Effects of sub-lethal doses of nisin on the virulence of Salmonella enterica in Galleria mellonella larvae

Salmonella enterica is a pathogen that induces self-limiting gastroenteritis and is of worldwide concern. Nisin, an antimicrobial peptide, has emerged as an alternative for the control of microbial growth but its effect on the virulence of pathogenic bacteria is not yet well-explored. This work aimed to evaluate the virulence of S. enterica in the presence of sub-inhibitory nisin using the experimental model Galleria mellonella. Sub-inhibitory concentrations of nisin of 11.72 and 46.88 μM did not affect the cellular viability of S. enterica but promoted changes in gene expression within 1 h of treatment, with increases of up to 3-fold of pagC, 1.8-fold of invA and 2.3-fold of invF. Larvae of G. mellonella inoculated with S. enterica combined with nisin at 46.88 μM presented mortality, and TL₅₀ noticeably increased to 50% and 80% at 24 and 48 h post-infection, respectively. Defence responses, such as melanisation, nodulation, pseudopodia, immune response, and expression of defence proteins of the larvae G. mellonella were enhanced when the treatments with S. enterica were combined with 11.72 or 46.88 μM nisin. These results show an increase in virulence of S. enterica by sub-MIC concentration of nisin that needs to be explored.     

Development and internal validation of a model for predicting 60-day risk of invasive mould disease in patients with haematological malignancies

ObjectiveOur objective was to develop a model that predicts a patient's risk of developing invasive mould disease (IMD) within 60 days of admission for treatment of a haematological malignancy.MethodsWe analysed 19 risk factors for IMD in a cohort of 1944 adult patients with haematological malignancies over 4127 admissions at a haematology referral centre in Northern Italy (2007-2016). We used a multivariable logistic regression to estimate the 60-day probability of developing probable or proven IMD. The model was internally validated using a bootstrap resampling procedure.ResultsThe prevalence of IMD was 3.3% (90 probable cases, 43 proven cases). Seven risk factors were retained in the final risk model: (1) uncontrolled malignancy, (2) high-risk chemotherapy regimen, (3) high-dose corticosteroids, (4) severe lymphopenia, (5) CMV reactivation or disease, (6) prolonged neutropenia, and (7) a history of previous IMD within 90 days. The model displayed good calibration and discrimination in both the derivation (aROC 0.85, 95% CI 0.84-0.86) and validation (aROC 0.83 95% CI 0.79-0.89) populations.ConclusionsOur model differentiated with 85% accuracy whether or not patients developed IMD within 60-days of admission. Individualized risk assessment, aided by validated prognostic models, could assist IMD management and improve antifungal stewardship.     

Cervical cancer screening rate differs by HPV vaccination status: An interim analysis

BackgroundThe incidence of cervical cancer has been increasing, especially in younger generation, in Japan. The females born between 1994 and 1999, who achieved rates of HPV vaccination approaching 70%, have become the target of cervical cancer screening programs. Here, we have analyzed the cervical cancer screening rates among the vaccinated and unvaccinated women.MethodsThe survey data for cervical cancer screening at age 20 in FY 2015 was derived from two cities, Toyonaka and Iwaki.ResultsAmong 2,727 females, in Toyonaka and Iwaki, who were born in FY 1995 and targeted in FY 2015 at age 20 for cervical cancer screening, their HPV vaccination rate was 64.2% (1,753/2,727). The screening rate was 6.4% (112/1,753) in the vaccinated and 3.9% (38/974) in the unvaccinated. This difference was statistically significant (p < 0.01).ConclusionsWe have demonstrated that HPV-vaccinated females tended to be effectively protected from future cervical cancer than the unvaccinated.     

Redox stress response and UV tolerance in the acidophilic iron-oxidizing bacteria Leptospirillum ferriphilum and Acidithiobacillus ferrooxidans

The oxidative stress response represents a sum of antioxidative mechanisms that are essential for determining the adaptation and abundance of microorganisms in the environment. Leptospirillum ferriphilum and Acidithiobacillus ferrooxidans are chemolithotrophic bacteria that obtain their energy from the oxidation of ferrous ion. Both microorganisms are important for bioleaching of sulfidic ores and both are tolerant to high levels of heavy metals and other factors that can induce oxidative stress. In this work, we compared the tolerance and response of L. ferriphilum and At. ferrooxidans to Fe³⁺, H₂O₂, K₂CrO₄, and UV-C radiation. We evaluated growth, generation of reactive oxygen species (ROS), oxidative damage to lipid membranes and DNA, and the activity of antioxidative proteins in cells exposed to these stressors. L. ferriphilum had higher cell density, lower ROS content and less lipid and DNA damage than At. ferrooxidans. Consistent with this, the activity levels of thioredoxin and superoxide dismutase in L. ferriphilum were upregulated and higher than in At. ferrooxidans. This indicated that L. ferriphilum has a higher capacity to respond to oxidative stress and to manage redox homeostasis. This capacity could largely contribute to the high abundance of this species in natural and anthropogenic sites.     

Novel approaches for mechanistic understanding and predicting preeclampsia

Despite intense investigation, preeclampsia (PE) remains largely enigmatic. Relatively late onset of diagnostic signs and heterogeneous nature of the disease further contribute to poor understanding of its etiology and clinical management. There exist no concrete animal models that can provide mechanistic underpinnings for evaluating targeted therapeutic intervention. Poor cross-sectional findings with potential biochemical markers reported so far have proved counterintuitive and suggest a need for novel approaches to predict the early onset of disease. Because of the co-onset of local placental anomalies and systemic manifestation of symptoms, it is highly likely that serum from PE patients can provide a “blueprint” of causative factors. Proteomic and/or functional analysis of maternal serum are expected to predict the onset of disease ahead of manifestation of clinical symptoms. A serum-based predictive assay should overcome complexities resulting from the heterogeneous etiology of PE. This review attempts to address some of these issues and discuss the signature biochemical serum factors and propose new and better ways to predict PE.     

High-density lipoprotein cholesterol to apolipoprotein A1 ratio and all-cause mortality among incident peritoneal dialysis patients

Background and aimsThe ratio of high-density lipoprotein cholesterol to apolipoprotein A1 (HAR) is associated with all-cause mortality in nonchronic kidney disease patients, but its role in predicting all-cause mortality in patients undergoing peritoneal dialysis (PD) is still unclear. The purpose of this study was to investigate the relationship between HAR and all-cause mortality in patients with PD.Methods and resultsThe medical records of 1199 patients with PD from November 1, 2005, to August 31, 2019, were collected retrospectively. The main outcome was defined as all-cause mortality. The HAR was divided into three groups by X-tile software. The association between HAR and all-cause mortality was evaluated by Cox models. The Kaplan–Meier method was used for the survival curve. The median follow-up period was 35 months (interquartile range: 20–57 months), with a total of 326 deaths recorded. After multiple adjustments, the risk of all-cause mortality in the high HAR group was 1.96-fold higher than that in the low HAR group (hazard ratio: 1.96; 95% CI, 1.22 to 3.15; P = 0.005). The restricted cubic splines showed that the risk of all-cause mortality increased gradually when HAR was >0.37. In the stratified analysis, a high HAR was linked to a high risk of all-cause mortality in males, patients under 55 years old, and patients without diabetes or cardiovascular disease (CVD).ConclusionThis study suggests that HAR is independently related to all-cause mortality in PD patients, especially in males, patients under 55 years old, and patients without diabetes or CVD.     

国产自主研发二维水箱应用于螺旋断层 加速器束流质控的可行性研究

目的 使用国产二维水箱在螺旋断层加速器(TOMO)上测量百分深度剂量(PDD)和射野离轴剂量分布,探索其应用于TOMO束流质控的可行性。方法 使用国产二维水箱在TOMO上采集数据。选择40.0 cm × 1.0 cm、40.0 cm × 2.5 cm、40. 0 cm × 5.0 cm 3个射野测量水下1.5、5.0、10.0、15.0、20.0 cm深度的横向离轴剂量分布,选择25.0 cm × 1.0 cm、25.0 cm × 2.5 cm、25.0 cm × 5.0 cm 3个射野测量百分深度剂量曲线以及水下1.5、5.0、10.0、15.0、20.0 cm 深度的纵向离轴剂量分布,将所有数据导入TEMS软件进行γ分析。结果 以厂家金标准数据为基准,国产水箱PDD曲线在3个射野条件下基本吻合,建成区差异偏大,PDD₂₀/PDD₁₀相对偏差>1%。横向离轴剂量分布在3个不同射野条件下除20.0 cm外其他4个深度处所测四分之一高宽(FWQM)均<1%;在3个不同射野、不同深度条件下所测数据在2%/1 mm标准下γ值均>1。纵向离轴剂量分布除射野25.0 cm × 1.0 cm外,其他两个射野不同深度条件下所测半高宽(FWHM)均<1%;除射野25.0 cm × 5.0 cm、深度为15.0和20.0 cm外,其他不同射野不同深度条件下所测数据在2%/1%射野宽度的分析标准下γ值均>1。结论 国产二维水箱部分满足TOMO日常质控需求但仍需进一步优化改进以完全满足TOMO的临床验收需求。     

Humoral immune response following the inactivated quadrivalent influenza vaccination among HIV-infected and HIV-uninfected adults

BackgroundA limited amount of information is available about the immunogenicity of the quadrivalent inactivated influenza vaccine among human immunodeficiency virus (HIV)-infected individuals, especially in low and middle-income countries (LMICs).MethodsHIV-infected adults and HIV-uninfected adults received a dose of quadrivalent inactivated influenza vaccine including strains of H1N1, H3N2, BV and BY. Enzyme-linked immunosorbent assay (ELISA) and hemagglutination-inhibition assay (HAI) were used to determine IgA, IgG antibody concentration and geometric mean titers (GMT) at day 0 and day 28, respectively. Associated factors contributing to seroconversion or GMT changes were analyzed using simple logistic regression model.ResultsA total of 131 HIV-infected and 55 HIV-uninfected subjects were included in the study. In both HIV-infected and uninfected arms, IgG and IgA against influenza A and B all increased significantly at day 28 after receiving QIV (P < 0.001). GMTs of post-vaccination at day 28 showed that HIV-infected persons with CD4 + T cell counts ≤ 350 cells/mm³ were statistically less immunogenic to all strains of QIV than HIV-uninfected ones (P < 0.05). HIV-infected participants with CD4 + T cell counts ≤ 350 cells/mm³ were less likely to achieve seroconversion to QIV (H1N1, BY and BV) than HIV-uninfected individuals at day 28 after vaccination (P < 0.05). Compared with HIV-infected patients with baseline CD4 + T cell counts ≤ 350 cells/mm³, individuals with baseline CD4 + T cell counts > 350 cell/mm³ seemed more likely to generate antibody responses to H1N1 (OR:2.65, 95 %CI: 1.07–6.56) and BY (OR: 3.43, 95 %CI: 1.37–8.63), and showed a higher probability of seroconversion to BY (OR: 3.59, 95 %CI: 1.03–12.48). Compared with nadir CD4 + T cell count ≤ 350 cell/mm³, individuals with nadir CD4 + T cell count > 350 cell/mm³ showed a higher probability of seroconversion to H1N1(OR: 3.15, 95 %CI: 1.14–8.73).ConclusionInfluenza vaccination of HIV-infected adults might be effective despite variable antibody responses. HIV-positive populations with CD4 + T cell counts ≤ 350 are less likely to achieve seroconversion. Further vaccination strategies could be developed for those with low CD4 T cell counts.