Non-Contrast-Enhanced MR Arteriography of Potential Living-Related Liver Donor: Using Contrast Enhanced CT Arteriography as Standard Reference.

BACKGROUND: Contrast-enhanced computed tomography angiography (CTA) and magnetic resonance angiography (MRA) are the primary modalities to assess donors' vessels before transplant surgery. Radiation and contrast medium are potentially harmful to donors. PURPOSE: To compare the image quality and visualization scores of hepatic arteries on CTA and balanced steady-state free-precession (bSSFP) non-contrast-enhanced MRA (NC-MRA), and to evaluate if bSSFP NC-MRA can potentially be a substitute for CTA. STUDY TYPE: Prospective. POPULATION: Fifty-six consecutive potential living-related liver donors (30.9 ± 8.4 years; 31 men). FIELD STRENGTH/SEQUENCE: 1.5T; four bSSFP NC-MRA sequences: respiratory-triggered (Inhance inflow inversion recovery [IFIR]) and three breath-hold (BH); and CTA. ASSESSMENT: The artery-to-liver contrast (Ca-l) was quantified. Three radiologists independently assigned visualization scores using a four-point scale to potential origins, segments, and branches of the hepatic arteries, determined the anatomical variants based on Hiatt's classification, and assessed the image quality of NC-MRA sequences. STATISTICAL TESTS: Fleiss' kappa to evaluate the readers' agreement. Repeat measured ANOVA or Friedman test to compare Ca-l of each NC-MRA. Friedman test to compare overall image quality and visualization scores; post hoc analysis using Wilcoxon signed-rank test. P-value <0.05 was considered statistically significant. RESULTS: Inhance IFIR Ca-l was significantly higher than all BH bSSFP Ca-l (0.56 [0.45-0.64] vs. 0.37 [0.29-0.47] to 0.41 [0.23-0.51]). Overall image quality score of BH bSSFP TI1200 was significantly higher than other NC-MRA (4 [4-4] vs. 4 [3 to 4-4]). The median visualization scores of almost all arteries on CTA were significantly higher than on NC-MRA (4 [3 to 4-4] vs. 1 [1-2] to 4 [4-4]). The median visualization scores were all 4 [4-4 ] on Inhance IFIR with >92.3% observed scores ≥3, except the segment 4 branch (3 [1-4], 53.6%). The identification rates of arterial variants were 92.9%-97% on Inhance IFIR. DATA CONCLUSIONS: Although CTA is superior to the NC-MRA, all NC-MRA depict the donor arterial anatomy well. Inhance IFIR can potentially be an alternative image modality for CTA to evaluate the arterial variants of living donors. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

A deep learning-based method for the diagnosis of vertebral fractures on spine MRI: retrospective training and validation of ResNet.

PURPOSE: To improve the performance of less experienced clinicians in the diagnosis of benign and malignant spinal fracture on MRI, we applied the ResNet50 algorithm to develop a decision support system. METHODS: A total of 190 patients, 50 with malignant and 140 with benign fractures, were studied. The visual diagnosis was made by one senior MSK radiologist, one fourth-year resident, and one first-year resident. The MSK radiologist also gave the binary score for 15 qualitative imaging features. Deep learning was implemented using ResNet50, using one abnormal spinal segment selected from each patient as input. The T1W and T2W images of the lesion slice and its two neighboring slices were considered. The diagnostic performance was evaluated using tenfold cross-validation. RESULTS: The overall reading accuracy was 98, 96, and 66% for the senior MSK radiologist, fourth-year resident, and first-year resident, respectively. Of the 15 imaging features, 10 showed a significant difference between benign and malignant groups with p < = 0.001. The accuracy achieved by using the ResNet50 deep learning model for the identified abnormal vertebral segment was 92%. Compared to the first-year resident's reading, the model improved the sensitivity from 78 to 94% (p < 0.001) and the specificity from 61 to 91% (p < 0.001). CONCLUSION: Our deep learning-based model may provide information to assist less experienced clinicians in the diagnosis of spinal fractures on MRI. Other findings away from the vertebral body need to be considered to improve the model, and further investigation is required to generalize our findings to real-world settings.

Preoptimized phage cocktail for use in aerosols against nosocomial transmission of carbapenem-resistant Acinetobacter baumannii: A 3-year prospective intervention study.

Using bacteriophages (phages) as environmental sanitizers has been recognized as a potential alternative method to remove bacterial contamination in vitro; however, very few studies are available on the application of phages for infection control in hospitals. Here, we performed a 3-year prospective intervention study using aerosolized phage cocktails as biocontrol agents against carbapenem-resistant Acinetobacter baumannii (CRAB) infection in the hospital. When a CRAB-infected patient was identified in an intensive care unit (ICU), their surrounding environment was chosen for phage aerosol decontamination. Before decontamination, 501 clinical specimens from the patients were subjected to antibiotic resistance analysis and phage typing. The optimal phage cocktails were a combination of different phage families or were constructed by next-evolutionary phage typing with the highest score for the host lysis zone to prevent the development of environmental CRAB phage resistance. The phage infection percentage of the antibiotic-resistant A. baumannii strains was 97.1%, whereas the infection percentage in the antibiotic-susceptible strains was 79.3%. During the phage decontamination periods from 2017 to 2019, the percentage of carbapenem-resistant A. baumannii in test ICUs decreased significantly from 65.3% to 55%. The rate of new acquisitions of CRAB infection over the three years was 4.4 per 1000 patient-days, which was significantly lower than that in the control wards (8.9 per 1000 patient-days) where phage decontamination had never been performed. In conclusion, our results support the potential of phage cocktails to decrease CRAB infection rates, and the aerosol generation process may make this approach more comprehensive and time-saving.

Trajectory of Body Mass Index from Ages 2 to 7 Years and Age at Peak Height Velocity in Boys and Girls.

OBJECTIVE: To examine the associations between body mass index (BMI) at 2-4 years and 5-7 years and age at peak height velocity (APHV), an objective measure of pubertal timing, among boys and girls from predominantly racial minorities in the US that have been historically underrepresented in this research topic. STUDY DESIGN: This study included 1296 mother-child dyads from the Boston Birth Cohort, a predominantly Black and low-income cohort enrolled at birth and followed prospectively during 1998-2018. The exposure was overweight or obesity, based on Centers for Disease Control and Prevention reference standards. The outcome was APHV, derived using a mixed effects growth curve model. Multiple regression was used to estimate the overweight or obesity-APHV association and control for confounders. RESULTS: Obesity at 2-4 years was associated with earlier APHV in boys (B in years, -0.19; 95% CI, -0.35 to -0.03) and girls (B, -0.22; 95% CI, -0.37 to -0.07). Obesity at 5-7 years was associated with earlier APHV in boys (B, -0.18; 95% CI, -0.32 to -0.03), whereas overweight and obesity at 5-7 years were both associated with earlier APHV in girls (overweight: B, -0.24; 95% CI, -0.40 to -0.08; obesity: B, -0.27; 95% CI, -0.40 to -0.13). With BMI trajectory, boys with persistent overweight or obesity and girls with overweight or obesity at 5-7 years, irrespective of overweight or obesity status at 2-4 years, had earlier APHV. CONCLUSIONS: This prospective birth cohort study found that overweight or obesity during 2-7 years was associated with earlier pubertal onset in both boys and girls. The BMI trajectory analyses further suggest that reversal of overweight or obesity may halt the progression toward early puberty.

The characteristics and genome analysis of vB_ApiP_XC38, a novel phage infecting Acinetobacter pittii.

Acinetobacter pittii is an important pathogen causing nosocomial infection worldwide. In this study, a multidrug-resistant A. pittii ABC38 was used as host bacterium to isolate the lytic phage vB_ApiP_XC38. The biological characteristics of vB_ApiP_XC38 were studied and the genome was sequenced and analyzed. vB_ApiP_XC38 belonged to Podoviridae family. The phage had double-stranded genome, which comprised 79,328 bp with 39.58% G+C content displaying very low similarity (< 1% identity) with published genomes of other phages and bacteria. A total of 97 open reading frames (ORFs) were predicted and contained nucleotide metabolism and replication module, structural components module, and lysis module. The ANI, AAI, and phylogenetic analysis indicated that all phages were found distant from vB_ApiP_XC38. Altogether, morphological, genomics, and phylogenetic analysis suggest that vB_ApiP_XC38 is more likely a novel phage of A. pittii.

A surface antigen of Orientia tsutsugamushi activates human monocyte-derived dendritic cells via nuclear factor-kB & p38 mitogen-activated protein kinase pathways.

BACKGROUND & OBJECTIVES: Scrub typhus is a chigger-borne disease caused by Orientia tsutsugamushi. The immunological reactions to O. tsutsugamushi infection are not completely understood. In this study, we investigated the response of dendritic cells (DCs) to a major 56-kDa scrub typhus antigen Sta56. METHODS: Monocyte-derived human DCs were incubated with different concentrations of recombinant Sta56 and analyzed for maturation based on phagocytic capacity, the ability to induce T-cell proliferation, expression of surface markers, cytokine secretion and activation of toll-like receptor (TLR)-dependent signalling pathways. RESULTS: Treatment of DCs with Sta56 induced cell surface expression of CD80, CD83, CD86 and MHC Class II increased the production of interleukin-12 (IL-12) p40, IL-12 p70 and IL-10 and decreased DC phagocytic capacity. Furthermore, Sta56 increased the ability of DCs to activate T-cell proliferation and interferon-γ secretion. TLR4-specific antibodies neutralized Sta56-elicited effects on DC maturation, suggesting direct interaction between Sta56 and TLR4. Moreover, Sta56 activated nuclear factor (NF)-κB and p38 mitogen-activated protein kinase (MAPK) signalling as evidenced by decrease in Sta56-induced cytokine production and surface marker expression by specific inhibitors helenalin and SB203580, respectively, and increase in IκBα and p38 phosphorylation and NF-κB-DNA binding. INTERPRETATION & CONCLUSIONS: Our results showed that the surface antigen of O. tsutsugamushi activated DCs through interaction with TLR4 and activation of MAPK and NF-κB signalling, suggesting Sta56 as a potential candidate molecule for the development of vaccine against scrub typhus.

Aspirin plus tirofiban inhibit the thrombosis induced by Russell's viper venom.

BACKGROUND: Thrombosis and coagulopathy are the commonest hematological manifestations of envenomation of Russell's viper venom (RVV). Factor X is activated by a factor X-activating enzyme from Russell's viper venom (RVV-X) to start the coagulation cascade. We established an animal model with local ischemic effects induced by RVV. We tried to treat RVV envenomation with antiplatelets and anticoagulants without recourse to antivenom. METHODS: RVV was injected into the foot pad of mice. We observed the effects at different intervals and compared local changes in ischemia with drug treatment after 30 min. RESULTS: A combination of aspirin plus tirofiban could prevent the ischemic change induced by RVV. The antithrombotic effects of single-use of aspirin or tirofiban were better than single-use of heparin or clopidogrel. CONCLUSION: The aspirin + tirofiban group had a better outcome with respect to prevention of tissue ischemia and gangrene. This indicates that the activation and aggregation of platelets is the major cause of thrombosis induced by RVV.

Genomic epidemiology of hypervirulent carbapenem-resistant Klebsiella pneumoniae at Jinshan local hospital, Shanghai, during 2014-2018.

BACKGROUND: Hypervirulent carbapenem-resistant Klebsiella pneumoniae (Hv-CRKP) triggered a significant public health challenge. This study explored the prevalence trends and key genetic characteristics of Hv-CRKP in one Shanghai suburbs hospital during 2014-2018. METHODS: During five years, Hv-CRKP strains identified from 2579 CRKP by specific PCR, were subjected to performed short- and long-read sequencing technology; epidemiological characteristics, antimicrobial-resistance genes (ARGs), virulence determinants, detailed plasmid profiles and conjugation efficiency were comprehensively investigated. RESULTS: 155 Hv-CRKP and 31 non-Hv-CRKP strains were sequenced. Hv-CRKP strains exhibited significant resistance to six common antibiotic classes (>92%). ST11 steadily increased and became the most prevalent ST (85.2%), followed by ST15 (8.5%), ST65 (2.6%), ST23 (1.9%), and ST86 (0.6%). ST11-KL64 (65.2%) rapidly increased from 0 in 2014 to 93.9% in 2018. blaKPC-2 was the primary carbapenemase gene (97.4%). Other ARGs switched from aac(3)-IId to aadA2 in aminoglycoside and from sul1 to sul2 in sulfanilamide. The time-dated phylogenetic tree was divided into four independent evolutionary clades. Clade 1 and 3 strains were mostly limited in the ICU, whereas Clade 2 strains were distributed among multiple departments. Compared to ybt14 in ICEKp12 in Clade 1, Clade 3 strains harbored ybt9 in ICEKp3 and blaCTX-M-65. Hv-CRKP infected more wards than non-Hv-CRKP and showed greater transmission capacity. Three plasmids containing crucial carbapenemase genes demonstrated their early transmission across China. CONCLUSION: The Hv-CRKP ST11-KL64 has rapidly replaced ST11-KL47 and emerged as the predominant epidemic subtype in various hospital wards, highlighting the importance of conducting comprehensive early surveillance for Hv-CRKP, especially in respiratory infections.

Potential of bacteriophage ΦAB2 as an environmental biocontrol agent for the control of multidrug-resistant Acinetobacter baumannii.

BACKGROUND: Multidrug-resistant Acinetobacter baumannii (MDRAB) is associated with nosocomial infections worldwide. To date, the use of a phage to prevent infections caused by MDRAB has not been demonstrated. RESULTS: The MDRAB-specific phage ϕAB2 was stable at 4°C and pH 7 in 0.5% chloroform solution, and showed a slight decrease in plaque-forming units (PFU)/ml of 0.3-0.9 log after 330 days of storage. The addition of ϕAB2 at a concentration of at least 105 PFU/ml to an A. baumannii M3237 suspension killed >99.9% of A. baumannii M3237 after 5 min, regardless of A. baumannii M3237 concentration (104, 105, or 106 colony-forming units (CFU)/ml). The addition of ϕAB2 at a concentration of 108 PFU/slide (>107 PFU/cm²) to glass slides containing A. baumannii M3237 at 104, 105, or 106 CFU/slide, significantly reduced bacterial numbers by 93%, 97%, and 99%, respectively. Thus, this concentration is recommended for decontamination of glass surfaces. Moreover, infusion of ϕAB2 into 10% glycerol exhibited strong anti-MDRAB activity (99.9% reduction), even after 90 days of storage. Treatment of a 10% paraffin oil-based lotion with ϕAB2 significantly reduced (99%) A. baumannii M3237 after 1 day of storage. However, ϕAB2 had no activity in the lotion after 1 month of storage. CONCLUSIONS: Phages may be useful for reducing MDRAB contamination in liquid suspensions or on hard surfaces. Phages may also be inoculated into a solution to produce an antiseptic hand wash. However, the phage concentration and incubation time (the duration of phage contact with bacteria) should be carefully considered to reduce the risk of MDRAB contamination.

Effect of taxane-based neoadjuvant chemotherapy on fibroglandular tissue volume and percent breast density in the contralateral normal breast evaluated by 3T MR.

The aim of this study was to evaluate the change of breast density in the normal breast of patients receiving neoadjuvant chemotherapy (NAC). Forty-four breast cancer patients were studied. MRI acquisition was performed before treatment (baseline), and 4 and 12 weeks after treatment. A computer-algorithm-based program was used to segment breast tissue and calculate breast volume (BV), fibroglandular tissue volume (FV), and percent density (PD) (the ratio of FV over BV × 100%). The reduction of FV and PD after treatment was compared with baseline using paired t-tests with a Bonferroni-Holm correction. The association of density reduction with age was analyzed. FV and PD after NAC showed significant decreases compared with the baseline. FV was 110.0 ml (67.2, 189.8) (geometric mean (interquartile range)) at baseline, 104.3 ml (66.6, 164.4) after 4 weeks (p < 0.0001), and 94.7 ml (60.2, 144.4) after 12 weeks (comparison with baseline, p < 0.0001; comparison with 4 weeks, p = 0.016). PD was 11.2% (6.4, 22.4) at baseline, 10.6% (6.6, 20.3) after 4 weeks (p < 0.0001), and 9.7% (6.2, 17.9) after 12 weeks (comparison with baseline, p = 0.0001; comparison with 4 weeks, p = 0.018). Younger patients tended to show a higher density reduction, but overall correlation with age was only moderate (r = 0.28 for FV, p = 0.07, and r = 0.52 for PD, p = 0.0003). Our study showed that breast density measured from MR images acquired at 3T MR can be accurately quantified using a robust computer-aided algorithm based on non-parametric non-uniformity normalization (N3) and an adaptive fuzzy C-means algorithm. Similar to doxorubicin and cyclophosphamide regimens, the taxane-based NAC regimen also caused density atrophy in the normal breast and showed reduction in FV and PD. The effect of breast density reduction was age related and duration related.

[Exploring the lived experiences of middle-aged males diagnosed with chronic kidney disease].

BACKGROUND: The majority of studies addressing chronic kidney disease (CKD) have been quantitative. The lived experiences of patients with early stage CKD have not been explored in the literature. Due to the lack of symptoms during the early stages of CKD, the progress of this disease is often ignored. PURPOSE: This study explores the lived experiences of middle-aged males diagnosed with CKD. Research focuses on the work experiences, interpersonal relationships, and dietary habits of this group. METHODS: This qualitative study used a narrative research method with purposive sampling. Ten middle-aged male patients were interviewed. We employed the 3 strategies of member checks, peer review, and debriefing in order to enhance the trustworthiness of the data analysis. RESULTS: Four major themes were identified: (1) keeping the same life pace as usual with concerns of deterioration; (2) continuing to support their family and play the role of father; (3) hoping to participate in family and friend relationships despite the illness; and (4) being challenged to maintain a healthy diet. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Although the physical status of participants was similar to the general middle-aged adult population, participants were concerned regarding disease deterioration. The results of this study suggest that health professionals: (1) provide appropriate information based on patients' personality, particularly at the first onset or apparent deterioration of the disease; (2) offer specialized healthcare information to patients relevant to their career choices; and (3) understand CKD-patient difficulties in daily life such as eating out habits and challenges faced in maintaining a healthy diet. Results may provide important information to healthcare providers in education planning and implementation and support programs for patients and families.

A highly efficient and accurate method of detecting and subtyping Influenza A pdm H1N1 and H3N2 viruses with newly emerging mutations in the matrix gene in Eastern Taiwan.

The rapid identification of Influenza A virus and its variants, which cause severe respiratory diseases, is imperative to providing timely treatment and improving patient outcomes. Conventionally, two separate assays (total test duration of up to 6 h) are required to initially differentiate Influenza A and B viruses and subsequently distinguish the pdm H1N1 and H3N2 serotypes of Influenza A virus. In this study, we developed a multiplex real-time RT-PCR method for simultaneously detecting Influenza A and B viruses and subtyping Influenza A virus, with a substantially reduced test duration. Clinical specimens from hospitalized patients and outpatients with influenza-like symptoms in Eastern Taiwan were collected between 2011 and 2015, transported to Hualien Tzu Chi Hospital, and analyzed. Conventional RT-PCR was used to subtype the isolated Influenza A viruses. Thereafter, for rapid identification, the multiplex real-time RT-PCR method was developed and applied to identify the conserved regions that aligned with the available primers and probes. Accordingly, a multiplex RT-PCR assay with three groups of primers and probes (MAF and MAR primers and MA probe; InfAF and InfAR primers and InfA probe; and MBF and MBR primers and MB probe) was established to distinguish these viruses in the same reaction. Thus, with this multiplex RT-PCR assay, Influenza B, Influenza A pdm H1N1, and Influenza A H3N2 viruses were accurately detected and differentiated within only 2.5 h. This multiplex RT-PCR assay showed similar analytical sensitivity to the conventional singleplex assay. Further, the phylogenetic analyses of our samples revealed that the characteristics of these viruses were different from those reported previously using samples collected during 2012-2013. In conclusion, we developed a multiplex real-time RT-PCR method for highly efficient and accurate detection and differentiation of Influenza A and B viruses and subtyping Influenza A virus with a substantially reduced test duration for diagnosis.

Isolation and characterization of bacteriophages with activities against multi-drug-resistant Acinetobacter nosocomialis causing bloodstream infection in vivo.

BACKGROUND: Acinetobacter nosocomialis (A. nosocomialis) is a glucose non-fermentative, gram-negative bacillus that belongs to the Acinetobacter calcoaceticus-baumannii complex. In recent years, studies have found an increased clinical prevalence of A. nosocomialis. However, given the increasing trend of antibiotic resistance, developing new antibacterial agents is vital. Currently, research regarding bacteriophage therapy against A. nosocomialis is only limited. METHODS: Two A. nosocomialis bacteriophages, TCUAN1 and TCUAN2, were isolated from sewage. Experiments such as transmission electron microscopy (TEM), host-range analysis, and sequencing were performed to determine their biological and genomic characteristics. TCUAN2 were further subjected to in vivo experiments and their derived-endolysin were cloned and tested against their bacteria host. RESULTS: Transmission electron microscopy revealed that TCUAN1 and TCUAN2 belong to Myoviridae and Podoviridae, respectively. Both phages show a broad host spectrum and rapid adsorption efficiency. Further biological analysis showed that TCUAN2 possesses a shorter latent period and larger burst size compared to TCUAN1. Because TCUAN2 showed a better antibacterial activity, it was injected into A. nosocomialis-infected mice which resulted in a significant decrease in bacterial load levels in the blood and increased the mice's survival. Finally, genomic analysis revealed that the complete nucleotide sequence of TCUAN1 is 49, 691 bps (containing 75 open reading frames) with a G + C content of 39.3%; whereas the complete nucleotide sequence of TCUAN2 is 41, 815 bps (containing 68 open reading frames) with a G + C content of 39.1%. The endolysin gene cloned and purified from TCUAN2 also showed antibacterial activity when used with a chelator EDTA.

Sufficient virus-neutralizing antibody in the central nerve system improves the survival of rabid rats.

BACKGROUND: Rabies is known to be lethal in human. Treatment with passive immunity for the rabies is effective only when the patients have not shown the central nerve system (CNS) signs. The blood-brain barrier (BBB) is a complex functional barrier that may compromise the therapeutic development in neurological diseases. The goal of this study is to determine the change of BBB integrity and to assess the therapeutic possibility of enhancing BBB permeability combined with passive immunity in the late stage of rabies virus infection. METHODS: The integrity of BBB permeability in rats was measured by quantitative ELISA for total IgG and albumin levels in the cerebrospinal fluid (CSF) and by exogenously applying Evans blue as a tracer. Western blotting of occludin and ZO-1, two tight junction proteins, was used to assess the molecular change of BBB structure.The breakdown of BBB with hypertonic arabinose, recombinant tumor necrosis factor-alpha (rTNF-γ), and focused ultrasound (FUS) were used to compare the extent of BBB disruption with rabies virus infection. Specific humoral immunity was analyzed by immunofluorescent assay and rapid fluorescent focus inhibition test. Virus-neutralizing monoclonal antibody (mAb) 8-10E was administered to rats with hypertonic breakdown of BBB as a passive immunotherapy to prevent the death from rabies. RESULTS: The BBB permeability was altered on day 7 post-infection. Increased BBB permeability induced by rabies virus infection was observed primarily in the cerebellum and spinal cord. Occludin was significantly decreased in both the cerebral cortex and cerebellum. The rabies virus-specific antibody was not strongly elicited even in the presence of clinical signs. Disruption of BBB had no direct association with the lethal outcome of rabies. Passive immunotherapy with virus-neutralizing mAb 8-10E with the hypertonic breakdown of BBB prolonged the survival of rabies virus-infected rats. CONCLUSIONS: We demonstrated that the BBB permeability was altered in a rat model with rabies virus inoculation. Delivery of neutralizing mAb to the infected site in brain combined with effective breakdown of BBB could be an aggressive but feasible therapeutic mode in rabies when the CNS infection has been established.

Consistency of breast density measured from the same women in four different MR scanners.

PURPOSE: To compare the breast volume (BV), fibroglandular tissue volume (FV), and percent density (PD) measured from breast MRI of the same women using four different MR scanners. METHODS: The study was performed in 34 healthy Asian volunteers using two 1.5T (GE and Siemens) and two 3T (GE and Philips) MR scanners. The BV, FV, and PD were measured on nonfat-suppressed T1-weighted images using a comprehensive computer algorithm-based segmentation method. The scanner-to-scanner measurement difference, and the coefficient of variation (CV) among the four scanners were calculated. The measurement variation between two density morphological patterns presenting as the central type and the intermingled type was separately analyzed and compared. RESULTS: All four scanners provided satisfactory image quality allowing for successful completion of the segmentation processes. The measured parameters between each pair of MR scanners were highly correlated, with R(2) ≥ 0.95 for BV, R(2) ≥ 0.99 for FV, and R(2) ≥ 0.97 for PD in all comparisons. The mean percent differences between each pair of scanners were 5.9%-7.8% for BV, 5.3%-6.5% for FV, 4.3%-7.3% for PD; with the overall CV of 5.8% for BV, 4.8% for FV, and 4.9% for PD. The variation of FV was smaller in the central type than in the intermingled type (p = 0.04). CONCLUSIONS: The results showed that the variation of FV and PD measured from four different MR scanners is around 5%, suggesting the parameters measured using different scanners can be used for a combined analysis in a multicenter study.

Hepatitis B virus surface antigen can activate human monocyte-derived dendritic cells by nuclear factor kappa B and p38 mitogen-activated protein kinase mediated signaling.

Hepatitis B virus Ag (HBsAg), a major antigen of hepatitis B virus (HBV), is also a vaccine component for prevention of HBV infection. Dendritic cells (DCs) of HBV carriers reportedly exhibit functional impairment. In this study, the aim was to investigate the effect of HBsAg on activation of human monocyte-derived dendritic cells (MD-DCs), and the subsequent signal transduction pathway. Treatment of MD-DCs with HBsAg resulted in enhanced cell surface expression of cluster of differentiation 80, CD83, CD86 and major histocompatibility complex class II, and increased interleukin (IL)-12 p40, IL-12p70, and IL-10 production. Furthermore, HBsAg treatment of MD-DCs with HBsAg resulted in enhanced T cell-stimulatory capacity and increased T cell secretion of interferon and IL-10. The pathway of MD-DCs activation by HBsAg was further investigated in the present study. Inhibition of nuclear factor (NF)-kappa B (κB) by helenalin and p38 mitogen-activated protein kinase (MAPK) by SB203580 prevented production of IL-12 p40, IL-12 p70, and IL-10. HBsAg also augmented MAPK phosphorylation. Thus, cytokine secretion of human MD-DCs by HBsAg is blocked by inhibition of the NF-κB and p38 MAPK pathways. Likewise, decreased inhibition of kappa B alpha concentrations and MAPK phosphorylation are critical for MD-DC maturation by HBsAg. These findings may provide a strategy for improving the prophylactic and therapeutic efficacy of vaccines and tumor therapies that utilize these pathways.

Involvement of extraneural tissues and upregulation of inducible nitric oxide synthase after experimental infection with rabies virus in BALB/c mice and LEW/SsN rats.

Rabies virus can cause fatal encephalomyelitis, but the involvement of extraneural organs has not been well characterized. In this study, we investigated the histopathological changes and the distribution of viral antigens in extraneural organs after pathogenic rabies virus infection in mouse and rat models. In histopathological examination, classical viral encephalitis and rabies-specific Negri body were observed in the brain. In addition to the central nervous system (CNS), inflammatory responses were found in other organs, such as the heart, kidney, liver, and lung. Similarly, immunohistochemical staining and reverse transcription-polymerase chain reaction revealed the presence of rabies virus in the CNS and extraneural tissues. Moreover, macrophages, especially in the lung and heart, were involved in the infection. Transcriptional analyses of the expression of inducible nitric oxide synthase (iNOS) demonstrated that rabies virus potentiated the gene expression of iNOS in the brain, lung, and heart. The immunoreactive iNOS-positive macrophages were detected adjacent to the infection. These results suggest that macrophages are involved in the extraneural infection and the expression of iNOS in macrophages contributes to the formation of tissue inflammation. Our study indicates the involvement of extraneural organs following rabies virus infection, which may aggravate the progression of this deadly disease.

Genomic analysis of bacteriophage ϕAB1, a ϕKMV-like virus infecting multidrug-resistant Acinetobacter baumannii.

We present the complete genomic sequence of a lytic bacteriophage ϕAB1 which can infect many clinical isolates of multidrug-resistant Acinetobacter baumannii. The recently isolated bacteriophage displays morphology resembling Podoviridae family. The ϕAB1 genome is a linear double-stranded DNA of 41,526 bp containing 46 possible open reading frames (ORFs). The majority of the predicted structural proteins were identified as part of the phage particle by mass spectrometry analysis. According to the virion morphology, overall genomic structure, and the phylogenetic tree of RNA polymerase, we propose that ϕAB1 is a new member of the ϕKMV-like phages. Additionally, we identified four ORFs encoding putative HNH endonucleases, one of which is presumed to integrate and create a genes-in-pieces DNA polymerase. Also, a potential lysis cassette was identified in the late genome. The lytic power of this bacteriophage combined with its specificity for A. baumannii makes ϕAB1 an attractive agent for therapeutic or disinfection applications.

Phage therapy for secondary bacterial infections with COVID-19.

With more than 200 million people affected and 4.5 million deaths so far, the coronavirus disease 2019 (COVID-19) pandemic has become one of the greatest disasters in human history. Secondary bacterial infections (SBIs) are a known complication of viral respiratory infections, and are significantly associated with poorer outcomes in COVID-19 patients despite antibiotic treatments. The increasing antimicrobial resistance (AMR) in bacteria and the decreasing options available in our antimicrobial armory worsen this crisis and call for alternative treatment options. As natural killers of bacteria, phages are recognized as promising alternatives to antibiotics in treating pulmonary bacterial infections, however, little is known about their use for treating SBIs during virus pandemics such as COVID-19. This review highlights the situation of SBIs in COVID-19 patients, and the distinct strengths and limitations of phage therapy for their containment.

Biological and genomic characterization of two newly isolated Elizabethkingia anophelis bacteriophages.

BACKGROUND: Elizabethkingia anophelis is an opportunistic pathogen that infects newborns and immunocompromised patients. Because the infection is associated with high mortality as a result of its intrinsic resistance to antibiotics, alternative treatment methods are needed. Our previous study successfully isolated the world's first E. anophelis phage, TCUEAP1, which showed beneficial protection to E. anophelis-infected mice. More new bacteriophages are needed in order to provide sufficient choices to combat E. anophelis infections. METHODS: In the current study, two new phages infecting E. anophelis were isolated from wastewater and were designated as TCUEAP2 and TCUEAP3. Further experiments, namely, transmission electron microscopy (TEM), infection assay, host-range analysis, and sequencing were performed to determine their biological and genomic characteristics. RESULTS: TEM analysis revealed that both TCUEAP2 and TCUEAP3 possess an icosahedral head with a non-contractile tail, and belong to the Siphoviridae family. Further experiments revealed that TCUEAP3 has a longer latent period and higher burst size compared to TCUEAP2. Host range analysis showed that both TCUEAP2 and TCUEAP3 have a narrow host range, infecting only their respective hosts. The genomic size of phage TCUEAP2 was 42,403 bps containing 61 predicted open reading frames (ORFs), whereas the genome size of TCUEAP3 was 37,073 bps containing 40 predicted ORFs. CONCLUSION: Due to the distinct biological characteristics of TCUEAP2 and TCUEAP3, they may be satisfactory for clinical uses such as preparation of phage cocktails or decontamination in clinical settings.