IgG, IgM, and Nonstructural Protein 1 Response Profiles after Receipt of Tetravalent Dengue Vaccine TAK-003 in a Phase 2 Randomized Controlled Trial.

The profiles of vaccine-induced dengue antibodies may differ from those produced following natural infection and could potentially interfere with the interpretation of diagnostic tests. We assessed anti-dengue IgG and IgM antibodies, and nonstructural protein 1 antigen profiles in the serum of adults who received a single dose of the tetravalent dengue vaccine TAK-003 as either an initially developed high-dose formulation or the standard approved formulation in a phase 2 study in Singapore (#NCT02425098). Immunoglobulin G and IgM profiles during the first 30 days postvaccination varied by baseline serostatus (microneutralization assay). Nonstructural protein 1 antigen was not detected in the serum of any participants. Vaccine-induced IgG and IgM antibodies can affect serological confirmation of subsequent dengue infection in vaccinees. These results highlight the limitations of using serological tests for dengue diagnosis, particularly in a postvaccination setting, and emphasize the need for more sensitive antigen- and molecular-based testing for accurate dengue diagnosis.

S1 hydrophobic residues modulate voltage sensing phosphatase enzymatic function and voltage sensing.

The voltage sensing domain (VSD) is a four-helix modular protein domain that converts electrical signals into conformational changes, leading to open pores and active enzymes. In most voltage sensing proteins, the VSDs do not interact with one another and the S1-S3 helices are considered mainly as scaffolding. The two exceptions are the voltage sensing phosphatase (VSP) and the proton channel (Hv). VSP is a voltage-regulated enzyme and Hvs are channels that only have VSDs. To investigate the S1 contribution to VSP function, we individually mutated four hydrophobic amino acids in S1 to alanine (F127, I131, I134 and L137). We also combined these mutations to generate quadruple mutation designated S1-Q. Most of these mutations shifted the voltage dependence of activity to higher voltages though interestingly, not all substrate reactions were the same. The kinetics of enzymatic activity were also altered with some mutations significantly slowing down dephosphorylation. The voltage dependence of VSD motions were consistently shifted to lower voltages and indicated a second voltage dependent motion. Co-immunoprecipitation demonstrated that none of the mutations broke the VSP dimer indicating that the S1 impact could stem from intrasubunit and/or intersubunit interactions. Lastly, when the same alanine mutations were introduced into a genetically encoded voltage indicator, they dramatically altered the optical readings, making some of the kinetics faster and shifting the voltage dependence. These results indicate that the S1 helix in VSP plays a critical role in tuning the enzymes conformational response to membrane potential transients and influencing the function of the VSD.

Transmission of Spinach Downy Mildew via Seed and Infested Leaf Debris.

Spinach downy mildew, caused by the obligate oomycete pathogen Peronospora effusa, is a worldwide constraint on spinach production. The role of airborne sporangia in the disease cycle of P. effusa is well established, but the role of the sexual oospores in the epidemiology of P. effusa is less clear and has been a major challenge to examine experimentally. To evaluate seed transmission of spinach downy mildew via oospores in this study, isolated glass chambers were employed in two independent experiments to grow out oospore-infested spinach seed and noninfested seeds mixed with oospore-infested crop debris. Downy mildew diseased spinach plants were observed 37 and 34 days after planting in the two isolator experiments, respectively, in the chambers that contained one of two oospore-infested seed lots or seeds coated with oospore-infested leaves. Spinach plants in isolated glass chambers initiated from seeds without oospores did not show downy mildew symptoms. Similar findings were obtained using the same seed lot samples in a third experiment conducted in a growth chamber. In direct grow out tests to examine oospore infection on seedlings performed in a containment greenhouse with oospore-infested seed of two different cultivars, characteristic Peronospora sporangiophores were observed growing from a seedling of each cultivar. The frequency of seedlings developing symptoms from 82 of these oospore-infested seed indicated that approximately 2.4% of seedlings from infested seed developed symptoms, and 0.55% of seedlings from total seeds assayed developed symptoms. The results provide evidence that oospores can serve as a source of inoculum for downy mildew and provide further evidence of direct seed transmission of the downy mildew pathogen to seedlings in spinach via seedborne oospores.

The role of technology in the care of diabetes mellitus in pregnancy: an expert review.

Diabetes mellitus is one of the most commonly encountered pregnancy complications and is associated with multiple adverse perinatal outcomes. Technology has progressed to address the unique challenges patients face in managing diabetes mellitus in pregnancy. Technology has bolstered diabetes mellitus education with smartphone applications focused on nutrition counseling and carbohydrate intake advice. Continuous glucose monitors and insulin infusion systems have shown benefit by simplifying glycemic monitoring and insulin administration. Improvements in glycemic control and perinatal outcomes have been seen with continuous glucose monitor use when compared with intermittent blood glucose monitoring, and more pregnant people are using insulin pumps instead of multiple daily insulin injections. Hybrid closed-loop systems are emerging and are able to integrate continuous glucose monitoring and insulin pump technologies while maximizing automated features in the nonpregnant population, but these have not been endorsed for use in pregnancy yet. Applying telehealth practices has been associated with high patient satisfaction among those with diabetes mellitus in pregnancy, and leveraging remote patient monitoring through telehealth platforms and short-range wireless technologies can reduce the burden of patient visits. As technology becomes more integrated into routine management of diabetes mellitus in pregnancy, practitioners should emphasize individualized counseling and device selection to ensure patient autonomy and safety.

Adult Outcomes of Justice Involved Indigenous Youth.

Juvenile arrest serves as a critical turning point in the life-course that disrupts the successful transition to adulthood and carries numerous consequences including diminished socioeconomic status. Despite their disproportionately high rates of contact with the criminal justice system (CJS), Indigenous people's experiences remain largely invisible in extant research. Further, colonization has left them in an extremely marginalized position in terms of social, economic, and political power, which is compounded by CJS involvement. In the current study, we apply propensity score matching to investigate whether being arrested in adolescence impacts early adult socioeconomic outcomes (i.e., education, employment, and income). Data come from the Healing Pathways project, a longitudinal, community-based participatory study of North American Indigenous young people that includes eight waves of data in adolescence and three waves in early adulthood. We find that being arrested at least once in adolescence is associated with significantly less education and income, and lower rates of full-time employment in young adulthood (mean age = 26.2 years). Criminal justice system involvement widens existing socioeconomic disparities, and remedying these consequences requires changes in how CJS policies are enacted as well as larger structural changes to address significant inequities in income, education, and employment for Indigenous people.

Community Engagement and Giving Back Among North American Indigenous Youth.

"Volunteer participation" refers to free engagement in activities that benefit someone or something else. Volunteering can produce many benefits for individuals and communities. However, current research examining volunteer participation often excludes diverse viewpoints on what constitutes volunteering, particularly the perspectives of North American Indigenous youth. This oversight may result from researchers' conceptualization and measurement of volunteering from a Western perspective. Utilizing data from the Healing Pathways (HP) project, a longitudinal, community-based participatory study in partnership with eight Indigenous communities in the United States and Canada, we provide a detailed description of volunteer participation and community and cultural engagement. Overall, we employ a community cultural wealth lens to emphasize the various strengths and sources of resilience that these communities possess. At the same time, we encourage scholars and the wider society to broaden their views of volunteering, community involvement, and giving back.

Persistence of Immunogenicity of a Purified Inactivated Zika Virus Vaccine Candidate in Healthy Adults: 2 Years of Follow-up Compared With Natural Infection.

BACKGROUND: We report 2-year persistence of immune response to Takeda's prophylactic purified formalin-inactivated whole Zika virus vaccine candidate (TAK-426) compared with that observed after natural infection. METHODS: A randomized, observer-blind, placebo-controlled, dose-selection, phase 1 trial was conducted in 18-49-year-old adults at 9 centers (7 in the United States, 2 in Puerto Rico) from 13 November 2017 to 24 November 2020. Primary objectives were safety, tolerability, and immunogenicity of 3 increasing doses of TAK-426 administered as 2 doses 28 days apart to flavivirus (FV)-naive and FV-primed adults. Here, we report on safety and persistence of immunity up to 2 years after primary vaccination with 10-µg TAK-426, the highest dose, and compare neutralizing antibody responses with those observed after natural infection. RESULTS: TAK-426 at 10-µg had an acceptable safety profile in FV-naive and FV-primed adults up to 24 months after dose 2. Seropositivity for neutralizing antibodies was 100% at 1 year, and 93.8% and 76.2% at 2 years in FV-naive and FV-primed groups, respectively. TAK-426 responses were comparable in magnitude and kinetics with those elicited by natural Zika virus infection. CONCLUSIONS: These results support the further clinical development of TAK-426 for both FV-naive and FV-primed populations. CLINICAL TRIALS REGISTRATION: NCT03343626.

Culturally Adapting Caring Contacts for Suicide Prevention in Four Alaska Native and American Indian Communities.

AIM: Despite substantial tribal, state, and federal effort, American Indian and Alaska Native (AI/AN) suicide rates have changed little in the last 30 years, prompting attention to new and innovative approaches to this persistent health disparity. Suicide prevention interventions with demonstrated success in other populations may be useful in AI/AN communities. Caring Contacts is a suicide prevention intervention that has been adapted and shown to reduce suicide ideation, attempts, and deaths in other populations. CONCLUSION: Overall, AI/AN study participants in four diverse AI/AN communities endorsed the use of Caring Contacts for suicide prevention in their communities. Intervention adaptations for use in these communities centered primarily on message frequency and timing as well as expanding access to Caring Contacts. The results of this study may be applicable to other populations that experience suicide-related health disparities. METHODS: We used a community-based participatory research approach to gather qualitative data from community members, healthcare providers, and leaders in four AI/AN communities. These data were analyzed thematically and used to adapt Caring Contacts for use in a subsequent clinical trial with AI/AN people at high risk for suicide. RESULTS: A total of 189 community members and other health system stakeholders in four tribal communities participated in focus groups and interviews. Caring Contacts was perceived in all communities to be acceptable. Feedback for intervention adaptations focused on the themes of trial eligibility criteria; instruments; message frequency, timing, and content; and cultural considerations.

Recovery from alcohol among urban Alaska Native and American Indian people.

Alaska Native and American Indian (ANAI) people experience dramatic alcohol-related health disparities compared to the general US population. Although the majority of ANAI people reside in urban settings (>70%), data are sparse on alcohol abstinence among urban ANAI people with alcohol use disorder (AUD). We conducted a qualitative study using a phenomenological approach to examine the experiences of 20 urban ANAI adults recovering from AUD. Participants' narratives had their own unique dimensions but shared a clear, interrelated trajectory of pre-alcohol recovery, a turning point, and ongoing alcohol recovery. All participants reported a combination of external and internal motivation to stop using alcohol.

A longitudinal study of positive mental health and coping among Indigenous adults with type 2 diabetes.

OBJECTIVE: Indigenous Peoples and scholars call for strengths-based approaches to research inclusive of Indigenous resiliency and positive outcomes. The purpose of this study was to examine positive mental health for Indigenous adults with type 2 diabetes and to determine if positive mental health is linked to community connectedness (a coping resource) and active coping (a coping response). METHODS: Participants (N = 194 at baseline) were randomly selected from clinical records, at least 18 years old with a type 2 diabetes diagnosis, and self-identified as American Indian. RESULTS: Latent growth curve models revealed that average positive mental health was predicted to decrease over the four waves of the study, although not for participants with above-average active coping at baseline. Community connectedness at baseline was associated with higher initial levels of positive mental health. Within-person change in active coping and community connectedness were both associated with increases in positive mental health. CONCLUSION: This study aligns with previous research demonstrating that coping can influence health outcomes, and furthers the stress process literature by showing that active coping and community connectedness can impact positive mental health for Indigenous adults with Type 2 Diabetes.

Mechanisms underlying interaction frequencies and robustness in a novel seed dispersal network: lessons for restoration.

As human-caused extinctions and invasions accumulate across the planet, understanding the processes governing ecological functions mediated by species interactions, and anticipating the effect of species loss on such functions become increasingly urgent. In seed dispersal networks, the mechanisms that influence interaction frequencies may also influence the capacity of a species to switch to alternative partners (rewiring), influencing network robustness. Studying seed dispersal interactions in novel ecosystems on O'ahu island, Hawai'i, we test whether the same mechanisms defining interaction frequencies can regulate rewiring and increase network robustness to simulated species extinctions. We found that spatial and temporal overlaps were the primary mechanisms underlying interaction frequencies, and the loss of the more connected species affected networks to a greater extent. Further, rewiring increased network robustness, and morphological matching and spatial and temporal overlaps between partners were more influential on network robustness than species abundances. We argue that to achieve self-sustaining ecosystems, restoration initiatives can consider optimal morphological matching and spatial and temporal overlaps between consumers and resources to maximize chances of native plant dispersal. Specifically, restoration initiatives may benefit from replacing invasive species with native species possessing characteristics that promote frequent interactions and increase the probability of rewiring (such as long fruiting periods, small seeds and broad distributions).

Early Detection of the Spinach Downy Mildew Pathogen in Leaves by Recombinase Polymerase Amplification.

Downy mildew of spinach, caused by Peronospora effusa, is a major economic threat to both organic and conventional spinach production. Symptomatic spinach leaves are unmarketable and spinach with latent infections are problematic because symptoms can develop postharvest. Therefore, early detection methods for P. effusa could help producers identify infection before visible symptoms appear. Recombinase polymerase amplification (RPA) provides sensitive and specific detection of pathogen DNA and is a rapid, field-applicable method that does not require advanced technical knowledge or equipment-heavy DNA extraction. Here, we used comparative genomics to identify a unique region of the P. effusa mitochondrial genome to develop an RPA assay for the early detection of P. effusa in spinach leaves. In tandem, we established a TaqMan quantitative PCR (qPCR) assay and used this assay to validate the P. effusa specificity of the locus across Peronospora spp. and to compare assay performance. Neither the TaqMan qPCR nor the RPA showed cross reactivity with the closely related beet downy mildew pathogen, P. schachtii. TaqMan qPCR and RPA have detection thresholds of 100 and 900 fg of DNA, respectively. Both assays could detect P. effusa in presymptomatic leaves, with RPA-based detection occurring as early as 5 days before the appearance of symptoms and TaqMan qPCR-based detection occurring after 24 h of plant exposure to airborne spores. Implementation of the RPA detection method could provide real-time information for point-of-care management strategies at field sites.

Cultural efficacy as a novel component of understanding linkages between culture and mental health in Indigenous communities.

We used a novel measure of cultural efficacy to examine empirical pathways between enculturation, efficacy, and two wellbeing outcomes. Cultural factors are not consistently linked to better wellbeing in the academic literature despite widespread understanding of these processes in Indigenous communities. Healing pathways is a community-based participatory study with eight reservations/reserves in the upper Midwest and Canada. This study uses data collected in 2017-2018 (n = 453, 58.1% women, mean age = 26.3 years) and structural equation modeling to test the relationships between enculturation, cultural efficacy, and mental health. The direct effect of enculturation on anxiety was positive. The indirect effect of enculturation via cultural efficacy was negatively associated with anxiety and positively associated with positive mental health. Cultural efficacy is an important linking variable through which the protective effects of culture manifest. The complex nature of culture must be met with innovative measures and deep understanding of Indigenous peoples to fully capture the protective role of culture.

1955: The Entre` of Medicine and Public Health into the Field of Agricultural Occupational Safety and Health.

The University of Iowa Institute of Agricultural Medicine (IAM) played a significant role in the development of the field of agricultural medicine. This article is an excerpt from the electronic book The Institute of Agricultural Medicine: an Iowa Idea - Worldwide Impact, 2021 (https://pressbooks.uiowa.edu/agriculturalmedicinehistory/) which provides a detailed history of this story.Olaus Magnus (a clergyman in the Christian Church) in Sweden in 1555, and Bernardon Ramazzini (a physician) in Italy in 1713 wrote of health conditions in farmers. However, there is no evidence found (in the Western Hemisphere) before 1955, where a specific institute was present for the preventive health and medicine for farmers, their families, and their workers. There was an absence of research and outreach in the medical and public health fields in agricultural medicine. The history of the Institute of Agricultural Medicine (IAM) provides a substantive grounding for the field as it stands today. Further, the institute serves as something of a precursor of the One Health Initiative. Here, we trace the history of the institute and highlight its contributions to today's field of agricultural medicine.

Combined Corneal Transplant, Glaucoma Drainage Implantation, and Pars Plana Vitrectomy Outcomes in a Pediatric Population.

PURPOSE: The combination of glaucoma drainage device (GDI), pars plana vitrectomy (PPV), and corneal transplantation is well reported in adults. However, little is known about the outcomes of such combined procedures in pediatric patients. We present a retrospective, single-center study to evaluate the safety and outcomes of concurrent GDI and/or PPV with corneal transplantation in patients 18 years and younger. METHODS: Retrospective chart review of pediatric patients (aged 0-18 years) who received either corneal transplants or keratoprosthesis in combination with at least 1 additional procedure (either GDI and/or PPV) at the Illinois Eye and Ear Infirmary, Chicago, IL, between 2003 and 2017. Primary outcomes included vision, intraocular pressure, and cup-to-disc ratio (C/D). Secondary outcomes included the number of repeat surgeries and intraoperative and postoperative complications. RESULTS: Thirty-six patients were included with a mean age of 8.4 years and an average follow-up of 49.7 months. Nineteen patients received corneal surgery, GDI, and PPV; 4 received corneal and GDI surgery; and 13 received corneal and PPV surgery. Of the 19 patients with all 3 procedures, 48% experienced an increase in vision with an average improvement of 0.9 lines at the last follow-up. Intraocular pressure decreased by an average of -7.2 mm Hg for all groups. Fifty-three percent of all patients experienced complications. CONCLUSIONS: Combined keratoplasty, GDI, and PPV seems to be effective in the management of complex pediatric eye disease. However, owing to the high risk of complications in this vulnerable patient population, careful consideration must be taken when determining a patient's surgical candidacy for combined cornea/glaucoma/retina procedures.

Historical trauma and oppression: Associations with internalizing outcomes among American Indian adults with type 2 diabetes.

American Indian (AI) people experience disproportionate exposure to stressors and health inequities, including type 2 diabetes (T2D) and mental health problems. There is increasing interest in how historical trauma and ongoing experiences of discrimination and marginalization (i.e., historical oppression) interact to influence AI health. The purpose of this study is to examine the relationships between historically traumatic experiences (i.e., boarding schools, relocation programs, and foster care), current reports of historical cultural loss, microaggressions, and their relationship to internalizing symptoms among AI adults living with T2D. This community-based participatory research study with five AI tribal communities includes data from 192 AI adults with T2D recruited from tribal clinics. Results from structural equation modeling revealed that personal experiences in foster care and ancestral experiences in boarding schools and/or relocation were associated with increased reports of historical loss, and indirectly associated with internalizing symptoms through racial microaggressions and historical losses. The findings highlight the importance of considering multiple dimensions of historical trauma and oppression in empirical and practice-based assessments of mental health problems.

Ancestral Chromosomes for Family Peronosporaceae Inferred from a Telomere-to-Telomere Genome Assembly of Peronospora effusa.

Downy mildew disease of spinach, caused by the oomycete Peronospora effusa, causes major losses to spinach production. In this study, the 17 chromosomes of P. effusa were assembled telomere-to-telomere, using Pacific Biosciences high-fidelity reads. Of these, 16 chromosomes are complete and gapless; chromosome 15 contains one gap bridging the nucleolus organizer region. This is the first telomere-to-telomere genome assembly for an oomycete. Putative centromeric regions were identified on all chromosomes. This new assembly enables a reevaluation of the genomic composition of Peronospora spp.; the assembly was almost double the size and contained more repeat sequences than previously reported for any Peronospora species. Genome fragments consistently underrepresented in six previously reported assemblies of P. effusa typically encoded repeats. Some genes annotated as encoding effectors were organized into multigene clusters on several chromosomes. Putative effectors were annotated on 16 of the 17 chromosomes. The intergenic distances between annotated genes were consistent with compartmentalization of the genome into gene-dense and gene-sparse regions. Genes encoding putative effectors were enriched in gene-sparse regions. The near-gapless assembly revealed apparent horizontal gene transfer from Ascomycete fungi. Gene order was highly conserved between P. effusa and the genetically oriented assembly of the oomycete Bremia lactucae; high levels of synteny were also detected with Phytophthora sojae. Extensive synteny between phylogenetically distant species suggests that many other oomycete species may have similar chromosome organization. Therefore, this assembly provides the foundation for genomic analyses of diverse oomycetes.[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Adaptation without Specialization Early in a Host Shift.

AbstractStudents of speciation debate the role of performance trade-offs across different environments early in speciation. We tested for early performance trade-offs with a host shift experiment using a member of the Enchenopa binotata species complex of treehoppers (Hemiptera: Membracidae). In this clade of plant-feeding insects, different species live on different host plants and exhibit strong behavioral and physiological host specialization. After five generations, the experimental host shifts resulted either in no adaptation or in adaptation without specialization. The latter result was more likely in sympatry; in allopatry, populations on novel host plants were more likely to become extinct. We conclude that in the early stages of speciation, adaptation to novel host plants does not necessarily bring about performance trade-offs on ancestral environments. Adaptation may be facilitated rather than hindered by gene flow, which prevents extinction. Additional causes of specialization and assortative mating may be required if colonization of novel environments is to result in speciation.

Spiritual connectedness through prayer as a mediator of the relationship between Indigenous language use and positive mental health.

OBJECTIVE: The objective of this study is to understand how Indigenous language and spirituality revitalization efforts may affect mental health within Indigenous communities. Although Indigenous communities experience disproportionate rates of mental health problems, research supporting language and spirituality's role in improving mental health is under-researched and poorly understood. METHOD: Data for this study are from a Community-based Participatory Research Project involving five Anishinaabe tribes in Minnesota and Wisconsin. Participants were sampled from clinic records of adults with a diagnosis of type 2 diabetes, living on or near the reservation, and self-identifying as American Indian (mean age = 46.3; n = 191). RESULT: Structural equation modeling illustrates that language use in the home is associated with positive mental health through spiritual connectedness. CONCLUSION: Results support tribal community expressions of the positive effects of cultural involvement for Indigenous wellbeing, and improve what is known about the interconnectedness of language and spirituality. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Cultural Sources of Strength and Resilience: A Case Study of Holistic Wellness Boxes for COVID-19 Response in Indigenous Communities.

The COVID-19 pandemic has had disproportionately severe impacts on Indigenous peoples in the United States compared to non-Indigenous populations. In addition to the threat of viral infection, COVID-19 poses increased risk for psychosocial stress that may widen already existing physical, mental, and behavioral health inequities experienced by Indigenous communities. In recognition of the impact of COVID-19 related psychosocial stressors on our tribal community partners, the Johns Hopkins Center for American Indian Health Great Lakes Hub began sending holistic wellness boxes to our community partners in 11 tribal communities in the Midwestern United States and Canada in summer of 2020. Designed specifically to draw on culturally relevant sources of strength and resilience, these boxes contained a variety of items to support mental, emotional, cultural, and physical wellbeing. Feedback from recipients suggest that these wellness boxes provided a unique form of COVID-19 relief. Additional Johns Hopkins Center for American Indian Health offices have begun to adapt wellness boxes for the cultural context of their regions. This case study describes the conceptualization, creation, and contents of these wellness boxes and orients this intervention within a reflection on foundations of community-based participatory research, holistic relief, and drawing on cultural strengths in responding to COVID-19.