Co-formulation of the rF1V plague vaccine with depot-formulated cytokines enhances immunogenicity and efficacy to elicit protective responses against aerosol challenge in mice.

This study evaluated a depot-formulated cytokine-based adjuvant to improve the efficacy of the recombinant F1V (rF1V) plague vaccine and examined the protective response following aerosol challenge in a murine model. The results of this study showed that co-formulation of the Alhydrogel-adsorbed rF1V plague fusion vaccine with the depot-formulated cytokines recombinant human interleukin 2 (rhuIL-2) and/or recombinant murine granulocyte macrophage colony-stimulating factor (rmGM-CSF) significantly enhances immunogenicity and significant protection at lower antigen doses against a lethal aerosol challenge. These results provide additional support for the co-application of the depot-formulated IL-2 and/or GM-CSF cytokines to enhance vaccine efficacy.

Effect of sarcopenia and frailty on outcomes among patients with brain metastases.

PURPOSE: Sarcopenia and frailty have been associated with increased mortality and duration of hospitalization in cancer. However, data investigating these effects in patients with brain metastases remain limited. This study aimed to investigate the effects of sarcopenia and frailty on clinical outcomes in patients with surgically treated brain metastases. METHODS: Patients who underwent surgical resection of brain metastases from 2011 to 2019 were included. Psoas cross-sectional area and temporalis thickness were measured by two independent radiologists (Cronbach's alpha > 0.98). Frailty was assessed using the Clinical Frailty Scale (CFS) pre-operatively and post-operatively. Overall mortality, recurrence, and duration of hospitalization were collected. Cox regression was performed for mortality and recurrence, and multiple linear regression for duration of hospitalization. RESULTS: 145 patients were included, with median age 60.0 years and 52.4% female. Psoas cross-sectional area was an independent risk factor for overall mortality (HR = 2.68, 95% CI 1.64-4.38, p < 0.001) and recurrence (HR = 2.31, 95% CI 1.14-4.65, p = 0.020), while post-operative CFS was an independent risk factor for overall mortality (HR = 1.88, 95% CI 1.14-3.09, p = 0.013). Post-operative CFS (ß = 15.69, 95% CI 7.67-23.72, p < 0.001) and increase in CFS (ß = 11.71, 95% CI 3.91-19.51, p = 0.004) were independently associated with increased duration of hospitalization. CONCLUSION: In patients with surgically treated brain metastases, psoas cross-sectional area was an independent risk factor for mortality and recurrence, while post-operative CFS was an independent risk factor for mortality. Post-operative frailty and increase in CFS significantly increased duration of hospitalization. Measurement of psoas cross-sectional area and CFS may aid in risk stratification of surgical candidates for brain metastases.

Integrative ATAC-seq and RNA-seq analysis associated with diabetic nephropathy and identification of novel targets for treatment by dapagliflozin.

Dapagliflozin (DAPA) are clinically effective in improving diabetic nephropathy (DN). However, whether and how chromatin accessibility changed by DN responds to DAPA treatment is unclear. Therefore, we performed ATAC-seq, RNA-seq, and weighted gene correlation network analysis to identify the chromatin accessibility, the messenger RNA (mRNA) expression, and the correlation between clinical phenotypes and mRNA expression using kidney from three mouse groups: db/m mice (Controls), db/db mice (case group), and those treated with DAPA (treatment group). RNA-Seq and ATAC-seq conjoint analysis revealed many overlapping pathways and networks suggesting that the transcriptional changes of DN and DAPA intervention largely occured dependently on chromatin remodeling. Specifically, the results showed that some key signal transduction pathways, such as immune dysfunction, glucolipid metabolism, oxidative stress and xenobiotic and endobiotic metabolism, were repeatedly enriched in the analysis of the RNA-seq data alone, as well as combined analysis with ATAC-seq data. Furthermore, we identified some candidate genes (UDP glucuronosyltransferase 1 family, Dock2, Tbc1d10c, etc.) and transcriptional regulators (KLF6 and GFI1) that might be associated with DN and DAPA restoration. These reversed genes and regulators confirmed that pathways related to immune response and metabolism pathways were critically involved in DN progression.

Atrophy of the cholinergic regions advances from early to late mild cognitive impairment.

PURPOSE: We investigated the volumetric changes in the components of the cholinergic pathway for patients with early mild cognitive impairment (EMCI) and those with late mild cognitive impairment (LMCI). The effect of patients' apolipoprotein 4 (APOE-ε4) allele status on the structural changes were analyzed. METHODS: Structural magnetic resonance imaging data were collected. Patients' demographic information, plasma data, and validated global cognitive composite scores were included. Relevant features were extracted for constructing machine learning models to differentiate between EMCI (n = 312) and LMCI (n = 541) and predict patients' neurocognitive function. The data were analyzed primarily through one-way analysis of variance and two-way analysis of covariance. RESULTS: Considerable differences were observed in cholinergic structural changes between patients with EMCI and LMCI. Cholinergic atrophy was more prominent in the LMCI cohort than in the EMCI cohort (P < 0.05 family-wise error corrected). APOE-ε4 differentially affected cholinergic atrophy in the LMCI and EMCI cohorts. For LMCI cohort, APOE-ε4 carriers exhibited increased brain atrophy (left amygdala: P = 0.001; right amygdala: P = 0.006, and right Ch123, P = 0.032). EMCI and LCMI patients showed distinctive associations of gray matter volumes in cholinergic regions with executive (R2 = 0.063 and 0.030 for EMCI and LMCI, respectively) and language (R2 = 0.095 and 0.042 for EMCI and LMCI, respectively) function. CONCLUSIONS: Our data confirmed significant cholinergic atrophy differences between early and late stages of mild cognitive impairment. The impact of the APOE-ε4 allele on cholinergic atrophy varied between the LMCI and EMCI groups.

Prognostication of Outcomes in Spontaneous Intracerebral Hemorrhage: A Propensity Score-Matched Analysis with Support Vector Machine.

OBJECTIVE: The role of surgery in spontaneous intracerebral hemorrhage (SICH) remains controversial. We aimed to use explainable machine learning (ML) combined with propensity-score matching to investigate the effects of surgery and identify subgroups of patients with SICH who may benefit from surgery in an interpretable fashion. METHODS: We conducted a retrospective study of a cohort of 282 patients aged ≥21 years with SICH. ML models were developed to separately predict for surgery and surgical evacuation. SHapley Additive exPlanations (SHAP) values were calculated to interpret the predictions made by ML models. Propensity-score matching was performed to estimate the effect of surgery and surgical evacuation on 90-day poor functional outcomes (PFO). RESULTS: Ninety-two patients (32.6%) underwent surgery, and 57 patients (20.2%) underwent surgical evacuation. A total of 177 patients (62.8%) had 90-day PFO. The support vector machine achieved a c-statistic of 0.915 when predicting 90-day PFO for patients who underwent surgery and a c-statistic of 0.981 for patients who underwent surgical evacuation. The SHAP scores for the top 5 features were Glasgow Coma Scale score (0.367), age (0.214), volume of hematoma (0.258), location of hematoma (0.195), and ventricular extension (0.164). Surgery, but not surgical evacuation of the hematoma, was significantly associated with improved mortality at 90-day follow-up (odds ratio, 0.26; 95% confidence interval, 0.10-0.67; P = 0.006). CONCLUSIONS: Explainable ML approaches could elucidate how ML models predict outcomes in SICH and identify subgroups of patients who respond to surgery. Future research in SICH should focus on an explainable ML-based approach that can identify subgroups of patients who may benefit functionally from surgical intervention.

Metabolic Risk Profile and Graft Function Deterioration 2 Years After Kidney Transplant.

Importance: Studies exploring the association of body weight and metabolic status with graft function deterioration (GFD) after kidney transplantation have produced inconsistent findings. Few studies have examined whether metabolically healthy overweight or obesity (MHO) may contribute to GFD. Objective: To evaluate associations of overweight or obesity and metabolic disorders with GFD in recipients of kidney transplant. Design, Setting, and Participants: This multicenter retrospective cohort study was conducted from January 1, 2020, through June 30, 2021, with a follow-up period of 2 years after kidney transplantation. Participants included adult recipients of cadaveric kidney transplant in 4 transplantation centers in China. Participants were classified as 4 metabolic phenotypes according to their BMI and metabolic status. Data were analyzed from July to August 2023. Exposures: Overweight and obesity were characterized by body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 24 or greater. Metabolic disorder was identified by existence of a minimum of 2 of 4 conditions: hypertension, hyperglycemia, increased triglyceride, and decreased high-density lipoprotein cholesterol. Main Outcome and Measures: The main outcome was GFD, defined as a decrease in estimated glomerular filtration rate of at least 25% within 6 months to 2 years after transplant. Results: A total of 1260 adult recipients of cadaveric kidney transplant (mean [SD] age, 43.97 [11.51] years; 755 [59.92%] male) were included in the study, and 127 (10.08%) participants experienced the primary outcome of GFD during follow-up. After accounting for confounding factors in multivariable analyses, overweight or obesity (odds ratio [OR], 1.64; 95% CI, 1.10-2.44; P = .02) and metabolic disorder (OR, 1.71; 95% CI, 1.12-2.63; P = .01) were associated with increased risk of GFD. The MHO subgroup exhibited a greater risk for GFD (OR, 2.37; 95% CI, 1.01-5.57; P = .048) compared with participants who did not have overweight or obesity or metabolic disorder. All components of metabolic disorder, with the exception of elevated triglyceride, were associated with GFD. There was a dose-response association of number of metabolic disorder components (OR per 1 additional condition, 1.40; 95% CI, 1.20-1.63; P < .001) and BMI (OR per 1-unit increase, 1.90; 95% CI, 1.03-1.15; P = .002) with increased risk for GFD. A nonlinear association was observed between BMI and risk of GFD. Conclusions and Relevance: In this cohort study of recipients of cadaveric kidney transplant, individuals with overweight or obesity or metabolic disorder had a significantly higher risk of experiencing GFD. Individuals with MHO had an elevated risk for graft function deterioration. Additional studies with larger sample size and longer follow-up are necessary to validate our findings.

A large-scale survey on epidemiology and underreporting of needlestick and sharp injuries among healthcare workers in China.

Background: Needlestick and sharp injuries (NSI) carry the risk of transmitting numerous bloodborne pathogens, leading to both health and economic burdens. The underreporting of NSIs among healthcare workers (HCWs) is a global issue of concern, as timely treatment and prevention of complications rely on proper reporting. Underreporting further impedes accurate surveillance and appropriate resource allocation, with developed and developing nations facing disparities due to differences in healthcare policy. Purpose: The purpose of this research is to examine the epidemiology of NSIs and NSI underreporting, as well as to identify the determinants associated with the occurrence of NSIs and the underreporting of such injuries. Method: A retrospective online survey was conducted from January 15 to January 31, 2022 among healthcare workers (HCWs) across Gansu Province, China. Results: A total of 7,283 healthcare workers (HCWs) from various institutions participated in this study. After quality assurance checks, 6,464 (88.77%) responses were included in the final analysis. Results revealed a 32.86% self-reported needlestick and sharp injury (NSI) incidence among respondents, with 28.53% of NSIs going unreported. Contrary to common belief, more experienced HCWs exhibited higher rates of both NSIs and underreporting compared to their less experienced peers. The primary reasons cited for NSIs and underreporting were lapses in concentration and not perceiving patients as infectious. Multivariate regression analysis exposes the significant influence of training frequency, occupation, department and years of services on the occurrence of NSIs. Conversely, the reporting of NSIs is primarily influenced by training, reimbursement,occupation, department and hospital grade. Compared to HCWs with no training, those who received ≥3 training sessions per year showed a 12.16% lower NSI incidence (27.12% vs. 39.28%, p < 0.001) and a 55.68% lower underreporting rate (14.61% vs. 70.29%, p < 0.001). Conclusion: There is a pressing need for enhanced surveillance, tailored training programs, and more efficient reporting mechanisms to combat this significant occupational health challenge.

Efficacy of levocetirizine in isolated rat tracheal smooth muscle.

Histamine receptor-1 (H1) antagonists like levocetirizine are frequently used nowadays to treat rhinitis patients who experience rhinorrhea and sneezing. The trachea may be affected by the H1 antagonist when it is used to treat nasal symptoms, either orally or through inhalation. The purpose of this study was to ascertain in vitro effects of levocetirizine on isolated tracheal smooth muscle. As a parasympathetic mimetic, methacholine (10-6 M) causes contractions in tracheal smooth muscle, which is how we tested effectiveness of levocetirizine on isolated rat tracheal smooth muscle. We also tested the drug's impact on electrically induced tracheal smooth muscle contractions. The impact of menthol (either before or after) on the contraction brought on by 10-6 M methacholine was also investigated. According to the results, the addition of levocetirizine at concentrations of 10-5 M or more caused a slight relaxation in response to methacholine's 10-6 M contraction. Levocetirizine could prevent spike contraction brought on by electrical field stimulation (EFS). As the concentration rose, it alone had a neglect effect on the trachea's basal tension. Before menthol was applied, levocetirizine might have also inhibited the function of the cold receptor. According to this study, levocetirizine might potentially impede the parasympathetic function of the trachea. If levocetirizine was used prior to menthol addition, it also reduced the function of cold receptors.

Screening of key genes in the pathogenesis of muscle atrophy in CKD-PEW children based on RNA sequencing.

BACKGROUND: In children with CKD, Protein Energy Wasting (PEW) is common, which affects the outcome of children and is an important cause of poor prognosis. We are aiming to explore the pathogenesis of muscle wasting in CKD-PEW children. METHODS: Blood samples of 32 children diagnosed with chronic kidney disease (CKD) and protein energy wasting (PEW) in our hospital from January 2016 to June 2021 were collected. RNA sequencing and bioinformatics analysis were performed. RESULTS: Based on GO (Gene Ontology) functional enrichment analysis, KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis and differential gene expression analysis, a total of 25 CKD-PEW related genes were obtained including CRP, IL6, TNF, IL1B, CXCL8, IL12B, IL12A, IL18, IL1A, IL4, IL10, TGFB2, TGFB1, TGFB3, ADIPOQ, NAMPT, RETN, RETNLB, LEP, CD163, ICAM1, VCAM1, SELE, NF-κB1, NF-κB2. The most significantly differentially expressed gene was NF-κB2 (adjusted P = 2.81 × 10-16), and its expression was up-regulated by 3.92 times (corresponding log2FoldChange value was 1.979). Followed by RETN (adjusted P = 1.63 × 10-7), and its expression was up-regulated by 8.306 times (corresponding log2FoldChange value was 2.882). SELE gene were secondly significant (adjusted P = 5.81 × 10-7), and its expression was down-regulated by 22.05 times (corresponding log2FoldChange value was -4.696). CONCLUSIONS: A variety of inflammatory factors are involved in the pathogenesis of CKD-PEW in children, and chronic inflammation may lead to the development of muscle atrophy in CKD-PEW. It is suggested for the first time that NF-κB is a key gene in the pathogenesis of muscle wasting in CKD-PEW children, and its increased expression may play an important role in the pathogenesis of muscle wasting in children with CKD-PEW.

Age estimation of bloodstains based on convolutional neural network algorithm and hyperspectral imaging technology.

The most common trace of evidence at a crime scene is blood. In judicial scientific proof, it is regarded as one of the most important material types of evidence. In this study, the spectral data of the bloodstain samples with different time were collected via a hyperspectral imaging system with a spectral range of 400-1000 nm and spectral sampling interval of 5 nm. The training model of blood aging was built using the Convolutional Neural Network (CNN) algorithm and the above hyperspectral spectral data. It was also compared with the traditional partial least squares (PLS) and extreme learning machine (ELM) models. The experimental results showed that the performance of CNN model was the best, with a determination coefficient (R2) of 0.987, which is higher compared to that of the PLS model (R2 = 0.883) and ELM model (R2 = 0.936). Besides, the root mean square error of prediction (RMSEP) of the CNN model was 6.949 hours, smaller than the PLS model (RMSEP = 18.752 hours) and the ELM model (RMSEP = 13.717 hours). The mean absolute percentage error (MAPE) of the prediction set was 0.49% when using the CNN algorithm, which was also the minimum of the three algorithms, and it represented that the prediction results were the best. The experimental data showed that the method proposed in this study could accurately estimate the age of bloodstains, providing a new technology reference for bloodstain detection.

[Effects of Fertilizer Application Strategy Adjustments on Nitrogen and Phosphorus Loss from Typical Crop Systems in Taihu Lake Region].

The intensity of crop farming fertilizer input is generally high in the Taihu Lake Region, with chemical fertilizer as the main form. Due to inappropriate fertilizer application, nitrogen and phosphorus loss have occurred, causing serious agricultural non-point source pollution. The Ministry of Agriculture and Rural Affairs of China has launched the "zero-growth action for chemical fertilizer use" and "replacement action with organic fertilizer" ("two actions" for short) campaigns since 2015. Local agricultural sectors adjusted fertilizer application strategies of crop farming to respond to the call of two actions. However, the current research is still focusing on reducing the total amount of fertilizer application and increasing the area of organic fertilizer application, which is mainly based on grain crops. The study of agricultural environment problems is still lacking, especially in vegetable, orchard, and tea systems. Therefore, a study was carried out in the typical agricultural area of Suzhou City Wuzhong District from 2019 to 2021. Based on the data of the amount of nitrogen and phosphorus removal by harvest crops and soil nitrogen and phosphorus residual in paddy, vegetable, orchard, and tea systems, the loss was estimated. The responses of nitrogen and phosphorus loss from typical crop systems to fertilizer application strategy adjustments were studied through analysis of different factors. The results showed that fertilizer application rate was the key to control nitrogen and phosphorus loss. Additionally, the suitable replacement ratio of organic fertilizer could further reduce the loss risk. It should be noted that the urgent demand for nutrients in crop growth should be considered to determine the timing of organic fertilizer application, and agricultural machinery should be used to assist organic fertilizer application to reduce labor output if possible. Fertilizer efficiency was the core of environmental friendliness and economic benefits of crop farming. Hence, improving fertilizer efficiency should be the guidance of fertilizer application strategy adjustment. Our suggestions on the adjustment of fertilizer application strategy in different crop systems in the study area are as follows:attention should be paid to the nitrogen, phosphorus, and potassium input ratio in paddy systems to further reduce nitrogen and phosphorus loss. Planting structure adjustment should be emphasized in vegetable systems to promote fertilizer efficiency. The strategy to satisfy both tea and orchard growth from a composite system perspective would help to build crop systems that meet the needs of green agricultural development.

Shear wave elastography parameters adds prognostic value to adverse outcome in kidney transplantation recipients.

INTRODUCTION: The tissue stiffness of donor kidneys in transplantation may increase due to pathological changes such as glomerulosclerosis and interstitial fibrosis, and those changes associate worse outcomes in kidney transplantation recipients. Ultrasound elastography is a noninvasive imaging examination with the ability to quantitatively reflect tissue stiffness. Aim of this study was to evaluate the prognostic value of ultrasound elastography for adverse kidney outcome in kidney transplantation recipients. METHODS: Shear wave elastography (SWE) examinations were performed by two independent operators in kidney transplantation recipients. The primary outcome was a composite of kidney graft deterioration, all-cause re-hospitalization, and all-cause mortality. Survival analysis was calculated by Kaplan-Meier curves with the log-rank test and Cox regression analysis. RESULTS: A total of 161 patients (mean age 46 years, 63.4% men) were followed for a median of 20.1 months. 27 patients (16.77%) reached the primary endpoint. The mean and median tissue stiffness at the medulla (hazard ratio: 1.265 and 1.229, respectively), estimated glomerular filtration rate (eGFR), and serum albumin level were associated with the primary outcome in univariate Cox regression. Adding mean or median medulla SWE to a baseline model containing eGFR and albumin significantly improved its discrimination (C-statistics: 0.736 for the baseline, 0.766 and 0.772 for the model added mean and median medulla SWE, respectively). CONCLUSION: The medullary tissue stiffness of kidney allograft measured by shear wave elastography may provide incremental prognostic value to adverse outcomes in kidney transplantation recipients. Including SWE parameters in kidney transplantation recipients management could be considered to improve risk stratification.

TRAF6 promotes osteogenesis in ADSCs through Raf-Erk-Merk-Hif1-a pathway.

Critical-size defects (CSDs) are challenging oral clinical issues that need to be solved. Adipose-derived mesenchymal stem cells (ADSCs) and gene therapy offer a new target to solve these issues. Consequently, ADSCs attract more and more attention because of advantages such as easy obtainability and no ethical concerns. TNF receptor-associated factor 6 (TRAF6) is a significant binding protein both of tumour necrosis factor superfamily and of the toll/interleukin-1 receptor superfamily. Evidence is accumulating that TRAF6 inhibited osteoclast formation and promoted the proliferation of multiple myeloma cell lines and bone resorption. Here, we reported that overexpression of TRAF6 enhanced the proliferation, migration and osteogenesis of ADSCs through Raf-Erk-Merk-Hif1a pathway. Cell sheet of ADSCs combined with TRAF6 accelerated the healing of CSDs. In a word, TRAF6 enhanced osteogenesis, migration and proliferation through Raf-Erk-Merk-Hif1a pathway.

Cleanup of Cr(VI)-polluted groundwater using immobilized bacterial consortia via bioreduction mechanisms.

Cr(VI) bioreduction has become a remedial alternative for Cr(VI)-polluted site cleanup. However, lack of appropriate Cr(VI)-bioreducing bacteria limit the field application of the in situ bioremediation process. In this study, two different immobilized Cr(VI)-bioreducing bacterial consortia using novel immobilization agents have been developed for Cr(VI)-polluted groundwater remediation: (1) granular activated carbon (GAC) + silica gel + Cr(VI)-bioreducing bacterial consortia (GSIB), and (2) GAC + sodium alginate (SA) + polyvinyl alcohol (PVA) + Cr(VI)-bioreducing bacterial consortia (GSPB). Moreover, two unique substrates [carbon-based agent (CBA) and emulsified polycolloid substrate (EPS)] were developed and used as the carbon sources for Cr(VI) bioreduction enhancement. The microbial diversity, dominant Cr-bioreducing bacteria, and changes of Cr(VI)-reducing genes (nsfA, yieF, and chrR) were analyzed to assess the effectiveness of Cr(VI) bioreduction. Approximately 99% of Cr(VI) could be bioreduced in microcosms with GSIB and CBA addition after 70 days of operation, which caused increased populations of total bacteria, nsfA, yieF, and chrR from 2.9 × 108 to 2.1 × 1012, 4.2 × 104 to 6.3 × 1011, 4.8 × 104 to 2 × 1011, and 6.9 × 104 to 3.7 × 107 gene copies/L. In microcosms with CBA and suspended bacteria addition (without bacterial immobilization), the Cr(VI) reduction efficiency dropped to 60.3%, indicating that immobilized Cr-bioreducing bacteria supplement could enhance Cr(VI) bioreduction. Supplement of GSPB led to a declined bacterial growth due to the cracking of the materials. The addition of GSIB and CBA could establish a reduced condition, which favored the growth of Cr(VI)-reducing bacteria. The Cr(VI) bioreduction efficiency could be significantly improved through adsorption and bioreduction mechanisms, and production of Cr(OH)3 precipitates confirmed the occurrence of Cr(VI) reduction. The main Cr-bioreducing bacteria included Trichococcus, Escherichia-Shigella, and Lactobacillus. Results suggest that the developed GSIB bioremedial system could be applied to cleanup Cr(VI)-polluted groundwater effectively.

Efficacy of Intravenously Administered Gepotidacin in Cynomolgus Macaques following a Francisella tularensis Inhalational Challenge.

Francisella tularensis (F. tularensis) is a Centers for Disease Control (CDC) category "A" Gram-negative biothreat pathogen. Inhalation of F. tularensis can cause pneumonia and respiratory failure and is associated with high mortality rates without early treatment. Gepotidacin is a novel, first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA replication by a distinct mechanism of action. Gepotidacin selectively inhibits bacterial DNA replication via a unique binding mode, has activity against multidrug-resistant target pathogens, and has demonstrated in vitro activity against diverse collections of F. tularensis isolates (MIC90 of 0.5 to 1 µg/mL). Gepotidacin was evaluated in the cynomolgus macaque model of inhalational tularemia, using the SCHU S4 strain, with treatment initiated after exposure and sustained fever. Macaques were dosed via intravenous (i.v.) infusion with saline or gepotidacin at 72 mg/kg/day to support a human i.v. infusion dosing regimen of 1,000 mg three times daily. The primary study endpoint was survival, with survival duration and bacterial clearance as secondary endpoints. Gepotidacin treatment resulted in 100% survival compared to 12.5% in the saline-treated control group (P < 0.0001) at Day 43 postinhalational challenge. All gepotidacin-treated animals were blood and organ culture negative for F. tularensis at the end of the study. In contrast, none of the saline control animals were blood and organ culture negative. Gepotoidacin's novel mechanism of action and the efficacy data reported here (aligned with the Food and Drug Administration Animal Rule) support gepotidacin as a potential treatment for pneumonic tularemia in an emergency biothreat situation.

Two putative novel serotypes of Tibet orbivirus isolated from Culicoides spp. in Yunnan, China.

Tibet orbivirus (TIBOV) was identified as a novel orbivirus in 2014. Antibodies against TIBOV were detected in cattle, Asian buffalo, and goats, while all the sequenced TIBOV strains were isolated from mosquitos and Culicoides. The known TIBOV strains have been classified into four putative serotypes. In this study, two TIBOV strains isolated from Culicoides spp. in Shizong County of Yunnan Province, China, were fully sequenced. The phylogenetic analysis of outer capsid protein 2 (VP2) indicated that these two viral strains belong to two novel putative serotypes of TIBOV. The updated putative serotypes may help in an investigation of the distribution and virulence of TIBOV.

Value of conventional ultrasound and contrast-enhanced ultrasound for the assessment of renal allograft dysfunction and prognosis.

BACKGROUND: Ultrasound (US) is the primary imaging modality for the assessment of transplanted kidneys. This study aims to investigate the ability of conventional US and contrast-enhanced US (CEUS) in assessing renal allograft function and prognosis. METHODS: A total of 78 consecutive renal allograft recipients were enrolled. Patients were classified as normal allograft function (n = 41) and allograft dysfunction (n = 37) groups. All patients underwent US and parameters were measured. The independent-samples t-test or Mann-Whitney U test, logistic regression analysis, Kaplan-Meier survival plots, and Cox regression analysis were used. RESULTS: In multivariable analysis, cortical echo intensity (EI) and cortical peak intensity (PI) were determinant US parameters for renal allograft dysfunction (p = .024 and p = .003, respectively). The combination of cortical EI and PI showed an area under the receiver operating characteristic curve (AUROC) of .785 (p < .001). Of 78 patients (median follow-up: 20mo), 16 (20.5%) exhibited composite end points. Cortical PI had a general prediction accuracy with an AUROC of .691, sensitivity of 87.5%, and specificity of 46.8% at the threshold of 22.08 dB in predicting prognosis (p = .019). The combination of estimated-glomerular filtration rate (e-GFR) and PI in predicting prognosis showed an AUROC of .845 with a cut-off value of .836, sensitivity of 84.0%, and specificity of 67.3% (p < .001). CONCLUSION: This study indicates that cortical EI and PI are useful US parameters for evaluating renal allograft function and e-GFR combined with PI may provide a more accurate predictor of survival.

The minimum weight and age of kidney donors: en bloc kidney transplantation from preterm neonatal donors weighing less than 1.2 kg to adult recipients.

En bloc kidney transplantation (EBKT) to adults from preterm neonates following donation after circulatory death has not been described in the literature. We report 2 successful cases of EBKT from preterm neonatal donation after circulatory death donors weighing <1.2 kg to adult recipients. The first case was a preterm female infant born at 29 weeks' gestational age, weighing 1.07 kg. The recipient was a 34-year-old woman weighing 75 kg. At the 9-month follow-up, the patient demonstrated excellent graft function with a creatinine concentration of 1.48 mg/dL. The second donor was a preterm female infant born at 29 weeks and 5 days' gestation, weighing 1.17 kg. The recipient was a 25-year-old woman weighing 46 kg. By 5 months post surgery, the serum creatinine level had gradually decreased to 1.47 mg/dL. In our experience, EBKT from preterm neonates <30 weeks' gestation and weighing <1.2 kg has demonstrated acceptable short- to medium-term results.