Multi-scale cortical bone traits vary in females and males from two mouse models of genetic diversity.

Understanding the genetic basis of cortical bone traits can allow for the discovery of novel genes or biological pathways regulating bone health. Mice are the most widely used mammalian model for skeletal biology and allow for the quantification of traits that cannot easily be evaluated in humans, such as osteocyte lacunar morphology. The goal of our study was to investigate the effect of genetic diversity on multi-scale cortical bone traits of 3 long bones in skeletally-mature mice. We measured bone morphology, mechanical properties, material properties, lacunar morphology, and mineral composition of mouse bones from 2 populations of genetic diversity. Additionally, we compared how intrabone relationships varied in the 2 populations. Our first population of genetic diversity included 72 females and 72 males from the 8 inbred founder strains used to create the Diversity Outbred (DO) population. These 8 strains together span almost 90% of the genetic diversity found in mice (Mus musculus). Our second population of genetic diversity included 25 genetically unique, outbred females and 25 males from the DO population. We show that multi-scale cortical bone traits vary significantly with genetic background; heritability values range from 21% to 99% indicating genetic control of bone traits across length scales. We show for the first time that lacunar shape and number are highly heritable. Comparing the 2 populations of genetic diversity, we show that each DO mouse does not resemble a single inbred founder, but instead the outbred mice display hybrid phenotypes with the elimination of extreme values. Additionally, intrabone relationships (eg, ultimate force vs. cortical area) were mainly conserved in our 2 populations. Overall, this work supports future use of these genetically diverse populations to discover novel genes contributing to cortical bone traits, especially at the lacunar length scale.

Rapidly improving ARDS differs clinically and biologically from persistent ARDS.

BACKGROUND: Rapidly improving acute respiratory distress syndrome (RIARDS) is an increasingly appreciated subgroup of ARDS in which hypoxemia improves within 24 h after initiation of mechanical ventilation. Detailed clinical and biological features of RIARDS have not been clearly defined, and it is unknown whether RIARDS is associated with the hypoinflammatory or hyperinflammatory phenotype of ARDS. The purpose of this study was to define the clinical and biological features of RIARDS and its association with inflammatory subphenotypes. METHODS: We analyzed data from 215 patients who met Berlin criteria for ARDS (endotracheally intubated) and were enrolled in a prospective observational cohort conducted at two sites, one tertiary care center and one urban safety net hospital. RIARDS was defined according to previous studies as improvement of hypoxemia defined as (i) PaO2:FiO2 > 300 or (ii) SpO2: FiO2 > 315 on the day following diagnosis of ARDS (day 2) or (iii) unassisted breathing by day 2 and for the next 48 h (defined as absence of endotracheal intubation on day 2 through day 4). Plasma biomarkers were measured on samples collected on the day of study enrollment, and ARDS phenotypes were allocated as previously described. RESULTS: RIARDS accounted for 21% of all ARDS participants. Patients with RIARDS had better clinical outcomes compared to those with persistent ARDS, with lower hospital mortality (13% vs. 57%; p value < 0.001) and more ICU-free days (median 24 vs. 0; p value < 0.001). Plasma levels of interleukin-6, interleukin-8, and plasminogen activator inhibitor-1 were significantly lower among patients with RIARDS. The hypoinflammatory phenotype of ARDS was more common among patients with RIARDS (78% vs. 51% in persistent ARDS; p value = 0.001). CONCLUSIONS: This study identifies a high prevalence of RIARDS in a multicenter observational cohort and confirms the more benign clinical course of these patients. We report the novel finding that RIARDS is characterized by lower concentrations of plasma biomarkers of inflammation compared to persistent ARDS, and that hypoinflammatory ARDS is more prevalent among patients with RIARDS. Identification and exclusion of RIARDS could potentially improve prognostic and predictive enrichment in clinical trials.

Symptom-based staging for logopenic variant primary progressive aphasia.

BACKGROUND AND PURPOSE: Logopenic variant primary progressive aphasia (lvPPA) is a major variant presentation of Alzheimer's disease (AD) that signals the importance of communication dysfunction across AD phenotypes. A clinical staging system is lacking for the evolution of AD-associated communication difficulties that could guide diagnosis and care planning. Our aim was to create a symptom-based staging scheme for lvPPA, identifying functional milestones relevant to the broader AD spectrum. METHODS: An international lvPPA caregiver cohort was surveyed on symptom development under an 'exploratory' survey (34 UK caregivers). Feedback from this survey informed the development of a 'consolidation' survey (27 UK, 10 Australian caregivers) in which caregivers were presented with six provisional clinical stages and feedback was analysed using a mixed-methods approach. RESULTS: Six clinical stages were endorsed. Early symptoms included word-finding difficulty, with loss of message comprehension and speech intelligibility signalling later-stage progression. Additionally, problems with hearing in noise, memory and route-finding were prominent early non-verbal symptoms. 'Milestone' symptoms were identified that anticipate daily-life functional transitions and care needs. CONCLUSIONS: This work introduces a new symptom-based staging scheme for lvPPA, and highlights milestone symptoms that could inform future clinical scales for anticipating and managing communication dysfunction across the AD spectrum.

Simultaneous detection of pathogens and antimicrobial resistance genes with the open source, cloud-based, CZ ID pipeline.

Antimicrobial resistant (AMR) pathogens represent urgent threats to human health, and their surveillance is of paramount importance. Metagenomic next generation sequencing (mNGS) has revolutionized such efforts, but remains challenging due to the lack of open-access bioinformatics tools capable of simultaneously analyzing both microbial and AMR gene sequences. To address this need, we developed the Chan Zuckerberg ID (CZ ID) AMR module, an open-access, cloud-based workflow designed to integrate detection of both microbes and AMR genes in mNGS and whole-genome sequencing (WGS) data. It leverages the Comprehensive Antibiotic Resistance Database and associated Resistance Gene Identifier software, and works synergistically with the CZ ID short-read mNGS module to enable broad detection of both microbes and AMR genes. We highlight diverse applications of the AMR module through analysis of both publicly available and newly generated mNGS and WGS data from four clinical cohort studies and an environmental surveillance project. Through genomic investigations of bacterial sepsis and pneumonia cases, hospital outbreaks, and wastewater surveillance data, we gain a deeper understanding of infectious agents and their resistomes, highlighting the value of integrating microbial identification and AMR profiling for both research and public health. We leverage additional functionalities of the CZ ID mNGS platform to couple resistome profiling with the assessment of phylogenetic relationships between nosocomial pathogens, and further demonstrate the potential to capture the longitudinal dynamics of pathogen and AMR genes in hospital acquired bacterial infections. In sum, the new AMR module advances the capabilities of the open-access CZ ID microbial bioinformatics platform by integrating pathogen detection and AMR profiling from mNGS and WGS data. Its development represents a critical step toward democratizing pathogen genomic analysis and supporting collaborative efforts to combat the growing threat of AMR.

The National Institutes of Health Lasker Clinical Research Scholars Program: A Decade of Launching Clinician-Scientist Careers.

PURPOSE: In response to the decades-long decrease in U.S. clinician-scientists, the National Institutes of Health (NIH) and the Albert and Mary Lasker Foundation launched the Lasker Clinical Research Scholars Program in academic year 2011 to 2012. The investigators examined the early outcomes of this program. METHOD: Thirty-nine scholars have matriculated into the program as of May 2023. Productivity was assessed for all scholars who joined the program before October 2020 (n = 31). Extramural early-stage investigators (ESIs) were used as a control group, and coarsened exact matching was used to compare the groups. The scholars were compared with the matched ESIs on 4 productivity metrics: publication count, weighted relative citation ratio, clinical impact, and approximate potential to translate. Publication records for both groups were compiled using the NIH Office of Portfolio Analysis' name disambiguation method and manually curated to ensure integrity of the data set. RESULTS: Of the 39 scholars, 29 were compared with 121 matched extramural ESIs. Five years before matriculation, the 2 groups had comparable numbers of publications, but scholars had a higher median weighted relative citation ratio, clinical impact, and approximate potential to translate score. Five years after matriculation, the scholars had a higher median number of publications than the ESIs, and the gap between scholars and ESIs, with scholars having higher scores, had widened for all metrics except approximate potential to translate scores. Of 10 of the 39 scholars at or approaching tenure eligibility, 6 have attained tenure (3 at NIH and 3 in academic institutions), and 4 are on track to attain tenure at NIH. CONCLUSIONS: All the Lasker clinical research scholars are substantially involved in clinical and translational research. Their productivity matches or exceeds that of a matched cohort of ESIs at U.S. academic institutions.

Host-microbe multiomic profiling reveals age-dependent immune dysregulation associated with COVID-19 immunopathology.

Age is a major risk factor for severe coronavirus disease 2019 (COVID-19), yet the mechanisms behind this relationship have remained incompletely understood. To address this, we evaluated the impact of aging on host immune response in the blood and the upper airway, as well as the nasal microbiome in a prospective, multicenter cohort of 1031 vaccine-naïve patients hospitalized for COVID-19 between 18 and 96 years old. We performed mass cytometry, serum protein profiling, anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody assays, and blood and nasal transcriptomics. We found that older age correlated with increased SARS-CoV-2 viral abundance upon hospital admission, delayed viral clearance, and increased type I interferon gene expression in both the blood and upper airway. We also observed age-dependent up-regulation of innate immune signaling pathways and down-regulation of adaptive immune signaling pathways. Older adults had lower naïve T and B cell populations and higher monocyte populations. Over time, older adults demonstrated a sustained induction of pro-inflammatory genes and serum chemokines compared with younger individuals, suggesting an age-dependent impairment in inflammation resolution. Transcriptional and protein biomarkers of disease severity differed with age, with the oldest adults exhibiting greater expression of pro-inflammatory genes and proteins in severe disease. Together, our study finds that aging is associated with impaired viral clearance, dysregulated immune signaling, and persistent and potentially pathologic activation of pro-inflammatory genes and proteins.

Otolaryngology residency program factors associated with female resident representation.

Objective: Female representation in the field of otolaryngology is lacking. Residency is the first point at which medical school graduates specialize in a chosen field and thus represents an opportunity to recruit and train more female otolaryngologists. This study sought to identify program factors associated with greater female representation among resident physicians. Methods: Departmental websites of all 124 otolaryngology residency programs in the United States and Puerto Rico were examined for a list of residents. For programs with a resident roster available, the genders of residents, faculty, program directors, and chairpersons were recorded. Location and city population for each program was also recorded, as was female resident representation. Programs were compared using Pearson Chi-squared univariate tests. Results: 1,632 residents and 2,605 faculty were included in the analysis of 109 programs. The median female resident representation was 40%. Programs with larger faculty sizes, more female faculty, and urban location were associated with an above-median female resident representation. Programs with a larger residency cohort approached significance regarding above-median female resident representation. Higher female faculty representation, program director gender, chairperson gender, and US region were not associated with variation in female resident representation. Conclusions: Greater female otolaryngology residency representation was associated with programs having an urban location and greater numbers of female and total faculty. It was also likely that a larger resident cohort size may affect female resident representation. The proportions of female faculty, program director, and chairperson gender, as well as the US region, were not associated with variation in female resident gender representation.

Clumped isotopes reveal relationship between mussel growth and river discharge.

Freshwater mussels preserve valuable information about hydrology, climate, and population dynamics, but developing seasonal chronologies can be problematic. Using clumped isotope thermometry, we produced high-resolution reconstructions of modern and historic (~ 1900) temperatures and δ18Owater from mussel shells collected from an impounded river, the Brazos in Texas, before and after damming. We also performed high-resolution growth band analyses to investigate relationships between mussel growth rate, rainfall, and seasonal temperature. Reconstructed δ18Owater and temperature vary little between the modern (3R5) and historic shell (H3R). However, a positive relationship between reconstructed δ18Owater and growth rate in H3R indicates that aside from diminished growth in winter, precipitation and flow rate are the strongest controls on mussel growth in both modern and pre-dam times. Overall, our results demonstrate (1) the impact, both positive and negative, of environmental factors such as flow alteration and temperature on mussel growth and (2) the potential for clumped isotopes in freshwater mussels as a paleohydrology and paleoclimate proxies in terrestrial environments.

Shoulder Hemiarthroplasty Is Associated With Higher 30-Day Complication Rates Compared With Total Shoulder Arthroplasty for Glenohumeral Osteoarthritis: A Propensity Score Matched Analysis.

BACKGROUND: Anatomical total shoulder arthroplasty (TSA) and shoulder hemiarthroplasty (HA) have both been shown to have good outcomes in patients with osteoarthritis of the glenohumeral joint. However, evidence comparing perioperative complications between these procedures in this population is heterogeneous. MATERIALS AND METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried between the years 2012 and 2021 (10 years in total) for records of patients who underwent either TSA or HA for osteoarthritis of the glenohumeral joint. Patients in each group underwent a 1:1 propensity match for demographic variables. Bivariate and multivariate analyses were performed to compare complications and risk factors between these cohorts. RESULTS: A total of 4376 propensity-matched patients, with 2188 receiving TSA and 2188 receiving HA, were included in the primary analyses. The HA cohort had a higher rate of any adverse event (7.18% vs 4.8%, P=.001), death (0.69% vs 0.1%, P=.004), sepsis (0.46% vs 0.1%, P=.043), postoperative transfusion (4.62% vs 2.2%, P<.001), postoperative intubation (0.5% vs 0.1%, P=.026), and extended length of stay (23.77% vs 13.1%, P<.001). HA was found to increase the odds of developing these complications when baseline demographics were controlled. Older age (odds ratio, 1.040; 95% CI, 1.021-1.059; P<.001) and lower body mass index (odds ratio, 0.949; 95% CI, 0.923-0.975; P<.001) increased the odds of having any adverse event in the HA cohort but not in the TSA cohort. CONCLUSION: Compared with TSA, HA appears to be associated with significantly higher rates of 30-day postoperative complications when performed for glenohumeral osteoarthritis. [Orthopedics. 202x;4x(x):xx-xx.].

Neuroanatomical and prognostic associations of depression in Parkinson's disease.

BACKGROUND: Depression is reported as a risk factor, prodromal feature and late consequence of Parkinson's disease (PD). We aimed to evaluate the timing, neuroanatomy and prognostic implications of depression in PD. METHODS: We used data from 434 023 participants from UK Biobank with 14.1 years of follow-up. Multivariable regression models established associations of depression with incident PD and regional brain volumes. Cox proportional hazards models assessed prognostic associations of depression in PD with incident dementia and all-cause mortality. RESULTS: Of 2632 individuals with incident PD, 539 (20.5%) were diagnosed with depression at some point. Depression was associated with an increased risk of subsequent PD (risk ratio 1.53, 95% CI 1.37 to 1.72). Among incident PD cases, depression prevalence rose progressively from 10 years pre-PD diagnosis (OR 2.10, 95% CI 1.57 to 2.83) to 10 years postdiagnosis (OR 3.51, 95% CI 1.33 to 9.22). Depression severity in PD was associated with reduced grey matter volume in structures including the thalamus and amygdala. Depression prior to PD diagnosis increased risk of dementia (HR 1.47, 95% CI 1.05 to 2.07) and mortality (HR 1.30, 95% CI 1.07 to 1.58). CONCLUSIONS: This large-scale prospective study demonstrated that depression prevalence increases from 10 years before PD diagnosis and is a marker of cortical and subcortical volume loss. Depression before PD diagnosis signals a worse prognosis in terms of dementia and mortality. This has clinical implications in stratifying people with poorer cognitive and prognostic trajectory in PD.

A case report and anesthetic implications of situs inversus totalis in video-assisted thoracoscopic pulmonary resection.

Introduction and importance: Reports are limited on video-assisted thoracoscopic surgery for lung malignancy of patients with situs inversus totalis (SIT). Patients with SIT have significant anatomic differences with implications that are important for surgery, anesthesia, and nursing to understand in order to provide care for this patient population. Case presentation: A 64-year-old man with SIT and lung adenocarcinoma needed flexible bronchoscopy and wedge resection of a 9×8 mm adenocarcinoma in the right upper lobe and underwent video-assisted thoracoscopic surgery. Clinical discussion: Preoperative planning, including collaboration with the surgical team, allowed safe monitoring, induction of anesthesia, and airway isolation in this patient allowing them to have successful resection of their pulmonary malignancy. Postoperative care was enhanced by detailed communication and understanding of the patient's anatomy and implications of this condition for post anesthesia care unit nursing care. Conclusion: Patients with rare clinical conditions and backgrounds may require surgical and anesthetic intervention. The authors describe important anesthetic considerations of preoperative evaluation, airway management, cardiac monitoring, and vascular access that should be noted and taken into account for patients with SIT. Proper preparation, planning, and communication allow for patients with SIT to safely undergo surgical procedures.

Patient reported outcome measures (PROMs) as primary and secondary outcomes in total hip and knee arthroplasty randomized controlled trials: a systematic review.

BACKGROUND: Significant heterogeneity exists regarding patient reported outcome measures (PROMs) used in total hip (THA) and knee (TKA) arthroplasty randomized controlled trials (RCTs). This study investigates the PROMs used as primary and secondary outcomes in contemporary arthroplasty RCTs. METHODS: A literature search identified THA and TKA RCTs that were published in top ten impact factor orthopaedic journals from 2017 to 2021. Screening identified 241 trials: 76 THA, 157 TKA, and eight combined. Data were extracted to identify PROMs utilized as either primary or secondary outcomes and the time period of measurement. RESULTS: Visual Analog Scale (VAS) Pain was the most reported primary PROM in THA (9.2%) and TKA (22.9%) trials. This was followed by Numeric Rating Scale (NRS) Pain (7.9%) and the Harris Hip score (6.6%) in THA trials and NRS Pain (4.5%) and the Knee Society score (4.5%) in TKA trials. Many THA (37.0%) and TKA (52.1%) trials did not clearly specify primary outcome time points. Only pain scales were reported at time points less than one week, while various joint-specific functional outcomes were reported at later time points. As secondary outcomes, the Harris Hip score (28.9%) was most common in THA trials and the Knee Society score (26.1%) was most common in TKA trials. Indeterminate primary or secondary outcomes were reported in 18.2% of studies. CONCLUSIONS: Contemporary THA and TKA trials exhibit heterogeneity of PROMs as study outcomes after the first postoperative week. Our findings highlight the need for consensus in PROM reporting and better methodological reporting to improve the interpretability of RCT outcomes. PROSPERO REGISTRATION NUMBER: CRD42022337255.

Classifying contaminated cell cultures using time series features.

We examine the use of time series data, derived from Electric Cell-substrate Impedance Sensing (ECIS), to differentiate between standard mammalian cell cultures and those infected with a mycoplasma organism. With the goal of easy visualization and interpretation, we perform low-dimensional feature-based classification, extracting application-relevant features from the ECIS time courses. We can achieve very high classification accuracy using only two features, which depend on the cell line under examination. Initial results also show the existence of experimental variation between plates and suggest types of features that may prove more robust to such variation. Our paper is the first to perform a broad examination of ECIS time course features in the context of detecting contamination; to combine different types of features to achieve classification accuracy while preserving interpretability; and to describe and suggest possibilities for ameliorating plate-to-plate variation.

Genotype-by-environment interactions and local adaptation shape selection in the US National Chip Processing Trial.

KEY MESSAGE: We find evidence of selection for local adaptation and extensive genotype-by-environment interaction in the potato National Chip Processing Trial (NCPT). We present a novel method for dissecting the interplay between selection, local adaptation and environmental response in plant breeding schemes. Balancing local adaptation and the desire for widely adapted cultivars is challenging for plant breeders and makes genotype-by-environment interactions (GxE) an important target of selection. Selecting for GxE requires plant breeders to evaluate plants across multiple environments. One way breeders have accomplished this is to test advanced materials across many locations. Public potato breeders test advanced breeding material in the National Chip Processing Trial (NCPT), a public-private partnership where breeders from ten institutions submit advanced chip lines to be evaluated in up to ten locations across the country. These clones are genotyped and phenotyped for important agronomic traits. We used these data to interrogate the NCPT for GxE. Further, because breeders submitting clones to the NCPT select in a relatively small geographic range for the first 3 years of selection, we examined these data for evidence of incidental selection for local adaptation, and the alleles underlying it, using an environmental genome-wide association study (envGWAS). We found genomic regions associated with continuous environmental variables and discrete breeding programs, as well as regions of the genome potentially underlying GxE for yield.

Genetic analysis of Octopus cyanea reveals high gene flow in the South-West Indian Ocean.

Octopus cyanea (Gray, 1849), abundant in the South-West Indian Ocean (SWIO), constitutes a vital resource for both subsistence and commercial fisheries. However, despite this socioeconomic importance, and recent indications of overfishing, little is known about the population structure of O. cyanea in the region. To inform sustainable management strategies, this study assessed the spatio-temporal population structure and genetic variability of O. cyanea at 20 sites in the SWIO (Kenya, Tanzania, Mozambique, Madagascar, Mauritius, Rodrigues, and the Seychelle Islands) by complementary analysis of mitochondrial DNA (mtDNA) noncoding region (NCR) sequences and microsatellite markers. MtDNA analysis revealed a shallow phylogeny across the region, with demographic tests suggesting historic population fluctuations that could be linked to glacial cycles. Contrary to expectations, NCR variation was comparable to other mtDNA regions, indicating that the NCR is not a hypervariable region. Both nuclear and mtDNA marker types revealed a lack of genetic structure compatible with high gene flow throughout the region. As adults are sedentary, this gene flow likely reflects connectivity by paralarval dispersal. All samples reported heterozygote deficits, which, given the overall absence of structure, likely reflect ephemeral larval recruitment variability. Levels of mtDNA and nuclear variability were similar at all locations and congruent with those previously reported for harvested Octopodidae, implying resilience to genetic erosion by drift, providing current stock sizes are maintained. However, as O. cyanea stocks in the SWIO represent a single, highly connected population, fisheries may benefit from additional management measures, such as rotational closures aligned with paralarval ecology and spanning geopolitical boundaries.

Exercise-induced ß2-adrenergic receptor activation enhances the anti-leukemic activity of expanded γδ T-Cells via DNAM-1 upregulation and PVR/Nectin-2 recognition.

Exercise mobilizes cytotoxic lymphocytes to blood which may allow superior cell products to be manufactured for cancer therapy. Gamma-Delta (γδ) T-cells have shown promise for treating solid tumors, but there is a need to increase their potency against hematologic malignancies. Here, we show that human γδ T-cells mobilized to blood in response to just 20-minutes of graded exercise have surface phenotypes and transcriptomic profiles associated with cytotoxicity, adhesion, migration and cytokine signaling. Following 14-days ex vivo expansion with zoledronic acid and interleukin (IL)-2, exercise mobilized γδ T-cells had surface phenotypes and transcriptomic profiles associated with enhanced effector functions, and demonstrated superior cytotoxic activity against multiple hematologic tumors in vitro, and in vivo in leukemia bearing xenogeneic mice. Infusing humans with the ß1+ß2-agonist isoproterenol and administering ß1 or ß1+ß2 antagonists prior to exercise revealed these effects to be ß2-adrenergic receptor (AR) dependent. Antibody blocking of DNAM-1 on expanded γδ T-cells, as well as the DNAM-1 ligands PVR and Nectin-2 on leukemic targets, abolished the enhanced anti-leukemic effects of exercise. These findings provide a mechanistic link between exercise, ß2-AR activation, and the manufacture of superior γδ T-cell products for adoptive cell therapy against hematological malignancies.

Improving Students Access to Primary Health Care Through School-Based Health Centers.

BACKGROUND: More than 20 million children in the United States lack access to primary health care. PRACTICE LEARNING: Research shows that students with regular access to physical and mental health services have fewer absences, are more social, less likely to participate in risky behaviors, have improved focus and higher test scores. IMPLICATION FOR SCHOOL HEALTH POLICY, PRACTICE, AND EQUITY: School-based health centers (SBHCs) can be an important, valuable and viable health care delivery option to meet the full-range of primary health care needs of students where they spend the majority of their wake hours, ie, in school. Children in rural and other underserved communities, as well as those underinsured, non-insured, economically challenged, underserved, and the most vulnerable among us are especially at risk. CONCLUSIONS: This paper discusses the history, value, and importance of SBHCs from myriad perspectives, including physical and emotional wellbeing, academic and social success, and the promotion of a positive transition to adulthood. In addition, the authors' experiences that resulted in building the first SBHC in the Mid-Hudson Valley Region of New York State are shared. These experiences form the foundation for creating an important roadmap for individuals and school leaders that are interested in bringing a SBHC to their school and district.

Vaccine Elicited Antibodies Restrict Glucose Availability to Control Brucella Infection.

The impact of vaccine-induced immune responses on host metabolite availability has not been well studied. Here we show prior vaccination alters the metabolic profile of mice challenged with Brucella melitensis. In particular, glucose levels were reduced in vaccinated mice in an antibody-dependent manner. We also found the glucose transporter gene, gluP, plays a lesser role in B. melitensis virulence in vaccinated wild-type mice relative to vaccinated mice unable to secrete antibodies. These data indicate vaccine-elicited antibodies protect the host in part by restricting glucose availability. Moreover, Brucella and other pathogens may need to employ different metabolic strategies in vaccinated hosts.