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Certain phenolic phytochemicals can kill cancer cells. Possible interference from antioxidants is a concern, and this issue has not been studied appreciably. Therefore, the effect of ascorbate and N-acetylcysteine on the ability of epigallocatechin gallate (EGCG) and curcumin to kill HCT116 colon cancer cells was examined. EGCG and curcumin each caused DNA damage in the cells. The DNA-damaging ability of EGCG, but not curcumin, was hindered by either ascorbate or NAC, which was also shown in HT29 and SW480 colon cancer cells. Also, iron chelators (deferoxamine and 2,2'-dipyridyl) inhibited the ability of EGCG, but not curcumin, to cause damage to the DNA in HCT116 cells. Interestingly, curcumin, but not EGCG, increased the expression of growth arrest and DNA damage-inducible gene 153 and also heme oxygenase-1, and this stress gene upregulation by curcumin was antioxidant-insensitive. With prolonged incubation of HCT116 cells with either EGCG or curcumin, cell shrinkage, membrane blebbing, apoptotic bodies, and chromatin condensation/fragmentation were observed. These morphological changes were not apparent in EGCG-treated cells that had been pretreated with either ascorbate or NAC. However, the ascorbate and NAC pretreatments did not prevent the occurrence of the morphological changes in curcumin-treated cells. Thus, these findings suggest that ascorbate and NAC interfere with the ability of EGCG, but not curcumin, to kill HCT116 cells. This basic knowledge may help to better plan and optimize strategies for chemoprevention or chemotherapy. [ABSTRACT FROM AUTHOR]

Socioeconomic status (SES) is a well-established predictor of individual differences in childhood language and cognitive functioning, including executive functions such as working memory. In infancy, intersensory processing-selectively attending to properties of events that are redundantly specified across the senses at the expense of non-redundant, irrelevant properties-also predicts language development. Our recent research demonstrates that individual differences in intersensory processing in infancy predict a variety of language outcomes in childhood, even after controlling for SES. However, relations among intersensory processing and cognitive outcomes such as working memory have not yet been investigated. Thus, the present study examines relations between intersensory processing in infancy and working memory in early childhood, and the role of SES in this relation. Children (N = 101) received the Multisensory Attention Assessment Protocol at 12-months to assess intersensory processing (face-voice and object-sound matching) and received the WPPSI at 36-months to assess working memory. SES was indexed by maternal education, paternal education, and income. A variety of novel findings emerged. 1) Individual differences in intersensory processing at 12-months predicted working memory at 36-months of age even after controlling for SES. 2) Individual differences in SES predicted intersensory processing at 12-months of age. 3) The well-established relation between SES and working memory was partially mediated by intersensory processing. Children from families of higher-SES have better intersensory processing skills at 12-months and this combination of factors predicts greater working memory two years later at 36-months. Together these findings reveal the role of intersensory processing in cognitive functioning., (Published by Elsevier Inc.)

Research demonstrates that contingent and appropriate maternal responsiveness to infant requests and bids for attention leads to better language outcomes. Research also indicates that infants who are less distracted by irrelevant competing stimulation and attend efficiently to audiovisual social events (e.g., faces and voices) show better language outcomes. However, few studies have assessed relations between maternal responsiveness, infant attention to faces and voices, and distractibility, and how together these factors lead to early language outcomes. A newly developed audiovisual protocol, the Multisensory Attention Assessment Protocol (MAAP; Bahrick et al., 2018), allows researchers to examine individual differences in attention to faces and voices and distractibility, and to assess relations with other variables. At 12 months, infants (n = 79) in an ongoing longitudinal study participated in the MAAP to assess intersensory matching of synchronous faces and voices and attention to an irrelevant competing visual distractor event. They also were observed in a brief play interaction to assess infant bids for attention and maternal responsiveness (accept, redirect, or ignore). At 18 months, receptive and expressive language were assessed using the Mullen Scales of Early Learning. Several noteworthy findings emerged: 1) mothers were generally responsive, accepting 74% and redirecting 14% of infant bids, 2) infants who had a greater number of their bids redirected by mothers, and who had better intersensory matching of synchronous faces and voices, showed less attention to the distractor, and 3) infants who showed less attention to the distractor had better receptive language. Findings demonstrate that maternal redirecting of infant attention by mothers who are generally responsive may promote better infant attentional control (lower distractibility) which in turn predicts better receptive language in toddlers., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

It is incumbent upon all researchers who use the electronic health record (EHR), including data scientists, to understand the quality of such data. EHR data may be subject to measurement error or misclassification that have the potential to bias results, unless one applies the available computational techniques specifically created for this problem. In this article, we begin with a discussion of data-quality issues in the EHR focusing on health outcomes. We review the concepts of sensitivity, specificity, positive and negative predictive values, and demonstrate how the imperfect classification of a dichotomous outcome variable can bias an analysis, both in terms of prevalence of the outcome, and relative risk of the outcome under one treatment regime (aka exposure) compared to another. This is then followed by a description of a generalizable approach to probabilistic (quantitative) bias analysis using a combination of regression estimation of the parameters that relate the true and observed data and application of these estimates to adjust the prevalence and relative risk that may have existed if there was no misclassification. We describe bias analysis that accounts for both random and systematic errors and highlight its limitations. We then motivate a case study with the goal of validating the accuracy of a health outcome, chronic infection with hepatitis C virus, derived from a diagnostic code in the EHR. Finally, we demonstrate our approaches on the case study and conclude by summarizing the literature on outcome misclassification and quantitative bias analysis.

Introduction: Evidence regarding the impact of prophylactic implantation of Extracorporeal Membrane Oxygenation (ECMO) during coronary or structural procedures is limited. The purpose of this paper is to evaluate the in-hospital and medium term outcomes of ECMO support in complex percutaneous coronary or structural intervention., Methods: The present is an observational prospective study including consecutive patients who underwent to prophylactic ECMO implantation for percutaneous coronary intervention (PCI), structural or combined interventions between July 2018 and July 2020 in Maria Pia Hospital GVM Care & Research, Turin, Italy. Primary endpoints were in-hospital and medium term all-cause death. Secondary endpoints were vascular complication, bleeding and procedural success., Results: 27 patients were included with a mean age of 80 ± 6 years, 10 (37%) being diabetics and 19 (70%) with severe left ventricle dysfunction. Mean Logistic Euroscore was 28.7 ± 18.7. Seven patients (26%) underwent complex coronary revascularization, 7 (26%) combined PCI + TAVI, 5 (19%) combined PCI + Mitraclip, 5 (19%) TAVI alone and finally 3 (11%) combined TAVI + Mitraclip. The procedural success was 96%, with only one in-hospital death due to major vascular complication at the ECMO vascular access. At a mean follow-up of 11 ± 6.8 months 4 deaths were recorded (3 from not cardiovascular causes)., Conclusions: Prophylactic use of ECMO may be beneficial for high risk patients undergoing complex combined coronary/structural percutaneous interventions with good in-hospital and mid-term outcomes in term of safety and procedural success., Competing Interests: Declaration of competing interest All the authors have no financial/personal interest or belief that could affect their objectivity., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To demonstrate how selection into a healthcare facility can induce bias in an electronic medical record-based study of community deprivation and chronic hepatitis C virus infection, in order to more accurately identify local risk factors and prevalence., Methods: We created a catchment model that attempted to define the probability of selection into a retrospective cohort. Then using the inverse of this probability, we compared naïve unweighted and weighted models to demonstrate the impact of selection bias., Results: ZIP code-level ecological plots of the cohort demonstrated that there was a pattern of the community deprivation, hepatitis C outcome, and distance to the health center (an intuitive proxy for being within catchments). The naïve multilevel analysis found that living in an area with greater deprivation resulted in 1.25 times greater odds of HCV (95% CI: 1.06, 1.48), whereas the weighted analysis found less certainty of this effect due to a selection bias., Conclusions: We observed that selection into the catchment area of the studied healthcare facility may bias the association of community deprivation and hepatitis C. This may be mitigated through inverse probability weighting., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: We conducted a qualitative study of primary care providers to assess the challenges and opportunities in implementing a universal screening program for Hepatitis C Virus (HCV) at an urban community-based health center serving a largely disadvantaged population., Methods: Qualitative semi-structured interviews of prescribing providers took place pre- and post-educational intervention, at a single federally qualified health center in Wilmington, Delaware, between September 2018 and July 2019. The intervention included a two-day didactic session and shadowing specialist providers. Data captured provider perspectives on universal screening and treatment. The interviews were transcribed verbatim, then grouped into codes, then finally, themes., Results: Emergent themes included hesitancy in managing universal screening programs in the primary care environment, positive attitudes surrounding treatment, fewer HCV cases than expected, and concern with both patient-level barriers and practice-level barriers. Pre-intervention and post-intervention themes were similar., Conclusions: Implementation programs exploring universal HCV screening in the primary care environment should include educational opportunities that are available to all individuals in the practice, sustained organizational support, and available patient literature targeted to patients with varying health literacy and in languages other than English. In short, universal HCV screening and treatment is feasible in the primary medical environment but requires ongoing support and education for providers to ensure success., Competing Interests: Conflict of Interest: The authors declare that they have no conflict of interest.

Background: . Oral administration of bovine antibodies active against enterotoxigenic Escherichia coli (ETEC) have demonstrated safety and efficacy against diarrhea in human challenge trials. The efficacy of bovine serum immunoglobulins (BSIgG) against recombinant colonization factor CS6 or whole cell ETEC strain B7A was assessed against challenge with the CS6-expressing B7A., Methods: . This was a randomized, double-blind, placebo-controlled trial in which healthy adults received oral hyperimmune BSIgG anti-CS6, anti-B7A whole cell killed or non-hyperimmune BSIgG (placebo) in a 1:1:1 ratio then challenged with ETEC B7A. Two days pre-challenge, volunteers began a thrice daily, seven day course of immunoprophylaxis. On day 3, subjects received 1 × 10 10 CFUs of B7A. Subjects were observed for safety and the primary endpoint of moderate-severe diarrhea (MSD)., Results: . A total of 59 volunteers received product and underwent ETEC challenge. The BSIgG products were well-tolerated across all subjects. Upon challenge, 14/20 (70%) placebo recipients developed MSD, compared to 12/19 (63%; p = .74) receiving anti-CS6 BSIgG and 7/20 (35%; p = .06) receiving anti-B7A BSIgG. Immune responses to the ETEC infection were modest across all groups., Conclusions: . Bovine-derived serum antibodies appear safe and well tolerated. Antibodies derived from cattle immunized with whole cell B7A provided 50% protection against MSD following B7A challenge; however, no protection was observed in subjects receiving serum antibodies targeting CS6. The lack of observed efficacy in this group may be due to low CS6 surface expression on B7A, the high dose challenge inoculum and/or the use of serum derived antibodies versus colostrum-derived antibodies.

Extracorporeal membrane oxygenation (ECMO) has been developed to provide hemodynamic support in patients with severe cardiac or respiratory failure. In the last few years, its use has become increasingly common in interventional cardiology rooms for high-risk coronary interventions and for transcatheter therapies for valvular disease, which are increasingly complex in subsets of fragile patients at high surgical risk and with multiple comorbidities.Here, we describe the treatment of an extremely critical patient for severe dual valvulopathy, severe impairment of post-infarct systolic function, advanced heart failure with prohibitive operative risk. In a single session, the double valvular volume defect was treated percutaneously, using ECMO with an additional drainage of the left ventricle, performing a transcatheter implantation of two aortic valve prostheses with the valve-in-valve technique and the implantation of two MitraClips with excellent final result.

Background: Hepatitis C virus (HCV) is the most common blood-borne pathogen in the U.S., and Delaware has one of the highest sero-prevalence rates in the country. As a cause of significant morbidity and mortality, it is a public health priority to identify and link individuals with HCV to care. The demand of patients with HCV far exceeds the current availability of providers in Delaware that offer HCV management. ., Objective: To propose a framework for enabling non-specialist providers within Westside Family Healthcare to manage patients with HCV., Methods: As a recipient of a Harrington Value Institute Community Partnership grant, the HIV Community Program of Christiana Care Health System (CCHS) started working together with the NE Wilmington pilot site of Westside in July 2018 to: 1) provide HCV education to Westside, 2) implement an HCV care model at Westside, and 3) conduct programmatic evaluation of this framework's effectiveness. Our goal is to improve Westside rates of HCV knowledge amongst patients and staff, as well as to improve the HCV care continuum, starting with universal HCV screening., Results and Conclusions: Results from the first year of collaboration will be available in August 2019.  Implementation of this partnership will enable future expansion and continuation of HCV management amongst Westside sites.

Adherens junctions and desmosomes are critical for embryogenesis and the integrity of adult tissues. To form these junctions, classical cadherins interact via alpha- and beta-catenin with the actin cytoskeleton, whereas desmosomal cadherins interact with the intermediate filament system. Here, we used a hormone-activated mutant N-cadherin expressed in fibroblasts to show the existence of a novel classical cadherin adhesion system. N-cadherin was fused at its C-terminus to a modified estrogen receptor ligand-binding domain (NcadER) that binds 4-hydroxytamoxifen (4OHT) and expressed in L cells, which lack an endogenous cadherin. Cells with the mutant cadherin (LNER cells) aggregated in the absence of 4OHT, but only in its presence formed tightly compacted aggregates like those formed by L cells expressing wild-type N-cadherin (LN cells). Compaction of LNER cells treated with 4OHT was accompanied by elevated levels of p120ctn in NcadER immunoprecipitates, compared to immunoprecipitates of non-treated cells, but without changes in alpha- and beta-catenin, or actin. Compaction induced by 4OHT was also accompanied by increased interaction of the NcadER with the cytoskeleton and increased vimentin organization. Vimentin co-immunoprecipitated with the NcadER/catenin complex, suggesting an interaction between cadherin and vimentin. The mechanism by which vimentin interacts with the cadherin appears to involve p120ctn as it co-immunoprecipitates and colocalizes with vimentin in the parent L cells, which lack a cadherin and alpha- and beta-catenins. Disrupting the actin cytoskeleton with cytochalasin B inhibited aggregation, whereas knocking down vimentin with specific siRNAs inhibited compaction. Based on our results we propose that a vimentin-based classical cadherin complex functions together with the actin-based complex to promote strong cell-cell adhesion in fibroblasts.

This article describes a two-pronged intervention by the health care Quality Improvement Organization (QIO) for Connecticut to address the disparity in rates of mammography screening between women eligible for both Medicare and Medicaid (i.e., "dually eligible") and other Medicare beneficiaries. The interventions were directed beneficiaries. One intervention addressed information and access needs of the target population: an education session was followed by a mobile mammography van session at low-income housing sites in specific geographic areas. The second intervention was a culturally-sensitive direct mailing to dually eligible beneficiaries across the state. Implementation methods are described including: defining and identifying the target population; specifying the disparity; developing community collaboration; and testing the mail materials. Preliminary results of the education sessions and community testing of the direct mail materials generated information about the target population. Issues in implementation and analysis include: reaching the target population, building community relations, and developing design approaches to test the intervention.

The effects of telephonic nursing case management and standard care in a low-income, high-risk pregnancy population, controlling for gestational age at referral and risk factors (medical, demographic, and behavioral) were compared. The hypothesis was that a program of telephonic perinatal nursing care coordination and case management would increase mean gestational ages and mean birth weights and would reduce clinical resource utilization, compared with standard nursing care. The methods focused on a telephonic model developed during the past 16 years that included risk assessment, patient education, coordination of care for home services and clinic appointments, coordination of interventions requested by care providers, and patient advocacy. The patient population, primarily of minority cultural and racial backgrounds, obtained prenatal care from two large obstetric clinics and delivered at a level-3 tertiary care center. They were randomly assigned to treatment (N = 61) and control (N = 50) conditions. Interpreters were used for any contacts with non-English-speaking patients. The results demonstrated increased mean birth weights for the treatment group when intervening variables were controlled. Mean gestational age at delivery was not significantly different between groups. Telephonic case management saved an average of 501.31 dollars per patient in inpatient and outpatient costs combined. In the treatment group, for every dollar spent on case management costs, the savings were 4.08 dollars.

The effect of telephonic nursing case management on patient satisfaction in a predominantly non-Caucasian low-income, high-risk pregnancy population was studied. Patient satisfaction of care was significantly higher for treatment group participants than for controls on 9 of 10 items measuring satisfaction. The satisfaction score of the treatment patients, constructed by summing scores for each item, averaged 8 points higher than the control group's score. Demographics made little difference. Telephonic case management was the strongest predictor of satisfaction in a multiple regression analysis. Satisfaction was unrelated to mode of delivery, infant birth weight, or gestational age. The satisfaction levels of treatment patients were high, whether or not they had outpatient charges. Participants rated the program highly for the nurses' ability to answer questions, overall program experience, the opportunity to ask the nurses questions, health teachings and instructions received, and confidence in the nurse coordinating their care or their child's care.