A prime-boost concept using a T-cell epitope-driven DNA vaccine followed by a whole virus vaccine effectively protected pigs in the pandemic H1N1 pig challenge model

Influenza A virus (IAV) vaccines in pigs generally provide homosubtypic protection but fail to prevent heterologous infections. In this pilot study, the efficacy of an intradermal pDNA vaccine composed of conserved SLA class I and class II T cell epitopes (EPITOPE) against a homosubtypic challenge was compared to an intramuscular commercial inactivated whole virus vaccine (INACT) and a heterologous prime boost approach using both vaccines. Thirty-nine IAV-free, 3-week-old pigs were randomly assigned to one of five groups including NEG-CONTROL (unvaccinated, sham-challenged), INACT-INACT-IAV (vaccinated with FluSure XP® at 4 and 7 weeks, pH1N1 challenged), EPITOPE-INACT-IAV (vaccinated with PigMatrix EDV at 4 and FluSure XP® at 7 weeks, pH1N1 challenged), EPITOPE-EPITOPE-IAV (vaccinated with PigMatrix EDV at 4 and 7 weeks, pH1N1 challenged), and a POS-CONTROL group (unvaccinated, pH1N1 challenged). The challenge was done at 9 weeks of age and pigs were necropsied at day post challenge (dpc) 5. At the time of challenge, all INACT-INACT-IAV pigs, and by dpc 5 all EPITOPE-INACT-IAV pigs were IAV seropositive. IFNγ secreting cells, recognizing vaccine epitope-specific peptides and pH1N1 challenge virus were highest in the EPITOPE-INACT-IAV pigs at challenge. Macroscopic lung lesion scores were reduced in all EPITOPE-INACT-IAV pigs while INACT-INACT-IAV pigs exhibited a bimodal distribution of low and high scores akin to naïve challenged animals. No IAV antigen in lung tissues was detected at necropsy in the EPITOPE-INACT-IAV group, which was similar to naïve unchallenged pigs and different from all other challenged groups. Results suggest that the heterologous prime boost approach using an epitope-driven DNA vaccine followed by an inactivated vaccine was effective against a homosubtypic challenge, and further exploration of this vaccine approach as a practical control measure against heterosubtypic IAV infections is warranted.     

The oncogenic impact of RNF2 on cell proliferation,invasion and migration through EMT on mammary carcinoma

Mammary carcinoma (MC) is one of most common malignancy in women, and ring finger protein 2 (RNF2) possesses various roles in vast human tumors. In MC tissues as well as in cell lines RNF2 exhibited high expression, had significant association with tumor size, lymph node status, TNM stage, patients’ poor survival, and promoted cell proliferation, colony formation, cell migration and invasion of MC cell lines which was mediated by downregulation of E-cadherin protein. These data reveal that RNF2 protein plays a vital role in the development of MC and may be a potential therapy target of MC.     

Inter-ictal assay of peripheral circulating inflammatory mediators in migraine patients under adjunctive cervical non-invasive vagus nerve stimulation (nVNS): A proof-of-concept study

Objective

To assay peripheral inter-ictal cytokine serum levels and possible relations with non-invasive vagus nerve stimulation (nVNS) responsiveness in migraineurs.

输卵管妊娠治疗方式及其对未来生育影响的研究进展

输卵管妊娠是一种临床常见的妇科急腹症。输卵管妊娠如能在包块尚未破裂前早期诊断，其相关的病死率大大降低。输卵管妊娠的治疗方式有很多，无论哪种治疗方式，都会导致患者生育功能的下降。临床中对于有生育要求的患者，选择哪种治疗方式更好地保护患者的生育功能并减少并发症仍是有争议的话题。近年有学者做了大量研究比较输卵管妊娠不同治疗方式的并发症及其对患者未来生育前景的影响，甚至提出更新的治疗方式以弥补传统治疗方式的不足。现就输卵管妊娠的治疗方式、并发症及对未来生育的影响的研究进展进行综述。     

Assessment of the uterine dose in digital mammography and digital breast tomosynthesis

IntroductionDigital Mammography (DM-2D) and more recently Digital Breast Tomosynthesis (DBT), are two of the most effective imaging modalities for breast cancer detection, often used in screening programmes. It may happen that exams using these two imaging modalities are inadvertently performed to pregnant women. The objective of this study is to assess the dose in the uterus due to DM-2D and DBT exams, according to two main irradiation scenarios: in the 1st scenario the exposure parameters were pre-selected directly by the imaging system, while in the 2nd scenario, the maximum exposure parameters were chosen.MethodsThe mammography equipment used was a Siemens Mammomat Inspiration. A physical anthropomorphic phantom, PMMA plates (simulating a breast thickness of 6 cm) and thermoluminescent dosimeters (TLDs) were used to measure entrance air kerma values on the phantom's breast and abdomen in order to successively estimate the mean glandular dose (MGD) and the dose in the uterus. For the two irradiation scenarios chosen, two-breast imaging modalities were selected: 1) DBT in Cranio-Caudal (CC) view (with 28 kV and 160 mAs as exposure parameters), 2) DBT and DM in Medio Lateral-Oblique (MLO) and CC views (with 34 kV and 250 mAs as exposure parameters).ResultsIn the 1st scenario, the TLD measurements did not detect significant dose values in the abdomen whereas the MGD estimated using the D.R. Dance model was in close agreement with data available in the literature. In the 2nd scenario, there was no significant difference in MGD estimation between the different views, whereas the air kerma values in the abdomen (in DBT mode, CC and MLO) were 0.049 mGy and 0.004 mGy respectively. In CC DM-2D mode the abdomen air kerma value was 0.026 mGy, with no significant detected value in MLO view.ConclusionsFor the dose in the uterus, the obtained values seem to indicate that DM-2D and DBT examinations inadvertently performed during pregnancy do not pose a significant radiological risk, even considering the case of overexposure in both breasts.Implications for practiceThe accurate knowledge of the doses in DM-2D and DBT will contribute to raise the awareness among medical practitioners involved in breast imaging empowering them to provide accurate information about dose levels in the uterus, improving their radiation risk communication skills and consequently helping to reduce the anxiety of pregnant women undergoing this type of examinations.     

Cold-passaged isolates and bat-swine influenza a chimeric viruses as modified live-attenuated vaccines against influenza a viruses in pigs

Swine influenza A virus (swIAV) infections in pig populations cause considerable morbidity and economic losses. Frequent reverse zoonotic incursions of human IAV boost reassortment opportunities with authentic porcine and avian-like IAV in swine herds potentially enhancing zoonotic and even pre-pandemic potential. Vaccination using adjuvanted inactivated full virus vaccines is frequently used in attempting control of swIAV infections. Accelerated antigenic drift of swIAV in large swine holdings and interference of maternal antibodies with vaccine in piglets can compromise these efforts. Potentially more efficacious modified live-attenuated vaccines (MLVs) bear the risk of reversion of MLV to virulence. Here we evaluated new MLV candidates based on cold-passaged swIAV or on reassortment-incompetent bat-IAV-swIAV chimeric viruses. Serial cold-passaging of various swIAV subtypes did not yield unambiguously temperature-sensitive mutants although safety studies in mice and pigs suggested some degree of attenuation. Chimeric bat-swIAV expressing the hemagglutinin and neuraminidase of an avian-like H1N1, in contrast, proved to be safe in mice and pigs, and a single nasal inoculation induced protective immunity against homologous challenge in pigs. Reassortant-incompetent chimeric bat-swIAV vaccines could aid in reducing the amount of swIAV circulating in pig populations, thereby increasing animal welfare, limiting economic losses and lowering the risk of zoonotic swIAV transmission.     

Botulinum toxin blocks mast cells and prevents rosacea like inflammation

Background

Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.

A DNA vaccine expressing an optimized secreted FAPα induces enhanced anti-tumor activity by altering the tumor microenvironment in a murine model of breast cancer

Cancer-associated fibroblasts (CAFs), major components of the tumor microenvironment (TME), promote tumor growth and metastasis and inhibit the anti-tumor immune response. We previously constructed a DNA vaccine expressing human FAPα, which is highly expressed by CAFs, to target these cells in the TME, and observed limited anti-tumor effects in the 4T1 breast cancer model. When the treatment time was delayed until tumor nodes formed, the anti-tumor effect of the vaccine completely disappeared. In this study, to improve the safety and efficacy, we constructed a new FAPα-targeted vaccine containing only the extracellular domain of human FAPα with a tissue plasminogen activator signal sequence for enhanced antigen secretion and immunogenicity. The number of CAFs was more effectively reduced by CD8⁺ T cells induced by the new vaccine. This resulted in decreases in CCL2 and CXCL12 expression, leading to a significant decrease in the ratio of myeloid-derived suppressor cells in the TME. Moreover, when mice were treated after the establishment of tumors, the vaccine could still delay tumor growth. To facilitate the future application of the vaccine in clinical trials, we further optimized the gene codons and reduced the homology between the vaccine and the original sequence, which may be convenient for evaluating the vaccine distribution in the human body. These results indicated that the new FAPα-targeted vaccine expressing an optimized secreted human FAPα induced enhanced anti-tumor activity by reducing the number of FAPα⁺ CAFs and enhancing the recruitment of effector T cells in the 4T1 tumor model mice.     

Predicting the initial spread of novel Asian origin influenza A viruses in the continental USA by wild waterfowl

Using data on waterfowl band recoveries, we identified spatially explicit hotspots of concentrated waterfowl movement to predict occurrence and spatial spread of a novel influenza A virus (clade 2.3.4.4) introduced from Asia by waterfowl from an initial outbreak in North America in November 2014. In response to the outbreak, the hotspots of waterfowl movement were used to help guide sampling for clade 2.3.4.4 viruses in waterfowl as an early warning for the US poultry industry during the outbreak . After surveillance sampling of waterfowl, we tested whether there was greater detection of clade 2.3.4.4 viruses inside hotspots. We found that hotspots defined using kernel density estimates of waterfowl band recoveries worked well in predicting areas with higher prevalence of the viruses in waterfowl. This approach exemplifies the value of ecological knowledge in predicting risk to agricultural security.     

二补助育汤对胚胎着床障碍小鼠子宫血管生成相关因子表达的影响

目的：探讨二补助育汤对胚胎着床障碍模型小鼠子宫内膜形态及血管生成素-1（Ang-1）mRNA、血管内皮生长因子（VEGF）mRNA的表达和定位的影响。方法：24只ICR雌性小鼠随机分为空白组、模型组、戊酸雌二醇组、二补助育汤组，每组6只，用米非司酮建立胚胎着床障碍动物模型，各组给予相应药物灌胃，妊娠第5天处死小鼠后，检测各组妊娠率、平均着床位点数、子宫内膜Ang-1和VEGF mRNA表达量及其蛋白定位。结果：模型组小鼠平均胚胎着床位点数、Ang-1 mRNA、VEGF mRNA表达量明显低于空白组（均P<0.05）；与模型组比较，二补助育汤组平均胚胎着床位点数、Ang-1 mRNA、VEGF mRNA表达量显著提高（均P<0.05）。结论：二补助育汤可提高子宫内膜Ang-1和VEGF蛋白表达量，促进子宫内膜血管生成，从而提高子宫内膜容受性。