Composition of thrombi in zebrafish: similarities and distinctions with mammals.

BACKGROUND: Blood clots are primarily composed of red blood cells (RBCs), platelets/thrombocytes, and fibrin. Despite the similarities observed between mammals and zebrafish, the composition of fish thrombi is not as well known. OBJECTIVES: To analyze the formation of zebrafish blood clots ex vivo and arterial and venous thrombi in vivo. METHODS: Transgenic zebrafish lines and laser-mediated endothelial injury were used to determine the relative ratio of RBCs and thrombocytes in clots. Scanning electron and confocal microscopy provided high-resolution images of the structure of adult and larval clots. Adult and larval thrombocyte spreading on fibrinogen was evaluated ex vivo. RESULTS: RBCs were present in arterial and venous thrombi, making up the majority of cells in both circulations. However, bloodless mutant fish demonstrated that fibrin clots can form in vivo in the absence of blood cells. Scanning electron and confocal microscopy showed that larval and adult zebrafish thrombi and mammalian thrombi look surprisingly similar externally and internally, even though the former have nucleated RBCs and thrombocytes. Although adult thrombocytes spread on fibrinogen, we found that larval cells do not fully activate without the addition of plasma from adult fish, suggesting a developmental deficiency of a plasma activating factor. Finally, mutants lacking αIIbß3 demonstrated that this integrin mediates thrombocyte spreading on fibrinogen. CONCLUSION: Our data showed strong conservation of arterial and venous and clot/thrombus formation across species, including developmental regulation of thrombocyte function. This correlation supports the possibility that mammals also do not absolutely require circulating cells to form fibrin clots in vivo.

Quantitative imaging features predict spinal tap response in normal pressure hydrocephalus.

PURPOSE: Gait improvement following high-volume lumbar puncture (HVLP) and continuous lumbar drain (cLD) is widely used to predict shunt response in patients with suspected normal pressure hydrocephalus (NPH). Here, we investigate differences in MRI volumetric and traditional measures between HVLP/cLD responders and non-responders to identify imaging features that may help predict HVLP/cLD response. METHODS: Eighty-two patients with suspected NPH were studied retrospectively. Gait testing was performed before and immediately/24 h/72 h after HVLP/cLD. A positive response was defined as improvement in gait post-procedure. Thirty-six responders (26 men; mean age 79.3 ± 6.3) and 46 non-responders (25 men; mean age 77.2 ± 6.1) underwent pre-procedure brain MRI including a 3D T1-weighted sequence. Subcortical regional volumes were segmented using FreeSurfer. After normalizing for total intracranial volume, two-way type III ANCOVA test and chi-square test were used to characterize statistical group differences. Evans' index, callosal angle (CA), and disproportionately enlarged subarachnoid space hydrocephalus were assessed. Multivariable logistic regression models were tested using Akaike information criterion to determine which combination of metrics most accurately predicts HVLP/cLD response. RESULTS: Responders and non-responders demonstrated no differences in total ventricular and white/gray matter volumes. CA (men only) and third and fourth ventricular volumes were smaller; and hippocampal volume was larger in responders (p < 0.05). Temporal horns volume correlated with degree of improvement in gait velocity in responders (p = 0.0006). The regression model was 76.8% accurate for HVLP/cLD response. CONCLUSION: CA and third and fourth ventricular volumes and hippocampal volume may serve as potentially useful imaging features that may help predict spinal tap response and hence potentially shunt response.

Socioeconomic Determinants of the Use of Molecular Testing in Stage IV Colorectal Cancer.

OBJECTIVES: Treatment with epidermal growth factor receptor monoclonal antibodies extends life for patients with advanced colorectal cancers (CRCs) whose tumors exhibit wild-type KRAS, but KRAS testing may be underused. We studied the role of socioeconomic factors in the application of KRAS testing. MATERIALS AND METHODS: We identified subjects with stage IV colorectal adenocarcinoma diagnosed 2010-2015 in the Surveillance, Epidemiology, and End Results (SEER) database. We used multivariable logistic regression models to evaluate associations between clinical/demographic factors and the rate of KRAS testing. We used multivariable-adjusted Cox proportional hazards models to assess survival. RESULTS: We identified 37,676 patients with stage IV CRC, 31.1% of whom were tested for KRAS mutations, of those who had documented KRAS testing, 44% were KRAS mutant. Patients were more likely to be tested if they were younger (odds ratio [OR]=5.10 for age 20 to 29 vs. 80+, 95% confidence interval [CI]: 3.99-6.54, P<0.01), diagnosed more recently (OR=1.92 for 2015 vs. 2010, 95% CI: 1.77-2.08, P<0.01), or lived in an area of high median household income (OR=1.24 for median household income of >$69,311 vs. <$49,265, 95% CI: 1.14-1.35, P<0.01). Patients were less likely to be tested if they had Medicaid (OR=0.83, 95% CI: 0.77-0.88, P<0.01) or were unmarried (OR=0.78, 95% CI: 0.75-0.82, P<0.0001). The risk of death was decreased in patients who received KRAS testing (hazard ratio=0.77, 95% CI: 0.75-0.80, P<0.01). CONCLUSIONS: We found a low rate of KRAS testing in CRC patients with those living in low-income areas less likely to be tested, even after controlling for Medicaid insurance. Our study suggests that socioeconomic disparities persist despite Medicaid insurance.

Democratizing ownership and participation in the 4th Industrial Revolution: challenges and opportunities in cellular agriculture.

The emergence of the "4th Industrial Revolution," i.e. the convergence of artificial intelligence, the Internet of Things, advanced materials, and bioengineering technologies, could accelerate socioeconomic insecurities and anxieties or provide beneficial alternatives to the status quo. In the post-Covid-19 era, the entities that are best positioned to capitalize on these innovations are large firms, which use digital platforms and big data to orchestrate vast ecosystems of users and extract market share across industry sectors. Nonetheless, these technologies also have the potential to democratize ownership, broaden political-economic participation, and reduce environmental harms. We articulate the potential sociotechnical pathways in this high-stakes crossroads by analyzing cellular agriculture, an exemplary 4th Industrial Revolution technology that synergizes computer science, biopharma, tissue engineering, and food science to grow cultured meat, dairy, and egg products from cultured cells and/or genetically modified yeast. Our exploration of this space involved multi-sited ethnographic research in both (a) the cellular agriculture community and (b) alternative economic organizations devoted to open source licensing, member-owned cooperatives, social financing, and platform business models. Upon discussing how these latter approaches could potentially facilitate alternative sociotechnical pathways in cellular agriculture, we reflect upon the broader implications of this work with respect to the 4th Industrial Revolution and the enduring need for public policy reform.

Acitretin mitigates uroporphyrin-induced bone defects in congenital erythropoietic porphyria models.

Congenital erythropoietic porphyria (CEP) is a rare genetic disorder leading to accumulation of uro/coproporphyrin-I in tissues due to inhibition of uroporphyrinogen-III synthase. Clinical manifestations of CEP include bone fragility, severe photosensitivity and photomutilation. Currently there is no specific treatment for CEP, except bone marrow transplantation, and there is an unmet need for treating this orphan disease. Fluorescent porphyrins cause protein aggregation, which led us to hypothesize that uroporphyrin-I accumulation leads to protein aggregation and CEP-related bone phenotype. We developed a zebrafish model that phenocopies features of CEP. As in human patients, uroporphyrin-I accumulated in the bones of zebrafish, leading to impaired bone development. Furthermore, in an osteoblast-like cell line, uroporphyrin-I decreased mineralization, aggregated bone matrix proteins, activated endoplasmic reticulum stress and disrupted autophagy. Using high-throughput drug screening, we identified acitretin, a second-generation retinoid, and showed that it reduced uroporphyrin-I accumulation and its deleterious effects on bones. Our findings provide a new CEP experimental model and a potential repurposed therapeutic.

Sustainable support solutions for community-based rehabilitation workers in refugee camps: piloting telehealth acceptability and implementation.

BACKGROUND: The lack of training and education of Community-Based Rehabilitation (CBR) workers poses one of the most significant barriers to receiving effective occupational, physical and speech therapy for individuals with disabilities in Low-to-Middle Income Countries (LMIC), especially in countries with significant refugee populations. The aim of this study was to successfully implement a telehealth support system for CBR workers, evaluate the feasibility and acceptability of this intervention's implementation among CBR workers in the CBR setting, and further identify strategies to address the deficit of skilled rehabilitation workers in LMIC through technological intervention. METHODS: This pilot study included CBR workers and CBR managers to inform feasibility, acceptability, and sustainable implementation. The RE-AIM and Dynamic Sustainability Framework were incorporated to guide procedural design, survey development, data collection, data evaluation, and increase success of telehealth implementation. CBR workers participate in trainings, telehealth sessions, surveys and focus groups to inform feasibility and acceptability. CBR Managers participated in focus groups to inform feasibility and sustainable implementation. NVIVO 12 Software was utilized to develop themes from CBR worker and CBR manager responses. RESULTS: Findings from this study demonstrate the need for additional training support for CBR workers in CBR settings throughout the entire treatment process. The telehealth system demonstrated successful short-term implementation across several domains of feasibility. Telehealth utilization was also proven acceptable, appropriate and necessary. Cultural beliefs, CBR worker training, and CBR Center infrastructure pose the most significant barriers to implementation of telehealth technologies in CBR Centers. CBR workers and managers confirmed the demand for future telehealth-based support systems, strengthening effort towards sustainability and scale-up. CONCLUSIONS: Telehealth can be utilized to support CBR workers that serve vulnerable and marginalized populations, and in turn improve the global health status among refugee populations by reducing inequitable access to quality health care. The results support the need for further research to rigorously evaluate effectiveness of telehealth interventions to support CBR workers.

Diabetes mellitus and colorectal carcinoma outcomes: a meta-analysis.

OBJECTIVES: The impact of diabetes mellitus (DM) on colorectal cancer (CRC) outcomes remains unknown. We studied this by conducting a meta-analysis to evaluate (1) CRC outcomes with and without DM and (2) treatment patterns. METHODS: We searched PubMed, EMBASE, Google Scholar, and CINAHL for full-text English studies from 1970 to 12/31/2017. We searched keywords, subject headings, and MESH terms to locate studies of CRC outcomes/treatment and DM. Studies were evaluated by two oncologists. Of 14,332, 48 met inclusion criteria. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method, we extracted study location, design, DM definition, covariates, comparison groups, outcomes, and relative risks and/or hazard ratios. We utilized a random-effects model to pool adjusted risk estimates. Primary outcomes were all-cause mortality (ACM), disease-free survival (DFS), relapse-free survival (RFS), and cancer-specific survival (CSS). The secondary outcome was treatment patterns. RESULTS: Forty-eight studies were included, 42 in the meta-analysis, and 6 in the descriptive analysis, totaling > 240,000 patients. ACM was 21% worse (OR 1.21, 95% CI 1.15-1.28) and DFS was 75% worse (OR 1.75, 95% CI: 1.33-2.31) in patients with DM. No differences were detected in CSS (OR 1.10, 95% CI 0.98-1.23) or RFS (OR 1.12, 95% CI 0.91-1.38). Descriptive analysis of treatment patterns in CRC and DM suggested potentially less adjuvant therapy use in cases with DM and CRC. CONCLUSIONS: Our meta-analysis suggests that patients with CRC and DM have worse ACM and DFS than patients without DM, suggesting that non-cancer causes of death in may account for worse outcomes.

Responses to bullying among individuals with intellectual and developmental disabilities: Support needs and self-determination.

BACKGROUND: Compared to the general population, individuals with intellectual and developmental disabilities (IDD) more often experience bullying and its negative social and emotional impacts. Prior studies explored bullying of individuals with IDD primarily through investigations of the perspectives of others and the negative impacts of bullying. The current study examined how individuals with IDD describe their responses to experiences of bullying, with a focus on whether responses included component skills of self-determination. METHOD: Eighteen adults with IDD (50% female) aged 18-63 years were interviewed about their experiences with bullying. Interviews were analysed to determine responses to bullying and the degree to which their responses demonstrated self-determination. RESULTS: Data analysis revealed two primary themes, outside support and self-determination, with additional subthemes. CONCLUSIONS: Findings provide a more nuanced description of the ways in which individuals with IDD respond to bullying, including the demonstration of self-determination skills. Implications for research and practice are discussed.

In Their Own Words: Perceptions and Experiences of Bullying Among Individuals With Intellectual and Developmental Disabilities.

Despite the high incidence of bullying among people with intellectual and developmental disabilities (IDD), little research has been conducted with people with IDD as participants reporting their own perceptions and experiences of bullying. To address this shortcoming, we interviewed 18 adults with IDD regarding these issues. Four major themes emerged from our qualitative analysis of the transcribed interviews: (a) bullying is hurtful, (b) why people bully, (c) bullying takes many forms, and (d) bullying can happen anywhere. Though participants' definitions of bullying and explanations for why people bully aligned well with traditional understandings, several reported incidents of bullying were discrepant from the traditional definition, including incidents of abuse and rude behavior. Implications for future research and practice are discussed.

Lived challenges and getting through them: Alaska Native youth narratives as a way to understand resilience.

Because of imposed rapid social change, Alaska Native youth are growing up in a context different from their elders and suffering far worse health and behavioral outcomes. This research seeks to understand (a) their everyday struggles and life challenges, (b) the practices and resources they rely on to get through challenges, and (c) the meaning they make from these experiences. Data were generated from interviews with 20 Alaska Native youth between the ages of 11 and 18 years, balanced by gender and age-group (early and late adolescence). Purposive sampling identified participants with a broad range of experiences. Following a semistructured guide, youth participated in face-to-face, audio-recorded interviews, transcribed verbatim. A codebook was developed using an iterative process and transcripts were coded using ATLAS.ti. The most commonly identified stressors were relationship loss, "not being there for me," nonsupportive/hostile experiences, transitioning into adulthood, and boredom. Resilience strategies included developing and maintaining relationships with others, being responsible, creating systems of reciprocity, practicing subsistence living, and giving back to family and the community. These opportunities allowed youth to gain a sense of competence and mastery. When difficult experiences align with opportunities for being responsible and competent, youth are most likely to exhibit resilience.

Developing leaders: implementation of a peer advising program for a public health sciences undergraduate program.

Peer advising is an integral part of our undergraduate advising system in the Public Health Sciences major at the University of Massachusetts Amherst. The program was developed in 2009 to address the advising needs of a rapidly growing major that went from 25 to over 530 majors between 2007 and 2014. Each year, 9-12 top performing upper-level students are chosen through an intensive application process. A major goal of the program is to provide curriculum and career guidance to students in the major and empower students in their academic and professional pursuits. The year-long program involves several components, including: staffing the drop-in advising center, attending training seminars, developing and presenting workshops for students, meeting prospective students and families, evaluating ways to improve the program, and collaborating on self-directed projects. The peer advisors (PAs) also provide program staff insight into the needs and perspectives of students in the major. In turn, PAs gain valuable leadership and communication skills, and learn strategies for improving student success. The Peer Advising Program builds community and fosters personal and professional development for the PAs. In this paper, we will discuss the undergraduate peer advising model, the benefits and challenges of the program, and lessons learned. Several methods were used to understand the perceived benefits and challenges of the program and experiences of students who utilized the Peer Advising Center. The data for this evaluation were drawn from three sources: (1) archival records from the Peer Advising Center; (2) feedback from PAs who completed the year-long internship; and (3) a survey of students who utilized the Peer Advising Center. Results of this preliminary evaluation indicate that PAs gain valuable skills that they can carry into their professional world. The program is also a way to engage students in building community within the major.

Teaching young adults with disabilities to respond appropriately to lures from strangers.

We taught 5 adults with mild intellectual disabilities to respond appropriately to lures from strangers. Skills were taught in the classroom first and then in situ. Before training, participants did not walk away from confederate strangers who tried to lure them away. Participants demonstrated appropriate responses during classroom and in situ training, although performance during assessments was somewhat inconsistent. Appropriate responses were observed during weekly maintenance probes and at follow-up assessments for up to 3 months after training.

Promoting positive youth development and highlighting reasons for living in Northwest Alaska through digital storytelling.

Using a positive youth development framework, this article describes how a 3-year digital storytelling project and the 566 digital stories produced from it in Northwest Alaska promote protective factors in the lives of Alaska Native youth and serve as digital "hope kits," a suicide prevention approach that emphasizes young people's reasons for living. Digital stories are short, participant-produced videos that combine photos, music, and voice. We present process data that indicate the ways that digital stories serve as a platform for youth to reflect on and represent their lives, important relationships and achievements. In so doing, youth use the digital storytelling process to identify and highlight encouraging aspects of their lives, and develop more certain and positive identity formations. These processes are correlated with positive youth health outcomes. In addition, the digital stories themselves serve as reminders of the young people's personal assets--their reasons for living--after the workshop ends. Young people in this project often showed their digital stories to those who were featured positively within as a way to strengthen these interpersonal relationships. Evaluation data from the project show that digital storytelling workshops and outputs are a promising positive youth development approach. The project and the qualitative data demonstrate the need for further studies focusing on outcomes related to suicide prevention.

Characteristics of inclusive faith communities: a preliminary survey of inclusive practices in the United States.

BACKGROUND: Although participation in faith communities is important to many individuals with disabilities, few studies have examined differences between communities that are more (versus less) inclusive. This study investigated characteristics of faith communities in the United States related to greater inclusion. METHODS: Participants were 160 respondents to an anonymous survey about inclusion. Survey items grouped together to form three inclusion-related outcomes: the degree to which faith communities welcome and include individuals with disabilities; the roles and contributions of congregants with disabilities; and physical accessibility. RESULTS: Across these outcomes, more inclusive communities (i) featured faith leaders who were more committed to inclusion; (ii) used educational resources to address disability-related issues; (iii) portrayed people with disabilities positively in their religious teachings; (iv) had stronger ties to disability organizations; and (v) had a stronger orientation towards promoting social justice. CONCLUSIONS: These five characteristics have important implications for promoting inclusion in faith communities.