available human data implicating B cells in atherosclerosis. We further discuss potential B cell-linked therapeutic approaches, including immunization and B cell-targeted biologics. Given recent evidence strongly supporting a role for B cells in human atherosclerosis and the expansion of immunomodulatory agents that affect B-cell biology in clinical use and clinical trials for other disorders, it is important that the cardiovascular field be cognizant of potential beneficial or untoward effects of modulating B-cell activity on atherosclerosis.

Analysis of protein denaturation, aggregation and post-translational modification by agarose native gel electrophoresis.

Agarose native gel electrophoresis has been developed to separate proteins and protein complexes in the native state. Here, we applied this technology to analyze proteins that undergo degradation, post-translational modification or chemical/physical changes. Antibodies showed aggregation/association upon acid or heat treatment. Limited reduction of disulfide bonds resulted in non-covalent aggregation of bovine serum albumin and cleavage of only inter-chain linkages of an antibody that had no effects on its overall structure. Native agarose gel analysis showed changes in mobility of human transferrin upon Fe3+ binding. Analysis of a commercial glycated human hemoglobin A1c showed no difference in electrophoretic pattern from un-modified hemoglobin. Native agarose gel showed aggregation of a virus upon acid or heat treatment. We have extracted bands of bovine serum albumin from the agarose native gel for sodium dodecylsulfate gel electrophoresis analysis, showing degradation of aged sample. Lastly, we analyzed phosphorylation of Zap70 kinase by native gel and Western blotting. These applications should expand the utility of this native gel electrophoresis technology.

Universal Qualification of Near Ultraviolet Circular Dichroism Spectroscopy: Method Performance Parameters and Limits of Detection for Structural Differences.

Analytical methods must be qualified as part of the method development lifecycle for product characterization of biotherapeutics. For higher order structure characterization methods, such as near ultraviolet circular dichroism spectroscopy, qualification is performed to determine the expected variability of the method and to establish criteria for analytical product comparability, reference standard qualification, and analytical similarity evaluations. Typical method qualifications require a single product to be tested across several days with multiple replicates, essential to establish a quantitative limit for future product evaluation studies, which may be burdensome with respect to time, instrumentation, and material requirements. In this note, a methodology is proposed to expedite the qualification process for the near ultraviolet circular dichroism spectroscopy method, decreasing the number of required qualification runs, in many cases, to just one for each product. The significant reduction in the number of assays for qualification is achieved by utilizing historical data that applies universally across products of variable classification, size, and test date. Despite their differences, the products exhibit comparable method performance when compared to a product-specific reference standard, and a universal detection threshold is established for application to future product evaluations that meet pre-determined method suitability criteria following a single verification run.

Nomenclature and semantic descriptions of ulcerative and inflammatory lesions seen in Crohn's disease in small bowel capsule endoscopy: An international Delphi consensus statement.

BACKGROUND: In the medical literature, the nomenclature and descriptions (ND) of small bowel (SB) ulcerative and inflammatory (U-I) lesions in capsule endoscopy (CE) are scarce and inconsistent. Inter-observer variability in interpreting these findings remains a major limitation in the assessment of the severity of mucosal lesions, which can impact negatively on clinical care, training and research on SB-CE. OBJECTIVE: Focusing on SB-CE in Crohn's disease (CD), our aim is to establish a consensus on the ND of U-I lesions. METHODS: An international panel of experienced SB-CE readers was formed during the 2016 United European Gastroenterology Week meeting. A core group of five CE and inflammatory bowel disease (IBD) experts established an Internet-based, three-round Delphi consensus but did not participate in the voting process. The core group built illustrated questionnaires, including SB-CE still frames of U-I lesions from patients with documented CD. Twenty-seven other experts were asked to rate and comment on the different proposals for the ND of the most frequent SB U-I lesions. For each round, we used a 6-point rating scale (varying from 'strongly disagree' to 'strongly agree'). The consensus was reached when at least 80 % of the voting members scored the statement within the 'agree' or 'strongly agree' categories. RESULTS: A 100% participation rate was obtained for all the rounds. Consensual ND were reached for the following seven U-I lesions: aphthoid erosion, deep ulceration, superficial ulceration, stenosis, edema, hyperemia and denudation. CONCLUSION: Considering the most frequent SB U-I lesions seen in CE in CD, a consensual ND was reached by the international group of experts. These descriptions and names are useful not only for daily practice and medical education, but also for medical research.

CAD-CAP: a 25,000-image database serving the development of artificial intelligence for capsule endoscopy.

Background and study aims Capsule endoscopy (CE) is the preferred method for small bowel (SB) exploration. With a mean number of 50,000 SB frames per video, SBCE reading is time-consuming and tedious (30 to 60 minutes per video). We describe a large, multicenter database named CAD-CAP (Computer-Assisted Diagnosis for CAPsule Endoscopy, CAD-CAP). This database aims to serve the development of CAD tools for CE reading. Materials and methods Twelve French endoscopy centers were involved. All available third-generation SB-CE videos (Pillcam, Medtronic) were retrospectively selected from these centers and deidentified. Any pathological frame was extracted and included in the database. Manual segmentation of findings within these frames was performed by two pre-med students trained and supervised by an expert reader. All frames were then classified by type and clinical relevance by a panel of three expert readers. An automated extraction process was also developed to create a dataset of normal, proofread, control images from normal, complete, SB-CE videos. Results Four-thousand-one-hundred-and-seventy-four SB-CE were included. Of them, 1,480 videos (35 %) containing at least one pathological finding were selected. Findings from 5,184 frames (with their short video sequences) were extracted and delimited: 718 frames with fresh blood, 3,097 frames with vascular lesions, and 1,369 frames with inflammatory and ulcerative lesions. Twenty-thousand normal frames were extracted from 206 SB-CE normal videos. CAD-CAP has already been used for development of automated tools for angiectasia detection and also for two international challenges on medical computerized analysis.

Agarose native gel electrophoresis for characterization of antibodies.

This study was conducted to evaluate applicability of the previously reported native agarose gel electrophoresis to the analysis of various monoclonal and polyclonal antibodies. Experiments were carried to test the electrophoresis system for characterization of different monoclonal antibodies and animal serum, analysis of expressed antibodies in cell culture and evaluation of antibody stability. An attempt to optimize the electrophoretic condition was made by adjusting the electrode buffer concentration, electrophoretic run time and agarose concentration.

Agarose native gel electrophoresis of proteins.

We have developed an agarose-based native gel electrophoresis system that works for both acidic and basic proteins using histidine-MES buffer. This electrophoresis can be done in a flat-bed mode or a vertical mode. While in the flat-bed mode both acidic and basic proteins can be simultaneously analyzed, the vertical gel can only be used for either protein. We have observed that while the migration of acidic bovine serum albumin (BSA) was independent of the buffer concentration, the behavior of basic lysozyme was greatly improved at higher buffer concentration, e.g., 100 mM histidine-100 mM MES. With this buffer system, BSA, lysozyme and chymotrypsin showed expected band mobility and Adeno associated virus particle and bovine gamma globulin showed apparent basic nature of the surface properties.

Feasibility of circular dichroism to study protein structure at extreme concentrations.

Circular dichroism (CD) is widely used for protein structure and interaction analyses. Here, we have studied the structure of four proteins at widely different concentrations ranging from 250 to 0.001 mg/ml using CD. These four proteins showed different concentration dependences of secondary and tertiary structures. Bovine gamma globulin showed near UV CD too weak to detect concentration dependence, while showing no concentration dependence of secondary structure. Lysozyme showed concentration and time dependent changes in secondary structure below 0.002 mg/ml, while showing no dependence of tertiary structure above 0.02 mg/ml. Chymotrypsin showed small, but significant, changes in both secondary and tertiary structures. Bovine serum albumin showed changes in secondary structure at pH 3.0 at low protein concentrations. In conclusion, we demonstrate feasibility of CD analysis to study protein structure at widely different protein concentrations.

Nomenclature and semantic description of vascular lesions in small bowel capsule endoscopy: an international Delphi consensus statement.

Background and study aims Nomenclature and descriptions of small bowel (SB) vascular lesions in capsule endoscopy (CE) are scarce in the medical literature. They are mostly based on the reader's opinion and thus differ between experts, with a potential negative impact on clinical care, teaching and research regarding SBCE. Our aim was to better define a nomenclature and to give a description of the most frequent vascular lesions in SBCE. Methods A panel of 18 European expert SBCE readers was formed during the UEGW 2016 meeting. Three experts constructed an Internet-based four-round Delphi consensus, but did not participate in the voting process. They built questionnaires that included various still frames of vascular lesions obtained with a third-generation SBCE system. The 15 remaining participants were asked to rate different proposals and description of the most common SB vascular lesions. A 6-point rating scale (varying from 'strongly disagree' to 'strongly agree') was used successive rounds. The consensus was reached when at least 80 % voting members scored the statement within the 'agree' or 'strongly agree'. Results Consensual terms and descriptions were reached for angiectasia/angiodysplasia, erythematous patch, red spot/dot, and phlebectasia. A consensual description was reached for more subtle vascular lesions tentatively named "diminutive angiectasia" but no consensus was reached for this term. Conclusion An international group has reached a consensus on the nomenclature and descriptions of the most frequent and relevant SB vascular lesions in CE. These terms and descriptions are useful in daily practice, for teaching and for medical research purposes.

A neural network algorithm for detection of GI angiectasia during small-bowel capsule endoscopy.

BACKGROUND AND AIMS: GI angiectasia (GIA) is the most common small-bowel (SB) vascular lesion, with an inherent risk of bleeding. SB capsule endoscopy (SB-CE) is the currently accepted diagnostic procedure. The aim of this study was to develop a computer-assisted diagnosis tool for the detection of GIA. METHODS: Deidentified SB-CE still frames featuring annotated typical GIA and normal control still frames were selected from a database. A semantic segmentation images approach associated with a convolutional neural network (CNN) was used for deep-feature extractions and classification. Two datasets of still frames were created and used for machine learning and for algorithm testing. RESULTS: The GIA detection algorithm yielded a sensitivity of 100%, a specificity of 96%, a positive predictive value of 96%, and a negative predictive value of 100%. Reproducibility was optimal. The reading process for an entire SB-CE video would take 39 minutes. CONCLUSIONS: The developed CNN-based algorithm had high diagnostic performances, allowing detection of GIA in SB-CE still frames. This study paves the way for future automated CNN-based SB-CE reading softwares.