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Abstract Seeding activities of disease-associated α-synuclein aggregates (αSynD), a hallmark of Parkinson’s disease (PD), are detectable by seed amplification assay (αSyn-SAA) and being developed as a diagnostic biomarker for PD. Sensitive and accurate αSyn-SAA for blood or saliva would greatly facilitate PD diagnosis. This prospective diagnostic study conducted αSyn-SAA analyses on serum and saliva samples collected from patients clinically diagnosed with PD or healthy controls (HC). 124 subjects (82 PD, 42 HC) donated blood and had extensive clinical assessments, of whom 74 subjects (48 PD, 26 HC) also donated saliva at the same visits. An additional 57 subjects (35 PD, 22 HC) donated saliva and had more limited clinical assessments. The mean ages were 69.21, 66.55, 69.58, and 64.71 years for PD serum donors, HC serum donors, PD saliva donors, and HC saliva donors, respectively. αSynD seeding activities in either sample type alone or both sample types together were evaluated for PD diagnosis. Serum αSyn-SAA data from 124 subjects showed 80.49% sensitivity, 90.48% specificity, and 0.9006 accuracy (AUC of ROC); saliva αSyn-SAA data from 131 subjects attained 74.70% sensitivity, 97.92% specificity, and 0.8966 accuracy. Remarkably, the combined serum and saliva αSyn-SAA from 74 subjects with both sample types achieved better diagnostic performance: 95.83% sensitivity, 96.15% specificity, and 0.98 accuracy. In addition, serum αSynD seeding activities correlated inversely with Montreal Cognitive Assessment in males and positively with Hamilton Depression Rating Scale in females and in the

Abstract Background Douglas-fir (Pseudotsuga menziesii [Mirb.] Franco) plays a critical role in the ecology and economy of Western North America. This conifer species comprises two distinct varieties: the coastal variety (var. menziesii) along the Pacific coast, and the interior variety (var. glauca) spanning the Rocky Mountains into Mexico, with instances of inter-varietal hybridization in Washington and British Columbia. Recent investigations have focused on assessing environmental pressures shaping Douglas-fir’s genomic variation for a better understanding of its evolutionary and adaptive responses. Here, we characterize range-wide population structure, estimate inter-varietal hybridization levels, identify candidate loci for climate adaptation, and forecast shifts in species and variety distribution under future climates. Results Using a custom SNP-array, we genotyped 540 trees revealing four distinct clusters with asymmetric admixture patterns in the hybridization zone. Higher genetic diversity observed in coastal and hybrid populations contrasts with lower diversity in inland populations of the southern Rockies and Mexico, exhibiting a significant isolation by distance pattern, with less marked but still significant isolation by environment. For both varieties, we identified candidate loci associated with local adaptation, with hundreds of genes linked to processes such as stimulus response, reactions to chemical compounds, and metabolic functions. Ecological niche modeling revealed contrasting potential distribution shifts among the varieties in the coming decades, with interior populations projected to lose habitat and become more vulnerable, while coastal populations are expected to gain suitable areas. Conclusions Overall, our findings provide crucial insights into the population structure and adaptive potential of Douglas-fir, with the coastal variety being the most likely to preserve its evolutionary path throughout the present century, which carry implications for the conservation and management of this species across their range.

Abstract Background Drastic increases in the rates of maternal depression and anxiety have been reported since the COVID-19 pandemic began. Most programs aim to improve maternal mental health or parenting skills separately, despite it being more effective to target both concurrently. The Building Emotional Awareness and Mental health (BEAM) program was developed to address this gap. BEAM is a mobile health program aiming to mitigate the impacts of pandemic stress on family well-being. Since many family agencies lack infrastructure and personnel to adequately treat maternal mental health concerns, a partnership will occur with Family Dynamics (a local family agency) to address this unmet need. The study’s objective is to examine the feasibility of the BEAM program when delivered with a community partner to inform a larger randomized controlled trial (RCT). Methods A pilot RCT will be conducted with mothers who have depression and/or anxiety with a child 6–18 months old living in Manitoba, Canada. Mothers will be randomized to the 10 weeks of the BEAM program or a standard of care (i.e., MoodMission). Back-end App data (collected via Google Analytics and Firebase) will be used to examine feasibility, engagement, and accessibility of the BEAM program; cost-effectiveness will also be examined. Implementation elements (e.g., maternal depression [Patient Health Questionnaire-9] and anxiety [Generalized Anxiety Disorder-7]) will be piloted to estimate the effect size and variance for future sample size calculations. Discussion In partnership with a local family agency, BEAM holds the potential to promote maternal-child health via a cost-effective and an easily accessible program designed to scale. Results will provide insight into the feasibility of the BEAM program and will inform future RCTs. Trial registration {2a} This trial was retrospectively registered with ClinicalTrial.gov ( NCT05398107 ) on May 31st, 2022.

Abstract Background Alzheimer’s disease (AD) is a neurodegenerative disorder that manifests sequential Aβ and tau brain pathology with age-dependent onset. Variants in the microglial immune receptor TREM2 are associated with enhanced risk of onset in sporadic Alzheimer’s disease (AD). While recent studies suggest TREM2 dysfunction can aggravate tau pathology, mechanisms underlying TREM2-dependent modulation of tau pathology remains elusive. Methods Here, we characterized differences in progressive tau spreading from the medial entorhinal cortex (MEC) to the hippocampus in wildtype (WT) and Trem2 knockout (KO) mice by injection of AAV-P301L tau into the MEC, and correlated changes in hippocampal tau histopathology with spatial and fear memory. We also compared effects of intraneuronal dispersion between cultured microglia and neurons using a microfluidic dispersion assay, analyzed differences in microglial tau trafficking following uptake, and quantified exosomal tau secretion and pathogenicity from purified WT and Trem2 KO exosomes. Results Trem2 deletion in mice (Trem2 KO) can enhance tau spreading from the medial entorhinal cortex (MEC) to the hippocampus, which coincides with impaired synaptic function and memory behavior. Trem2 deletion in microglia enhances intraneuronal dispersion of tau in vitro between neuronal layers cultured in a microfluidic chamber, and the presence of exosome inhibitors can significantly reduce tau in exosomes and extracellular media from tau-loaded microglia. Although microglial Trem2 deletion has no effect on tau uptake, Trem2 deletion enhances distribution to endosomal and cellular pre-exosomal compartments following internalization. Trem2 deletion has little effect on exosome size, however, proteomic analysis indicates that Trem2 deletion can modulate changes in the microglial proteomic landscape with tau and LPS/ATP treatment conditions associated with exosome induction. Furthermore, exosomes from Trem2 KO microglia show elevated tau levels, and feature enhanced tau-seeding capacity in a tau FRET reporter line compared to exosomes from WT microglia. Conclusion Together, our results reveal a role for Trem2 in suppressing exosomal tau pathogenicity, and demonstrates that Trem2 deletion can enhance tau trafficking, distribution and seeding through microglial exosomes. Graphical abstract

Abstract Background Refugees are screened for TB overseas using Technical Instructions (TIs) issued by the U.S. Centers for Disease Control and Prevention and after arrival during their refugee health assessment (RHA). We examined RHA results and TB outcomes of refugees to Minnesota. Methods Demographic and RHA results for 70,290 refugee arrivals to Minnesota from January 1993 to August 2019 were matched to 3595 non-U.S. born individuals diagnosed with TB disease during that time. Results Seven hundred fifty-nine (1.1%) were diagnosed with TB disease. Fifty-four percent were diagnosed within 2 years of U.S. arrival. Refugees screened using TIs implemented in 1991 were twice as likely to be diagnosed with TB disease within 1 year of arrival, compared to those evaluated using improved TIs implemented in 2007. Conclusion Few refugees were diagnosed with TB disease during the period examined. Enhancements to overseas protocols significantly reduced the proportion of refugees diagnosed within 1 year of arrival.

Abstract Background Early breastfeeding cessation is a societal concern given its importance to the health of mother and child. More effective interventions are needed to increase breastfeeding duration. Prior to developing such interventions more research is needed to examine breastfeeding supports and barriers from the perspective of breastfeeding stakeholders. One such framework that can be utilized is the Socio-Ecological Model which stems from Urie Broffenbrenner’s early theoretical frameworks (1973–1979). The purpose of this study was to examine supports and barriers to breastfeeding across environmental systems. Methods A total of 49 representatives participated in a telephone interview in Nebraska, USA in 2019. Interviewees represented various levels of the model, based on their current breastfeeding experience (i.e., mother or significant other) or occupation. A direct content analysis was performed as well as a constant comparative analysis to determine differences between level representatives. Results At the Individual level, breastfeeding is a valued behavior, however, women are hindered by exhaustion, isolation, and the time commitment of breastfeeding. At the Interpersonal level, social media, peer-to-peer, and family were identified as supports for breastfeeding, however lack of familial support was also identified as a barrier. At the community level, participants were split between identifying cultural acceptance of breastfeeding as support or barrier. At the organizational level, hospitals had supportive breastfeeding friendly policies in place however lacked enough personnel with breastfeeding expertise. At the policy level, breastfeeding legislation is supportive, however, more specific breastfeeding legislation is needed to ensure workplace breastfeeding protections. Conclusion Future efforts should target hospital-community partnerships, family-centered education, evidence-based social media strategies and improved breastfeeding legislation to ensure breastfeeding women receive effective support throughout their breastfeeding journey.

Abstract Background SARS-CoV-2 has swept across the globe, causing millions of deaths worldwide. Though most survive, many experience symptoms of COVID-19 for months after acute infection. Successful prevention and treatment of acute COVID-19 infection and its associated sequelae is dependent on in-depth knowledge of viral pathology across the spectrum of patient phenotypes and physiologic responses. Longitudinal biobanking provides a valuable resource of clinically integrated, easily accessed, and quality-controlled samples for researchers to study differential multi-organ system responses to SARS-CoV-2 infection, post-acute sequelae of COVID-19 (PASC), and vaccination. Methods Adults with a history of a positive SARS-CoV-2 nasopharyngeal PCR are actively recruited from the community or hospital settings to enroll in the Northern Colorado SARS-CoV-2 Biorepository (NoCo-COBIO). Blood, saliva, stool, nasopharyngeal specimens, and extensive clinical and demographic data are collected at 4 time points over 6 months. Patients are assessed for PASC during longitudinal follow-up by physician led symptom questionnaires and physical exams. This clinical trial registration is NCT04603677 . Results We have enrolled and collected samples from 119 adults since July 2020, with 66% follow-up rate. Forty-nine percent of participants assessed with a symptom surveillance questionnaire (N = 37 of 75) had PASC at any time during follow-up (up to 8 months post infection). Ninety-three percent of hospitalized participants developed PASC, while 23% of those not requiring hospitalization developed PASC. At 90–174 days post SARS-CoV-2 diagnosis, 67% of all participants had persistent symptoms (N = 37 of 55), and 85% percent of participants who required hospitalization during initial infection (N = 20) still had symptoms. The most common symptoms reported after 15 days of infection were fatigue, loss of smell, loss of taste, exercise intolerance, and cognitive dysfunction. Conclusions Patients who were hospitalized for COVID-19 were significantly more likely to have PASC than those not requiring hospitalization, however 23% of patients who were not hospitalized also developed PASC. This patient-matched, multi-matrix, longitudinal biorepository from COVID-19 survivors with and without PASC will allow for current and future research to better understand the pathophysiology of disease and to identify targeted interventions to reduce risk for PASC. Registered 27 October 2020 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04603677 .

Abstract Background Despite scientific evidence that climate change has profound and far reaching implications for public health, translating this knowledge in a manner that supports citizen engagement, applied decision-making, and behavioural change can be challenging. This is especially true for complex vector-borne zoonotic diseases such as Lyme disease, a tick-borne disease which is increasing in range and impact across Canada and internationally in large part due to climate change. This exploratory research aims to better understand public risk perceptions of climate change and Lyme disease in order to increase engagement and motivate behavioural change. Methods A focus group study involving 61 participants was conducted in three communities in the Canadian Prairie province of Manitoba in 2019. Focus groups were segmented by urban, rural, and urban-rural geographies, and between participants with high and low levels of self-reported concern regarding climate change. Results Findings indicate a broad range of knowledge and risk perceptions on both climate change and Lyme disease, which seem to reflect the controversy and complexity of both issues in the larger public discourse. Participants in high climate concern groups were found to have greater climate change knowledge, higher perception of risk, and less skepticism than those in low concern groups. Participants outside of the urban centre were found to have more familiarity with ticks, Lyme disease, and preventative behaviours, identifying differential sources of resilience and vulnerability. Risk perceptions of climate change and Lyme disease were found to vary independently rather than correlate, meaning that high climate change risk perception did not necessarily indicate high Lyme disease risk perception and vice versa. Conclusions This research contributes to the growing literature framing climate change as a public health issue, and suggests that in certain cases climate and health messages might be framed in a way that strategically decouples the issue when addressing climate skeptical audiences. A model showing the potential relationship between Lyme disease and climate change perceptions is proposed, and implications for engagement on climate change health impacts are discussed.

Abstract Background Parents play a key role in infant’s development through their interactions and the type of environment they provide to promote active play. The amount of time parents are able to spend with their infant is dependent on their working status, yet few studies have explored parent perception of their infant’s active play by working status. The purpose of this study was to explore parent perception of active play and compare responses between working and stay-at-home parents. Methods Twenty-nine parents participated in this qualitative study by completing a one-time, in-person semi-structured interview based on the Theory of Planned Behavior. Themes were developed and compared based on parental working status using a directed content analysis approach. Results All parents believed active play could have a positive effect on their child’s development through physical, social and emotional, cognitive, and/or language and communication development. However, stay-at-home parents reported a broader impact of active play across these domains; whereas working parents most often referenced active play as impacting infant’s physical development. Social and emotional interactions were the highest reported form of active play among all parents. Additionally, all parents described similar barriers to increasing the time for active play. The most commonly reported barrier for all parents was time or schedule followed by care needs of the infant, environmental concerns, and need for restrictive devices (e.g., car seats). More stay-at-home parents than working parents reported the care needs of the infant as being a barrier. Recommendations for active play were not widely known amongst all parents, with a higher percentage of working parents reporting they would desire advice from a healthcare provider. Conclusions Working status of parents appears to have implications on perceptions of active play which in turn may influence infants’ development. Future studies should objectively assess the impact of parents’ working status on infant development and explore how gender of the parent may serve as a confounding variable.

Abstract Background Eating healthy, being physically active and breastfeeding can greatly support a new mother’s physiological and psychological health. However, within the United States, only 8.5% of women are meeting fruit and vegetable recommendations and only 35% of women are maintaining their pre-pregnancy physical activity after childbirth. Preliminary investigations suggest barriers such as lack of time and knowledge hinder a breastfeeding woman’s ability to eat well and be physically active. The purpose of this study was to explore women’s perceptions of healthy eating and physical activity while breastfeeding. Methods This qualitative study utilized a 33-question semi-structured interview guide developed using the constructs of Self-Determination Theory. Data were analyzed via the process of immersion/crystallization. Results A total of 24 breastfeeding women completed a roughly 40-min telephone interview. The mean age of the mother was 32 ± .88 and the mean age of the child being breastfed was 8.5 ± 1.4 months old. Findings demonstrate mothers see value in engaging in physical activity primarily for reasons related to self-care. In addition, breastfeeding women have a lack of information and support regarding healthy eating and physical activity while breastfeeding and many are receiving misinformation through resources such as Facebook support groups. Finally, mothers want more resources available that focus specifically on healthy behaviors while breastfeeding. Conclusion Women need greater access to education and resources regarding healthy eating and physical activity while breastfeeding. Ideally, information and resources would come from an educated health professional such as their healthcare provider rather than an internet source.

Abstract Background Luminal breast cancer (L-BCa) comprises the majority of incurable, distally metastatic breast cancer cases. Estrogen supports growth of L-BCa cells but suppresses invasiveness. Estrogen also induces the progesterone receptor (PR). Invasiveness and metastasis of L-BCa cells is supported by the short PR isoform (PR-A), in response to the range of pre- and post-menopausal plasma hormone levels, by counteracting the effects of estrogen via micro RNA-mediated cross-talk with the estrogen receptor (ER). PR-B directly supports L-BCa invasion and metastasis and also inhibits tumor growth, both only at high progesterone levels. As public datasets on L-BCa tumors cannot distinguish PR-A, this study was designed to seek clinical evidence for the role of PR-A in metastasis in comparison with PR-B and ER. Methods Measurement of tumor PR-A, PR-B and ER mRNA expression in 125 treatment-naive primary L-BCa patients with differential node involvement and analysis using linear mixed effects models. Transcriptional activity assays of PR-A and PR-B. Results Lymph node involvement was strongly associated with PR-A expression (median, 3-fold higher vs. node-negative), independent of age, pathologic type, tumor grade, HER2 and PR-B. PR-B and ER correlated weakly with PR-A, but whereas PR-B and the PR-A/PR-B ratio were not significantly associated with node involvement, ER weakly negatively correlated with node positivity. PR-A was hypersensitive to mifepristone compared with PR-B. Conclusions Taken together with previous mechanistic studies, the findings provide clinical evidence in support of the role of PR-A in L-BCa metastasis. They also suggest the possibility of developing selective PR-A modulators for future interventions in appropriate clinical situations.

Abstract Background Rates of obesity among children ages zero to five are rapidly increasing. Greater efforts are needed to promote healthy behaviors of young children. Mothers are especially important targets for promoting health as mothers’ views play a vital role in helping their children foster healthy habits from an early age. Research has found parents’ views of infants’ weight may influence their feeding practices; however, limited research has explored mothers’ view of infants’ weight in relation to the promotion of physical activity. Therefore, the purpose of this study was to explore the perceptions of mothers of normal weight infants and overweight infants about their infant’s weight and physical activity. Methods Semi-structured interviews were conducted with mothers of normal weight (n = 18) and of overweight (n = 11) infants (6.5 ± 0.5 month) in a Midwestern city in the United States. A thematic analysis was used to analyze the data. Results A majority of mothers thought infants could be overweight. However, no mothers referenced their own infant as overweight. Mothers most commonly noted infants could be overweight only if they were formula fed and/or were overfed, not if they were breastfed. Mothers views were not negatively influenced by others who mentioned that their child was either “big” or “small” and only one mother had been told her infant was overweight. A majority of mothers thought an infant could be physically active. When discussing infant activity, mothers primarily referred to it in terms of general mobility and a few thought activity level was related to a personality characteristic. Mothers intended to promote physical activity in the future either through outdoor play or specific organized activities such as sports. Despite a majority of mothers stating they were currently physically active themselves, only a few talked about interacting with their infant to promote their infant’s physical activity. Conclusions Efforts are needed by healthcare professionals and other public health professionals to inform mothers about the dangers of increased weight during infancy as well as the importance of interacting with infants to promote physical activity.

Abstract Background Health care providers (HCPs) play an important role in public health emergency preparedness and response (PHEPR) so need to be aware of public health threats and emergencies. To inform HCPs, public health issues PHEPR messages that provide guidelines and updates, and facilitate surveillance so HCPs will recognize and control communicable diseases, prevent excess deaths and mitigate suffering. Public health agencies need to know that the PHEPR messages sent to HCPs reach their target audience and are effective and informative. Public health agencies need to know that the PHEPR messages sent to HCPs reach their target audience and are effective and informative. We conducted a literature review to investigate the systems and tools used by public health to generate PHEPR communications to HCPs, and to identify specific characteristics of message delivery mechanisms and formats that may be associated with effective PHEPR communications. Methods A systematic review of peer- and non-peer-reviewed literature focused on the following questions: 1) What public health systems exist for communicating PHEPR messages from public health agencies to HCPs? 2) Have these systems been evaluated and, if yes, what criteria were used to evaluate these systems? 3) What have these evaluations discovered about characterizations of the most effective ways for public health agencies to communicate PHEPR messages to HCPs? Results We identified 25 systems or tools for communicating PHEPR messages from public health agencies to HCPs. Few articles assessed PHEPR communication systems or messaging methods or outcomes. Only one study compared the effectiveness of the delivery format, device or message itself. We also discovered that the potential is high for HCPs to experience "message overload" given redundancy of PHEPR messaging in multiple formats and/or through different delivery systems. Conclusions We found that detailed descriptions of PHEPR messaging from public health to HCPs are scarce in the literature and, even when available are rarely evaluated in any systematic fashion. To meet present-day and future information needs for emergency preparedness, more attention needs to be given to evaluating the effectiveness of these systems in a scientifically rigorous manner.