Predictors of Blood Transfusion in Patients Undergoing Cytoreductive Surgeries for Ovarian Malignancy.

OBJECTIVES: The aims of this study were to describe the baseline estimated blood loss (EBL) in surgery and transfusion rate in patients undergoing cytoreductive surgeries for ovarian malignancy, and identify perioperative variables associated with blood loss and transfusion. METHODS: A retrospective cohort study at a single institution was performed that included patients with known or suspected ovarian malignancy undergoing cytoreductive surgery between 2016 and 2021. t tests, χ2 tests, and multiple logistic regression analyses were used. RESULTS: Among 44 patients meeting inclusion criteria, 61% received perioperative blood transfusion. There were significant differences in EBL and preoperative hemoglobin levels between patients who did and did not receive transfusion (EBL 442.6 vs 236.8 mL, P = 0.0008; preoperative hemoglobin 10.2 vs 11.2 g/dL, P = 0.049). After adjusting for preoperative hemoglobin, the risk of transfusion increased for each additional 200 mL of EBL (odds ratio [OR] 3.8, 95% confidence interval [CI] 1.5-9.5). Stratified by race, the association between EBL and transfusion risk remained statistically significant only for non-Latinx White patients (OR 6.1, 95% CI 1.7-21.9), who made up 77% of the study population, but not for patients of other races and ethnicities (OR 1.0, 95% CI 0.16-6.42). CONCLUSIONS: Perioperative blood transfusion is common in patients undergoing cytoreductive surgery. In this study, EBL and preoperative hemoglobin levels were significantly associated with transfusion receipt. Clinicians should optimize hemoglobin levels and intraoperative blood conservation strategies to reduce the need for transfusion. The results also highlight the importance of considering racial and ethnic differences when developing strategies to reduce transfusion risk.

Photoinduced Photocatalyst-Free Cascade Cyclization of Alkynes with Sodium Sulfinates for the Synthesis of Benzothiophenes and Thioflavones.

The subject of this investigation is a new method for the construction of sulfonylated heterocycles which overcomes the limitations of classical approaches using a cheap feedstock sulfonylating agent, especially under photocatalyst- and metal-free conditions.

The MexE/MexF/AmeC Efflux Pump of Agrobacterium tumefaciens and Its Role in Ti Plasmid Virulence Gene Expression.

Expression of the tumor-inducing (Ti) plasmid virulence genes of Agrobacterium tumefaciens is required for the transfer of DNA from the bacterium into plant cells, ultimately resulting in the initiation of plant tumors. The vir genes are induced as a result of exposure to certain phenol derivatives, monosaccharides, and low pH in the extracellular milieu. The soil, as well as wound sites on a plant-the usual site of the virulence activity of this bacterium-can contain these signals, but vir gene expression in the soil would be a wasteful utilization of energy. This suggests that mechanisms may exist to ensure that vir gene expression occurs only at the higher concentrations of inducers typically found at a plant wound site. In a search for transposon-mediated mutations that affect sensitivity for the virulence gene-inducing activity of the phenol, 3,5-dimethoxy-4-hydroxyacetophenone (acetosyringone [AS]), an RND-type efflux pump homologous to the MexE/MexF/OprN pump of Pseudomonas aeruginosa was identified. Phenotypes of mutants carrying an insertion or deletion of pump components included hypersensitivity to the vir-inducing effects of AS, hypervirulence in the tobacco leaf explant virulence assay, and hypersensitivity to the toxic effects of chloramphenicol. Furthermore, the methoxy substituents on the phenol ring of AS appear to be critical for recognition as a pump substrate. These results support the hypothesis that the regulation of virulence gene expression is integrated with cellular activities that elevate the level of plant-derived inducers required for induction so that this occurs preferentially, if not exclusively, in a plant environment.IMPORTANCE Expression of genes controlling the virulence activities of a bacterial pathogen is expected to occur preferentially at host sites vulnerable to that pathogen. Host-derived molecules that induce such activities in the plant pathogen Agrobacterium tumefaciens are found in the soil, as well as in the plant. Here, we tested the hypothesis that mechanisms exist to suppress the sensitivity of Agrobacterium species to a virulence gene-inducing molecule by selecting for mutant bacteria that are hypersensitive to its inducing activity. The mutant genes identified encode an efflux pump whose proposed activity increases the concentration of the inducer necessary for vir gene expression; this pump is also involved in antibiotic resistance, demonstrating a relationship between cellular defense activities and the control of virulence in Agrobacterium.

Involvement of Agrobacterium tumefaciens Galacturonate Tripartite ATP-Independent Periplasmic (TRAP) Transporter GaaPQM in Virulence Gene Expression.

Monosaccharides capable of serving as nutrients for the soil bacterium Agrobacterium tumefaciens are also inducers of the vir regulon present in the tumor-inducing (Ti) plasmid of this plant pathogen. One such monosaccharide is galacturonate, the predominant monomer of pectin found in plant cell walls. This ligand is recognized by the periplasmic sugar binding protein ChvE, which interacts with the VirA histidine kinase that controls vir gene expression. Although ChvE is also a member of the ChvE-MmsAB ABC transporter involved in the utilization of many neutral sugars, it is not involved in galacturonate utilization. In this study, a putative tripartite ATP-independent periplasmic (TRAP) transporter, GaaPQM, is shown to be essential for the utilization of galacturonic acid; we show that residue R169 in the predicted sugar binding site of the GaaP is required for activity. The gene upstream of gaaPQM (gaaR) encodes a member of the GntR family of regulators. GaaR is shown to repress the expression of gaaPQM, and the repression is relieved in the presence of the substrate for GaaPQM. Moreover, GaaR is shown to bind putative promoter regions in the sequences required for galacturonic acid utilization. Finally, A. tumefaciens strains carrying a deletion of gaaPQM are more sensitive to galacturonate as an inducer of vir gene expression, while the overexpression of gaaPQM results in strains being less sensitive to this vir inducer. This supports a model in which transporter activity is crucial in ensuring that vir gene expression occurs only at sites of high ligand concentration, such as those at a plant wound site.

Agrobacterium tumefaciens recognizes its host environment using ChvE to bind diverse plant sugars as virulence signals.

Agrobacterium tumefaciens is a broad host range plant pathogen that combinatorially recognizes diverse host molecules including phenolics, low pH, and aldose monosaccharides to activate its pathogenic pathways. Chromosomal virulence gene E (chvE) encodes a periplasmic-binding protein that binds several neutral sugars and sugar acids, and subsequently interacts with the VirA/VirG regulatory system to stimulate virulence (vir) gene expression. Here, a combination of genetics, X-ray crystallography, and isothermal calorimetry reveals how ChvE binds the different monosaccharides and also shows that binding of sugar acids is pH dependent. Moreover, the potency of a sugar for vir gene expression is modulated by a transport system that also relies on ChvE. These two circuits tune the overall system to respond to sugar concentrations encountered in vivo. Finally, using chvE mutants with restricted sugar specificities, we show that there is host variation in regard to the types of sugars that are limiting for vir induction.

GxySBA ABC transporter of Agrobacterium tumefaciens and its role in sugar utilization and vir gene expression.

Monosaccharides available in the extracellular milieu of Agrobacterium tumefaciens can be transported into the cytoplasm, or via the periplasmic sugar binding protein, ChvE, play a critical role in controlling virulence gene expression. The ChvE-MmsAB ABC transporter is involved in the utilization of a wide range of monosaccharide substrates but redundant transporters are likely given the ability of a chvE-mmsAB deletion strain to grow, albeit more slowly, in the presence of particular monosaccharides. In this study, a putative ABC transporter encoded by the gxySBA operon is identified and shown to be involved in the utilization of glucose, xylose, fucose, and arabinose, which are also substrates for the ChvE-MmsAB ABC transporter. Significantly, GxySBA is also shown to be the first characterized glucosamine ABC transporter. The divergently transcribed gene gxyR encodes a repressor of the gxySBA operon, the function of which can be relieved by a subset of the transported sugars, including glucose, xylose, and glucosamine, and this substrate-induced expression can be repressed by glycerol. Furthermore, deletion of the transporter can increase the sensitivity of the virulence gene expression system to certain sugars that regulate it. Collectively, the results reveal a remarkably diverse set of substrates for the GxySBA transporter and its contribution to the repression of sugar sensitivity by the virulence-controlling system, thereby facilitating the capacity of the bacterium to distinguish between the soil and plant environments.

Effect of mind-body exercise on risk factors for metabolic syndrome including insulin resistance: a meta-analysis.

Objective: To systematically evaluate the effects of mind-body exercise on risk factors of metabolic syndrome such as insulin resistance. Methods: Web of Science, PubMed, The Cochrane Library, EBSCO host, Embase, China Knowledge Network, China Biomedical Literature Database, Wanfang, and VIP were searched for the period from the establishment of the database to 1 July 2023, and randomized controlled trials of mind-body exercise interventions in patients with metabolic syndrome were collected. We applied the Cochrane Risk of Bias tool RoB2 to evaluate the methodological quality of the included literature and used RevMan5.4 software and Stata15.1 for statistical analysis. Results: A total of 14 randomized controlled trials with 1148 patients were included in this study. Meta-analysis showed that mind-body exercise significantly improved insulin resistance [SMD=-0.78, 95% CI: (-1.13, -0.43), P<0.0001], waist circumference [SMD=-2.20, 95% CI: (-3.34, -1.06), P=0.0001], body mass index (SMD=-1.50, 95% CI: [-2.03, -0.97), P<0.00001], systolic blood pressure [SMD=-3.65, 95% CI: 9-5.56, -1.74), P=0.0002], diastolic blood pressure [SMD=-3.32, 95% CI: (- 3.77, -2.87), P<0.00001], fasting blood glucose [SMD=-0.57, 95% CI: (-0.99, -0.15), P=0.008], triglycerides [SMD=-0.27, 95% CI: (-0.46, -0.08), P=0.004], high-density lipoprotein cholesterol [SMD=0.58, the 95% CI: (0.28, 0.87), P=0.0001]. Subgroup analysis showed that the intervention program with exercise form of fitness qigong, exercise cycle of 24-48 weeks, and exercise frequency of 6-7 times/week could significantly improve each risk factor. Conclusion: Mind-body exercise is effective in improving risk factors in patients with metabolic syndrome. Current evidence recommends an intervention program of low to moderate intensity fitness qigong, with 6-7 sessions per week for 24-48 weeks in patients with metabolic syndrome. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023454135.

Lung Cancer Prevalence in Virginia: A Spatial Zipcode-Level Analysis via INLA.

BACKGROUND: Examining lung cancer (LC) cases in Virginia (VA) is essential due to its significant public health implications. By studying demographic, environmental, and socioeconomic variables, this paper aims to provide insights into the underlying drivers of LC prevalence in the state adjusted for spatial associations at the zipcode level. METHODS: We model the available VA zipcode-level LC counts via (spatial) Poisson and negative binomial regression models, taking into account missing covariate data, zipcode-level spatial association and allow for overdispersion. Under latent Gaussian Markov Random Field (GMRF) assumptions, our Bayesian hierarchical model powered by Integrated Nested Laplace Approximation (INLA) considers simultaneous (spatial) imputation of all missing covariates through elegant prediction. The spatial random effect across zip codes follows a Conditional Autoregressive (CAR) prior. RESULTS: Zip codes with elevated smoking indices demonstrated a corresponding increase in LC counts, underscoring the well-established connection between smoking and LC. Additionally, we observed a notable correlation between higher Social Deprivation Index (SDI) scores and increased LC counts, aligning with the prevalent pattern of heightened LC prevalence in regions characterized by lower income and education levels. On the demographic level, our findings indicated higher LC counts in zip codes with larger White and Black populations (with Whites having higher prevalence than Blacks), lower counts in zip codes with higher Hispanic populations (compared to non-Hispanics), and higher prevalence among women compared to men. Furthermore, zip codes with a larger population of elderly people (age ≥ 65 years) exhibited higher LC prevalence, consistent with established national patterns. CONCLUSIONS: This comprehensive analysis contributes to our understanding of the complex interplay of demographic and socioeconomic factors influencing LC disparities in VA at the zip code level, providing valuable information for targeted public health interventions and resource allocation. Implementation code is available at GitHub.

Type IV pili of Enterobacteriaceae species.

Type IV pili (T4Ps) are surface filaments widely distributed among bacteria and archaea. T4Ps are involved in many cellular functions and contribute to virulence in some species of bacteria. Due to the diversity of T4Ps, different properties have been observed for homologous proteins that make up T4Ps in various organisms. In this review, we highlight the essential components of T4Ps, their functions, and similarities to related systems. We emphasize the unique T4Ps of enteric pathogens within the Enterobacteriaceae family, which includes pathogenic strains of Escherichia coli and Salmonella. These include the bundle-forming pilus (BFP) of enteropathogenic E. coli (EPEC), longus (Lng) and colonization factor III (CFA/III) of enterotoxigenic E. coli (ETEC), T4P of Salmonella enterica serovar Typhi, Colonization Factor Citrobacter (CFC) of Citrobacter rodentium, T4P of Yersinia pseudotuberculosis, a ubiquitous T4P that was characterized in enterohemorrhagic E. coli (EHEC), and the R64 plasmid thin pilus. Finally, we highlight areas for further study.

Correlation of exercise participation, behavioral inhibition and activation systems, and depressive symptoms in college students.

To clarify the pathways and effects of the behavioral inhibition and activation systems in the relationship between exercise participation and depressive symptoms among college students. A cross-sectional research design was employed to survey 2606 college students using physical activity questionnaires, the Behavioral Inhibition/Activation Systems Scale, and the Beck Depression Inventory. Data were analyzed using methods including one-way ANOVA, independent sample t-tests, non-parametric tests, chi-square tests, correlation analysis, and structural equation modeling. Depressive symptoms were significantly negatively correlated with exercise participation (r = - 0.107, P < 0.001), reward responsiveness (r = - 0.201, P < 0.001), drive (r = - 0.289, P < 0.001), and fun seeking (r = - 0.102, P < 0.001), and positively correlated with behavioral inhibition (r = 0.084, P < 0.001). Exercise participation was positively correlated with reward responsiveness (r = 0.067, P = 0.001), drive (r = 0.085, P < 0.001), and fun seeking (r = 0.063, P = 0.001). Exercise participation had a significant direct effect (B = - 0.079, 95% CI - 0.116 to - 0.043) and total effect (B = - 0.107, 95% CI - 0.148 to - 0.069) on depressive symptoms. The mediating effects of drive (B = - 0.028, 95% CI - 0.043 to - 0.016) and fun seeking (B = 0.005, 95% CI - 0.001 to 0.011) were significant. The more college students engage in exercise, the lower their depressive symptom scores. Drive and fun seeking mediate the relationship between college students' exercise participation and depressive symptoms. Encouraging exercise participation among college students and enhancing their sensitivity to behavioral activation strategies and reward information may have a significant role in preventing and alleviating depressive symptoms.

The Effect of Low Intensity Resistance Training with Blood Flow Restriction on Fall Resistance in Middle-Aged and Older Adults: A Meta-Analysis.

OBJECTIVE: To systematically evaluate the effect of low intensity resistance training with blood flow restriction on fall resistance in middle-aged and older adults. METHODS: PubMed, The Cochrane Library, Web of Science, Embase, EBSCO host, CNKI Database, VIP, Wanfang Database and CBMdisc were searched, and the retrieval period was from the beginning of each database to 25 July 2022. Randomized controlled trials were collected concerning the intervention of low intensity resistance training with blood flow restriction on lower limb muscle strength, muscle mass, muscle function, balance, walking and other fall resistance indicators in middle-aged and older adults. Cochrane Risk of Bias Tool was used for methodological quality assessment of the included literature. Statistical analysis was performed using RevMan 5.4 software and Stata 15.1. RESULTS: A total of 14 randomized controlled trials (419 participants in total) were included in the study. Meta-analysis results revealed that low intensity resistance training with blood flow restriction significantly improved lower limb muscle strength (SMD = 0.51, 95%CI: [0.28, 0.74], p < 0.0001), lower limb muscle mass (MD = 1.99, 95%CI: [0.77, 3.22], p = 0.001) and walking ability (SMD = -0.89, 95% CI. [-1.71, -0.06], p = 0.03), while there was no apparent intervention effect on lower limb muscle function (SMD = 0.25, 95%CI: [-0.23, 0.73], p = 0.31) and balance (SMD = 0.22, 95%CI: [-0.08, 0.52], p = 0.15). The results of subgroup analysis showed that the intervention effect of low intensity resistance training with blood flow restriction on lower limb muscle strength was more significant in subjects aged 55-64 years, with exercise cycles of 4-8 weeks, exercise frequency of three times per week, exercise intensity of 20-30% 1RM, and vascular flow blocking pressure ≥ 120 mmHg. CONCLUSION: Low intensity resistance training with blood flow restriction can effectively improve lower limb muscle strength, muscle mass and walking ability in middle-aged and older adults, and can serve as an important form of fall resistance training for the older adults.

Cryo-EM Structure of the Type IV Pilus Extension ATPase from Enteropathogenic Escherichia coli.

Type 4 pili (T4P) are retractable surface appendages found on numerous bacteria and archaea that play essential roles in various microbial functions, including host colonization by pathogens. An ATPase is required for T4P extension, but the mechanism by which chemical energy is transduced to mechanical energy for pilus extension has not been elucidated. Here, we report the cryo-electron microscopy (cryo-EM) structure of the BfpD ATPase from enteropathogenic Escherichia coli (EPEC) in the presence of either ADP or a mixture of ADP and AMP-PNP. Both structures, solved at 3 Å resolution, reveal the typical toroid shape of AAA+ ATPases and unambiguous 6-fold symmetry. This 6-fold symmetry contrasts with the 2-fold symmetry previously reported for other T4P extension ATPase structures, all of which were from thermophiles and solved by crystallography. In the presence of the nucleotide mixture, BfpD bound exclusively AMP-PNP, and this binding resulted in a modest outward expansion in comparison to the structure in the presence of ADP, suggesting a concerted model for hydrolysis. De novo molecular models reveal a partially open configuration of all subunits where the nucleotide binding site may not be optimally positioned for catalysis. ATPase functional studies reveal modest activity similar to that of other extension ATPases, while calculations indicate that this activity is insufficient to power pilus extension. Our results reveal that, despite similarities in primary sequence and tertiary structure, T4P extension ATPases exhibit divergent quaternary configurations. Our data raise new possibilities regarding the mechanism by which T4P extension ATPases power pilus formation. IMPORTANCE Type 4 pili are hairlike surface appendages on many bacteria and archaea that can be extended and retracted with tremendous force. They play a critical role in disease caused by several deadly human pathogens. Pilus extension is made possible by an enzyme that converts chemical energy to mechanical energy. Here, we describe the three-dimensional structure of such an enzyme from a human pathogen in unprecedented detail, which reveals a mechanism of action that has not been seen previously among enzymes that power type 4 pilus extension.

The relationship between physical activity and trait anxiety in college students: The mediating role of executive function.

Objectives: Aimed to analyze the mediating effect of executive function between physical activity level and trait anxiety in college students. Methods: The International Physical Activity Questionnaire, State-Trait Anxiety Inventory, Stroop task, 1-back task, and More-odd shifting task were used to analyze 248 college students. Results: Trait anxiety were significantly correlated with shifting function (r = 0.182, P = 0.004) and inhibition function (r = 0.163, P = 0.010) and not with working memory (r = 0.056, P = 0.385). Vigorous physical activity (VPA) was most highly correlated with inhibition function (Beta = -0.144, P = 0.024) and working memory (Beta = -0.208, P = 0.001), and light physical activity (LPA) was most highly correlated with shifting function (Beta = -0.211, P = 0.001). Physical activity had a 72.31% association with trait anxiety (B = -0.195), with 11.79% mediated by inhibition function (B = -0.023) and 15.90% by shifting function (B = -0.031). Conclusion: College students' physical activity promotes both inhibition and shifting functions, which in turn affect trait anxiety. VPA had a direct effect, while the effect of moderate physical activity (MPA) and LPA was completely mediated exclusively through executive functions, and the mediating effect of shifting function was the highest. It is recommended that college workers should motivate students with high trait anxiety to engage in more VPA and pay attention to changes in their inhibition and shifting functions.

Characterization of the mmsAB-araD1 (gguABC) genes of Agrobacterium tumefaciens.

The chvE-gguABC operon plays a critical role in both virulence and sugar utilization through the activities of the periplasmic ChvE protein, which binds to a variety of sugars. The roles of the GguA, GguB, and GguC are not known. While GguA and GguB are homologous to bacterial ABC transporters, earlier genetic analysis indicated that they were not necessary for utilization of sugars as the sole carbon source. To further examine this issue, in-frame deletions were constructed separately for each of the three genes. Our growth analysis clearly indicated that GguA and GguB play a role in sugar utilization and strongly suggests that GguAB constitute an ABC transporter with a wide range of substrates, including L-arabinose, D-fucose, D-galactose, D-glucose, and D-xylose. Site-directed mutagenesis showed that a Walker A motif was vital to the function of GguA. We therefore propose renaming gguAB as mmsAB, for multiple monosaccharide transport. A gguC deletion affected growth only on L-arabinose medium, suggesting that gguC encodes an enzyme specific to L-arabinose metabolism, and this gene was renamed araD1. Results from bioinformatics and experimental analyses indicate that Agrobacterium tumefaciens uses a pathway involving nonphosphorylated intermediates to catabolize L-arabinose via an L-arabinose dehydrogenase, AraA(At), encoded at the Atu1113 locus.

Phase-shifting shadow moiré based on iterative self-tuning algorithm.

We proposed a general algorithm for phase-shifting shadow moiré by an iterative self-tuning algorithm. In our proposed system, the grating is translated in equal distance to introduce phase shifts across the field of view. The proposed algorithm produces accurate phase information with five interferograms and can calibrate the precise phase step during the process of the height demodulation. Compared with the traditional method, the proposed algorithm is insensitive to the height dependent effects, which is the main systematic source of error in phase-shift shadow moiré when reconstructing surfaces from fringe patterns. Numerical simulations and optical experiments show that the proposed method can eliminate the nonuniform phase-shift error and possesses a superior performance to existing typical phase-shifting algorithms.

The pathway-specific regulator AveR from Streptomyces avermitilis positively regulates avermectin production while it negatively affects oligomycin biosynthesis.

The function of the regulatory protein AveR in Streptomyces avermitilis was examined. An aveR deletion mutant abolished avermectin production and produced more oligomycin, and its phenotype was complemented by a single copy of the aveR gene. Removal of the C-terminal HTH domain of AveR abolished avermectin biosynthesis, indicating the importance of HTH domain for AveR function. Promoter titration and promoter probe assays suggested that the transcription of aveA1, encoding polypeptide AVES1 of avermectin PKS, was activated by AveR. Chromatin immunoprecipitation (ChIP) assay showed that the predicted promoter regions of both the ave cluster and the olm cluster were target sites of AveR, and the DNA-binding activity of AveR was dependent on its HTH domain. RT-PCR analysis revealed that the transcriptions of ave structural genes were dependent on AveR, but that of olm structural genes and putative pathway-specific regulatory genes increased in the aveR mutants. Consistent with these observations, overexpression of aveR successfully increased avermectin production. These results indicated that aveR encodes a pathway-specific activator essential for avermectin biosynthesis and it also negatively affects oligomycin biosynthesis.

Exercise, brain plasticity, and depression.

Depression is a common mental disorder characterized by high incidence, high disability, and high fatality, causing great burden to the society, families, and individuals. The changes in brain plasticity may be a main reason for depression. Recent studies have shown that exercise plays a positive role in depression, but systematic and comprehensive studies are lacking on brain plasticity changes in depression. To further understand the antidepressive effect of exercise and the changes in brain plasticity, we retrieved related literatures using key words "depression," "depressive disorder," "exercise," "brain plasticity," "brain structure," and "brain function" from the database of Web of Science, PubMed, EBSCO host, and CNKI, hoping to provide evidence for exercise in preventing and treating depression. Increase in exercise has been found negatively correlated with the risk of depression. Randomized controlled experiments have shown that aerobic exercise, resistance exercise, and mind-body exercise can improve depressive symptoms and levels. The intensity and long-term effect of exercise are now topical research issues. Exercise has been proven to reshape the brain structure of depression patients, activate the function of related brain areas, promote behavioral adaptation changes, and maintain the integrity of hippocampal and white matter volume, thus improving the brain neuroprocessing and delaying cognitive degradation in depression patients. Future studies are urgently needed to establish accurate exercise prescriptions for improving depressive symptoms, and studies on different depressive populations and studies using multimodal brain imaging combined with multiple analytical methods are also needed.

Chasing the rate: An interrupted time series analysis of interventions targeting reported hospital onset Clostridioides difficile, 2013-2018.

OBJECTIVE: To assess the impact of major interventions targeting infection control and diagnostic stewardship in efforts to decrease Clostridioides difficile hospital onset rates over a 6-year period. DESIGN: Interrupted time series. SETTING: The study was conducted in an 865-bed academic medical center. METHODS: Monthly hospital-onset C. difficile infection (HO-CDI) rates from January 2013 through January 2019 were analyzed around 5 major interventions: (1) a 2-step cleaning process in which an initial quaternary ammonium product was followed with 10% bleach for daily and terminal cleaning of rooms of patients who have tested positive for C. difficile (February 2014), (2) UV-C device for all terminal cleaning of rooms of C. difficile patients (August 2015), (3) "contact plus" isolation precautions (June 2016), (4) sporicidal peroxyacetic acid and hydrogen peroxide cleaning in all patient areas (June 2017), (5) electronic medical record (EMR) decision support tool to facilitate appropriate C. difficile test ordering (March 2018). RESULTS: Environmental cleaning interventions and enhanced "contact plus" isolation did not impact HO-CDI rates. Diagnostic stewardship via EMR decision support decreased the HO-CDI rate by 6.7 per 10,000 patient days (P = .0079). When adjusting rates for test volume, the EMR decision support significance was reduced to a difference of 5.1 case reductions per 10,000 patient days (P = .0470). CONCLUSION: Multiple aggressively implemented infection control interventions targeting CDI demonstrated a disappointing impact on endemic CDI rates over 6 years. This study adds to existing data that outside of an outbreak situation, traditional infection control guidance for CDI prevention has little impact on endemic rates.