Mechanisms and risk factors associated with spinal cord injury, facet fracture, and level of dislocation, in occupants with cervical spine dislocations sustained in motor vehicle crashes.

OBJECTIVE: Motor vehicle crashes (MVCs) are the leading cause of cervical spine dislocation. The mechanisms underlying this injury are unclear, limiting the development of injury prevention devices and strategies. MVC databases contain occupant, medical, vehicle, and crash details that are not routinely collected elsewhere, providing a unique resource for investigating injury mechanisms and risk factors. In this study, a comprehensive standalone analysis of cervical spine dislocations captured in MVC databases was performed. METHODS: Epidemiologic, biomechanical, and injury data were extracted from three MVC databases. Logistic regression models were developed to determine the occupant, vehicle, and crash characteristics, as well as the global (inertial or impact) and regional (flexion, compression, etc.) loading mechanisms associated with the level of cervical spine dislocation (axial or sub-axial), and the occurrence of spinal cord injury (SCI) or facet fracture concomitant to dislocation. RESULTS: There was no association between global or regional injury mechanisms and the level of cervical spine dislocation. Sub-axial dislocations were typically due to head/face impact with the airbag or upper interior components, or a result of seatbelt restraint of the torso. Higher occupant age, lower BMI, partial/no ejection, and frontal and side configuration crashes (compared to rollovers) were associated with a higher likelihood of sub-axial, versus axial, dislocation. Amongst all dislocations, an increased likelihood of SCI was associated with impact injuries, airbag non-deployment, and complete ejection, while concomitant facet fracture was associated with the presence of regional compression. Severe crashes, partial ejections, and "utility vehicles" and "vans and trucks" (compared with "passenger vehicles") were associated with a higher risk of facet fracture concomitant to sub-axial dislocation. CONCLUSION: The findings of this study may be used to inform the loading modes to be simulated in future ex vivo or computational models seeking a better understanding of cervical spine dislocations.

The prescription and monitoring of conventional synthetic disease-modifying anti-rheumatic drugs: British Society for Rheumatology guideline scope.

This guideline will provide up-to-date, evidence-based recommendations on the safe use of non-biologic DMARDs, also called conventional synthetic DMARDs (csDMARD), across the full spectrum of autoimmune rheumatic diseases. The guideline will update the guideline published in 2017 and will be expanded to include people of all ages. Updated information on the monitoring of DMARDs and vaccinations will be included. The guideline will be developed using the methods and processes described in the British Society for Rheumatology's 'Creating clinical guidelines: our protocol', updated 2023.

An Extended Neck Position is Likely to Produce Cervical Spine Injuries Through Buckling in Accidental Head-First Impacts During Rugby Tackling.

Catastrophic cervical spine injuries in rugby often occur during tackling. The underlying mechanisms leading to these injuries remain unclear, with neck hyperflexion and buckling both proposed as the causative factor in the injury prevention literature. The aim of this study was to evaluate the effect of pre-impact head-neck posture on intervertebral neck loads and motions during a head-first rugby tackle. Using a validated, subject-specific musculoskeletal model of a rugby player, and computer simulations driven by in vivo and in vitro data, we examined the dynamic response of the cervical spine under such impact conditions. The simulations demonstrated that the initial head-neck sagittal-plane posture affected intervertebral loads and kinematics, with an extended neck resulting in buckling and supraphysiologic intervertebral shear and flexion loads and motions, typical of bilateral facet dislocation injuries. In contrast, an initially flexed neck increased axial compression forces and flexion angles without exceeding intervertebral physiological limits. These findings provide objective evidence that can inform injury prevention strategies or rugby law changes to improve the safety of the game of rugby.

Facet deflection and strain are dependent on axial compression and distraction in C5-C7 spinal segments under constrained flexion.

Background: Facet fractures are frequently associated with clinically observed cervical facet dislocations (CFDs); however, to date there has only been one experimental study, using functional spinal units (FSUs), which has systematically produced CFD with concomitant facet fracture. The role of axial compression and distraction on the mechanical response of the cervical facets under intervertebral motions associated with CFD in FSUs has previously been shown. The same has not been demonstrated in multi-segment lower cervical spine specimens under flexion loading (postulated to be the local injury vector associated with CFD). Methods: This study investigated the mechanical response of the bilateral inferior C6 facets of thirteen C5-C7 specimens (67±13 yr, 6 male) during non-destructive constrained flexion, superimposed with each of five axial conditions: (1) 50 N compression (simulating weight of the head); (2-4) 300, 500, and 1000 N compression (simulating the spectrum of intervertebral compression resulting from neck muscle bracing prior to head-first impact and/or externally applied compressive forces); and, (5) 2 mm of C6/C7 distraction (simulating the intervertebral distraction present during inertial loading of the cervical spine by the weight of the head). Linear mixed-effects models (α = 0.05) assessed the effect of axial condition. Results: Increasing amounts of intervertebral compression superimposed on flexion rotations, resulted in increased facet surface strains (range of estimated mean difference relative to Neutral: maximum principal = 77 to 110 µÎµ, minimum principal = 126 to 293 µÎµ, maximum shear = 203 to 375 µÎµ) and angular deflection of the bilateral inferior C6 facets relative to the C6 vertebral body (range of estimated mean difference relative to Neutral = 0.59° to 1.47°). Conclusions: These findings suggest increased facet engagement and higher load transfer through the facet joint, and potentially a higher likelihood of facet fracture under the compressed axial conditions.

Kinematics, kinetics, and new insights from a contemporary analysis of the first experiments to produce cervical facet dislocations in the laboratory.

Background: The first experimental study to produce cervical facet dislocation (CFD) in cadaver specimens captured the vertebral motions and axial forces that are important for understanding the injury mechanics. However, these data were not reported in the original manuscript, nor been presented in the limited subsequent studies of experimental CFD. Therefore, the aim of this study was to re-examine the analog data from the first experimental study to determine the local and global spinal motions, and applied axial force, at and preceding CFD. Methods: In the original study, quasistatic axial loading was applied to 14 cervical spines by compressing them between two metal plates. Specimens were fixed caudally via a steel spindle positioned within the spinal canal and a bone pin through the inferior-most vertebral body. Global rotation of the occiput was restricted but its anterior translation was unconstrained. The instant of CFD was identified on sagittal cineradiograph films (N = 10), from which global and intervertebral kinematics were also calculated. Corresponding axial force data (N = 6) were extracted, and peak force and force at the instant of injury were determined. Results: CFD occurred in eight specimens, with an intervertebral flexion angle of 34.8 ± 5.6 degrees, and a 3.1 ± 1.9 mm increase in anterior translation, at the injured level. For seven specimens, CFD was produced at the level of transition from upper neck lordosis to lower neck kyphosis. Five specimens with force data underwent CFD at 545 ± 147 N, preceded by a peak axial force (755 ± 233 N) that appeared to coincide with either fracture or soft tissue failure. Conclusions: Re-examining this rich dataset has provided quantitative evidence that small axial compression forces, combined with anterior eccentricity and upper neck extension, can cause flexion and shear in the lower neck, leading to soft tissue rupture and CFD.

Neck stiffness and range of motion for young males and females.

Well characterised mechanical response of the normal head-neck complex during passive motion is important to inform and verify physical surrogate and computational models of the human neck, and to inform normal baseline for clinical assessments. For 10 male and 10 female participants aged 20 to 29, the range of motion (ROM) of the neck about three anatomical axes was evaluated in active-seated, passive-lying and active-lying configurations, and the neck stiffness was evaluated in passive-lying. Electromyographic signals from the agonist muscles, normalised to maximum voluntary contractions, were used to provide feedback during passive motions. The effect of sex and configuration on ROM, and the effect of sex on linear estimates of stiffness in three regions of the moment-angle curve, were assessed with linear mixed models and generalised linear models. There were no differences in male and female ROM across all motion directions and configurations. Flexion and axial rotation ROM were configuration dependent. The passive-lying moment-angle relationship was typically non-linear, with higher stiffness (slope) closer to end of ROM. When normalising the passive moment-angle curve to active lying ROM, passive stiffness was sex dependent only for lateral bending region 1 and 2. Aggregate moment-angle corridors were similar for males and females in flexion and extension, but exhibited a higher degree of variation in applied moment for males in lateral bending and axial rotation. These data provide the passive response of the neck to low rate bending and axial rotation angular displacement, which may be useful for computational and surrogate modelling of the human neck.

Evaluation of Apparatus and Protocols to Measure Human Passive Neck Stiffness and Range of Motion.

Understanding of human neck stiffness and range of motion (ROM) with minimal neck muscle activation ("passive") is important for clinical and bioengineering applications. The aim of this study was to develop, implement, and evaluate the reliability of methods for assessing passive-lying stiffness and ROM, in six head-neck rotation directions. Six participants completed two assessment sessions. To perform passive-lying tests, the participant's head and torso were strapped to a bending (flexion, extension, lateral bending) or a rotation (axial rotation) apparatus, and clinical bed, respectively. The head and neck were manually rotated by the researcher to the participant's maximum ROM, to assess passive-lying stiffness. Participant-initiated ("active") head ROM was also assessed in the apparatus, and seated. Various measures of apparatus functionality were assessed. ROM was similar for all assessment configurations in each motion direction except flexion. In each direction, passive stiffness generally increased throughout neck rotation. Within-session reliability for stiffness (ICC > 0.656) and ROM (ICC > 0.872) was acceptable, but between-session reliability was low for some motion directions, probably due to intrinsic participant factors, participant-apparatus interaction, and the relatively low participant number. Moment-angle corridors from both assessment sessions were similar, suggesting that with greater sample size, these methods may be suitable for estimating population-level corridors.

Dual DAT and sigma receptor inhibitors attenuate cocaine effects on nucleus accumbens dopamine dynamics in rats.

Psychostimulant use disorders (PSUD) are prevalent; however, no FDA-approved medications have been made available for treatment. Previous studies have shown that dual inhibitors of the dopamine transporter (DAT) and sigma receptors significantly reduce the behavioral/reinforcing effects of cocaine, which have been associated with stimulation of extracellular dopamine (DA) levels resulting from DAT inhibition. Here, we employ microdialysis and fast scan cyclic voltammetry (FSCV) procedures to investigate the effects of dual inhibitors of DAT and sigma receptors in combination with cocaine on nucleus accumbens shell (NAS) DA dynamics in naïve male Sprague Dawley rats. In microdialysis studies, administration of rimcazole (3, 10 mg/kg; i.p.) or its structural analog SH 3-24 (1, 3 mg/kg; i.p.), compounds that are dual inhibitors of DAT and sigma receptors, significantly reduced NAS DA efflux stimulated by increasing doses of cocaine (0.1, 0.3, 1.0 mg/kg; i.v.). Using the same experimental conditions, in FSCV tests, we show that rimcazole pretreatments attenuated cocaine-induced stimulation of evoked NAS DA release but produced no additional effect on DA clearance rate. Under the same conditions, JJC8-091, a modafinil analog and dual inhibitor of DAT and sigma receptors, similarly attenuated cocaine-induced stimulation of evoked NAS DA release but produced no additional effect on DA clearance rate. Our results provide the neurochemical groundwork towards understanding actions of dual inhibitors of DAT and sigma receptors on DA dynamics that likely mediate the behavioral effects of psychostimulants like cocaine.

Conspiracy theory beliefs in the adolescent population: A systematic review.

INTRODUCTION: While the study of conspiracy theory beliefs is a relatively new research area, there has been a rise in academic interest in recent years. The literature provides evidence of relationships between conspiracy theory beliefs and a range of factors, but the vast majority of studies are limited to adult samples, and it is unclear how such beliefs present in adolescence. METHODS: The systematic review was conducted according to the PRISMA-S format. Relevant databases were searched up to February 23, 2023, for quantitative studies related to adolescent conspiracy theory beliefs. RESULTS: The six included articles show that conspiracy theory beliefs are present from the start of adolescence, and stable from age 14 upwards, with correlations reported for mistrust and paranoid thinking. Negative relationships were reported for cognitive factors such as ontological confusion, cognitive ability, and actively open-minded thinking. Health-related beliefs correlated with adverse childhood experiences, peer problems, conduct, and sociodemographic factors. Right-wing authoritarianism and anxiety positively correlated with intergroup conspiracy theory beliefs. CONCLUSION: While some factors from adult studies are replicated in the review, there are differences between age groups. The age at which conspiracy theory beliefs begin to form indicate developmental aspects of adolescence, and possibly childhood, that require further examination. Cognitive factors show promise for interventions and should be explored further. However, the lack of studies using adolescent populations is an issue that must be resolved for a greater understanding of conspiracy theory beliefs and a move toward effective interventions.

Building Healthy Babies: A Mixed-Methods Needs Assessment for a Pre-Conception Program in Ontario.

OBJECTIVES: The objective of this study was to gather Ontario clinicians' and public members' views on the design of a pre-conception patient education program. METHODS: In this mixed-methods study, online surveys comprised of rank order, multiple choice, and short answer questions were completed by clinicians and public members. Semi-structured focus groups consisting of 2-6 participants each were then held via videoconference. Demographic variables and survey responses were analyzed quantitatively using descriptive and summary statistics. Descriptive thematic qualitative analysis using the constant comparative method of grounded theory was completed on each transcript to generate themes. RESULTS: A total of 168 public members and 43 clinicians in Ontario completed surveys, while 11 clinicians and 11 public members participated in the focus groups. A pre-conception program in Ontario was felt to be important. An individual appointment with a primary care provider was the favoured program format per survey responses, whereas a virtual format with an interactive component was preferred among focus group participants. Important topics to include were pre-conception health (infertility, genetic screening, folic acid), prenatal and postpartum counselling (diet, activity, substance use, prenatal care, postpartum course), and medical optimization in pregnancy (high-risk medical conditions, medications, mental health). Both groups emphasized the need to consider accommodations for marginalized populations and various cultures and languages. CONCLUSION: A standardized pre-conception patient education program is felt to be of high value by Ontario clinicians and public members. A pre-conception program may help improve obstetrical outcomes and decrease rates of major congenital anomalies in Ontario.

Treatment of polymyalgia rheumatica: British Society for Rheumatology guideline scope.

The last British Society for Rheumatology (BSR) guideline on PMR was published in 2009. The guideline needs to be updated to provide a summary of the current evidence for pharmacological and non-pharmacological management of adults with PMR. This guideline is aimed at healthcare professionals in the UK who directly care for people with PMR, including general practitioners, rheumatologists, nurses, physiotherapists, occupational therapists, pharmacists, psychologists and other health professionals. It will also be relevant to people living with PMR and organisations that support them in the public and third sector, including charities and informal patient support groups. This guideline will be developed using the methods and processes outlined in the BSR Guidelines Protocol. Here we provide a brief summary of the scope of the guideline update in development.

Bridge improvement work: maximising non-linear optical performance in polyoxometalate derivatives.

New phenyl and stilbene-bridged polyoxometalate (POM) charge-transfer chromophores with diphenylamino donor groups produce, respectively, the highest intrinsic and absolute quadratic hyperpolarisabilities measured for such species. The ß0,zzz obtained for the phenyl bridge - at 180 × 10-30 esu - is remarkable for a short conjugated system while changing to the stilbene (260 × 10-30 esu) produces a substantial increase in non-linearity for a minimal red-shift in the absorption profile. Together with TD-DFT calculations, the results show that maximising conjugation in the π-bridge is vital to high performance in such "POMophores".

A pilot feasibility randomised controlled trial of bone antiresorptive agents on bone turnover markers in critically ill women.

Critical illness is associated with increased bone turnover, loss of bone density, and increased risk of fragility fractures. The impact of bone antiresorptive agents in this population is not established. This trial examined the efficacy, feasibility, and safety of antiresorptive agents administered to critically ill women aged fifty years or greater. Women aged 50 years or greater admitted to an intensive care unit for at least 24 h were randomised to receive an antiresorptive agent (zoledronic acid or denosumab) or placebo, during critical illness and six months later (denosumab only). Bone turnover markers and bone mineral density (BMD) were monitored for 1 year. We studied 18 patients over 35 months before stopping the study due to the COVID-19 pandemic. Antiresorptive medications decreased the bone turnover marker type 1 cross-linked c-telopeptide (CTX) from day 0 to 28 by 43% (± 40%), compared to an increase of 26% (± 55%) observed with placebo (absolute difference - 69%, 95% CI - 127% to - 11%), p = 0.03). Mixed linear modelling revealed differences in the month after trial drug administration between the groups in serum CTX, alkaline phosphatase, parathyroid hormone, and phosphate. Change in BMD between antiresorptive and placebo groups was not statistically analysed due to small numbers. No serious adverse events were recorded. In critically ill women aged 50-years and over, antiresorptive agents suppressed bone resorption markers without serious adverse events. However, recruitment was slow. Further phase 2 trials examining the efficacy of these agents are warranted and should address barriers to enrolment.Trial registration: ACTRN12617000545369, registered 18th April 2017.

Validation of epidermal AMBRA1 and loricrin (AMBLor) as a prognostic biomarker for nonulcerated American Joint Committee on Cancer stage I/II cutaneous melanoma.

BACKGROUND: Combined expression of the autophagy-regulatory protein AMBRA1 (activating molecule in Beclin1-regulated autophagy) and the terminal differentiation marker loricrin in the peritumoral epidermis of stage I melanomas can identify tumour subsets at low risk of -metastasis. OBJECTIVES: To validate the combined expression of peritumoral AMBRA1 and loricrin (AMBLor) as a prognostic biomarker able to identify both stage I and II melanomas at low risk of tumour recurrence. METHODS: Automated immunohistochemistry was used to analyse peritumoral AMBRA1 and loricrin expression in geographically distinct discovery (n = 540) and validation (n = 300) cohorts of nonulcerated American Joint Committee on Cancer (AJCC) stage I and II melanomas. AMBLor status was correlated with clinical outcomes in the discovery and validation cohorts separately and combined. RESULTS: Analysis of AMBLor in the discovery cohort revealed a recurrence-free survival (RFS) rate of 95.5% in the AMBLor low-risk group vs. 81.7% in the AMBLor at-risk group (multivariate log-rank, P < 0.001) and a negative predictive value (NPV) of 96.0%. In the validation cohort, AMBLor analysis revealed a RFS rate of 97.6% in the AMBLor low-risk group vs. 78.3% in the at-risk group (multivariate log-rank, P < 0.001) and a NPV of 97.6%. In a multivariate model considering AMBLor, Breslow thickness, age and sex, analysis of the combined discovery and validation cohorts showed that the estimated effect of AMBLor was statistically significant, with a hazard ratio of 3.469 (95% confidence interval 1.403-8.580, P = 0.007) and an overall NPV of 96.5%. CONCLUSIONS: These data provide further evidence validating AMBLor as a prognostic biomarker to identify nonulcerated AJCC stage I and II melanoma tumours at low risk of disease recurrence.

Patients' and providers' perspectives on the decision to undergo non-urgent egg freezing: a needs assessment.

BACKGROUND: Previous research has demonstrated that patients have difficulty with the decision to undergo non-urgent egg freezing (EF). This study aimed to investigate the decisional difficulties and possible decisional support mechanisms for patients considering EF, and for their providers. METHODS: This qualitative study involved a needs assessment via individual interviews. Participants included patients considering EF at one academic fertility clinic and providers from across Canada who counsel patients considering EF. 25 participants were included (13 providers and 12 patients). The interview guide was developed according to the Ottawa Decision Support Framework. Interviews were transcribed, and transcripts analyzed for themes and concepts using NVIVO 12. FINDINGS: Multiple factors contributing to decisional difficulty were identified, including: (1) multiple reproductive options available with differing views from patients/providers regarding their importance; (2) a decision typically made under the pressure of reproductive aging; (3) uncertainty surrounding the technology/inadequate outcome data; (4) the financial burden of EF; (5) inherent uncertainty relating to potential decision regret; and (6) differing perceptions between patients/providers regarding the role providers should play in the decision. Additionally, potential sources of decisional support were identified, including provision of basic information before and/or during initial consultation, followed by an opportunity during or after initial consultation for clarifying information and helping with value judgements. Individualized counselling based on patient values, adequate follow-up, psychosocial counselling, and peer support were also emphasized. CONCLUSIONS: More decisional support for women considering EF is needed. Suggestions include a patient decision aid in conjunction with modified healthcare provider counselling, support and follow up.

Dicer deficiency in microglia leads to accelerated demyelination and failed remyelination.

Microglia are the resident immune cells of the central nervous system (CNS) and are important regulators of normal brain functions. In CNS demyelinating diseases like multiple sclerosis (MS), the functions of these cells are of particular interest. Here we probed the impact of microRNA (miRNA)-mediated post-transcriptional gene regulation using a mouse model lacking microglia/macrophage-specific Dicer expression during demyelination and remyelination. Conditional Dicer ablation and loss of miRNAs in adult microglia led to extensive demyelination and impaired myelin processing. Interestingly, demyelination was accompanied by increased apoptosis of mature oligodendrocytes (OLs) and arresting OL progenitor cells (OPCs) in the precursor stage. At the transcriptional level, Dicer -deficient microglia led to downregulation of microglial homeostatic genes, increased cell proliferation, and a shift towards a disease-associated phenotype. Loss of remyelination efficiency in these mice was accompanied by stalling of OPCs in the precursor stage. Collectively, these results highlight a new role of microglial miRNAs in promoting a pro-regenerative phenotype in addition to promoting OPC maturation and differentiation during demyelination and remyelination.

The Structural Response of the Human Head to a Vertex Impact.

In experimental models of cervical spine trauma caused by near-vertex head-first impact, a surrogate headform may be substituted for the cadaveric head. To inform headform design and to verify that such substitution is valid, the force-deformation response of the human head with boundary conditions relevant to cervical spine head-first impact models is required. There are currently no biomechanics data that characterize the force-deformation response of the isolated head supported at the occiput and compressed at the vertex by a flat impactor. The effect of impact velocity (1, 2 or 3 m/s) on the response of human heads (N = 22) subjected to vertex impacts, while supported by a rigid occipital mount, was investigated. 1 and 2 m/s impacts elicited force-deformation responses with two linear regions, while 3 m/s impacts resulted in a single linear region and skull base ring fractures. Peak force and stiffness increased from 1 to 2 and 3 m/s. Deformation at peak force and absorbed energy increased from 1 to 2 m/s, but decreased from 2 to 3 m/s. The data reported herein enhances the limited knowledge on the human head's response to a vertex impact, which may allow for validation of surrogate head models in this loading scenario.

Common sleep disorders in pregnancy: a review.

In this review, we provide a comprehensive overview of common sleep disorders during pregnancy, including their characterization, prevalence, risk factors, and possible contribution to maternal and fetal outcomes. We conducted a quasi-systematic literature search of the MEDLINE database and identified 744 studies from 1991 through 2021, inclusive, that met our inclusion criteria. We synthesized the existing literature on sleep disorders during pregnancy and highlighted controversies, research gaps, and needed clinical developments. Our review covers a range of sleep disorders, including insomnia, obstructive sleep apnea, restless legs syndrome, and circadian rhythm disorders. We discuss the prevalence of these disorders in pregnancy and their potential impact on maternal and fetal health outcomes. We also explore the relationship between sleep disorders, pre-pregnancy comorbidities such as obesity, and pregnancy-related conditions such as gestational diabetes mellitus and preeclampsia. In addition to summarizing the existing literature on sleep disorders during pregnancy, we also highlight opportunities for further research in this area. We suggest that future studies should strive to employ validated and objective measurement tools for sleep disorders and prioritize utilization of longitudinal methods with participant follow-up through postpartum, mid-life, menopause, and beyond. We also put forward investigation into the impact of circadian rhythm disruption on reproductive physiology and early pregnancy outcomes as an area of important work. Overall, our review provides valuable insights on sleep and reproduction and into common sleep disorders during pregnancy and their potential impact on maternal and fetal health outcomes.

Early transcriptional responses to human enteric fever challenge.

Enteric fever, caused by oral infection with typhoidal Salmonella serovars, presents as a non-specific febrile illness preceded by an incubation period of 5 days or more. The enteric fever human challenge model provides a unique opportunity to investigate the innate immune response during this incubation period, and how this response is altered by vaccination with the Vi polysaccharide or conjugate vaccine. We find that on the same day as ingestion of typhoidal Salmonella, there is already evidence of an immune response, with 199 genes upregulated in the peripheral blood transcriptome 12 hours post-challenge (false discovery rate <0.05). Gene sets relating to neutrophils, monocytes, and innate immunity were over-represented (false discovery rate <0.05). Estimating cell proportions from gene expression data suggested a possible increase in activated monocytes 12 hours post-challenge (P = 0.036, paired Wilcoxon signed-rank test). Furthermore, plasma TNF-α rose following exposure (P = 0.011, paired Wilcoxon signed-rank test). There were no significant differences in gene expression (false discovery rate <0.05) in the 12 hours response between those who did and did not subsequently develop clinical or blood culture confirmed enteric fever or between vaccination groups. Together, these results demonstrate early perturbation of the peripheral blood transcriptome after enteric fever challenge and provide initial insight into early mechanisms of protection.