A candidate multi-epitope vaccine against porcine reproductive and respiratory syndrome virus and Mycoplasma hyopneumoniae induces robust humoral and cellular response in mice

Porcine reproductive and respiratory syndrome virus (PRRSV) and Mycoplasma hyopneumoniae (M. hyopneumoniae, Mhp) are two of the most common pathogens involved in the porcine respiratory disease complex (PRDC) resulting in significant economic losses worldwide. Vaccination is the most effective approach to disease prevention. Since PRRSV and Mhp co-infections are very common, an efficient dual vaccine against these pathogens is required for the global swine industry. Compared with traditional vaccines, multi-epitope vaccines have several advantages, they are comparatively easy to produce and construct, are chemically stable, and do not have an infectious potential. In this study, to develop a safe and effective vaccine, B cell and T cell epitopes of PRRSV-GP5, PRRSV-M, Mhp-P46, and Mhp-P65 protein had been screened to construct a recombinant epitope protein rEP-PM that has good hydrophilicity, strong antigenicity, and high surface accessibility, and each epitope is independent and complete. After immunization in mice, rEP-PM could induce the production of high levels of antibodies, and it had good immunoreactivity with anti-rEP-PM, anti-PRRSV, and anti-Mhp antibodies. The anti-rEP-PM antibody specifically recognizes proteins from PRRSV and Mhp. Moreover, rEP-PM induced a Th1-dominant cellular immune response in mice. Our results showed that the rEP-PM protein could be a potential candidate for the development of a safe and effective multi-epitope peptide combined vaccine to control PRRSV and Mhp infections.     

Vaccine innovation model: A technology transfer perspective in pandemic contexts

This work identifies the innovations that made it possible for the Bio-Manguinhos/Fiocruz Immunobiological Technology Institute to engage in the entire production of the Oxford/AstraZeneca vaccine (ChAdOx1 nCov-19) in Brazil, just 1.8 years after the COVID-19 pandemic was declared. The results were summarized in a case-based innovation model composed of 11 workstreams, 32 stages, 22 gates, 11 innovations, and 38 events. In terms of research contributions, three were found: (i) the identification of firm and government-level innovations allowing the substantial reduction in the COVID-19 vaccine time-to-market in Brazil; (ii) the presentation of empirical evidence supporting the new Outbreak Paradigm for vaccine research, development, and production; and (iii) the proposition of a conceptual model for describing innovations through the vaccine value chain in pandemic contexts, particularly when technology transfer is involved.     

Características y resultados oncológicos del carcinoma epidermoide de ano: análisis comparativo entre los pacientes inmunocompetentes y los inmunodeprimidos

ObjectiveMost evidence, including recent randomized controlled trials, analysing anal squamous cell carcinoma (SCC) do not consider immunocompromise patient population. The aim of this study was to compare clinical and oncological outcomes among immunocompetent and immunocompromised patients with anal squamous cell carcinoma.MethodMulticentric retrospective comparative study including 2 cohorts of consecutive patients, immunocompetent and immunocompromised, diagnosed with anal SCC. This study evaluated clinical characteristics, clinical response to radical chemoradiotherapy (CRT) and long-term oncological results including both local and distant recurrence, overall survival (OS) and disease-free survival (DFS).ResultsA total of 84 patients, 47 (55.6%) female, diagnosed with anal SCC from January 2012 to December 2017 were included, 22 (26%) and 62 (74%) patients in immunocompromised and immunocompetent groups respectively. Patients in immunocompromised group were significantly younger (53 vs. 61 years; P=0.001), with smaller tumoral size (P=0.044) and reported higher rates of substance abuse.including tobacco use (P=0.034) and parenteral drug consumption (P=0.001). No differences were found in administered therapies (P=301) neither in clinical response to chemoradiotherapy (83 vs. 100%). Moreover, similar 5-year OS (60 vs. 64%; P=0.756) and DFS (65 vs. 68%; P=0.338) were observed.ConclusionThe present study shows no significant differences in long-term oncological results among immunocompetent and immunocompromised patients diagnosed with anal SCC, with a similar oncologic treatment. This evidence might be explained due to the close monitoring and adequate therapeutic control of HIV positive patients.     

蒙药绿松石的质量标准研究＊

目的 建立蒙药绿松石的质量标准。方法 收集不同产地绿松石，共10批。观察绿松石样品和粉末的性状并进行理化鉴别；按2020年版《中国药典》（四部）通则方法测定绿松石样品中水分、浸出物含量；采用原子吸收光谱法测定绿松石样品铜元素含量。结果 绿松石为不规则、周围带有黑石的块状物，表面蓝绿色，体重，质硬脆，难砸碎，断面呈贝壳状，蜡样光泽，粉末呈灰绿色，无臭，味淡；理化鉴别结果显示，呈铜盐反应；10批次样品中水分含量为0.41%-3.94%（SD=1.37%），浸出物含量为0.21%-0.81%（SD=0.21%），铜元素含量为3.03%-4.63%（SD=0.63%）。结论 初步拟定绿松石中水分含量不得超多5.0%、浸出物含量不得低于0.10%，铜元素含量应为2.60%-4.84%，制定的标准可用于蒙药材绿松石的质量控制。     

Preoperative comprehensive malignancy risk estimation for thyroid nodules: Development and verification of a network-based prediction model

BackgroundIn order to avoid excessive treatment of thyroid nodules in the clinic, it is necessary to find a simple and practical analysis method to comprehensively and accurately reflect benign or malignant thyroid nodules. This study aimed to construct and validate a comprehensive and reliable network-based predictive model using a variety of imaging and laboratory criteria for thyroid nodules to stratify the risk of malignancy prior to surgery.MethodsWe retrospectively analyzed data from patients who underwent surgical treatment for thyroid nodules at the Thyroid and Breast Diagnosis and Treatment Center of Weifang Hospital of Traditional Chinese Medicine between January 2018 and December 2020. Binary logical regression analysis was performed to predict whether nodules were malignant or benign. The developmental dataset included 457 patients (January 2018–December 2020). The validation set included separate data points (n = 225, January 2018–December 2020).ResultsIn this study, criteria that showed significant predictive value for malignant nodules included TI-RADS: 4b (p = 0.065); Bethesda IV, Bethesda V, Bethesda VI (P < 0.0001); BRAF^V600E mutation (P < 0.0001); Calcitonin>5 pg/ml (p = 0.0037); and FNA-Tg>30 ng/ml (p = 0.0003). A 10-grade risk scoring system was developed. The risk of malignancy risk ranged from 2.06% to 100% and was positively associated with increasing risk grade. The areas under the receiver-operating characteristic curve of the development and validation sets were 0.972 and 0.946, respectively.ConclusionA simple, comprehensive and reliable web-based predictive model was designed using a variety of imaging and laboratory criteria to stratify thyroid nodules by probability of malignancy.     

The Role of Oral Health in the Acquisition and Severity of SARS-CoV-2: A Retrospective Chart Review

ObjectiveStudies have shown that gingival crevices may be a significant route for SARS-CoV-2 entry. However, the role of oral health in the acquisition and severity of COVID-19 is not known.DesignA retrospective analysis was performed using electronic health record data from a large urban academic medical center between 12/1/2019 and 8/24/2020. A total of 387 COVID-19 positive cases were identified and matched 1:1 by age, sex, and race to 387 controls without COVID-19 diagnoses. Demographics, number of missing teeth and alveolar crestal height were determined from radiographs and medical/dental charts. In a subgroup of 107 cases and controls, we also examined the rate of change in alveolar crestal height. A conditional logistic regression model was utilized to assess association between alveolar crestal height and missing teeth with COVID-19 status and with hospitalization status among COVID-19 cases.ResultsIncreased alveolar bone loss, OR = 4.302 (2.510 – 7.376), fewer missing teeth, OR = 0.897 (0.835–0.965) and lack of smoking history distinguished COVID-19 cases from controls. After adjusting for time between examinations, cases with COVID-19 had greater alveolar bone loss compared to controls (0.641 ± 0.613 mm vs 0.260 ± 0.631 mm, p < 0.01.) Among cases with COVID-19, increased number of missing teeth OR = 2.1871 (1.146– 4.174) was significantly associated with hospitalization.ConclusionsAlveolar bone loss and missing teeth are positively associated with the acquisition and severity of COVID-19 disease, respectively.     

Cytokine and LL-37 gene expression levels in Bartonella spp. seropositive and seronegative patients of a rheumatology clinic

PurposeThe variation in the immune response to Bartonella spp. infection in humans remains unclear. The present study compares the expression of selected interleukins, cytokines and cathelicidin (LL-37) in rheumatology clinic patients suffering from musculoskeletal symptoms with healthy blood donors. The patients had previously been tested for the presence of Bartonella henselae antibodies.MethodsGene expression of LL-37, interleukin (IL)-2, IL-4, IL-6, IL-12, interferon-(IFN)-γ, and tumor necrosis factor (TNF-α)-α was determined in blood samples using quantitative Polymerase Chain Reaction (qPCR). Statistical analysis was prepared with STATISTICA.ResultsStatistically significant differences in the mRNA levels of the tested cytokines (IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-12; p<0.0001) were observed between the healthy controls and patients; however, no difference was observed for LL37 mRNA (p ?= ?0.1974). No significant differences in mRNA expression were observed between IgG in anti-Bartonella seropositive and seronegative individuals (p>0.05). The only significant differences between the Bartonella spp. DNA positive and negative patients, indicated by PCR, were observed for TNF-α and IL-12 mRNA (p ?= ?0.0045 and p ?= ?0.0255, respectively).ConclusionA broadly similar immune response to the tested cytokines was observed among the participants irrespective of anti-Bartonella spp. IgG seropositivity. However, the Bartonella DNA-positive participants demonstrated significantly lower expression of IL-12 and TNF-α mRNA; this may indicate that these bacteria have a suppressive influence on the immune system.