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Objectives: This study sought to determine the knowledge, attitudes, and practices of male professional or semi-professional footballers towards concussion from two member countries of the Caribbean Football Union. Methods: A cross-sectional survey was conducted targeting footballers from Jamaica’s Premier league and Guyana’s Elite League. The Rosenbaum Concussion Knowledge and Attitude Scale student version (RocKAS-ST) was used to collect data on knowledge and attitude. Five questions were added to examine practice and one question examined athletes’ agreement with a ban on ball heading for young children in the Caribbean region. Results: The mean Concussion Knowledge Index (CKI) score for Jamaican footballers was 16.5 ± 3.4 [95% CI = 13.5, 14.6; range 8 - 25] and mean CKI for Guyanese footballers was 14.0 ± 2.9 [95% CI = 15.8; range 8 - 25]. There was a weak correlation between years playing and CKI score for Guyanese footballers (r = 0.3, p < 0.01). The mean Concussion Attitude Index (CAI) scores for Jamaican footballers was 56.8 ± 8.4 [95% CI 55.2, 58.5; Range 33 - 75], and for Guyanese footballers the mean was 58.2 ± 3.6 [95% CI 57.5, 59.0; Range 45 - 70]. There was no significant correlation between age or number of years playing in the league and CAI scores. Conclusion: There is room for improvement of knowledge, attitudes, and practices of footballers from both countries with respect to sport-related concussion. This gap could potentially be addressed by the development of culturally specific educational programs which integrate behaviour change theories.

There is little evidence on optimizing the effectiveness and implementation of evidence-based early childhood development (ECD) interventions when task-shifted to frontline workers. In this Methods Forum paper, we describe our adaptation of the International Guide for Monitoring Child Development (GMCD) for task-shifting to frontline workers in Guatemala and India. In 2021–2022, implementers, trainers, frontline workers, caregivers, and international GMCD experts collaborated to adapt the GMCD for a task shifted implementation by frontline workers. We used an eight-step co-creating process: assembling a multidisciplinary team, training on the existing package, working groups to begin modifications, revision of draft modifications, tailoring of visual materials and language, train-the-trainers activities, pilot frontline worker trainings, final review and feedback. Preliminary effectiveness of adaptations was evaluated through narrative notes and group-based qualitative feedback following pilot trainings with 16 frontline workers in India and 6 in Guatemala. Final adaptations included: refining training techniques to match skill levels and learning styles of frontline workers; tailoring all visual materials to local languages and contexts; design of job aids for providing developmental support messages; modification of referral and triage processes for children in need of enhanced support and speciality referral; and creation of post-training support procedures. Feedback from pilot trainings included: (1) group consensus that training improved ECD skills and knowledge across multiple domains; and (2) feedback on ongoing needed adjustments to pacing, use of video-based vs. role-playing materials, and time allocated to small group work. We use the Framework for Reporting Adaptations and Modifications to Evidence-based Implementation Strategies (FRAME-IS) framework to document our adaptations. The co-creating approach we use, as well as systematic documentation of adaptation decisions will be of use to other community-based early childhood interventions and implementation strategies.

IntroductionBlast injury has been implicated as the major cause of traumatic brain injury (TBI) and ocular system injury, in military operations in Iraq and Afghanistan. Soldiers exposed to traumatic stress also have undiagnosed, chronic vision problems. Here we hypothesize that excessive intake of ω-6 fatty acid linoleic acid (LA) and insufficiency of dietary long chain ω-3 polyunsaturated fatty acids (PUFAs, e.g., docosahexaenoic acid; DHA) would dysregulate endocannabinoid-mediated neuronal plasticity and immune response. The study objective was to determine the effect of blast-TBI and traumatic stress on retinal gene expression and assess the role of dietary deficiency of long chain ω-3 PUFAs on the vulnerability to these injury models.MethodsLinoleic acid was used as an independent variable to reflect the dietary increase in LA from 1 percent of energy (en%) to 8 en% present in the current western diets, and these custom LA diets were also devoid of long chain ω-3 PUFAs. Animals were exposed to a simulated blast overpressure wave followed by a weight drop head-concussion to induce TBI. A Separate group of rats were subjected to traumatic stress by a forced immersion underwater.ResultsOur findings showed that blast-TBI exposure, post 14 days, produced significant neuropathological changes such as axonal degeneration in the brain optic tracts from all the three diet groups, especially in rats fed the DHA-deprived 1 en% LA diet. Transcriptomic analysis showed that presence of DHA in the house chow diet prevented blast-induced disruption of neuronal plasticity by activating molecular networks like SNARE signaling, endocannabinoid pathway, and synaptic long-term depression when compared to DHA-deprived 8 en% LA diet group. Under traumatic stress, retinal synaptic function, neurovascular coupling, and opioid signaling mechanisms were dysregulated in rodents fed DHA-deficient diets (i.e., 8 en% LA and 1 en% LA), where reducing the levels of ω-6 linoleic acid from 8 en% to 1 en% was associated with increased neuronal plasticity and suppressed immune signaling.ConclusionThe findings of our study suggest that deprivation of long chain ω-3 PUFAs in the diet affects endocannabinoid-mediated neuronal plasticity, vascular function and inflammatory response that could influence the resistance of veterans to TBI and psychological trauma.

IntroductionSequelae from traumatic brain injuries (TBIs) and post-traumatic stress disorder (PTSD) are major career-limiting factors for combat soldiers. Overlap between TBI and PTSD symptoms alongside other common comorbidities complicate the diagnosis and treatment. Systems-level and high-throughput approaches are key in understanding the underlying biomolecular mechanisms and differentiating these conditions.MethodsThe present study identifies dietary factors and proposes mechanisms behind psychological stress and TBI, using established preclinical animal models and a multi-omics approach. Here, we used microbiome characterizations of rats exposed to simulations of blast-induced TBI and underwater trauma (UWT)-induced psychological stress. We further studied the effect of dietary omega-6 versus omega-3 polyunsaturated fatty acid (n-6, n-3 PUFA) enrichment on the insult responses. The use of excess n-6 PUFA was chosen due to its high prevalence in the Western diet and pro-inflammatory nature. Prior to TBI or UWT, animals were maintained for 6 weeks and continued thereafter on either a standard diet or two customized chows imbalanced and diminished in omega-3 content. Corresponding shams were carried out for all groups. Fecal bacterial microbiome populations were assessed using 16S rRNA gene sequencing.ResultsPhysiologic outcome modeling identified that dietary status affected post-TBI lactate dehydrogenase (LDH) and triglyceride levels, with n-3 PUFA having a large attenuating influence. The UWT model showed similar trends, with diet significantly altering LDH, terminal corticosterone (14 days post-exposure), and a fear behavior susceptibility. Fecal microbiome alpha diversity was significantly reduced by high levels of n-3 PUFA. Likewise, beta diversity of the microbiome was significantly affected by both diet and time but not exposure to TBI or UWT. Compositionally, temporal effects on the microbiome were more likely to be observed with the diets. The most affected features fell within the Proteobacteria phyla, in which n-3 PUFA enrichment significantly reduced Alphaproteobacteria in the TBI model and increased Gammaproteobacteria in the UWT group.DiscussionAll these observations can influence the vulnerability or resilience of the warfighter to blast-induced TBI and acute psychological stress. The microbiome mechanisms facilitate and provide a knowledge-driven unbiased panel of signatures to discriminate between the two insults and is an essential tool for designing precise care management.

Rehabilitation from musculoskeletal injuries (MSKI) complicate healing dynamics typically by sustained disuse of bone and muscles. Microgravity naturally allows limb disuse and thus an effective model to understand MSKI. The current study examined epigenetic changes in a segmental bone defect (SBD) mouse model in a prolonged unloading condition after spaceflight (FLT). We further connected potential miRNA-mRNA regulatory pathways impacting bone healing. Here, SBD surgery was performed on nine-week-old male mice that were launched into space for approximately 4 weeks. Sham with no surgery and ground controls were included in the study. The midshaft of the ipsilateral femur (with callus on the surgical mice) as well as the ipsilateral quadriceps tissue were used for analysis. Femur and quadriceps had a distinct miRNA profile. There was a stronger surgery effect as observed by miRNA expression when compared to microgravity effects. Leukopoiesis, granulopoiesis, myelopoiesis of leukocytes, differentiation of myeloid leukocytes, and differentiation of progenitor cells were all altered because of surgery in the femur. The biological functions such as apoptosis, necrosis, and activation of cell migration and viability were altered because of surgery in quadriceps. Integrating the transcriptome and microRNA data indicated pronounced changes because of microgravity. According to pathway analysis, microgravity had a greater impact on the quadriceps tissue than the bone tissue in the absence of surgery. The altered biological functions resulting from microgravity were validated by integrating limited proteomics data to miRNA-mRNA. Thus, this study highlights the importance of dynamic interplay of gene-epigene regulations as they appear to be intrinsically interconnected and influence in combination for the biological outcome.

Abstract Background To assess patient and primary care provider (PCP) factors associated with adherence to American Cancer Society (ACS) and United States Preventive Services Task Force (USPSTF) guidelines for average risk colorectal cancer (CRC) screening. Methods Retrospective case-control study of medical and pharmacy claims from the Optum Research Database from 01/01/2014 − 12/31/2018. Enrollee sample was adults aged 50 − 75 years with ≥ 24 months continuous health plan enrollment. Provider sample was PCPs listed on the claims of average-risk patients in the enrollee sample. Enrollee-level screening opportunities were based on their exposure to the healthcare system during the baseline year. Screening adherence, calculated at the PCP level, was the percent of average-risk patients up to date with screening recommendations each year. Logistic regression modelling was used to examine the association between receipt of screening and enrollee and PCP characteristics. An ordinary least squares model was used to determine the association between screening adherence among the PCP’s panel of patients and patient characteristics. Results Among patients with a PCP, adherence to ACS and USPSTF screening guidelines ranged from 69 to 80% depending on PCP specialty and type. The greatest enrollee-level predictors for CRC screening were having a primary/preventive care visit (OR = 4.47, p

While colorectal cancer (CRC) is the second leading cause of cancer-related mortality in the United States (US), outcomes can be improved through timely screening. Despite the benefits and widespread availability of screening tests, adherence to recommended screening strategies is low. The study aimed to provide recent evidence regarding screening rates and adherence to screening recommendations among adults at average risk for CRC in a commercially insured and Medicare Advantage population. De-identified administrative data from a large US research database were examined to determine screening rates for the years 2009 through 2018. The study population included adults aged 50–75 years and annual study population counts ranged from 1,390,594 in 2009 to 1,654,544 in 2018. Incident screening rates were found to be relatively stable across the study years (approximately 15 %) with adherence lowest in the youngest age group (ages 50–54 years). Colonoscopies accounted for approximately 50 % of all screening tests performed, while there was a substantial increase in the use of home-based screening tests over the study timeframe. The use of the fecal immunochemical test increased from 17.2 % in 2009 to 28.9 % in 2018 and the multi-target stool DNA test increased from 0.4 % in 2015 to 9.0 % in 2018. Overall though, CRC screening and adherence rates remain relatively low among adults at average risk for CRC in the US. Improving adherence rates with CRC screening recommendations among individuals at average risk for CRC is required to improve health outcomes.

Abstract Background While prevalence of up-to-date screening status is the usual reported statistic, annual screening incidence may better reflect current clinical practices and is more actionable. Our main purpose was to examine incident colorectal cancer (CRC) screening rates in Medicare beneficiaries and to explore characteristics associated with CRC screening. Methods Using 20% Medicare random sample data, the study population included 2016–2018 Medicare fee-for-service beneficiaries covered by Parts A and B aged 66–75 years at average CRC risk. For each study year, we excluded individuals who had a Medicare claim for a colonoscopy within 9 years, flexible sigmoidoscopy within 4 years, and multitarget stool DNA test (mt-sDNA) within 2 years prior; therefore, any observed screening during study year was considered an “incident screening”. Incident screening rates were calculated as number of incident screenings per 1000 Medicare beneficiaries. Overall rates were normalized to 2018 Medicare population distributions of age, sex, and race. Results Each year, > 1.4 million individuals met the inclusion/exclusion criteria from > 6.5 million Medicare beneficiaries. The overall adjusted incident CRC screening rate per 1000 Medicare beneficiaries increased from 85.2 in 2016 to 94.3 in 2018. Incident screening rates decreased 11.4% (22.9 to 20.3) for colonoscopy and 2.4% (58.3 to 56.9) for fecal immunochemical test/guaiac-based fecal occult blood test; they increased 201.5% (6.5 to 19.6) for mt-sDNA. The 2018 unadjusted rate was 76.0 for men and 110.4 for women. By race/ethnicity, the highest 2018 rate was for Asian individuals and the lowest rate was for Black individuals (113.4 and 72.8, respectively). Conclusions The 2016–2018 observed incident CRC screening rate in average-risk Medicare beneficiaries, while increasing, was still low. Our findings suggest more work is needed to improve CRC screening overall and, especially, among male and Black Medicare beneficiaries.

Abstract Background Guidelines include several options for average‐risk colorectal cancer (CRC) screening that vary in aspects such as invasiveness, recommended frequency, and precision. Thus, patient and provider preferences can help identify an appropriate screening strategy. This study elicited CRC screening preferences of physicians and individuals at average risk for CRC (IAR). Methods IAR aged 45–75 years and licensed physicians (primary care or gastroenterology) completed an online discrete choice experiment (DCE). Participants were recruited from representative access panels in the US. Within the DCE, participants traded off preferences between screening type, screening frequency, true‐positive, true‐negative, and adenoma true positive (physicians only). A mixed logit model was used to obtain predicted choice probabilities for colonoscopy, multi‐target stool DNA (mt‐sDNA), fecal immunochemical test (FIT), and methylated septin 9 (mSEPT9) blood test. Results Preferences of IAR and physicians were affected by screening precision and screening type. IAR also valued more regular screening. Physicians preferred colonoscopy (96.8%) over mt‐sDNA (2.8%; p

From February 2020 to March 2022, four southern sea otters (Enhydra lutris nereis) stranded in California with severe protozoal steatitis and systemic toxoplasmosis. Three of the infected otters stranded within 26 km of each other, and all four animals died during periods of increased rainfall-driven surface water runoff. High parasite burdens were observed in all tissues except the central nervous system, and toxoplasmosis with severe protozoal steatitis was the primary cause of death for all cases. This lesion pattern differs substantially from all prior reports of toxoplasmosis in sea otters. All cases were T. gondii-positive via serology, immunohistochemistry, and PCR. Multilocus sequence typing at 13 loci revealed that all were infected with the same strain of T. gondii, previously characterized as an atypical and rare genotype in North America (TgCgCa1, or COUG). The COUG genotype was first isolated from mountain lions in British Columbia, Canada during investigation of a waterborne outbreak of toxoplasmosis in humans. This genotype has not been previously reported from sea otters, nor any aquatic species. All prior T. gondii strains obtained from >140 southern sea otters represent Type II or Type X strains, or variants of these genotypes. Archival necropsy data (>1,000 animals over 24 years) were negative for prior cases of severe T. gondii-associated steatitis prior to the cases described herein, and no sublethal COUG T. gondii infections have been previously indentified in sea otters. According to prior studies, the T. gondii COUG genotype is highly virulent in mice and is unusual among T. gondii isolates in eliciting a Type I interferon response in murine and human cells in vitro; this unusual immunomodulatory response could explain the apparent high virulence of this atypical T. gondii strain. Our findings reveal a novel and concerning lesion pattern for sea otters with toxoplasmosis. Due to high zoonotic potential and the risk of infection via shared marine food resources, these findings may also indicate potential health threats for other animals and humans.

Abstract Although rhinoceros conservation efforts are focused on anti‐poaching and combating wildlife trade, infectious diseases are an increasing threat to both free‐ranging and captive rhinoceros populations. Among these, clostridial infections with Clostridium perfringens, Paeniclostridium sordellii, and Clostridium novyi have caused acute disease in black and white rhinoceroses, characterized by a high mortality rate within very brief time spans. The acute nature, as well as limited knowledge of epidemiology, diagnosis, and management, make clostridial diseases an important threat to rhinoceros conservation. This article reviews historical cases of clostridial disease in rhinoceros with the aim of formulating a clearer understanding of the disease's epidemiology and using this information to make recommendations for its management in free‐ranging rhinoceroses. Acute colic and sudden death in rhinoceroses, together with necropsy findings of segmental hemorrhagic enteritis, should lead towards a tentative diagnosis of enteric clostridial disease, although detection and identification of specific toxins are required for a definitive diagnosis. Our findings indicate the need for further research into clostridial disease dynamics in wildlife species and provide the basis for this research in rhinoceroses.

Colorectal cancer screening rates are important metrics for public health and quality indicators for health care systems; however, published estimates of colorectal cancer screening rates often include both high-risk and average-risk patients, and the use of different epidemiologic methods makes between-study comparisons tenuous. The objective of this study was to measure the proportion of average-risk American adults who are up to date with colorectal cancer screening guidelines and examine the impact of evaluation methods on screening rate estimates. This repeated cross-sectional study used administrative claims to identify individuals aged 50–75 years between 2015 and 2018 with ≥ 1-year of continuous health plan enrollment. Sensitivity analyses to replicate prior studies in the literature included: 1) retrospective cohort study requiring ≥ 10 years of continuous enrollment to identify the most current screening rates (2018), and 2) inclusion of individuals with higher colorectal cancer risk. A total of 2,579,898; 2,948,064; 3,312,882; and 2,752,864 individuals were included in the 2015, 2016, 2017, and 2018 populations, respectively. In the cross-sectional sample, the proportion of individuals with up-to-date colorectal cancer screening was 51.8%, 51.3%, 51.0%, and 51.1% in 2015, 2016, 2017, and 2018, respectively. The inclusion of high-risk individuals increased estimates approximately 37%. Using a retrospective cohort design, 67.5% of average-risk individuals were up to date in 2018. This study demonstrated the impact of methodological differences on rate estimates. Efforts to track screening rates require transparency in measurement methods to accurately evaluate progress in improving rates.

Widely endorsed screening modalities for colorectal cancer (CRC) include structural visualization (e.g. colonoscopy) and stool-based tests including multitarget stool DNA (mt-sDNA), fecal immunochemical tests (FIT), or high-sensitivity guaiac-based fecal occult blood tests (gFOBT). However, CRC screenings are underutilized, hence understanding the screening utilization trends is important, particularly with respect to the newest guideline-endorsed option (mt-sDNA). The objective of this study was to assess patterns in overall CRC screenings following clinical availability of the mt-sDNA test among average-risk individuals in the Ascension Wisconsin healthcare system focusing primarily on individuals aged 50–75 years old. We also reported CRC screening behaviors among individuals 75 years old. Electronic medical records of individuals aged ≥ 40 years from 2015 to 2018 were reviewed to identify average-risk and screen-eligible members. For those with screening data available, we determined the proportion who were up-to-date with any United States Preventive Services Task Force (USPSTF) recommended screening strategy; the number of screening tests performed in the measurement year; and the distribution of screening modalities. Temporal trends were assessed using regression analysis, including subgroup analyses across age groups and screening modalities. A total of 172,045 unique patients aged ≥ 40 years were included, of which 115,708 individuals aged 50–75 years. When considering all individuals up-to-date and screened in the measurement year, overall adherence increased significantly over the 4-year study period, from 39,105 to 49,698 patients or 47 % to 59 % (p 75 years old. Growing adoption, higher preference, and the broad availability of mt-sDNA testing may be associated with an increase in overall CRC screening rates in the average-risk population, in parallel with a slight increase in the use of other non-invasive CRC screening tests.

Colorectal cancer (CRC) is the third leading cause of cancer death in the US. Early detection improves CRC outcomes and multiple options are endorsed for CRC screening; however, adherence remains challenging. Among Medicaid enrollees, the fecal immunochemical test (FIT) is often used for average-risk CRC screening, with suboptimal adherence rates reported (12.3–23.2 %). The navigation-supported (personalized outreach by phone, mail, email and text), at home collection, multi-target stool DNA (mt-sDNA) test represents a relatively recent and broadly accessible option for average-risk CRC screening in Medicaid enrollees. We assessed cross-sectional mt-sDNA adherence in a national sample of Medicaid patients. Data from Exact Sciences Laboratories LLC (ESL; Madison, WI) were retrospectively analyzed. Participants included individuals 45 + years covered by Fee-For-Service (FFS)- or Managed-Medicaid. Primary analysis focused on the 50–74 age cohort and included those with valid mt-sDNA orders between January 1–December 31, 2018. Data from 25,794 individuals who received valid orders for mt-sDNA were included in analysis (61.2 % women; mean age at order 57.5 years). Overall adherence – completion of an ordered test – was 51.3 %. Adherence was 54.6 % in Managed-Medicaid and 38.9 % in FFS-Medicaid. Adherence by age was: 51.5 % for 50–64 years and 47.7 % for 65–74 years. Mt-sDNA tests ordered by gastroenterologists had higher adherence (60.5 %) compared with primary care clinicians (51.3 %). These data from a large, national sample of Medicaid-insured patients substantiate mt-sDNA testing as a viable patient-supported, home-based option to improve average-risk CRC screening participation in Medicaid enrollees.

Abstract Introduction Hazardous alcohol use (HAU), defined as a pattern of alcohol consumption that increases the risk of harmful consequences for the user or others, is associated with an elevated risk of human immunodeficiency virus (HIV) infection and poor health outcomes. We describe the association between people living with HIV (PLHIV) who report HAU and key HIV indicators. Gaps in current literature in estimating HAU on HIV outcomes at the regional level of Eastern and Southern Africa still exist and our analysis aims to address this issue. Methods We used weighted pooled data (2015–2017) from the nationally representative Population‐based HIV Impact Assessments among adults who provided written consent aged 18–59 years from Eswatini, Malawi, Namibia, Tanzania, Zambia and Zimbabwe. We estimated differences in the prevalence of HIV infection and The Joint United Nations Programme on HIV and AIDS (UNAIDS) 90‐90‐90 indicators between PLHIV by HAU status using log‐binomial regression, stratified by sex. HAU was determined using the Alcohol Use Identification Test—Consumption. Results Among the 9755 women and 4444 men who tested HIV positive, 6.6% of women and 21.8% of men engaged in HAU. Women who reported HAU were more likely to be HIV positive (adjusted prevalence ratio [aPR] = 1.31, 95% CI: 1.18–1.46) compared to those who did not report HAU. For the UNAIDS 90‐90‐90 targets, women who engaged in HAU were more likely to be unaware of their HIV‐positive status (aPR = 1.22, 95% CI: 1.01–1.47) and not on antiretroviral therapy (ART) (aPR = 1.73, 95% CI: 1.26–2.37). Men who engaged in HAU were more likely to be unaware of their HIV‐positive status (aPR = 1.56, 95% CI 1.39–1.76) and not on ART (aPR = 1.72, 95% CI: 1.30–2.29). No difference in viral load suppression, defined as

Introduction Chronic musculoskeletal pain causes a significant burden on health and quality of life and may result from inadequate treatment of acute musculoskeletal pain. The emergency department (ED) represents a novel setting in which to test non-pharmacological interventions early in the pain trajectory to prevent the transition from acute to chronic pain. Acupuncture is increasingly recognised as a safe, affordable and effective treatment for pain and anxiety in the clinic setting, but it has yet to be established as a primary treatment option in the ED.Methods and analysis This pragmatic clinical trial uses a two-stage adaptive randomised design to determine the feasibility, acceptability and effectiveness of acupuncture initiated in the ED and continued in outpatient clinic for treating acute musculoskeletal pain. The objective of the first (treatment selection) stage is to determine the more effective style of ED-based acupuncture, auricular acupuncture or peripheral acupuncture, as compared with no acupuncture. All arms will receive usual care at the discretion of the ED provider blinded to treatment arm. The objective of the second (effectiveness confirmation) stage is to confirm the impact of the selected acupuncture arm on pain reduction. An interim analysis is planned at the end of stage 1 based on probability of being the best treatment, after which adaptations will be considered including dropping the less effective arm, sample size re-estimation and unequal treatment allocation ratio (eg, 1:2) for stage 2. Acupuncture treatments will be delivered by licensed acupuncturists in the ED and twice weekly for 1 month afterward in an outpatient clinic.Ethics and dissemination This study has been reviewed and approved by the Duke University Health System Institutional Review Board. Informed consent will be obtained from all participants. Results will be disseminated through peer-review publications and public and conference presentations.Trial registration number NCT04290741.

Regular and timely screenings for colorectal cancer (CRC) can improve survival through early cancer detection. The current prospective intervention study assessed the effectiveness of a CRC screening outreach campaign via a multi-media campaign featuring articles in a multi-topic benefits newsletter that was both printed/mailed to homes and emailed to Metro Nashville Public Schools (MNPS) employees and their dependents in the United States. Individuals were included if they were between 45 and 64 years old. The mailed newsletter was sent to 5631 active employees, 868 under 65 retirees, and 4046 retirees with Medicare. The open rate was the highest for the third email (n = 3018; 53.3%). The click-through rate was also the highest for the third email (n = 203;6.7%). Among those who opened at least one of the emails or received a mailed newsletter, 119 members completed the assessment (conversion rate = 3.9%). Among this population, the mt-sDNA completion rate was 64.5% (69 orders completed out of 107 ordered mt-sDNA kits). All 6 patients with a positive mt-sDNA result underwent a follow-up colonoscopy (FU-CY) with the mean (±SD) days to FU-CY among those with positive mt-sDNA test results was 49 (±27) days (median = 42 days). Using emails in conjunction with other targeted interventions to outreach and educate members regarding CRC screening may be an effective strategy to enhance mt-sDNA completion rates.

Objective: Hypercalcemia is a common finding in patients who have an underlying malignancy. Only a few cases of hypercalcemia of malignancy have been linked to more than one mechanism of hypercalcemia. Here, we present a patient with liposarcoma and hypercalcemia of malignancy in the setting of simultaneous elevations in parathyroid hormone-related peptide (PTHrP) and 1,25 dihydroxyvitamin D [1,25(OH)2D] levels. Sarcoma-associated hypercalcemia is a rare disorder. Methods: The patient was an 89-year-old woman with sarcoma-associated hypercalcemia. Multiple mechanisms were uncovered, and treatments were adjusted for them. Literature search for hypercalcemia of malignancy with multiple mechanisms was conducted. Results: This is the first report describing dual mechanisms of sarcoma-associated hypercalcemia and only the fifth report on PTHrP and 1,25(OH)2D simultaneously causing hypercalcemia of malignancy. Conclusion: Based on this finding, we recommend measuring the 1,25(OH)2D levels in conjunction with the PTHrP level in patients with malignancy as this would allow for a more proactive approach to the diagnosis and treatment of hypercalcemia of malignancy.

We investigated the globally distributed red algal genus Pterocladiella, comprising 24 described species, many of which are economically important sources of agar and agarose. We used DNA-based species delimitation approaches, phylogenetic, and historical biogeographical analyses to uncover cryptic diversity and infer the drivers of biogeographic patterns. We delimited 43 species in Pterocladiella, of which 19 are undescribed. Our multigene time-calibrated phylogeny and ancestral area reconstruction indicated that Pterocladiella most likely originated during the Early Cretaceous in the Tethys Sea. Ancient Tethyan vicariance and long-distance dispersal have shaped current distribution patterns. The ancestor of Eastern Pacific species likely arose before the formation of the formidable Eastern Pacific Barrier—a first confirmation using molecular data in red algae. Divergences of Northeast and Southeast Pacific species have been driven by the Central American Seaway barrier, which, paradoxically, served as a dispersal pathway for Atlantic species. Both long- and short-distance dispersal scenarios are supported by genetic relationships within cosmopolitan species based on haplotype analysis. Asymmetrical distributions and the predominance of peripatry and sympatry between sister species suggest the importance of budding speciation in Pterocladiella. Our study highlights the underestimation of global diversity in these crucial components of coastal ecosystems and provides evidence for the complex evolution of current species distributions.

Abstract Background Scrub typhus causes up to 35% mortality if left untreated. One billion people living in the endemic regions are at risk. In spite of its heavy disease burden in some of the most populated areas in the world, there is no vaccine available. Although the disease can be effectively treated by proper antibiotics, timely and accurate diagnosis remains a challenge. Orientia tsutsugamushi infects a variety of mammalian cells in vitro and replicates in the cytoplasm of the infected cells. Microarray analysis has been used extensively to study host-pathogen interactions in in vitro models to understand pathogenesis. However there is a lack of in vivo studies. Results In this study, C3HeB/FeJ (C3H) mice were infected by O. tsutsugamushi via the intraperitoneal route and monitored gene expression at 10 different time points post infection. We observed two distinct types of expression profiles in the genes that we analyzed. There are two valleys (4–18 h and 2–4 days) with low number of differentially expressed genes (DEG) with three peaks with high number of DEG at 2 h, 1-day and 7-day post infection. Further analysis revealed that pathways like complement and coagulation cascade, and blood clotting cascade pathways showed significant global changes throughout entire time course. Real time quantitative Polymerase Chain Reaction (RT-qPCR) confirmed the change of expression for genes involved in complement and coagulation cascade. These results suggested dynamic regulation of the complement and coagulation cascades throughout most of the time post infection while some other specific pathways, such as fatty acid metabolism and tryptophan metabolism, are turned on or off at certain times post infection. Conclusions The findings highlight the complex interconnection among all different biological pathways. It is conceivable that specific pathways such as cell growth control and cell development in the host are affected by Orientia in the initial phase of infection for Orientia to grow intracellularly. Once Orientia is replicating successfully inside the host as infection progresses, the infection could activate pathways involved in cellular immune responses to defend for host cell survival and try to eliminate the pathogen.

PURPOSEMore than 80% of cervical cancer cases and deaths occur in low- and middle-income countries. Here, we analyze a large geographically extensive cross-sectional data set from the Western rural highlands of Guatemala. Our objective is to better characterize weak points in care along the cervical cancer care continuum and investigate sociodemographic and clinical correlates of loss to follow-up.METHODSWe conducted a retrospective review of electronic health records data from July 21, 2015, through December 10, 2020 for a cytology-based screening and cervical cancer treatment program. We used a care cascade analysis to characterize the progression of individuals through screening, confirmatory testing, and treatment. We examined demographic and clinical factors correlated with screening and loss to follow-up using multivariate logistic regression.RESULTSA total of 8,872 individuals were included in the analysis. Five thousand nine hundred thirteen cervical cancer screenings were conducted. 4.1% of all screening tests were abnormal, including 0.61% cervical intraepithelial neoplasia or overt cervical cancer. Care cascade analysis showed that 67% of eligible women accepted screening. Of those requiring confirmatory testing or treatment, 73% completed recommended follow-up. In adjusted multivariable analysis, prior history of sexual transmitted infection, prior experience with cervical cancer screening, older age, and current contraceptive use were associated with accepting screening. Age and contraceptive use were also associated with retention in care after a positive first screen.CONCLUSIONIn a large rural Guatemalan retrospective cohort, a care continuum analysis showed that both declining the opportunity to receive cervical cancer screening as well as declining confirmatory testing after a first positive screen were both important weak points along the care continuum. These data support the need for comprehensive and culturally appropriate initiatives to improve screening uptake and retention in care.

Introduction Despite national efforts to establish patient-centered medical homes (PCMH), 57.3% of children with special health care needs are receiving care that does not meet medical home criteria. Project DOCC, a national curriculum designed by parents of children with disabilities or chronic disease, has shown documented strengths in medical resident learner education of children with special health care needs from the parent perspectives for over a decade. Because of the importance of PCMH and the need to provide compassionate care, our team adapted the curriculum to incorporate team-based learning in the rural setting. Materials and Methods Reading materials were distributed to learners prior to an in-person workshop at which time, learners reviewed a video and discussed PCMH materials to identify elements of the PCMH. Learners then engaged with parent mentors across three breakout sessions. A final group reflection was completed to review and discuss efforts providers would take to establish and maintain the PCMH in their own practice. Baseline and post-workshop PCMH perceptions and parent mentor reflections were collected and compared using t-test comparisons. Results Learner knowledge, perceptions, and comfort significantly increased after the workshop. Parent mentor comments also highlighted an increased understanding for the provider. Discussion: The adapted PCMH curriculum significantly impacted learner outcomes using a feasible approach that fit nicely within health professional curricula and limited resources of the rural setting. Parents enjoyed the opportunity to serve as mentors and valued the instruction format.

Introduction/Objectives: Despite compelling evidence of clinical and economic benefits, adherence to colorectal cancer (CRC) screening remains low. Increasing public awareness through various outreach methods may improve screening uptake. The objective of this study was to evaluate the uptake of non-invasive multi-target stool DNA (mt-sDNA) by different outreach methods in an average-risk employer population. Methods: This retrospective observational study included CRC screening-eligible individuals aged ≥50 years insured by the Metropolitan Nashville Public Schools (MNPS) employee healthcare plan. The study intervention arms included population-based outreach and office visit-based interaction. The mt-sDNA completion rate (proportion of individuals who return the mt-sDNA kit after consenting to have it shipped to their home), proportion of patients who performed follow-up colonoscopy after a positive test, and time to follow-up colonoscopy were assessed. Results: A total of 167 mt-sDNA kits were shipped to eligible participants (aged 50-64 years) in the population-based outreach arm. In the office visit-based interaction arm, a total of 132 mt-sDNA kits were shipped to eligible participants (aged ≥50 years). The mt-sDNA completion rate was significantly higher for office visit-based interaction as compared to population-based outreach (76.8% vs 53.5%; P

In late September 2017, Bwabwata National Park in Namibia experienced a sudden die-off of hippopotamuses and Cape buffalo. A multiorganizational response was initiated, involving several ministries within Namibia and the US Centers for Disease Control and Prevention. Rapid interventions resulted in zero human or livestock cases associated with this epizootic.

Mycobacterium bovis and other Mycobacterium tuberculosis complex (MTBC) pathogens that cause domestic animal and wildlife tuberculosis have received considerably less attention than M. tuberculosis, the primary cause of human tuberculosis (TB). Human TB studies have shown that different stages of infection can exist, driven by host–pathogen interactions. This results in the emergence of heterogeneous subpopulations of mycobacteria in different phenotypic states, which range from actively replicating (AR) cells to viable but slowly or non-replicating (VBNR), viable but non-culturable (VBNC), and dormant mycobacteria. The VBNR, VBNC, and dormant subpopulations are believed to underlie latent tuberculosis (LTB) in humans; however, it is unclear if a similar phenomenon could be happening in animals. This review discusses the evidence, challenges, and knowledge gaps regarding LTB in animals, and possible host–pathogen differences in the MTBC strains M. tuberculosis and M. bovis during infection. We further consider models that might be adapted from human TB research to investigate how the different phenotypic states of bacteria could influence TB stages in animals. In addition, we explore potential host biomarkers and mycobacterial changes in the DosR regulon, transcriptional sigma factors, and resuscitation-promoting factors that may influence the development of LTB.

Introduction: Hypoglycemia harbors a broad differential diagnosis but is most often thought of in relation to poorly controlled diabetes. Recently however, there is growing evidence that genetic mutations, in the setting of hyperinsulinemic hypoglycemia (HH), are more common than previously noted as the primary cause of symptomatic hypoglycemia. One of 16 known genetic mutations implicated in HH is the gene that codes for the enzyme glucokinase, which has an integral role in glucose metabolism. Case: We describe the case of a 36-year-old relatively healthy male presenting with acute on chronic spells of shakiness relieved by eating who, after thorough work up for metabolic, hormonal, and structural causes of hypoglycemia, was determined to carry a previously undiscovered mutation in glucokinase that was responsible for his symptoms. Of note, his four-year-old son had already been diagnosed with HH that was successfully controlled with diazoxide by this time. Genetic testing confirmed that the patient and his son, along with the patient's father, all carried the same GCK missense variant Tyr215Phe which has not yet been documented in the scientific literature. Discussion: The patient, his father, and his son all had markedly different presentations, in both disease severity and treatment response, despite carrying the same mutation. This clinical variability within families with HH has been described before, but the specific explanation for this finding, given the apparent autosomal dominant transmission, remains poorly understood and understudied. The roles of micro RNA, the immune system, tissue specific promoters, and other individual metabolic differences in people with HH have all been explored with this in mind. We also discuss the short-term physiologic response to hypoglycemia and analyze compensatory mechanisms that those with HH may harbor to endure longer durations of hypoglycemia. Conclusion: The discovery of the new variant in the GCK gene located on chromosome 7 in this case suggests that there are still undiscovered mutations responsible for HH. This case also highlights the need for further research characterizing the physiology, phenotypic variability, and natural history of the disease, particularly as its prevalence increases in the setting of more advanced diagnostic methods.

Namibia faces a critical shortage of skilled public health workers to perform emergency response operations, preparedness activities and real-time surveillance. The Namibia Field Epidemiology and Laboratory Training Programme (NamFELTP) increases the number of skilled public health professionals and strengthens the public health system in Namibia. We describe the NamFELTP during its first 7 years, assess its impact on the public health workforce and provide recommendations to further strengthen the workforce. We reviewed disease outbreak investigations and response reports, field projects and epidemiological investigations conducted during 2012–2019. The data were analysed using descriptive methods such as frequencies and rates. Maps representing the geographical distribution of NamFELTP workforce were produced using QGIS software V.3.2. There were no formally trained field epidemiologists working in Namibia before the NamFELTP. In its 7 years of operation, the programme graduated 189 field epidemiologists, of which 28 have completed the Advanced FELTP. The graduates increased epidemiological capacity for surveillance and response in Namibia at the national and provincial levels, and enhanced epidemiologist-led outbreak responses on 35 occasions, including responses to outbreaks of human and zoonotic diseases. Trainees analysed data from 51 surveillance systems and completed 31 epidemiological studies. The NamFELTP improved outcomes in the Namibia’s public health systems; including functional and robust public health surveillance systems that timely and effectively respond to public health emergencies. However, the current epidemiological capacity is insufficient and there is a need to continue training and mentorship to fill key leadership and strategic roles in the public health system.

BackgroundIn the 21st century, understanding how population migration impacts human health is critical. Namibia has high migration rates and HIV prevalence, but little is known about how these intersect. We examined the association between migration and HIV-related outcomes using data from the 2017 Namibia Population-based HIV Impact Assessment (NAMPHIA).Methods and findingsThe NAMPHIA survey selected a nationally representative sample of adults in 2017. All adults aged 15-64 years were invited to complete an interview and home-based HIV test. Recent infection (1000 copies/mL) and antiretroviral analyte data. Awareness of HIV status and antiretroviral use were based on self-report and/or detectable antiretrovirals in blood. Viremia was defined as having a viral load ≥1000 copies/mL, including all participants in the denominator regardless of serostatus. We generated community viremia values as a weighted proportion at the EA level, excluding those classified as recently infected. Significant migrants were those who had lived outside their current region or away from home >one month in the past three years. Recent cross-community in-migrants were those who had moved to the community two years ago to determine the association of migration and timing with recent infection or viral load suppression (VLS). All proportions are weighted. Of eligible adults, we had HIV results and migration data on 9,625 (83.9%) of 11,474 women and 7,291 (73.0%) of 9,990 men. Most respondents (62.5%) reported significant migration. Of cross-community in-migrants, 15.3% were recent. HIV prevalence was 12.6% and did not differ by migration status. Population VLS was 77.4%. Recent cross-community in-migration was associated with recent HIV infection (aOR: 4.01, 95% CI 0.99-16.22) after adjusting for community viremia. Significant migration (aOR 0.73, 95% CI: 0.55-0.97) and recent cross-community in-migration (aOR 0.57, 95% CI: 0.35-0.92) were associated with lower VLS, primarily due to lack of awareness of HIV infection. The study was limited by lack of precise data on trajectory of migration.ConclusionsDespite a high population-level VLS, Namibia still has migrant populations that are not accessing effective treatment for HIV. Targeting migrants with effective prevention and testing programs in communities with viremia could enable further epidemic control.

Background: In the United States (US), colorectal cancer (CRC) is the second leading cause of cancer-related deaths. With the majority of the US population covered by employer-based health plans, employers can play a critical role in increasing CRC screening adherence, which may help avert CRC-related deaths. Therefore, it is important for self-insured employers to consider the impact of appropriate utilization of CRC screening options. Objective: To evaluate the impact of increasing multitarget stool DNA [mt-sDNA (Cologuard®)] use among CRC screeners from the perspective of a US self-insured employer. Methods:A 5-year Markov model was developed to quantify the budget impact of increasing mt-sDNA from 6% to 15% among average-risk screeners using colonoscopy, fecal immunological test, and mt-sDNA. Data on direct medical costs were obtained from published literature, Medicare CPT codes, and the Healthcare cost and Utilization project. Indirect costs included productivity loss due to workplace absenteeism for CRC screening and treatment. Results: With a hypothetical population of 100,000 employees with screeners aged 50–64 years, compared to status quo, increased mt-sDNA utilization resulted in no differences in the numbers of cancers detected and the overall direct and indirect cost savings were ~$214,000 ($0.04 per-employee-per-month) over 5 years. Most of the savings were due to a reduction in the direct medical expenditure related to CRC screening, adverse events, and productivity loss due to colonoscopy screening. Similar results were observed in the model simulation among screeners aged 45–64 years. Conclusion: Increased utilization of mt-sDNA for CRC screening averts direct and indirect medical costs from a self-insured US employer perspective.

Staphylococcus aureus, a gram-positive bacterium, causes toxic shock through the production of superantigenic toxins (sAgs) known as Staphylococcal enterotoxins (SE), serotypes A-J (SEA, SEB, etc.), and toxic shock syndrome toxin-1 (TSST-1). The chronology of host transcriptomic events that characterizes the response to the pathogenesis of superantigenic toxicity remains uncertain. The focus of this study was to elucidate time-resolved host responses to three toxins of the superantigenic family, namely SEA, SEB, and TSST-1. Due to the evolving critical role of melanocytes in the host’s immune response against environmental harmful elements, we investigated herein the transcriptomic responses of melanocytes after treatment with 200 ng/mL of SEA, SEB, or TSST-1 for 0.5, 2, 6, 12, 24, or 48 h. Functional analysis indicated that each of these three toxins induced a specific transcriptional pattern. In particular, the time-resolved transcriptional modulations due to SEB exposure were very distinct from those induced by SEA and TSST-1. The three superantigens share some similarities in the mechanisms underlying apoptosis, innate immunity, and other biological processes. Superantigen-specific signatures were determined for the functional dynamics related to necrosis, cytokine production, and acute-phase response. These differentially regulated networks can be targeted for therapeutic intervention and marked as the distinguishing factors for the three sAgs.

We have isolated a chlorophyll-d-containing cyanobacterium from the intertidal field site at Moss Beach, on the coast of Central California, USA, where Manning and Strain (1943) originally discovered this far-red chlorophyll. Here, we present the cyanobacterium’s environmental description, culturing procedure, pigment composition, ultrastructure, and full genome sequence. Among cultures of far-red cyanobacteria obtained from red algae from the same site, this strain was an epiphyte on a brown macroalgae. Its Qyin vivo absorbance peak is centered at 704–705 nm, the shortest wavelength observed thus far among the various known Acaryochloris strains. Its Chl a/Chl d ratio was 0.01, with Chl d accounting for 99% of the total Chl d and Chl a mass. TEM imagery indicates the absence of phycobilisomes, corroborated by both pigment spectra and genome analysis. The Moss Beach strain codes for only a single set of genes for producing allophycocyanin. Genomic sequencing yielded a 7.25 Mbp circular chromosome and 10 circular plasmids ranging from 16 kbp to 394 kbp. We have determined that this strain shares high similarity with strain S15, an epiphyte of red algae, while its distinct gene complement and ecological niche suggest that this strain could be the closest known relative to the original Chl d source of Manning and Strain (1943). The Moss Beach strain is designated Acaryochloris sp. (marina) strain Moss Beach.

Scholars and policy-makers agree that cross-border and multi-sector cooperation are essential components of coordinated efforts to contain the spread of COVID-19 infections. This paper examines the responses of ASEAN (Association of Southeast Asian Nation) member countries to the COVID-19 pandemic, including the limits of regional cooperation. ASEAN has pre-existing cooperative frameworks in place, including regional health security measures, which, at least theoretically, could assist the region's efforts to formulate cooperative responses to containing a global pandemic. With its overarching “One Vision, One Identity, One Community”, ASEAN cooperation has extended to include region-wide disaster responses, framed as “One Asean, One Response”. Using content analysis, this paper examines media statements and policies from ASEAN member states and the ASEAN Secretariat to assess the collective response to COVID-19 during the period from January to August 2020. By identifying gaps and opportunities in government responses to COVID-19 as the virus spread throughout Southeast Asia, this paper provides new insights as well as recommendations for the future.

Although complete mitogenomic data have been widely applied in human and other animal population studies, they are extremely limited for florideophycean red algal populations. Gelidiella fanii is a recently described rhodophyta, previously misidentified as G. acerosa, a cosmopolitan agar-yielding species from tropical to subtropical waters. To decipher patterns in genetic diversity and geographic distribution for G. fanii, we obtained 10 complete mitogenomes including two outgroups, G. acerosa and G. flabella. The mitogenomes ranged in size from 25,223 to 25,281 bp and had 48 genes, which are similar in general structure, gene order and content, and presence of a group II intron. Phylogenomic analysis revealed that G. fanii was monophyletic and clearly separate from G. acerosa. The range of G. fanii was extended from Southeast Asia and northern Australia to Eritrea, Juan de Nova Island, and Kenya in the west, and to Hawai‘i and Tetiaroa Atoll to the east. Haplotype network analysis of cox1 revealed seven geographically structured groups: Southeast Asia, Kenya/Juan de Nova Island, Indonesia, northern Australia, the Philippines, Tetiaroa Atoll, and Hawai‘i. This regional structure has likely resulted from the separation and isolation of an ancient widespread population during the Pleistocene. This study demonstrates that mitogenome sequencing is a powerful genotyping tool for studies of genetic diversity, biogeography, and conservation of economically valuable marine algal species.

Glanzmann Thrombasthenia is a rare bleeding disorder causing life-threatening bleeding at menarche in the adolescent female. Bleeding often necessitates admission and multiple blood transfusions. Due to the rarity of the disease, management of acute bleeding in new-onset menarche poses a particular challenge. A 12-year-old menarchial female had persistent vaginal bleeding despite multiple treatment modalities including aminocaproic acid, recombinant factor VIIa, intravenous estrogen, and gonadotropin receptor hormone agonists. Although the standard treatment of bleeding in patients with GT is primarily rFVIIa, new-onset menstrual bleeding in conjunction with an immature hypothalamic-pituitary-ovarian axis often requires expanding treatment to include multiple drug modalities. In our case, a two-step approach was necessary. The first is targeting the cessation of the first menses. The second is optimizing ongoing management of long-term control of heavy menstrual bleeding to achieve amenorrhea, prevent further hospital admissions, and avoid recurrent transfusions.

Abstract Background The immune response against tuberculosis in lions is still poorly defined and our understanding is hampered by the lack of lion specific reagents. The process for producing antibodies against a specific antigen is laborious and not available to many research laboratories. As the search for antibody cross-reactivity is an important strategy for immunological studies in veterinary medicine, we have investigated the use of commercially available antibodies to characterize T cell subsets in African lions (Panthera leo). Results Commercially available antibodies were screened and investigated the influence of two different sample processing methods, as well as the effect of time delay on cell surface marker expression on lion lymphocytes. Using commercially available antibodies, we were able to identify CD4+, CD5+, CD8+, CD14+, CD25+, CD44+ and CD45+ T lymphocytes in samples obtained by density gradient centrifugation as well as red cell lysis of lion whole blood. Two distinct lymphocyte populations, which differed in size and phenotype, were observed in the samples processed by density gradient centrifugation. Conclusion Commercially available antibodies are able to differentiate between T lymphocyte subsets including immune effector cells in African lion whole blood, and possibly give insight into unique specie phenotypes.

Cosmopolitan Acrosorium species with hook-forming thalli have been merged under the name of Acrosorium ciliolatum (Harvey) Kylin through a long and complicated nomenclatural history. We examined the specimens of ‘A. ciliolatum’ and related taxa from the northwestern (NW) Pacific, the UK, southern Spain, Australia, New Zealand, and Chile, using morphological and molecular analyses. We confirmed that these specimens are separated into four clades based on rbcL phylogeny, and the absence or presence of terminal hook-like structures represent intraspecific variation. Our results indicated that Acrosorium flabellatum Yamada, Cryptopleura hayamensis Yamada, Cryptopleura membranacea Yamada and the entities known as ‘A. ciliolatum’ in the NW Pacific are conspecific; the name A. flabellatum is the oldest and has priority. This taxon exhibits extreme variations in external blade morphology. We also confirmed that the position of the tetrasporangial sori is a valuable diagnostic characteristic for distinguishing A. flabellatum in the NW Pacific. We also discussed the need for further study of European and southern hemisphere specimens from type localities, as well as the ambiguous position of California specimens.

Initiation of treatment during the pre-symptomatic phase of Yersinia pestis (Y. pestis) infection is particularly critical. The rapid proliferation of Y. pestis typically couples with the manifestation of common flu-like early symptoms that often misguides the medical intervention. Our study used African green monkeys (AGM) that did not exhibit clear clinical symptoms for nearly two days after intranasal challenge with Y. pestis and succumbed within a day after showing the first signs of clinical symptoms. The lung, and mediastinal and submandibular lymph nodes (LN) accumulated significant Y. pestis colonization immediately after the intranasal challenge. Hence, organ-specific molecular investigations are deemed to be the key to elucidating mechanisms of the initial host response. Our previous study focused on the whole blood of AGM, and we found early perturbations in the ubiquitin-microtubule-mediated host defense. Altered expression of the genes present in ubiquitin and microtubule networks indicated an early suppression of these networks in the submandibular lymph nodes. In concert, the upstream toll-like receptor signaling and downstream NFκB signaling were inhibited at the multi-omics level. The inflammatory response was suppressed in the lungs, submandibular lymph nodes and mediastinal lymph nodes. We posited a causal chain of molecular mechanisms that indicated Y. pestis was probably able to impair host-mediated proteolysis activities and evade autophagosome capture by dysregulating both ubiquitin and microtubule networks in submandibular lymph nodes. Targeting these networks in a submandibular LN-specific and time-resolved fashion could be essential for development of the next generation therapeutics for pneumonic plague.