Effectiveness of Bio-K+ for the prevention of Clostridioides difficile infection: Stepped-wedge cluster-randomized controlled trial.

OBJECTIVE: To evaluate the impact of administering probiotics to prevent Clostridioides difficile infection (CDI) among patients receiving therapeutic antibiotics. DESIGN: Stepped-wedge cluster-randomized trial between September 1, 2016, and August 31, 2019. SETTING: This study was conducted in 4 acute-care hospitals across an integrated health region. PATIENTS: Hospitalized patients, aged ≥55 years. METHODS: Patients were given 2 probiotic capsules daily (Bio-K+, Laval, Quebec, Canada), containing 50 billion colony-forming units of Lactobacillus acidophilus CL1285, L. casei LBC80R, and L. rhamnosus CLR2. We measured hospital-acquired CDI (HA-CDI) and the number of positive C. difficile tests per 10,000 patient days as well as adherence to administration of Bio-K+ within 48 and 72 hours of antibiotic administration. Mixed-effects generalized linear models, adjusted for influenza admissions and facility characteristics, were used to evaluate the impact of the intervention on outcomes. RESULTS: Overall adherence of Bio-K+ administration ranged from 76.9% to 84.6% when stratified by facility and periods. Rates of adherence to administration within 48 and 72 hours of antibiotic treatment were 60.2% -71.4% and 66.7%-75.8%, respectively. In the adjusted analysis, there was no change in HA-CDI (incidence rate ratio [IRR], 0.92; 95% confidence interval [CI], 0.68-1.23) or C. difficile positivity rate (IRR, 1.05; 95% CI, 0.89-1.24). Discharged patients may not have received a complete course of Bio-K+. Our hospitals had a low baseline incidence of HA-CDI. Patients who did not receive Bio-K+ may have differential risks of acquiring CDI, introducing selection bias. CONCLUSIONS: Hospitals considering probiotics as a primary prevention strategy should consider the baseline incidence of HA-CDI in their population and timing of probiotics relative to the start of antimicrobial administration.

Implementation strategies for hospital-based probiotic administration in a stepped-wedge cluster randomized trial design for preventing hospital-acquired Clostridioides difficile infection.

BACKGROUND: Clostridioides difficile infection (CDI) is associated with considerable morbidity and mortality in hospitalized patients, especially among older adults. Probiotics have been evaluated to prevent hospital-acquired (HA) CDI in patients who are receiving systemic antibiotics, but the implementation of timely probiotic administration remains a challenge. We evaluated methods for effective probiotic implementation across a large health region as part of a study to assess the real-world effectiveness of a probiotic to prevent HA-CDI (Prevent CDI-55 +). METHODS: We used a stepped-wedge cluster-randomized controlled trial across four acute-care adult hospitals (n = 2,490 beds) to implement the use of the probiotic Bio-K + ® (Lactobacillus acidophilus CL1285®, L. casei LBC80R® and L. rhamnosus CLR2®; Laval, Quebec, Canada) in patients 55 years and older receiving systemic antimicrobials. The multifaceted probiotic implementation strategy included electronic clinical decision support, local site champions, and both health care provider and patient educational interventions. Focus groups were conducted during study implementation to identify ongoing barriers and facilitators to probiotic implementation, guiding needed adaptations of the implementation strategy. Focus groups were thematically analyzed using the Theoretical Domains Framework and the Consolidated Framework of Implementation Research. RESULTS: A total of 340 education sessions with over 1,800 key partners and participants occurred before and during implementation in each of the four hospitals. Site champions were identified for each included hospital, and both electronic clinical decision support and printed educational resources were available to health care providers and patients. A total of 15 individuals participated in 2 focus group and 7 interviews. Key barriers identified from the focus groups resulted in adaptation of the electronic clinical decision support and the addition of nursing education related to probiotic administration. As a result of modifying implementation strategies for identified behaviour change barriers, probiotic adherence rates were from 66.7 to 75.8% at 72 h of starting antibiotic therapy across the four participating acute care hospitals. CONCLUSIONS: Use of a barrier-targeted multifaceted approach, including electronic clinical decision support, education, focus groups to guide the adaptation of the implementation plan, and local site champions, resulted in a high probiotic adherence rate in the Prevent CDI-55 + study.

Detecting emerald green in 19thC book bindings using vis-NIR spectroscopy.

Detection and identification of heavy metal-based pigments in 19th-century bookbindings is crucial to avoid human user exposure to toxic substances. Vibrant green bookbindings with arsenical emerald green are particularly problematic due to their friability. A pilot study at St Andrews University tested 800 green bookbindings for arsenic presence using visible near-infrared spectrometry, a technique not previously applied to the detection of heavy metals in bindings. The ASD TerraSpec Halo portable spectrometer that is normally used in geology to identify minerals in rocks, is used here to collect hyperspectral reflectance data between 350 and 2500 nm. Raman spectroscopy and Scanning Electron Microscopy with Energy Dispersive X-ray Spectroscopy (SEM-EDS) are used here to validate hyperspectral test results. The study finds that bookbindings containing emerald green have a distinctive pattern in the visible part of the spectrum that is distinguishable from other green pigments. This finding opens up the possibility for all collecting institutions to test bindings for this toxic compound in a non-destructive, cost-effective and efficient manner.

Spatial analysis of nanoparticle distribution in human breast xenografts reveals nanoparticles targeted to cancer cells localized with tumor-associated stromal cells.

The biological influence of physicochemical parameters of "targeted" nanoparticles on their delivery to cancer tumors remains poorly understood. A comparative analysis of nanoparticle distributions in tumors following systemic delivery across several models can provide valuable insights. Methods: Bionized nanoferrite nanoparticles (iron oxide core coated with starch), either conjugated with a targeted anti-HER2 antibody (BH), or unconjugated (BP), were intravenously injected into athymic nude or NOD-scid gamma (NSG) female mice bearing one of five human breast cancer tumor xenografts growing in a mammary fat pad. Tumors were harvested 24 hours after nanoparticle injection, fixed, mounted, and stained. We performed detailed histopathology analysis by comparing spatial distributions of nanoparticles (Prussian blue) with various stromal cells (CD31, SMA, F4/80, CD11c, etc.) and the target antigen-expressing (HER2) tumor cells. Results: Only BH nanoparticles were retained in tumors and generally concentrated in the tumor periphery, with nanoparticle content diminishing towards the tumor interior. Nanoparticle distribution correlated strongly with specific stromal cells within each tumor type, which varied among tumor types and between mouse strains. Weak or no correlation between nanoparticle distribution and HER2 positive cells, or CD31 cells was observed. Conclusion: Antibody-labeled nanoparticles were retained across all tumors, irrespective of presence of the "target" antigen. Though presence of antibody on nanoparticles correlated with retention, non-cancerous host stromal cells were responsible for their retention in the tumor microenvironment. This study highlights gaps in our understanding of the complex biological interplay between disease and host immune biology, and the need to account for the influence of underlying aberrant tumor biology as factors determining nanoparticle fate in vivo.

Update on Vaccine-Derived Poliovirus Outbreaks - Worldwide, January 2021-December 2022.

Circulating vaccine-derived poliovirus (cVDPV) outbreaks* can occur when oral poliovirus vaccine (OPV, containing one or more Sabin-strain serotypes 1, 2, and 3) strains undergo prolonged circulation in under-vaccinated populations, resulting in genetically reverted neurovirulent virus (1,2). Following declaration of the eradication of wild poliovirus type 2 in 2015 and the global synchronized switch from trivalent OPV (tOPV, containing Sabin-strain types 1, 2, and 3) to bivalent OPV (bOPV, containing types 1 and 3 only) for routine immunization activities† in April 2016 (3), cVDPV type 2 (cVDPV2) outbreaks have been reported worldwide (4). During 2016-2020, immunization responses to cVDPV2 outbreaks required use of Sabin-strain monovalent OPV2, but new VDPV2 emergences could occur if campaigns did not reach a sufficiently high proportion of children. Novel oral poliovirus vaccine type 2 (nOPV2), a more genetically stable vaccine than Sabin OPV2, was developed to address the risk for reversion to neurovirulence and became available in 2021. Because of the predominant use of nOPV2 during the reporting period, supply replenishment has frequently been insufficient for prompt response campaigns (5). This report describes global cVDPV outbreaks during January 2021-December 2022 (as of February 14, 2023) and updates previous reports (4). During 2021-2022, there were 88 active cVDPV outbreaks, including 76 (86%) caused by cVDPV2. cVDPV outbreaks affected 46 countries, 17 (37%) of which reported their first post-switch cVDPV2 outbreak. The total number of paralytic cVDPV cases during 2020-2022 decreased by 36%, from 1,117 to 715; however, the proportion of all cVDPV cases that were caused by cVDPV type 1 (cVDPV1) increased from 3% in 2020 to 18% in 2022, including the occurrence of cocirculating cVDPV1 and cVDPV2 outbreaks in two countries. The increased proportion of cVDPV1 cases follows a substantial decrease in global routine immunization coverage and suspension of preventive immunization campaigns during the COVID-19 pandemic (2020-2022) (6); outbreak responses in some countries were also suboptimal. Improving routine immunization coverage, strengthening poliovirus surveillance, and conducting timely and high-quality supplementary immunization activities (SIAs) in response to cVDPV outbreaks are needed to interrupt cVDPV transmission and reach the goal of no cVDPV isolations in 2024.

Vaccine-derived poliovirus serotype 2 outbreaks and response in the Democratic Republic of the Congo, 2017-2021.

Vaccine-derived polioviruses (VDPVs) can emerge from Sabin strain poliovirus serotypes 1, 2, and 3 contained in oral poliovirus vaccine (OPV) after prolonged person-to-person transmission where population vaccination immunity against polioviruses is suboptimal. VDPVs can cause paralysis indistinguishable from wild polioviruses and outbreaks when community circulation ensues. VDPV serotype 2 outbreaks (cVDPV2) have been documented in The Democratic Republic of the Congo (DRC) since 2005. The nine cVDPV2 outbreaks detected during 2005-2012 were geographically-limited and resulted in 73 paralysis cases. No outbreaks were detected during 2013-2016. During January 1, 2017-December 31, 2021, 19 cVDPV2 outbreaks were detected in DRC. Seventeen of the 19 (including two first detected in Angola) resulted in 235 paralysis cases notified in 84 health zones in 18 of DRC's 26 provinces; no notified paralysis cases were associated with the remaining two outbreaks. The DRC-KAS-3 cVDPV2 outbreak that circulated during 2019-2021, and resulted in 101 paralysis cases in 10 provinces, was the largest recorded in DRC during the reporting period in terms of numbers of paralysis cases and geographic expanse. The 15 outbreaks occurring during 2017-early 2021 were successfully controlled with numerous supplemental immunization activities (SIAs) using monovalent OPV Sabin-strain serotype 2 (mOPV2); however, suboptimal mOPV2 vaccination coverage appears to have seeded the cVDPV2 emergences detected during semester 2, 2018 through 2021. Use of the novel OPV serotype 2 (nOPV2), designed to have greater genetic stability than mOPV2, should help DRC's efforts in controlling the more recent cVDPV2 outbreaks with a much lower risk of further seeding VDPV2 emergence. Improving nOPV2 SIA coverage should decrease the number of SIAs needed to interrupt transmission. DRC needs the support of polio eradication and Essential Immunization (EI) partners to accelerate the country's ongoing initiatives for EI strengthening, introduction of a second dose of inactivated poliovirus vaccine (IPV) to increase protection against paralysis, and improving nOPV2 SIA coverage.

Assessing maternal alcohol consumption in pregnancy: comparison of confidential postnatal maternal interview and measurement of alcohol biomarkers in meconium.

OBJECTIVE: Knowledge of alcohol consumption in pregnancy is important for early identification of children with fetal alcohol spectrum disorder. We investigated whether alcohol biomarkers fatty acid ethyl esters (FAEEs) and ethyl glucuronide (EtG) in meconium are predicted by maternal or newborn demographics and/or correlate with confidential early postnatal self-report of alcohol consumption in pregnancy. DESIGN: Anonymised, observational population-based study. SETTING: Inner-city maternity unit, Glasgow, UK. PATIENTS: Singleton mother/infant dyads delivering every fourth day. INTERVENTIONS: Mother: confidential postnatal interview. Baby: meconium sample for FAEEs and EtG. RESULTS: 840/908 mothers consented. 370 (46.4%) reported alcohol consumption in pregnancy, generally of modest amount; for 114 (13.6%) this was after 20 weeks' gestation. Alcohol consumption in later pregnancy was more commonly reported by older (31.3 vs 29.5 years) women of white British ethnicity (p<0.05); their babies were on average 118 g heavier (p=0.032). FAEEs were identified in all meconium samples; concentration was ≥600 ng/g in 39.6%. EtG concentration was ≥30 ng/g in 14.5%. Neither biomarker was associated with maternal age, body mass index or socioeconomic status but when EtG was ≥30 ng/g, the mother was less likely to identify as white British (71.3% vs 81.8%, p=0.028). Sensitivities of FAEEs ≥600 ng/g and EtG ≥30 ng/g were 43.1% and 11.6%, respectively for postnatal self-report of alcohol use in later pregnancy (specificities 60.6% and 84.8%). CONCLUSIONS: FAEEs and EtG measured in meconium have low sensitivity and specificity for self-reported alcohol consumption after 20 weeks' gestation in an unselected Scottish population.

Genetic and epidemiological description of an outbreak of circulating vaccine-derived polio-virus type 2 (cVDPV2) in Angola, 2019-2020.

After six years without any detection of poliomyelitis cases, Angola reported a case of circulating vaccine-derived poliovirus type 2 (cVDPV2) with paralysis onset date of 27 March 2019. Ultimately, 141 cVDPV2 polio cases were reported in all 18 provinces in 2019-2020, with particularly large hotspots in the south-central provinces of Luanda, Cuanza Sul, and Huambo. Most cases were reported from August to December 2019, with a peak of 15 cases in October 2019. These cases were classified into five distinct genetic emergences (emergence groups) and have ties with cases identified in 2017-2018 in the Democratic Republic of Congo. From June 2019 to July 2020, the Angola Ministry of Health and partners conducted 30 supplementary immunization activity (SIA) rounds as part of 10 campaign groups, using monovalent OPV type 2 (mOPV2). There were Sabin 2 vaccine strain detections in the environmental (sewage) samples taken after mOPV2 SIAs in each province. Following the initial response, additional cVDPV2 polio cases occurred in other provinces. However, the national surveillance system did not detect any new cVDPV2 polio cases after 9 February 2020. While reporting subpar indicator performance in epidemiological surveillance, the laboratory and environmental data as of May 2021 strongly suggest that Angola successfully interrupted transmission of cVDPV2 early in 2020. Additionally, the COVID-19 pandemic did not allow a formal Outbreak Response Assessment (OBRA). Improving the sensitivity of the surveillance system and the completeness of AFP case investigations will be vital to promptly detect and interrupt viral transmission if a new case or sewage isolate are identified in Angola or central Africa.

Assessing maternal alcohol consumption in pregnancy: does phosphatidylethanol measured from day 5 newborn blood spot cards have any value? An observational, population-based study.

OBJECTIVE: Prenatal alcohol exposure (PAE) places children at risk of fetal alcohol spectrum disorder (FASD) but ascertainment of PAE is problematic. Early intervention for children at risk of FASD may help mitigate long-term difficulties. Phosphatidylethanol (PEth), a metabolite of alcohol, is incorporated into red cell membranes and can be measured in dried blood spot (DBS) cards. In the UK, DBS samples are collected on day 5 for routine newborn screening. We sought to examine if PEth measured from DBS correlates with postnatal maternal self-report of alcohol consumption in pregnancy. DESIGN: Observational population-based study. Comparison of infant PEth concentration and self-report of maternal alcohol use during pregnancy. SETTING: Large maternity unit in Glasgow, Scotland. PARTICIPANTS: All singleton mother-infant dyads delivered during each fourth consecutive 24-hour period. INTERVENTIONS: Mother: direct, confidential, immediate postnatal interview by a single researcher examining alcohol use during pregnancy. Infant: one extra DBS collected coincident with routine newborn screening if bleeding continued. RESULTS: 92.5% of eligible mothers agreed to participate. 510 DBS were obtained of which 502 were successfully analysed. 216 (43%) samples contained PEth at a concentration of ≥8 ng/mL and 148 (29.5%) at ≥20 ng/mL. The sensitivity of PEth ≥8 ng/mL and ≥20 ng/mL in identifying women who self-reported modest alcohol use after 36 weeks' gestation was 50% and 36.4%, respectively. CONCLUSION: PEth measured from DBS obtained on day 5 of life does not reliably identify modest PAE after 36 weeks' gestation from maternal self-report.

Degradation of GSPT1 causes TP53-independent cell death in leukemia while sparing normal hematopoietic stem cells.

Targeted protein degradation is a rapidly advancing and expanding therapeutic approach. Drugs that degrade GSPT1 via the CRL4CRBN ubiquitin ligase are a new class of cancer therapy in active clinical development with evidence of activity against acute myeloid leukemia in early-phase trials. However, other than activation of the integrated stress response, the downstream effects of GSPT1 degradation leading to cell death are largely undefined, and no murine models are available to study these agents. We identified the domains of GSPT1 essential for cell survival and show that GSPT1 degradation leads to impaired translation termination, activation of the integrated stress response pathway, and TP53-independent cell death. CRISPR/Cas9 screens implicated decreased translation initiation as protective following GSPT1 degradation, suggesting that cells with higher levels of translation are more susceptible to the effects of GSPT1 degradation. We defined 2 Crbn amino acids that prevent Gspt1 degradation in mice, generated a knockin mouse with alteration of these residues, and demonstrated the efficacy of GSPT1-degrading drugs in vivo with relative sparing of numbers and function of long-term hematopoietic stem cells. Our results provide a mechanistic basis for the use of GSPT1 degraders for the treatment of cancer, including TP53-mutant acute myeloid leukemia.

Long-Term Effects of Nanoscale Magnetite on Human Forebrain-like Tissue Development in Stem-Cell-Derived Cortical Spheroids.

The environmental nanoscale iron magnetite may contribute to the risk of developing neurodegenerative diseases. In addition, iron oxides can be used as the contrast agents in magnetic resonance imaging of neural tissues. The potential long-term impact of nanoscale iron oxides on cellular stress and neuro-inflammation remains unknown. The objective of this study is to evaluate the long-term effects of nanoscale iron oxide exposure on human pluripotent stem cell-derived cortical spheroids that mimic human forebrain-like tissue development. In particular, the cortical spheroids were treated with 8 nm and 15-20 nm magnetite at 0.023, 2.3, and 23 µg/mL for 4-30 days. The cell viability did not show significant differences among different test groups. The neuronal marker ß-tubulin III, cell proliferation marker Ki67, and antioxidant enzyme SOD2 did not show significant changes either. The molecular levels of cellular stress, inflammation, cell apoptosis, DNA damage and repair, and the reactive oxygen species (ROS) response were measured. A negative effect (i.e., increased inflammation and ROS response genes) of 8 nm iron oxide exposure and a positive effect (i.e., decreased inflammation, apoptosis, and ROS response and clean up genes) for 15-20 nm iron oxide exposure were observed. It is postulated that the intracellular iron content and the aggregation of iron oxides contribute to the observed differential response. Although our results demonstrate similar intracellular iron content for 8 nm and 15-20 nm groups, the aggregation is more severe for the 8 nm group (∼500 nm) than the 15 nm group (∼220-250 nm). Therefore, our data indicate an iron oxide aggregate size-dependent effects on cellular stress, inflammation, cell apoptosis, DNA damage, and the ROS response in the developing human forebrain-like tissue.

Conceptualizing Suicide Prevention in Firefighters Through the lens of the Interpersonal-Psychological Theory of Suicide: A Narrative Review.

Suicide is the 10th leading cause of death in the United States and is a significant public health problem. Suicide has also become a major concern among career American firefighters with rates for suicidal ideation and attempts in firefighters two to three times higher than rates in the general population. Firefighter suicide and mental health are major issues facing fire service leaders, mental health professionals, and most recently suicide experts. Despite an increased focus on understanding suicide in the fire service, there is little empirical evidence on the effectiveness of prevention in this population. The juxtaposition of elevated suicide rates with a dearth of empirical prevention data specific to firefighters warrants new approaches and conceptualizations of suicide prevention in this population. Grounded in the framework of the interpersonal-psychological theory of suicide (IPTS), this narrative review integrates select relevant firefighter specific suicide risk/protective factors and multi-level intervention/prevention literature to provide a structured approach to identifying current suicide intervention/prevention efforts with promising transportability to firefighters. Several recommendations for future intervention research specific to firefighters are also proposed.

Update on Vaccine-Derived Poliovirus Outbreaks - Worldwide, January 2020-June 2021.

As of May 1, 2016, use of oral poliovirus vaccine (OPV) type 2 for routine and supplementary immunization activities ceased after a synchronized global switch from trivalent OPV (tOPV; containing Sabin strain types 1, 2, and 3) to bivalent OPV (bOPV; containing Sabin strain types 1 and 3) subsequent to the certified eradication of wild type poliovirus (WPV) type 2 in 2015 (1-3). Circulating vaccine-derived poliovirus (cVDPV) outbreaks* occur when transmission of Sabin strain poliovirus is prolonged in underimmunized populations, allowing viral genetic reversion to neurovirulence, resulting in cases of paralytic polio (1-3). Since the switch, monovalent OPV type 2 (mOPV2, containing Sabin strain type 2) has been used for response to cVDPV type 2 (cVDPV2) outbreaks; tOPV is used if cVDPV2 co-circulates with WPV type 1, and bOPV is used for cVDPV type 1 (cVDPV1) or type 3 (cVDPV3) outbreaks (1-4). In November 2020, the World Health Organization (WHO) Emergency Use Listing procedure authorized limited use of type 2 novel OPV (nOPV2), a vaccine modified to be more genetically stable than the Sabin strain, for cVDPV2 outbreak response (3,5). In October 2021, the Strategic Advisory Group of Experts on Immunization (WHO's principal advisory group) permitted wider use of nOPV2; however, current nOPV2 supply is limited (6). This report updates that of July 2019-February 2020 to describe global cVDPV outbreaks during January 2020-June 2021 (as of November 9, 2021)† (3). During this period, there were 44 cVDPV outbreaks of the three serotypes affecting 37 countries. The number of cVDPV2 cases increased from 366 in 2019 to 1,078 in 2020 (7). A goal of the Global Polio Eradication Initiative's (GPEI) 2022-2026 Strategic Plan is to better address the challenges to early CVDPV2 outbreak detection and initiate prompt and high coverage outbreak responses with available type 2 OPV to interrupt transmission by the end of 2023 (8).

Conceptualizing Suicidal Ideation Among Firefighters Through the Lens of an Integrated Theoretical Model.

Suicide is the 10th leading cause of death in the United States and is a major concern among professional American firefighters, with rates for suicidal ideation in firefighters two times higher than rates in the general population. The Neuman systems model integrated with the interpersonal-psychological theory of suicide provides a better understanding of the specific occupational and cultural aspects of firefighting that lead to a greater risk for suicidal ideation. This model provides an innovative lens that can inform the development and the implementation of interventions aimed at preventing suicidal ideation among firefighters.

Using administrative data to determine rates of surgical site infections following spinal fusion and laminectomy procedures.

OBJECTIVE: Surgical site infections (SSIs) are a serious and costly post-op complication. Generating SSI rates often requires labor-intensive methods, but increasing numbers of publications reported SSI rates using administrative data. METHODS: Index laminectomy and spinal fusion procedures were identified using Canadian Classification of Health Interventions (CCI) procedure codes for inpatients and outpatients in the province of Alberta, Canada between 2008 and 2015. SSIs occurring in the year postsurgery were identified using the International Classification of Diseases, 10th Revision, Canada (ICD-10-CA) diagnosis and CCI procedure codes indicative of post-op infection. Rates of SSIs and case characteristics were reported. RESULTS: Over the 8-year study period, 21,222 index spinal procedures were identified of which 12,027 (56.7%) were laminectomy procedures, with 322 SSIs identified, an SSI rate of 2.7 per 100 procedures. Of the 9,195 (43.3%) fusion procedures, 298 were identified as an SSI, an SSI rate of 3.2 per 100 procedures. This study found SSI rates increased from 2008 and 2015, and rates were the highest in the 0-18 year age group. CONCLUSIONS: The rates reported in this study were similar to published SSI rates using traditional surveillance methods, suggesting administrative data may be a viable method for reporting SSI rates following spinal procedures. Further work is needed to validate SSIs identified using administrative data by comparing to traditional surveillance.

Eastern Equine Encephalitis Virus Seroprevalence in Maine Cervids, 2012-2017.

Eastern equine encephalitis virus (EEEV) first emerged in Maine in the early 2000s and resulted in an epizootic outbreak in 2009. Since 2009, serum samples from cervids throughout Maine have been collected and assessed for the presence of neutralizing antibodies to EEEV to assess EEEV activity throughout the state. We tested 1,119 Odocoileus virginianus (white-tailed deer) and 982 Alces americanus (moose) serum samples collected at tagging stations during the hunting seasons from 2012 to 2017 throughout the state of Maine. Odocoileus virginianus from all 16 counties were EEEV seropositive, whereas A. americanus were seropositive in the northwestern counties of Aroostook, Somerset, Piscataquis, and Franklin counties. Seroprevalence in O. virginianus ranged from 6.6% to 21.2% and in A. americanus from 6.6% to 10.1%. Data from this report in conjunction with findings previously reported from 2009 to 2011 indicate that EEEV is endemic throughout Maine.

Anthrax toxin component, Protective Antigen, protects insects from bacterial infections.

Anthrax is a major zoonotic disease of wildlife, and in places like West Africa, it can be caused by Bacillus anthracis in arid nonsylvatic savannahs, and by B. cereus biovar anthracis (Bcbva) in sylvatic rainforests. Bcbva-caused anthrax has been implicated in as much as 38% of mortality in rainforest ecosystems, where insects can enhance the transmission of anthrax-causing bacteria. While anthrax is well-characterized in mammals, its transmission by insects points to an unidentified anthrax-resistance mechanism in its vectors. In mammals, a secreted anthrax toxin component, 83 kDa Protective Antigen (PA83), binds to cell-surface receptors and is cleaved by furin into an evolutionary-conserved PA20 and a pore-forming PA63 subunits. We show that PA20 increases the resistance of Drosophila flies and Culex mosquitoes to bacterial challenges, without directly affecting the bacterial growth. We further show that the PA83 loop known to be cleaved by furin to release PA20 from PA63 is, in part, responsible for the PA20-mediated protection. We found that PA20 binds directly to the Toll activating peptidoglycan-recognition protein-SA (PGRP-SA) and that the Toll/NF-κB pathway is necessary for the PA20-mediated protection of infected flies. This effect of PA20 on innate immunity may also exist in mammals: we show that PA20 binds to human PGRP-SA ortholog. Moreover, the constitutive activity of Imd/NF-κB pathway in MAPKK Dsor1 mutant flies is sufficient to confer the protection from bacterial infections in a manner that is independent of PA20 treatment. Lastly, Clostridium septicum alpha toxin protects flies from anthrax-causing bacteria, showing that other pathogens may help insects resist anthrax. The mechanism of anthrax resistance in insects has direct implications on insect-mediated anthrax transmission for wildlife management, and with potential for applications, such as reducing the sensitivity of pollinating insects to bacterial pathogens.

A Rare Case of Hypereosinophilic Syndrome-Induced Shower Thrombus Responsive to Nilotinib.

Hypereosinophilic syndrome (HES) is a rare clinical disease that affects 0.036/100,000 patients, with a minority of patients having associated genetic markers which can encompass PDGFRA/B or FGFR1 mutations. The prognosis is dependent on the timing of diagnosis and early treatment, with a mortality rate ranging from 48% to 75% if there is a delayed diagnosis. Eosinophilic myocarditis is characterized by invasion of the myocardium with eosinophils. Myeloid neoplasms are a rare, but known cause of HES induced myocarditis. Signs and symptoms can range from being asymptomatic to retrosternal pain, arrhythmias, and even sudden death. HES myocarditis is a diagnosis of exclusion that is made via endomyocardial biopsy. Peripheral eosinophilia is the only specific sign to suggest eosinophilic myocarditis with traditional biomarkers, electrocardiogram, and echocardiogram. Treatment modalities include systemic corticosteroids and symptomatic management. Complications from HES myocarditis may include embolic events, eosinophilic vegetations, and dysrhythmias, or conduction disturbances. We present a case of a 62-year-old male who initially presented with epigastric pain, and then suffered a myocardial infarction. After testing, the probable diagnosis of eosinophilic myocarditis was made. His clinical course was complicated by the development of shower thrombus associated with acute encephalopathy. Although HES has classically been treated with imatinib, in this case, an alternative biologic agent was used, resulting in a good prognosis and ultimate patient survival. This case details the importance of early clinical suspicion, diagnosing the condition, and early initiation of treatment to prevent worsening clinical status.

Surveillance to Track Progress Toward Polio Eradication - Worldwide, 2018-2019.

Since the Global Polio Eradication Initiative (GPEI) was launched in 1988, the number of polio cases worldwide has declined approximately 99.99%; only two countries (Afghanistan and Pakistan) have never interrupted wild poliovirus (WPV) transmission (1). The primary means of detecting poliovirus circulation is through surveillance for acute flaccid paralysis (AFP) among children aged <15 years with testing of stool specimens for WPV and vaccine-derived polioviruses (VDPVs) (genetically reverted strains of the vaccine virus that regain neurovirulence) in World Health Organization (WHO)-accredited laboratories (2,3). In many locations, AFP surveillance is supplemented by environmental surveillance, the regular collection and testing of sewage to provide awareness of the extent and duration of poliovirus circulation (3). This report presents 2018-2019 poliovirus surveillance data, focusing on 40 priority countries* with WPV or VDPV outbreaks or at high risk for importation because of their proximity to a country with an outbreak. The number of priority countries rose from 31 in 2018 to 40 in 2019 because of a substantial increase in the number of VDPV outbreaks† (2,4). In areas with low poliovirus immunity, VDPVs can circulate in the community and cause outbreaks of paralysis; these are known as circulating vaccine derived polioviruses (cVDPVs) (4). In 2019, only 25 (63%) of the 40 designated priority countries met AFP surveillance indicators nationally; subnational surveillance performance varied widely and indicated focal weaknesses. High quality, sensitive surveillance is important to ensure timely detection and response to cVDPV and WPV transmission.