Unique Cohorts of Salivary Gland Cancer Cells as an in-vitro Model of Circulating Tumor Cells.

Introduction: The characterization of circulating tumor cells (CTC) and circulating tumor microemboli (CTM) has emerged as both a challenge to the standard view of metastasis, and as a valuable means for understanding genotypic and phenotypic variability shown even within the same cancer type. However, in the case of salivary gland neoplasms, limited data are available for the role that CTCs and CTMs play in metastasis and secondary tumor formation.ru.AQ1 In response to this, we propose that similarities between in vitro clusters of cultured salivary gland cancer cells may act as a surrogate model for in vivo CTCs and CTMs isolated from patients. Materials and Methods: Using techniques in immunofluorescence, immunoblotting, and 2-dimensional migration, we isolated and characterized a group of cohort cells from a commercially available cell line (HTB-41). Results: Here, cells exhibited a hybrid phenotype with simultaneous expression of both epithelial and mesenchymal markers (E-cadherin, vimentin, and α-SMA). Cohort cells also exhibited increased migration in comparison to parental cells. Conclusion: Data suggest that these isolated cell clusters may fucntion as a potential in vitro model of CTCs and CTMs.

Evaluating the validity of a functional electrical stimulation clinical decision making tool: A qualitative study.

Introduction: Following central nervous system damage, the recovery of motor function is a priority. For some neurological populations, functional electrical stimulation (FES) is recommended in best practice guidelines for neurorehabilitation. However, limited resources exist to guide FES application, despite clinicians reporting that a lack of FES knowledge prevents use in clinical practice. The FES Clinical Decision Making Tool was developed to assist clinicians with FES application and translation into clinical practice. The purpose of this study was to evaluate the content validity of the Tool from the perspectives of Canadian physical and occupational therapists using FES in neurorehabilitation. Methods: Thirteen participants (twelve women, one man), aged 40.5 ± 10.3 years, participated in individual semi-structured interviews to explore their clinical decision making experiences when applying FES and to evaluate the content validity (i.e., appropriateness, comprehensibility, and comprehensiveness) of the Tool. Interviews were analyzed using a qualitative conventional content analysis following the DEPICT model. Results: Three themes were identified. 1) Clinician context influences FES usage. Participants' experiences with FES use varied and application was influenced by treatment goals. 2) Parameter selection in clinical practice. Participants identified decision-making strategies and the challenges of parameter selection. 3) With modifications, the Tool is a valid resource to inform FES applications. Participants discussed its strengths, limitations, and suggested changes. While the Tool is useful, a more extensive resource (e.g., appendix) for the Tool is warranted. Discussion: A revised Tool was created to improve its comprehensiveness and comprehensibility. Thus, the Tool is a valid resource for applying FES in neurorehabilitation.

"You are not alone": Connecting through a bereaved parent mentor program for parents whose child died of cancer.

BACKGROUND: Bereavement after the death of a child is devastating and associated with worse physical and psychosocial well-being in parents. Evidence suggests that parents desire and benefit from support provided by other bereaved parents. To foster this peer support, an institutional peer-to-peer mentorship program for bereaved parents was established, through which trained bereaved parent mentors offer support for newly bereaved parents. METHODS: Using a retrospective cohort design, we describe the characteristics of participants of the Bereaved Parent Mentorship program. Trained bereaved parent mentors documented encounters with newly bereaved parent mentees using a secure internet-based form. Mentors summarized each encounter including any concerns or need for professional psychosocial support. Descriptive statistics were used to describe mentor and mentee characteristics; free text from encounter summaries was qualitatively analyzed using content analysis. RESULTS: A total of 1368 documented encounters occurred between 150 mentees and 39 mentors from January 1, 2014 to February 29, 2020. Only seven encounters (0.5%) were flagged as serious concern necessitating professional psychosocial support. Four key themes in the encounters between mentors and mentees emerged, including: descriptions of the grief experience, ways in which a mentor supported their mentee, challenges the mentor experienced in supporting the mentee, and personal benefit gained by the mentor from supporting their mentee. CONCLUSION: This structured Bereaved Parent Mentorship program fostered rich interactions between bereaved parent participants, with very few encounters requiring professional assistance. Future research will assess the impact of bereaved mentor programs on resilience and psychosocial, physical, and functional well-being of parents.

Leveraging Grief: Involving Bereaved Parents in Pediatric Palliative Oncology Program Planning and Development.

As pediatric palliative care (PPC) became a recognized medical specialty, our developing clinical PPC team longitudinally partnered with bereaved parents to understand the care that their children received as they transitioned towards end of life. Families developed Eight Priorities, shared within, to improve care for children with a poor chance of survival based on their experience of losing a child to cancer. In this paper, we delineate the top eight PPC needs from a parent perspective to offer multi-layered, individually tailored resources for patients and families. One of these Eight Priorities noted that bereavement care for the remaining family members is vital for healing after the death of a child to promote meaning making and resilience in bereaved families. Here, we outline the creation of a bereaved parent-designed bereavement support program as one example of how we have partnered with parents to fulfill their Eight Priorities for quality care.

Development of a Structured Peer Mentoring Program for Support of Parents and Caregivers of Children with Cancer.

BACKGROUND: Parents of children newly diagnosed with cancer have increased anxiety, depression, and numerous questions. Many of these concerns can only be answered by parents who have undergone a similar experience. LOCAL PROBLEM: Our institution lacked a formal parent-to-parent mentoring program for parents of children newly diagnosed with cancer. METHODS: The Parent Family Advisory Council (PFAC) recommended implementation of a formalized program that would promote a structured approach to mentoring, with a formal referral process and designated parent mentors who had been vetted, trained, and supported by the institution. INTERVENTION: In 2010, a pilot parent-to-parent mentoring program was initiated. RESULTS: Since the programs initiation, 4062 encounters have been documented. This represents an annual average of 72 mentees paired with 20 mentors, averaging 677 annual encounters. Parents view the mentoring relationship as positive and report that they feel understood, less anxious, and less isolated. CONCLUSION: We show that a parent-to-parent mentoring program is feasible and sustainable over time. Our model is now transitioning from a staff referral to self-referral, as well as incorporating real-time mentoring into the new commons area for patients and their families. A formal volunteer mentoring program can assist parents in navigating the trajectory of childhood cancer, decreasing isolation.

The Role of Active Rehabilitation in Concussion Management: A Systematic Review and Meta-analysis.

PURPOSE: This study aimed to conduct a systematic review and meta-analysis of active rehabilitation on concussion management. We also examined moderator variables that may contribute to differences across studies: symptom scale, physical activity type, time of injury to recruitment, and mechanism of injury. METHODS: The standardized effect size of physical activity on concussion management was computed for 23 studies (29 effect sizes). Effect sizes were coded as positive when studies reported an improvement in symptom scores, which was represented by a decrease in postconcussive symptom scores. RESULTS: The overall effect size of physical activity on concussion recovery was large and positive (g = 1.03). Subthreshold aerobic activity provided the largest effect size (g = 1.71), whereas multimodal interventions had a moderate effect size (g = 0.70). All other moderator variables produced positive effect sizes ranging from g = 0.59 to g = 1.46. CONCLUSIONS: This systematic review and meta-analysis demonstrates that current evidence supports the notion that physical activity is beneficial in decreasing postconcussive symptoms in both the acute and chronic phases after concussion. The results indicate that unimodal subthreshold aerobic activity may be the best course of action compared with multimodal interventions. Despite this growing body of evidence, additional research is needed to determine the optimal intensity, duration, and time to initiation of aerobic exercise after concussion.

Developing a science outreach program and promoting "PhUn" all year with rural K-12 students.

Demonstrating how science relates to human health is an important step for generating K-12 student interest in health-related careers. Science outreach is often performed in urban areas; however, ~20% of K-12 schools are in rural areas. Michigan Technological University is located in Michigan's upper peninsula, which accounts for 30% of the state's land mass but only 3% of the total population. Our goal was to create a science outreach program for reaching K-12 students in our rural region. We assembled a team of undergraduate and graduate students, staff, and faculty to implement science outreach with K-12 students. Specifically, we leveraged existing national and international science outreach events [Physiology Friday, Physiology Understanding (PhUn) Week, National Biomechanics Day] to offer hands-on physiology and biomechanics activities during the year. Between 2016 and 2019, we connected with 31 K-12 schools and impacted 327 elementary (19%), 351 middle school (21%), and 1,018 high school (60%) students (total impact 1,696). Over 90% of the outreach visits took place at the K-12 schools. The hands-on activities were delivered by more than 85 undergraduate and graduate students and 10 faculty. Together, the supportive culture and resources within the department (e.g., outreach coordinator, participation from students and faculty, grant funding) were key to developing the program. We recommend starting with a single outreach event, working as a team, and being flexible with K-12 schools. The program also provided service-learning and professional development opportunities for undergraduate and graduate students and faculty. Our robust science outreach program promoted "PhUn" all year-round with rural K-12 students.

An outside-the-box activity to demonstrate how humans and animals turn.

Developing hands-on activities that engage and excite K-12 students is critical for stimulating interest in science-based careers. We created an activity for high school students that required them to integrate biology and physics concepts to experience how humans and animals maneuver through their environments (i.e., turning). Understanding how turning works is important because it accounts for up to 50% of daily walking steps and is needed for survival when animals elude predators and capture prey. For this activity, student groups used 2 × 4 lumber, wood screws, and a power drill to build an apparatus that, when connected to the body, altered rotational inertia (object's resistance to change in angular motion, I = mass × radius2). Students navigated through a slalom course with the apparatus (increased radius and rotational inertia) and without the apparatus (mass-matched control). Times to complete the course were compared between trials to determine the influence of rotational inertia on turning performance. Students compiled their data, graphed their results, and found that increased rotational inertia decreased turning performance. Results were connected to sports, rehabilitation, and dinosaur evolution. This activity was implemented during local, regional, national, and international outreach events and adapted for use in undergraduate courses as well (total impact, 250 students). At the end of the activity, students were able to 1) describe whether their results supported their hypothesis; 2) explain how radius influences rotational inertia and turning performance; and 3) apply results to real-world examples. Students and teachers appreciated this "outside-the-box" activity with an engineering twist and found it entertaining.

Calcitriol-mediated reduction in IFN-γ output in T cell large granular lymphocytic leukemia requires vitamin D receptor upregulation.

Constitutively activated STAT1 and elevated IFN-γ are both characteristic of T cell large granular lymphocytic leukemia (T-LGLL), a rare incurable leukemia with clonal expansion of cytotoxic T cells due to defective apoptosis. Interferon gamma (IFN-γ) is an inflammatory cytokine that correlates with worse progression and symptomology in multiple autoimmune diseases and cancers. In canonical IFN-γ-STAT1 signaling, IFN-γ activates STAT1, a transcription factor, via phosphorylation of tyrosine residue 701 (p-STAT1). p-STAT1 then promotes transcription of IFN-γ, creating a positive feedback loop. We previously found that calcitriol treatment of the TL-1 cell line, a model of T-LGLL, significantly decreased IFN-γ secretion and p-STAT1 while increasing the vitamin D receptor (VDR) protein. Here we further explore these observations. Using TL-1 cells, IFN-γ decreased starting at 4h following calcitriol treatment, with a reduction in the intracellular and secreted protein levels as well as the mRNA content. A similar reduction in IFN-γ transcript levels was observed in primary T-LGLL patient peripheral blood mononuclear cells (PBMCs). p-STAT1 inhibition followed a similar temporal pattern and VDR upregulation inversely correlated with IFN-γ levels. Using EB1089 and 25(OH)D3, which have high or low affinity for VDR, respectively, we found that the decrease in IFN-γ correlated with the ability of EB1089, but not 25(OH)D3, to upregulate VDR. However, both compounds inhibited p-STAT1; thus the reduction of p-STAT1 is not solely responsible for IFN-γ inhibition. Conversely, cells treated with VDR siRNA exhibited decreased basal IFN-γ production upon VDR knockdown in a dose-dependent manner. Calcitriol treatment upregulated VDR and decreased IFN-γ regardless of initial VDR knockdown efficiency, strengthening the connection between VDR upregulation and IFN-γ reduction. Our findings suggest multiple opportunities to further explore the clinical relevance of the vitamin D pathway and the potential role for vitamin D supplementation in T-LGLL.

Understanding the genetic and environmental specificity and overlap between well-being and internalizing symptoms in adolescence.

Moderate inverse correlations are typically found between well-being and mental illness. We aimed to investigate the role of genes and environments in explaining the relationships between two aspects of well-being and two measures of internalizing symptoms. Altogether, 4700 pairs of 16-year-old twins contributed data on subjective happiness and life satisfaction, as well as symptoms of depression and emotional problems. Well-being was moderately correlated with internalizing symptoms (range = -0.45, -0.58). Multivariate twin model-fitting indicated both genetic and environmental overlap. Life satisfaction and happiness demonstrated different patterns of overlap, with stronger genetic links between life satisfaction and depression. Non-shared environmental influences were largely specific to each trait. This study supports the theory of mental health and illness being partly (but not entirely) correlated dimensions. There are also significant genetic and environmental factors to identify for well-being that go beyond the absence of mental illness. It is therefore possible that different interventions are needed for treating mental illness and promoting mental health.

Stability and Change in Genetic and Environmental Influences on Well-Being in Response to an Intervention.

Genetic and environmental influences on complex traits can change in response to developmental and environmental contexts. Here we explore the impact of a positive activity intervention on the genetic and environmental influences on well-being and mental health in a sample of 750 adolescent twins. Twins completed a 10-week online well-being intervention, consisting of kindness and gratitude tasks and matched control activities. The results showed significant improvements both in well-being and in internalizing symptoms in response to the intervention activities. We used multivariate twin analyses of repeated measures, tracking stability and change in genetic and environmental influences, to assess the impact of this environmental intervention on these variance components. The heritability of well-being remained high both before and after the intervention, and the same genetic effects were important at each stage, even as well-being increased. The overall magnitude of environmental influences was also stable across the intervention; however, different non-shared environmental influences emerged during the intervention. Our study highlights the value of exploring the innovations in non-shared environmental influences that could provide clues to the mechanisms behind improvements in well-being. The findings also emphasize that even traits strongly influenced by genetics, like well-being, are subject to change in response to environmental interventions.

Blended learning within an undergraduate exercise physiology laboratory.

In physiological education, blended course formats (integration of face-to-face and online instruction) can facilitate increased student learning, performance, and satisfaction in classroom settings. There is limited evidence on the effectiveness of using blending course formats in laboratory settings. We evaluated the impact of blended learning on student performance and perceptions in an undergraduate exercise physiology laboratory. Using a randomized, crossover design, four laboratory topics were delivered in either a blended or traditional format. For blended laboratories, content was offloaded to self-paced video demonstrations (∼15 min). Laboratory section 1 (n = 16) completed blended laboratories for 1) neuromuscular power and 2) blood lactate, whereas section 2 (n = 17) completed blended laboratories for 1) maximal O2 consumption and 2) muscle electromyography. Both sections completed the same assignments (scored in a blinded manner using a standardized rubric) and practicum exams (evaluated by two independent investigators). Pre- and postcourse surveys were used to assess student perceptions. Most students (∼79%) watched videos for both blended laboratories. Assignment scores did not differ between blended and traditional laboratories (P = 0.62) or between sections (P = 0.91). Practicum scores did not differ between sections (both P > 0.05). At the end of the course, students' perceived value of the blended format increased (P < 0.01) and a greater percentage of students agreed that learning key foundational content through video demonstrations before class greatly enhanced their learning of course material compared with a preassigned reading (94% vs. 78%, P < 0.01). Blended exercise physiology laboratories provided an alternative method for delivering content that was favorably perceived by students and did not compromise student performance.

Facilitating Early-In-Day Discharge for Multiple Sclerosis Patients Treated With Intravenous Methylprednisolone: A Quality Improvement Project.

BACKGROUND AND PURPOSE: Delays in patient hospital discharge affect care value through costs of prolonged length of stay and barriers to patient flow within the hospital. We sought to facilitate early-in-day discharges (EIDDs) without extending length of stay for inpatients with multiple sclerosis admitted for acute exacerbations and treated with intravenous (IV) methylprednisolone. METHODS: We developed a standardized admission order set, a provider checklist, and a patient checklist to better coordinate in-hospital care and discharge planning for patients with multiple sclerosis admitted for IV methylprednisolone treatment. The order set allowed providers to enter an accelerated dosing schedule of methylprednisolone, as appropriate, to ensure administration of the final dose of methylprednisolone in the morning on the anticipated day of discharge. We compared a prospective intervention cohort to a retrospective, preintervention baseline cohort. RESULTS: At baseline (N = 25), 12.0% of patients were EIDD compared to 40.7% of intervention patients (N = 27; P = .03). In all, 85.2% of intervention patients compared to 64.0% of baseline patients were discharged on the same day as last methylprednisolone treatment (P = .11). No difference was observed in median length of stay and 30-day readmission rate between groups. CONCLUSIONS: Use of a standard admission order set as well as provider and patient checklists can facilitate EIDD and hospital bed availability without compromising care quality for a select group of neurology inpatients.

Development of a respite care program for caregivers of pediatric oncology patients and their siblings.

Children with chronic health care needs, including those with cancer, require complex care under direct caregiver supervision. This intensive care management may result in increased stress and psychological distress for the caregiver and family. Respite care services are needed in providing alleviation of caregiver stress among families of children with complex health care needs. This report describes the feasibility of a pilot hospital-based respite care program for caregivers of pediatric oncology patients and their siblings and development of a permanent, expanded service to include both inpatient and outpatient units under the supervision of hospital volunteer services. During the feasibility pilot, 39 respite care requests were made by caregivers for care of patients, with 67% of these requests for care of infants and toddlers. The respite care providers were hospital volunteers. Reasons for the caregiver respite care request included a need to leave the hospital for running an errand, eating a meal, taking a mental break, or talking with the medical team. At the completion of the pilot, caregivers and staff were surveyed and expressed a strong desire for continuation of the service. The success of the pilot led to the implementation of a formal respite care program, Helping Hands, which provides services 7 days a week for inpatients, outpatients, and their siblings. Although this respite care service is specific to children with cancer, the program model is feasible within most pediatric care facilities.

Munchausen syndrome by proxy caused by ipecac poisoning.

OBJECTIVE: To present a case of Munchausen syndrome by proxy caused by ipecac poisoning to increase the awareness of their warning signs and symptoms so that they may be recognized and diagnosed earlier. CASE: Report of one case of a child who was determined to be a victim of Munchausen syndrome by proxy by ipecac poisoning who was hospitalized multiple times over a 4-year period at 2 different hospitals before an accurate diagnosis was made.