Spinal Cord Stimulator Inequities Within the US Military Health System.

OBJECTIVES: Although studies have described inequities in spinal cord stimulation (SCS) receipt, there is a lack of information to inform system-level changes to support health care equity. This study evaluated whether Black patients exhaust more treatment options than do White patients, before receiving SCS. MATERIALS AND METHODS: This retrospective cohort study included claims data of Black and non-Latinx White patients who were active-duty service members or military retirees who received a persistent spinal pain syndrome (PSPS) diagnosis associated with back surgery within the US Military Health System, January 2017 to January 2020 (N = 8753). A generalized linear model examined predictors of SCS receipt within two years of diagnosis, including the interaction between race and number of pain-treatment types received. RESULTS: In the generalized linear model, Black patients (10.3% [8.7%, 12.0%]) were less likely to receive SCS than were White patients (13.6% [12.7%, 14.6%]) The interaction term was significant; White patients who received zero to three different types of treatments were more likely to receive SCS than were Black patients who received zero to three treatments, whereas Black and White patients who received >three treatments had similar likelihoods of receiving a SCS. CONCLUSIONS: In a health care system with intended universal access, White patients diagnosed with PSPS tried fewer treatment types before receiving SCS, whereas the number of treatment types tried was not significantly related to SCS receipt in Black patients. Overall, Black patients received SCS less often than did White patients. Findings indicate the need for structured referral pathways, provider evaluation on equity metrics, and top-down support.

Biliary Dyskinesia-Controversies, Diagnosis, and Management: A Review.

Importance: Biliary dyskinesia is a disorder characterized by biliary pain, a sonographically normal gallbladder, and a reduced gallbladder ejection fraction on cholecystokinin-cholescintigraphy (CCK-HIDA) scan. Laparoscopic cholecystectomy remains a common treatment for biliary dyskinesia despite a lack of high-quality evidence supporting the practice. The following review summarizes the current biliary dyskinesia outcomes data, the diagnostic strategies and their limitations, biliary dyskinesia in the pediatric population, the emerging phenomenon of the hyperkinetic gallbladder, and suggestions for addressing identified knowledge gaps. Observations: The majority of studies on the topic are retrospective, with wide variations in inclusion criteria and definition of biliary pain. Most report a very short follow-up interval, often a single office visit, with variable and nonstandardized definitions of a satisfactory outcome. Despite a published Society of Nuclear Medicine guideline for its performance, CCK-HIDA scan protocols vary among institutions, which has led to considerable variability in the consistency and reproducibility of CCK-HIDA results. The few prospective studies available, although small and heterogeneous, support a role for cholecystectomy in the treatment of adult biliary dyskinesia. Despite these knowledge gaps, biliary dyskinesia is now the number 1 indication for cholecystectomy in children. Cholecystectomy for the hyperkinetic gallbladder appears to be an emerging phenomenon, despite, as in biliary dyskinesia, a lack of quality data supporting this practice. Randomized trials addressing these gaps are needed but have been difficult to conduct owing to strong clinician and patient bias toward surgery and the lack of a criterion-standard nonsurgical treatment for the control arm. Conclusions and Relevance: The use of cholecystectomy for adult biliary dyskinesia is reasonable based on the available data. Insufficient data exist regarding laparoscopic cholecystectomy for pediatric dyskinesia and the hyperkinetic gallbladder population. Large-scale prospective studies, either randomized trials or large prospectively followed cohort studies, are needed to address the knowledge gaps surrounding this controversial diagnosis.

Popularizing Surgical Cures: Walter Dandy and the Vestibular Neurectomy for Menière's Disease at the Johns Hopkins Hospital.

OBJECTIVES: To uncover the context that allowed for the vestibular neurectomy to grow in favor and practice at the Johns Hopkins Hospital in the early 20th century, and the reasons for its broad abandonment since. METHODS: The Walter E. Dandy (1905-1946) and Samuel J. Crowe collections (1905-1920) at the Alan Mason Chesney Medical Archives were reviewed, as well as the Samuel J. Crowe and Stacy Guild Temporal Bone Collection. RESULTS: Speculation on the etiology of Menière's disease (MD) has been countless, as have the medical and surgical interventions aimed at treating it. At the Johns Hopkins Hospital, Walter Dandy popularized the neurectomy for MD and performed 692 procedures from 1924 to 1946, believing it to be a curative therapy for vertigo. When he later modified the procedure from a total cranial nerve section to a partial vestibular neurectomy preserving auditory function, surgical candidacy expanded to include nearly any patient with vestibular symptoms. After his passing, trainees' attention shifted to traumatic injuries, likely influenced by WWII. This left the procedure scarcely used until third parties rekindled interest decades later. CONCLUSIONS: Neurectomy as the preferential treatment for MD at the Johns Hopkins Hospital was not driven by pure scientific reasoning but was rather contingent on historical context and sponsorship by a prominent figure like Walter Dandy. Appreciation of MD's natural history has since curtailed the favorability of destructive procedures in preference for conservative management.

Cauldrons of Bronze Age nomads reveals 2700 year old yak milk and the deep antiquity of food preparation techniques.

Cauldrons, vessels that are simultaneously common and enigmatic, offer insights into past cultural and social traditions. While assumed to possess a special function, what these cauldrons contained is still largely mysterious. These vessels, such as those made from bronze or copper alloys, function as reservoirs for ancient organics through the antibacterial qualities provided by the metal surfaces. Here we show, through protein analysis, that cauldrons from the Final Bronze Age (ca. 2700 BP) were primarily used to collect blood from ruminants, primarily caprines, likely for the production of sausages in a manner similar to contemporary practices in Mongolia's rural countryside. Our findings present a different function from the recent findings of cooked meat in copper-alloy vessels from the northern Caucasus 2000 years earlier, exposing the diversity in food preparation techniques. Our secondary findings of bovine milk within the cauldron, including peptides specific to Bos mutus, pushes back their regional domestication into the Bronze Age.

The impact of abstinence from chronic alcohol consumption on the mouse striatal proteome: sex and subregion-specific differences.

Alcohol misuse is the third leading preventable cause of death in the world. The World Health Organization currently estimates that 1 in 20 deaths are directly alcohol related. One of the ways in which consuming excessive levels of alcohol can both directly and indirectly affect human mortality and morbidity, is through chronic inflammation. Recently, studies have suggested a link between increased alcohol use and the incidence of neuroinflammatory-related diseases. However, the mechanism in which alcohol potentially influences neuroinflammatory processes is still being uncovered. We implemented an unbiased proteomics exploration of alcohol-induced changes in the striatum, with a specific emphasis on proteins related to inflammation. The striatum is a brain region that is critically involved with the progression of alcohol use disorder. Using mass spectrometry following voluntary alcohol self-administration in mice, we show that distinct protein abundances and signaling pathways in different subregions of the striatum are disrupted by chronic exposure to alcohol compared to water drinking control mice. Further, in mice that were allowed to experience abstinence from alcohol compared to mice that were non-abstinent, the overall proteome and signaling pathways showed additional differences, suggesting that the responses evoked by chronic alcohol exposure are dependent on alcohol use history. To our surprise we did not find that chronic alcohol drinking or abstinence altered protein abundance or pathways associated with inflammation, but rather affected proteins and pathways associated with neurodegeneration and metabolic, cellular organization, protein translation, and molecular transport processes. These outcomes suggest that in this drinking model, alcohol-induced neuroinflammation in the striatum is not a primary outcome controlling altered neurobehavioral function, but these changes are rather mediated by altered striatal neuronal structure and cellular health.

Alzheimer Disease Cerebrospinal Fluid Biomarkers in a Tertiary Neurology Practice.

OBJECTIVE: To evaluate the performance of Alzheimer disease (AD) cerebrospinal fluid (CSF) biomarkers in a tertiary neurology clinic setting with high frequency of non-AD cases, including normal pressure hydrocephalus (NPH). METHODS: There were 534 patients who underwent AD CSF biomarkers (Roche Elecsys Aß42, p-Tau181, total-Tau) from April 1, 2020, through April 23, 2021. A behavioral neurologist blinded to CSF results assigned a clinical diagnosis retrospectively on the basis of consensus criteria, and a neuroradiologist blinded to the diagnosis and CSF studies graded brain magnetic resonance images for indicators of CSF dynamics disorders. Associations between biomarkers, diagnoses, and imaging were assessed by χ2, analysis of covariance, and linear regression methods. RESULTS: Median age at time of testing was 67 years (range, 19 to 96 years), median symptom duration was 2 years (range, 0.4 to 28 years), and median Short Test of Mental Status score was 30 (range, 0 to 38). Clinical diagnoses significantly correlated with different CSF biomarker values (χ2=208.3; P=10e-4). p-Tau181/Aß42 ratios above 0.023 positively correlated with Alzheimer dementia (more than individual measures). This ratio also had the best performance for differentiating Alzheimer dementia from NPH (area under the curve, 0.869). Imaging markers supportive of CSF dynamics disorders correlated with low Aß42, p-Tau181, and total-Tau. CONCLUSION: In a heterogeneous clinical population, abnormal p-Tau181/Aß42 ratios (>0.023) have the strongest association with Alzheimer dementia and probably represent a comorbid AD pathologic component in persons clearly matching non-AD neurodegenerative syndromes. Altered CSF dynamics were associated with lower concentrations of AD CSF biomarkers regardless of clinical diagnosis, but the ratio compensates for these changes. In the appropriate clinical setting, an isolated abnormal Aß42 should prompt consideration of NPH.

The Growth of Complex Syntax in School-Age African American Children Who Speak African American English.

PURPOSE: Syntax provides critical support for both academic success and linguistic growth, yet it has not been a focus of language research in school-age African American children. This study examines complex syntax performance of African American children in second through fifth grades. METHOD: The current study explores the syntactic performances of African American children (N = 513) in Grades 2-5 on the Test of Language Development-Intermediate who speak African American English. Multilevel modeling was used to evaluate the growth and associated changes between dialect density and syntax. Analyzed data were compared both to the normative sample and within the recruited sample. RESULTS: The results suggest that dialect density exerted its impact early but did not continue to influence syntactic growth over time. Additionally, it was not until dialect density was accounted for in growth models that African American children's syntactic growth resembled normative expectations of a standardized language instrument. CONCLUSION: The current study suggests that failure to consider cultural language differences obscures our understanding of African American students' linguistic competence on standardized language assessments.

Phase I trial of single-photon emission computed tomography-guided liver-directed radiotherapy for patients with low functional liver volume.

BACKGROUND: Traditional constraints specify that 700 cc of liver should be spared a hepatotoxic dose when delivering liver-directed radiotherapy to reduce the risk of inducing liver failure. We investigated the role of single-photon emission computed tomography (SPECT) to identify and preferentially avoid functional liver during liver-directed radiation treatment planning in patients with preserved liver function but limited functional liver volume after receiving prior hepatotoxic chemotherapy or surgical resection. METHODS: This phase I trial with a 3 + 3 design evaluated the safety of liver-directed radiotherapy using escalating functional liver radiation dose constraints in patients with liver metastases. Dose-limiting toxicities were assessed 6-8 weeks and 6 months after completing radiotherapy. RESULTS: All 12 patients had colorectal liver metastases and received prior hepatotoxic chemotherapy; 8 patients underwent prior liver resection. Median computed tomography anatomical nontumor liver volume was 1584 cc (range = 764-2699 cc). Median SPECT functional liver volume was 1117 cc (range = 570-1928 cc). Median nontarget computed tomography and SPECT liver volumes below the volumetric dose constraint were 997 cc (range = 544-1576 cc) and 684 cc (range = 429-1244 cc), respectively. The prescription dose was 67.5-75 Gy in 15 fractions or 75-100 Gy in 25 fractions. No dose-limiting toxicities were observed during follow-up. One-year in-field control was 57%. One-year overall survival was 73%. CONCLUSION: Liver-directed radiotherapy can be safely delivered to high doses when incorporating functional SPECT into the radiation treatment planning process, which may enable sparing of lower volumes of liver than traditionally accepted in patients with preserved liver function. TRIAL REGISTRATION: NCT02626312.

Parkinson's Disease Associated with G2019S LRRK2 Mutations without Lewy Body Pathology.

BACKGROUND: The G2019S leucine-rich repeat kinase 2 (LRRK2) gene mutation is an important and commonly found genetic determinant of Parkinson's disease (PD). The neuropathological findings associated with this mutation have thus far been varied but are most often associated with Lewy body (LB) pathology. OBJECTIVE: Describe a case of clinical Parkinson's disease with levodopa responsiveness found to have LRRK2 mutations and the absence of Lewy bodies. METHOD: We present an 89-year-old man with a 10-year history of slowly progressive parkinsonism suspected to be secondary to Parkinson's disease. RESULTS: Neuropathological evaluation revealed nigral degeneration without Lewy bodies or Lewy neurites, but there were frequent tau-immunopositive neurites and astrocytes in the putamen and substantia nigra, neocortical glial tau positive astrocytes associated with aging-related tau astrogliopathy (ARTAG), as well as neurofibrillary tangles, beta amyloid plaques, and amyloid angiopathy typical of advanced Alzheimer's disease. G2019S LRRK2 homozygous mutations were found. CONCLUSION: This case illustrates that levodopa-responsive clinical PD caused by G2019S LRRK2 mutations can occur without Lewy bodies.

SVPath: A Deep Learning Tool for Analysis of Stria Vascularis from Histology Slides.

INTRODUCTION: The stria vascularis (SV) may have a significant role in various otologic pathologies. Currently, researchers manually segment and analyze the stria vascularis to measure structural atrophy. Our group developed a tool, SVPath, that uses deep learning to extract and analyze the stria vascularis and its associated capillary bed from whole temporal bone histopathology slides (TBS). METHODS: This study used an internal dataset of 203 digitized hematoxylin and eosin-stained sections from a normal macaque ear and a separate external validation set of 10 sections from another normal macaque ear. SVPath employed deep learning methods YOLOv8 and nnUnet to detect and segment the SV features from TBS, respectively. The results from this process were analyzed with the SV Analysis Tool (SVAT) to measure SV capillaries and features related to SV morphology, including width, area, and cell count. Once the model was developed, both YOLOv8 and nnUnet were validated on external and internal datasets. RESULTS: YOLOv8 implementation achieved over 90% accuracy for cochlea and SV detection. nnUnet SV segmentation achieved a DICE score of 0.84-0.95; the capillary bed DICE score was 0.75-0.88. SVAT was applied to compare both the ears used in the study. There was no statistical difference in SV width, SV area, and average area of capillary between the two ears. There was a statistical difference between the two ears for the cell count per SV. CONCLUSION: The proposed method accurately and efficiently analyzes the SV from temporal histopathology bone slides, creating a platform for researchers to understand the function of the SV further.

Active Direction: A new observational measure of African American parenting.

A new observational measure of a culturally salient, supportive African American parenting style, Active Direction, was developed. Ratings were compared to standard qualitative ratings and across two ethnic groups. Active Direction represents the provision of structure to interactions in the form of corrective direction with clear and concise feedback that is assessed for supportiveness rather than simple content or tone. The 7-point rating item was examined in observations of African American (n = 172) and Hispanic American (n = 196) mother-child interactions collected at age 2.5 years in families from low-income households. Ratings were compared and associations to previously reported ratings of the interactions were examined. Active Direction was often observed among the African American mothers (81%) but rarely observed among the Hispanic mothers (16%), with a large effect size difference, supporting the hypothesis that Active Direction may represent a culturally specific approach to parenting for African American parents. Maternal behavior correlations of Active Direction with cognitive stimulation, intrusiveness, scaffolding, and calm authority and with child affiliative obedience and dyadic routines and rituals were significantly higher and detachment significantly lower in the African American compared to the Hispanic sample. The new measure of Active Direction, centered around culturally salient values and differences in both historical and lived experiences, addresses characteristics of parenting in African American families that are supportive of their children's development and provides a fruitful direction for future research.

Drivers and implications of alternative routes to fuels decarbonization in net-zero energy systems.

Energy transition scenarios are characterized by increasing electrification and improving efficiency of energy end uses, rapid decarbonization of the electric power sector, and deployment of carbon dioxide removal (CDR) technologies to offset remaining emissions. Although hydrocarbon fuels typically decline in such scenarios, significant volumes remain in many scenarios even at the time of net-zero emissions. While scenarios rely on different approaches for decarbonizing remaining fuels, the underlying drivers for these differences are unclear. Here we develop several illustrative net-zero systems in a simple structural energy model and show that, for a given set of final energy demands, assumptions about the use of biomass and CO2 sequestration drive key differences in how emissions from remaining fuels are mitigated. Limiting one resource may increase reliance on another, implying that decisions about using or restricting resources in pursuit of net-zero objectives could have significant tradeoffs that will need to be evaluated and managed.

Race/Ethnicity and Social Determinants of Health and Their Impact on Receiving Appropriate Chemotherapy for Colon Cancer.

INTRODUCTION: Despite the heightened understanding and improved treatment for colorectal cancer in the United States, social determinants of health (SDH) play a significant role in the colorectal cancer outcomes. We sought to investigate the relationship between SDH and appropriate utilization of adjuvant chemotherapy in stage III colon cancer. METHODS: For this retrospective study, we utilized data from the National Cancer Data Base (NCDB). Descriptive statistics are reported, including means and 95% confidence intervals for continuous variables and frequency and proportions for categorical variables. Univariate hypothesis testing to identify categorical level factors associated with treatment used Wilcoxon rank sum or Kruskal-Wallis tests, with multivariate analyses performed using regression analysis. RESULTS: Significant differences were as follows: Metro-non-Hispanic White patients received treatment less frequently (69.7%) when compared to Metro-non-Hispanic Black patients (73.4%) (P < .001). Increasing age was a negative predictor of likelihood to receive with those over 65 years old having an 83% decrease in likelihood to receive chemotherapy when compared to those under 65 (P < .001). Medicaid patients were 47% less likely and Medicare patients were 40% less likely to receive chemotherapy when compared to those with private insurance (P < .001). Rural patients were statistically more likely to receive chemotherapy (OR 1.42, 1.32-2.52, P < .001) as were urban patients, (OR 1.26, 1.20-1.31, P < .001) when compared to patients residing in metro areas. CONCLUSION: Age, living in a Metro area, and government insurance status at diagnosis are negatively correlated with the likelihood of receiving chemotherapy. Race was not associated with differences in receiving chemotherapy.

Putting theory to the test: An integrated computational/experimental chemostat model of the tragedy of the commons.

Cooperation via shared public goods is ubiquitous in nature, however, noncontributing social cheaters can exploit the public goods provided by cooperating individuals to gain a fitness advantage. Theory predicts that this dynamic can cause a Tragedy of the Commons, and in particular, a 'Collapsing' Tragedy defined as the extinction of the entire population if the public good is essential. However, there is little empirical evidence of the Collapsing Tragedy in evolutionary biology. Here, we experimentally demonstrate this outcome in a microbial model system, the public good-producing bacterium Pseudomonas aeruginosa grown in a continuous-culture chemostat. In a growth medium that requires extracellular protein digestion, we find that P. aeruginosa populations maintain a high density when entirely composed of cooperating, protease-producing cells but completely collapse when non-producing cheater cells are introduced. We formulate a mechanistic mathematical model that recapitulates experimental observations and suggests key parameters, such as the dilution rate and the cost of public good production, that define the stability of cooperative behavior. We combine model prediction with experimental validation to explain striking differences in the long-term cheater trajectories of replicate cocultures through mutational events that increase cheater fitness. Taken together, our integrated empirical and theoretical approach validates and parametrizes the Collapsing Tragedy in a microbial population, and provides a quantitative, mechanistic framework for generating testable predictions of social behavior.

A Deep Learning Framework for Analysis of the Eustachian Tube and the Internal Carotid Artery.

OBJECTIVE: Obtaining automated, objective 3-dimensional (3D) models of the Eustachian tube (ET) and the internal carotid artery (ICA) from computed tomography (CT) scans could provide useful navigational and diagnostic information for ET pathologies and interventions. We aim to develop a deep learning (DL) pipeline to automatically segment the ET and ICA and use these segmentations to compute distances between these structures. STUDY DESIGN: Retrospective cohort. SETTING: Tertiary referral center. METHODS: From a database of 30 CT scans, 60 ET and ICA pairs were manually segmented and used to train an nnU-Net model, a DL segmentation framework. These segmentations were also used to develop a quantitative tool to capture the magnitude and location of the minimum distance point (MDP) between ET and ICA. Performance metrics for the nnU-Net automated segmentations were calculated via the average Hausdorff distance (AHD) and dice similarity coefficient (DSC). RESULTS: The AHD for the ET and ICA were 0.922 and 0.246 mm, respectively. Similarly, the DSC values for the ET and ICA were 0.578 and 0.884. The mean MDP from ET to ICA in the cartilaginous region was 2.6 mm (0.7-5.3 mm) and was located on average 1.9 mm caudal from the bony cartilaginous junction. CONCLUSION: This study describes the first end-to-end DL pipeline for automated ET and ICA segmentation and analyzes distances between these structures. In addition to helping to ensure the safe selection of patients for ET dilation, this method can facilitate large-scale studies exploring the relationship between ET pathologies and the 3D shape of the ET.

Bench Press Range-of-Motion and Velocity-based Repetition Control: Effects on Ballistic Push-up Performance in Males.

The purpose of this study was to investigate whether the ballistic push-up (BPU) is responsive to post-activation performance enhancement (PAPE) after a bench press conditioning exercise using velocity-based repetition control. Additionally, we aimed to evaluate the effects of range of motion (ROM) conditions on subsequent BPU performance. In a randomized crossover design, 18 males performed two conditions (full ROM and self-selected partial ROM) of bench press at 80% of their 1RM until mean concentric velocity dropped 10%. Each participant performed two pre- and six post-test BPUs to assess the PAPE effect. Paired sample t-tests assessed bench press performance measures. Multiple two-way repeated measures ANOVAs assessed differences in flight time, impulse, and peak power for the pre- and post-test BPUs. No significant differences existed between ROM conditions for total repetitions, volume load, or peak velocity. Compared to partial ROM, full ROM showed greater displacement (0.42 ± 0.05 vs. 0.34 ± 0.05 m), work (331.99 ± 67.72 vs. 270.92 ± 61.42 J), and mean velocity (0.46 ± 0.09 vs. 0.44 ± 0.08 m/s). Neither bench press ROM condition enhanced the BPU and were detrimental in some cases. Several time points showed partial ROM (flight time: 2 min post, impulse: 12 min post, peak power: 12 min post) significantly greater than full ROM, possibly indicating less fatigue accumulation. The BPU may require a different stimulus or may not be practical for PAPE effects in college-aged males. Partial ROM can be an alternative that achieves similar peak velocities while requiring less overall work.

Race/Ethnicity and Social Determinants of Health and Their Impact on the Timely Receipt of Appropriate Operative Treatment of Colon Cancer.

INTRODUCTION: Rates of appropriate surgical treatment of colon cancer are historically worse in traditionally marginalized populations. We sought to examine which social determinants of health may be associated with longer time to appropriate operative intervention. METHODS: The National Cancer Databank was queried for this retrospective study. Adult patients (18 to 90 years of age) diagnosed between 2004 and 2018 with single or primary, stage III colon cancer were included. Patient demographic variables included age at diagnosis, sex, ethnicity (Hispanic or non-Hispanic), comorbidity score, median household income, education status, rural/urban status, treatment facility type and location, and insurance status. Disease characteristics include stage (stage 3), primary site, surgical margins, tumor size, and number of nodes resected. Reported descriptive statistics include means and 95% confidence intervals for continuous variables and frequency and proportions for categorical variables. Univariate and multivariate analyses were performed. RESULTS: A total of 134,601 individuals diagnosed with stage 3 colon cancer were included. Time to surgery in all cases had a mean of 26.4 ± 19.0 days. Multivariate analysis of time to surgery indicated that receiving surgery at a Community Cancer Program, Charlson-Deyo Score of 0, younger age, and non-Hispanic-White race/ethnicity are associated with decreased time to surgery (P < .001). CONCLUSION: Patients who receive surgery at a Community Cancer Program, have fewer comorbidities, have lower household income, are younger, and receive surgery within 50 miles of their primary residence are more likely to have timely surgery.

Effects of a multispecies direct-fed microbial on gastrointestinal permeability during feed restriction in a growing heifer model.

The objectives were to evaluate the effects of a 4-strain direct-fed microbial (DFM) on gastrointestinal tract (GIT) permeability and inflammation during feed restriction (FR) in heifers. Holstein heifers (n = 32; mean ± standard deviation; 295 ± 25 kg body weight; 287 ± 17 d of age) were used in an experiment conducted in 2 replicates (16/replicate). Heifers were randomly assigned to 1 of 2 top-dressed dietary treatments: (1) control (CON; 10 g/d dried lactose; n = 16) or (2) DFM containing a commercial blend of Lactobacillus animalis, Propionibacterium freudenreichii, Bacillus licheniformis, and Bacillus subtilis at 11.8 × 109 cfu/d (PRO; 10 g/d 4-strain DFM; n = 16). The trial consisted of 2 experimental periods (P): P1 (14 d) served as baseline for P2 (5 d), when all heifers were restricted to 40% of their P1 dry matter intake (DMI). On P1 d 12 and P2 d 2 and 5, GIT permeability was evaluated using oral chromium (Cr)-EDTA. By design, FR decreased DMI (60%) and body weight (∼18 kg) in all heifers. Regardless of treatment, during FR, all heifers had decreased circulating glucose, ß-hydroxybutyrate, insulin, and l-lactate (4, 14, 45, and 19%, respectively), but increased nonesterified fatty acids, serum amyloid A, and haptoglobin (3.0-, 1.7-, and 5.0-fold, respectively). Circulating white blood cells, neutrophils, lymphocytes, and basophils decreased (4, 7, 5, and 6%, respectively), whereas eosinophils increased (41%) during P2 irrespective of dietary treatment. Circulating IFN-γ inducible protein-10 increased (23%) during FR compared with P1 regardless of treatment. Plasma Cr area under the curve increased in all heifers on d 2 and 5 (10 and 14%, respectively) of P2 relative to P1, but this was unaltered by dietary treatment. In summary, FR compromised GIT barrier function and stimulated an inflammatory response, but this did not appear to be ameliorated by PRO.