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, benefits of these interventions are often evaluated for older adults and their family care partners separately, even when controlling for interdependence. Without understanding 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 pre-test risk level. RESEARCH DESIGN AND METHODS: We used secondary data from a quasi-experimental trial involving 39 couples in which one member of the dyad was living with Parkinson's Disease as an exemplar demonstration of three proposed approaches: an above-zero approach, a pre-test 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 carry 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 rationale for more intentional evaluation of small-sample, early-phase dyadic interventions.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Evaluation of a 16-channel transceiver loop + dipole antenna array for human head imaging at 10.5 tesla.

We evaluated a 16-channel loop + dipole (LD) transceiver antenna array with improved specific absorption rate (SAR) efficiency for 10.5 Tesla (T) human head imaging apsplications. Three different array designs with equal inner dimensions were considered: an 8-channel dipole antenna, an 8-channel loop, and a 16-channel LD antenna arrays. Signal-to-noise ratio (SNR) and B1 + efficiency (in units of µT per √W) were simulated and measured in 10.5 T magnetic resonance imaging (MRI) experiments. For the safety validation, 10 g SAR and SAR efficiency (defined as the B1 + over √ (peak 10 g SAR)) were calculated through simulation. Finally, high resolution porcine brain images were acquired with the 16-channel LD antenna array, including a fast turbo-spin echo (TSE) sequence incorporating B1 shimming techniques. Both the simulation and experiments demonstrated that the combined 16-channel LD antenna array showed similar B1 + efficiency compared to the 8-channel dipole antenna and the 8-channel loop arrays in a circular polarized (CP) mode. In a central 2 mm × 2 mm region of the phantom, however, the 16-channel LD antenna array showed an improvement in peak 10 g SAR of 27.5 % and 32.5 % over the 8-channel dipole antenna and the 8-channel loop arrays, respectively. We conclude that the proposed 16-channel head LD antenna array design is capable of achieving ~7% higher SAR efficiency at 10.5 T compared to either the 8-channel loop-only or the 8-channel dipole-only antenna arrays of the same dimensions.

Oncolytic Viruses: Priming Time for Cancer Immunotherapy.

New immuno-oncology therapies are improving cancer treatments beyond the former standard of care, as evidenced by the recent and continuing clinical approvals for immunotherapies in a broad range of indications. However, a majority of patients (particularly those with immunologically cold tumors) still do not benefit, highlighting the need for rational combination approaches. Oncolytic viruses (OV) both directly kill tumor cells and inflame the tumor microenvironment. While OV spread can be limited by the generation of antiviral immune responses, the initial local tumor cell killing can reverse the immunosuppressive tumor microenvironment, resulting in more effective release of tumor-associated antigens (TAAs), cross-presentation, and antitumoral effector T cell recruitment. Moreover, many OVs can be engineered to express immunomodulatory genes. Rational combination approaches to cancer immunotherapy include the use of OVs in combination with immune checkpoint inhibitors (ICIs) or adoptive T cell therapy (ACT) to promote sustained antitumoral immune responses. OV combinations have additive or synergistic efficacy in preclinical tumor models with ICIs or ACT. Several preclinical studies have confirmed systemic reactivation and proliferation of adoptively transferred antitumoral T cells in conjunction with oncolytic OVs (expressing cytokines or TAAs) resulting from the specific tumor cell killing and immunostimulation of the tumor microenvironment which leads to increased tumor trafficking, activity, and survival. Recent clinical trials combining OVs with ICIs have shown additive effects in melanoma. Additional clinical data in an expanded range of patient indications are eagerly awaited. The relative timings of OV and ICI combination remains under-studied and is an area for continued exploration. Studies systematically exploring the effects of systemic ICIs prior to, concomitantly with, or following OV therapy will aid in the future design of clinical trials to enhance efficacy and increase patient response rates.

Stepfathers' affinity-seeking with stepchildren, stepfather-stepchild relationship quality, marital quality, and stepfamily cohesion among stepfathers and mothers.

Because of the potential stepparent-stepchild relationships have for tension and conflict, clinicians have identified the development of a positive stepparent-stepchild connection as one of the major tasks of stepfamily life. Stepparents often are advised to focus initially on developing friendships with stepchildren, or seeking affinity with them, particularly early in the life of the relationship. Both family systems theory and evolutionary theory suggest that stepparents' affinity-seeking behaviors are related to the quality and functioning of other stepfamily dyads, such as couple relationships, and the whole stepfamily. We extend prior work on stepparents' affinity seeking by including perceptions of both members of the stepcouple about affinity seeking, stepfather-stepchild conflicts, couple relationship quality, and stepfamily cohesion. Stepfathers and mothers from 234 stepcouples independently completed online surveys. After accounting for covariates (i.e., duration of mothers' previous relationships, duration of the stepcouple relationship, focal child's biological sex and age, number of children in the household, and mothers' report of household income), stepfathers' perceptions of affinity-seeking with the focal child significantly predicted both partners' perceptions of stepfather-stepchild conflict, marital quality, marital confidence, and stepfamily cohesion. Mothers' perceptions of stepfathers' affinity-seeking were significantly related to her marital confidence and perceptions of stepfamily cohesion. Stepfathers' perceptions of their affinity-seeking explained more variance in stepfathers' and mothers' outcomes than did mothers' perceptions. The results suggest benefits associated with stepfather affinity-seeking-less conflict with stepchildren, better couple relationships, and closer stepfamily ties. Our findings provide evidence for encouraging stepparents to focus on building affinity with stepchildren. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Suppression of HMGB1 Released in the Glioblastoma Tumor Microenvironment Reduces Tumoral Edema.

HMGB1 is a ubiquitously expressed intracellular protein that binds DNA and transcription factors and regulates chromosomal structure and function. Under conditions of cell death or stress, it is actively or passively released by cells into the extracellular environment, where it functions as damage-associated molecular pattern (DAMP) that orchestrates pro-inflammatory cytokine release and inflammation. Our results demonstrate that HMGB1 is secreted in the tumor microenvironment after oncolytic HSV (oHSV) infection in vitro and in vivo. The impact of secreted HMGB1 on tumor growth and response to oncolytic viral therapy was evaluated by using HMGB1-blocking antibodies in vitro and in mice bearing intracranial tumors. IVIS and MRI imaging was utilized to visualize in real time virus spread, tumor growth, and changes in edema in mice. Our data showed that HMGB1 released in tumor microenvironment orchestrated increased vascular leakiness and edema. Further HMGB1 blocking antibodies rescued vascular leakiness and enhanced survival of intracranial glioma-bearing mice treated with oHSV.