Parents' Discussions of the COVID-19 Pandemic and Death With Young Children.

Death and loss are often uncomfortable topics for adults to discuss with young children. Disruptions caused by the COVID-19 pandemic, however, made the avoidance of these topics nearly impossible. The current study explored how 20 parents engaged with their young children (ages 3-6) in discussions about death, dying, and loss as they jointly experienced this global crisis. Interviews were conducted both prepandemic (Summer/Fall 2019) and a year later, at the early stage of the COVID-19 pandemic, before vaccines were approved (Summer 2020). Results suggest parents largely sought to balance sheltering children from stress and socializing them with socioemotional competencies. The pandemic context, however, brought parents a sense of urgency to scaffold their children's ability to remain resilient after experiencing losses. Practical implications are discussed regarding how family nurses and other practitioners can provide support to families of young children during the COVID-19 pandemic and potential future global crises.

Family Structure Diversity and Youth Health Care Access and Interactions With Health Care Providers.

Using data from the 2019 National Survey of Children's Health, we evaluated family structure differences in youth health care access and experiences. We found youth living with their married biological/adoptive parents generally had greater health care access than youth living in structurally diverse families. Differences, however, varied based on which aspect of health care access was examined and the specific types of structurally diverse families youth were living in. Youth living in single-father and other relative-headed families showed the most consistent differences in health care access from youth living with their married biological/adoptive parents. In terms of health care experiences, youth living in several structurally diverse families were more likely to have had time alone with health care providers. Furthermore, there were differences in family-centered care, but the effect size and magnitude of the differences were small.

Evaluation of 8-Channel Radiative Antenna Arrays for Human Head Imaging at 10.5 Tesla.

For human head magnetic resonance imaging at 10.5 tesla (T), we built an 8-channel transceiver dipole antenna array and evaluated the influence of coaxial feed cables. The influence of coaxial feed cables was evaluated in simulation and compared against a physically constructed array in terms of transmit magnetic field (B1+) and specific absorption rate (SAR) efficiency. A substantial drop (23.1% in simulation and 20.7% in experiment) in B1+ efficiency was observed with a tight coaxial feed cable setup. For the investigation of the feed location, the center-fed dipole antenna array was compared to two 8-channel end-fed arrays: monopole and sleeve antenna arrays. The simulation results with a phantom indicate that these arrays achieved ~24% higher SAR efficiency compared to the dipole antenna array. For a human head model, we observed 30.8% lower SAR efficiency with the 8-channel monopole antenna array compared to the phantom. Importantly, our simulation with the human model indicates that the sleeve antenna arrays can achieve 23.8% and 21% higher SAR efficiency compared to the dipole and monopole antenna arrays, respectively. Finally, we obtained high-resolution human cadaver images at 10.5 T with the 8-channel sleeve antenna array.

Parents' Anticipated Discussions About Death With Young Children.

Guided by family communication patterns theory and terror management theory this mixed-methods investigation explored how parents (N = 112) of young children (ages 3-6) described the way they would discuss death when it comes up in conversations. Responses were coded inductively, resulting in four themes: explanations that death is inevitable, explanations that death is in the distance, the use of religion to frame discussions of death, and finally, discussing afterlife connections to deceased family members. Logistic regression analyses were used to evaluate whether parents' conformity or conversation orientations were associated with the frequency with which parents discussed death with their child and the content of parent vignette responses. Quantitative analysis revealed parents' conversation orientations were associated with the frequency with which they discussed death with their child and conformity orientations were associated with parents' use of religion and discussing afterlife connections to deceased family members in their responses.

Family-Centered Care and Positive Developmental Outcomes for Youth With Special Health Care Needs: Variations Across Family Structures.

Drawing on a social determinants of health framework, we evaluated associations between perceived family-centered care (FCC) and positive developmental outcomes for youth with special health care needs across six different family structures (married biological families, cohabiting biological families, married stepfamilies, cohabiting stepfamilies, divorced/separated single-mother families, and never-married single-mother families). Using data from the 2011-2012 National Survey of Children's Health, we found that married biological families perceive greater FCC than do other family structures. Perceived FCC was positively associated with all three positive youth outcomes evaluated (children's health, participation in extracurricular activities, and flourishing) in married biological families, and two of the three outcomes (children's health and flourishing) in married stepfamilies and divorced/separated single-mother families. Implications for health care provision and future research with structurally diverse families are discussed.

Divorce and Childhood Chronic Illness: A Grounded Theory of Trust, Gender, and Third-Party Care Providers.

Divorced parents face distinct challenges in providing care for chronically ill children. Children's residence in two households necessitates the development of family-specific strategies to ensure coparents' supervision of regimen adherence and the management of children's health care. Utilizing a risk and resilience perspective, a grounded theory study was conducted with 14 divorced parents of children with chronic illnesses. The importance of trust, gender, and relationships with third-party care providers emerged as key themes related to the development of effective coparenting relationships for maintaining children's health. Divorced parents were best able to support the management of their children's chronic conditions when care providers operated as neutral third parties and intermediaries. Collaborative family care may require health care practitioners to avoid being drawn into contentious inter-parental conflicts.

Faster replication and higher expression levels of viral glycoproteins give the vesicular stomatitis virus/measles virus hybrid VSV-FH a growth advantage over measles virus.

UNLABELLED: VSV-FH is a hybrid vesicular stomatitis virus (VSV) with a deletion of its G glycoprotein and encoding the measles virus (MV) fusion (F) and hemagglutinin (H) envelope glycoproteins. VSV-FH infects cells expressing MV receptors and is fusogenic and effective against myeloma xenografts in mice. We evaluated the fusogenic activities of MV and VSV-FH in relationship to the density of receptor on the target cell surface and the kinetics of F and H expression in infected cells. Using a panel of cells expressing increasing numbers of the MV receptor CD46, we evaluated syncytium size in MV- or VSV-FH-infected cells. VSV-FH is not fusogenic at low CD46 density but requires less CD46 for syncytium formation than MV. The size of each syncytium is larger in VSV-FH-infected cells at a specific CD46 density. While syncytium size reached a plateau and did not increase further in MV-infected CHO cells expressing ≥4,620 CD46 copies/cell, there was a corresponding increase in syncytium size with increases in CD46 levels in VSV-FH-infected CD46-expressing CHO (CHO-CD46) cells. Further analysis in VSV-FH-infected cell lines shows earlier and higher expression of F and H mRNAs and protein. However, VSV-FH cytotoxic activity was reduced by pretreatment of the cells with type I interferon. In contrast, the cytopathic effects are not affected in MV-infected cells. In summary, VSV-FH has significant advantages over MV as an oncolytic virus due to its higher viral yield, faster replication kinetics, and larger fusogenic capabilities but should be used in cancer types with defective interferon signaling pathways. IMPORTANCE: We studied the cytotoxic activity of a vesicular stomatitis/measles hybrid virus (VSV-FH), which is superior to that of measles virus (MV), in different cancer cell lines. We determined that viral RNA and protein were produced faster and in higher quantities in VSV-FH-infected cells. This resulted in the formation of larger syncytia, higher production of infectious particles, and a more potent cytopathic effect in permissive cells. Importantly, VSV-FH, similar to MV, can discriminate between low- and high-expressing CD46 cells, a phenotype important for cancer therapy as the virus will be able to preferentially infect cancer cells that overexpress CD46 over low-CD46-expressing normal cells.

Effects of CCN1 and Macrophage Content on Glioma Virotherapy: A Mathematical Model.

Oncolytic virus (OV) is a genetically engineered virus that can selectively replicate in and kill tumor cells while not harming normal cells. OV therapy has been explored as a treatment for numerous cancers including glioblastoma, an aggressive and devastating brain tumor. Experiments show that extracellular matrix protein CCN1 limits OV therapy of glioma by orchestrating an antiviral response and enhancing the proinflammatory activation and migration of macrophages. Neutralizing CCN1 by antibody has been demonstrated to improve OV spread and tends to increase the time to disease progression. In this paper, we develop a mathematical model to investigate the effects of CCN1 on the treatment of glioma with oncolytic herpes simplex virus. We show that numerical simulations of the model are in agreement with the experimental results and then use the model to explore the anti-tumor effects of combining antibodies with OV therapy. Model simulations suggest that the macrophage content of the tumor is a critical factor to the success of OV therapy and to the reduction in tumor volume gained with the CCN1 antibody.

Role of cysteine-rich 61 protein (CCN1) in macrophage-mediated oncolytic herpes simplex virus clearance.

Glioblastoma is a devastating disease, and there is an urgent need to develop novel therapies, such as oncolytic HSV1 (OV) to effectively target tumor cells. OV therapy depends on tumor-specific replication leading to destruction of neoplastic tissues. Host responses that curtail virus replication limit its efficacy in vivo. We have previously shown that cysteine-rich 61 protein (CCN1) activates a type 1 IFN antiviral defense response in glioblastoma cells. Incorporating TCGA data, we found CCN1 expression to be a negative prognostic factor for glioblastoma patients. Based on this, we used neutralizing antibodies against CCN1 to investigate its effect on OV therapy. Use of an anti-CCN1 antibody in mice bearing glioblastomas treated with OV led to enhanced virus expression along with reduced immune cell infiltration. OV-induced CCN1 increases macrophage migration toward infected glioblastoma cells by directly binding macrophages and also by enhancing the proinflammatory activation of macrophages inducing MCP-1 expression in glioblastoma cells. Activation of macrophages by CCN1 also increases viral clearance. Neutralization of integrin αMß2 reversed CCN1-induced macrophage activation and migration, and reduced MCP-1 expression by glioblastoma cells. Our findings reveal that CCN1 plays a novel role in pathogen clearance; increasing macrophage infiltration and activation resulting in increased virus clearance in tumors.

Evaluating the Dyadic Benefits of Early-Phase Behavioral Interventions: An Exemplar Using Data From Couples Living With Parkinson's Disease.

BACKGROUND AND OBJECTIVES: There are a growing number of early-phase (i.e., Stage I, NIH Stage Model) interventions targeted at family care dyads navigating chronic health conditions in older adults. Currently, the benefits of these interventions are often evaluated for older adults and their family care partners separately, even when controlling for interdependence. Without understanding the benefits (and potential harms) for dyads as a whole, understanding of program impact is incomplete. Moreover, few health behavior interventions involving dyads include relational measures to ensure no unintended consequences for the dyad or account for within-dyad pretest risk level. RESEARCH DESIGN AND METHODS: We used secondary data from a quasi-experimental trial involving 39 couples in which 1 member of the dyad was living with Parkinson's disease as an exemplar demonstration of 3 proposed approaches: an above-zero approach, a pretest risk status approach, and an expanded pattern analysis matrix approach. RESULTS: Approaches provided evidence for dyadic benefits of the intervention compared to the wait-list comparison condition, but carried different assumptions that did not always categorize dyads similarly. DISCUSSION AND IMPLICATIONS: Implications of using each approach and selecting different benchmarks for defining success are discussed. The descriptive approaches proposed, provide a rationale for more intentional evaluation of small-sample, early-phase dyadic interventions.

College students' intentions to assist peers with chronic medical conditions.

Objective This study identified influences on college students' intentions to assist peers with chronic medical conditions. Participants: A panel of 293 U.S. full-time college students completed online surveys in July, 2017. Methods: Participants reported the number of people they knew with chronic medical conditions, and completed measures of general empathy, stigma toward chronic conditions, self-efficacy to provide support, and expected likelihood of assisting a peer with a chronic medical condition. Path Analysis and mediation tests were performed. Results: Low stigma, and high confidence in providing support were directly associated with intentions to assist student peers if needed. Empathy and number of people known with chronic conditions were additional indirect predictors. Conclusions: Peer support is important for students with chronic medical conditions. Intention to provide assistance if needed is partially explained by holding low stigma and high confidence in providing support, both of which may be enhanced through education and intervention.

Family functioning, contributions to college expenses, access to mentors, and college student's health and flourishing: Examining moderation by family structure.

Objective: To evaluate how family functioning, family contributions to college expenses, and access to mentors are associated with college student's self-reported health and flourishing, and to test for moderation by family structure. Participants: Undergraduate college students (N = 238) recruited through an email list-serve at a large midwestern state university. Methods: Participants completed an online survey (distributed through Qualtrics) in February 2020. Data were analyzed using linear regression (in SPSS 28) and simple slope analyses. Results: College students' access to mentors is associated with their self-reported health, and family structure moderates the association between family strengths and self-reported health. Family functioning and access to mentors are both associated with college students' flourishing. Conclusions: College students' health and flourishing may benefit from access to mentors and functional family dynamics. Though students from post-divorce families see fewer benefits from family strengths compared to peers in nuclear biological families.

Boosting of SARS-CoV-2 immunity in nonhuman primates using an oral rhabdoviral vaccine.

An orally active vaccine capable of boosting SARS-CoV-2 immune responses in previously infected or vaccinated individuals would help efforts to achieve and sustain herd immunity. Unlike mRNA-loaded lipid nanoparticles and recombinant replication-defective adenoviruses, replicating vesicular stomatitis viruses with SARS-CoV-2 spike glycoproteins (VSV-SARS2) were poorly immunogenic after intramuscular administration in clinical trials. Here, by G protein trans-complementation, we generated VSV-SARS2(+G) virions with expanded target cell tropism. Compared to parental VSV-SARS2, G-supplemented viruses were orally active in virus-naive and vaccine-primed cynomolgus macaques, powerfully boosting SARS-CoV-2 neutralizing antibody titers. Clinical testing of this oral VSV-SARS2(+G) vaccine is planned.

Characteristics and comparative clinical outcomes of prisoner versus non-prisoner populations hospitalized with COVID-19.

Prisons in the United States have become a hotbed for spreading COVID-19 among incarcerated individuals. COVID-19 cases among prisoners are on the rise, with more than 143,000 confirmed cases to date. However, there is paucity of data addressing clinical outcomes and mortality in prisoners hospitalized with COVID-19. An observational study of all patients hospitalized with COVID-19 between March 10 and May 10, 2020 at two Henry Ford Health System hospitals in Michigan. Clinical outcomes were compared amongst hospitalized prisoners and non-prisoner patients. The primary outcomes were intubation rates, in-hospital mortality, and 30-day mortality. Multivariable logistic regression and Cox-regression models were used to investigate primary outcomes. Of the 706 hospitalized COVID-19 patients (mean age 66.7 ± 16.1 years, 57% males, and 44% black), 108 were prisoners and 598 were non-prisoners. Compared to non-prisoners, prisoners were more likely to present with fever, tachypnea, hypoxemia, and markedly elevated inflammatory markers. Prisoners were more commonly admitted to the intensive care unit (ICU) (26.9% vs. 18.7%), required vasopressors (24.1% vs. 9.9%), and intubated (25.0% vs. 15.2%). Prisoners had higher unadjusted inpatient mortality (29.6% vs. 20.1%) and 30-day mortality (34.3% vs. 24.6%). In the adjusted models, prisoner status was associated with higher in-hospital death (odds ratio, 2.32; 95% confidence interval (CI), 1.33 to 4.05) and 30-day mortality (hazard ratio, 2.00; 95% CI, 1.33 to 3.00). In this cohort of hospitalized COVID-19 patients, prisoner status was associated with more severe clinical presentation, higher rates of ICU admissions, vasopressors requirement, intubation, in-hospital mortality, and 30-day mortality.

Comparison of 16-Channel Asymmetric Sleeve Antenna and Dipole Antenna Transceiver Arrays at 10.5 Tesla MRI.

Multi-element transmit arrays with low peak 10 g specific absorption rate (SAR) and high SAR efficiency (defined as ( [Formula: see text]SAR [Formula: see text] are essential for ultra-high field (UHF) magnetic resonance imaging (MRI) applications. Recently, the adaptation of dipole antennas used as MRI coil elements in multi-channel arrays has provided the community with a technological solution capable of producing uniform images and low SAR efficiency at these high field strengths. However, human head-sized arrays consisting of dipole elements have a practical limitation to the number of channels that can be used due to radiofrequency (RF) coupling between the antenna elements, as well as, the coaxial cables necessary to connect them. Here we suggest an asymmetric sleeve antenna as an alternative to the dipole antenna. When used in an array as MRI coil elements, the asymmetric sleeve antenna can generate reduced peak 10 g SAR and improved SAR efficiency. To demonstrate the advantages of an array consisting of our suggested design, we compared various performance metrics produced by 16-channel arrays of asymmetric sleeve antennas and dipole antennas with the same dimensions. Comparison data were produced on a phantom in electromagnetic (EM) simulations and verified with experiments at 10.5 Tesla (T). The results produced by the 16-channel asymmetric sleeve antenna array demonstrated 28 % lower peak 10 g SAR and 18.6 % higher SAR efficiency when compared to the 16-channel dipole antenna array.

Oncolytic herpes simplex virus infects myeloma cells in vitro and in vivo.

Because most patients with multiple myeloma (MM) develop resistance to current regimens, novel approaches are needed. Genetically modified, replication-competent oncolytic viruses exhibit high tropism for tumor cells regardless of cancer stage and prior treatment. Receptors of oncolytic herpes simplex virus 1 (oHSV-1), NECTIN-1, and HVEM are expressed on MM cells, prompting us to investigate the use of oHSV-1 against MM. Using oHSV-1-expressing GFP, we found a dose-dependent increase in the GFP+ signal in MM cell lines and primary MM cells. Whereas NECTIN-1 expression is variable among MM cells, we discovered that HVEM is ubiquitously and highly expressed on all samples tested. Expression of HVEM was consistently higher on CD138+/CD38+ plasma cells than in non-plasma cells. HVEM blocking demonstrated the requirement of this receptor for infection. However, we observed that, although oHSV-1 could efficiently infect and kill all MM cell lines tested, no viral replication occurred. Instead, we identified that oHSV-1 induced MM cell apoptosis via caspase-3 cleavage. We further noted that oHSV-1 yielded a significant decrease in tumor volume in two mouse xenograft models. Therefore, oHSV-1 warrants exploration as a novel potentially effective treatment option in MM, and HVEM should be investigated as a possible therapeutic target.

Stromal Platelet-Derived Growth Factor Receptor-ß Signaling Promotes Breast Cancer Metastasis in the Brain.

Platelet-derived growth factor receptor-beta (PDGFRß) is a receptor tyrosine kinase found in cells of mesenchymal origin such as fibroblasts and pericytes. Activation of this receptor is dependent on paracrine ligand induction, and its preferred ligand PDGFB is released by neighboring epithelial and endothelial cells. While expression of both PDGFRß and PDGFB has been noted in patient breast tumors for decades, how PDGFB-to-PDGFRß tumor-stroma signaling mediates breast cancer initiation, progression, and metastasis remains unclear. Here we demonstrate this paracrine signaling pathway that mediates both primary tumor growth and metastasis, specifically, metastasis to the brain. Elevated levels of PDGFB accelerated orthotopic tumor growth and intracranial growth of mammary tumor cells, while mesenchymal-specific expression of an activating mutant PDGFRß (PDGFRßD849V) exerted proproliferative signals on adjacent mammary tumor cells. Stromal expression of PDGFRßD849V also promoted brain metastases of mammary tumor cells expressing high PDGFB when injected intravenously. In the brain, expression of PDGFRßD849V was observed within a subset of astrocytes, and aged mice expressing PDGFRßD849V exhibited reactive gliosis. Importantly, the PDGFR-specific inhibitor crenolanib significantly reduced intracranial growth of mammary tumor cells. In a tissue microarray comprised of 363 primary human breast tumors, high PDGFB protein expression was prognostic for brain metastases, but not metastases to other sites. Our results advocate the use of mice expressing PDGFRßD849V in their stromal cells as a preclinical model of breast cancer-associated brain metastases and support continued investigation into the clinical prognostic and therapeutic use of PDGFB-to-PDGFRß signaling in women with breast cancer. SIGNIFICANCE: These studies reveal a previously unknown role for PDGFB-to-PDGFRß paracrine signaling in the promotion of breast cancer brain metastases and support the prognostic and therapeutic clinical utility of this pathway for patients.See related article by Wyss and colleagues, p. 594.