The contrasting phenotypes of neutrophils during asymptomatic versus symptomatic Leishmania braziliensis infection.

BACKGROUND: The mechanisms that mediate immune protection in individuals with subclinical (SC) or asymptomatic infection with L. braziliensis are largely unknown. Neutrophils (PMNs) have been implicated in progressive symptomatic cutaneous leishmaniasis (CL), but their potential participation in maintenance of subclinical infection is unexplored. The aim of this study was to compare the phenotypic and functional profiles of PMNs in individuals with SC infection versus patients with symptomatic CL due to L. braziliensis. METHODS: Subjects were recruited in the endemic region of Corte de Pedra, Bahia, Brazil. Surface markers to define activation status were characterized by flow cytometry. Functional responses of PMNs including phagocytic capacity, production of oxidative species, and oxidative killing of intracellular parasites were studied in vitro. RESULTS: PMNs from individuals with SC infection displayed a more activated phenotype and greater ability to control the infection than PMNs from patients with CL. In contrast, PMNs from patients with CL exhibited higher expression of HLA-DR and higher production of oxidative species than PMNs from subjects with SC infection. CONCLUSION: PMNs from individuals with SC infection can control the infection more efficiently than PMNs from patients with CL, despite the lower production of oxidants. Our observations suggest that L. braziliensis may evade microbicidal mechanisms of PMNs from patients with CL, contributing to parasite dissemination and the establishment of disease.

Apolipoprotein E Is Upregulated in Blood and Circulating Monocytes of Indian Patients With Visceral Leishmaniasis.

Apolipoprotein E (ApoE) has been associated with several diseases including Parkinson's disease, Alzheimer's and multiple sclerosis. ApoE also has documented immunomodulatory functions. We investigated gene expression in circulating monocytes and in bone marrows of patients with visceral leishmaniasis (VL) living in an endemic area in Bihar, India, and contrasted these with control healthy subjects or other diagnostic bone marrows from individuals in the same region. Samples from VL patients were obtained prior to initiating treatment. Our study revealed significant upregulated expression of the apoE transcript in patients with VL. Furthermore, the levels of ApoE protein were elevated in serum samples of subjects with VL compared with healthy endemic controls. These observations may provide clues regarding the complex interactions between lipid metabolism and immunoregulation of infectious and inflammatory diseases.

Differences in dietary acceptability, restraint, disinhibition, and hunger among African American participants randomized to either a vegan or omnivorous soul food diet.

The Nutritious Eating with Soul study was a 24-month, randomized behavioral nutrition intervention among African American adults. This present study, which is a secondary analysis of the NEW Soul study, examined changes in dietary acceptability, restraint, disinhibition, and hunger. Participants (n = 159; 79% female, 74% with ≥ college degree, mean age 48.4 y) were randomized to either a soul food vegan (n = 77) or soul food omnivorous (n = 82) diet and participated in a two-year behavioral nutrition intervention. Questionnaires assessing dietary acceptability (Food Acceptability Questionnaire; FAQ) and dietary restraint, disinhibition, and hunger (Three-Factor Eating Questionnaire; TFEQ) were completed at baseline, 3, 6, 12, and 24 months. Mixed models were specified with main effects (group and time) and interaction effects (group by time) to estimate mean differences in FAQ and TFEQ scores using intent-to-treat analysis. After adjusting for employment, education, food security status, sex, and age, there were no differences in any of the FAQ items, total FAQ score, dietary restraint, disinhibition, and hunger at any timepoint except for one item of the FAQ at 12 months. Participants in the vegan group reported a greater increase in satisfaction after eating a meal than the omnivorous group (mean difference 0.80 ± 0.32, 95% CI 0.18, 1.42; P = 0.01). This is one of the first studies to examine differences in dietary acceptability, hunger, and other eating factors among African American adults randomized to either a vegan or omnivorous soul food diet. The findings highlight that plant-based eating styles are equally acceptable to omnivorous eating patterns and have similar changes in hunger, restraint, and disinhibition. These results suggest that plant-based eating styles can be an acceptable dietary pattern to recommend for cardiovascular disease prevention and may result in greater post-meal satisfaction.

A 12-Week Randomized Intervention Comparing the Healthy US, Mediterranean, and Vegetarian Dietary Patterns of the US Dietary Guidelines for Changes in Body Weight, Hemoglobin A1c, Blood Pressure, and Dietary Quality among African American Adults.

BACKGROUND: The US Dietary Guidelines (USDG) form the basis of nutrition guidelines, but the research informing the 3 USDG dietary patterns (Healthy US-Style [H-US], Mediterranean [Med], and vegetarian [Veg]) has been drawn largely from observational studies among White populations. OBJECTIVES: The Dietary Guidelines 3 Diets study was a 3-arm, 12-wk randomly assigned intervention among African American (AA) adults at risk of type 2 diabetes mellitus that tested the 3 USDG dietary patterns. METHODS: The AAs (ages 18-65 y, BMI 25-49.9 kg/m2, and BMI was measured in kg/m2) with ≥3 type 2 diabetes mellitus risk factors were recruited. Weight, HbA1c, blood pressure, and dietary quality (healthy eating index [HEI]) were collected at baseline and 12 wk. In addition, participants attended weekly online classes that were designed using material from the USDG/MyPlate. Repeated measures, mixed models with maximum likelihood estimation, and robust computation of standard errors were tested. RESULTS: Of the 227 participants screened, 63 were eligible (83% female; age 48.0 ± 10.6 y, BMI 35.9 ± 0.8 kg/m2) and randomly assigned to the Healthy US-Style Eating Pattern (H-US) (n = 21, 81% completion), healthy Mediterranean-style eating pattern (Med) (n = 22, 86% completion), or healthy vegetarian eating pattern (Veg) (n = 20, 70% completion) groups. Within-group, but not between groups, weight loss was significant (-2.4 ± 0.7 kg H-US, -2.6 ± 0.7 kg Med, -2.4 ± 0.8 kg Veg; P = 0.97 between group). There was also no significant difference between groups for changes in HbA1c (0.03 ± 0.05% H-US, -0.10 ± 0.05% Med, 0.07 ± 0.06% Veg; P = 0.10), systolic BP (-5.5 ± 2.7 mmHg H-US, -3.2 ± 2.5 mmHg Med, -2.4 ± 2.9 mmHg Veg; P = 0.70), diastolic blood pressure (-5.2 ± 1.8 mmHg H-US, -2.0 ± 1.7 mmHg Med, -3.4 ± 1.9 mmHg Veg; P = 0.41), or HEI (7.1 ± 3.2 H-US, 15.2 ± 3.1 Med, 4.6 ± 3.4 Veg; P = 0.06). Post hoc analyses showed that the Med group had significantly greater improvements in HEI compared to the Veg group (difference = -10.6 ± 4.6; 95% CI: -19.7, -1.4; P = 0.02). CONCLUSIONS: The present study demonstrates that all 3 USDG dietary patterns lead to significant weight loss among AA adults. However, none of the outcomes were significantly different between groups. This trial was registered at clinicaltrials.gov as NCT04981847.

Ensuring Indigenous co-leadership in health research: a Can-SOLVE CKD case example.

BACKGROUND: Indigenous people are insightful and informed about their own health and wellness, yet their visions, strengths and knowledge are rarely incorporated into health research. This can lead to subpar engagement or irrelevant research practices, which exacerbates the existing health inequities Indigenous people experience compared to the non-Indigenous population. Data consistently underscores the importance of Indigenous self-determination in research as a means to address health inequities. However, there are few formal methods to support this goal within the existing research context, which is dominated by Western perspectives. MAIN TEXT: Canadians Seeking Solutions and Innovations to Overcome Chronic Kidney Disease (Can-SOLVE CKD) is a patient-oriented research network in Canada that recognizes the need to create the space to facilitate Indigenous self-determination in research. Indigenous members of the network therefore created and evolved a unique group, called the Indigenous Peoples' Engagement and Research Council (IPERC). IPERC plays a critical role in informing Can-SOLVE CKD research priorities, as well as creating tools to support Indigenous-specific research and engagement. This approach ensures that Indigenous voices and knowledge are critical threads within the fabric of the network's operations and research projects. Here, we describe the methods taken to create a council such as IPERC, and provide examples of initiatives by the council that aim to increase Indigenous representation, participation and partnership in research. We share lessons learned on what factors contribute to the success of IPERC, which could be valuable for other organizations interested in creating Indigenous-led research councils. CONCLUSION: Indigenous self-determination in research is critical for addressing health inequities. Here, we present a unique model, led by a council of diverse Indigenous people, which could help reduce health equities and lead to a better era of research for everyone.

The Language of Research: Creating Spaces to Better Understand How We Speak and How We Are Heard.

Anti-Indigenous racism education and cultural safety training can help cultivate greater awareness and hold the potential to encourage Western-trained researchers to work in solidarity with Indigenous partners to resist the structural status quo. The purpose of this article is to provide an overview and author reflections on an immersive educational series "The Language of Research: How Do We Speak? How Are We Heard?". The series was developed by a Canadian group that included an Indigenous Knowledge Keeper, non-Indigenous researchers, and parent partners, all of whom have training or experience in Westernized research and/or health care. The 6-session virtual series was made available through a provincial pediatric neurodevelopment and rehabilitation research group in Canada. Participation was open to a broad audience, including but not limited to researchers, clinicians, families, and health-care professionals. This learning opportunity was developed as a starting point for ongoing integration of an anti-racism perspective within our provincial research group and began through conversation about how words or language typically used in Western approaches to research, ("recruit," "consent," "participant") could be unwelcoming, exclusionary, and harmful. Topics that were explored during the sessions included Using Descriptive Language/Communication; Relationships and Connection; and, Trust, Healing, and Allyship. The article aims to contribute to the ongoing dialogue related to disrupting racism and decolonizing research in the fields of neurodevelopment and rehabilitation. Reflections about the series are offered by the authorship team throughout the article, to solidify and share learning. We acknowledge this is only one of many steps in our learning.

Impact of an Emergency Department Saturation Tool on a Pediatric Hospital's Capacity Management Policy.

OBJECTIVE: We sought to describe how the Emergency Department Work Index (EDWIN) saturation tool (1) correlates with PED overcrowding during a capacity management activation policy, known internally as Purple Alert and (2) compare overall hospital-wide capacity metrics on days in which the alert was instituted versus days it was not. METHODS: This study was conducted between January 1, 2017 and December 31, 2019 in a 30-bed academic quaternary care, urban PED within a university hospital. The EDWIN tool was implemented in January 2019 and objectively measured the busyness of the PED. To determine correlation with overcrowding, EDWIN scores were calculated at alert initiation. Mean alert hours per month were plotted on a control chart before and after EDWIN implementation. We also compared daily numbers of PED visits, inpatient admissions, and patients left without being seen (LWBS) for days with and without alert initiation to assess whether or not Purple Alert correlated with high PED usage. RESULTS: During the study period, the alert was activated a total of 146 times; 43 times after EDWIN implementation. Mean EDWIN score was 2.5 (SD 0.5, min 1.5, max 3.8) at alert initiation. There were no alert occurrences for EDWIN scores less than 1.5 (not overcrowded). There was no statistically significant difference for mean alert hours per month before and after EDWIN was instituted (21.4 vs 20.2, P = 0.08). Mean numbers of PED visits, inpatient admissions, and patients left without being seen were higher on days with alert activation ( P < 0.001 for all). CONCLUSIONS: The EDWIN score correlated with PED busyness and overcrowding during alert activation and correlated with high PED usage. Future studies could include implementing a real-time Web-based EDWIN score as a prediction tool to prevent overcrowding and verifying EDWIN generalizability at other PED sites.

Implementation of a novel vocal cord dysfunction management pathway using the consolidated framework for implementation research.

Every year in Australia over a thousand children who are born with congenital heart disease require surgical intervention. Vocal cord dysfunction (VCD) can be an unavoidable and potentially devastating complication of surgery for congenital heart disease. Structured, multidisciplinary care pathways help to guide clinical care and reduce mortality and morbidity. An implementation study was conducted to embed a novel, multidisciplinary management pathway into practice using the consolidated framework for implementation research (CFIR). The goal of the pathway was to prepare children with postoperative vocal cord dysfunction to safely commence and transition to oral feeding. Education sessions to support pathway rollout were completed with clinical stakeholders. Other implementation strategies used included adaptation of the pre-procedural pathway to obtain consent, improving the process of identifying patients on the VCD pathway, and nominating a small team who were responsible for the ongoing monitoring of patients following recruitment. Implementation success was evaluated according to compliance with pathway defined management. Our study found that while there were several barriers to pathway adoption, implementation of the pathway was feasible despite pathway adaptations that were required in response to COVID-19.

Designing and Implementing a Zero Harm Falls Prevention Program: A Quality Improvement Study.

BACKGROUND: Inpatient falls with harm have severe implications on patients and the health care system. PURPOSE: We implemented a zero harm approach to falls prevention, which aimed to reduce falls with injury by 25% within 1 year. METHODS: We implemented a multifaceted and multidisciplinary quality improvement falls prevention strategy that included facilitating organization-wide education, adopting the Morse Fall Risk Assessment tool, displaying real-time unit-specific falls rates, and implementing a transparent root-cause analysis process after falls. Our outcome measure was falls with injury per 1000 patient-days. RESULTS: We observed a decrease in the rate of patient falls with injury from 2.03 (baseline period) to 1.12 (1 year later) per 1000 patient-days. We also observed increases in awareness around falls prevention and patient safety incident reporting. CONCLUSIONS: Our zero harm approach reduced falls with injury while improving our patient safety culture.

Anti-Interleukin-10 Unleashes Transcriptional Response to Leishmanial Antigens in Visceral Leishmaniasis Patients.

Visceral leishmaniasis (VL; Leishmania donovani) cases produce interferon-γ and tumor necrosis factor in response to soluble leishmanial antigen (SLA) in whole-blood assays. Using transcriptional profiling, we demonstrate the impact of interleukin-10 (IL-10), a cytokine implicated in VL, on this response. SLA stimulation identified 28 differentially expressed genes (DEGs), 17/28 in a single network with TNF as hub. SLA plus anti-IL-10 produced 454 DEGs, 292 in a single network with TNF, IFNG, NFKBIA, IL6, and IL1B as hubs in concert with a remarkable chemokine/cytokine storm. Our data demonstrate the singular effect of IL-10 as a potent immune modulator in VL.

Breast cancer incidence and early diagnosis in a family history risk and prevention clinic: 33-year experience in 14,311 women.

PURPOSE: Women at increased familial breast cancer risk have been offered screening starting at an earlier age and increased frequency than national Screening Programmes for over 30 years. There are limited data on longer-term largescale implementation of this approach on cancer diagnosis. METHODS: Women at our institution at ≥ 17% lifetime breast cancer risk have been offered enhanced screening with annual mammography starting at age 35 or 5-years younger than youngest affected relative, with upper age limit 50 for moderate and 60 for high-risk. Breast cancer pathology, stage and receptor status were assessed as well as survival from cancer diagnosis by Kaplan-Meier analysis. RESULTS: Overall 14,311 women were seen and assessed for breast cancer risk, with 649 breast cancers occurring in 129,119 years follow up (post-prevalent annual incidence = 4.55/1000). Of 323/394 invasive breast cancers occurring whilst on enhanced screening, most were lymph-node negative (72.9%), T1 (≤ 20 mm, 73.2%) and stage-1 (61.4%), 126/394 stage2-4 (32%). 10-year breast cancer specific survival was 91.3% (95% CI 87.4-94.0) better than the 75.9% (95% CI 74.9-77.0) published for England in 2013-2017. As expected, survival was significantly better for women with screen detected cancers (p < 0.001). Ten-year survival was particularly good for those diagnosed ≤ 40 at 93.8% (n = 75; 95% CI 84.2-97.6). Women with lobular breast cancers had worse 10-year survival at 85.9% (95% CI 66.7-94.5). Breast cancer specific survival was good for 119 BRCA1/2 carriers with 20-year survival in BRCA1:91.2% (95% CI 77.8-96.6) and 83.8% (62.6-93.5) for BRCA2. CONCLUSIONS: Targeted breast screening in women aged 30-60 years at increased familial risk is associated with good long-term survival that is substantially better than expected from population data.

How coronavirus disease will change the face of travel medicine.

PURPOSE OF REVIEW: The current article will review how the coronavirus disease 2019 pandemic has changed travel and travel medicine. RECENT FINDINGS: Travelers spread severe acute respiratory syndrome coronavirus 2 globally and continue to spread variants. The characteristics of the virus, the place, and time created a perfect storm that allowed the virus to quickly spread globally. The virus spread by every mode of travel with risk of transmission influenced by proximity to an infected person, duration of trip, physical characteristics of the space, and ventilation. Superspreading events were common; a small percentage of infected people accounted for most of transmission. The travel and tourist industry was devastated as lockdowns and quarantines severely restricted domestic and international travel. A trip includes multiple segments and shared sequential spaces, mostly indoors. Creating safe travel requires attention to all segments of a trip. SUMMARY: The coronavirus disease 2019 pandemic has affected every part of travel and travel medicine. The rapid development of multiple safe and effective vaccines and their deployment is allowing resumption of travel, yet many populations lack access to vaccines, and high levels of transmission continue in many areas. Providing documentation of vaccination or immunity in a consistent, verifiable, interoperable system is one of many active issues.

High-Throughput CRISPR-Cas13 SARS-CoV-2 Test.

BACKGROUND: The ability to control the spread of COVID-19 continues to be hampered by a lack of rapid, scalable, and easily deployable diagnostic solutions. METHODS: We developed a diagnostic method based on CRISPR (clustered regularly interspaced short palindromic repeats) that can deliver sensitive, specific, and high-throughput detection of Sudden Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2). The assay utilizes SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing) for the qualitative detection of SARS-CoV-2 RNA and may be performed directly on a swab or saliva sample without nucleic acid extraction. The assay uses a 384-well format and provides results in <1 hour. RESULTS: Assay performance was evaluated with 105 (55 negative, 50 positive) remnant SARS-CoV-2 specimens previously tested using Food and Drug Administration emergency use authorized assays and retested with a modified version of the Centers for Disease Control and Prevention (CDC) quantitative PCR with reverse transcription (RT-qPCR) assay. When combined with magnetic bead-based extraction, the high-throughput SHERLOCK SARS-CoV-2 assay was 100% concordant (n = 60) with the CDC RT-qPCR. When used with direct sample addition the high-throughput assay was also 100% concordant with the CDC RT-qPCR direct method (n = 45). With direct saliva sample addition, the negative and positive percentage agreements were 100% (15/15, 95% CI: 81.8-100%) and 88% (15/17, 95% CI: 63.6-98.5%), respectively, compared with results from a collaborating clinical laboratory. CONCLUSIONS: This high-throughput assay identifies SARS-CoV-2 from patient samples with or without nucleic acid extraction with high concordance to RT-qPCR methods. This test enables high complexity laboratories to rapidly increase their testing capacities with simple equipment.

Inflammatory profile in a canine model of hypothermic circulatory arrest.

BACKGROUND: Hypothermic circulatory arrest (HCA) is a technique used for complex repair of the aorta, but it can be associated with neurologic morbidity. To better understand the molecular changes that underlie ischemic brain injury, we assessed gene expression and cytokine/chemokine polypeptide concentration in brain tissue and cerebrospinal fluid (CSF) of canines that underwent two hours of HCA. MATERIALS AND METHODS: Adult male canines were cannulated peripherally for cardiopulmonary bypass, cooled to 18°C, and arrested for two hours. Animals were euthanized two, eight, or 24 hours post-HCA (n = 8 per group), and their brains were compared to brains from eight normal canines, using gene expression microarray analysis, cytokine assay, and histopathology. RESULTS: Two to eight hours after HCA, pro-inflammatory cytokine mRNAs increased markedly, and gene expression was enriched within signaling pathways related to neuroinflammation or ischemic injury. Concentrations of pro-inflammatory cytokine polypeptides IL-6, IL-8, IL-1ß, and CCL2 were very low in normal canine brain, whereas anti-inflammatory IL-10 and TGF-ß1 were expressed at moderate levels. Pro-inflammatory cytokine concentrations rose robustly in cerebral tissue and CSF after HCA. IL-6 and IL-8 peaked at eight hours and declined at 24 hours, while IL-1ß and CCL2 remained elevated. Concentrations of anti-inflammatory IL-10 and TGF-ß1 were maintained after HCA, with a significant increase in TGF-ß1 at 24 hours. CONCLUSIONS: These cytokines represent potential diagnostic markers for ischemic neurologic injury that could be used to assess neurologic injury in patients undergoing HCA. The cellular mechanisms underlying this pro-inflammatory, ischemic-induced injury represent potential targets for neuroprotection in the future.

NMDA Receptor Antagonism for Neuroprotection in a Canine Model of Hypothermic Circulatory Arrest.

BACKGROUND: Hypothermic circulatory arrest (HCA) is associated with neurologic morbidity, in part mediated by activation of the N-methyl-D-aspartate glutamate receptor causing excitotoxicity and neuronal apoptosis. Using a canine model, we hypothesized that the N-methyl-D-aspartate receptor antagonist MK801 would provide neuroprotection and that MK801 conjugation to dendrimer nanoparticles would improve efficacy. MATERIALS AND METHODS: Male hound dogs were placed on cardiopulmonary bypass, cooled to 18°C, and underwent 90 min of HCA. Dendrimer conjugates (d-MK801) were prepared by covalently linking dendrimer surface OH groups to MK801. Six experimental groups received either saline (control), medium- (0.15 mg/kg) or high-dose (1.56 mg/kg) MK801, or low- (0.05 mg/kg), medium-, or high-dose d-MK801. At 24, 48, and 72 h after HCA, animals were scored by a standardized neurobehavioral paradigm (higher scores indicate increasing deficits). Cerebrospinal fluid was obtained at baseline, eight, 24, 48, and 72 h after HCA. At 72 h, brains were examined for histopathologic injury in a blinded manner (higher scores indicate more injury). RESULTS: Neurobehavioral deficit scores were reduced by low-dose d-MK801 on postoperative day two (P < 0.05) and by medium-dose d-MK801 on postoperative day 3 (P = 0.05) compared with saline controls, but free drug had no effect. In contrast, high-dose free MK801 significantly improved histopathology scores compared with saline (P < 0.05) and altered biomarkers of injury in cerebrospinal fluid, with a significant reduction in phosphorylated neurofilament-H for high-dose MK801 versus saline (P < 0.05). CONCLUSIONS: Treatment with MK-801 demonstrated significant improvement in neurobehavioral and histopathology scores after HCA, although not consistently across doses and conjugates.

Within and Across Language Predictors of Word Learning Processes in Dual Language Learners.

This study investigated the relation between Dual Language Learners' (N = 90) vocabulary and grammar comprehension and word learning processes in preschool (aged 3-through-5 years). Of interest was whether: (a) performance in Spanish correlated with performance in English within each domain; and (b) comprehension predicted novel word learning within and across languages. Dual-language experience was evaluated as a potential moderator. Hierarchical linear modeling revealed stronger predictive associations within each language than across languages. Across languages, results varied by experience and domain. Structural sensitivity theory suggests exposure to two languages heightens awareness of parameters along which languages vary and provides a framework for interpreting complex associations within and across languages. Knowledge from one language may influence learning in both.

Complement receptor 3 mediates ruffle-like, actin-rich aggregates during phagocytosis of Leishmania infantum metacyclics.

The parasitic protozoan Leishmania infantum resides primarily in macrophages throughout mammalian infection. Infection is initiated by deposition of the metacyclic promastigote into the dermis of a mammalian host by the sand fly vector. Promastigotes enter macrophages by ligating surface receptors such as complement receptor 3 (CR3), inducing phagocytosis of the parasite. At the binding site of metacyclic promastigotes, we observed large asymmetrical aggregates of macrophage membrane with underlying actin, resembling membrane ruffles. Actin accumulation was observed at the point of initial contact, before phagosome formation and accumulation of peri-phagosomal actin. Ruffle-like structures did not form during phagocytosis of attenuated promastigotes or during phagocytosis of the intracellular amastigote form of L. infantum. Entry of promastigotes through massive actin accumulation was associated with a subsequent delay in fusion of the parasitophorous vacuole (PV) with the lysosomal markers LAMP-1 and Cathepsin D. Actin accumulation was also associated with entry through CR3, since macrophages from CD11b knockout (KO) mice did not form massive aggregates of actin during phagocytosis of metacyclic promastigotes. Furthermore, intracellular survival of L. infantum was significantly decreased in CD11b KO compared to wild type macrophages, although entry rates were similar. We conclude that both promastigote virulence and host cell CR3 are needed for the formation of ruffle-like membrane structures at the site of metacyclic promastigote phagocytosis, and that formation of actin-rich aggregates during entry correlates with the intracellular survival of virulent promastigotes.

Effective recruitment strategies for African-American men and women: the Nutritious Eating with Soul study.

Previous studies have found it challenging to recruit African-American (AA) participants into health education research studies. The goal of this article is to describe the recruitment methods used for the Nutritious Eating with Soul (NEW Soul) study, a 2-year randomized behavioral health education intervention, conducted in two cohorts, with emphasis on methods used for reaching men. Participants indicated how they learned about the study on an online screening questionnaire from a list of the recruitment strategies we employed. Due to limited recruitment of men in Cohort 1, recruitment strategies for Cohort 2 focused on reaching men. Across the two cohorts, a total of 568 (23% men) participants completed the online screener and 159 (21% men) completed all baseline assessments and enrolled in the study. The most effective methods for completing screening questionnaires were radio ads, referrals from friends and family, TV interviews, social media posts and community events. Men were primarily recruited via radio ads, whereas women were more often recruited through TV and social media. Radio was an effective way to recruit AA adults into nutrition interventions, particularly men. In addition, low-cost methods, such as personal referrals, social media posts and community events were also effective strategies.

Bayesian compartmental models and associated reproductive numbers for an infection with multiple transmission modes.

Zoonotic visceral leishmaniasis (ZVL) is a serious neglected tropical disease that is endemic in 98 countries. ZVL is primarily transmitted via a sand fly vector. In the United States, it is enzootic in some canine populations; it is transmitted from infectious mother to pup transplacentally, and vector-borne transmission is absent. This absence affords a unique opportunity to study (1) vertical transmission dynamics in dogs and (2) the importance of vertical transmission in maintaining an infectious reservoir in the presence of a vector. In this paper, we present Bayesian compartmental models and reproductive number formulations to examine (1) and (2), providing a mechanism to plan and evaluate interventions in regions where both transmission modes are present. First, we propose an individual-level susceptible, infectious, removed (SIR) model to study the effect of maternal infection status during pregnancy on pup infection progression. We provide evidence that pups born to diagnostically positive mothers during pregnancy are more likely to become diagnostically positive both earlier in life, and at some point during their lifetime, than those born to diagnostically negative mothers. Second, we propose a population-level SIR model to study the impact of a vertically maintained reservoir on propagating infection in a naive canine population through emergent vector transmission using simulation studies. We also present reproductive numbers to quantify contributions of vertically infected and vector-infected dogs to maintaining infection in the population. We show that a vertically maintained canine reservoir can propagate infection in a theoretical naive population in the presence of a vector.

Nlrp12 Mediates Adverse Neutrophil Recruitment during Influenza Virus Infection.

Exaggerated inflammatory responses during influenza A virus (IAV) infection are typically associated with severe disease. Neutrophils are among the immune cells that can drive this excessive and detrimental inflammation. In moderation, however, neutrophils are necessary for optimal viral control. In this study, we explore the role of the nucleotide-binding domain leucine-rich repeat containing receptor family member Nlrp12 in modulating neutrophilic responses during lethal IAV infection. Nlrp12-/- mice are protected from lethality during IAV infection and show decreased vascular permeability, fewer pulmonary neutrophils, and a reduction in levels of neutrophil chemoattractant CXCL1 in their lungs compared with wild-type mice. Nlrp12-/- neutrophils and dendritic cells within the IAV-infected lungs produce less CXCL1 than their wild-type counterparts. Decreased CXCL1 production by Nlrp12-/- dendritic cells was not due to a difference in CXCL1 protein stability, but instead to a decrease in Cxcl1 mRNA stability. Together, these data demonstrate a previously unappreciated role for Nlrp12 in exacerbating the pathogenesis of IAV infection through the regulation of CXCL1-mediated neutrophilic responses.