A guide to oral vaccination: Highlighting electrospraying as a promising manufacturing technique toward a successful oral vaccine development

Most vaccines approved by regulatory bodies are administered via intramuscular or subcutaneous injections and have shortcomings, such as the risk of needle-associated blood infections, pain and swelling at the injection site. Orally administered vaccines are of interest, as they elicit both systemic and mucosal immunities, in which mucosal immunity would neutralize the mucosa invading pathogen before the onset of an infection. Hence, oral vaccination can eliminate the injection associated adverse effects and enhance the person's compliance. Conventional approaches to manufacturing oral vaccines, such as coacervation, spray drying, and membrane emulsification, tend to alter the structural proteins in vaccines that result from high temperature, organic and toxic solvents during production. Electrohydrodynamic processes, specifically electrospraying, could solve these challenges, as it also modulates antigen release and has a high loading efficiency. This review will highlight the mucosal immunity and biological basis of the gastrointestinal immune system, different oral vaccine delivery approaches, and the application of electrospraying in vaccines development.     

Arterial spin labeling MR image denoising and reconstruction using unsupervised deep learning

Arterial spin labeling (ASL) imaging is a powerful magnetic resonance imaging technique that allows to quantitatively measure blood perfusion non-invasively, which has great potential for assessing tissue viability in various clinical settings. However, the clinical applications of ASL are currently limited by its low signal-to-noise ratio (SNR), limited spatial resolution, and long imaging time. In this work, we propose an unsupervised deep learning-based image denoising and reconstruction framework to improve the SNR and accelerate the imaging speed of high resolution ASL imaging. The unique feature of the proposed framework is that it does not require any prior training pairs but only the subject's own anatomical prior, such as T1-weighted images, as network input. The neural network was trained from scratch in the denoising or reconstruction process, with noisy images or sparely sampled k-space data as training labels. Performance of the proposed method was evaluated using in vivo experiment data obtained from 3 healthy subjects on a 3T MR scanner, using ASL images acquired with 44-min acquisition time as the ground truth. Both qualitative and quantitative analyses demonstrate the superior performance of the proposed txtc framework over the reference methods. In summary, our proposed unsupervised deep learning-based denoising and reconstruction framework can improve the image quality and accelerate the imaging speed of ASL imaging.     

Pulmonary Hypertension Registry of Kerala,India (PRO-KERALA): One-year outcomes

BackgroundShort term outcomes of patients with pulmonary hypertension are not available from low and middle-income countries including India.MethodsWe conducted a prospective study of 2003 patients with pulmonary hypertension, from 50 centres (PROKERALA) in Kerala, who were followed up for one year. Pulmonary hypertension (PH) was mainly diagnosed on the basis of Doppler echocardiography. The primary outcome was a composite end-point of all-cause death and hospital admission for heart failure. All cause hospitalisation events constituted the secondary outcome.ResultsMean age of study population was 56 ± 16 years. Group 1 and Group 2 PH categories constituted 21.2% and 59% of the study population, respectively. Nearly two-thirds (65%) of the study participants had functional class II symptoms. 31% of Group 1 PH patients were on specific vasodilator drugs.In total, 83 patients (4.1%) died during the one-year follow-up period. Further, 1235 re-hospitalisation events (61.7%) were reported. In the multivariate model, baseline NYHA class III/IV (OR 1.87, 95% C.I. 1.35–2.56), use of calcium channel blockers (OR 0.18, 95% C.I. 0.04–0.77), vasodilator therapy (OR 0.5, 95% C.I. 0.28–0.87) and antiplatelet agents (OR 1.80, 95% C.I. 1.29–2.51) were associated with primary composite outcome at one-year (p < 0.05).ConclusionIn the PROKERALA registry, annual mortality rate was 4%. More than half of the patients reported re-hospitalisation events on follow up. Uptake of guideline directed therapies were suboptimal in the study population. Quality improvement programmes to improve guideline directed therapy may improve clinical outcomes of PH patients in India.     

人髌下脂肪垫干细胞的分离培养鉴定及初步研究

目的建立人髌下脂肪垫干细胞分离、培养和鉴定的平台，验证其可作为可靠的干细胞来源，并可作为细胞模型参与科学研究。 方法人髌下脂肪垫取自膝关节置换手术患者，经Ⅰ型胶原酶消化，在高糖Dulbecco改良Eagle培养基(DMEM)内扩增，取P5代细胞用于检测其"干性"及三向分化能力。与微尺度支架结合，通过RT－PCR检测成骨基因的表达，应用最小显著性差异法进行组间两两比较，用于验证微尺度支架的成骨诱导特性。 结果人髌下脂肪垫干细胞具备间充质干细胞相关特性，包括黏附贴壁性；成脂肪、成软骨及成骨分化；表达相关表面标记，如分化抗原簇(CD)73、CD90和CD105；不表达造血细胞系的分子表面标记，如c-kit、CD14、CD11b、CD34、CD45、CD19、CD79和人白细胞抗原(HLA)-DR。本课题中人髌下脂肪垫来源干细胞成功作为一种干细胞模型，证明HaCG微尺度支架具备成骨诱导特性，表现为三组中成骨基因ALP、COL1、Runx2表达差异有统计学意义(分别为F＝150，P<0.01；F＝68，P<0.01；F＝16，P<0.01)。HaCG微尺度支架组高于纯明胶微尺度支架组及二维培养组，纯明胶微尺度支架组高于二维培养组(P值均小于0.05)。 结论人髌下脂肪垫干细胞分离、培养和鉴定平台的建立，未来可作为细胞模型应用于多种不同实验。     

Sonication of Antibiotic Loaded Cement Spacers: A Valuable Technique for Detection of Infection Persistence in Two-stage Revision for Infected Joint Arthroplasty

We evaluated the diagnostic utility of sonication of antibiotic loaded cement spacers comparing with periprosthetic tissue cultures for the detection of persisting infection in 14 patients undergoing staged procedures. Sonication improved microbial detection of intraoperative cultures from 14.2% to 28.5% (P = 0.481). Routine sonication of spacers is recommended.     

Proteases and their inhibitors as prognostic factors for high-grade serous ovarian cancer

Ovarian carcinoma is one of the most lethal malignancies, but only very few prognostic biomarkers are known. The degradome, comprising proteases, protease non-proteolytic homologues and inhibitors, have been involved in the prognosis of many cancer types, including ovarian carcinoma. The prognostic significance of the whole degradome family has not been specifically studied in high-grade serous ovarian cancer. A targeted DNA microarray known as the CLIP-CHIP microarray was used to identify potential prognostic factors in ten high-grade serous ovarian cancer women who had early recurrence (<1.6 years) or late/no recurrence after first line surgery and chemotherapy. In women with early recurrence, we identified seven upregulated genes (TMPRSS4, MASP1/3, SPC18, PSMB1, IGFBP2, CFI – encoding Complement Factor I – and MMP9) and one down-regulated gene (ADAM-10). Using immunohistochemistry, we evaluated the prognostic effect of these 8 candidate genes in an independent cohort of 112 high-grade serous ovarian cancer women. Outcomes were progression, defined according to CA-125 criteria, and death. Multivariate Cox proportional hazard regression models were done to estimate the associations between each protein and each outcome. High ADAM-10 expression (intensity of 2–3) was associated with a lower risk of progression (adjusted hazard ratio (HR): 0.51; 95% confidence interval (CI): 0.29-0.87). High complement factor I expression (intensity 2–3) was associated with a higher risk of progression (adjusted HR: 2.30, 95% CI: 1.17–4.53) and death (adjusted HR: 3.42; 95% CI: 1.72–6.79). Overall, we identified the prognostic value of two proteases, ADAM-10 and complement factor I, for high-grade serous ovarian cancer which could have clinical significance.     

Ehlers-Danlos Syndrome: It’s Not Your Normal Hoofbeats

The purpose of this article is to acquaint the reader with the presentation, diagnosis, and management of Ehlers-Danlos syndrome (EDS), a group of genetic connective tissue disorders. Progressive weakness of connective tissue is the underlying cause of all types of EDS. The symptoms of EDS are numerous, with variability in presentation. However, decreased quality of life caused by chronic pain and fatigue is a commonality of all types of EDS. This article will assist the nurse practitioner in recognizing EDS and offer guidance for treatment.     

Stem cells for babies and their surgeons: The future is now

Pediatric surgeons are ideal allies for the translation of basic science including stem cell therapies. In the spirit of Robert E. Gross, of applying creative solutions to pediatric problems with technical expertise, we describe the impending cellular therapies that may be derived from stem and progenitor cells. Understanding the types and capabilities of stem and progenitor cells is important for pediatric surgeons to join and facilitate progress for babies. We are developing an induced pluripotent stem cell therapy for enteric neuropathies such as Hirschsprung disease that might be helpful for children in the near future. Our goals, which we hope to share with other surgeons and scientists, include working to establish safe clinical trials and meeting regulatory standards in a thoughtful way that balances patients need and unknown risks.