Unraveling Molecular Signatures of Immunostimulatory Adjuvants in the Female Genital Tract through Systems Biology

Sexually transmitted infections (STIs) unequivocally represent a major public health concern in both industrialized and developing countries. Previous efforts to develop vaccines for systemic immunization against a large number of STIs in humans have been unsuccessful. There is currently a drive to develop mucosal vaccines and adjuvants for delivery through the genital tract to confer protective immunity against STIs. Identification of molecular signatures that can be used as biomarkers for adjuvant potency can inform rational development of potent mucosal adjuvants. Here, we used systems biology to study global gene expression and signature molecules and pathways in the mouse vagina after treatment with two classes of experimental adjuvants. The Toll-like receptor 9 agonist CpG ODN and the invariant natural killer T cell agonist alpha-galactosylceramide, which we previously identified as equally potent vaginal adjuvants, were selected for this study. Our integrated analysis of genome-wide transcriptome data determined which signature pathways, processes and networks are shared by or otherwise exclusive to these 2 classes of experimental vaginal adjuvants in the mouse vagina. To our knowledge, this is the first integrated genome-wide transcriptome analysis of the effects of immunomodulatory adjuvants on the female genital tract of a mammal. These results could inform rational development of effective mucosal adjuvants for vaccination against STIs

Telecardiology and Remote Monitoring of Implanted Electrical Devices: The Potential for Fresh Clinical Care Perspectives

Telecardiology may help confront the growing burden of monitoring the reliability of implantable defibrillators/pacemakers. Herein, we suggest that the evolving capabilities of implanted devices to monitor patients’ status (heart rhythm, fluid overload, right ventricular pressure, oximetry, etc.) may imply a shift from strictly device-centered follow-up to perspectives centered on the patient (and patient-device interactions). Such approaches could provide improvements in health care delivery and clinical outcomes, especially in the field of heart failure. Major professional, policy, and ethical issues will have to be overcome to enable real-world implementation. This challenge may be relevant for the evolution of our health care systems

A quasi-experimental test of an intervention to increase the use of thiazide-based treatment regimens for people with hypertension

BACKGROUND: Despite recent high-quality evidence for their cost-effectiveness, thiazides are underused for controlling hypertension. The goal of this study was to design and test a practice-based intervention aimed at increasing the use of thiazide-based antihypertensive regimens. METHODS: This quasi-experimental study was carried out in general medicine ambulatory practices of a large, academically-affiliated Veterans Affairs hospital. The intervention group consisted of the practitioners (13 staff and 215 trainees), nurses, and patients (3,502) of the teaching practice; non-randomized concurrent controls were the practitioners (31 providers) and patients (18,292) of the non-teaching practices. Design of the implementation intervention was based on Rogers' Diffusion of Innovations model. Over 10.5 months, intervention teams met weekly or biweekly and developed and disseminated informational materials among themselves and to trainees, patients, and administrators. These teams also reviewed summary electronic-medical-record data on thiazide use and blood pressure (BP) goal attainment. Outcome measures were the proportion of hypertensive patients prescribed a thiazide-based regimen, and the proportion of hypertensive patients attaining BP goals regardless of regimen. Thirty-three months of time-series data were available; statistical process control charts, change point analyses, and before-after analyses were used to estimate the intervention's effects. RESULTS: Baseline use of thiazides and rates of BP control were higher in the intervention group than controls. During the intervention, thiazide use and BP control increased in both groups, but changes occurred earlier in the intervention group, and primary change points were observed only in the intervention group. Overall, the pre-post intervention difference in proportion of patients prescribed thiazides was greater in intervention patients (0.091 vs. 0.058; p = 0.0092), as was the proportion achieving BP goals (0.092 vs. 0.044; p = 0.0005). At the end of the implementation period, 41.4% of intervention patients were prescribed thiazides vs. 30.6% of controls (p < 0.001); 51.6% of intervention patients had achieved BP goals vs. 44.3% of controls (p < 0.001). CONCLUSION: This multi-faceted intervention appears to have resulted in modest improvements in thiazide prescribing and BP control. The study also demonstrates the value of electronic medical records for implementation research, how Rogers' model can be used to design and launch an implementation strategy, and how all members of a clinical microsystem can be involved in an implementation effort

Assessing dysphagia via telerehabilitation: patient perceptions and satisfaction

To gain insight into factors which may infl uence future acceptance of dysphagia management via telerehabilitation, patients’ perceptions were examined before and after a telerehabilitation assessment session. Forty adult patients with dysphagia(M = 66 years, SD = 16.25) completed pre- and post-session questionnaires which consisted of 14 matched questions worded to suit pre- and post-conditions. Questions explored comfort with the use of telerehabilitation, satisfaction with audio and video quality, benefi ts of telerehabilitation assessments and patients’ preferred assessment modality. Questions were rated on a 5-point scale (1 = strongly disagree, 3 = unsure, 5 = strongly agree). Patients’ comfort with assessment via telerehabilitation was high in over 80% of the group both pre- and post-assessment. Pre-assessment, patients were unsure what to expect with the auditory and visual aspects of the videoconference, however there were signifi cant positive changes reported post-experience. In relation to perceived benefits of telerehabilitation services in general, most patients believed in the value of telerehabilitation and post-assessment this increased to 90 – 100% agreement. Although 92% felt they would be comfortable receiving services via telerehabilitation, 45% of patients indicated ultimate preference for a traditional faceto-face assessment. The data highlight that patients are interested in and willing to receive services via telerehabilitation; however, any concerns should be addressed pre-assessment

Brain classification reveals the right cerebellum as the best biomarker of dyslexia

Background Developmental dyslexia is a specific cognitive disorder in reading acquisition that has genetic and neurological origins. Despite histological evidence for brain differences in dyslexia, we recently demonstrated that in large cohort of subjects, no differences between control and dyslexic readers can be found at the macroscopic level (MRI voxel), because of large variances in brain local volumes. In the present study, we aimed at finding brain areas that most discriminate dyslexic from control normal readers despite the large variance across subjects. After segmenting brain grey matter, normalizing brain size and shape and modulating the voxels' content, normal readers' brains were used to build a 'typical' brain via bootstrapped confidence intervals. Each dyslexic reader's brain was then classified independently at each voxel as being within or outside the normal range. We used this simple strategy to build a brain map showing regional percentages of differences between groups. The significance of this map was then assessed using a randomization technique. Results The right cerebellar declive and the right lentiform nucleus were the two areas that significantly differed the most between groups with 100% of the dyslexic subjects (N = 38) falling outside of the control group (N = 39) 95% confidence interval boundaries. The clinical relevance of this result was assessed by inquiring cognitive brain-based differences among dyslexic brain subgroups in comparison to normal readers' performances. The strongest difference between dyslexic subgroups was observed between subjects with lower cerebellar declive (LCD) grey matter volumes than controls and subjects with higher cerebellar declive (HCD) grey matter volumes than controls. Dyslexic subjects with LCD volumes performed worse than subjects with HCD volumes in phonologically and lexicon related tasks. Furthermore, cerebellar and lentiform grey matter volumes interacted in dyslexic subjects, so that lower and higher lentiform grey matter volumes compared to controls differently modulated the phonological and lexical performances. Best performances (observed in controls) corresponded to an optimal value of grey matter and they dropped for higher or lower volumes. Conclusion These results provide evidence for the existence of various subtypes of dyslexia characterized by different brain phenotypes. In addition, behavioural analyses suggest that these brain phenotypes relate to different deficits of automatization of language-based processes such as grapheme/phoneme correspondence and/or rapid access to lexicon entries. article available here: http://www.biomedcentral.com/1471-2202/10/6

A Live-Attenuated HSV-2 ICP0− Virus Elicits 10 to 100 Times Greater Protection against Genital Herpes than a Glycoprotein D Subunit Vaccine

Glycoprotein D (gD-2) is the entry receptor of herpes simplex virus 2 (HSV-2), and is the immunogen in the pharmaceutical industry's lead HSV-2 vaccine candidate. Efforts to prevent genital herpes using gD-2 subunit vaccines have been ongoing for 20 years at a cost in excess of $100 million. To date, gD-2 vaccines have yielded equivocal protection in clinical trials. Therefore, using a small animal model, we sought to determine if a live-attenuated HSV-2 ICP0− virus would elicit better protection against genital herpes than a gD-2 subunit vaccine. Mice immunized with gD-2 and a potent adjuvant (alum+monophosphoryl lipid A) produced high titers of gD-2 antibody. While gD-2-immunized mice possessed significant resistance to HSV-2, only 3 of 45 gD-2-immunized mice survived an overwhelming challenge of the vagina or eyes with wild-type HSV-2 (MS strain). In contrast, 114 of 115 mice immunized with a live HSV-2 ICP0− virus, 0ΔNLS, survived the same HSV-2 MS challenges. Likewise, 0ΔNLS-immunized mice shed an average 125-fold less HSV-2 MS challenge virus per vagina relative to gD-2-immunized mice. In vivo imaging demonstrated that a luciferase-expressing HSV-2 challenge virus failed to establish a detectable infection in 0ΔNLS-immunized mice, whereas the same virus readily infected naïve and gD-2-immunized mice. Collectively, these results suggest that a HSV-2 vaccine might be more likely to prevent genital herpes if it contained a live-attenuated HSV-2 virus rather than a single HSV-2 protein

data protection and ethical issues in european p5 ehealth

In spite of its promise to significantly ameliorate health and care practices, the momentous rise of eHealth technologies has been fraught with significant ethical and societal concerns. Focusing on the unfolding of eHealth within the European Union, this contribution will explore its underpinning regulatory landscape with regard to data protection, focusing on the impact of the recently enforced Regulation (EU) 2016/679, also known as the General Data Protection Regulation. In addition, this chapter will chart relevant ethical issues related to the emergence of novel eHealth technologies. Finally, the conclusion will briefly explore ethical issues and their solutions in the light of the P5 approach