Impact of exercise on brain-bone marrow interactions in chronic stress: potential mechanisms preventing stress-induced hypertension.

We examined the effect of chronic restraint stress and the counteractive effects of daily exercise on the molecular basis of the brain-bone marrow (BM) interactions, by especially focusing on the paraventricular nucleus (PVN) of the hypothalamus. Male Wistar rats were assigned into control, restraint stress, and stress + daily spontaneous exercise (SE) groups. BM and hypothalamic gene expression profiles were examined through the undertaking of RT-PCR and microarrays, respectively. The inflammatory blood cell population was investigated through flow cytometry. Through the use of immunohistochemistry, we examined the presence of BM-derived C-C chemokine receptor type 2 (CCR2)-expressing microglial cells in the rat PVN. The gene expression levels of BM inflammatory factors such as those of interleukin 1 beta and CCR2, and the inflammatory blood cell population were found to be significantly higher in both restrained groups compared with control group. Interestingly, chronic restraint stress alone activated the recruitment of BM-derived CCR2-expressing microglial cells into the PVN, whereas daily spontaneous exercise prevented it. A notable finding was that restraint stress upregulated relative gene expression of hypothalamic matrix metalloproteinase 3 (MMP3), which increases the permeability of the blood-brain barrier (BBB), and that exercise managed to normalize it. Moreover, relative expression of some hypothalamic genes directly involved in the facilitation of cell migration was downregulated by daily exercise. Our findings suggest that daily spontaneous exercise can reduce the numbers of BM-derived CCR2-expressing microglial cells into the PVN through the prevention of stress-induced changes in the hypothalamic gene expression.NEW & NOTEWORTHY Chronic restraint stress can upregulate MMP3 gene expression in the rat hypothalamus, whereas daily spontaneous exercise can prevent this stress-induced effect. Stress-induced BM-derived inflammatory cell recruitment into the rat PVN can be prevented by daily spontaneous exercise. Stress-induced increase of hypothalamic MMP3 gene expression may be responsible for BBB injury, thereby allowing for BM-derived inflammatory cells to be recruited and to accumulate in the rat PVN, and to be subsequently involved in the onset of stress-induced hypertension.

Supplementation with Amino Acid Sources Facilitates Fermentative Growth of Shewanella oneidensis MR-1 in Defined Media.

Shewanella oneidensis MR-1 is a facultative anaerobe that grows by respiration using a variety of electron acceptors. This organism serves as a model to study how bacteria thrive in redox-stratified environments. A glucose-utilizing engineered derivative of MR-1 has been reported to be unable to grow in glucose minimal medium (GMM) in the absence of electron acceptors, despite this strain having a complete set of genes for reconstructing glucose to lactate fermentative pathways. To gain insights into why MR-1 is incapable of fermentative growth, this study examined a hypothesis that this strain is programmed to repress the expression of some carbon metabolic genes in the absence of electron acceptors. Comparative transcriptomic analyses of the MR-1 derivative were conducted in the presence and absence of fumarate as an electron acceptor, and these found that the expression of many genes involved in carbon metabolism required for cell growth, including several tricarboxylic acid (TCA) cycle genes, was significantly downregulated in the absence of fumarate. This finding suggests a possibility that MR-1 is unable to grow fermentatively on glucose in minimal media owing to the shortage of nutrients essential for cell growth, such as amino acids. This idea was demonstrated in subsequent experiments that showed that the MR-1 derivative fermentatively grows in GMM containing tryptone or a defined mixture of amino acids. We suggest that gene regulatory circuits in MR-1 are tuned to minimize energy consumption under electron acceptor-depleted conditions, and that this results in defective fermentative growth in minimal media. IMPORTANCE It is an enigma why S. oneidensis MR-1 is incapable of fermentative growth despite having complete sets of genes for reconstructing fermentative pathways. Understanding the molecular mechanisms behind this defect will facilitate the development of novel fermentation technologies for the production of value-added chemicals from biomass feedstocks, such as electro-fermentation. The information provided in this study will also improve our understanding of the ecological strategies of bacteria living in redox-stratified environments.

Genomic evidence for convergent evolution of gene clusters for momilactone biosynthesis in land plants.

Momilactones are bioactive diterpenoids that contribute to plant defense against pathogens and allelopathic interactions between plants. Both cultivated and wild grass species of Oryza and Echinochloa crus-galli (barnyard grass) produce momilactones using a biosynthetic gene cluster (BGC) in their genomes. The bryophyte Calohypnum plumiforme (formerly Hypnum plumaeforme) also produces momilactones, and the bifunctional diterpene cyclase gene CpDTC1/HpDTC1, which is responsible for the production of the diterpene framework, has been characterized. To understand the molecular architecture of the momilactone biosynthetic genes in the moss genome and their evolutionary relationships with other momilactone-producing plants, we sequenced and annotated the C. plumiforme genome. The data revealed a 150-kb genomic region that contains two cytochrome P450 genes, the CpDTC1/HpDTC1 gene and the "dehydrogenase momilactone A synthase" gene tandemly arranged and inductively transcribed following stress exposure. The predicted enzymatic functions in yeast and recombinant assay and the successful pathway reconstitution in Nicotiana benthamiana suggest that it is a functional BGC responsible for momilactone production. Furthermore, in a survey of genomic sequences of a broad range of plant species, we found that momilactone BGC is limited to the two grasses (Oryza and Echinochloa) and C. plumiforme, with no synteny among these genomes. These results indicate that while the gene cluster in C. plumiforme is functionally similar to that in rice and barnyard grass, it is likely a product of convergent evolution. To the best of our knowledge, this report of a BGC for a specialized plant defense metabolite in bryophytes is unique.

BSR1, a Rice Receptor-like Cytoplasmic Kinase, Positively Regulates Defense Responses to Herbivory.

Crops experience herbivory by arthropods and microbial infections. In the interaction between plants and chewing herbivores, lepidopteran larval oral secretions (OS) and plant-derived damage-associated molecular patterns (DAMPs) trigger plant defense responses. However, the mechanisms underlying anti-herbivore defense, especially in monocots, have not been elucidated. The receptor-like cytoplasmic kinase Broad-Spectrum Resistance 1 (BSR1) of Oryza sativa L. (rice) mediates cytoplasmic defense signaling in response to microbial pathogens and enhances disease resistance when overexpressed. Here, we investigated whether BSR1 contributes to anti-herbivore defense responses. BSR1 knockout suppressed rice responses triggered by OS from the chewing herbivore Mythimna loreyi Duponchel (Lepidoptera: Noctuidae) and peptidic DAMPs OsPeps, including the activation of genes required for biosynthesis of diterpenoid phytoalexins (DPs). BSR1-overexpressing rice plants exhibited hyperactivation of DP accumulation and ethylene signaling after treatment with simulated herbivory and acquired enhanced resistance to larval feeding. As the biological significance of herbivory-induced accumulation of rice DPs remains unexplained, their physiological activities in M. loreyi were analyzed. The addition of momilactone B, a rice DP, to the artificial diet suppressed the growth of M. loreyi larvae. Altogether, this study revealed that BSR1 and herbivory-induced rice DPs are involved in the defense against chewing insects, in addition to pathogens.

Transcriptional response of a target plant to benzoxazinoid and diterpene allelochemicals highlights commonalities in detoxification.

BACKGROUND: Plants growing in proximity to other plants are exposed to a variety of metabolites that these neighbors release into the environment. Some species produce allelochemicals to inhibit growth of neighboring plants, which in turn have evolved ways to detoxify these compounds. RESULTS: In order to understand how the allelochemical-receiving target plants respond to chemically diverse compounds, we performed whole-genome transcriptome analysis of Arabidopsis thaliana exposed to either the benzoxazinoid derivative 2-amino- 3H-phenoxazin-3-one (APO) or momilactone B. These two allelochemicals belong to two very different compound classes, benzoxazinoids and diterpenes, respectively, produced by different Poaceae crop species. CONCLUSIONS: Despite their distinct chemical nature, we observed similar molecular responses of A. thaliana to these allelochemicals. In particular, many of the same or closely related genes belonging to the three-phase detoxification pathway were upregulated in both treatments. Further, we observed an overlap between genes upregulated by allelochemicals and those involved in herbicide detoxification. Our findings highlight the overlap in the transcriptional response of a target plant to natural and synthetic phytotoxic compounds and illustrate how herbicide resistance could arise via pathways involved in plant-plant interaction.

Analysis of risk factors for patients with early-stage cervical cancer: A study of 374 patients.

AIM: This study aimed to identify the postoperative histological features affecting the prognosis of patients with early-stage cervical cancer who underwent open radical hysterectomy. METHODS: This retrospective study enrolled 374 patients with pT1a, 1b1 and 2a1 early-stage cervical cancer who underwent open radical hysterectomy between 2001 and 2018. Survival outcomes were analyzed by Kaplan-Meier method and compared with log-rank test. Using the Cox proportional hazards regression test, we conducted a multivariate analysis for disease-free survival and overall survival. RESULTS: Others histology, including other epithelial tumors and neuroendocrine tumors, had a significantly worse prognosis in both disease-free survival and overall survival than those of squamous cell carcinoma and adenocarcinoma (hazard ratio, 4.37 and 11.76; P = 0.006 and P = 0.002, respectively), along with lymph node metastasis (hazard ratio, 2.99 and 7.03; P = 0.009 and P = 0.001, respectively). CONCLUSION: Others histology including adenosquamous carcinoma had a poor prognosis in early-stage cervical cancer as with high-risk factors.

Development of a microchip electrophoresis-based, high-throughput PCR-RFLP method to type Tax 233 variants of bovine leukemia virus in Japan.

Bovine leukemia virus (BLV) is the causative agent of enzootic bovine leukosis (EBL). We used microchip electrophoresis in combination with automatic image analysis to develop a novel high-throughput PCR-RFLP to type the gene sequences that encode BLV Tax 233. This method revealed that 233L-Tax is more prevalent than 233P-Tax in cattle in Japan. The proportion infected with BLV carrying the gene encoding 233L-Tax was significantly higher in Holstein cattle than in Japanese Black cattle. Holsteins infected with BLV encoding 233L-Tax had higher proviral loads than did Holsteins infected with BLV encoding 233P-Tax and Japanese Blacks infected with BLV encoding 233L-Tax or 233P-Tax. The novel method developed in this study will be a useful tool for identifying cattle harboring BLV with a higher risk of EBL and viral transmission.

Non-invasive monitoring using photoplethysmography technology.

We evaluated the accuracy and precision of a novel non-invasive monitoring device in comparison with conventional monitoring methods used in intensive care units (ICU). The study device was developed to measure blood pressure, pulse rate, respiratory rate, and oxygen saturation, continuously with a single sensor using the photoplethysmographic technique. Patients who were monitored with arterial pressure lines in the ICU were enrolled. Systolic and diastolic blood pressure, pulse rate, respiratory rate, and arterial oxygen saturation were measured continuously for 30 min at 5-min intervals using the conventional methods and the study device. The primary outcome variable was blood pressure. Blood pressure measured by the study device highly correlated with the arterial pressure line values (correlation coefficients > 0.95). Percent errors for systolic, diastolic and mean blood pressures were 2.4% and 6.7% and 6.5%, respectively. Percent errors for pulse rate, respiratory rate and oxygen saturation were 3.4%, 5.6% and 1.4%, respectively. The non-invasive, continuous, multi-parameter monitoring device presented high level of agreement with the invasive arterial blood pressure monitoring, along with sufficient accuracy and precision in the measurements of pulse rate, respiratory rate, and oxygen saturation.

Proteome analysis of hemofilter adsorbates to identify novel substances of sepsis: a pilot study.

Blood purification therapy using hemofilters with high adsorbing capabilities has been reported to remove excessive humoral mediators from the blood of patients with sepsis. However, there are insufficient studies of the adsorbates bound to hemofilter membranes. We hypothesized that these adsorbates in acute kidney injury (AKI) patients with sepsis were different from those in patients without sepsis and that proteome analysis of the adsorbates would identify novel substances of sepsis. This study included 20 patients who had AKI upon admission to intensive care units (ICUs) and who received continuous renal replacement therapy using polymethyl methacrylate hemofilters. We isolated adsorbates from the hemofilters after use and performed comprehensive proteome analysis. A total of 429 proteins were identified in these adsorbates. Adsorbates from the hemofilters of patients with sepsis had significantly increased frequency of proteins associated with "immune system process" and "biological adhesion" functions compared to those of non-sepsis patients (P < 0.05). Of 429 proteins, 197 were identified only in sepsis adsorbates. Of these, 3 proteins including carbonic anhydrase 1 (CA1) and leucine-rich alpha-2-glycoprotein (LRG1) were identified in all samples from sepsis patients and have not been previously reported in sepsis patients. Validation analysis of patient serum revealed that patients with sepsis had increased serum levels of CA1 and LRG1 compared to patients without sepsis (P < 0.05). To conclude, there were significant differences in the characteristics of the adsorbates from sepsis and non-sepsis patients. CA1 and LRG1 appear to be novel substances associated with sepsis.

Fewer REBOA complications with smaller devices and partial occlusion: evidence from a multicentre registry in Japan.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) performed by emergency physicians has been gaining acceptance as a less invasive technique than resuscitative thoracotomy. OBJECTIVE: To evaluate access-related complications and duration of occlusions during REBOA. METHODS: Patients with haemorrhagic shock requiring REBOA, from 18 hospitals in Japan, included in the DIRECT-IABO Registry were studied. REBOA-related characteristics were compared between non-survivors and survivors at 24 hours. 24-Hour survivors were categorised into groups with small (≤8 Fr), large (≥9 Fr) or unusual sheaths (oversized or multiple) to assess the relationship between the sheath size and complications. Haemodynamic response, occlusion duration and outcomes were compared between groups with partial and complete REBOA. RESULTS: Between August 2011 and December 2015, 142 adults undergoing REBOA were analysed. REBOA procedures were predominantly (94%) performed by emergency medicine (EM) physicians. The median duration of the small sheath (n=53) was 19 hours compared with 7.5 hours for the larger sheaths (P=0.025). Smaller sheaths were more likely to be removed using external manual compression (96% vs 45%, P<0.001). One case of a common femoral artery thrombus (large group) and two cases of amputation (unusual group) were identified. Partial REBOA was carried out in more cases (n=78) and resulted in a better haemodynamic response than complete REBOA (improvement in haemodynamics, 92% vs 70%, P=0.004; achievement of stability, 78% vs 51%, P=0.007) and allowed longer occlusion duration (median 58 vs 33 min, P=0.041). No statistically significant difference in 24-hour or 30-day survival was found between partial and complete REBOA. CONCLUSION: In Japan, EM physicians undertake the majority of REBOA procedures. Smaller sheaths appear to have fewer complications despite relatively prolonged placement and require external compression on removal. Although REBOA is a rarely performed procedure, partial REBOA, which may extend the occlusion duration without a reduction in survival, is used more commonly in Japan.

Functional computed tomography scanning for evaluating fusion status after anterior cervical decompression fusion.

INTRODUCTION: Nonunion is a major complication of anterior cervical fusion that causes poor outcomes and occasionally requires additional operative intervention. The purpose of this study is to evaluate the accuracy of functional computed tomography (CT) scanning for determining fusion status after anterior cervical fusion by comparing with functional radiographs. MATERIALS AND METHODS: The fusion status in 59 patients treated by anterior cervical fusion was assessed by functional radiography and functional CT scanning at 6 and 12 months after surgery. Fusion rates and clinical symptoms were evaluated. Fusion on functional radiography was defined as less than 2 mm of motion between adjacent spinous processes and a particular bony trabeculation on functional CT; fusion was defined as nonexistence of a clear zone or a gas pattern and a particular bone connection on reconstructed sagittal-view images. RESULTS: Functional radiographs demonstrated solid fusion in 83.9% at 6 months and 91.1% at 12 months postoperatively; functional CT showed solid fusion in 55.3 and 78.6%, respectively. The fusion rate detected on functional CT images was significantly lower than that on functional radiographs at each period. At 6 months postoperatively, patients with incomplete union on functional CT were more likely to have neck pain than those who had complete union on functional CT. (46.2 vs 13.3%, P < 0.05) CONCLUSION: Functional CT can detect nonunion more clearly than functional radiography. At 6 months postoperatively, patients with incomplete union on functional CT images were likely to have more neck pain. Functional CT may allow accurate detection of symptomatic nonunion after anterior cervical fusion.

Treatment outcomes of intradiscal steroid injection/selective nerve root block for 161 patients with cervical radiculopathy.

Patients with cervical radiculopathy (CR) were treated with intradiscal injection of steroids (IDIS) and/or selective nerve root block (SNRB) at our hospital. We retrospectively report the outcomes of these nonsurgical treatments for CR. 161 patients who were followed up for >2months were enrolled in this study. Patients' clinical manifestations were classified as arm pain, arm numbness, neck and/or scapular pain, and arm paralysis. Improvement in each manifestation was classified as "disappeared," "improved," "poor," or "worsened." Responses of "disappeared" or "improved" manifestations suggested treatment effectiveness. Final clinical outcomes were evaluated using the Odom criteria. Changes in herniated disc size were evaluated by comparing the initial and final MRI scans. On the basis of these changes, the patients were divided into regression, no-change, or progression groups. We investigated the relationship between the Odom criteria and changes observed on MRI. Effectiveness rates were 89% for arm pain, 77% for arm numbness, 82% for neck and/or scapular pain, and 76% for arm paralysis. In total, 91 patients underwent repeated MRI. In 56 patients (62%), the size of the herniated disc decreased, but 31 patients (34%) exhibited no change in disc size. The regression group showed significantly better Odom criteria results than the no-change group. In conclusion, IDIS and SNRB for CR are not widely performed. However, other extremely effective therapies that can rapidly improve neuralgia should be considered before surgery.

Machine learning algorithm for predicting 30-day mortality in patients receiving rapid response system activation: A retrospective nationwide cohort study.

This study investigated the accuracy of a machine learning algorithm for predicting mortality in patients receiving rapid response system (RRS) activation. This retrospective cohort study used data from the In-Hospital Emergency Registry in Japan, which collects nationwide data on patients receiving RRS activation. The missing values in the dataset were replaced using multiple imputations (mode imputation, BayseRidge sklearn. linear model, and K-nearest neighbor model), and the enrolled patients were randomly assigned to the training and test cohorts. We established prediction models for 30-day mortality using the following four types of machine learning classifiers: Light Gradient Boosting Machine (LightGBM), eXtreme Gradient Boosting, random forest, and neural network. Fifty-two variables (patient characteristics, details of RRS activation, reasons for RRS initiation, and hospital capacity) were used to construct the prediction algorithm. The primary outcome was the accuracy of the prediction model for 30-day mortality. Overall, the data from 4,997 patients across 34 hospitals were analyzed. The machine learning algorithms using LightGBM demonstrated the highest predictive value for 30-day mortality (area under the receiver operating characteristic curve, 0.860 [95 % confidence interval, 0.825-0.895]). The SHapley Additive exPlanations summary plot indicated that hospital capacity, site of incidence, code status, and abnormal vital signs within 24 h were important variables in the prediction model for 30-day mortality.

Usability evaluation of a glove-type wearable device for efficient biometric collection during triage.

To efficiently allocate medical resources at disaster sites, medical workers perform triage to prioritize medical treatments based on the severity of the wounded or sick. In such instances, evaluators often assess the severity status of the wounded or sick quickly, but their measurements are qualitative and rely on experience. Therefore, we developed a wearable device called Medic Hand in this study to extend the functionality of a medical worker's hand so as to measure multiple biometric indicators simultaneously without increasing the number of medical devices to be carried. Medic Hand was developed to quantitatively and efficiently evaluate "perfusion" during triage. Speed is essential during triage at disaster sites, where time and effort are often spared to attach medical devices to patients, so the use of Medic Hand as a biometric measurement device is more efficient for collecting biometric information. For Medic Hand to be handy during disasters, it is essential to understand and improve upon factors that facilitate its public acceptance. To this end, this paper reports on the usability evaluation of Medic Hand through a questionnaire survey of nonmedical workers.

Involvement of D1 dopamine receptor in the nucleus of the solitary tract of rats in stress-induced hypertension and exercise.

OBJECTIVE: Chronic stress can cause hypertension, whereas daily exercise promotes healthy well being through destressing. Although the nucleus of the solitary tract (NTS) is involved in the development of hypertension, the molecular and physiological mechanisms of stress and exercise remain unclear. In this study, we tested whether gene expression in the NTS is altered by stress and daily exercise and whether this is involved in cardiovascular regulation. METHODS: We have performed RT2 Profiler PCR arrays targeting a panel of neurotransmitter receptor genes in the NTS of Wistar rats subjected to chronic restraint stress (1 h a day over 3 weeks) with or without voluntary wheel exercise. We also performed immunohistochemistry to determine whether the identified molecules were expressed at the protein level. Additionally, microinjection studies in anesthetized rats were performed to examine whether validated molecules exhibit physiological roles in cardiovascular regulation of the NTS. RESULTS: We observed that blood pressure was significantly increased by stress and the increase was suppressed by exercise. Using PCR analysis, we determined that the expression levels of four genes in the NTS, including the dopamine receptor D1 gene (Drd1), were significantly affected by stress and suppressed by exercise. We also examined dopamine D1 receptor (D1R) expression in NTS neurons and found significantly greater expression in the stressed than nonstressed animals. Furthermore, the microinjection of a D1R agonist into the NTS in anesthetized rats induced hypotensive effects. CONCLUSION: These results suggest that NTS D1R plays a role in the counteracting processes of stress-induced hypertension.

Electrogenetic control of gene expression in Shewanella oneidensis MR-1 using Arc-dependent transcriptional promoters.

Electrochemically active bacteria (EAB) are capable of electrically interacting with electrodes, enabling their application in bioelectrochemical systems (BESs). As the performance of BES is related to the metabolic activities of EAB, the development of methods to control their metabolic activities is important to facilitate BES applications. A recent study found that the EAB Shewanella oneidensis MR-1 uses the Arc system to regulate the expression of catabolic genes in response to electrode potentials, suggesting that a methodology for electrical control of gene expression in EAB, referred to as electrogenetics, can be developed by using electrode potential-responsive, Arc-dependent transcriptional promoters. Here, we explored Arc-dependent promoters in the genomes of S. oneidensis MR-1 and Escherichia coli to identify electrode potential-responsive promoters that are differentially activated in MR-1 cells exposed to high- and low-potential electrodes. LacZ reporter assays using electrode-associated cells of MR-1 derivatives revealed that the activities of promoters located upstream of the E. coli feo gene (Pfeo) and the MR-1 nqrA2 (SO_0902) gene (Pnqr2) were significantly increased when S. oneidensis cells were exposed to electrodes poised at +0.7 V and -0.4 V (versus the standard hydrogen electrode), respectively. Additionally, we developed a microscopic system for in situ monitoring of promoter activity in electrode-associated cells and found that Pnqr2 activity was persistently induced in MR-1 cells associated with an electrode poised at -0.4 V. Our results indicate that these electrode potential-responsive promoters enable efficient regulation of gene expression in EAB, providing a molecular basis for the development of electrogenetics.

Cut-Off Value of Capillary Refill Time for Peripheral Circulatory Failure Diagnosis.

INTRODUCTION: Capillary refill time (CRT) is an indicator of peripheral circulation and is recommended in the 2021 guidelines for treating and managing sepsis. STUDY OBJECTIVE: This study developed a portable device to realize objective CRT measurement. Assuming that peripheral blood flow obstruction by the artery occlusion test (AOT) or venous occlusion test (VOT) increases the CRT, the cut-off value for peripheral circulatory failure was studied by performing a comparative analysis with CRT with no occlusion test (No OT). METHODS: Fourteen (14) healthy adults (age: 20-26 years) participated in the study. For the vascular occlusion test, a sphygmomanometer was placed on the left upper arm of the participant in the supine position, and a pressure of 30mmHg higher than the systolic pressure was applied for AOT, a pressure of 60mmHg was applied for VOT, respectively, and no pressure was applied for No OT. The CRT was measured from the index finger of the participant's left hand. RESULTS: Experimental results revealed that CRT was significantly longer in the AOT and did not differ significantly in the VOT. The cut-off value for peripheral circulatory failure was found to be 2.88 seconds based on Youden's index by using receiver operating characteristic (ROC) analysis with AOT as positive and No OT as negative. CONCLUSION: Significant results were obtained in a previous study on the evaluation of septic shock patients when CRT > three seconds was considered abnormal, and the cut-off value for peripheral circulatory failure in the current study validated this.

Associations between fluid overload and outcomes in critically ill patients with acute kidney injury: a retrospective observational study.

Increased fluid overload (FO) is associated with poor outcomes in critically ill patients, especially in acute kidney injury (AKI). However, the exact timing from when FO influences outcomes remains unclear. We retrospectively screened intensive care unit (ICU) admitted patients with AKI between January 2011 and December 2015. Logistic or linear regression analyses were performed to determine when hourly %FO was significant on 90-day in-hospital mortality (primary outcome) or ventilator-free days (VFDs). In total, 1120 patients were enrolled in this study. Univariate analysis showed that a higher %FO was significantly associated with higher mortality from the first hour of ICU admission (odds ratio 1.34, 95% confidence interval 1.15-1.56, P < 0.001), whereas multivariate analysis adjusted with age, sex, APACHE II score, and sepsis etiology showed the association was significant from the 27th hour. Both univariate and multivariate analyses showed that a higher %FO was significantly associated with shorter VFDs from the 1st hour. The significant associations were retained during all following observation periods after they showed significance. In patients with AKI, a higher %FO was associated with higher mortality and shorter VFDs from the early phase after ICU admission. FO should be administered with a physiological target or goal in place from the initial phase of critical illness.