Efficiency and Patient-Reported Outcome Measures From Clinic to Home: The Human Empowerment Aging and Disability Program for Digital-Health Rehabilitation

Background: The recent exponential growth of Digital Health (DH) in the healthcare system provides a crucial transformation in healthcare, answering to alarming threats related to the increasing number of Chronic Neurological Diseases (CNDs). New long-term integrated DH-care approaches, including rehabilitation, are warranted to address these concerns. Methods: The Human Empowerment Aging and Disability (HEAD) rehabilitation program, a new long-term integrated care including DH-care system, was evaluated in terms of efficiency and patient-reported outcome measures (PROMs) in 107 CND patients (30 with Parkinson's Disease, PD; 32 with Multiple Sclerosis, MS; 45 with stroke in chronic stage). All participants followed 1-month of HEAD rehabilitation in clinic (ClinicHEAD: 12 sessions, 3/week), then 1:3 patient was consecutively allocated to 3-months telerehabilitation at home (HomeHEAD: 60 sessions, 5/week). Efficiency (i.e., adherence, usability, and acceptability) and PROMs (i.e., perceived functioning in real-world) were analyzed. Results: The rate of adherence to HEAD treatment in clinic (≥90%) and at home (77%) was high. Usability of HEAD system was judged as good (System Usability Scale, median 70.00) in clinic and even more at home (median 80.00). Similarly, administering the Technology Acceptance Model 3 questionnaire we found high scores both in clinic/at home (Usefulness, mean 5.39 ± 1.41 SD/mean 5.33 ± 1.29 SD; Ease of use, mean 5.55 ± 1.05 SD/ mean 5.45 ± 1.17 SD, External Control, mean 4.94 ± 1.17 SD/mean 5.07 ± 1.01 SD, Relevance, mean 5.68 ± 1.29 SD/mean 5.70 ± 1.13 SD and Enjoyment, mean 5.70 ± 1.40 SD/mean 6.01 ± 1.08 SD). After ClinicHEAD, participation and autonomy in daily routine was maintained or even ameliorated (PD and stroke > MS). Whereas, increased functionality and participation in the MS group was found only after HomeHEAD intervention. Discussion: Our results suggest that a tele-health-based approach is both feasible and efficient in providing rehabilitation care to CNDs from clinic to home. Increasing and maintaining participation as well as autonomy in daily routine are promising findings that open up scenarios for the continuity of care at home through DH-care for CNDs

Real-time sweat pH monitoring based on a wearable chemical barcode micro-fluidic platform incorporating ionic liquids

This work presents the fabrication, characterisation and the performance of a wearable, robust, flexible and disposable chemical barcode device based on a micro-fluidic platform that incorporates ionic liquid polymer gels (ionogels). The device has been applied to the monitoring of the pH of sweat in real time during an exercise period. The device is an ideal wearable sensor for measuring the pH of sweat since it does not contents any electronic part for fluidic handle or pH detection and because it can be directly incorporated into clothing, head- or wristbands, which are in continuous contact with the skin. In addition, due to the micro-fluidic structure, fresh sweat is continuously passing through the sensing area providing the capability to perform continuous real time analysis. The approach presented here ensures immediate feedback regarding sweat composition. Sweat analysis is attractive for monitoring purposes as it can provide physiological information directly relevant to the health and performance of the wearer without the need for an invasive sampling approac

Safety Profile of a Virus-Like Particle-Based Vaccine Targeting Self-Protein Interleukin-5 in Horses

Background: Insect bite hypersensitivity (IBH) is an eosinophilic allergic dermatitis of horses caused by type I/IVb reactions against mainly Culicoides bites. The vaccination of IBH-affected horses with equine IL-5 coupled to the Cucumber mosaic virus-like particle (eIL-5-CuMVTT) induces IL-5-specific auto-antibodies, resulting in a significant reduction in eosinophil levels in blood and clinical signs. Objective: the preclinical and clinical safety of the eIL-5-CuMVTT vaccine. Methods: The B cell responses were assessed by longitudinal measurement of IL-5- and CuMVTT-specific IgG in the serum and plasma of vaccinated and unvaccinated horses. Further, peripheral blood mononuclear cells (PBMCs) from the same horses were re-stimulated in vitro for the proliferation and IFN-γ production of specific T cells. In addition, we evaluated longitudinal kidney and liver parameters and the general blood status. An endogenous protein challenge was performed in murine IL-5-vaccinated mice. Results: The vaccine was well tolerated as assessed by serum and cellular biomarkers and also induced reversible and neutralizing antibody titers in horses and mice. Endogenous IL-5 stimulation was unable to re-induce anti-IL-5 production. The CD4+ T cells of vaccinated horses produced significantly more IFN-γ and showed a stronger proliferation following stimulation with CuMVTT as compared to the unvaccinated controls. Re-stimulation using E. coli-derived proteins induced low levels of IFNγ+CD4+ cells in vaccinated horses; however, no IFN-γ and proliferation were induced following the HEK-eIL-5 re-stimulation. Conclusions: Vaccination using eIL-5-CuMVTT induces a strong B-cell as well as CuMVTT-specific T cell response without the induction of IL-5-specific T cell responses. Hence, B-cell unresponsiveness against self-IL-5 can be bypassed by inducing CuMVTT carrier-specific T cells, making the vaccine a safe therapeutic option for IBH-affected horses

A cancer-associated BRCA2 mutation reveals masked nuclear export signals controlling localization.

Germline missense mutations affecting a single BRCA2 allele predispose humans to cancer. Here we identify a protein-targeting mechanism that is disrupted by the cancer-associated mutation, BRCA2(D2723H), and that controls the nuclear localization of BRCA2 and its cargo, the recombination enzyme RAD51. A nuclear export signal (NES) in BRCA2 is masked by its interaction with a partner protein, DSS1, such that point mutations impairing BRCA2-DSS1 binding render BRCA2 cytoplasmic. In turn, cytoplasmic mislocalization of mutant BRCA2 inhibits the nuclear retention of RAD51 by exposing a similar NES in RAD51 that is usually obscured by the BRCA2-RAD51 interaction. Thus, a series of NES-masking interactions localizes BRCA2 and RAD51 in the nucleus. Notably, BRCA2(D2723H) decreases RAD51 nuclear retention even when wild-type BRCA2 is also present. Our findings suggest a mechanism for the regulation of the nucleocytoplasmic distribution of BRCA2 and RAD51 and its impairment by a heterozygous disease-associated mutation

Age and influenza-specific pre-vaccination antibodies strongly affect influenza vaccine responses in the icelandic population whereas disease and medication have small effects

Influenza vaccination remains the best strategy for the prevention of influenza virus-related disease and reduction of disease severity and mortality. However, there is large individual variation in influenza vaccine responses. In this study, we investigated the effects of gender, age, underlying diseases, and medication on vaccine responses in 1,852 Icelanders of broad age range who received trivalent inactivated influenza virus vaccination in 2012, 2013, or 2015. Hemagglutination inhibition (HAI) and microneutralization (MN) titers were measured in pre- and post-vaccination sera. Of the variables tested, the strongest association was with level of pre-vaccination titer that explained a major part of the variance observed in post-vaccination titers, ranging from 19 to 29%, and from 7 to 21% in fold change (FC), depending on the strain and serological (HAI or MN) analysis performed. Thus, increasing pre-vaccination titer associated with decreasing FC (P = 1.1 × 10-99-8.6× 10-30) and increasing post-vaccination titer (P = 2.1 × 10-159-1.1 × 10-123). Questionnaires completed by 87% of the participants revealed that post-vaccination HAI titer showed association with repeated previous influenza vaccinations. Gender had no effect on vaccine response whereas age had a strong effect and explained 1.6-3.1% of HAI post-vaccination titer variance and 3.1% of H1N1 MN titer variance. Vaccine response, both fold increase and seroprotection rate (percentage of individuals reaching HAI ≥ 40 or MN ≥ 20), was higher in vaccinees ≤37 years of age (YoA) than all other age groups. Furthermore, a reduction was observed in the H1N1 MN titer in people ≥63 YoA, demonstrating a decreased neutralizing functionality of vaccine-induced antibodies at older age. We tested the effects of underlying autoimmune diseases, asthma and allergic diseases and did not observe significant associations with vaccine responses. Intake of immune modulating medication did not show any association. Taken together, our results show that previous encounter of influenza vaccination or infection, reflected in high HAI and MN pre-vaccination titer has the strongest negative effect on vaccine responses measured as FC and the strongest positive effect on post-vaccination titer. Increasing age had also an effect but not gender, underlying disease or medication

Multiple genetic loci for bone mineral density and fractures

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldBACKGROUND: Bone mineral density influences the risk of osteoporosis later in life and is useful in the evaluation of the risk of fracture. We aimed to identify sequence variants associated with bone mineral density and fracture. METHODS: We performed a quantitative trait analysis of data from 5861 Icelandic subjects (the discovery set), testing for an association between 301,019 single-nucleotide polymorphisms (SNPs) and bone mineral density of the hip and lumbar spine. We then tested for an association between 74 SNPs (most of which were implicated in the discovery set) at 32 loci in replication sets of Icelandic, Danish, and Australian subjects (4165, 2269, and 1491 subjects, respectively). RESULTS: Sequence variants in five genomic regions were significantly associated with bone mineral density in the discovery set and were confirmed in the replication sets (combined P values, 1.2x10(-7) to 2.0x10(-21)). Three regions are close to or within genes previously shown to be important to the biologic characteristics of bone: the receptor activator of nuclear factor-kappaB ligand gene (RANKL) (chromosomal location, 13q14), the osteoprotegerin gene (OPG) (8q24), and the estrogen receptor 1 gene (ESR1) (6q25). The two other regions are close to the zinc finger and BTB domain containing 40 gene (ZBTB40) (1p36) and the major histocompatibility complex region (6p21). The 1p36, 8q24, and 6p21 loci were also associated with osteoporotic fractures, as were loci at 18q21, close to the receptor activator of the nuclear factor-kappaB gene (RANK), and loci at 2p16 and 11p11. CONCLUSIONS: We have discovered common sequence variants that are consistently associated with bone mineral density and with low-trauma fractures in three populations of European descent. Although these variants alone are not clinically useful in the prediction of risk to the individual person, they provide insight into the biochemical pathways underlying osteoporosis