CpG-A and CpG-B oligonucleotides differentially enhance human peptide-specific primary and memory CD8+ T-cell responses in vitro

Two distinct types of CpG oligodeoxynucleotide (ODN) have been identified that differ in their capacity to stimulate antigen-presenting cells: CpG-A induces high amounts of interferon-alpha (IFN-alpha) and IFN-beta in plasmacytoid dendritic cells (PDCs), whereas CpG-B induces PDC maturation and is a potent activator of B cells but stimulates only small amounts of IFN-alpha and IFN-beta. Here we examined the ability of these CpG ODNs to enhance peptide-specific CD8+ T-cell responses in human peripheral blood mononuclear cells (PBMCs). The frequency of influenza matrix-specific "memory" CD8+ T cells was increased by both types of CpG ODN, whereas the frequency of Melan-A specific "naive" CD8+ T cells increased on stimulation with CpG-B but not with CpG-A. The presence of PDCs in PBMCs was required for this CpG ODN-mediated effect. The expanded cells were cytotoxic and produced IFN- on peptide restimulation. Soluble factors induced by CpG-A but not CpG-B increased the granzyme-B content and cytotoxicity of established CD8+ T-cell clones, each of which was IFN-alpha/-beta dependent. In conclusion, CpG-B seems to be superior for priming CD8+ T-cell responses, and CpG-A selectively enhances memory CD8+ T-cell responses and induces cytotoxicity. These results demonstrate distinct functional properties of CpG-A and CpG-B with regard to CD8 T cells.     

Transapical mitral valved stent implantation: Enhanced survival and decreased paravalvular leakages

Background/Objectives

This study presents the recent results of transapical implantation of a new design of a mitral valved stent with up to three months follow-up.

Methods

A self-expanding re-designed mitral valved stent was implanted via transapical approach into the beating heart of eight pigs. Echocardiographic- and hemodynamic parameters were assessed before (n = 8), at 1 h (n = 8), at one month (n = 6), at two months (n = 2), and at three months (n = 1) after implantation and a cardiac CT was conducted.

Results

The stent was successfully deployed in all animals. Two animals died within the first month due to incorrect fixation force. Echocardiographic evaluation showed low gradients (3.9 ± 1.4 mm Hg and 1.9 ± 0.8 mm Hg across the valved stent and aortic valve) and a normal mitral annular plane systolic excursion (1.1 ± 0.2 cm) after one month. No paravalvular leakages (PVL) were detected after 1 h. The pulmonary artery pressure did not increase after valved stent implantation (p ≥ 0.106). The pulmonary capillary wedge pressure (PCWP) slightly increased to 16 ± 3 mm Hg after one month (p = 0.033). The left ventricular end-diastolic pressure was mildly elevated (15.8 ± 8.6 mm Hg) after one month.

Conclusions

Secure deployment and correct position of the valved stents were reproducibly achieved in the off-pump implantation procedure. No paravalvular leakages after 1 h as well as low gradients, few stent fractures and a normal longitudinal function after one month were achieved with this newly developed and well-aligned prototype. However, a number of challenges have been identified during this study and potential for improvement has been identified.     

Social Media: A Review and Tutorial of Applications in Medicine and Health Care

Background

Social media are dynamic and interactive computer-mediated communication tools that have high penetration rates in the general population in high-income and middle-income countries. However, in medicine and health care, a large number of stakeholders (eg, clinicians, administrators, professional colleges, academic institutions, ministries of health, among others) are unaware of social media’s relevance, potential applications in their day-to-day activities, as well as the inherent risks and how these may be attenuated and mitigated.

Objective

We conducted a narrative review with the aim to present case studies that illustrate how, where, and why social media are being used in the medical and health care sectors.

Methods

Using a critical-interpretivist framework, we used qualitative methods to synthesize the impact and illustrate, explain, and provide contextual knowledge of the applications and potential implementations of social media in medicine and health care. Both traditional (eg, peer-reviewed) and nontraditional (eg, policies, case studies, and social media content) sources were used, in addition to an environmental scan (using Google and Bing Web searches) of resources.

Results

We reviewed, evaluated, and synthesized 76 articles, 44 websites, and 11 policies/reports. Results and case studies are presented according to 10 different categories of social media: (1) blogs (eg, WordPress), (2) microblogs (eg, Twitter), (3) social networking sites (eg, Facebook), (4) professional networking sites (eg, LinkedIn, Sermo), (5) thematic networking sites (eg, 23andMe), (6) wikis (eg, Wikipedia), (7) mashups (eg, HealthMap), (8) collaborative filtering sites (eg, Digg), (9) media sharing sites (eg, YouTube, Slideshare), and others (eg, SecondLife). Four recommendations are provided and explained for stakeholders wishing to engage with social media while attenuating risk: (1) maintain professionalism at all times, (2) be authentic, have fun, and do not be afraid, (3) ask for help, and (4) focus, grab attention, and engage.

Conclusions

The role of social media in the medical and health care sectors is far reaching, and many questions in terms of governance, ethics, professionalism, privacy, confidentiality, and information quality remain unanswered. By following the guidelines presented, professionals have a starting point to engage with social media in a safe and ethical manner. Future research will be required to understand the synergies between social media and evidence-based practice, as well as develop institutional policies that benefit patients, clinicians, public health practitioners, and industry alike.     

Promoting Business and Entrepreneurial Awareness in Health Care Professionals: Lessons From Venture Capital Panels at Medicine 2.0 Conferences

There are few mechanisms that bring the academic and business worlds together in a way that would maximize the success of health technology (health tech) start-ups by increasing researchers’ knowledge about how to operate in the business world. Existing solutions (eg, technology transfer offices and dual degree MD/MBA programs) are often unavailable to researchers from outside the institution or to those who have already completed their primary education, such as practicing physicians. This paper explores current solutions and offers a partial solution: include venture capital (VC) panels in medical conferences. These VC panels educate academics on 2 important and interconnected issues: how to “pitch” their ideas in the business world and what to consider when creating a company. In these sessions, academia-based start-up companies present their ideas before a VC panel composed of professional investors and receive feedback on their idea, business plan, and presentation techniques. Recent panel recommendations from Medicine 2.0 conferences fell into 7 categories: (1) the product, service, or idea you are developing into a company, (2) determine market forces and identify the target audience, (3) describe your competitive advantage, (4) the business plan, (5) current and future resources and capabilities, (6) legal aspects, and (7) general advice on the art of pitching. The academic and business literature validates many of these recommendations suggesting that VC panels may be a viable and cost-effective introduction to business and entrepreneurial education for physicians and other health care professionals. Panels benefit not only the presenting companies, but also the physicians, psychologists, and other health care professionals attending the session. Incorporating VC panels into academic conferences might also illuminate the need for incorporating relevant business training within academia.     

Other transgenic mutation assays: Tissue specificity of spontaneous point mutations in λsupF transgenic mice

Transgenic mice carrying multiple copies of a recoverable λ phage shuttle vector carrying the supF mutation reporter gene (λsupF) were constructed for the purpose of studying mutagenesis in a whole animal. Spontaneous mutations in rescued supF target genes from mouse liver and skin were analyzed. The mutation frequency was similar in both tissues (in the range of 2 × 10⁻⁵), but the spectrum of point mutations was distinct, with transitions common in the skin and transversions more prominent in the liver (P = 0.01). These results may help to elucidate pathways of endogenous mutagenesis in vivo, and they illustrate potentially important tissue-specific differences in genetic instability. © 1996 Wiley-Liss, Inc.     

Measurements of scapular position and rotation: a reliability study

Smooth motion of the scapula and humerus with respect to the thorax is essential for shoulder function and abnormalities may indicate clinical entities. Recent studies have made an attempt to devise simple, practical means of quantifying scapular position. The aim of this study was to examine the intra-tester and inter-tester reliability of two methods and to determine if significant differences existed between the dominant versus non-dominant extremity. Seventeen healthy volunteers (4 M; 13 F) were examined by two testers. The tape measurements consisted of the classic methods of Kibler and DiVeta in three sitting postures, expanded by the measurement of the linear distance from the medial border to the thoracic mid-line, and the scapular size measure. The SAS software package was used for data analysis. The Intraclass Correlation Coefficient (ICC) intra-tester reliability ranged between 0.96–0.8 for both methods without significant differences, whereas the ICC for inter-tester reliability ranged between 0.42–0.9 with higher values (moderate and good) for the Kibler technique. In the additional tests high values were also obtained for ICC intra-tester, except for the measurements of the linear distance of the medial border of the scapula to the thoracic mid-line and the distance of the inferior process of the acromion to the third vertebra, both in 90° abduction and internal rotation. The ICC for inter-tester was only acceptable for the DiVeta measurement on 45° abduction. Significant differences were noted between both testers on the following measures: Kibler in 45° abduction, DiVeta in 45° abduction and 90° abduction and the scapular size measure. The comparison of dominant versus non-dominant extremity revealed larger but not significantly different means for the dominant extremity in the classic methods. Significant differences occurred for Tester 1 in the measurement of the distance of the medial border to the thoracic mid-line and Tester 2 in DiVita in 45° abduction. The SEM values never exceeded 1 cm. We believe that the Kibler technique holds promise for further studies, has the advantage of measuring in three positions and with some familiarisation can be reliable. Further research is necessary in patients with pathological conditions. Copyright © 1996 Whurr Publishers Ltd.