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Introduction: Vidutolimod, a CpG-A TLR9 agonist, was investigated in a phase 1b study (CMP-001-003; ClinicalTrials.gov, NCT03438318) in combination with atezolizumab with and without radiation therapy (RT) in patients with advanced NSCLC. Methods: Patients with progressive disease after anti–programmed cell death protein 1 or programmed death-ligand 1 therapy received either vidutolimod and atezolizumab (part A) or vidutolimod, atezolizumab, and RT (part B). The primary objective was to evaluate the safety of vidutolimod and atezolizumab with and without RT. Key secondary end point was best objective response rate per Response Evaluation Criteria in Solid Tumors, version 1.1. Results: Between March 28, 2018, and July 25, 2019, a total of 29 patients were enrolled and received at least one dose of vidutolimod (part A, n = 13; part B, n = 16). Intratumoral injections of vidutolimod were administered successfully, including injection of visceral lesions. The most common treatment-related adverse events (≥30%) were flu-like symptoms and hypotension. No objective responses were observed; 23.1% and 50.0% of the patients in parts A and B, respectively, had stable disease as best response. In parts A and B, 15.4% and 25.0% of the patients, respectively, had tumor shrinkage (

PURPOSE: The purpose of this article is (1) to investigate if type 2 diabetes management programs with Latino participants address emotional well-being in addition to the standard diabetes self-care behaviors and (2) to describe the approaches taken to improve psychological and diabetes management outcomes. METHODS: Online article and research databases, Internet searches, and review of article citations were used to identify relevant articles published 1995-2008. Type 2 diabetes management interventions with a psychological (emotion or cognitive) component or outcome measure and Latino sample were selected. Articles were limited to randomized clinical/controlled trials and pre-post comparative studies. RESULTS: Thirteen interventions met the inclusion criteria for this review. Eight studies included emotion outcome measures, and 13 included at least one cognitive outcome measure. One study was specifically designed to improve emotional well-being. This study was not targeted for Latinos but did include Latino participants. A specialized depression case manager and collaborative care model showed significant improvements in depression and mental functioning. Psychological improvements were also found in those studies that assessed cognitive outcomes and were based on cognitive theories. The most frequent cognitive outcomes assessed were diabetes knowledge, problem solving, and self-efficacy. CONCLUSIONS: Few type 2 diabetes interventions address emotional well-being in Latinos. More attention has been directed toward designing culturally sensitive community-based programs for improving behavior and physical outcomes. Because some Latino groups believe that negative emotions cause diabetes and because depression and anxiety are associated with poor self-management, programs should address emotional well-being as an important aspect of diabetes management. [ABSTRACT FROM AUTHOR]

This paper describes how a school of nursing has conceptualized and embodied social responsibility in its core values, curricular design, admission standards, clinical practice, and service learning opportunities. The school's engagement in the process of practicing social responsibility and clarifying its meaning and application has made apparent the natural linkage between social responsibility and professionalism and the deep and complex relationship between social responsibility and nursing itself. It has also revealed how a commitment to social responsibility impacts and determines for whom nurses care. Claiming social responsibility as a core value and working to refine its meaning and place has increased the school's commitment to it, concomitantly impacting education, practice, and recruitment and evaluation of faculty and students. The school views the conceptualization of social responsibility as a deepening and unfolding evolution, rather than as a formulaic understanding, and expects that its ongoing work of claiming social responsibility as a core value will continue to be enriching. [ABSTRACT FROM AUTHOR]

The purpose of this study was to provide a culturally specific intervention program for African American women to alter selected behavioral risk factors, psychosocial responses, and breast self-care variables. Two primary directional hypotheses were tested with an alpha set at 0.05. These hypotheses were: 1) a Culturally Appropriate Breast Educational Intervention Program (CABHEIP) will lower selected behavioral risk factors (high fat intake, inadequate amount of physical activity, inadequate fiber intake) and selected psychosocial responses (perceived stress, negative coping, low self-efficacy, perceived barriers to Breast Self Examination [BSE] and Clinical Breast Examination [CBE]) in African American women, 20 to 40 years of age, who participate in the program as compared to whose who do not participate; and 2) a CABHEIP will raise compliance with BSE, proficiency of BSE, and perceived benefits of BSE and CBE in African American women, 20 to 40 years of age, who participate in the program as compared to those who do not participate. A sample of 120 (N = 120) African American women was randomly assigned to the control and treatment groups (60 women per group; (n = 60 intervention group; n = 60 attention control group). The sample was obtained from a population of African American women from four southern and three central Mississippi counties. The intervention group, in clusters of 3 to 9 women, received education on breast cancer, breast self-exams, healthy eating, exercise, and stress management; and heard stories from breast cancer survivors. The attention control group, in clusters of 3 to 8 women, received education on poison control in the home environment. Data was collected and analyzed using descriptive statistics, correlation coefficients, and repeated measures of analysis of covariance (ANCOVA) controlling for covariates. Significant differences between groups for BSE proficiency I (p<0.0001), BSE proficiency II (p = 0.013), and benefit BSE (p = 0.053) were found. Compliance for BSE approached significance between groups (p = 0.053). Significance to nursing is that education can change outcomes in health promotion for breast cancer in African American women. Further studies with similar interventions and larger sample sizes are needed to determine other avenues to decrease modifiable risk factors for breast cancer in African-American women. [ABSTRACT FROM AUTHOR]

Abstract Background Magnesium sulfate is an affordable and effective treatment for pre-eclampsia and eclampsia. In settings where infusion pumps are not available to regulate the flow rate of intravenous delivery, healthcare providers must administer magnesium sulfate (MgSO4) via time-consuming and painful, large-volume intramuscular injections. As an alternative to costly commercially available syringe pumps, we developed AutoSyp, an accurate, low-cost, and low-powered syringe pump designed to meet the needs and constraints these low-resource settings. This paper describes results of a pilot study to evaluate the feasibility of using AutoSyp to administer MgSO4 intravenously to women suffering from pre-eclampsia at a referral hospital in Blantyre, Malawi. Methods AutoSyp was programmed to deliver MgSO4 following the Zuspan regimen to pregnant and post-partum women suffering from pre-eclampsia at Queen Elizabeth Central Hospital in Blatnyre, Malawi. Given the selection of either loading or maintenance dose on AutoSyp’s user interface, the flow rate was automatically programmed to dispense 60 mL/h or 5 mL/h of 20% MgSO4 solution, respectively. During each treatment, the dispensed volume was automatically calculated by the device based on the plunger position and stored on a computer for accuracy analysis of the mean flow rate and total volume delivered. The clinical results for both the loading and maintenance dose administrations were compared to the device’s accuracy during tests performed in the laboratory setting. Results Twenty-two women were enrolled in this study. In both the clinical and laboratory settings, the mean flow rate errors for the loading and maintenance dose infusions were under 2%. During 466 h of testing, the device sounded 129 occlusion alarms across 14 subjects. Of these, 71 alarms were false positives. Conclusion Results of this study support the use of AutoSyp as a less painful and accurate means of MgSO4 administration in clinical environments that lack infusion systems. There were a large number of false alarms in the current system which will be addressed in future designs. AutoSyp maintains the comfort of intravenous MgSO4 administration, but unlike commercially available syringe pumps, it is capable of operating with a variety of syringe brands and sizes and requires no additional consumables. AutoSyp’s appropriate design will benefit its implementation and sustained use in low-resource settings. Trial Registration Trial registered prospectively on November 18, 2014 with ClinicalTrials.gov ( NCT02296931 )

OBJECTIVES: As part of a larger study exploring psychosocial factors that influence self-care and use of health care services during pregnancy, we investigated the process of pregnancy discovery and acceptance among a culturally diverse group of women who had given birth to their first child in the year preceding data collection. METHODS: Eighty-seven low-income women from four cultural groups (African American, Mexican, Puerto Rican, and white) participated in eight focus groups held in their communities. The focus groups were ethnically homogenous and stratified by early and late entry into prenatal care. A social influence model guided the development of focus group questions, and the study followed a participatory action research model, with community members involved in all phases of the research. RESULTS: Issues that emerged from the focus groups as possible influences on timing of pregnancy recognition include the role of pregnancy signs and symptoms and pregnancy risk perception in the discovery process, the role of social network members in labeling and affirming the pregnancy, concerns about disclosure, 'planning' status of the pregnancy, and perceived availability of choices for resolving an unintended pregnancy. CONCLUSIONS: The pregnancy discovery process is complex, and when protracted, can potentially result in delayed initiation of both prenatal care and healthful pregnancy behaviors. Enhancing our understanding of pregnancy discovery and acceptance has clear implications for primary and secondary prevention. Future research is needed to further explain the trajectory of pregnancy discovery and acceptance and its influence on health behaviors and pregnancy outcome. [ABSTRACT FROM AUTHOR]

Reversing low adherence rates of minority women in the use of early detection protocols. [ABSTRACT FROM AUTHOR]

One hundred forty mothers of children with chronic illnesses seen in two pediatric specialty clinics of a major urban teaching hospital were surveyed regarding their primary care arrangements and satisfaction with care received. Three dimensions of maternal satisfaction were measured: general satisfaction, satisfaction with access to care and satisfaction with doctor conduct (physician humaneness and technical quality). Results of multivariate analyses indicate that receipt of anticipatory guidance, access to care during evening hours and having a child in excellent reported health status were significantly associated with at least two of the three dimensions of maternal satisfaction. Findings have implications for organizing comprehensive, accessible primary care in the community, which is consistent with recent trends in child health policy. Results supported the need for enrichment of primary care for children with chronic illnesses to allow for physician continuity, provision of information and advice to families and extended office hours. [ABSTRACT FROM AUTHOR]

Objectives: This study describes the use of a Medicaid managed care list to prospectively recruit into a research project pregnant women receiving care from a variety of providers. Method: A list of women enrolled in Medicaid managed care was used to recruit pregnant African-American and Latina women into a study of prenatal care satisfaction. Due to privacy concerns, the researchers were not able to directly access names from the list. Instead, a managed care contract agency sent recruitment letters to 1009 pregnant African-American and Latina Medicaid recipients. Response rates by ethnicity and several other key variables are calculated. The biases associated with this method of recruiting pregnant women from a variety of providers are discussed. Results: Thirty-five percent of the women contacted returned consent forms and agreed to have researchers approach them; the response rate for African-American women was 43% and for Latinas was 29% (p < 0.0001). Respondents were younger and later in their pregnancies than nonrespondents, but did not differ from them by zip code of residence. The women recruited into the study obtained prenatal care from a diverse group of providers. Conclusions: While the use of a prospectively generated list of pregnant Medicaid recipients to recruit low-income pregnant women into a research study may be associated with some selection bias, the potential cost savings, decreased effort and diminished recall bias may make their use a feasible sampling alternative, particularly when the researcher desires to recruit women seeking care from a variety of provider arrangements. [ABSTRACT FROM AUTHOR]

Women's roles have undergone rapid transformation in recent decades and appear to affect the decision to breast-feed. Research in this area has been hampered by the lack of valid instruments to measure the relevant domains of gender-role related considerations. This study developed a scale to measure gender-role attitudes toward breast-feeding in primiparous women. Ninety-one married women, recruited during childbirth education classes in the Chicago metropolitan area, were surveyed by mail at eight weeks postpartum regarding their experiences as new mothers. Questionnaire items measuring infant feeding method (breast-feeding, bottle feeding) and attitudes toward breast-feeding were developed specifically for this investigation. Validity and reliability were assessed by structural equations analysis using LISREL. The LISREL fit statistics supported a one factor measurement model and combining the six items into a scale. Reliability analysis yielded a standardized alpha coefficient of .74. If results of future research are promising, the scale could be used to target new mothers with multiple roles for education and support and to evaluate interventions designed to promote positive breast-feeding attitudes and behavior. [ABSTRACT FROM AUTHOR]

African-American women of child-bearing age residing in three high-risk communities in Chicago were surveyed regarding their primary care arrangements and access to care (n = 552). This study examined factors which differentiated women who used office-based practices from those who used institutional settings (community clinics, health department clinics, hospital-based clinics) for primary care. Results of multivariate analysis indicate that women who used office-based practices were more likely than those who used institutional settings to see the same provider, to walk to their provider, to have less travel time and to walk in without an appointment. They were less likely to be hospitalized in the past year and less likely to report the availability of family planning at their usual source of care. Satisfaction with care, insurance status and sociodemographic characteristics were not associated with use of a particular facility type. Implications for organizing comprehensive health services for this population are discussed. [ABSTRACT FROM AUTHOR]

Necroptosis is a highly pro-inflammatory mode of cell death regulated by RIP (or RIPK)1 and RIP3 kinases and mediated by the effector MLKL. We report that diverse bacterial pathogens that produce a pore-forming toxin (PFT) induce necroptosis of macrophages and this can be blocked for protection against Serratia marcescens hemorrhagic pneumonia. Following challenge with S. marcescens, Staphylococcus aureus, Streptococcus pneumoniae, Listeria monocytogenes, uropathogenic Escherichia coli (UPEC), and purified recombinant pneumolysin, macrophages pretreated with inhibitors of RIP1, RIP3, and MLKL were protected against death. Alveolar macrophages in MLKL KO mice were also protected during S. marcescens pneumonia. Inhibition of caspases had no impact on macrophage death and caspase-1 and -3/7 were determined to be inactive following challenge despite the detection of IL-1β in supernatants. Bone marrow-derived macrophages from RIP3 KO, but not caspase-1/11 KO or caspase-3 KO mice, were resistant to PFT-induced death. We explored the mechanisms for PFT-induced necroptosis and determined that loss of ion homeostasis at the plasma membrane, mitochondrial damage, ATP depletion, and the generation of reactive oxygen species were together responsible. Treatment of mice with necrostatin-5, an inhibitor of RIP1; GW806742X, an inhibitor of MLKL; and necrostatin-5 along with co-enzyme Q10 (N5/C10), which enhances ATP production; reduced the severity of S. marcescens pneumonia in a mouse intratracheal challenge model. N5/C10 protected alveolar macrophages, reduced bacterial burden, and lessened hemorrhage in the lungs. We conclude that necroptosis is the major cell death pathway evoked by PFTs in macrophages and the necroptosis pathway can be targeted for disease intervention.

Abstract Introduction Despite the substantial global burden of preterm and stillbirth, little attention has been given to the ethical considerations related to research and interventions in the global context. Ethical dilemmas surrounding reproductive decisions and the care of preterm newborns impact the delivery of interventions, and are not well understood in low-resource settings. Issues such as how to address the moral and cultural attitudes surrounding stillbirths, have cross-cutting implications for global visibility of the disease burden. This analysis identifies ethical issues impacting definitions, discovery, development, and delivery of effective interventions to decrease the global burden of preterm birth and stillbirth. Methods This review is based on a comprehensive literature review; an ethical analysis of other articles within this global report; and discussions with GAPPS's Scientific Advisory Council, team of international investigators, and a community of international experts on maternal, newborn, and child health and bioethics from the 2009 International Conference on Prematurity and Stillbirth. The literature review includes articles in PubMed, Academic Search Complete (EBSCO), and Philosopher's Index with a range of 1995-2008. Results Advancements in discovery science relating to preterm birth and stillbirth require careful consideration in the design and use of repositories containing maternal specimens and data. Equally important is the need to improve clinical translation from basic science research to delivery of interventions, and to ensure global needs inform discovery science agenda-setting. Ethical issues in the development of interventions include a need to balance immediate versus long-term impacts—such as caring for preterm newborns rather than preventing preterm births. The delivery of interventions must address: women's health disparities as determinants of preterm birth and stillbirth; improving measurements of impact on equity in coverage; balancing maternal and newborn outcomes in choosing interventions; and understanding the personal and cross-cultural experiences of preterm birth and stillbirth among women, families and communities. Conclusion Efforts to improve visibility, funding, research and the successful delivery of interventions for preterm birth and stillbirth face a number of ethical concerns. Thoughtful input from those in health policy, bioethics and international research ethics helped shape an interdisciplinary global action agenda to prevent preterm birth and stillbirth.

Abstract Background In the United States, an estimated 70 stillbirths occur each day, on average 25,000 each year. Research into the prevalence and causes of stillbirth is ongoing, but meanwhile, many parents suffer this devastating loss, largely in silence, due to persistent stigma and taboo; and many health providers report feeling ill equipped to support grieving parents. Interventions to address bereavement after neonatal death are increasingly common in U.S. hospitals, and there is growing data on the nature of parent bereavement after a stillbirth. However, further research is needed to evaluate supportive interventions and to investigate the parent-clinician encounter during hospitalization following a stillbirth. Qualitative inquiry offers opportunities to better understand the lived experience of parents against the backdrop of clinicians’ beliefs, intentions, and well-meaning efforts to support grieving parents. Methods We present a secondary qualitative analysis of transcript data from 3 semi-structured focus groups conducted with parents who had experienced a stillbirth and delivered in a hospital, and 2 focus groups with obstetrician-gynecologists. Participants were drawn from the greater Seattle region in Washington State. We examine parents’ and physicians’ experiences and beliefs surrounding stillbirth during the clinical encounter using iterative discourse analysis. Results Women reported that the cheery, bustling environment of the labor and delivery setting was a painful place for parents who had had a stillbirth, and that the well-meaning attempts of physicians to offer comfort often had the opposite effect. Parents also reported that their grief is deeply felt but not socially recognized. While physicians recognized patients’ grief, they did not grasp its depth or duration. Physicians viewed stillbirth as an unexpected clinical tragedy, though several considered stillbirth less traumatic than the death of a neonate. In the months and years following a stillbirth, these parents continue to memorialize their children as part of their family. Conclusions Hospitals need to examine the physical environment for deliveries and, wherever possible, offer designated private areas with staff trained in stillbirth care. Training programs in obstetrics need to better address the bereavement needs of parents following a stillbirth, and research is needed to evaluate effective bereavement interventions, accounting for cultural variation. Critical improvements are also needed for mental health support beyond hospitalization. Finally, medical professionals and parents can play an important role in reversing the stigma that surrounds stillbirth.

Abstract Background Limited controlled data exist to guide treatment choices for clinicians caring for patients with major depressive disorder (MDD). Although many putative predictors of treatment response have been reported, most were identified through retrospective analyses of existing datasets and very few have been replicated in a manner that can impact clinical practice. One major confound in previous studies examining predictors of treatment response is the patient’s treatment history, which may affect both the predictor of interest and treatment outcomes. Moreover, prior treatment history provides an important source of selection bias, thereby limiting generalizability. Consequently, we initiated a randomized clinical trial designed to identify factors that moderate response to three treatments for MDD among patients never treated previously for the condition. Methods/design Treatment-naïve adults aged 18 to 65 years with moderate-to-severe, non-psychotic MDD are randomized equally to one of three 12-week treatment arms: (1) cognitive behavior therapy (CBT, 16 sessions); (2) duloxetine (30–60 mg/d); or (3) escitalopram (10–20 mg/d). Prior to randomization, patients undergo multiple assessments, including resting state functional magnetic resonance imaging (fMRI), immune markers, DNA and gene expression products, and dexamethasone-corticotropin-releasing hormone (Dex/CRH) testing. Prior to or shortly after randomization, patients also complete a comprehensive personality assessment. Repeat assessment of the biological measures (fMRI, immune markers, and gene expression products) occurs at an early time-point in treatment, and upon completion of 12-week treatment, when a second Dex/CRH test is also conducted. Patients remitting by the end of this acute treatment phase are then eligible to enter a 21-month follow-up phase, with quarterly visits to monitor for recurrence. Non-remitters are offered augmentation treatment for a second 12-week course of treatment, during which they receive a combination of CBT and antidepressant medication. Predictors of the primary outcome, remission, will be identified for overall and treatment-specific effects, and a statistical model incorporating multiple predictors will be developed to predict outcomes. Discussion The PReDICT study’s evaluation of biological, psychological, and clinical factors that may differentially impact treatment outcomes represents a sizeable step toward developing personalized treatments for MDD. Identified predictors should help guide the selection of initial treatments, and identify those patients most vulnerable to recurrence, who thus warrant maintenance or combination treatments to achieve and maintain wellness. Trial registration Clinicaltrials.gov Identifier: NCT00360399. Registered 02 AUG 2006. First patient randomized 09 FEB 2007.

Abstract Preterm birth is the leading cause of neonatal mortality and perinatal morbidity. The etiology of preterm is multi-factorial and still unclear. As evidence increases for a genetic contribution to PTB, so does the need to explore genomics, transcriptomics, proteomics and metabolomics in its study. This review suggests research guidelines for the conduct of high throughput systems biology investigations into preterm birth with the expectation that this will facilitate the sharing of samples and data internationally through consortia, generating the power needed to study preterm birth using integrated "-omics" technologies. The issues to be addressed include: (1) integrated "-omics" approaches, (2) phenotyping, (3) sample collection, (4) data management-integrative databases, (5) international consortia and (6) translational feasibility. This manuscript is the product of discussions initiated by the "-Omics" Working Group at the Preterm Birth International Collaborative Meeting held at the World Health Organization, Geneva, Switzerland in April 2009.

Abstract Background An aging population, rise in chronic illnesses, increase in life expectancy and shift towards care being provided at the community level are trends that are collectively creating an urgency to advance hospice palliative care (HPC) planning and provision in Canada. The purpose of this study was to analyze the evolution of HPC in seven provinces in Canada so as to inform such planning and provision elsewhere. We have endeavoured to undertake this research out of awareness that good future planning for health and social care, such as HPC, typically requires us to first look backwards before moving forward. Methods To identify key policy and practice events in HPC in Canada, as well as describe facilitators of and barriers to progress, a qualitative comparative case study design was used. Specifically, the evolution and development of HCP in 7 strategically selected provinces is compared. After choosing the case study provinces, the grey literature was searched to create a preliminary timeline for each that described the evolution of HPC beginning in 1970. Key informants (n = 42) were then interviewed to verify the content of each provincial timeline and to discuss barriers and facilitators to the development of HPC. Upon completion of the primary data collection, a face-to-face meeting of the research team was then held so as to conduct a comparative study analysis that focused on provincial commonalities and differences. Results Findings point to the fact that HPC continues to remain at the margins of the health care system. The development of HPC has encountered structural inheritances that have both sped up progress as well as slowed it down. These structural inheritances are: (1) foundational health policies (e.g., the Canada Health Act); (2) service structures and planning (e.g., the dominance of urban-focused initiatives); and (3) health system decisions (e.g., regionalization). As a response to these inheritances, circumventions of the established system of care were taken, often out of necessity. Three kinds of circumventions were identified from the data: (1) interventions to shift the system (e.g., the role of advocacy); (2) service innovations (e.g., educational initiatives); and (3) new alternative structures (e.g., the establishment of independent hospice organizations). Overall, the evolution of HPC across the case study provinces has been markedly slow, but steady and continuous. Conclusions HPC in Canada remains at the margins of the health care system. Its integration into the primary health care system may ensure dedicated and ongoing funding, enhanced access, quality and service responsiveness. Though demographics are expected to influence HPC demand in Canada, our study confirms that concerned citizens, advocacy organizations and local champions will continue to be the agents of change that make the necessary and lasting impacts on HPC in Canada.

Abstract Background Wnt proteins play roles in many biological processes, including axon guidance and cell migration. In the mammalian hindbrain, facial branchiomotor (FBM) neurons undergo a striking rostral to caudal migration, yet little is known of the underlying molecular mechanisms. In this study, we investigated a possible role of Wnts and the planar cell polarity (PCP) pathway in this process. Results Here we demonstrate a novel role for Wnt proteins in guiding FBM neurons during their rostral to caudal migration in the hindbrain. We found that Wnt5a is expressed in a caudalhigh to rostrallow gradient in the hindbrain. Wnt-coated beads chemoattracted FBM neurons to ectopic positions in an explant migration assay. The rostrocaudal FBM migration was moderately perturbed in Wnt5a mutant embryos and severely disrupted in Frizzled3 mutant mouse embryos, and was aberrant following inhibition of Wnt function by secreted Frizzled-related proteins. We also show the involvement of the Wnt/PCP pathway in mammalian FBM neuron migration. Thus, mutations in two PCP genes, Vangl2 and Scribble, caused severe defects in FBM migration. Inhibition of JNK and ROCK kinases strongly and specifically reduced the FBM migration, as well as blocked the chemoattractant effects of ectopic Wnt proteins. Conclusion These results provide in vivo evidence that Wnts chemoattract mammalian FBM neurons and that Wnt5a is a candidate to mediate this process. Molecules of the PCP pathway and the JNK and ROCK kinases also play a role in the FBM migration and are likely mediators of Wnt signalling.

Abstract Background Oxygen toxicity is a major cause of lung injury. The base excision repair pathway is one of the most important cellular protection mechanisms that responds to oxidative DNA damage. Lesion-specific DNA repair enzymes include hOgg1, hMYH, hNTH and hMTH. Methods The above lesion-specific DNA repair enzymes were expressed in human alveolar epithelial cells (A549) using the pSF91.1 retroviral vector. Cells were exposed to a 95% oxygen environment, ionizing radiation (IR), or H2O2. Cell growth analysis was performed under non-toxic conditions. Western blot analysis was performed to verify over-expression and assess endogenous expression under toxic and non-toxic conditions. Statistical analysis was performed using the paired Student's t test with significance being accepted for p < 0.05. Results Cell killing assays demonstrated cells over-expressing hMYH had improved survival to both increased oxygen and IR. Cell growth analysis of A549 cells under non-toxic conditions revealed cells over-expressing hMYH also grow at a slower rate. Western blot analysis demonstrated over-expression of each individual gene and did not result in altered endogenous expression of the others. However, it was observed that O2 toxicity did lead to a reduced endogenous expression of hNTH in A549 cells. Conclusion Increased expression of the DNA glycosylase repair enzyme hMYH in A549 cells exposed to O2 and IR leads to improvements in cell survival. DNA repair through the base excision repair pathway may provide an alternative way to offset the damaging effects of O2 and its metabolites.

Jacksonville, Florida, provides services to persons living with the HIV. A federal call for integrated HIV prevention and treatment was published on June 19, 2015. This study unveils the principles that guided the local response to that call. Service providers have not systematically engaged in strategic planning for system improvement, the absence of which defines the boundaries and properties of the service system. Integration requires a unifying strategy as it draws leaders from their respective silos. Directed leadership, community-based participatory research, and action research provided a science-based framework for integration. Quantitatively, one-third of the planning implementation journey has elapsed, and 46% of the 75 planned activities have either reached fulfillment or are ongoing. Another one-fourth is in progress and slightly more than one-fourth (28%) are pending. Qualitatively, this study recorded 7 system-level changes. Progress to date is a harbinger of future system-level changes.

Vitamin D deficiency is epidemiologically linked to prostate, breast, and colon cancer. When compared with European American (EA) men, African American (AA) men have increased risk of prostate cancer, but few studies evaluate vitamin D status in AA men. The authors evaluate the biological and environmental predictors of vitamin D deficiency in AA and EA men in Chicago, Illinois, a low ultraviolet radiation environment. Blood samples were collected from 492 men, aged between 40 and 79 years, from urology clinics at three hospitals in Chicago, along with demographic and medical information, body mass index, and skin melanin content using a portable narrow-band reflectometer. Vitamin D intake and ultraviolet radiation exposure were assessed using validated questionnaires. The results demonstrated that Black race, cold season of blood draw, elevated body mass index, and lack of vitamin D supplementation increase the risk of vitamin D deficiency. Supplementation is a high-impact, modifiable risk factor. Race and sunlight exposure should be taken into account for recommended daily allowances for vitamin D intake.

Background: The role of altruism in the acceptance of novel preventive healthcare technologies like vaccines has not been thoroughly elucidated., Methods: We 1:1 randomized n = 2004 Amazon Mechanical Turk (MTurk) participants residing in the USA into a control or treatment arm with vaccination decisions framed altruistically, to elicit their preferences for COVID-19 vaccination using web-based discrete choice experiments. We used conditional and mixed logit models to estimate the impact of framing decisions in terms of altruism on vaccination acceptance., Results: Valid responses were provided by 1674 participants (control, n = 848; treatment, n = 826). Framing vaccination decisions altruistically had no significant effect on vaccination acceptance. Further, respondents' degree of altruism had no association with vaccination acceptance., Limitations: The MTurk sample may not be representative of the American population. We were unable to ascertain concordance between stated and revealed preferences., Conclusions and Implications: Framing vaccination decisions in terms of altruism does not appear to significantly influence vaccination acceptance and may not be an effective nudging mechanism to increase the uptake of novel vaccines. Instead, a favorable vaccination profile appears to be the primary driver of uptake., (© The Author(s) 2024. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We examined 3,046,538 acute respiratory infection (ARI) encounters with 6,103 national telehealth physicians from January 2019 to October 2021. The antibiotic prescribing rates were 44% for all ARIs; 46% were antibiotic appropriate; 65% were potentially appropriate; 19% resulted from inappropriate diagnoses; and 10% were related to coronavirus disease 2019 (COVID-19) diagnosis.

Background: There has been research documenting the rising numbers of racial and ethnic minority groups in the United States. With this rise, there is increasing concern over the health disparities that often affect these populations. Attention has turned to how clinicians can improve health outcomes and how the need exists to educate healthcare professionals on the practice of cultural competence. Here we present one successful approach for teaching cultural competence in the healthcare curriculum with the development of an educational session on cultural competence consisting of case-based, role-play exercises, class group discussions, online discussion boards, and a lecture PowerPoint presentation., Methods: Cultural competence sessions were delivered in a pre-dental master's program to 178 students between 2017 and 2020. From 2017 to 2019, the sessions were implemented as in-person, case-based, role-play exercises. In 2020, due to in-person limitations caused by the COVID-19 pandemic, students were asked to read the role-play cases and provide a reflection response using the online Blackboard Learn discussion board platform. Evaluation of each session was performed using post-session survey data., Results: Self-reported results from 2017 to 2020 revealed that the role-play exercises improved participant's understanding of components of cultural competence such as communication in patient encounters (95%), building rapport with patients (94%), improving patient interview skills (95%), and recognition of students own cultural biases when working with patients (93%)., Conclusions: Students were able to expand their cultural awareness and humility after completion of both iterations of the course session from 2017 to 2019 and 2020. This session can be an effective method for training healthcare professionals on cultural competence., (© 2024. The Author(s).)

Prior work has demonstrated that personalized letters are effective at reducing opioid and benzodiazepine prescribing, but it is unclear whether If/when-then planning prompts would enhance this effect. We conducted a decedent-clustered trial which randomized 541 clinicians in Los Angeles County to receive a standard (n = 284), or comparator (n = 257) version of a letter with If/when-then prompts. We found a significant 12.85% (6.83%, 18.49%) and 8.32% (2.34%, 13.93%) decrease in the primary outcomes morphine (MME) and diazepam milligram equivalents (DME), respectively. This study confirms the benefit of planning prompts, and repeat letter exposure among clinicians with poor patient outcomes. Limitations include lack of generalizability and small sample size. Clinicaltrials.gov registration: NCT03856593., (© 2024. The Author(s).)

Thrombin is an enzyme produced during blood coagulation that is crucial to the formation of a stable clot. Thrombin cleaves soluble fibrinogen into fibrin, which polymerizes and forms an insoluble, stabilizing gel around the growing clot. A small fraction of circulating fibrinogen is the variant γA/γ', which has been associated with high-affinity thrombin binding and implicated as a risk factor for myocardial infarctions, deep vein thrombosis, and coronary artery disease. Thrombin is also known to be strongly sequestered by polymerized fibrin for extended periods of time in a way that is partially regulated by γA/γ'. However, the role of γA/γ'-thrombin interactions during fibrin polymerization is not fully understood. Here, we present a mathematical model of fibrin polymerization that considered the interactions between thrombin, fibrinogen, and fibrin, including those with γA/γ'. In our model, bivalent thrombin-fibrin binding greatly increased thrombin residency times and allowed for thrombin-trapping during fibrin polymerization. Results from the model showed that early in fibrin polymerization, γ' binding to thrombin served to localize the thrombin to the fibrin(ogen), which effectively enhanced the enzymatic conversion of fibrinogen to fibrin. When all the fibrin was fully generated, however, the fibrin-thrombin binding persisted but the effect of fibrin on thrombin switched quickly to serve as a sink, essentially removing all free thrombin from the system. This dual role for γ'-thrombin binding during polymerization led to a paradoxical decrease in trapped thrombin as the amount of γ' was increased. The model highlighted biochemical and biophysical roles for fibrin-thrombin interactions during polymerization and agreed well with experimental observations., Competing Interests: The authors have declared that no competing interests exist.

Alien limb phenomenon (ALP) is a clinical finding seen in numerous neurological disorders, including Creutzfeldt-Jakob disease (CJD). We aimed to conduct a systematic review to update advances in understanding the classification and pathophysiology of ALP in CJD. We used PubMed advanced-strategy searches and only included full-text observational studies and case reports conducted on humans and written in English. We used the PRISMA protocol for this systematic review and the Methodological Quality of Case Reports tool to assess the bias encountered in each study. After applying the inclusion/exclusion criteria, 10 case reports were reviewed. Two independent reviewers analyzed data and confirmed the phenotype of each case of the alien limb in CJD separately. Overall, the most prevalent ALP phenotype presenting in patients with CJD was the posterior phenotype, usually in the early stages of the disease. Our findings corroborate previous research in demonstrating the pathophysiology behind ALP in CJD. We suggest physicians suspect CJD whenever patients present with ALP as the initial symptom., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Sen et al.)

Objectives: Since 2020, COVID-19 has infected tens of millions and caused hundreds of thousands of fatalities in the United States. Infection waves lead to increased emergency department utilization and critical care admission for patients with respiratory distress. Although many individuals develop symptoms necessitating a ventilator, some patients with COVID-19 can remain at home to mitigate hospital overcrowding. Remote pulse-oximetry (pulse-ox) monitoring of moderately ill patients with COVID-19 can be used to monitor symptom escalation and trigger hospital visits, as needed., Methods: We analyzed the cost-utility of remote pulse-ox monitoring using a Markov model with a 3-week time horizon and daily cycles from a US health sector perspective. Costs (US dollar 2020) and outcomes were derived from the University Hospitals' real-world evidence and published literature. Costs and quality-adjusted life-years (QALYs) were used to determine the incremental cost-effectiveness ratio at a cost-effectiveness threshold of $100 000 per QALY. We assessed model uncertainty using univariate and probabilistic sensitivity analyses., Results: Model results demonstrated that remote monitoring dominates current standard care, by reducing costs ($11 472 saved) and improving outcomes (0.013 QALYs gained). There were 87% fewer hospitalizations and 77% fewer deaths among patients with access to remote pulse-ox monitoring. The incremental cost-effectiveness ratio was not sensitive to uncertainty ranges in the model., Conclusions: Patient with COVID-19 remote pulse-ox monitoring increases the specificity of those requiring follow-up care for escalating symptoms. We recommend remote monitoring adoption across health systems to economically manage COVID-19 volume surges, maintain patients' comfort, reduce community infection spread, and carefully monitor needs of multiple individuals from one location by trained experts., (Copyright © 2021 International Society for Pharmacoeconomics and Outcomes Research, Inc. Published by Elsevier Inc. All rights reserved.)

This article provides an overview of the social determinants of adolescents and young adults' (AYAs') sexual and reproductive health (SRH), from a global health perspective. The status of AYAs' SRH constitutes leading health indicators across nations and globally, and reveals the well-being of this population. Throughout the article, AYAs' SRH is approached from a health equity perspective, which includes SRH health rights and reproductive justice. Using this health equity lens, salient topics are presented: sexual abuse/assault among AYAs; immigrant and refugee populations; child, early, and forced marriage; human trafficking; and female genital mutilation. The article also discusses access to SRH services and comprehensive education. Practical implications and resources are offered for healthcare providers for their daily encounters with AYAs, as well as for community, institutional level, and advocacy action. Healthcare providers are well positioned to advance AYAs SRH through mitigating inequities and in so doing, they are assuring the health of the population and future generations., Competing Interests: Y.E. is an employee of the Gates Foundation at the time of writing; however, the views expressed do not necessarily represent the views of the Gates Foundation., (Thieme. All rights reserved.)

Background: High levels of opioid prescribing in the United States has resulted in an alarming trend in opioid-related harms. The objective of Trial 2 of the Application of Economics & Social psychology to improve Opioid Prescribing Safety (AESOPS-2) is to dampen the intensity and frequency of opioid prescribing in accordance with the Centers for Disease Control and Prevention recommendation to "go low and slow". We aim to accomplish this by notifying clinicians of harmful patient outcomes, which we expect to increase the mental availability of risks associated with opioid use., Methods: The trial is multi-site. Random assignment determines if prescribers to persons who suffer an opioid overdose (fatal or nonfatal) learn of this event (intervention) or practice usual care (control). Clinicians in the intervention group receive a letter notifying them of their patient's overdose. The primary outcome is the change in clinician weekly milligram morphine equivalent (MME) prescribed in a 6-month period before and after receiving the letter. Additional outcomes are the change in the proportion of patients prescribed at least 50 daily MME and in the proportion of patients referred to medication assisted treatment. Group differences in these outcomes will be compared using an intent-to-treat difference-in-differences framework with a mixed-effects regression model to estimate clinician MME., Discussion: The AESOPS-2 trial will provide new knowledge about whether increasing prescribers' awareness of patients' opioid-related overdoses leads to a reduction in opioid prescribing. Additionally, this trial may better inform how to reduce opioid use disorder and opioid overdoses by lowering population exposure to these drugs., Trial Registration: ClinicalTrials.gov: NCT04758637., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Opioid-related morbidity and mortality has increased during the COVID-19 pandemic, yet specific information about the communities most affected remains unknown. Our objective is to evaluate decedent-level associations with an opioid-related death following the implementation of stay-at-home orders in Los Angeles County., Methods: This retrospective cohort study used data from the L.A. County Medical Examiner-Coroner to identify opioid-related deaths in 2019 and 2020. We used logistic regression to analyze the change in opioid-related deaths following a 30-day washout period after the start of stay-at-home orders. Independent variables included decedent age, gender, race and ethnicity, heroin or fentanyl present at the time of death, census tract-level education, and a scheduled drug prescription in the year before death., Results: Opioid-related deaths in L.A. County are most common in census tracts where a small percentage of the population has a Bachelor's degree. Following stay-at-home orders, Non-Hispanic Caucasian individuals had significantly more opioid-related deaths than Hispanic individuals (risk ratio (RR): 1.82 [95 % CI, 1.10-3.02]; P < 0.05) after adjusting for age, gender, and heroin or fentanyl use. Racial and ethnic differences in mortality were not explained by census tract-level education or recent scheduled drug prescriptions., Discussion: There has been an alarming rise in opioid-related deaths in L.A. County during 2020. The increase in opioid-related overdose deaths following the onset of COVID-19 and related policies occurred most often among Non-Hispanic Caucasian individuals. Further research on this trend's underlying cause is needed to inform policy recommendations during these simultaneous public health crises., (Copyright © 2021. Published by Elsevier B.V.)

This study examined whether various levels of physical activity among older adults predicted levels of depression and whether there were racial differences in the levels and types of physical activities engaged in by adults aged 50 and older., Method: Data from the 2015-2016 National Health and Nutrition Examination Survey (NHANES) were analyzed for 2,474 adults aged 50 years and older. Variables of focus were demographics, physical activity and depression, assessed using the Physical Activity Questionnaire and the Mental Health - Depression Screener., Results: There was a significant positive relationship between income and depression; individuals with higher income had lower levels of depression. Simple linear regression revealed income significantly predicted depression scores, b = -.20, F(1, 2296) = 96.35, p < .001, explaining 4% of the variance, R2 = .04. As age increased, all levels of physical activity declined, regardless of the category. Vigorous recreation-related activity and moderate recreation-related activity each made significant, unique contributions to depression scores., Conclusion: Findings from the current study suggest that physical activity interventions should be culturally appropriate and tailored to the needs and abilities of individual older adults to maximize benefits and minimize adverse events, particularly among community dwelling older adults.

Background: There is a lack of evidence that long-term opioid use offers benefit for noncancer pain and an abundance of evidence of harm. Despite clinical guidelines and education, prescribing continues at a higher rate than before the opioids crisis. The objective of trial 1 of the Application of Economics & Social psychology to improve Opioid Prescribing Safety (AESOPS-1) is to discourage unnecessary opioid prescribing in primary care by applying "behavioral insights"-empirically-tested social and psychological interventions that affect choice., Methods: AESOPS-1 randomizes primary care clinics in Illinois and California to behavioral intervention or control. Both arms receive opioid guideline education. Clinics randomized to the behavioral intervention arm receive nudges within the electronic health record (EHR) including: 1) an "accountable justification" entered in the chart, 2) a precommitment to address high-risk prescriptions, and 3) a "PainTracker" that broadens discussions about pain. The control arm receives no EHR-based intervention. The primary outcome is the change in weekly milligram morphine equivalents (MME) prescribed. The secondary outcome is the change in the proportion of patients prescribed at least 50 daily MME. To evaluate these outcomes, we will use a difference-in-differences mixed-effects regression model on clinician MME weekly or daily dose. The analysis will be "intent-to-treat." The intervention period is 18-months, with a 6-month follow-up period to measure persistence of effects., Discussion: The AESOPS-1 trial will evaluate the effect of EHR-based interventions in reducing noncancer opioid prescribing in primary care. AESOPS-1 may demonstrate practical and scalable strategies to lower unnecessary population exposure to opioids., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Small fiber neuropathy (SFN) is a type of peripheral neuropathy that occurs from damage to the small A-delta and C nerve fibers that results in the clinical condition known as SFN. This pathology may be the result of metabolic, toxic, immune-mediated, and/or genetic factors. Small fiber symptoms can be variable and inconsistent and therefore require an objective biomarker confirmation. Small fiber dysfunction is not typically captured by diagnostic tests for large-fiber neuropathy (nerve conduction and electromyographic study). Therefore, skin biopsies stained with PGP 9.5 are the universally recommended objective test for SFN, with quantitative sensory tests, autonomic function testing, and corneal confocal imaging as secondary or adjunctive choices. Fibromyalgia (FM) is a heterogenous syndrome that has many symptoms that overlap with those found in SFN. A growing body of research has shown approximately 40-60% of patients carrying a diagnosis of FM have evidence of SFN on skin punch biopsy. There is currently no clearly defined phenotype in FM at this time to suggest whom may or may not have SFN, though research suggests it may correlate with severe cases. The skin punch biopsy provides an objective tool for use in quantifying small fiber pathology in FM. Skin punch biopsy may also be repeated for surveillance of the disease as well as measuring response to treatments. Evaluation of SFN in FM allows for better classification of FM and guidance for patient care as well as validation for their symptoms, leading to better use of resources and outcomes.