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Background: Underserved ethnic minorities with psychiatric disorders are at an increased risk of COVID-19. This study aims to examine the effectiveness of one-to-one counseling on COVID-19 vaccination and vaccination readiness among underserved African American and Latinx individuals with mental illnesses and adult caregivers of children with mental illness., Methods: Through an academic-community partnered collaboration, a multidisciplinary and culturally sensitive training on COVID-19 was co-developed and delivered to 68 therapists from January to March 2021. Mental health clients and their caregivers were recruited to participate in pre- and post-intervention surveys to evaluate the impact of the intervention on their perceptions of COVID-19 public health guidelines, testing, and vaccination. Mental health therapists delivered four lessons of the COVID-19 educational intervention with 254 clients from March to June 2021, when vaccine availability was widely available. Of those clients, we collected 180 baseline and 115 follow-up surveys. The main outcome was the uptake in COVID-19 vaccine., Results: There was a positive shift in participant vaccine acceptance and receptivity. Pre-intervention survey shows that only 56% of adult clients and 48% of caregivers had indicated a likelihood of getting the vaccine for themselves at baseline. Post-intervention documented that more than 57% of each group had been vaccinated, with another 11-15% of the unvaccinated individuals reporting that they were somewhat or very likely to get the vaccine., Conclusion: This study demonstrated that multidisciplinary academic-community and theoretical-based educational intervention delivered by mental health therapists is an effective strategy in increasing COVID-19 vaccine acceptance and reducing the negative impact and disruption that COVID-19 caused in the daily life of mental health patients and caregivers., (© 2022. W. Montague Cobb-NMA Health Institute.)

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) provide great opportunities for mechanistic dissection of human cardiac pathophysiology; however, hiPSC-CMs remain immature relative to the adult heart. To identify novel signaling pathways driving the maturation process during heart development, we analyzed published transcriptional and epigenetic datasets from hiPSC-CMs and prenatal and postnatal human hearts. These analyses revealed that several components of the MAPK and PI3K-AKT pathways are downregulated in the postnatal heart. Here, we show that dual inhibition of these pathways for only 5 days significantly enhances the maturation of day 30 hiPSC-CMs in many domains: hypertrophy, multinucleation, metabolism, T-tubule density, calcium handling, and electrophysiology, many equivalent to day 60 hiPSC-CMs. These data indicate that the MAPK/PI3K/AKT pathways are involved in cardiomyocyte maturation and provide proof of concept for the manipulation of key signaling pathways for optimal hiPSC-CM maturation, a critical aspect of faithful in vitro modeling of cardiac pathologies and subsequent drug discovery., Competing Interests: Conflicts of interest The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

More than 60% of hypertrophic cardiomyopathy (HCM)-causing mutations are found in the gene loci encoding cardiac myosin-associated proteins including myosin heavy chain (MHC) and myosin binding protein C (MyBP-C). Moreover, patients with more than one independent HCM mutation may be at increased risk for more severe disease expression and adverse outcomes. However detailed mechanistic understanding, especially at early stages of disease progression, is limited. To identify early-stage HCM triggers, we generated single ( MYH7 c.2167C > T [R723C] with a known pathogenic significance in the MHC converter domain) and double ( MYH7 c.2167C > T [R723C]; MYH6 c.2173C > T [R725C] with unknown significance) myosin gene mutations in human induced pluripotent stem cells (hiPSCs) using a base-editing strategy. Cardiomyocytes (CMs) derived from hiPSCs with either single or double mutation exhibited phenotypic characteristics consistent with later-stage HCM including hypertrophy, multinucleation, altered calcium handling, metabolism, and arrhythmia. We then probed mutant CMs at time points prior to the detection of known HCM characteristics. We found MYH7/MYH6 dual mutation dysregulated extracellular matrix (ECM) remodeling, altered integrin expression, and interrupted cell-ECM adhesion by limiting the formation of focal adhesions. These results point to a new phenotypic feature of early-stage HCM and reveal novel therapeutic avenues aimed to delay or prohibit disease onset., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hsieh, Becklin, Givens, Komosa, Lloréns, Kamdar, Moriarity, Webber, Singh and Ogle.)

The extracellular matrix (ECM) provides essential cues to promote endothelial specification during tissue development in vivo; correspondingly, ECM is considered essential for endothelial differentiation outside of the body. However, systematic studies to assess the precise contribution of individual ECM proteins to endothelial differentiation have not been conducted. Further, the multi-component nature of differentiation protocols makes it challenging to study the underlying mechanisms by which the ECM contributes to cell fate. In this study, we determined that Laminin 411 alone increases endothelial differentiation of induced pluripotent stem cells over collagen I or Matrigel. The effect of ECM was shown to be independent of vascular endothelial growth factor (VEGF) binding capacity. We also show that ECM-guided endothelial differentiation is dependent on activation of focal adhesion kinase (FAK), integrin-linked kinase (ILK), Notch, and β-catenin pathways. Our results indicate that ECM contributes to endothelial differentiation through multiple avenues, which converge at the expression of active β-catenin., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

This study examined the six critical parameters for evaluating interventions, including necessity, acceptability, feasibility, safety, fidelity, and effectiveness, of a heart rate variability (HRV) biofeedback training intervention in a sample of 20 grandmothers who were the primary caregivers of their grandchildren. After the grandmothers completed the HRV biofeedback training, they answered open-ended questions to provide data on the six parameters during face-to-face interviews. The findings of the study provided evidence for the necessity, acceptability, feasibility, safety, fidelity, and effectiveness of the HRV biofeedback intervention for reducing the stress experienced by grandmothers in raising their grandchildren.

Purpose: This study describes the experiences of early implementers of primary care-focused cancer survivorship delivery models., Methods: Snowball sampling was used to identify innovators. Twelve participants (five cancer survivorship primary care innovators and seven content experts) attended a working conference focused on cancer survivorship population strategies and primary care transformation. Data included meeting discussion transcripts/field notes, transcribed in-depth innovator interviews, and innovators' summaries of care models. We used a multistep immersion/crystallization analytic approach, guided by a primary care organizational change model., Results: Innovative practice models included: (1) a consultative model in a primary care setting; (2) a primary care physician (PCP)-led, blended consultative/panel-based model in an oncology setting; (3) an oncology nurse navigator in a primary care practice; and (4) two subspecialty models where PCPs in a general medical practice dedicated part of their patient panel to cancer survivors. Implementation challenges included (1) lack of key stakeholder buy-in; (2) practice resources allocated to competing (non-survivorship) change efforts; and (3) competition with higher priority initiatives incentivized by payers., Conclusions: Cancer survivorship delivery models are potentially feasible in primary care; however, significant barriers to widespread implementation exist. Implementation efforts would benefit from increasing the awareness and potential value-add of primary care-focused strategies to address survivors' needs., Implications for Cancer Survivors: Current models of primary care-based cancer survivorship care may not be sustainable. Innovative strategies to provide quality care to this growing population of survivors need to be developed and integrated into primary care settings., Competing Interests: None of the authors have any potential conflicts of interest to disclose.

This study presents findings of a mixed-method descriptive exploration of the role of friends and spirituality/religiosity in easing the burden of families with the rare inherited disorder, Li-Fraumeni Syndrome (LFS). LFS is caused by germline mutations in the TP53 gene and is associated with very high lifetime risk of developing one or more malignancies. During the first clinical visit we assessed several types of social support among a subset of study participants (N = 66) using an established interactive research tool called the Colored Eco-Genetic Relationship Map (CEGRM). We performed both quantitative and qualitative analyses of social relationships with LFS family members and close non-kin. Distress scores (N = 59) were mostly low normal, with some outliers. We found that reported friendships varied widely, that the friendships were often deep and enduring, and were important sources of informational, tangible, emotional and spiritual support. Confidantes tended to be best friends and/or spouses. Organized religion was important in selected families, typically from mainstream traditions. However, a number of people identified themselves as "spiritual" and reported spiritual and humanist explorations. Our results shed preliminary light on how some people in families with LFS cope in the face of tremendous medical, social and emotional challenges.

The results presented in this work show for the first time that an electric field used to macroscopically align polymer nanofibers can also align polymer chains parallel to the fiber axis. This important result indicates that anisotropic structural properties (mechanical, electrical, etc.) can be induced in polymer nanofibers during the electrospinning process. Such uniaxially oriented nanofibers exhibit a variety of potential applications in biomedicine, microelectronics, and optics. A simple technique of vertical electrospinning with an electric field induced, stationary collection was employed to obtain the molecular orientation in polymer nanofibers. This manuscript describes the orientation process via electrospinning and verifies this molecular orientation in the polymer nanofibers using three independent methods: polarized Fourier transform infrared spectroscopy, polarized Raman scattering, and X-ray diffraction.

Double-blind placebo-controlled clinical trials in metastatic bone disease considered counts of morbid events as the clinical outcome measure. These (recurrent) skeletal events were derived from a composite endpoint based on the necessity of medical interventions against bone pain or incident fractures. The trials were conducted for regulatory approval of therapy with bisphosphonates and were intended to demonstrate that an active treatment reduces the occurrence of skeletal events. The advanced morbidity of the patients led to a substantial amount of premature discontinuations, because of early death or because of progression of the basic disease. In some trials the discontinuations were unbalanced between treatment arms, where there were more dropouts under placebo. These effects contribute to a high portion of patients with no morbidity events. This background presents difficulties for the task of defining statistics that validly quantify skeletal morbidity in these trials while keeping the necessary simplicity so as to be accepted by health authorities and a clinical audience. Guided by this regulatory context, this paper compares the performance of five (simple) approaches to quantifying skeletal morbidity. Key criteria are bias and validity under different dropout scenarios, as well as the capability to demonstrate treatment effects. Based on theoretical considerations, two simulation studies, and real data results, a morbidity measure in the form of a smoothed rate was favored: this is a rate estimate in the individual patient of the form (y + c)(T + d)(-1), where y is the count of events, T is the patient's observation time, and c, d are constants to be appropriately chosen. This morbidity measure performed well in the simulation studies and showed a wanted insensitivity to dropout patterns. It outperforms the simple rate y/T due to the high portion of patients without events. Rates of this type were used before in the quantal bioassay and have a strong relationship to Bayesian approaches. Hence, these measures represent a good approach to handle the inherent difficulties of morbid event data in severely diseased patient populations, still offering sufficient simplicity.

Public policy decisions directly affect the health care of women and children and also affect the practice of maternal and child nursing. The past quarter century has seen a shift in nursing involvement in the public policy process. Heightened awareness of the collective power of nurses, greater independence of the nursing profession, the increasing capability for generating research to guide the formulation of public policy, and nurses' better understanding of the political process have all contributed to the increasing influence of our nation's 2.6 million nurses. The passage of several significant pieces of legislation, such as expansions of the Medicaid program for pregnant women and children in the late 1980s, have opened up new opportunities for nurses to further shape the nation's health care agenda for women and children. Nurses can and should become more involved with the policy-making process at local, state, and national levels to assure that decisions are made that benefit this important population group. Leadership in the public policy arena will give nurses the best opportunities for putting forth the agendas that will accomplish these goals.

Computer-assisted NDAs (CANDAs) have evolved from an instrument that provides information to regulators to also providing information to internal researchers. They are still not as useful internally during the NDA process as they will be in the future. The portion of CANDA that allows summary, display, and query of the raw data is the most complicated part of the CANDA. Roche's current CANDA system, as well as the challenges in using, documenting, and validating such a system, is described, stressing the features that make it usable in-house. Roche's vision of the future is outlined, covering the strategies, targets, and expected savings.

Objective: The perceived function of wild-type p53 is suppression of cell proliferation. An alteration in the p53 tumor suppressor gene is a common defect in human malignancies. The purpose of this study was to prospectively determine whether p53 expression, as quantified by image analysis, was related to traditional prognostic indicators as well as survival in patients epithelial ovarian cancer., Methods: Eighty-three consecutive patients with epithelial ovarian cancer had their p53 expression studied by immunohistochemical staining and quantified by image analysis. Unless otherwise noted, p53 expression was reported as the percentage positive nuclear area staining., Results: The mean follow-up was 37 months (median, 30 months; range 24-55 months). In patients with serous carcinomas of the ovary, the mean p53 expression was 29.4%, whereas in patients with other histologies, the mean was 10.5% (P < 0.001). The tumors of patients with stage III or IV tumors stained significantly higher (mean 28. 7%) than the tumors of patients with stage I or II disease (mean 8. 36%) (P < 0.001). The tumors of patients with disease which could be optimally cytoreduced stained significantly lower (mean 23.0%) than the tumors of patients whose disease was unable to be optimally cytoreduced (mean 28.6%) (P = 0.041). Utilizing survival as the endpoint for multivariate analysis, FIGO stage (P = 0.006), p53 expression (P = 0.046), and the level of cytoreduction (P < 0.001) were independent prognostic indicators., Conclusion: Image analysis allows quantitative measurements of p53 staining. p53 staining is significantly higher in advanced-stage, high-grade tumors which are unable to be cytoreduced than in early-stage, low-grade tumors which can be optimally cytoreduced. p53 expression is an independent prognostic indicator of survival in patients with epithelial ovarian carcinomas., (Copyright 1997 Academic Press.)

The health of pregnant women and children has improved substantially since the 1960s. In the past decade, however, progress in preventing infant deaths, reducing the incidence of low-birth-weight infants, and ensuring first trimester prenatal care has slowed. African-American infants suffer a significantly higher risk of poor pregnancy outcome. Immunization rates for preschoolers remain low. Changing social conditions including a rising child poverty rate, a high teenage birth rate, an increased rate of births to unmarried women, and higher levels of unintended pregnancy may be contributing to stalled progress.

Split fields are commonly used for a variety of treatments for which local shielding is desired; a single field is split into two fields by means of lead blocks placed in the beam. The condition for assuming independence of the two fields is investigated by using the area over perimeter calculational method and comparing this to experimental depth-dose data measured in a water phantom using a Shonka ionization chamber. Two principal variations affecting dose distributions are examined: block width and position of the block expressed as the fractional perpendicular distance between the central ray of the overall field and the center of the block. An intercomparison between calculation and experimental data shows that the right and left sides of the split field behave as independent fields giving TAR values in agreement with experimental data to within +/-1%. If the fields are asymmetric and if the larger field is less than 70% of the total area including the blocked part, then the dosimetry should be based on average TARs, off-center ratios, and backscatter factors for the two fields. If the larger area is greater than 70% of the total area, then the treatment time can be calculated from the larger field only.

Lasalocid was given to horses in a series of sequentially increasing single oral doses ranging between 5 and 30 mg/kg of body weight, with an appropriate washout period between treatments. One of the 5 horses died after a dosage of 15 mg/kg, 1 of 3 horses died after 21 mg/kg, 1 of 3 horses died after 22 mg/kg, and 1 of 2 horses died after 26 mg/kg. The LD50 of lasalocid for horses was estimated to be 21.5 mg/kg. Monensin was given to horses in a similar manner at dosages of 1, 2, and 3 mg/kg of body weight. One of the 2 horses died after a dosage of 2 mg/kg and 1 horse died after a dosage of 3 mg/kg. The clinical signs of toxicosis observed in horses given either drug were progressive and included depression, ataxia, paresis, and paralysis with partial anorexia. Intermittent profuse sweating was observed before death in horses given monensin.

The effect of oral cibenzoline on steady-state digoxin concentrations was studied in 12 healthy subjects ranging from 41 to 55 years of age. Each subject received an oral dose of 0.25 mg or 0.375 mg digoxin once daily for 27 days. On days 14 to 21, 160 mg of oral cibenzoline were administered concomitantly every 12 hours for a total of 15 doses. Plasma digoxin concentration-time profiles obtained before, during, and after cibenzoline coadministration were compared to determine the effect of oral cibenzoline on steady-state digoxin concentrations. The maximum plasma concentration, time of maximum concentration, area under the curve during a dosing interval and steady-state trough plasma concentration for digoxin, during and after concomitant doses of cibenzoline were similar to those before administration, indicating that cibenzoline did not affect the pharmacokinetics of digoxin. In addition, plasma cibenzoline concentration-time profiles after the first and last dose of cibenzoline were similar to those observed in previous studies in which multiple doses of cibenzoline alone were administered. The results of this study indicate that there is no pharmacokinetic interaction between digoxin and cibenzoline when the two drugs are coadministered to healthy subjects in multiple doses.

A single, oral, 1.5-mg dose of trimoprostil was taken before a standard meal and a matching placebo was taken after a standard meal by 10 subjects (group A). A second group of 10 subjects took placebo before a meal and trimoprostil after the meal (group B), while a third group took placebo both before and after the standard meal (group C). Food-stimulated gastric acid production was measured by intragastric titration for 6.5 hr after dosing. Trimoprostil taken after the meal had a greater effect on gastric acid secretion than when taken before the meal: Duration of effect was 5 to 5.5 hr in group B and 2 to 2.5 hr in group A. Blood samples were drawn and assayed for trimoprostil by gas chromatography-mass spectrometry. Mean trimoprostil plasma concentration and mean inhibition of gastric acid secretion data were fit to two models by the Hill equation. The mean plasma concentration associated with 50% inhibition of gastric acid secretion was 1.25 ng/ml. Trimoprostil plasma concentrations between 3 and 4 ng/ml were associated with 70% to 80% gastric acid inhibition. Overall, there appears to be a pharmacokinetic-pharmacologic correlation between trimoprostil plasma concentrations and inhibition of gastric acid secretion. Trimoprostil (1.5 mg) in the presence of food appears to have a therapeutic advantage, in that it decreases acid secretion longer than when taken without food and suffers no loss of bioavailability.

The effect of single 0.25 mg, 0.75 mg, 1.5 mg, and 3.0-mg oral doses of trimoprostil and placebo on the inhibition of meal-stimulated gastric acid secretion was investigated in duodenal ulcer patients. Drug and placebo were administered in a double-blind, randomized, crossover study under fasting conditions. A bactopeptone meal was administered 30 minutes after dosing. Gastric acid output was measured by intragastric titation (pH 5.5) and trimoprostil plasma concentrations were measured by a specific gas chromatography-negative chemical ionization-mass spectrometric method. Meal-stimulated gastric acid secretion was significantly reduced when compared to placebo for one hour after 0.25 mg, 1.5 hours after 0.75 mg, and for 2.5-3.0 hours after both 1.5 mg and 3.0 mg doses. The maximal inhibition of gastric acid ranged from 65% reduction after 0.75 mg to 74% after 1.5 mg to 82% after 3.0-mg doses. Trimoprostil was rapidly absorbed and eliminated; terminal elimination half-life ranged from 21 to 45 minutes. Both maximum concentration and area under the plasma concentration-time curve increased proportionately with an increase in the dose. The concentration-effect data at a given dose were simultaneously fit to a pharmacokinetic/pharmacologic effect model. An IC50 (plasma concentration needed to elicit a 50% inhibition effect) value of 0.2 ng/mL was observed at doses of 0.75 mg to 3.0 mg. Overall, trimoprostil was effective in inhibiting acid output in a dose-related manner in duodenal ulcer patients.

Lasalocid (.0125%) alone and combined with roxarsone (.005%) was evaluated for its effect on lesion reduction and oocyst suppression in thirty-five controlled replicated battery experiments, using in excess of 6200 broiler chickens. The chickens were inoculated with field isolates containing predominantly Eimeria tenella species. Lasalocid (.0125%) used alone exhibited a high degree of anticoccidial activity. Lasalocid (.0125%) fed in combination with roxarsone (.005%) showed, in addition to high anticoccidial activity, a further reduction in gross lesion (P less than .01) and oocyst production (P less than .05) over lassalocid used alone.

Branhamella (Neisseria) catarrhalis is a saprophytic inhabitant of the human oropharynx with the capacity to cause infection, particularly in immunodeficient hosts. There have been 2 cases of Branhamella catarrhalis pneumonia reported in the literature. Two additional cases are described and the subject reviewed. An 80-yr-old woman with chronic lymphocytic leukemia presented with left lower lobe pneumonia. Gram stain of transtracheal aspirate revealed intraleukocytic and extraleukocytic gram-negative diplococci, and a beta-lactamase producing strain of Branhamella catarrhalis was cultured. Therapy with erythromycin resulted in resolution of symptoms and eradication of the organism. A 64-ye-old alcoholic man presented with fever and multiple seizures. Chest roentgenogram revealed left lower lobe pneumonia. Cultures of endotracheal aspirate and blood grew a strain of Branhamella catarrhalis sensitive to penicillin. Penicillin treatment resulted in resolution of pulmonary infiltrate and eradication of the organism. The potential for Branhamella catarrhalis to produce pneumonia and the choice of antimicrobial therapy is discussed. It is emphasized that this organism should not be assumed to be a "normal" isolate and that penicillin may be ineffective in the treatment of Branhamella catarrhalis infections.

To compare the relative merits of two different administration regimens, tyramine was administered intravenously in ascending doses to 12 healthy subjects to raise systolic blood pressure slightly more than 30 mm Hg. Six subjects received tyramine by bolus injection and six other subjects received tyramine by infusion. The bolus dose of tyramine needed was 4.34 +/- 1.51 mg (X +/- SD) and the infusion rate needed was 1.11 +/- 0.33 mg/min. Four blood pressure response patterns to continuous tyramine infusion were observed. Because different units were measured for the quantity of tyramine administered, the between-subject variance estimate to within-subject variance estimate ratios were calculated. The two techniques had equivalent consistency. With the bolus method, in contrast to the infusion procedure, the dose-response relationship was obvious in most subjects. Therefore the bolus method was judged to be more useful than the infusion method.

Lasalocid at the concentration of .0075% (68 g/ton) with and without roxarsone 45.4 g/ton was fed in combination with the growth promotants bacitracin methylene disalicylate 200 g/ton, bambermycins 2 g/ton, lincomycin 4 g/ton, nosiheptide 2.5 g/ton, zinc bacitracin 200 g/ton g/ton, and virginiamycin 20 g/ton exhibited a high degree of anticoccidial activity against mixed Eimeria infection in chickens in 9 day challenged battery trials. In these short term challenge trials chicks fed lasalocid, and the lasalocid growth promotant combinations, performed significantly better (P < .05) for growth and anticoccidial efficacy than those fed the growth promotants alone, and the infected, unmedicated controls. In almost all instances, the lasalocid-roxarsone-antibiotic combinations allowed for numerical increases in gains, improvement in feed conversion, and numerical decreases in lesions (in some cases, statistically significant (P < .05) over chicks fed lasalocid alone and/or the lasalocid antibiotic combination. The growth promotants did not interfere with the anticoccidial activity of lasalocid. The growth promotants fed alone exhibited no anticoccidial activity. However, when roxarsone was combined with the antibiotics, the combination resulted in numerically improved performance, reduced mortality, and in most instances, statistically significant decreases in lesions (P .05) over the infected, unmedicated control.