An adapted protocol to derive microglia from stem cells and its application in the study of CSF1R-related disorders.

BACKGROUND: Induced pluripotent stem cell-derived microglia (iMGL) represent an excellent tool in studying microglial function in health and disease. Yet, since differentiation and survival of iMGL are highly reliant on colony-stimulating factor 1 receptor (CSF1R) signaling, it is difficult to use iMGL to study microglial dysfunction associated with pathogenic defects in CSF1R. METHODS: Serial modifications to an existing iMGL protocol were made, including but not limited to changes in growth factor combination to drive microglial differentiation, until successful derivation of microglia-like cells from an adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) patient carrying a c.2350G > A (p.V784M) CSF1R variant. Using healthy control lines, the quality of the new iMGL protocol was validated through cell yield assessment, measurement of microglia marker expression, transcriptomic comparison to primary microglia, and evaluation of inflammatory and phagocytic activities. Similarly, molecular and functional characterization of the ALSP patient-derived iMGL was carried out in comparison to healthy control iMGL. RESULTS: The newly devised protocol allowed the generation of iMGL with enhanced transcriptomic similarity to cultured primary human microglia and with higher scavenging and inflammatory competence at ~ threefold greater yield compared to the original protocol. Using this protocol, decreased CSF1R autophosphorylation and cell surface expression was observed in iMGL derived from the ALSP patient compared to those derived from healthy controls. Additionally, ALSP patient-derived iMGL presented a migratory defect accompanying a temporal reduction in purinergic receptor P2Y12 (P2RY12) expression, a heightened capacity to internalize myelin, as well as heightened inflammatory response to Pam3CSK4. Poor P2RY12 expression was confirmed to be a consequence of CSF1R haploinsufficiency, as this feature was also observed following CSF1R knockdown or inhibition in mature control iMGL, and in CSF1RWT/KO and CSF1RWT/E633K iMGL compared to their respective isogenic controls. CONCLUSIONS: We optimized a pre-existing iMGL protocol, generating a powerful tool to study microglial involvement in human neurological diseases. Using the optimized protocol, we have generated for the first time iMGL from an ALSP patient carrying a pathogenic CSF1R variant, with preliminary characterization pointing toward functional alterations in migratory, phagocytic and inflammatory activities.

Inoviridae prophage and bacterial host dynamics during diversification, succession, and Atlantic invasion of Pacific-native Vibrio parahaemolyticus.

IMPORTANCE: An understanding of the processes that contribute to the emergence of pathogens from environmental reservoirs is critical as changing climate precipitates pathogen evolution and population expansion. Phylogeographic analysis of Vibrio parahaemolyticus hosts combined with the analysis of their Inoviridae phage resolved ambiguities of diversification dynamics which preceded successful Atlantic invasion by the epidemiologically predominant ST36 lineage. It has been established experimentally that filamentous phage can limit host recombination, but here, we show that phage loss is linked to rapid bacterial host diversification during epidemic spread in natural ecosystems alluding to a potential role for ubiquitous inoviruses in the adaptability of pathogens. This work paves the way for functional analyses to define the contribution of inoviruses in the evolutionary dynamics of environmentally transmitted pathogens.

mTOR Pathway Somatic Pathogenic Variants in Focal Malformations of Cortical Development: Novel Variants, Topographic Mapping, and Clinical Outcomes.

Background and Objectives: Somatic and germline pathogenic variants in genes of the mammalian target of rapamycin (mTOR) signaling pathway are a common mechanism underlying a subset of focal malformations of cortical development (FMCDs) referred to as mTORopathies, which include focal cortical dysplasia (FCD) type II, subtypes of polymicrogyria, and hemimegalencephaly. Our objective is to screen resected FMCD specimens with mTORopathy features on histology for causal somatic variants in mTOR pathway genes, describe novel pathogenic variants, and examine the variant distribution in relation to neuroimaging, histopathologic classification, and clinical outcomes. Methods: We performed ultra-deep sequencing using a custom HaloPlexHS Target Enrichment kit in DNA from 21 resected fresh-frozen histologically confirmed FCD type II, tuberous sclerosis complex, or hemimegalencephaly specimens. We mapped the variant alternative allele frequency (AAF) across the resected brain using targeted ultra-deep sequencing in multiple formalin-fixed paraffin-embedded tissue blocks. We also functionally validated 2 candidate somatic MTOR variants and performed targeted RNA sequencing to validate a splicing defect associated with a novel DEPDC5 variant. Results: We identified causal mTOR pathway gene variants in 66.7% (14/21) of patients, of which 13 were somatic with AAF ranging between 0.6% and 12.0%. Moreover, the AAF did not predict balloon cell presence. Favorable seizure outcomes were associated with genetically clear resection borders. Individuals in whom a causal somatic variant was undetected had excellent postsurgical outcomes. In addition, we demonstrate pathogenicity of the novel c.4373_4375dupATG and candidate c.7499T>A MTOR variants in vitro. We also identified a novel germline aberrant splice site variant in DEPDC5 (c.2802-1G>C). Discussion: The AAF of somatic pathogenic variants correlated with the topographic distribution, histopathology, and postsurgical outcomes. Moreover, cortical regions with absent histologic FCD features had negligible or undetectable pathogenic variant loads. By contrast, specimens with frank histologic abnormalities had detectable pathogenic variant loads, which raises important questions as to whether there is a tolerable variant threshold and whether surgical margins should be clean, as performed in tumor resections. In addition, we describe 2 novel pathogenic variants, expanding the mTORopathy genetic spectrum. Although most pathogenic somatic variants are located at mutation hotspots, screening the full-coding gene sequence remains necessary in a subset of patients.

Global dissemination of influenza A virus is driven by wild bird migration through arctic and subarctic zones.

Influenza A viruses (IAV) circulate endemically among many wild aquatic bird populations that seasonally migrate between wintering grounds in southern latitudes to breeding ranges along the perimeter of the circumpolar arctic. Arctic and subarctic zones are hypothesized to serve as ecologic drivers of the intercontinental movement and reassortment of IAVs due to high densities of disparate populations of long distance migratory and native bird species present during breeding seasons. Iceland is a staging ground that connects the East Atlantic and North Atlantic American flyways, providing a unique study system for characterizing viral flow between eastern and western hemispheres. Using Bayesian phylodynamic analyses, we sought to evaluate the viral connectivity of Iceland to proximal regions and how inter-species transmission and reassortment dynamics in this region influence the geographic spread of low and highly pathogenic IAVs. Findings demonstrate that IAV movement in the arctic and subarctic reflects wild bird migration around the perimeter of the circumpolar north, favouring short-distance flights between proximal regions rather than long distance flights over the polar interior. Iceland connects virus movement between mainland Europe and North America, consistent with the westward migration of wild birds from mainland Europe to Northeastern Canada and Greenland. Though virus diffusion rates were similar among avian taxonomic groups in Iceland, gulls play an outsized role as sinks of IAVs from other avian hosts prior to onward migration. These data identify patterns of virus movement in northern latitudes and inform future surveillance strategies related to seasonal and emergent IAVs with potential public health concern.

Preventing Suicidal Behavior Among American Indian and Alaska Native Adolescents and Young Adults.

From 2009 to 2018, overall suicide rates in the United States increased by 20.3% and increased by 43.5% among non-Hispanic American Indian and Alaska Native (AI/AN) communities. Combining years 2009 through 2018, suicide rates per 100 000 population among non-Hispanic AI/AN adolescents and young adults aged 15 to 34 years were 2 to 4 times higher than those of adolescents and young adults of other races and ethnicities. An estimated 14% to 27% of non-Hispanic AI/AN adolescents attempted suicide during that time. The elevated rates of suicidal behavior among non-Hispanic AI/AN adolescents and young adults reflect inequities in the conditions that create health. In this topical review, we describe school-based educational efforts that are driven by local AI/AN communities, such as the American Indian Life Skills curriculum, that teach stress and coping skills and show promise in reducing suicidal ideation attempts and fatalities among AI/AN adolescents. Using a social-determinants-of-health lens, we review the availability and quality of employment as an important influencer of suicidal behavior, as well as the role of the workplace as an environment for suicide prevention in AI/AN communities. Working with tribal, state, local, and federal colleagues, the public health community can implement programs known to be effective and create additional comprehensive strategies to reduce inequities and ultimately reduce suicide rates.

Interpersonal Media and Face-to-Face Communication: Relationship with Life Satisfaction and Loneliness.

Framed by need to belong theory, this study considers the role of communication modality, geographic proximity, and the number of close relationship partners to predict life satisfaction and loneliness. A quota sample of American adults (N = 1,869) completed four name generation tasks to identify up to 16 alters, resulting in four alters per participant (n = 7,471). Participants reported the frequency with which they communicated with each alter in the past year in person and through eight interpersonal media. Results suggest that number of relationship partners and frequency of face-to-face interaction were robust predictors of life satisfaction and loneliness. Those living alone faced significant threats to well-being. Video chat and voice call frequency were also associated with greater life satisfaction. Mediation analyses showed voice call frequency was indirectly associated with less loneliness through greater relationship maintenance satisfaction, while lean media was indirectly associated with greater loneliness through relationship maintenance frustration. Supplementary Information: The online version contains supplementary material available at 10.1007/s10902-022-00581-8.

Telehealth and Public Health Practice in the United States-Before, During, and After the COVID-19 Pandemic.

Telehealth is the use of electronic information and telecommunication technologies to provide care when the patient and the provider are not in the same room at the same time. Telehealth accounted for less than 1% of all Medicare Fee-for-Service outpatient visits in the United States in 2019 but grew to account for 46% of all visits in April 2020. Changes in reimbursement and licensure policies during the COVID-19 pandemic appeared to greatly facilitate this increased use. Telehealth will continue to account for a substantial portion of care provided in the United States and globally. A better understanding of telehealth approaches and their evidence base by public health practitioners may help improve their ability to collaborate with health care organizations to improve population health. The article summarizes the Centers for Disease Control and Prevention's (CDC's) approach to understanding the evidence base for telehealth in public health practice, possible applications for telehealth in public health practice, and CDC's use of telehealth to improve population health.

Spatiotemporal changes in influenza A virus prevalence among wild waterfowl inhabiting the continental United States throughout the annual cycle.

Avian influenza viruses can pose serious risks to agricultural production, human health, and wildlife. An understanding of viruses in wild reservoir species across time and space is important to informing surveillance programs, risk models, and potential population impacts for vulnerable species. Although it is recognized that influenza A virus prevalence peaks in reservoir waterfowl in late summer through autumn, temporal and spatial variation across species has not been fully characterized. We combined two large influenza databases for North America and applied spatiotemporal models to explore patterns in prevalence throughout the annual cycle and across the continental United States for 30 waterfowl species. Peaks in prevalence in late summer through autumn were pronounced for dabbling ducks in the genera Anas and Spatula, but not Mareca. Spatially, areas of high prevalence appeared to be related to regional duck density, with highest predicted prevalence found across the upper Midwest during early fall, though further study is needed. We documented elevated prevalence in late winter and early spring, particularly in the Mississippi Alluvial Valley. Our results suggest that spatiotemporal variation in prevalence outside autumn staging areas may also represent a dynamic parameter to be considered in IAV ecology and associated risks.

Development and Evaluation of a Commercial Direct-Fed Microbial (Zymospore®) on the Fecal Microbiome and Growth Performance of Broiler Chickens under Experimental Challenge Conditions.

Direct-fed microbials (DFM) are added to broiler chicken diets in order to promote the proliferation of beneficial intestinal bacterial populations, which may lead to gains in performance efficiency and, potentially, reduce the level of enteric pathogens in the broiler chickens. The selection and laboratory evaluation of Bacillus subtilis strains as well as the experimental trial results of a novel Bacillus-based commercial DFM product are described. Fifteen wild-type Bacillus subtilis strains were characterized and assayed for their enzyme production capability, spore resistance to pH, salinity, and temperature, and ability to inhibit the growth of E. coli and Salmonella spp. The final DFM formulation was evaluated and compared to an antibiotic growth promoter (AGPs) in two experimental trials. In Experiment 1, broilers were given a defined challenge of Eimeria spp. and Clostridium perfringens to induce intestinal dysbiosis. The optimal dose of the DFM was determined to be 0.3 kg/ton of feed. At this dose, the broilers fed the DFM performed as well as the Flavomycin®-fed broilers. Further, intestinal microbiome analysis indicates that the use of the DFM enhances bacterial diversity of the gut flora by day 5 of age, increasing levels of lactic acid bacteria (LAB) and Clostridiales by 25 days of age, which may enhance the digestion of feed and promote growth of the birds. In Experiment 2, the broilers were raised on recycled litter and given an undefined challenge orally to mimic commercial growth conditions. In this trial, the DFM performed as well as the bacitracin methylene disalicylate (BMD)-11%-fed birds. The results of the present studies suggest that this novel DFM, Zymospore®, improves the performance of broiler chickens under experimental challenge conditions as effective as an AGP, providing a safe and effective substitute to the poultry industry.

Streptococcus gordonii Poised for Glycan Feeding through a MUC5B-Discriminating, Lipoteichoic Acid-Mediated Outside-In Signaling Circuit.

Many oral bacteria employ cell wall-anchored adhesins to bind to the salivary films coating the teeth and mucosal surfaces. Surface binding prevents clearance and facilitates catabolism of salivary film glycoproteins. We asked whether Streptococcus gordonii adhesin expression changes in response to surface salivary cues using a eukaryote-like, outside-in recognition and signaling circuit. To determine whether the cues were discriminated, S. gordonii was tested during cell adhesion and biofilm formation on a MUC5B-rich or lower-molecular-mass salivary fraction or an uncoated abiotic surface. Cells were recovered and analyzed for differences in gene expression and proteins in cell wall fractions. In salivary-free conditions, planktonic S. gordonii presented three prominent cell wall LPXTG-motif proteins, SGO_1487, SGO_0890, and MbpA (mucin-binding protein A; SGO_0707). During biofilm formation on MUC5B-coated surfaces, MbpA, a MUC5B-binding protein, and key genes in the tagatose and quorum-sensing pathways were strongly promoted. The response to MUC5B required the two-component system (TCS), streptococcal regulator of adhesins sensor and regulator (SraSR, SGO_1180/81), lipoteichoic acid (LTA), and the homologous paired adhesins, SspA and SspB (SspAB). LTA appears to link the outside signal (MUC5B) to intramembrane SraSR. Tagatose pathway gene expression may poise cells to metabolize MUC5B glycans and, with a quorum-sensing gene (luxS), may direct formation of a consortium to facilitate glycan cross-feeding by S. gordonii. We now show that a Gram-positive bacterium discriminates specific surface environmental cues using an outside-in signaling mechanism to apparently optimize colonization of saliva-coated surfaces. IMPORTANCE All organisms throughout the tree of life sense and respond to their surface environments. To discriminate among mucosal surface environmental cues, we report that Streptococcus gordonii recognizes a high-molecular-weight mucin glycoprotein, MUC5B, using the paired adhesins SspAB and lipoteichoic acid; the latter bridges the outside signal to an intramembrane two-component system to transcriptionally regulate a MUC5B-specific adhesin and genes that may facilitate glycan catabolism.

Ecological divergence of wild birds drives avian influenza spillover and global spread.

The diversity of influenza A viruses (IAV) is primarily hosted by two highly divergent avian orders: Anseriformes (ducks, swans and geese) and Charadriiformes (gulls, terns and shorebirds). Studies of IAV have historically focused on Anseriformes, specifically dabbling ducks, overlooking the diversity of hosts in nature, including gull and goose species that have successfully adapted to human habitats. This study sought to address this imbalance by characterizing spillover dynamics and global transmission patterns of IAV over 10 years at greater taxonomic resolution than previously considered. Furthermore, the circulation of viral subtypes in birds that are either host-adapted (low pathogenic H13, H16) or host-generalist (highly pathogenic avian influenza-HPAI H5) provided a unique opportunity to test and extend models of viral evolution. Using Bayesian phylodynamic modelling we uncovered a complex transmission network that relied on ecologically divergent bird hosts. The generalist subtype, HPAI H5 was driven largely by wild geese and swans that acted as a source for wild ducks, gulls, land birds, and domestic geese. Gulls were responsible for moving HPAI H5 more rapidly than any other host, a finding that may reflect their long-distance, pelagic movements and their immuno-naïve status against this subtype. Wild ducks, long viewed as primary hosts for spillover, occupied an optimal space for viral transmission, contributing to geographic expansion and rapid dispersal of HPAI H5. Evidence of inter-hemispheric dispersal via both the Pacific and Atlantic Rims was detected, supporting surveillance at high latitudes along continental margins to achieve early detection. Both neutral (geographic expansion) and non-neutral (antigenic selection) evolutionary processes were found to shape subtype evolution which manifested as unique geographic hotspots for each subtype at the global scale. This study reveals how a diversity of avian hosts contribute to viral spread and spillover with the potential to improve surveillance in an era of rapid global change.

Social media use, social displacement, and well-being.

Social displacement is the proposition that time spent on social media replaces time spent in face-to-face interaction, particularly with close friends and family, thus reducing well-being. There is clear evidence of growing mobile and social media use, and some evidence of a decline in face-to-face communication. This essay concludes, however, there is very little direct or causal evidence of social media time displacing face-to-face time. This article concludes that increasing social media use most likely displaces other media activities. To explain findings that seem to support social displacement, this essay examines the difference between population-level trends and within-individual behavior, and the difference between within-person and between-person displacement.

Clinical Yield of Electromagnetic Source Imaging and Hemodynamic Responses in Epilepsy: Validation With Intracerebral Data.

OBJECTIVES: Accurate delineation of the seizure-onset zone (SOZ) in focal drug-resistant epilepsy often requires stereo-electroencephalography (SEEG) recordings. We aimed at: (1) proposing a truly objective and quantitative comparison between electro-encephalography/magnetoencephalography (EEG/MEG) source-imaging (EMSI), EEG/functional MRI (EEG/fMRI) responses for similar spikes with primary-irritative zone (PIZ) and SOZ defined by SEEG and (2) evaluating the value of EMSI and EEG/fMRI to predict postsurgical outcome. METHODS: We identified patients with drug-resistant epilepsy who underwent EEG/MEG, EEG/fMRI, and subsequent SEEG at the Epilepsy Service from the Montreal Neurological Institute and Hospital. We quantified multimodal concordance within the SEEG channel-space, as spatial overlap with PIZ/SOZ and distances to the Spike-onset, Spike-maximum-amplitude and Seizure-core intracerebral channels, by applying a new methodology consisting of converting EMSI results into SEEG electrical potentials (EMSIe-SEEG) and projecting the most significant fMRI response on the SEEG channels (fMRIp-SEEG). Spatial overlaps with PIZ/SOZ (AUCPIZ, AUCSOZ) were assessed by using the area under the receiver operating characteristic curve (AUC). Here, AUC represents the probability that a randomly picked active contact exhibited higher amplitude when located inside the spatial reference than outside. RESULTS: Seventeen patients were included. Mean spatial overlaps with the primary-irritative zone and seizure-onset zone were 0.71 and 0.65 for EMSIe-SEEG, and 0.57 and 0.62 for fMRIp-SEEG. Good EMSIe-SEEG  spatial overlap with the primary-irritative zone was associated with smaller distance from the maximum EMSIe-SEEG contact to the Spike-maximum-amplitude channel (median distance 14 mm). Conversely, good fMRIp-SEEG spatial overlap with the seizure-onset zone was associated with smaller distances from the maximum  fMRIp-SEEG contact to the Spike-onset and Seizure-core channels (median distances 10 mm and 5mm respectively). Surgical outcomes were correctly predicted by EEG/MEG in 12/15 (80%) patients and EEG/fMRI in 6/11(54%) patients. CONCLUSIONS: Using a unique quantitative approach estimating EMSI and fMRI results in the reference SEEG channel-space, EEG/MEG and EEG/fMRI accurately localized the seizure-onset zone as well as the primary-irritative zone. Precisely, EEG/MEG more accurately localized the primary-irritative zone, whereas EEG/fMRI was more sensitive to the seizure-onset zone. Both neuro-imaging techniques provide complementary localization that can help guiding SEEG implantation and selecting good candidates for surgery.

Association of hypoxic ischemic brain injury on early CT after out of hospital cardiac arrest with neurologic outcome.

AIM: This study aimed to describe the prevalence of hypoxic-ischemic brain injury (HIBI) on head CT (HCT) obtained within two hours of return of spontaneous circulation (ROSC) care in the Emergency Department following out-of-hospital cardiac arrest (OHCA) and evaluate the association between early HIBI and neurologic outcome. METHODS: Retrospective single center observational study of post-OHCA patients between 2009 and 2017. Two cohorts were analyzed: those who underwent non-contrast HCT within two hours of ROSC and all others who survived to ICU admission. HIBI was defined as the presence of cerebral edema and/or abnormal gray-white matter differentiation in the HCT interpretation by a neuroradiologist. The primary outcomes were the prevalence of HIBI on early HCT and the magnitude of the association between HIBI and survival with good neurologic outcome using multivariable logistic regression. RESULTS: Following OHCA, 333 of 520 patients (64%) underwent HCT within two hours of ROSC and HIBI was present in 96 of 333 patients (29%). Of the early HCT cohort, those with HIBI had a significantly lower hospital survival (2%) and favorable neurologic outcome (1%). In those without HIBI on imaging, 88 of 237 patients (37%) had a favorable outcome. After adjustment for confounding variables, HIBI on early HCT was independently associated with a decreased likelihood of good neurologic outcome (aOR 0.015, 95% CI 0.002-0.12). CONCLUSION: HIBI was present on 29% of HCTs obtained within 2 h of ROSC in the patients selected for early imaging by emergency physicians and was strongly and inversely associated with survival with a good neurologic outcome.

Racial and Ethnic Disparities in Receipt of Medications for Treatment of COVID-19 - United States, March 2020-August 2021.

The COVID-19 pandemic has magnified longstanding health care and social inequities, resulting in disproportionately high COVID-19-associated illness and death among members of racial and ethnic minority groups (1). Equitable use of effective medications (2) could reduce disparities in these severe outcomes (3). Monoclonal antibody (mAb) therapies against SARS-CoV-2, the virus that causes COVID-19, initially received Emergency Use Authorization (EUA) from the Food and Drug Administration (FDA) in November 2020. mAbs are typically administered in an outpatient setting via intravenous infusion or subcutaneous injection and can prevent progression of COVID-19 if given after a positive SARS-CoV-2 test result or for postexposure prophylaxis in patients at high risk for severe illness.† Dexamethasone, a commonly used steroid, and remdesivir, an antiviral drug that received EUA from FDA in May 2020, are used in inpatient settings and help prevent COVID-19 progression§ (2). No large-scale studies have yet examined the use of mAb by race and ethnicity. Using COVID-19 patient electronic health record data from 41 U.S. health care systems that participated in the PCORnet, the National Patient-Centered Clinical Research Network,¶ this study assessed receipt of medications for COVID-19 treatment by race (White, Black, Asian, and Other races [including American Indian or Alaska Native, Native Hawaiian or Other Pacific Islander, and multiple or Other races]) and ethnicity (Hispanic or non-Hispanic). Relative disparities in mAb** treatment among all patients†† (805,276) with a positive SARS-CoV-2 test result and in dexamethasone and remdesivir treatment among inpatients§§ (120,204) with a positive SARS-CoV-2 test result were calculated. Among all patients with positive SARS-CoV-2 test results, the overall use of mAb was infrequent, with mean monthly use at 4% or less for all racial and ethnic groups. Hispanic patients received mAb 58% less often than did non-Hispanic patients, and Black, Asian, or Other race patients received mAb 22%, 48%, and 47% less often, respectively, than did White patients during November 2020-August 2021. Among inpatients, disparities were different and of lesser magnitude: Hispanic inpatients received dexamethasone 6% less often than did non-Hispanic inpatients, and Black inpatients received remdesivir 9% more often than did White inpatients. Vaccines and preventive measures are the best defense against infection; use of COVID-19 medications postexposure or postinfection can reduce morbidity and mortality and relieve strain on hospitals but are not a substitute for COVID-19 vaccination. Public health policies and programs centered around the specific needs of communities can promote health equity (4). Equitable receipt of outpatient treatments, such as mAb and antiviral medications, and implementation of prevention practices are essential to reducing existing racial and ethnic inequities in severe COVID-19-associated illness and death.

Leveraging Social and Structural Determinants of Health at the Centers for Disease Control and Prevention: A Systems-Level Opportunity to Improve Public Health.

CONTEXT: Social and structural determinants of health (SDOH) have become part of the public health and health care landscape. The need to address SDOH is reinforced by morbidity and mortality trends, including a recent multiyear decrease in life expectancy and persistent health disparities. Leadership on SDOH-related efforts has come from public health, health care, private philanthropy, and nongovernmental entities. STRATEGY: The Centers for Disease Control and Prevention (CDC) has been addressing SDOH through both disease- or condition-specific programs and crosscutting offices. Guidance from public health partners in the field has led the CDC to consider more strategic approaches to incorporating SDOH into public health activities. IMPLEMENTATION: The CDC's crosscutting SDOH Workgroup responded to external recommendations to develop a specific vision and plan that aims to integrate SDOH into the agency's infrastructure. The group also sponsors CDC forums for sharing research and trainings on embedding SDOH in programs. The group created a Web site to centralize CDC SDOH research, data sources, practice tools, programs, and policies. PROGRESS: The CDC has shown strong leadership in prioritizing SDOH in recent years. Individual programs and crosscutting offices have developed various models aimed at ensuring that public health research and practice address SDOH. DISCUSSION: Building sustainable SDOH infrastructures in public health institutions that reach across multiple health topics and non-health organizations could increase chances of meeting public health morbidity and mortality reduction goals, including decreasing health disparities. Although public health priorities and socioeconomic trends will change over time, experience suggests that social and structural factors will continue to influence the public's health. The CDC and state, tribal, local, and territorial public health institutions have played important leadership roles in the system of community and service organizations that interface with communities they mutually serve to address SDOH. Continued capacity-building could help grow and sustain an SDOH infrastructure that advances this work.

Acute oral toxicity and tissue residues of saxitoxin in the mallard (Anas platyrhynchos).

Since 2014, widespread, annual mortality events involving multiple species of seabirds have occurred in the Gulf of Alaska, Bering Sea, and Chukchi Sea. Among these die-offs, emaciation was a common finding with starvation often identified as the cause of death. However, saxitoxin (STX) was detected in many carcasses, indicating exposure of these seabirds to STX in the marine environment. Few data are available that describe the effects of STX in birds, thus presenting challenges for determining its contributions to specific mortality events. To address these knowledge gaps, we conducted an acute oral toxicity trial in mallards (Anas platyrhynchos), a common laboratory avian model, using an up-and-down method to estimate the median lethal dose (LD50) for STX. Using an enzyme-linked immunosorbent assay (ELISA), we tested select tissues from all birds and feces from those individuals that survived initial dosing. Samples with an ELISA result that exceeded approximately 10 µg 100 g-1 STX and randomly selected ELISA negative samples were further tested by high-performance liquid chromatography (HPLC). Tissues collected from mallards were also examined grossly at necropsy and then later by microscopy to identify lesions attributable to STX. The estimated LD50 was 167 µg kg-1 (95% CI = 69-275 µg kg-1). Saxitoxin was detected in fecal samples of all mallards tested for up to 48 h after dosing and at the end of the sampling period (7 d) in three birds. In those individuals that died or were euthanized <2 h after dosing, STX was readily detected throughout the gastrointestinal tract but only infrequently in heart, kidney, liver, lung, and breast muscle. No gross or microscopic lesions were observed that could be attributable to STX exposure. Given its acute toxicity, limited detectability, and frequent occurrence in the Alaska marine environment, additional research on STX in seabirds is warranted.

Evaluation of a subunit vaccine candidate (Biotech Vac Cox) against Eimeria spp. in broiler chickens.

This study evaluated growth performance and cross-protection against Eimeria spp. using a subunit coccidia vaccine in 2 independent challenge experiments. In both trials, chickens were challenged with E. acervulina, E. maxima, and E. tenella oocysts. In Exp 1, 1000-day-old chickens were allocated in one of 2 treatments 1) Control group; 2) Biotech Vac Cox group. The vaccine was orally gavaged on d 2 and 16 of life and coccidia challenge was on d 21. Performance parameters were evaluated on d 21, 35, and 42. On d 34, coccidia lesions were scored. Oocysts per gram of feces (OPG) were evaluated on d 28, 35, and 42. In Exp 2, 900-day-old chickens were assigned in one of 2 treatments 1) Control group; 2) Biotech Vac Cox group. The vaccine was orally gavaged on d 2 and 16 of life and coccidia challenge was on d 21. Performance parameters were evaluated on d 21, 27, 35, and 42, and lesion scores and OPG at d 27. In Exp 1, chickens vaccinated had significantly lower feed intake (FI) at d 21 and feed conversion ratio (FCR) at d 35 compared to control chickens (P < 0.05). Vaccinated chickens showed a significant reduction (P ≤ 0.05) in OPG for E. maxima to nondetectable levels and for all coccidian species at d 42 compared to control chickens. In Exp 2, the chickens vaccinated showed a significant increase in BW, BW gain (BWG) and reduction in FCR on d 27, 35, and 42 (P ≤ 0.05). Vaccinated chickens had significantly lower (P ≤ 0.05) lesion scores for all 3 Eimeria species. Moreover, vaccinated chickens had a reduction in total OPG of 35.50% (P = 0.0739). Studies to evaluate the serological and mucosal immune response are currently being evaluated. This inactivated, orally delivered subunit vaccine offers significant cross-protection to Eimeria spp. and eliminates the needs to treat broilers with live oocysts, enhanced ease of use, and greater biosecurity to producers.