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Abstract Therapy targeting the BRAF-MEK cascade created a treatment revolution for patients with BRAF mutant advanced melanoma. Unfortunately, 80% patients treated will progress by 5 years follow-up. Thus, it is imperative we study mechanisms of melanoma progression and therapeutic resistance. We created a scRNA (single cell RNA) atlas of 128,230 cells from 18 tumors across the treatment spectrum, discovering melanoma cells clustered strongly by transcriptome profiles of patients of origins. Our cell-level investigation revealed gains of 1q and 7q as likely early clonal events in metastatic melanomas. By comparing patient tumors and their derivative cell lines, we observed that PD1 responsive tumor fraction disappears when cells are propagated in vitro. We further established three anti-BRAF-MEK treatment resistant cell lines using three BRAF mutant tumors. ALDOA and PGK1 were found to be highly expressed in treatment resistant cell populations and metformin was effective in targeting the resistant cells. Our study suggests that the investigation of patient tumors and their derivative lines is essential for understanding disease progression, treatment response and resistance.

Objective. To compare the adequacy, agreement, and acceptability of Papanicolaou testing (cytology) for cervical cancer screening using self-collected samples compared to physician-collected samples in Grenada in the Caribbean. Furthermore, the study identifies the human papillomavirus (HPV) genotypes present among asymptomatic women testing positive for HPV, the etiologic cause of cervical cancer. Methods. Participants were divided into two groups and two cervical samples were collected from the women in each group: a self-collected sample and a physician-collected sample. Cervical specimens were tested for cytology and HPV. HPV genotyping was performed on positive specimens. Results. Self-collected samples were adequate and in agreement with physician-collected samples, showing no difference between the two sampling methods. Oncogenic high-risk HPV genotypes were identified in cervical samples which were positive for atypical squamous cells and low-grade squamous intraepithelial lesions. The high-risk HPV genotypes found, notably HPV 45 and 53, differed from those most commonly reported. Although the commonly reported high-risk genotypes HPV 16 and 18 were found, so were 31, 33, 35, 52, 66, 68, and 82. Conclusions. Using self-collection facilitated the discovery of unexpected HPV genotypes among asymptomatic women in Grenada. These findings add new information to the literature regarding cervical cancer and neoplasia screening and HPV genotypes in the Caribbean. This genotype information may impact surveillance of women with low-grade lesions, HPV vaccine selection, and possibly further vaccine research. Research regarding HPV in Caribbean pathology samples of cervical neoplasia and cancer is needed.

Objectives This study was undertaken to identify potential predictors of atrial fibrillation after cardiac surgery (AFACS) through a modified Delphi process and expert consensus. These will supplement predictors identified through a systematic review and cohort study to inform the development of two AFACS prediction models as part of the PARADISE project (NCT05255224). Atrial fibrillation is a common complication after cardiac surgery. It is associated with worse postoperative outcomes. Reliable prediction of AFACS would enable risk stratification and targeted prevention. Systematic identification of candidate predictors is important to improve validity of AFACS prediction tools.Design This study is a Delphi consensus exercise.Setting This study was undertaken through remote participation.Participants The participants are an international multidisciplinary panel of experts selected through national research networks.Interventions This is a two-stage consensus exercise consisting of generating a long list of variables, followed by refinement by voting and retaining variables selected by at least 40% of panel members.Results The panel comprised 15 experts who participated in both stages, comprising cardiac intensive care physicians (n=3), cardiac anaesthetists (n=2), cardiac surgeons (n=1), cardiologists (n=4), cardiac pharmacists (n=1), critical care nurses (n=1), cardiac nurses (n=1) and patient representatives (n=2). Our Delphi process highlighted candidate AFACS predictors, including both patient factors and those related to the surgical intervention. We generated a final list of 72 candidate predictors. The final list comprised 3 demographic, 29 comorbidity, 4 vital sign, 13 intraoperative, 10 postoperative investigation and 13 postoperative intervention predictors.Conclusions A Delphi consensus exercise has the potential to highlight predictors beyond the scope of existing literature. This method proved effective in identifying a range of candidate AFACS predictors. Our findings will inform the development of future AFACS prediction tools as part of the larger PARADISE project.Trial registration number NCT05255224.

BackgroundThe use of telemedicine (TELE) increased exponentially during the COVID-19 pandemic. While patient experience with TELE has been studied in other medical disciplines, its impact and applicability to integrative medicine practices remain unknown. ObjectiveThe aim of this study is to assess the impact of visit modality, TELE versus face-to-face (F2F) encounters, on patient experience at an integrative medicine practice at a single academic medical center. Given the significant role of the patient-physician relationship, therapeutic presence, and touch in integrative medicine, we hypothesized that TELE would result in reduced patient experience compared to traditional F2F encounters. MethodsA retrospective examination of Press Ganey surveys at an academic, consultative, and integrative medicine practice was conducted. Anonymous surveys completed by patients, older than 18 years of age, who had TELE or F2F appointments from April 1, 2020, to March 31, 2023, were included. At our medical center, patients commonly travel in from out of state for complex care. We examined percentage “top box” scores (ie, the percentage of respondents who selected the most positive response category on the survey, “very good”), across a variety of experience metrics. ANOVA and chi-square analyses were completed, with a significance threshold of P

The fossil record of the U.S. Pacific Northwest preserves many Middle Miocene floras with potential for revealing long-term climate-vegetation dynamics during the Miocene Climatic Optimum. However, the possibility of strong, eccentricity-paced climate oscillations and concurrent, intense volcanism may obscure the signature of prevailing, long-term Miocene climate change. To test the hypothesis that volcanic disturbance drove Middle Miocene vegetation dynamics, high-resolution, stratigraphic pollen records and other paleobotanical data from nine localities of the Sucker Creek Formation were combined with sedimentological and geochemical evidence of disturbance within an updated chronostratigraphic framework based on new U-Pb zircon ages from tuffs. The new ages establish a refined, minimum temporal extent of the Sucker Creek Formation, ~15.8 to ~14.8 Ma, and greatly revise the local and regional chronostratigraphic correlations of its dispersed outcrop belt. Our paleoecological analysis at one ~15.52 Ma locality reveals two abrupt shifts in pollen spectra coinciding with the deposition of thick ash-flow tuffs, wherein vegetation dominated by Cupressaceae/Taxaceae, probably representing a Glyptostrobus oregonensis swamp, and upland conifers was supplanted by early-successional forests with abundant Alnus and Betula. Another ephemeral shift from Cupressaceae/Taxaceae swamp taxa in favor of upland conifers Pinus and Tsuga correlates with a shift from low-Ti shale to high-Ti claystone, suggesting a link between altered surface hydrology and vegetation. In total, three rapid vegetation shifts coincide with ash-flow tuffs and are attributed to volcanic disturbance. Longer-term variability between localities, spanning ~1 Myr of the Miocene Climatic Optimum, is chiefly attributed to eccentricity-paced climate change. Overall, Succor Creek plant associations changed frequently over ≤105 years timespans, reminiscent of Quaternary vegetation records. Succor Creek stratigraphic palynology suggests that numerous and extensive collection of stratigraphically controlled samples is necessary to understand broader vegetation trends through time.

BackgroundDementia with Lewy bodies (DLB) is one of the most common degenerative dementias, but research on end-of-life experiences for people with DLB and their caregivers is limited.MethodDyads of individuals with moderate-advanced DLB and their primary informal caregivers were recruited from specialty clinics, advocacy organizations, and research registries and followed prospectively every 6 months. The current study examines results of caregiver study visits 3 months after the death of the person with DLB. These visits included the Last Month of Life survey, study-specific questions, and a semi-structured interview querying end-of-life experiences.ResultsIndividuals with DLB (n = 50) died 3.24 ± 1.81 years after diagnosis, typically of disease-related complications. Only 44% of caregivers reported a helpful conversation with clinicians regarding what to expect at the end of life in DLB. Symptoms commonly worsening prior to death included: cognition and motor function, ADL dependence, behavioral features, daytime sleepiness, communication, appetite, and weight loss. Almost 90% of participants received hospice care, but 20% used hospice for ConclusionMost caregivers of individuals who died with DLB reported positive end-of-life experiences. However, the study identified multiple opportunities for improvement relating to clinician counseling of patients/families, support/hospice referrals, and monitoring individuals with DLB to identify approaching end of life. Future research should quantitatively identify changes that herald end of life in DLB and develop tools that can assist clinicians in evaluating disease stage to better inform counseling and timely hospice referrals.Trial registrationTrial registration information: NCT04829656.

BackgroundCurrent guidelines for gender-affirming hormone therapy (GAHT) for transgender women are mostly based on clinical experience from experts in the field and treatments used on postmenopausal women. While care is currently provided with the best available evidence, there is a critical gap in knowledge about the safest and most effective estradiol routes of administration for GAHT in transgender women; this statement is supported by the World Professional Association for Transgender Health on their Standards of Care for the Health of Transgender and Gender Diverse People, version 8. Furthermore, the reported rates of cardiometabolic adverse events in transgender women highlight the importance of investigating changes in lipoproteins, glucose, and insulin sensitivity, among other markers while receiving GAHT. ObjectiveThis study aims to evaluate the degree of testosterone suppression achieved at 1, 6, and 12 months in treatment-naive transgender women when randomized to GAHT with estradiol and spironolactone as antiandrogens. As a secondary aim, this study will assess the treatment effect on metabolic and coagulation factors from baseline to 6 and 12 months after initiating GAHT. MethodsThis is a prospective pilot, open-label, randomized clinical trial conducted at an adult transgender clinic in a tertiary medical center. The 3 treatment arms include once-daily sublingual 17-β estradiol, twice-daily sublingual 17-β estradiol, and transdermal 17-β estradiol. All participants received spironolactone as an antiandrogen. Transgender women aged 18 to 45 years who are being evaluated for the initiation of GAHT with 17-β estradiol and did not have a history of coagulopathy, cigarette smoking, liver disease, dyslipidemia requiring treatment, or use of gonadotropin-releasing hormone agonist were eligible to enroll. The main outcome is the total testosterone suppression at 1 and 6 months after the initiation of GAHT, and the secondary outcome is to assess treatment effect in a lipid panel; homeostatic model assessment for insulin resistance; coagulation factors II, IX, and XI; Von Willebrand factor; activated protein C resistance; protein C; and protein S at baseline, 6 months, and 12 months after therapy is initiated. ResultsThis study was funded in March 2022, and enrollment concluded in August 2022. It was concluded in July 2023, and currently, the results are being analyzed for publication. ConclusionsThe Transgender Estradiol Affirming Therapy (TREAT) study offers a rigorous and reproducible approach to answer important questions regarding GAHT in transgender women, specifically, the most effective 17-β estradiol regimen to suppress testosterone levels to 50 ng/dL, as currently recommended. Trial RegistrationClinicalTrials.gov NCT05010707; https://clinicaltrials.gov/study/NCT05010707 International Registered Report Identifier (IRRID)DERR1-10.2196/53092

Introduction The health and well-being of Aboriginal Australians is inextricably linked to culture and Country. Our study challenges deficit approaches to health inequities by seeking to examine how cultural connection, practice and resilience among Aboriginal peoples through participation in ‘cultural camps’ held on sites of cultural significance promotes health and well-being.Methods and analysis The study will be undertaken in close collaboration and under the governance of traditional cultural knowledge holders from Yuwaalaraay, Gamilaraay and Yuin nation groups in New South Wales, Australia. Three cultural camps will be facilitated, where participants (n=105) will engage in activities that foster a connection to culture and cultural landscapes. A survey assessing connection to culture, access to cultural resources, resilience, self-rated health and quality of life will be administered to participants pre-camp and post-camp participation, and to a comparative group of Aboriginal adults who do not attend the camp (n=105). Twenty participants at each camp (n=60) will be invited to participate in a yarning circle to explore cultural health, well-being and resilience. Quantitative analysis will use independent samples’ t-tests or χ2 analyses to compare camp and non-camp groups, and linear regression models to determine the impact of camp attendance. Qualitative analysis will apply inductive coding to data, which will be used to identify connections between coded concepts across the whole data set, and explore phenomenological aspects. Results will be used to collaboratively develop a ‘Model of Cultural Health’ that will be refined through a Delphi process with experts, stakeholders and policymakers.Ethics and dissemination The study has ethics approval from the Aboriginal Health and Medical Research Council (#1851/21). Findings will be disseminated through a combination of peer-reviewed articles, media communication, policy briefs, presentations and summary documents to stakeholders.

Children with postpericardiotomy syndrome may develop hemodynamically significant pericardial effusions warranting drainage by surgical pericardial window or pericardiocentesis. The optimal approach is unknown. We performed a retrospective observational study at two pediatric cardiac centers. We included 42 children aged

Abstract Biomaterials with antimicrobial activity are gaining attention due to their biodegradability and efficacy in interacting with a wide range of microorganisms. A new cellulose nano-biomaterial, endospermic nanocellulose crystals (ENC) obtained from parenchymal tissue of ivory nut endosperm, has a natural capacity as a universal binder. This feature is enhanced when it is chemically functionalized, and can be exploited in the fight against microbes. We tested the ability of sulfated ENC in aqueous suspension to encapsulate viruses through a crosslinking reaction mediated by cations. 0.25% w/v ENC suspensions efficiently encapsulated spike (S) protein, preventing its interaction with ACE2 receptor. ENC was further able to encapsulate SARS-CoV-2 pseudoviruses and prevent infection of 293T-hsACE2 cells. ENC also suppressed infection of MT-4 cells with HIV-1LAI.04. This antiviral activity of sulfated ENC is due to the irreversible interaction of ENC with viral particles mediated by crosslinking, as antiviral activity was less effective in the absence of cations. Additionally, ENC was used as a matrix to immobilize recombinant ACE2 receptors and anti-S IgG, creating molecular lures that efficiently inhibited SARS-CoV-2 infections in vitro. These results show that sulfated ENC from ivory nuts can be used as an efficient antiviral material.

Introduction Catecholamine vasopressors such as norepinephrine are the standard drugs used to maintain mean arterial pressure during liver transplantation. At high doses, catecholamines may impair organ perfusion. Angiotensin II is a peptide vasoconstrictor that may improve renal perfusion pressure and glomerular filtration rate, a haemodynamic profile that could reduce acute kidney injury. Angiotensin II is approved for vasodilatory shock but has not been rigorously evaluated for treatment of hypotension during liver transplantation. The objective is to assess the efficacy of angiotensin II as a second-line vasopressor infusion during liver transplantation. This trial will establish the efficacy of angiotensin II in decreasing the dose of norepinephrine to maintain adequate blood pressure. Completion of this study will allow design of a follow-up, multicentre trial powered to detect a reduction of organ injury in liver transplantation.Methods and analysis This is a double-blind, randomised clinical trial. Eligible subjects are adults with a Model for End-Stage Liver Disease Sodium Score ≥25 undergoing deceased donor liver transplantation. Subjects are randomised 1:1 to receive angiotensin II or saline placebo as the second-line vasopressor infusion. The study drug infusion is initiated on reaching a norepinephrine dose of 0.05 µg kg-1 min-1 and titrated per protocol. The primary outcome is the dose of norepinephrine required to maintain a mean arterial pressure ≥65 mm Hg. Secondary outcomes include vasopressin or epinephrine requirement and duration of hypotension. Safety outcomes include incidence of thromboembolism within 48 hours of the end of surgery and severe hypertension. An intention-to-treat analysis will be performed for all randomised subjects receiving the study drug. The total dose of norepinephrine will be compared between the two arms by a one-tailed Mann-Whitney U test.Ethics and dissemination The trial protocol was approved by the local Institutional Review Board (#20–30948). Results will be posted on ClinicalTrials.gov and published in a peer-reviewed journal.Trial registration number ClinicalTrials.govNCT04901169

BackgroundCommunity violence is a persistent and challenging public health problem. Community violence not only physically affects individuals, but also its effects reverberate to the well-being of families and entire communities. Being exposed to and experiencing violence are adverse community experiences that affect the well-being and health trajectories of both children and adults. In the United States, community violence has historically been addressed through a lens of law enforcement and policing; the impact of this approach on communities has been detrimental and often ignores the strengths and experiences of community members. As such, community-centered approaches to address violence are needed, yet the process to design, implement, and evaluate these approaches is complex. Alternatives to policing responses are increasingly being implemented. However, evidence and implementation guidance for community-level public health approaches remain limited. This study protocol seeks to address community violence through a resilience framework—Adverse Community Experiences and Resilience (ACE|R)—being implemented in a major US city and leveraging a strategy of community organizing to advance community violence prevention. ObjectiveThe objective of this research is to understand the impact of community-level violence prevention interventions. Furthermore, we aim to describe the strategies of implementation and identify barriers to and facilitators of the approach. MethodsThis study uses a hybrid type 1 effectiveness-implementation design. Part 1 of the study will assess the effectiveness of the ACE|R framework plus community organizing by measuring impacts on violence- and health-related outcomes. To do so, we plan to collect quantitative data on homicides, fatal and nonfatal shootings, hospital visits due to nonaccidental injuries, calls for service, and other violence-related data. In Part 2 of the study, to assess the implementation of ACE|R plus community organizing, we will collect process data on community engagement events, deliver community trainings on community leadership and organizing, and conduct focus groups with key partners about violence and violence prevention programs in Milwaukee. ResultsThis project received funding on September 1, 2020. Prospective study data collection began in the fall of 2021 and will continue through the end of 2023. Data analysis is currently underway, and the first results are expected to be submitted for publication in 2024. ConclusionsCommunity violence is a public health problem in need of community-centered solutions. Interventions that center community and leverage community organizing show promise in decreasing violence and increasing the well-being of community members. Methods to identify the impact of community-level interventions continue to evolve. Analysis of outcomes beyond violence-specific outcomes, including norms and community beliefs, may help better inform the short-term and proximal impacts of these community-driven approaches. Furthermore, hybrid implementation-effectiveness trials allow for the inevitable contextualization required to disseminate community interventions where communities drive the adaptations and decision-making. International Registered Report Identifier (IRRID)DERR1-10.2196/50444

BackgroundIncreasing attention is being given to the growing concerns about social isolation, loneliness, and compromised emotional well-being experienced by young adults and older individuals affected by Alzheimer disease and related dementias (ADRD). Studies suggest that reminiscence strategies combined with an intergenerational approach may yield significant social and mental health benefits for participants. Experts also recommended the production of a digital life story book as part of reminiscence. Reminiscence is typically implemented by trained professionals (eg, social workers and nurses); however, there has been growing interest in using trained volunteers owing to staffing shortages and the costs associated with reminiscence programs. ObjectiveThe proposed study will develop and test how reminiscence offered by trained young adult volunteers using a digital storytelling platform may help older adults with ADRD to improve their social and emotional well-being. MethodsThe proposed project will conduct a randomized controlled trial to assess the effects of the intervention. The older and young adult participants will be randomly assigned to the intervention (reminiscence based) or control groups and then be randomly matched within each group. Data will be collected at baseline before the intervention, in the middle of the intervention, at end of the intervention, and at 3 months after the intervention. An explanatory sequential mixed methods design will be used to take advantage of the strengths of both quantitative and qualitative methods. The quantitative data from surveys will be entered into SPSS and analyzed using covariate-adjusted linear mixed models for repeated measures to compare the intervention and control groups over time on the major outcomes of participants. Conventional content analysis of qualitative interviews will be conducted using data analysis software. ResultsThe project was modified to a telephone-based intervention owing to the COVID-19 pandemic. Data collection started in 2020 and ended in 2022. In total, 103 dyads were matched at the beginning of the intervention. Of the 103 dyads, 90 (87.4%) dyads completed the midtest survey and 64 (62.1%) dyads completed the whole intervention and the posttest survey. Although we are still cleaning and finalizing data analyses, the preliminary results from both quantitative and qualitative data showed promising results of this intergenerational reminiscence approach that benefits both the older adults who have cognitive impairments and the young adult participants. ConclusionsIntergenerational reminiscence provided by young adult college student offers promising benefits for both the younger and older generations. Future studies may consider scaling up this pilot into a trackable, replicable model that includes more participants with diverse background (eg, public vs private college students and older adults from other agencies) to test the effectiveness of this intervention for older adults with ADRD. Trial RegistrationClinicalTrials.gov NCT05984732; https://classic.clinicaltrials.gov/ct2/show/NCT05984732 International Registered Report Identifier (IRRID)DERR1-10.2196/49752

Abstract The United Nations projects that one in every six people will be over the age of 65 by the year 2050. With a rapidly aging population, the risk of Alzheimer's disease (AD) becomes a major concern. AD is a multifactorial disease that involves neurodegeneration in the brain with mild dementia and deficits in memory and other cognitive domains. Additionally, it has been established that individuals with Human Immunodeficiency Virus-1 (HIV-1) experience a 5 to 10-year accelerated aging and an increased risk of developing HIV-associated neurocognitive disorders (HAND). Despite a significant amount of clinical evidence pointing towards a potential overlap between neuropathogenic processes in HAND and AD, the underlying epigenetic link between these two diseases is mostly unknown. This study is focused on identifying differentially expressed genes observed in both AD and HAND using linear regression models and a more robust significance analysis of microarray. The results established that the dysregulated type 1 and 2 interferon pathways observed in both AD and HAND contribute to the similar pathologies of these diseases within the brain. The current study identifies the important roles of interferon pathways in AD and HAND, a relationship that may be useful for earlier detection in the future.

The Coronavirus Disease 2019 (COVID-19) pandemic had a profound impact on sleep and psychological well-being for individuals worldwide. This pre-registered investigation extends our prior study by tracking self-reported social jetlag (SJL), social sleep restriction (SSR), and perceived life stress from May 2020 through October 2021. Using web-based surveys, we collected self-reported sleep information with the Ultrashort Munich Chronotype Questionnaire at three additional timepoints (September 2020, February 2021 and October 2021). Further, we measured perceived life stress with the Perceived Stress Scale at two additional timepoints (February 2021 and October 2021). In a subsample of 181, predominantly female (87%), United States adults aged 19–89 years, we expanded our prior findings by showing that the precipitous drop in SJL during the pandemic first wave (May 2020), compared to pre-pandemic (February, 2020), rapidly rose with loosening social restrictions (September 2020), though never returned to pre-pandemic levels. This effect was greatest in young adults, but not associated with self-reported chronotype. Further, perceived life stress decreased across the pandemic, but was unrelated to SJL or SSR. These findings suggest that sleep schedules were sensitive to pandemic-related changes in social restrictions, especially in younger participants. We posit several possible mechanisms supporting these findings.

Abstract Long-duration spaceflight impacts human physiology, including well documented immune system dysregulation. The space food system has the potential to serve as a countermeasure to maladaptive physiological changes during spaceflight. However, the relationship between dietary requirements, the food system, and spaceflight adaptation requires further investigation to adequately define countermeasures and prioritize resources on future spaceflight missions. We evaluated the impact of an enhanced spaceflight diet, with increased quantity and variety of fruits, vegetables, fish, and other foods rich in flavonoids and omega-3 fatty acids, compared to a standard spaceflight diet on multiple health and performance outcomes in 16 subjects over four 45-day closed chamber missions in the NASA Human Exploration Research Analog (HERA). Subjects consuming the enhanced spaceflight diet had lower cholesterol levels, lower stress (i.e. cortisol levels), better cognitive speed, accuracy, and attention, and a more stable microbiome and metatranscriptome than subjects consuming the standard diet. Although no substantial changes were observed in the immune response, there were also no immune challenges, such as illness or infection, so the full benefits of the diet may not have been apparent in these analog missions. These results indicate that a spaceflight diet rich in fruits, vegetables, and omega-3 fatty acids produces significant health and performance benefits even over short durations. Further investigation is required to fully develop dietary countermeasures to physiological decrements observed during spaceflight. These results will have implications for food resource prioritization on spaceflight missions.

BackgroundAlzheimer disease and related dementias (ADRD) pose significant challenges as chronic health conditions in the United States. Additionally, there are notable disparities in the diagnosis and prevalence of ADRD among diverse populations. Specifically, African American populations have a higher risk of developing late-onset ADRD than White people, and missed diagnoses of ADRD are more common among older African American populations than older White populations. These disparities also impact African American ADRD family caregivers. ObjectiveThe overall goal of this project is to develop a culturally informed, lay provider psychoeducational intervention named Senior Companion Program Plus (SCP Plus), which is specifically designed for African American ADRD caregivers and is potentially accessible, affordable, and sustainable. MethodsIn the proposed explanatory sequential mixed methods study, a randomized controlled trial will be used that includes 114 African American family caregivers of a relative with ADRD who will participate in the 3-month SCP Plus program. ResultsThe study was funded on September 15, 2018, by the National Institutes of Health (1R15AG058182-01A1). Data collection began on May 16, 2019, but due to COVID-19 restrictions, ended 12 months into the planned 27-month recruitment period on March 31, 2023. The study was completed in June 30, 2023, and currently the results are being analyzed. ConclusionsThe SCP Plus offers promise as an intervention that utilizes an existing platform for the delivery of a lay provider intervention and offers a novel approach for addressing gaps in accessible, community-based support for caregivers of people with ADRD. Trial RegistrationClinicalTrials.gov NCT03602391; https://classic.clinicaltrials.gov/ct2/show/NCT03602391 International Registered Report Identifier (IRRID)RR1-10.2196/49679

BackgroundResearch and policy demonstrate the value of and need for systematically identifying and preparing care partners for their caregiving responsibilities while their family member or friend living with dementia is hospitalized. The Care Partner Hospital Assessment Tool (CHAT) has undergone content and face validation and has been endorsed as appropriate by clinicians to facilitate the timely identification and preparation of care partners of older adult patients during their hospitalization. However, the CHAT has not yet been adapted or prospectively evaluated for use with care partners of hospitalized people living with dementia. Adapting and testing the CHAT via a pilot study will provide the necessary evidence to optimize feasibility and enable future efficacy trials. ObjectiveThe purpose of this paper is to describe the study protocol for the adaptation and testing of the CHAT for use among care partners of hospitalized people living with dementia to better prepare them for their caregiving responsibilities after hospital discharge. MethodsOur protocol is based on the National Institutes of Health Stage Model and consists of 2 sequential phases, including formative research and the main trial. In phase 1, we will use a participatory human-centered design process that incorporates people living with dementia and their care partners, health care administrators, and clinicians to adapt the CHAT for dementia care (ie, the Dementia CHAT [D-CHAT]; stage IA). In phase 2, we will partner with a large academic medical system to complete a pilot randomized controlled trial to examine the feasibility and estimate the size of the effect of the D-CHAT on care partners’ preparedness for caregiving (stage IB). We anticipate this study to take approximately 60 months to complete, from study start-up procedures to dissemination. The 2 phases will take place between December 1, 2022, and November 30, 2027. ResultsThe study protocol will yield (1) a converged-upon, ready-for-feasibility testing D-CHAT; (2) descriptive and feasibility characteristics of delivering the D-CHAT; and (3) effect size estimates of the D-CHAT on care partner preparedness. We anticipate that the resultant D-CHAT will provide clinicians with guidance on how to identify and better prepare care partners for hospitalized people living with dementia. In turn, care partners will feel equipped to fulfill caregiving roles for their family members or friends living with dementia. ConclusionsThe expected results of this study are to favorably impact hospital-based care processes and outcomes for people living with dementia and their care partners and to elucidate the essential caregiving role that so many care partners of people living with dementia assume. Trial RegistrationClinicalTrials.gov NCT05592366; https://clinicaltrials.gov/ct2/show/NCT05592366 International Registered Report Identifier (IRRID)PRR1-10.2196/46808

Background: Multimorbidity is linked to worse health outcomes than single health conditions. However, recent studies show that obesity may reduce the risk of developing substance use disorders (SUDs), particularly in vulnerable populations. We investigated how comorbid obesity and tobacco use disorder (TUD) relate to the risk of SUDs and psychiatric conditions. Methods: Data was used from 36,309 individuals who completed the National Epidemiological Survey on Alcohol and Related Conditions - Wave III. Individuals who met the DSM-5 criteria for TUD in the last year were defined as the TUD group. Obesity was defined as having a body mass index (BMI) greater than 30 kg/m2. Using this information, individuals were grouped into categories, with people being identified as either having obesity, TUD, both obesity and TUD, or not having either obesity or TUD (comparison). Groups were compared against their comorbid diagnoses of either an additional SUD or psychiatric conditions. Results: Controlling for demographic characteristics, we found that individuals with obesity including those individuals with TUD, had lower rates of comorbid SUD diagnosis than individuals with TUD alone. Additionally, individuals with combined TUD and obesity, and those with TUD alone, had the highest rates of comorbid psychiatric disorder diagnosis. Conclusions: The current study aligns with previous research suggesting that obesity may reduce risk of substance use disorders, even in individuals who have other risk factors promoting harmful substance use (e.g., tobacco use). These findings may inform targeted intervention strategies for this clinically relevant subpopulation.

Abstract Background 3D printed models are becoming increasingly popular in healthcare as visual and tactile tools to enhance understanding of anatomy and pathology in medical trainee education, provide procedural simulation training, and guide surgical procedures. Patient-specific 3D models are currently being used preoperatively for trainee medical education in planning surgical approaches and intraoperatively to guide decision-making in several specialties. Our study group utilized a modified Delphi process to create a standardized assessment for trainees using patient-specific 3D models as a tool in medical education during pre-surgical planning. Methods A literature review was conducted to identify survey questions administered to clinicians in published surgical planning studies regarding the use of patient-specific 3D models. A core study team reviewed these questions, removed duplicates, categorized them, mapped them to overarching themes, and, where applicable, modified individual questions into a form generalizable across surgical specialties. The core study panel included a physician, physician-scientist, social scientist, engineer/medical student, and 3D printing lab manager. A modified Delphi process was then used to solicit feedback on the clarity and relevance of the individual questions from an expert panel consisting of 12 physicians from specialties including anesthesiology, emergency medicine, radiology, urology, otolaryngology, and obstetrics/gynecology. When the Radiological Society of North America (RSNA)/American College of Radiology (ACR) 3D Printing Registry Data Dictionary was released, additional survey questions were reviewed. A final cross-disciplinary survey of the utility of 3D printed models in surgical planning medical education was developed. Results The literature review identified 100 questions previously published in surveys assessing patient-specific 3D models for surgical planning. Following the review, generalization, and mapping of survey questions from these studies, a list of 24 questions was generated for review by the expert study team. Five additional questions were identified in the RSNA/ACR 3D Printing Registry Data Dictionary and included for review. A final questionnaire consisting of 20 questions was developed. Conclusions As 3D printed models become more common in medical education, the need for standardized assessment is increasingly essential. The standardized questionnaire developed in this study reflects the interests of a variety of stakeholders in patient-specific 3D models across disciplines.

Abstract COVID-19 is associated with significant extrapulmonary symptoms. Myocardial involvement has been described for infections with SARS-CoV-2 which may lead to an increase in morbidity and mortality. The objective of our study was to investigate the association of COVID-19 and atrial fibrillation (AF) or atrial flutter (AFl) in hospitalized patients. This retrospective study used electronic medical records to detect patients with COVID-19 and their comorbidities within the Mass General Brigham hospital system. All patients ≥ 18 years who were hospitalized and received a PCR test for SARS-CoV-2 were screened for inclusion as well as patients from a pre-pandemic cohort. We matched on common risk factors for AF and then used multivariable logistic regression to estimate the odds for AF or AFl. Of 78,725 patients eligible for analysis, 11,004 COVID-19 negative patients were matched to 3,090 COVID-19 positive patients and 5005 pre-pandemic patients were matched to 2283 COVID-19 positive patients. After adjusting for demographics and comorbidities, COVID-19 positive patients had 1.19 times the odds (95% CI 1.00, 1.41) of developing AF compared to COVID-19 negative patients and 1.57 times the odds (95% CI 1.23, 2.00) of developing AF compared to pre-pandemic patients. Our study demonstrated an increased risk for AF, directing the attention for improved screening and treatment regimens for the sequelae of COVID-19. While COVID-19 continues to affect many people around the world, AF may be a significant cause for morbidity and mortality. Adequate detection and treatment of AF is essential to reduce the burden of disease.

BackgroundResearch and policy demonstrate the value and need for the systematic inclusion of care partners in hospital care delivery of people living with Alzheimer disease and related dementias (ADRD). Support provided to care partners through information and training regarding caregiving responsibilities is important to facilitating their active inclusion and ultimately improving hospital outcomes of people living with ADRD. To promote care partners’ active inclusion, a toolkit that guides health systems in the identification, assessment, and training of care partners is needed. User-centered approaches can address this gap in practice by creating toolkits that are practical and responsive to the needs of care partners and their hospitalized family members and friends living with ADRD. ObjectiveThis paper describes the study protocol for the development and refinement of the ADRD Systematic Hospital Inclusion Family Toolkit (A-SHIFT). A-SHIFT will provide health care systems with guidance on how to effectively identify, assess, and train care partners of hospitalized persons living with ADRD. MethodsThe A-SHIFT study protocol will use a 3-aimed, convergent mixed method approach to iteratively develop and refine the toolkit. In Aim 1, we will use a systems-engineering approach to characterize patterns of care partner inclusion in hospital care for people living with ADRD. In Aim 2, we will partner with stakeholders to identify and prioritize health care system facilitators and barriers to the inclusion for care partners of hospitalized people living with ADRD. In Aim 3, we will work with stakeholders to co-design an adaptable toolkit to be used by health systems to facilitate the identification, assessment, and training of care partners of hospitalized people living with ADRD. Our convergent mixed method approach will facilitate triangulation across all 3 aims to increase the credibility and transferability of results. We anticipate this study to take 24 months between September 1, 2022, and August 31, 2024. ResultsThe A-SHIFT study protocol will yield (1) optimal points in the hospital workflow for care partner inclusion, (2) a prioritized list of potentially modifiable barriers and facilitators to including care partners in the hospitalization of people living with ADRD, and (3) a converged-upon, ready for feasibility testing of the toolkit to guide the inclusion of care partners of people living with ADRD in hospital care. ConclusionsWe anticipate that the resultant A-SHIFT will provide health systems with a readiness checklist, implementation plan, and resources for identifying, assessing, and training care partners on how to fulfill their caregiving roles for people living with ADRD after hospital discharge. A-SHIFT has the potential to not only improve care partner preparedness but also help reduce health and service use outcomes for people living with ADRD after hospital discharge. International Registered Report Identifier (IRRID)DERR1-10.2196/45274

Temporal synchrony of signals arriving from different neurons or brain regions is essential for proper neural processing. Nevertheless, it is not well understood how such synchrony is achieved and maintained in a complex network of time-delayed neural interactions. Myelin plasticity, accomplished by oligodendrocytes (OLs), has been suggested as an efficient mechanism for controlling timing in brain communications through adaptive changes of axonal conduction velocity and consequently conduction time delays, or latencies; however, local rules and feedback mechanisms that OLs use to achieve synchronization are not known. We propose a mathematical model of oligodendrocyte-mediated myelin plasticity (OMP) in which OLs play an active role in providing such feedback. This is achieved without using arrival times at the synapse or modulatory signaling from astrocytes; instead, it relies on the presence of global and transient OL responses to local action potentials in the axons they myelinate. While inspired by OL morphology, we provide the theoretical underpinnings that motivated the model and explore its performance for a wide range of its parameters. Our results indicate that when the characteristic time of OL’s transient intracellular responses to neural spikes is between 10 and 40 ms and the firing rates in individual axons are relatively low (10 Hz), the OMP model efficiently synchronizes correlated and time-locked signals while latencies in axons carrying independent signals are unaffected. This suggests a novel form of selective synchronization in the CNS in which oligodendrocytes play an active role by modulating the conduction delays of correlated spike trains as they traverse to their targets.

Introduction Dozens of multivariable prediction models for atrial fibrillation after cardiac surgery (AFACS) have been published, but none have been incorporated into regular clinical practice. One of the reasons for this lack of adoption is poor model performance due to methodological weaknesses in model development. In addition, there has been little external validation of these existing models to evaluate their reproducibility and transportability. The aim of this systematic review is to critically appraise the methodology and risk of bias of papers presenting the development and/or validation of models for AFACS.Methods We will identify studies that present the development and/or validation of a multivariable prediction model for AFACS through searches of PubMed, Embase and Web of Science from inception to 31 December 2021. Pairs of reviewers will independently extract model performance measures, assess methodological quality and assess risk of bias of included studies using extraction forms adapted from a combination of the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies checklist and the Prediction Model Risk of Bias Assessment Tool. Extracted information will be reported by narrative synthesis and descriptive statistics.Ethics and dissemination This systemic review will only include published aggregate data, so no protected health information will be used. Study findings will be disseminated through peer-reviewed publications and scientific conference presentations. Further, this review will identify weaknesses in past AFACS prediction model development and validation methodology so that subsequent studies can improve upon prior practices and produce a clinically useful risk estimation tool.PROSPERO registration number CRD42019127329.

Abstract Rheumatoid arthritis (RA) is a chronic autoimmune disorder affecting joints with a hallmark of autoantibody production. Mannan-enhanced collagen type II (COL2) antibody induced arthritis (mCAIA) in neutrophil cytosolic factor 1(Ncf1) mutation mouse is a chronic disease model imitating RA in mice. In this study, we characterize the chronic phase of mCAIA in Ncf1 mutated (BQ.Ncf1 m1j/m1j) mice. Arthritis was induced by an intravenous injection of anti-COL2 monoclonal antibodies on day 0 followed by intra-peritoneal injections of mannan (from Saccharomyces cerevisiae) on days 3 and 65 in BQ.Ncf1 m1j/m1j and BQ mice. Bone erosion was analysed by computed tomography (CT) and blood cell phenotypes by flow cytometry. Cytokines and anti-COL2 antibodies were analyzed with multiplex bead-based assays. The arthritis in the Ncf1 m1j/m1j mice developed with a chronic and relapsing disease course, which was followed for 200 days and bone erosions of articular joints were evaluated. An increased number of circulating CD11b+ Ly6G+ neutrophils were observed during the chronic phase, together with a higher level of G-CSF (granulocyte colony-stimulating factor) and TNF-α. In conclusion, the chronic relapsing arthritis of mCAIA in the Ncf1 m1j/m1j mice develop bone erosions associated with a sustained neutrophil type of inflammatory responses.

BackgroundGay, bisexual, and other sexual minority men have expressed the acceptability of patient portals as tools for supporting HIV prevention behaviors, including facilitating disclosure of HIV and other sexually transmitted infection (STI/HIV) laboratory test results to sex partners. However, these studies, in which Black or African American sexual minority men were undersampled, failed to determine the relationship of reported history of discussing HIV results with sex partners and anticipated willingness to disclose web-based STI/HIV test results using a patient portal. ObjectiveAmong a sample of predominantly Black sexual minority men, this study aimed to (1) determine preferences for patient portal use for HIV prevention and (2) test the associations between reported history of discussing HIV results and anticipated willingness to disclose web-based STI/HIV test results with most recent main and nonmain partners using patient portals. MethodsData come from audio-computer self-assisted interview survey data collected during the 3-month visit of a longitudinal cohort study. Univariate analysis assessed patient portal preferences by measuring the valuation rankings of several portal features. Multiple Poisson regression models with robust error variance determined the associations between history of discussing HIV results and willingness to disclose those results using web-based portals by partner type, and to examine criterion validity of the enhancing dyadic communication (EDC) scale to anticipated willingness. ResultsOf the 245 participants, 71% (n=174) were Black and 22% (n=53) were White. Most participants indicated a willingness to share web-based STI/HIV test results with their most recent main partner. Slightly fewer, nonetheless a majority, indicated a willingness to share web-based test results with their most recent nonmain partner. All but 2 patient portal features were valued as high or moderately high priority by >80% of participants. Specifically, tools to help manage HIV (n=183, 75%) and information about pre- and postexposure prophylaxis (both 71%, n=173 and n=175, respectively) were the top-valuated features to include in patient portals for HIV prevention. Discussing HIV test results was significantly associated with increased prevalence of willingness to disclose web-based test results with main (adjusted prevalence ratio [aPR] 1.46, 95% CI 1.21-1.75) and nonmain partners (aPR 1.54, 95% CI 1.23-1.93). ConclusionsOur findings indicate what features Black sexual minority men envision may be included in the patient portal’s design to optimize HIV prevention, further supporting the criterion validity of the EDC scale. Efforts should be made to support Black sexual minority men’s willingness to disclose STI/HIV testing history and status with partners overall as it is associated significantly with a willingness to disclose testing results digitally via patient portals. Future studies should consider discussion behaviors regarding past HIV test results with partners when tailoring interventions that leverage patient portals in disclosure events.

Obstructive sleep apnea is increasing worldwide, leading to disordered sleep patterns and inflammatory responses in brain and peripheral tissues that predispose individuals to chronic disease. Pro-inflammatory cytokines activate the inflammatory response and are normally regulated by glucocorticoids secreted from adrenal glands. However, the temporal dynamics of inflammatory responses and hypothalamic-pituitary-adrenal (HPA) axis activation in relation to acute sleep fragmentation (ASF) are undescribed. Male C57BL/6J mice were exposed to ASF or control conditions (no ASF) over specified intervals (1, 2, 6, or 24 h) and cytokine gene expression (IL-1β, TNF-α) in brain and peripheral tissues as well as serum glucocorticoid and interleukin-6 (IL-6) concentration were assessed. The HPA axis was rapidly activated, leading to elevated serum corticosterone from 1-24 h of ASF compared with controls. This activation was followed by elevated serum IL-6 concentration from 6-24 h of ASF. The tissue to first exhibit increased pro-inflammatory gene expression from ASF was heart (1 h of ASF). In contrast, pro-inflammatory gene expression was suppressed in hypothalamus from 1 h of ASF, but elevated at 6 h. Because the HPA axis was activated throughout ASF, this suggests that brain, but not peripheral, pro-inflammatory responses were rapidly inhibited by glucocorticoid immunosuppression.

BackgroundUnderstanding the drivers of SARS-CoV-2 transmission can inform the development of interventions. We evaluated transmission identified by contact tracing investigations between March-May 2020 in Salt Lake County, Utah, to quantify the impact of this intervention and identify risk factors for transmission.MethodsRT-PCR positive and untested symptomatic contacts were classified as confirmed and probable secondary case-patients, respectively. We compared the number of case-patients and close contacts generated by different groups, and used logistic regression to evaluate factors associated with transmission.ResultsData were collected on 184 index case-patients and up to six generations of contacts. Of 1,499 close contacts, 374 (25%) were classified as secondary case-patients. Decreased transmission odds were observed for contacts aged ConclusionsGiven sufficient resources and complementary public health measures, contact tracing can contain known chains of SARS-CoV-2 transmission. Transmission is associated with age and exposure setting, and can be highly variable, with a few infections generating a disproportionately high share of onward transmission.

Outcomes and costs of coronavirus disease (COVID-19) contact tracing are limited. During March–May 2020, we constructed transmission chains from 184 index cases and 1,499 contacts in Salt Lake County, Utah, USA, to assess outcomes and estimate staff time and salaries. We estimated 1,102 staff hours and $29,234 spent investigating index cases and contacts. Among contacts, 374 (25%) had COVID-19; secondary case detection rate was ≈31% among first-generation contacts, ≈16% among second- and third-generation contacts, and ≈12% among fourth-, fifth-, and sixth-generation contacts. At initial interview, 51% (187/370) of contacts were COVID-19–positive; 35% (98/277) became positive during 14-day quarantine. Median time from symptom onset to investigation was 7 days for index cases and 4 days for first-generation contacts. Contact tracing reduced the number of cases between contact generations and time between symptom onset and investigation but required substantial resources. Our findings can help jurisdictions allocate resources for contact tracing.

OBJECTIVES/GOALS: Effective translation of data to inform real-time patient care is lacking in addiction inpatient settings. The current study presents the optimization of a Comprehensive Rehabilitation Assessment summary report that is used by clinicians to individualize treatment. METHODS/STUDY POPULATION: A multi-aim approach was taken that utilized aspects of various implementation science frameworks. Participants were clinical staff (N = 7; female = 71%). A quantitative survey was used for aims 1 and 2 to assess motives and context around the report as well as evaluate the design of it. Aim 3 focused on optimization via semi-structured interviews. Descriptive and modified content analyses were utilized appropriately for each aim. RESULTS/ANTICIPATED RESULTS: Five versions of the assessment report were created between February 2021 and August 2022, the most recent of was adapted into patients’electronic medical records based on study results. Each report version, participants’results/feedback, and researchers’perceived barriers to this translational process will be discussed. DISCUSSION/SIGNIFICANCE: The current study highlights a replicable approach for optimizing the translation of assessment data into treatment for patients with disorders of addiction.

Abstract Proteasome inhibitors bortezomib and carfilzomib are approved for the treatment of multiple myeloma and mantle cell lymphoma and have demonstrated clinical efficacy for the treatment of acute lymphoblastic leukemia (ALL). The t(4;11)(q21;q23) chromosomal translocation that leads to the expression of MLL–AF4 fusion protein and confers a poor prognosis, is the major cause of infant ALL. This translocation sensitizes tumor cells to proteasome inhibitors, but toxicities of bortezomib and carfilzomib may limit their use in pediatric patients. Many of these toxicities are caused by on-target inhibition of proteasomes in non-lymphoid tissues (e.g., heart muscle, gut, testicles). We found that MLL–AF4 cells express high levels of lymphoid tissue-specific immunoproteasomes and are sensitive to pharmacologically relevant concentrations of specific immunoproteasome inhibitor ONX-0914, even in the presence of stromal cells. Inhibition of multiple active sites of the immunoproteasomes was required to achieve cytotoxicity against ALL. ONX-0914, an inhibitor of LMP7 (ß5i) and LMP2 (ß1i) sites of the immunoproteasome, and LU-102, inhibitor of proteasome ß2 sites, exhibited synergistic cytotoxicity. Treatment with ONX-0914 significantly delayed the growth of orthotopic ALL xenograft tumors in mice. T-cell ALL lines were also sensitive to pharmacologically relevant concentrations of ONX-0914. This study provides a strong rationale for testing clinical stage immunoproteasome inhibitors KZ-616 and M3258 in ALL.

Early in 2021, India embarked on the uphill journey of the COVID-19 vaccination of the largest population group in the world in a prioritized manner and in the shortest possible time. Considering the endless variety of geography and diverse socio-economic demographic, religious, and community contexts, there was a high likelihood of certain population subgroups with known vulnerabilities facing inequities, which were anticipated to be further accentuated by a digital divide. This necessitated devising solutions for such communities in a localized manner to aid the local government in breaking the service access and uptake barriers with an inclusive approach. To bridge this vital gap, the Momentum Routine Immunization Transformation and Equity project implemented a three-tiered collaboration, viz., government, non-governmental organizations (NGOs), and a wide range of vulnerable and at-risk communities, utilizing knowledge exchange and use of data. The project implemented localization strategies through the NGOs for community engagement in conjunction with government vaccination teams to universalize COVID-19 vaccination uptake up to the last mile. The collaboration resulted in reaching close to 50 million beneficiaries through messaging and facilitated the administration of more than 14 million vaccine doses, including 6.1 million doses for vulnerable and marginalized communities in 18 States and Union territories in India, along with suggesting implications for public health practice and research.

Mass vaccination, currently the most promising solution to contain communicable diseases, including COVID-19 requires collaboration between a variety of partners to improve the supply and demand and alleviate vaccine inequity. Vaccine hesitancy features in WHO’s list of top 10 threats to global health, and there is plethora of disinformation instigating conflict between COVID-19 vaccination drive and religious sentiments. Negotiating public health partnerships with FBOs (Faith Based Organizations) has always been challenging. A handful of faith leaders have always shown resistance to ideas such as child immunization, and family planning. Many others have been supportive on other fronts like helping people with food, shelter, and medical aid in the times of public health crisis. Religion is an important part of life for the majority of the Indian population. People confide in faith-based leaders in the times of difficulty. This article presents experiences from the strategic engagement with FBOs (entities dedicated to specific religious identities, often including a social or moral component) to promote uptake of COVID-19 vaccination, especially among the vulnerable and marginalized communities. The project team collaborated with 18 FBOs and more than 400 religious institutions to promote COVID-19 vaccination and build confidence for the vaccination program. As a result, a sustainable network of sensitized FBOs from diverse faiths was created. The FBOs mobilized and facilitated vaccination of 0.41 million beneficiaries under the project.

Background: The importance of immunization for child survival underscores the need to eliminate immunization inequalities. Few existing studies of inequalities use approaches that view the challenges and potential solutions from the perspective of caregivers. This study aimed to identify barriers and context-appropriate solutions by engaging deeply with caregivers, community members, health workers, and other health system actors through participatory action research, intersectionality, and human-centered design lenses. Methods: This study was conducted in the Demographic Republic of Congo, Mozambique and Nigeria. Rapid qualitative research was followed by co-creation workshops with study participants to identify solutions. We analyzed the data using the UNICEF Journey to Health and Immunization Framework. Results: Caregivers of zero-dose and under-immunized children faced multiple intersecting and interacting barriers related to gender, poverty, geographic access, and service experience. Immunization programs were not aligned with needs of the most vulnerable due to the sub-optimal implementation of pro-equity strategies, such as outreach vaccination. Caregivers and communities identified feasible solutions through co-creation workshops and this approach should be used whenever possible to inform local planning. Conclusions: Policymakers and managers can integrate HCD and intersectionality mindsets into existing planning and assessment processes, and focus on overcoming root causes of sub-optimal implementation.

Virus shedding in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can occur before onset of symptoms; less is known about symptom progression or infectiousness associated with initiation of viral shedding. We investigated household transmission in 5 households with daily specimen collection for 5 consecutive days starting a median of 4 days after symptom onset in index patients. Seven contacts across 2 households implementing no precautionary measures were infected. Of these 7, 2 tested positive for SARS-CoV-2 by reverse transcription PCR on day 3 of 5. Both had mild, nonspecific symptoms for 1–3 days preceding the first positive test. SARS-CoV-2 was cultured from the fourth-day specimen in 1 patient and from the fourth- and fifth-day specimens in the other. We also describe infection control measures taken in the households that had no transmission. Persons exposed to SARS-CoV-2 should self-isolate, including from household contacts, wear a mask, practice hand hygiene, and seek testing promptly.

BackgroundAdolescents and young adults (AYA) aged younger than 25 years have the highest rates of sexually transmitted infections (STIs) in the United States. Current STI prevention strategies for AYA rely primarily on individual approaches, leaving sexual partners with significant unmet sexual and reproductive health care and health education needs. Dyadic interventions may hold promise for harnessing the power of communal coping within relationship dynamics to enhance sexual decision making, communication, and behavior changes that reduce the future risk of STIs. ObjectiveThis paper describes the protocol and research methods of a dyad-based behavioral intervention that augments individual evidence-based interventions with joint health education counseling for heterosexual AYA dyads within a primary care setting. The trial aims to improve partner communication and collaborative sexual decision making and promote the adoption of sexual behaviors such as consistent condom use. The primary objective of this study is to assess the feasibility, acceptability, and effectiveness of a dyadic intervention targeted at preventing STIs in heterosexual couples in an urban setting. MethodsA total of 100 AYA (50 dyads) aged 16 to 25 years, engaged in heterosexual intercourse, who reside in the city and are willing to recruit their main sexual partner for the study will be recruited and randomized into 2 groups, an intervention arm and a control arm. Participants will be recruited from an AYA medicine clinic and by using social media (Facebook and Instagram). The index participant and partner will complete a single individual session separately (Sister to Sister or Focus on the Future) with a gender-matched health educator. Dyads will then be randomized to receive an additional joint debriefing session together to discuss relationship dynamics, condom negotiation, etc. Participants will separately complete a telephone interview 6 weeks postintervention to determine the feasibility, acceptability, and impact of the intervention on mutual sexual negotiation, consistency of condom use, and communal coping skills, etc. ResultsSo far, 25.4% (44/173) of eligible participants have been enrolled and randomized. Participants are mostly female (20/22, 91%), with at least a high school diploma (19/22, 86%), and 9 average lifetime sexual partners. Acceptability is high, with 98% (43/44) of participants expressing satisfaction with their study experience; 100% of dyads recruited were still together at 6-week follow-up. ConclusionsFindings from this study will add to the current literature on the approaches to STI prevention, and its success will inform its application in risk reduction counseling for youth who are most at risk. Trial RegistrationClinical Trials.gov NCT03275168; https://www.clinicaltrials.gov/ct2/history/NCT03275168 International Registered Report Identifier (IRRID)DERR1-10.2196/29389

BackgroundSouthern China is at risk for arborvirus disease transmission, including Zika virus and dengue. Patients often present to clinical care with non-specific acute febrile illnesses (AFI). To better describe the etiology of AFI, we implemented a two-year AFI surveillance project at five sentinel hospitals in Yunnan and Guangdong Provinces.MethodsBetween June 2017 and August 2019, we enrolled patients between 2 and 65 years of age presenting at one sentinel hospital in Mengla County, Yunnan, and four in Jiangmen City, Guangdong, with symptoms of AFI (acute onset of fever ≥ 37.5°C within the past 7 days) without respiratory symptoms or diarrhea. Demographic, epidemiologic, and clinical information was obtained and entered into a web-based AFI surveillance database. A custom TaqMan Array card (TAC) was used to test patients' whole blood specimens for 27 different pathogens using real-time polymerase chain reaction assays.ResultsDuring the two-year project period, 836 patients were enrolled; 443 patients from Mengla County and 393 patients from Jiangmen City. The median age was 33 years [range: 2-65], and most were hospitalized [641, 77%]. Of 796 patients with valid TAC results, 341 (43%) were positive for at least one of the 10 unique pathogens detected. This included 205 (26%) patients positive for dengue virus, 60 (8%) for Orientia tsutsugamushi, and 42 (5%) for Coxiella burnetii. Ten patients (1%) in Jiangmen City tested positive for malaria, 8 of whom reported recent travel outside of China. TAC results were negative for 455 (57%) patients. None of the patients had a positive TAC detection for Zika virus.ConclusionsThe project detected variability in the etiology of AFI in Southern China and highlighted the importance of differential diagnosis. Dengue, O. tsutsugamushi, and C. burnetii were the most frequently identified pathogens among enrolled AFI patients. As a non-notifiable disease, the frequent detection of C. burnetii is noteworthy and warrants additional investigation. The project provided a framework for routine surveillance for persons presenting with AFI.

IntroductionThe need for caregiver respite is well-documented for the care of persons with IDD. Social Assistive Robotics (SAR) offer promise in addressing the need for caregiver respite through 'complementary caregiving' activities that promote engagement and learning opportunities for a care recipient (CR) with IDD. This study explored the acceptability and usefulness of a SAR caregiver respite program responsive to feedback from both young adults with IDD and their older family caregivers (age 55+).MethodYoung adults with IDD and caregiver dyads (N = 11) were recruited. A mixed methods research design was deployed in three phases: Phase I with four focus groups to inform the program design; Phase II for program demonstration and evaluation with pre- and post-surveys; and Phase III with post-program interviews for feedback and suggestions.ResultsBoth young adults with IDD and their caregivers scored favorably the social presence of, social engagement, and satisfaction with robot Pepper. Though there was no significant improvement of caregiving burden/stress as well as well-being of the young adults with IDD based on surveys, results from interviews suggested that the SAR may offer physical/emotional respite to caregivers by providing companionship/friendship as well as promoting independence, safety/monitoring, and interactive engagement with children.DiscussionSAR has potential in providing respite for older family caregivers. Future studies need a longer program design and larger sample size to develop a promising intervention and test its feasibility and efficacy.

Aflatoxin contamination of corn is a major threat to the safe food and feed. The United States Federal Grain Inspection Service (FGIS) monitors commercial grain shipments for the presence of aflatoxin. A total of 146 Aspergillus flavus were isolated from 29 highly contaminated grain samples to characterize the visual phenotypes, aflatoxin-producing potential, and genotypes to explore the etiological cause of high aflatoxin contamination of US corn. Five of the isolates had reduced sensitivity (43–49% resistant) to the fungicide azoxystrobin, with the remainder all being over 50% resistant to azoxystrobin at the discriminating dose of 2.5 µg/mL. Only six isolates of the highly aflatoxigenic S morphotype were found, and 48 isolates were non-aflatoxigenic. Analysis of the mating type locus revealed 45% MAT 1-1 and 55% MAT 1-2. The A. flavus population originating from the highly aflatoxin contaminated grain samples was compared to a randomly selected subset of isolates originating from commercial corn samples with typical levels of aflatoxin contamination (average < 50 ppb). Use of simple sequence repeat (SSR) genotyping followed by principal component analysis (PCoA) revealed a similar pattern of genotypic distribution in the two populations, but greater diversity in the FGIS-derived population. The noticeable difference between the two populations was that genotypes identical to strain NRRL 21882, the active component of the aflatoxin biocontrol product Afla-Guard™, were ten times more common in the commercial corn population of A. flavus compared to the population from the high-aflatoxin corn samples. The other similarities between the two populations suggest that high aflatoxin concentrations in corn grain are generally the result of infection with common A. flavus genotypes.

Increasingly, routine surveillance and monitoring of foodborne pathogens using whole-genome sequencing is creating opportunities to study foodborne illness epidemiology beyond routine outbreak investigations and case–control studies. Using a global phylogeny of Salmonella enterica serotype Typhimurium, we found that major livestock sources of the pathogen in the United States can be predicted through whole-genome sequencing data. Relatively steady rates of sequence divergence in livestock lineages enabled the inference of their recent origins. Elevated accumulation of lineage-specific pseudogenes after divergence from generalist populations and possible metabolic acclimation in a representative swine isolate indicates possible emergence of host adaptation. We developed and retrospectively applied a machine learning Random Forest classifier for genomic source prediction of Salmonella Typhimurium that correctly attributed 7 of 8 major zoonotic outbreaks in the United States during 1998–2013. We further identified 50 key genetic features that were sufficient for robust livestock source prediction.

Human papilloma virus (HPV) is the most common sexually transmitted infection in the United States. Disease-associated strains of HPV can cause genital warts and six cancer types. HPV-associated cervical cancer disproportionately impacts medically underserved women including Black and Latina women with respect to incidence, prevalence, and mortality rates. Although safe and effective vaccines are available, HPV vaccination rates remain low among low-income individuals and women of color. The current study examined individual and structural motivators and barriers to HPV vaccination among medically underserved women utilizing a Planned Parenthood health center in Southeast Pennsylvania. Guided by narrative engagement theory (NET), qualitative interviews (N = 24) were used to elicit HPV vaccine decision stories from both vaccinated and unvaccinated women. Using a phronetic iterative data analysis approach, we identified three motivators to vaccinate against HPV: (1) receiving an explicit vaccine recommendation from a healthcare provider (a structural determinant), (2) feeling empowered to take control of one’s health (an individual determinant), and (3) knowing someone infected with HPV (an individual determinant). Among unvaccinated participants, barriers to HPV vaccination included: (1) not receiving an explicit vaccine recommendation from a healthcare provider (a structural determinant), (2) low perceived risk for acquiring HPV or that HPV is not severe (an individual determinant), and (3) lack of maternal support to vaccinate (a structural determinant). Healthcare providers are optimally positioned to fill the gap in prior missed vaccine opportunities and empower women by recommending HPV vaccination.

Introduction Dementia with Lewy bodies (DLB) is one of the most common degenerative dementias. Despite the fact that most individuals with DLB die from complications of the disease, little is known regarding what factors predict impending end of life or are associated with a quality end of life.Methods and analysis This is a multisite longitudinal cohort study. Participants are being recruited from five academic centres providing subspecialty DLB care and volunteers through the Lewy Body Dementia Association (not receiving specialty care). Dyads must be US residents, include individuals with a clinical diagnosis of DLB and at least moderate-to-severe dementia and include the primary caregiver, who must pass a brief cognitive screen. The first dyad was enrolled 25 February 2021; recruitment is ongoing. Dyads will attend study visits every 6 months through the end of life or 3 years. Study visits will occur in-person or virtually. Measures include demographics, DLB characteristics, caregiver considerations, quality of life and satisfaction with end-of-life experiences. For dyads where the individual with DLB dies, the caregiver will complete a final study visit 3 months after the death to assess grief, recovery and quality of the end-of-life experience. Terminal trend models will be employed to identify significant predictors of approaching end of life (death in the next 6 months). Similar models will assess caregiver factors (eg, grief, satisfaction with end-of-life experience) after the death of the individual with DLB. A qualitative descriptive analysis approach will evaluate interview transcripts regarding end-of-life experiences.Ethics and dissemination This study was approved by the University of Florida institutional review board (IRB202001438) and is listed on clinicaltrials.gov (NCT04829656). Data sharing follows National Institutes of Health policies. Study results will be disseminated via traditional scientific strategies (conferences, publications) and through collaborating with the Lewy Body Dementia Association, National Institute on Aging and other partnerships.

IntroductionTwitter represents a mainstream news source for the American public, offering a valuable vehicle for learning how citizens make sense of pandemic health threats like Covid-19. Masking as a risk mitigation measure became controversial in the US. The social amplification risk framework offers insight into how a risk event interacts with psychological, social, institutional, and cultural communication processes to shape Covid-19 risk perception.MethodsQualitative content analysis was conducted on 7,024 mask tweets reflecting 6,286 users between January 24 and July 7, 2020, to identify how citizens expressed Covid-19 risk perception over time. Descriptive statistics were computed for (a) proportion of tweets using hyperlinks, (b) mentions, (c) hashtags, (d) questions, and (e) location.ResultsSix themes emerged regarding how mask tweets amplified and attenuated Covid-19 risk: (a) severity perceptions (18.0%) steadily increased across 5 months; (b) mask effectiveness debates (10.7%) persisted; (c) who is at risk (26.4%) peaked in April and May 2020; (d) mask guidelines (15.6%) peaked April 3, 2020, with federal guidelines; (e) political legitimizing of Covid-19 risk (18.3%) steadily increased; and (f) mask behavior of others (31.6%) composed the largest discussion category and increased over time. Of tweets, 45% contained a hyperlink, 40% contained mentions, 33% contained hashtags, and 16.5% were expressed as a question.ConclusionsUsers ascribed many meanings to mask wearing in the social media information environment revealing that COVID-19 risk was expressed in a more expanded range than objective risk. The simultaneous amplification and attenuation of COVID-19 risk perception on social media complicates public health messaging about mask wearing.

Maps of bottom type are essential to the management of marine resources and biodiversity because of their foundational role in characterizing species’ habitats. They are also urgently needed as countries work to define marine protected areas. Current approaches are time consuming, focus largely on grain size, and tend to overlook shallow waters. Our random forest classification of almost 200,000 observations of bottom type is a timely alternative, providing maps of coastal substrate at a combination of resolution and extents not previously achieved. We correlated the observations with depth, depth-derivatives, and estimates of energy to predict marine substrate at 100 m resolution for Canada’s Pacific shelf, a study area of over 135,000 km2. We built five regional models with the same data at 20 m resolution. In addition to standard tests of model fit, we used three independent data sets to test model predictions. We also tested for regional, depth, and resolution effects. We guided our analysis by asking: 1) does weighting for prevalence improve model predictions? 2) does model resolution influence model performance? And 3) is model performance influenced by depth? All our models fit the build data well with true skill statistic (TSS) scores ranging from 0.56 to 0.64. Weighting models with class prevalence improved fit and the correspondence with known spatial features. Class-based metrics showed differences across both resolutions and spatial regions, indicating non-stationarity across these spatial categories. Predictive power was lower (TSS from 0.10 to 0.36) based on independent data evaluation. Model performance was also a function of depth and resolution, illustrating the challenge of accurately representing heterogeneity. Our work shows the value of regional analyses to assessing model stationarity and how independent data evaluation and the use of error metrics can improve understanding of model performance and sampling bias.