Gut microbiome predicts cognitive function and depressive symptoms in late life.

Depression in older adults with cognitive impairment increases progression to dementia. Microbiota is associated with current mood and cognition, but the extent to which it predicts future symptoms is unknown. In this work, we identified microbial features that reflect current and predict future cognitive and depressive symptoms. Clinical assessments and stool samples were collected from 268 participants with varying cognitive and depressive symptoms. Seventy participants underwent 2-year follow-up. Microbial community diversity, structure, and composition were assessed using high-resolution 16 S rRNA marker gene sequencing. We implemented linear regression to characterize the relationship between microbiome composition, current cognitive impairment, and depressive symptoms. We leveraged elastic net regression to discover features that reflect current or future cognitive function and depressive symptoms. Greater microbial community diversity associated with lower current cognition in the whole sample, and greater depression in participants not on antidepressants. Poor current cognitive function associated with lower relative abundance of Bifidobacterium, while greater GABA degradation associated with greater current depression severity. Future cognitive decline associated with lower cognitive function, lower relative abundance of Intestinibacter, lower glutamate degradation, and higher baseline histamine synthesis. Future increase in depressive symptoms associated with higher baseline depression and anxiety, lower cognitive function, diabetes, lower relative abundance of Bacteroidota, and lower glutamate degradation. Our results suggest cognitive dysfunction and depression are unique states with an overall biological effect detectable through gut microbiota. The microbiome may present a noninvasive readout and prognostic tool for cognitive and psychiatric states.

The effects of urban green space and road proximity to indoor traffic-related PM2.5, NO2, and BC exposure in inner-city schools.

BACKGROUND: Since there are known adverse health impacts of traffic-related air pollution, while at the same time there are potential health benefits from greenness, it is important to examine more closely the impacts of these factors on indoor air quality in urban schools. OBJECTIVE: This study investigates the association of road proximity and urban greenness to indoor traffic-related fine particulate matter (PM2.5), nitrogen dioxide (NO2), and black carbon (BC) in inner-city schools. METHODS: PM2.5, NO2, and BC were measured indoors at 74 schools and outdoors at a central urban over a 10-year period. Seasonal urban greenness was estimated using the Normalized Difference Vegetation Index (NDVI) with 270 and 1230 m buffers. The associations between indoor traffic-related air pollution and road proximity and greenness were investigated with mixed-effects models. RESULTS: The analysis showed linear decays of indoor traffic-related PM2.5, NO2, and BC by 60%, 35%, and 22%, respectively for schools located at a greater distance from major roads. The results further showed that surrounding school greenness at 270 m buffer was significantly associated (p < 0.05) with lower indoor traffic-related PM2.5: -0.068 (95% CI: -0.124, -0.013), NO2: -0.139 (95% CI: -0.185, -0.092), and BC: -0.060 (95% CI: -0.115, -0.005). These associations were stronger for surrounding greenness at a greater distance from the schools (buffer 1230 m) PM2.5: -0.101 (95% CI: -0.156, -0.046) NO2: -0.122 (95% CI: -0.169, -0.075) BC: -0.080 (95% CI: -0.136, -0.026). These inverse associations were stronger after fully adjusting for regional pollution and meteorological conditions. IMPACT STATEMENT: More than 90% of children under the age of 15 worldwide are exposed to elevated air pollution levels exceeding the WHO's guidelines. The study investigates the impact that urban infrastructure and greenness, in particular green areas and road proximity, have on indoor exposures to traffic-related PM2.5, NO2, and BC in inner-city schools. By examining a 10-year period the study provides insights for air quality management, into how road proximity and greenness at different buffers from the school locations can affect indoor exposure.

Monovalent and trivalent VSV-based COVID-19 vaccines elicit neutralizing antibodies and CD8+ T cells against SARS-CoV-2 variants.

Recombinant vesicular stomatitis virus (rVSV) vaccines expressing spike proteins of Wuhan, Beta, and/or Delta variants of SARS-CoV-2 were generated and tested for induction of antibody and T cell immune responses following intramuscular delivery to mice. rVSV-Wuhan and rVSV-Delta vaccines and an rVSV-Trivalent (mixed rVSV-Wuhan, -Beta, -Delta) vaccine elicited potent neutralizing antibodies (nAbs) against live SARS-CoV-2 Wuhan (USAWA1), Beta (B.1.351), Delta (B.1.617.2), and Omicron (B.1.1.529) viruses. Prime-boost vaccination with rVSV-Beta was less effective in this capacity. Heterologous boosting of rVSV-Wuhan with rVSV-Delta induced strong nAb responses against Delta and Omicron viruses, with the rVSV-Trivalent vaccine consistently effective in inducing nAbs against all the SARS-CoV-2 variants tested. All vaccines, including rVSV-Beta, elicited a spike-specific immunodominant CD8+ T cell response. Collectively, rVSV vaccines targeting SARS-CoV-2 variants of concern may be considered in the global fight against COVID-19.

Evaluation of the efficacy and safety of NVP-1203 and aceclofenac in patients with acute low back pain and muscle spasm: A randomized, double-blind, active-controlled, parallel, multicenter, phase 3 clinical trial.

OBJECTIVE: Acute low back pain (LBP) is a common condition that can be chronic if not properly treated. Aceclofenac and eperisone hydrochloride are commonly prescribed drugs for acute LBP and muscle spasms. Therefore, NVP-1203, a fixed-dose combination of 100 mg aceclofenac and 75 mg eperisone hydrochloride, is being developed. This study aimed to evaluate the efficacy and safety of NVP-1203 compared to those of a single administration of 100 mg aceclofenac in patients with acute LBP and muscle spasms. PATIENTS AND METHODS: Overall, 455 patients with acute LBP and muscle spasms were enrolled. The patients were assigned to NVP-1203 or Airtal group (aceclofenac 100 mg). The primary efficacy endpoint was the mean change in the 100 mm pain movement and resting visual analog scale (VAS) scores on treatment day 7. RESULTS: The mean change in the 100 mm pain movement/resting VAS scores from baseline to day 7 was -49.7 ± 21.5/-41.0 ± 19.4 mm and -38.8 ± 18.9/-33.8 ± 18.0 mm for the NVP-1203 and Airtal groups, respectively. The differences between the two groups were statistically significant (movement, p < 0.0001; resting, p = 0.0002). Differences in least-square (LS) mean change of the 100 mm pain movement/resting VAS score between the two groups using the analysis of covariance (ANCOVA) model was -10.2/-7.4 mm, and the upper limit of the 95% confidence interval was -6.44/-4.16 mm. CONCLUSIONS: NVP-1203 is more effective in reducing pain than the 100 mg aceclofenac alone. However, the two drugs have similar safety profiles in patients with acute LBP and muscle spasms.

Impact of discontinuing isolation in a private room for patients infected or colonized with vancomycin-resistant enterococci (VRE) on the incidence of healthcare-associated VRE bacteraemia in a hospital with a predominantly shared-room setting.

BACKGROUND: Isolating patients infected or colonized with vancomycin-resistant enterococci (VRE) in a private room or cohort room to prevent hospital transmission is controversial. AIM: To evaluate the effect of a relaxed isolation policy for VRE-infected or colonized patients on healthcare-associated (HA) VRE bacteraemia in an acute care hospital with a predominantly shared-room setting. METHODS: The incidence of HA VRE bacteraemia was compared during a private isolation era (October 2014-September 2017), a cohort isolation era (October 2017-June 2020), and a no isolation era (July 2020-June 2022). Using Poisson regression modelling, an interrupted time-series analysis was conducted to analyse level changes and trends in incidences of HA VRE bacteraemia for each era. FINDINGS: The proportion of VRE-infected or -colonized patients staying in shared rooms increased from 18.3% in the private isolation era to 82.6% in the no isolation era (P < 0.001). There was no significant difference in the incidences of HA VRE bacteraemia between the private isolation era and the cohort isolation era (relative risk: 1.01; 95% confidence interval: 0.52-1.98; P = 0.977) or between the cohort isolation era and the no isolation era (0.99; 0.77-1.26; P = 0.903). In addition, there was no significant slope increase in the incidence of HA VRE bacteraemia between any of the eras. CONCLUSION: In a hospital with predominantly shared rooms, the relaxation of isolation policy did not result in increased HA VRE bacteraemia, when other infection control measures were maintained.

Stress analysis of self-tightness metal sealing against ultrahigh pressure medium.

Stress is one of the most important factors in metal-to-metal sealing. In this paper, two methods (theoretical and empirical) were adopted to calculate the normal stress of the brass sealing surfaces against different ultrahigh pressure liquid. The theoretical formula was derived in terms of force balance, and the empirical formula was obtained by polynomial curve fitting, which the fitted data were from simulated results; besides, the results calculated using the empirical formula agree well with the results by theoretical formula. Meanwhile, the equivalent stresses of the brass seal, normal stress and contact stress on the brass seal surfaces were simulated by finite element method, and the simulated results indicated these stresses are increased with the increase of liquid pressure, and the maximum stresses always appear on the tip of the brass seal.

Effectiveness of transarterial embolisation for intractable postpartum haemorrhage in a disseminated intravascular coagulation state, despite emergency hysterectomy.

PURPOSE: We evaluated the effectiveness of transarterial embolization (TAE) for intractable postpartum hemorrhage in patients with disseminated intravascular coagulation (DIC) despite emergency hysterectomy. MATERIALS AND METHODS: We retrospectively assessed TAE performed after emergency hysterectomy in 15 patients between July 2008 and January 2022. Underlying condition, technical success, clinical success, angiographic findings, laboratory findings, pregnancy-modified DIC score (The International Society on Thrombosis and Haemostasis), blood transfusion, ICU (Intensive care unit) admission day, hospital day, in-hospital mortality, and long-term sequelae were evaluated. RESULTS: All patients were diagnosed with DIC before embolization, with a 43.9 mean DIC score. All patients showed positive angiographic findings for active bleeding. Thirty-eight bleeding arteries were confirmed. The remnant uterine artery (n=25) was the most common focus of persistent bleeding, followed by the cervicovaginal artery (n=6), pudendal artery (n=3), obturator artery (n=2), vesical artery (n=1), and unspecified artery from the internal iliac artery (n=1). Technical and clinical success rates were 100% (15/15) and 93.3% (14/15), respectively. Mean nadir hemoglobin (Hb) level before embolization was 4.9 g/dL. All patients underwent massive transfusion before embolization (mean 33.2 packs of RBC). Postoperatively, a smaller amount of blood was transfused than before the procedure (mean 10.6 packs of RBC). Mean nadir Hb level after embolization was 8.2 g/dL. There was one instance each of in-hospital death, hypoxic brain damage, and ischemic acute kidney injury. CONCLUSION: Despite hysterectomy for postpartum bleeding, there could be multiple residual or uncontrolled bleeding foci, especially in case of DIC, for which TAE could be an effective treatment.

Correction: A vesicular stomatitis virus-based prime-boost vaccination strategy induces potent and protective neutralizing antibodies against SARS-CoV-2.

[This corrects the article DOI: 10.1371/journal.ppat.1010092.].

Investigation on the transmission rate of carbapenemase-producing carbapenem-resistant Enterobacterales among exposed persons in a tertiary hospital using whole-genome sequencing.

BACKGROUND: To reduce transmission of carbapenemase-producing carbapenem-resistant Enterobacterales (CP-CRE), screening is recommended for patients sharing rooms with CP-CRE-detected patients and healthcare workers caring for them. AIM: The aim of this study was to investigate the transmission rate of CP-CRE among exposed people in a tertiary hospital using whole-genome sequencing. METHODS: This study was conducted in a 1751-bed tertiary teaching hospital from January 2017 to December 2019. Index patients were defined as those with positive results in CP-CRE tests during hospitalization. When an index patient was detected in a shared room, we performed CRE screening tests for patients whose stay overlapped with an index patient's stay for at least one day. Where a second case was found, healthcare worker contacts were also screened. CP-CRE were confirmed, and the carbapenemase type identified, by PCR. Whole-genome sequencing was used to compare isolates from index and exposed patients. RESULTS: During the study period, 47 index patients were identified, and they had been in contact with 152 patients in shared rooms and 54 healthcare workers. None of the healthcare workers had CRE. Among the 152 exposed patients, four patients had the same type of carbapenemases as their CP-CRE index patients and all of them were KPC. Whole-genome sequencing revealed that three of these four pairs showed genotypic accordance between the index and the exposed. CONCLUSION: The CP-CRE transmission rate among the exposed patients was calculated as 2.0% (= 3/152).

Foot care knowledge and self-care practices among diabetic patients in Penang: A primary care study.

INTRODUCTION: In Malaysia, the prevalence of diabetes mellitus has been increasing annually, currently affecting 18.3% of the population. Diabetic foot ulcer, a common complication of diabetes, is associated with high morbidity and mortality, consequently increasing health care expenditure. A previous study showed that foot care knowledge and foot self-care practices help to reduce the development of ulcers.1,2 This study aims to identify the level of foot care knowledge and self-care practices among diabetic patients in the primary care setting. OBJECTIVE: This study was to determine the level of foot care knowledge and foot self-care practices among diabetic patients in the primary care setting in Penang Island and its determinants and the correlation between level of foot care knowledge and self-care practices among diabetic patients. MATERIAL AND METHODS: A cross sectional study was performed on 311 diabetic patients who were registered to two government health clinics in Penang. Information regarding respondents' demographic status, foot care knowledge, and foot self-care practices were gathered using a self-administered questionnaire. Data were analysed using the Statistical Package for the Social Sciences (SPSS) 22. The Mann-Whitney U test and Kruskal-Wallis test were applied to the analysis. Multiple linear regression was performed to identify the determinants. Correlation between knowledge and self-care practice was determined using the linear regression model. RESULTS: One hundred and sixty-five (53.1%) respondents achieved good knowledge scores and 196 respondents (63%) achieved good self-care practice scores. The median age of respondents was 61 years, who were mostly females (56.6%), Malays (41.2%), and unemployed (48.6%). Median HbA1c level was 7.5%, and 42.8% of respondents had diabetes for 5 to 10 years. Lowest scores for knowledge and self-care practices were observed in foot skin care questions. Formal foot care education was found to be a significant predictor of foot care knowledge (p<0.05, 95% CI -1.102, -0.098). Foot care knowledge was significantly and positively correlated with foot self-care practices (p<0.001, 95% CI 0.548, 0.727). CONCLUSION: Foot care knowledge has significant positive correlation with foot self-care practices. Empowering diabetic patients with foot care knowledge may lead to significantly better foot self-care practices.

Midline versus paramedian mandibulotomy for tongue cancer surgery: analysis of complications.

Midline and paramedian mandibulotomies both have distinct anatomical and surgical strengths. A retrospective study was performed at Chang Gung Memorial Hospital, Linkou Branch between 2014 and 2019 to investigate how the osteotomy site (midline (n = 221) or paramedian (n = 44)) and type (straight, notched, or stair-stepped) affect postoperative and post-radiotherapy complications in patients undergoing wide excision of tongue cancer with flap reconstruction. Midline mandibulotomies were predominantly of the straight osteotomy type, while paramedian mandibulotomies were mostly notched type (P < 0.001). Comparably low elective tooth extraction rates were found in both approaches (P = 0.556). Paramedian mandibulotomy showed a higher osteoradionecrosis rate (P = 0.026), but there was no significance in the sub-analysis of individual types. Paramedian sites were associated with more early infection (P = 0.036) and plate exposure (P = 0.036) than midline sites with the straight osteotomy type, but complication rates did not differ significantly for the notched and stair-stepped types. Paramedian sites (P = 0.020) and notched types (P = 0.006) were associated with higher odds of osteoradionecrosis in the univariable logistic regression analysis, but only the notched type remained significant in the multivariable analysis (P = 0.048). In conclusion, paramedian sites increased the rate of osteoradionecrosis, and correlation with the osteotomy type resulted in more osteoradionecrosis in notched types and more complications in straight paramedian mandibulotomies.

Reduction in the acquisition rate of carbapenem-resistant Acinetobacter baumannii (CRAB) after room privatization in an intensive care unit.

BACKGROUND: Acinetobacter baumannii is one of the major pathogens responsible for healthcare-associated infections, especially in intensive care units (ICUs). AIM: To evaluate the effect of room privatization in an ICU on the acquisition of carbapenem-resistant A. baumannii (CRAB). METHODS: Between March and August 2017, a medical ICU was renovated from a multi-bed bay room to single rooms. Acquisition of CRAB was compared between patients admitted to the ICU over 18 months pre-renovation (September 2015 to February 2017) and post-renovation (September 2017 to February 2019). A Cox proportional hazard model was used with adjustment for demographics and comorbidities. FINDINGS: Of the 901 patients, who contributed 8276 patient-days, 95 (10.5%) acquired CRAB during their ICU stay. The CRAB acquisition rate was significantly higher during the pre-renovation period (1.87 per 100 patient-days) than during the post-renovation period (0.39 per 100 patient-days) (P<0.001). In the multi-variable Cox regression model, CRAB acquisition was significantly associated with the presence of a feeding tube (adjusted hazard ratio (aHR), 6.08; 95% confidence interval (CI), 2.46-15.06; P<0.001), continuous renal replacement therapy (aHR, 1.66; 95% CI, 1.09-2.53; P=0.019) and admission after renovation of the ICU to single rooms (aHR, 0.23; 95% CI, 0.12-0.41; P<0.001). CONCLUSIONS: Renovation of ICUs to single rooms is an efficient strategy to prevent transmission of multi-drug-resistant organisms and hospital-acquired infections.

A vesicular stomatitis virus-based prime-boost vaccination strategy induces potent and protective neutralizing antibodies against SARS-CoV-2.

The development of safe and effective vaccines to prevent SARS-CoV-2 infections remains an urgent priority worldwide. We have used a recombinant vesicular stomatitis virus (rVSV)-based prime-boost immunization strategy to develop an effective COVID-19 vaccine candidate. We have constructed VSV genomes carrying exogenous genes resulting in the production of avirulent rVSV carrying the full-length spike protein (SF), the S1 subunit, or the receptor-binding domain (RBD) plus envelope (E) protein of SARS-CoV-2. Adding the honeybee melittin signal peptide (msp) to the N-terminus enhanced the protein expression, and adding the VSV G protein transmembrane domain and the cytoplasmic tail (Gtc) enhanced protein incorporation into pseudotype VSV. All rVSVs expressed three different forms of SARS-CoV-2 spike proteins, but chimeras with VSV-Gtc demonstrated the highest rVSV-associated expression. In immunized mice, rVSV with chimeric S protein-Gtc derivatives induced the highest level of potent neutralizing antibodies and T cell responses, and rVSV harboring the full-length msp-SF-Gtc proved to be the superior immunogen. More importantly, rVSV-msp-SF-Gtc vaccinated animals were completely protected from a subsequent SARS-CoV-2 challenge. Overall, we have developed an efficient strategy to induce a protective response in SARS-CoV-2 challenged immunized mice. Vaccination with our rVSV-based vector may be an effective solution in the global fight against COVID-19.

Combination of Limosilactobacillus fermentum MG4231 and MG4244 attenuates lipid accumulation in high-fat diet-fed obese mice.

We investigated the anti-obesity effect and the underlying mechanisms of action of human-derived Limosilactobacillus fermentum MG4231, MG4244, and their combination, in high-fat diet-induced obese mice. Administration of the Limosilactobacillus strains decreased body weight gain, liver and adipose tissue weight, and glucose tolerance. Serum levels of total cholesterol, low-density lipoprotein-cholesterol, and leptin were reduced, while adiponectin increased. The administration of Limosilactobacillus strains improved the histopathological features of liver tissue, such as hepatic atrophy and inflammatory penetration, and significantly reduced the content of triglyceride in the liver. Limosilactobacillus administration discovered a significant reduction in the size of the adipocytes in the epididymal tissue. Limosilactobacillus treatment significantly reduced the expression of important regulators in lipid metabolism, including peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein α, fatty acid synthase (FAS), adipocyte-protein 2, and lipoprotein lipase in the epididymal tissue. Also, Limosilactobacillus lowered sterol regulatory element-binding protein 1-c and FAS in the liver tissue. Such changes in the expression of these regulators in both liver and epididymis tissue were caused by Limosilactobacillus upregulating phosphorylation of AMP-activated protein kinase and acetyl-CoA carboxylase. Therefore, we suggest that the use of the combination of L. fermentum MG4231 and MG4244, as probiotics could effectively inhibit adipogenesis and lipogenesis from preventing obesity.

Bioreactor production of rVSV-based vectors in Vero cell suspension cultures.

The Vero cell line is the most used continuous cell line in viral vaccine manufacturing. This adherent cell culture platform requires the use of surfaces to support cell growth, typically roller bottles, or microcarriers. We have recently compared the production of rVSV-ZEBOV on Vero cells between microcarrier and fixed-bed bioreactors. However, suspension cultures are considered superior with regard to process scalability. Therefore, we further explore the Vero suspension system for recombinant vesicular stomatitis virus (rVSV)-vectored vaccine production. Previously, this suspension cell line was only able to be cultivated in a proprietary medium. Here, we expand the adaptation and bioreactor cultivation to a serum-free commercial medium. Following small-scale optimization and screening studies, we demonstrate bioreactor productions of highly relevant vaccines and vaccine candidates against Ebola virus disease, HIV, and coronavirus disease 2019 in the Vero suspension system. rVSV-ZEBOV, rVSV-HIV, and rVSVInd -msp-SF -Gtc can replicate to high titers in the bioreactor, reaching 3.87 × 107 TCID50 /ml, 2.12 × 107 TCID50 /ml, and 3.59 × 109 TCID50 /ml, respectively. Furthermore, we compare cell-specific productivities, and the quality of the produced viruses by determining the ratio of total viral particles to infectious viral particles.

Induction of protective immune responses against a lethal Zika virus challenge post-vaccination with a dual serotype of recombinant vesicular stomatitis virus carrying the genetically modified Zika virus E protein gene.

The development of a vaccine to prevent Zika virus (ZIKV) infection has been one of the priorities in infectious disease research in recent years. There have been numerous attempts to develop an effective vaccine against ZIKV. It is imperative to choose the safest and the most effective ZIKV vaccine from all candidate vaccines to control this infection globally. We have employed a dual serotype of prime-boost recombinant vesicular stomatitis virus (VSV) vaccine strategy, to develop a ZIKV vaccine candidate, using a type 1 IFN-receptor knock-out (Ifnar-/-) mouse model for challenge studies. Prime vaccination with an attenuated recombinant VSV Indiana serotype (rVSVInd) carrying a genetically modified ZIKV envelope (E) protein gene followed by boost vaccination with attenuated recombinant VSV New Jersey serotype (rVSVNJ) carrying the same E gene induced robust adaptive immune responses. In particular, rVSV carrying the ZIKV E gene with the honeybee melittin signal peptide (msp) at the N terminus and VSV G protein transmembrane domain and cytoplasmic tail (Gtc) at the C terminus of the E gene induced strong protective immune responses. This vaccine regimen induced highly potent neutralizing antibodies and T cell responses in the absence of an adjuvant and protected Ifnar-/- mice from a lethal dose of the ZIKV challenge.

Perceived usefulness and ease of use of fundoscopy by medical students: a randomised crossover trial of six technologies (eFOCUS 1).

BACKGROUND: Fundoscopy outside ophthalmology is in decline, and the technical demands of the traditional direct ophthalmoscope examination are likely contributing. Alternative fundoscopy technologies are increasingly available, yet valid comparisons between fundoscopy technologies are lacking. We aimed to assess medical students' perceptions of usefulness and ease of use of traditional and contemporary fundus-viewing technologies including smartphone fundoscopy. METHODS: One hundred forty-six second-year medical students participated in a cross-sectional, randomised, cross-over study of fundoscopy methods. Medical students completed small group training sessions using six current fundoscopy technologies including: a non-mydriatic fundus camera; two types of direct fundoscopy; and three types of smartphone fundoscopy. A novel survey of perceived usefulness and ease of use was then completed by students. RESULTS: Repeated-measures ANOVA found students rated both the perceived usefulness (p< 0.001) and ease of use (p< 0.001) of smartphone fundoscopy significantly higher than both the non-mydriatic camera and direct fundoscopy. CONCLUSIONS: Smartphone fundoscopy was found to be significantly more useful and easier to use than other modalities. Educators should optimise student access to novel fundoscopy technologies such as smartphone fundoscopy which may mitigate the technical challenges of fundoscopy and reinvigorate use of this valuable clinical examination.

Enhanced antimicrobial stewardship based on rapid phenotypic antimicrobial susceptibility testing for bacteraemia in patients with haematological malignancies: a randomized controlled trial.

OBJECTIVES: Recently, rapid phenotypic antimicrobial susceptibility testing (AST) based on microscopic imaging analysis has been developed. The aim of this study was to determine whether implementation of antimicrobial stewardship programmes (ASP) based on rapid phenotypic AST can increase the proportion of patients with haematological malignancies who receive optimal targeted antibiotics during early periods of bacteraemia. METHODS: This randomized controlled trial enrolled patients with haematological malignancies and at least one positive blood culture. Patients were randomly assigned 1:1 to conventional (n = 60) or rapid phenotypic (n = 56) AST. The primary outcome was the proportion of patients receiving optimal targeted antibiotics 72 hr after blood collection for culture. RESULTS: The percentage receiving optimal targeted antibiotics at 72 hr was significantly higher in the rapid phenotypic AST group (45/56, 80.4%) than in conventional AST group (34/60, 56.7%) (relative risk (RR) 1.42, 95% confidence interval (CI) 1.09-1.83). The percentage receiving unnecessary broad-spectrum antibiotics at 72 hr was significantly lower (7/26, 12.5% vs 18/60, 30.0%; RR 0.42, 95% CI 0.19-0.92) and the mean time to optimal targeted antibiotic treatment was significantly shorter (38.1, standard deviation (SD) 38.2 vs 72.8, SD 93.0 hr; p < 0.001) in the rapid phenotypic AST group. The mean time from blood collection to the AST result was significantly shorter in the rapid phenotypic AST group (48.3, SD 17.6 vs 83.1, SD 22.2 hr). DISCUSSION: ASP based on rapid phenotypic AST can rapidly optimize antibiotic treatment for bacteraemia in patients with haematological malignancy. Rapid phenotypic AST can improve antimicrobial stewardship in immunocompromised patients.

KLF15 reduces the level of apoptosis in mouse liver induced by sepsis by inhibiting p38MAPK/ERK1/2 signaling pathway.

OBJECTIVE: Sepsis-induced acute liver injury (ALI) involves multiple systems in the body. The disease is acute and critical, with various symptoms, including extensive necrosis of liver cells. There is currently no effective treatment to deal with ALI in a timely manner. This study verified the therapeutic effect of Krüppel-like factor 15 (KLF15) on ALI by studying its anti-apoptotic effect on the liver. MATERIALS AND METHODS: We induced ALI in mice with lipopolysaccharide (LPS)/D-galactosamine (D-GaIN). Recombinant mouse KLF15 was used to treat mice to examine the protective effects of KLF15 on mouse liver and the effects of apoptosis-related molecules. In addition, we cultured Kupffer cells and determined the anti-inflammatory and anti-apoptotic effects of KLF15 and its mechanism by overexpressing KLF15. RESULTS: Exogenous KLF15 effectively reduced the levels of TIBL, ALT, AST, and inflammatory factors (COX-2, MCP-1, IL-1ß, and TNF-α) in mouse serum. The results of HE staining also demonstrate that KLF15 improves the morphology of liver tissue. In addition, the expression of KLF15 in LPS-induced Kupffer cells was significantly reduced and KLF15 increased the viability of Kupffer cells and decreased the level of inflammation in Kupffer cells. In both in vivo and in vitro experiments, KLF15 reduced the level of apoptosis in hepatocytes or Kupffer cells and inhibited the activity of the p38MAPK/ERK1/2 signaling pathway. CONCLUSIONS: KLF15 reduces the apoptosis and inflammation levels of liver and Kupffer cells by inhibiting the p38MAPK/ERK1/2 signaling pathway and alleviates LPS/D-GaIN-induced ALI.