Insights into cytomegalovirus-associated T cell receptors in recipients following allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Cytomegalovirus (CMV) reactivation is a serious problem in recipients of allogeneic hematopoietic stem cell transplantation. Long-term latency depends on specific T cell immune reconstitution, which identifies various pathogens by T cell receptors (TCRs). However, the mechanisms underlying the selection of CMV-specific TCRs in recipients after transplantation remain unclear. METHODS: Using high-throughput sequencing and bioinformatics analysis, the T cell immune repertoire of seven CMV reactivated recipients (CRRs) were analyzed and compared to those of seven CMV non-activated recipients (CNRs) at an early stage after transplant. RESULTS: The counts of unique complementarity-determining region 3 (CDR3) were significantly higher in CNRs than in CRRs. The CDR3 clones in the CNRs exhibit higher homogeneity compared to the CRRs. With regard to T cell receptor ß-chain variable region (TRBV) and joint region (TRBJ) genotypes, significant differences were observed in the frequencies of TRBV6, BV23, and BV7-8 between the two groups. In addition to TRBV29-1/BJ1-2, TRBV2/BJ2-2, and TRBV12-4/BJ1-5, 11 V-J combinations had significantly different expression levels between CRRs and CNRs. CONCLUSIONS: The differences in TCR diversity, TRBV segments, and TRBV-BJ combinations observed between CNRs and CRRs might be associated with post-transplant CMV reactivation and could serve as a foundation for further research.

Prehospital ultrasound scanning for abdominal free fluid detection in trauma patients: a systematic review and meta-analysis.

INTRODUCTION: Focused assessment with sonography for trauma helps detect abdominal free fluid. Prehospital ultrasound scanning is also important because the early diagnosis of hemoperitoneum may reduce the time to definitive treatment in the hospital. This study investigated whether prehospital ultrasound scanning can help detect abdominal free fluid. MATERIALS AND METHODS: In this systematic review, relevant databases were searched for studies investigating prehospital ultrasound examinations for abdominal free fluid in trauma patients. The prehospital ultrasound results were compared with computed tomography, surgery, or hospital ultrasound examination data. The pooled sensitivity and specificity values were analyzed using forest plots. The overall predictive power was calculated by the summary receiver operating characteristic curve. The quality of the included studies was assessed using the quality assessment of diagnostic accuracy studies tool. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was performed to assess the certainty of evidence. RESULT: This meta-analysis comprised six studies that included 1356 patients. The pooled sensitivity and specificity values were 0.596 (95% confidence interval [CI] = 0.345-0.822) and 0.970 (95% CI = 0.953-0.983), respectively. The pooled area under the summary receiver operating characteristic curve was 0.998. The quality assessment tool showed favorable results. In the GRADE analysis, the quality of evidence was very low for sensitivity and high for specificity when prehospital ultrasound was used for hemoperitoneum diagnosis. CONCLUSION: The specificity of abdominal free fluid detection using prehospital ultrasound examinations in trauma patients was very high.

A Multi-institutional Analysis of the Combined Effect of Micropapillary Component and Consolidation-to-Tumor Ratio >0.5 on the Prognosis of Pathological, Stage IA3, Lung Adenocarcinoma.

INTRODUCTION: The study investigated the synergistic effect of the micropapillary (MIP) component and consolidation-to-tumor ratio (CTR) on the recurrence and survival of patients with pathologic stage IA3 lung adenocarcinoma. METHODS: We enrolled 419 patients confirmed pathological stage IA3 adenocarcinoma from four institutions. Kaplan-Meier analysis was performed to examine the value of the MIP component and CTR on relapse-free survival (RFS) and overall survival (OS). The cumulative recurrence between different stages was analyzed by using cumulative event curves. RESULTS: RFS (P < 0.0001) and OS (P = 0.008) in the presence of the MIP group were significantly lower than those in the absence of the MIP group, and CTR > 5 only reduced RFS (P = 0.0004), but not OS (P = 0.063), in the patients. In addition, the prognosis of patients with both the MIP component and CTR > 5 was worse than that of those without the MIP component or CTR ≤ 5. Therefore, we established new subtypes of the stage IA3: IA3a, IA3b, and IA3c. RFS and OS for IA3c staging were significantly lower than those for IA3a and IA3b. For IA3c, the cumulative incidence of local recurrence (P < 0.001) and that of distant metastasis (P = 0.004) were significantly higher than those for IA3a and IA3b. CONCLUSIONS: The MIP component combined with CTR > 0.5 can effectively predict the prognosis of patients with pathological stage IA3 lung adenocarcinoma and may offer more detailed recurrence and survival information according to the established subtype stage of IA3.

The Coronary Reperfusion Effect and Safety of Prehospital P2Y12 Inhibitor in Primary-PCI STEMI Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: The concept of early administration of P2Y12 inhibitor in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) is widely accepted, but whether prehospital administration results in greater coronary reperfusion remains unclear. Our study aims to analyze the benefit and safety of prehospital P2Y12 inhibitor compared to in-hospital P2Y12 inhibitor administration. METHOD: Three databases (PubMed, EMBASE, and Cochrane Library) were searched from database inception to June 2023. We included all types of studies except for conference publications, abstract presentations, reviews, and case reports. The primary outcomes were pre-PCI TIMI flow grade 2-3 (TIMI = Thrombolysis in Myocardial Infarction) and major bleeding. The secondary outcomes included post-PCI TIMI flow grade 2-3, major adverse cardiac events (MACE), recurrent myocardial infarction (MI), and short-term (30-day) mortality. RESULT: Eight individual studies with a total of 10823 patients were included in our meta-analysis. Compared with in-hospital P2Y12 inhibitor, prehospital P2Y12 inhibitor were associated with significantly higher rates of pre-PCI TIMI flow grade 2-3 (OR 1.32, 95% CI: 1.09-1.61, p = 0.005) and post-PCI TIMI flow grade 2-3 (OR 1.43, 95% CI: 1.04-1.97, p = 0.03), and a significantly lower risk of recurrent MI (OR 0.69, 95% CI: 0.49-0.96, p = 0.03). There were no significant difference in the risk of major bleeding (OR 1.00, 95% CI: 0.75-1.32, p = 0.98), MACE (OR 0.94, 95% CI: 0.70-1.25, p = 0.65), or short-term mortality (OR 0.87, 95% CI: 0.50-1.51, p = 0.61). CONCLUSION: Prehospital P2Y12 inhibitor compared to in-hospital P2Y12 inhibitor is associated with a significantly higher rate of pre-PCI and post-PCI TIMI flow grade 2-3, a reduced risk of recurrent MI, and no increase in major bleeding in STEMI patients undergoing primary PCI.

The adjusted impact of different severities of acute exacerbations and medications on the risk of developing dementia in COPD patients.

BACKGROUND: Although a relationship between chronic obstructive pulmonary disease (COPD) and dementia has been reported, the initial severity upon emergency department (ED) visits and the medications used have not been well evaluated as risk factors for increased dementia occurrence. We aimed to analyze the risks of dementia development over 5 years among patients with COPD compared to matched controls (primary) and the impact of different severities of acute exacerbations (AEs) of COPD and medications on the risk of dementia development among COPD patients (secondary). METHOD: This study used the Taiwanese government deidentified health care database. We enrolled patients during the 10-year study period (January 1, 2000, to December 31, 2010), and each patient was followed up for 5 years. Once these patients received a diagnosis of dementia or died, they were no longer followed up. The study group included 51,318 patients who were diagnosed with COPD and 51,318 matched (in terms of age, sex, and the number of hospital visits) non-COPD patients from the remaining patients as the control group. Each patient was followed up for 5 years to analyze the risk of dementia with Cox regression analysis. Data on medications (antibiotics, bronchodilators, corticosteroids) and severity at the initial ED visit (ED treatment only, hospital admission, or ICU admission) were collected for both groups, as well as demographics and baseline comorbidities, which were considered confounding factors. RESULTS: In the study and control groups, 1,025 (2.0%) and 423 (0.8%) patients suffered from dementia, respectively. The unadjusted HR for dementia was 2.51 (95% CI: 2.24-2.81) in the study group. Bronchodilator treatment was associated with the HRs, especially among those who received long-term (> 1 month) treatment (HR = 2.10, 95% CI: 1.91-2.45). Furthermore, among 3,451 AE of COPD patients who initially visited the ED, patients who required ICU admission (n = 164, 4.7%) had a higher risk of dementia occurrence (HR = 11.05, 95% CI: 7.77-15.71). CONCLUSION: Bronchodilator administration might be associated with a decreased risk of dementia development. More importantly, patients who suffered AEs of COPD and initially visited the ED and required ICU admission had a higher risk of developing dementia.

Intelligent Fault Diagnosis of Hydraulic Multi-Way Valve Using the Improved SECNN-GRU Method with mRMR Feature Selection.

Hydraulic multi-way valves as core components are widely applied in engineering machinery, mining machinery, and metallurgical industries. Due to the harsh working environment, faults in hydraulic multi-way valves are prone to occur, and the faults that occur are hidden. Moreover, hydraulic multi-way valves are expensive, and multiple experiments are difficult to replicate to obtain true fault data. Therefore, it is not easy to achieve fault diagnosis of hydraulic multi-way valves. To address this problem, an effective intelligent fault diagnosis method is proposed using an improved Squeeze-Excitation Convolution Neural Network and Gated Recurrent Unit (SECNN-GRU). The effectiveness of the method is verified by designing a simulation model for a hydraulic multi-way valve to generate fault data, as well as the actual data obtained by establishing an experimental platform for a directional valve. In this method, shallow statistical features are first extracted from data containing fault information, and then fault features with high correlation with fault types are selected using the Maximum Relevance Minimum Redundancy algorithm (mRMR). Next, spatial dimension features are extracted through CNN. By adding the Squeeze-Excitation Block, different weights are assigned to features to obtain weighted feature vectors. Finally, the time-dimension features of the weighted feature vectors are extracted and fused through GRU, and the fused features are classified using a classifier. The fault data obtained from the simulation model verifies that the average diagnostic accuracy of this method can reach 98.94%. The average accuracy of this method can reach 92.10% (A1 sensor as an example) through experimental data validation of the directional valve. Compared with other intelligent diagnostic algorithms, the proposed method has better stationarity and higher diagnostic accuracy, providing a feasible solution for fault diagnosis of the hydraulic multi-way valve.

Identification of a protective Bacteroides strain of alcoholic liver disease and its synergistic effect with pectin.

The depletion of Bacteroides in the gut is closely correlated with the progression of alcoholic liver disease (ALD). This study aimed to identify Bacteroides strains with protective effects against ALD and evaluate the synergistic effects of Bacteroides and pectin in this disease. Mice were fed Lieber-DeCarli alcohol diet to establish an experimental ALD model and pre-treated with 4 Bacteroides strains. The severity of the liver injury, hepatic steatosis, and inflammation was evaluated through histological and biochemical assays. We found that Bacteroides fragilis ATCC25285 had the best protective effects against ALD strains by alleviating both ethanol-induced liver injury and steatosis. B. fragilis ATCC25285 could counteract inflammatory reactions in ALD by producing short-chain fat acids (SCFAs) and enhancing the intestinal barrier. In the subsequent experiment, the synbiotic combination of B. fragilis ATCC25285 and pectin was evaluated and the underlying mechanisms were investigated by metabolomic and microbiome analyses. The combination elicited superior anti-ALD effects than the individual agents used alone. The synergistic effects of B. fragilis ATCC25285 and pectin were driven by modulating gut microbiota, improving tryptophan metabolism, and regulating intestinal immune function. Based on our findings, the combination of B. fragilis ATCC25285 and pectin can be considered a potential treatment for ALD. KEY POINTS: • B. fragilis ATCC25285 was identified as a protective Bacteroides strain against ALD. • The synbiotic combination of B. fragilis and pectin has better anti-ALD effects. • The synbiotic combination modulates gut microbiota and tryptophan metabolism.

Lower testosterone levels predict increasing severity and worse outcomes of hepatitis B virus-related acute-on-chronic liver failure in males.

BACKGROUND: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a serious liver disease with pathogenesis remaining unclear. This study aims to investigate the association between testosterone levels, stage (early, middle, or late, categorized according to clinical manifestation), severity scores, and clinical outcomes of HBV-ACLF. METHODS: This single-center observational study involved 160 male patients with HBV-ACLF, 151 chronic hepatitis B patients without liver failure (CHB) and 106 healthy controls (HC). Morning blood samples were collected and androgen levels analyzed by chemi-bioluminescent immunoassay. Time to death or liver transplantation within 90 days comprised the primary composite outcome. RESULTS: Serum levels of total testosterone (TT), free testosterone index (FTI), dehydroepiandrosterone sulfate and cortisol were significantly lower among HBV-ACLF than CHB and HC, while androstenedione was higher. Low TT, sex hormone binding globulin and FTI were associated with increased stage (of HBV-ACLF, ascites, and hepatic encephalopathy) and severity scores (Model for End-stage Liver Disease and Chinese Group on the Study of Severe Hepatitis B-ACLF scores). Low TT (< 142.39 ng/dL) was a risk factor for both the composite outcome and for death alone within 90 days. Multivariate analysis revealed TT to be an independent predictor for the composite outcome (hazard ratio 2.57, 95% CI 1.09-6.02; P = 0.030). CONCLUSION: Low serum testosterone is common among male patients with HBV-ACLF and predictive of increased severity and worse outcome of the disease and may play an important role in the progression of HBV-ACLF.

The effect of the head-up position on cardiopulmonary resuscitation: a systematic review and meta-analysis.

OBJECTIVE: Experimental studies of head-up positioning (HUP) during cardiopulmonary resuscitation (CPR) have had some degree of conflicting published results. The current study aim was to analyze and reconcile those discrepancies in order to better clarify the effects of HUP CPR compared to conventional supine (SUP) CPR. METHODS: Three databases (PubMed, EMBASE and Cochrane Library) were searched comprehensively (from each respective database's inception to May 2021) for articles addressing HUP CPR. The primary outcome to be observed was cerebral perfusion pressure (CerPP), and secondary outcomes were mean intracranial pressure (ICP), mean arterial pressure (MAP), coronary perfusion pressure (CoPP) and frequencies of return of spontaneous circulation (ROSC). RESULTS: Seven key studies involving 131 animals were included for analysis. Compared to SUP CPR, CerPP (MD 10.37; 95% CI 7.11-13.64; p < 0.01; I2 = 58%) and CoPP (MD 7.56; 95% CI 1.84-13.27, p = 0.01; I2 = 75%) increased significantly with HUP CPR, while ICP (MD - 13.66; 95% CI - 18.6 to -8.71; p < 0.01; I2 = 96%) decreased significantly. Combining all study methodologies, there were no significant differences detected in MAP (MD - 1.63; 95% CI - 10.77-7.52; p = 0.73; I2 = 93%) or frequency of ROSC (RR 0.9; 95% CI 0.31-2.60; p = 0.84; I2 = 65%). However, in contrast to worse outcomes in studies using immediate elevation of the head in a reverse Trendelenburg position, study outcomes were significantly improved when HUP (head and chest only) was introduced in a steady, graduated manner following a brief period of basic CPR augmented by active compression-decompression (ACD) and impedance threshold (ITD) devices. CONCLUSION: In experimental models, gradually elevating the head and chest following a brief interval of circulatory priming with ACD and ITD devices can enhance CoPP, lower ICP and improve CerPP significantly while maintaining MAP. This effect is immediate, remains sustained and is associated with improved outcomes.

Modulation of the immune response and metabolism in germ-free rats colonized by the probiotic Lactobacillus salivarius LI01.

The gut microbiota plays an important role in multifaceted physiological functions in the host. Previous studies have assessed the probiotic effects of Lactobacillus salivarius LI01. In this study, we aimed to investigate the potential effects and putative mechanism of L. salivarius LI01 in immune modulation and metabolic regulation through the monocolonization of germ-free (GF) Sprague-Dawley (SD) rats with L. salivarius LI01. The GF rats were separated into two groups and administered a gavage of L. salivarius LI01 or an equal amount of phosphate-buffered saline. The levels of serum biomarkers, such as interleukin (IL)-1α, IL-5, and IL-10, were restored by L. salivarius LI01, which indicated the activation of Th0 cell differentiation toward immune homeostasis. L. salivarius LI01 also stimulated the immune response and metabolic process by altering transcriptional expression in the ileum and liver. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed significant enrichment of the 5'-adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, which indicated that L. salivarius LI01 exerts an effect on energy accumulation. The LI01 group showed alterations in fecal carbohydrates accompanied by an increased body weight gain. In addition, L. salivarius LI01 produced indole-3-lactic acid (ILA) and enhanced arginine metabolism by rebalancing the interconversion between arginine and proline. These findings provide evidence showing that L. salivarius LI01 can directly impact the host by modulating immunity and metabolism. KEY POINTS : • Lactobacillus salivarius LI01 conventionalizes the cytokine profile and activates the immune response. • LI01 modulates carbohydrate metabolism and arginine transaction. • LI01 generates tryptophan-derived indole-3-lactic acid. • The cytochrome P450 family contributes to the response to altered metabolites.

AMBtalk: A Cardiovascular IoT Device for Ambulance Applications.

Acute Coronary Syndrome (ACS) and other heart emergency events require immediate chest pain identification in the ambulance. Specifically, early identification and triage is required so that patients with chest pain can be quickly sent to a hospital with appropriate care facilities for treatment. In the traditional approach, ambulance personnel often use symptom checklists to examine the patient and make a quick decision for the target hospital. However, not every hospital has specialist facilities to handle such emergency cases. If the result of the subsequent cardiac enzyme test performed at the target hospital strongly suggests the occurrence of myocardial infarction, the patient may need to be sent to another hospital with specialist facilities, such as Percutaneous Coronary Intervention. The standard procedure is time consuming, which may result in delayed treatment and reduce patent survival rate. To resolve this issue, we propose AMBtalk (Ambulance Talk) for accurate, early ACS identification in an ambulance. AMBtalk provides real-time connection to hospital resources, which reduces the elapsed time for treatment, and therefore, improves the patient survival rate. The key to success for AMBtalk is the development of the AllCheck® Internet of Things (IoT) device, which can accurately and quickly provide cardiovascular parameter values for early ACS identification. The interactions between the AllCheck® IoT device, the emergency medical service center, the ambulance personnel and the hospital are achieved through the AMBtalk IoT server in the cloud network. AllCheck® outperforms the existing cardiovascular IoT device solutions for ambulance applications. The testing results of the AllCheck® device show 99% correlation with the results of the hospital reports. Due to its excellent performance in quick ACS identification, the AllCheck® device was awarded the 17th Taiwan Innovators Award in 2020.

Alterations of the Gut Microbiota in Patients With Coronavirus Disease 2019 or H1N1 Influenza.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging serious global health problem. Gastrointestinal symptoms are common in COVID-19 patients, and severe acute respiratory syndrome coronavirus 2 RNA has been detected in stool specimens. However, the relationship between the gut microbiome and disease remains to be established. METHODS: We conducted a cross-sectional study of 30 patients with COVID-19, 24 patients with influenza A(H1N1), and 30 matched healthy controls (HCs) to identify differences in the gut microbiota by 16S ribosomal RNA gene V3-V4 region sequencing. RESULTS: Compared with HCs, COVID-19 patients had significantly reduced bacterial diversity; a significantly higher relative abundance of opportunistic pathogens, such as Streptococcus, Rothia, Veillonella, and Actinomyces; and a lower relative abundance of beneficial symbionts. Five biomarkers showed high accuracy for distinguishing COVID-19 patients from HCs with an area under the curve (AUC) up to 0.89. Patients with H1N1 displayed lower diversity and different overall microbial composition compared with COVID-19 patients. Seven biomarkers were selected to distinguish the 2 cohorts (AUC = 0.94). CONCLUSIONS: The gut microbial signature of patients with COVID-19 was different from that of H1N1 patients and HCs. Our study suggests the potential value of the gut microbiota as a diagnostic biomarker and therapeutic target for COVID-19, but further validation is needed.

The fiber metabolite butyrate reduces gp130 by targeting TRAF5 in colorectal cancer cells.

BACKGROUND: Dietary fiber is effective for colorectal cancer (CRC) treatment. Interleukin-6 (IL-6) and its adaptors are potential targets for CRC therapy. Butyrate, a metabolite of dietary fiber, is a new, highly safe type of targeted drug. METHODS: In this study, Cell Counting Kit-8 cell viability and wound healing assays, western blot analysis, immunofluorescence staining, and xenograft tumor mouse models were used to evaluate the anticancer effect of butyrate and its possible mechanism in vivo and in vitro. RESULTS: Dietary fiber and sodium butyrate (NaB) decreased CRC burden by decreasing IL-6 receptor gp130 and blocking IL-6/JAK2/STAT3 axis activation in vitro and in vivo. Furthermore, NaB reduced the gp130 protein level by regulating its degradation rate via targeting TRAF5. CONCLUSIONS: The fiber metabolite butyrate inhibits CRC development by reducing gp130 via TRAF5.

Diffusion kurtosis imaging differs between primary central nervous system lymphoma and high-grade glioma and is correlated with the diverse nuclear-to-cytoplasmic ratio: a histopathologic, biopsy-based study.

OBJECTIVES: To determine whether water kurtosis and diffusional metrics derived from diffusional kurtosis imaging (DKI) within primary central nervous system lymphomas (PCNSLs) and high-grade gliomas (HGGs) correlate with cellularity and/or nuclear-to-cytoplasmic (N/C) ratio. METHODS: Forty-four and 43 pathologically confirmed high-grade glioma and primary central nervous system lymphoma specimens between May 2013 and November 2016 were retrospectively reviewed. Diffusional metrics, kurtosis metrics, cellularity, and N/C ratios in PCNSLs and HGGs were compared using the Mann-Whitney U test (significant level, p < 0.007 [0.05/7]); Bonferroni correction). RESULTS: Mean kurtosis (MK), axial kurtosis (K//), and radial kurtosis (K⊥) in PCNSLs were 0.857 (0.693-0.924), 0.837 (0.660-0.941), and 0.834 (0.685-0.937), respectively; and 0.629 (0.524-0.716), 0.575 (0.511-0.689), and 0.675 (0.532-0.766), respectively, in HGGs (all p < 0.001). No significant differences in fractional anisotropy (FA), mean diffusion (MD), axial diffusion (λ//), and radial diffusion (λ⊥) were found between HGGs and PCNSLs. Cellularity was higher in PCNSLs than in HGGs (p = 0.125); whereas, the N/C ratio in PCNSLs was significantly higher than that in HGGs (p < 0.001). All DKI metrics (FA, MD, λ//, λ⊥, MK, K//, and K⊥) were significantly correlated with N/C ratio in PCNSLs with correlation coefficients being rho = 0.418, - 0.722, - 0.525, - 0.768, 0.704, 0.579, and 0.686, respectively. Cellularity in PCNSLs and HGGs did not correlate with any kurtosis or diffusional metrics. CONCLUSIONS: Difference of kurtosis parameters between PCNSLs and HGGs is correlated with their diverse N/C ratio. KEY POINTS: • DKI has considerable value in differentiating between PCNSLs and HGGs. • DKI can provide important information on nuclear-to-cytoplasmic ratio. • Difference of kurtosis parameters between PCNSLs and HGGs correlated well with their diverse N/C ratios.

Lactobacillus salivarius LI01 encapsulated in alginate-pectin microgels ameliorates D-galactosamine-induced acute liver injury in rats.

Acute liver failure is a clinical emergency associated with high mortality. Accumulating evidence indicates that gut microbiota participates in the progression of liver injury, and preventive therapies based on altering gut microbiota are of great interest. Previous studies demonstrated that Lactobacillus salivarius LI01 attenuates hepatic injury, though efficiency in curtailed in the harsh environment in the gastrointestinal tract. In this study, a system to encapsulate LI01 in alginate-pectin (AP) microgels was investigated. Encapsulation significantly enhances probiotic viability for long-term storage and heat treatment, and in simulated gastrointestinal fluids (SGF or SIF) and bile salt solutions. Acute liver injury was induced in Sprague-Dawley (SD) rats by D-galactosamine (D-GaIN) injection following pretreatment with probiotics. Liver and gut barrier function, cytokines, liver and gut histology, bacterial translocation, and gut microbiota were assessed. Administration of encapsulated LI01 more effectively upregulates hepatic anti-inflammatory cytokine IL-10 and TLR-3, restores expressions of gut barrier biomarkers Claudin-1 and MUC2 and attenuates destruction of mucosal ultrastructure compared with unencapsulated probiotics pretreatment. Pretreatment with AP-LI01 microgels altered the microbial community, decreasing the abundance of pathogenic taxa Ruminiclostridium, Dorea and Ruminococcaceae_UCG-004 and enriching beneficial taxa Ruminococcaceae_UCG-014, Eubacterium, and Prevotella_1 that produce short-chain fatty acids. These results suggest that AP encapsulation of LI01 boosts viability and attenuates liver injury by reducing inflammation and restoring intestinal barrier function. These beneficial effects are probably due to alternation of gut flora. These findings provide new insight into encapsulation technology and prevention of liver failure. KEY POINTS: • Alginate-pectin encapsulation enhances the viability of Lactobacillus salivarius LI01 under simulated commercial conditions and simulated gastrointestinal environment. • AP-LI01 microgel attenuates hepatic and intestinal inflammation and restores gut barrier function. • AP-LI01 microgel alters gut microbial community with increased SCFAs producers and decreased pathogenic microbes. • Beneficial improvements after administration of probiotics are highly associated with alternation of gut microbial community.

Reducing the consumption of personal protective equipment by setting up a multifunctional sampling station in the emergency department to screen for COVID-19 infection in Taiwan.

In Taiwan, high-risk patients have been identified and tested for preventing community spread of COVID-19. Most sample collection was performed in emergency departments (EDs). Traditional sample collection requires substantial personal protective equipment (PPE), healthcare professionals, sanitation workers, and isolation space. To solve this problem, we established a multifunctional sample collection station (MSCS) for COVID-19 testing in front of our ED. The station is composed of a thick and clear acrylic board (2 cm), which completely separates the patient and medical personnel. Three pairs of gloves (length, 45 cm) are attached and fixed on the outside wall of the MSCS. The gloves are used to conduct sampling of throat/nasal swabs, sputum, and blood from patients. The gap between the board and the building is only 0.2 cm (sealed with silicone sealant). ED personnel communicate with patients using a small two-way broadcast system. Medical waste is put in specific trashcans installed in the table outside the MSCS. With full physical protection, the personnel conducting the sampling procedure need to wear only their N95 mask and gloves. After we activated the station, our PPE, sampling time, and sanitization resources were considerably conserved during the 4-week observation period. The MSCS obviously saved time and PPE. It elevated the efficiency and capacity of the ED for handling potential community infections of COVID-19.

Determination of the Absolute Configuration of Super-Carbon-Chain Compounds by a Combined Chemical, Spectroscopic, and Computational Approach: Gibbosols†A and B.

Marine dinoflagellates produce remarkable organic molecules, particularly those with polyoxygenated long-carbon-chain backbones, namely super-carbon-chain compounds (SCCCs), characterized by the presence of numerous stereogenic carbon centers on acyclic polyol carbon chains. Even today, it is a challenge to determine the absolute configurations of these compounds. In this work, the planar structures and absolute configurations of two highly flexible SCCCs, featuring either a C69 - or C71 -linear carbon backbone, gibbosols A and B, respectively, each containing thirty-seven stereogenic carbon centers, were unambiguously established by a combined chemical, spectroscopic, and computational approach. The discovery of gibbosols A and B with two hydrophilic acyclic polyol chains represents an unprecedented class of SCCCs. A reasonable convergent strategy for the biosynthesis of these SCCCs was proposed.

Time to epinephrine treatment is associated with the risk of mortality in children who achieve sustained ROSC after traumatic out-of-hospital cardiac arrest.

BACKGROUND: The benefits of early epinephrine administration in pediatric with nontraumatic out-of-hospital cardiac arrest (OHCA) have been reported; however, the effects in pediatric cases of traumatic OHCA are unclear. Since the volume-related pharmacokinetics of early epinephrine may differ obviously with and without hemorrhagic shock (HS), beneficial or harmful effects of nonselective epinephrine stimulation (alpha and beta agonists) may also be enhanced with early administration. In this study, we aimed to analyze the therapeutic effect of early epinephrine administration in pediatric cases of HS and non-HS traumatic OHCA. METHODS: This was a multicenter retrospective study (2003-2014). Children (aged ≤ 19 years) who experienced traumatic OHCA and were administered epinephrine for resuscitation were included. Children were classified into the HS (blood loss > 30% of total body fluid) and non-HS groups. The demographics, outcomes, postresuscitation hemodynamics (the first hour) after the sustained return of spontaneous circulation (ROSC), and survival durations were analyzed and correlated with the time to epinephrine administration (early < 15, middle 15-30, late > 30 min) in the HS and non-HS groups. Cox regression analysis was used to adjust for risk factors of mortality. RESULTS: A total of 509 children were included. Most of them (n = 348, 68.4%) had HS OHCA. Early epinephrine administration was implemented in 131 (25.7%) children. In both the HS and non-HS groups, early epinephrine administration was associated with achieving sustained ROSC (both p < 0.05) but was not related to survival or good neurological outcomes (without adjusting for confounding factors). However, early epinephrine administration in the HS group increased cardiac output but induced metabolic acidosis and decreased urine output during the initial postresuscitation period (all p < 0.05). After adjusting for confounding factors, early epinephrine administration was a risk factor of mortality in the HS group (HR 4.52, 95% CI 2.73-15.91). CONCLUSION: Early epinephrine was significantly associated with achieving sustained ROSC in pediatric cases of HS and non-HS traumatic OHCA. For children with HS, early epinephrine administration was associated with both beneficial (increased cardiac output) and harmful effects (decreased urine output and metabolic acidosis) during the postresuscitation period. More importantly, early epinephrine was a risk factor associated with mortality in the HS group.

Bifidobacterium adolescentis CGMCC 15058 alleviates liver injury, enhances the intestinal barrier and modifies the gut microbiota in D-galactosamine-treated rats.

Acute liver failure is a drastic, unpredictable clinical syndrome with high mortality. Various preventive and adjuvant therapies based on modulating the gut flora have been proposed for hepatic injury. We aimed to explore the preventive and therapeutic effects of Bifidobacterium adolescentis CGMCC15058 on rat liver failure, as well as the potential microecological and immunological mechanisms of those effects. B. adolescentis CGMCC15058 (3 × 109 CFU), isolated from healthy human stool, was gavaged to Sprague-Dawley rats for 14 days. Acute liver injury was induced on the 15th day by intraperitoneal injection of D-galactosamine. After 24 h, liver and terminal ileum histology, liver function, plasma cytokines, bacterial translocation and gut microbiota composition were assessed. We found that pretreatment with B. adolescentis significantly relieved elevated serum levels of alanine aminotransferase (ALT), total bile acid and lipopolysaccharide-binding protein and enhanced the expression of mucin 4 and the tight junction protein zonula occludens-1. B. adolescentis exhibited anti-inflammatory properties as indicated by decreased levels of mTOR and the inflammatory cytokines TNF-α and IL-6, as well as elevated levels of the anti-inflammatory cytokine interleukins-10 in the liver. Similar anti-inflammatory signs were also found in plasma. B. adolescentis significantly altered the microbial community, depleting the common pathogenic taxon Proteus and markedly enriching the taxa Coriobacteriaceae, Bacteroidales and Allobaculum, which are involved in regulating the metabolism of lipids and aromatic amino acids. Our findings not only suggest B. adolescentis acts as a prospective probiotic against liver failure but also provide new insights into the prevention and treatment of liver disease.

Lactobacillus helveticus R0052 alleviates liver injury by modulating gut microbiome and metabolome in D-galactosamine-treated rats.

The liver is an important digestive gland, and acute liver failure results in high mortality. Probiotics are considered potential adjuvant therapies for liver disease. This study aimed to investigate the beneficial effects of Lactobacillus helveticus R0052 on acute liver injury and the underlying mechanisms. Sprague-Dawley rats were gavaged with L. helveticus R0052 suspensions (3 × 109 CFU) for 1 week. Subsequently, acute liver injury was induced by intraperitoneal D-galactosamine injection on the eighth day. After 24 h, samples (blood, liver, ileum, faeces) were collected and assessed for histological injury, inflammation, intestinal barrier, gut microbiome and metabolome. L. helveticus R0052 alleviated aminotransferase, bilirubin and total bile acid elevation and histological hepatic injuries. Additionally, L. helveticus R0052 exhibited anti-inflammatory properties by downregulating Toll-like receptors, tumour necrosis factor-α and nuclear factor-κb transcription in liver samples and decreasing proinflammatory cytokine plasma concentrations. Additionally, L. helveticus R0052 ameliorated intestinal abnormalities and regulated Toll-like receptors, claudin2 and mucin3 gene transcription in the intestine. These effects were associated with gut microbiome and metabolome modulation by L. helveticus R0052. Probiotic pretreatment enriched Lactobacillus and Bacteroides and depleted Flavonifractor and Acetatifactor in the gut microbiome. Meanwhile, L. helveticus R0052 improved carbohydrate and fatty acid metabolism and reduced lithocholic acid levels. These results indicate that L. helveticus R0052 is promising for alleviating acute liver injury and provide new insights regarding the correlations among the microbiome, the metabolome, the intestinal barrier and liver disease.