Special Issue "Body Sensors Networks for E-Health Applications".

Body Sensor Networks (BSN) have emerged as a particularization of Wireless Sensor Networks (WSN) in the context of body monitoring environments, closely linked to healthcare applications. These networks are made up of smart biomedical sensors that allow the monitoring of physiological parameters and serve as the basis for e-Health applications. This Special Issue collects some of the latest developments in the field of BSN related to new developments in biomedical sensor technologies, the design and experimental characterization of on-body/in-body antennas and new communication protocols for BSN, including some review studies.

Sensor Technologies to Manage the Physiological Traits of Chronic Pain: A Review.

Non-oncologic chronic pain is a common high-morbidity impairment worldwide and acknowledged as a condition with significant incidence on quality of life. Pain intensity is largely perceived as a subjective experience, what makes challenging its objective measurement. However, the physiological traces of pain make possible its correlation with vital signs, such as heart rate variability, skin conductance, electromyogram, etc., or health performance metrics derived from daily activity monitoring or facial expressions, which can be acquired with diverse sensor technologies and multisensory approaches. As the assessment and management of pain are essential issues for a wide range of clinical disorders and treatments, this paper reviews different sensor-based approaches applied to the objective evaluation of non-oncological chronic pain. The space of available technologies and resources aimed at pain assessment represent a diversified set of alternatives that can be exploited to address the multidimensional nature of pain.

Lessons Learned about the Design and Active Characterization of On-Body Antennas in the 2.4 GHz Frequency Band.

This work addresses the design and experimental characterization of on-body antennas, which play an essential role within Body Sensor Networks. Four antenna designs were selected from a set of eighteen antenna choices and finally implemented for both passive and active measurements. The issues raised during the process of this work (requirements study, technology selection, development and optimization of antennas, impedance matching, unbalanced to balanced transformation, passive and active characterization, off-body and on-body configurations, etc.) were studied and solved, driving a methodology for the characterization of on-body antennas, including transceiver effects. Despite the influence of the body, the antennas showed appropriate results for an in-door environment. Another novelty is the proposal and validation of a phantom to emulate human experimentation. The differences between experimental and simulated results highlight a set of circumstances to be taken into account during the design process of an on-body antenna: more comprehensive simulation schemes to take into account the hardware effects and a custom design process that considers the application for which the device will be used, as well as the effects that can be caused by the human body.

Smart Bioimpedance Spectroscopy Device for Body Composition Estimation.

The purpose of this work is to describe a first approach to a smart bioimpedance spectroscopy device for its application to the estimation of body composition. The proposed device is capable of carrying out bioimpedance measurements in multiple configurable frequencies, processing the data to obtain the modulus and the bioimpedance phase in each of the frequencies, and transmitting the processed information wirelessly. Another novelty of this work is a new algorithm for the identification of Cole model parameters, which is the basis of body composition estimation through bioimpedance spectroscopy analysis. Against other proposals, the main advantages of the proposed method are its robustness against parasitic effects by employing an extended version of Cole model with phase delay and three dispersions, its simplicity and low computational load. The results obtained in a validation study with respiratory patients show the accuracy and feasibility of the proposed technology for bioimpedance measurements. The precision and validity of the algorithm was also proven in a validation study with peritoneal dialysis patients. The proposed method was the most accurate compared with other existing algorithms. Moreover, in those cases affected by parasitic effects the proposed algorithm provided better approximations to the bioimpedance values than a reference device.

Smart Vest for Respiratory Rate Monitoring of COPD Patients Based on Non-Contact Capacitive Sensing.

In this paper, a first approach to the design of a portable device for non-contact monitoring of respiratory rate by capacitive sensing is presented. The sensing system is integrated into a smart vest for an untethered, low-cost and comfortable breathing monitoring of Chronic Obstructive Pulmonary Disease (COPD) patients during the rest period between respiratory rehabilitation exercises at home. To provide an extensible solution to the remote monitoring using this sensor and other devices, the design and preliminary development of an e-Health platform based on the Internet of Medical Things (IoMT) paradigm is also presented. In order to validate the proposed solution, two quasi-experimental studies have been developed, comparing the estimations with respect to the golden standard. In a first study with healthy subjects, the mean value of the respiratory rate error, the standard deviation of the error and the correlation coefficient were 0.01 breaths per minute (bpm), 0.97 bpm and 0.995 (p < 0.00001), respectively. In a second study with COPD patients, the values were −0.14 bpm, 0.28 bpm and 0.9988 (p < 0.0000001), respectively. The results for the rest period show the technical and functional feasibility of the prototype and serve as a preliminary validation of the device for respiratory rate monitoring of patients with COPD.

Whole exome sequencing of Rett syndrome-like patients reveals the mutational diversity of the clinical phenotype.

Classical Rett syndrome (RTT) is a neurodevelopmental disorder where most of cases carry MECP2 mutations. Atypical RTT variants involve mutations in CDKL5 and FOXG1. However, a subset of RTT patients remains that do not carry any mutation in the described genes. Whole exome sequencing was carried out in a cohort of 21 female probands with clinical features overlapping with those of RTT, but without mutations in the customarily studied genes. Candidates were functionally validated by assessing the appearance of a neurological phenotype in Caenorhabditis elegans upon disruption of the corresponding ortholog gene. We detected pathogenic variants that accounted for the RTT-like phenotype in 14 (66.6 %) patients. Five patients were carriers of mutations in genes already known to be associated with other syndromic neurodevelopmental disorders. We determined that the other patients harbored mutations in genes that have not previously been linked to RTT or other neurodevelopmental syndromes, such as the ankyrin repeat containing protein ANKRD31 or the neuronal acetylcholine receptor subunit alpha-5 (CHRNA5). Furthermore, worm assays demonstrated that mutations in the studied candidate genes caused locomotion defects. Our findings indicate that mutations in a variety of genes contribute to the development of RTT-like phenotypes.

How technology is empowering patients? A literature review.

BACKGROUND: The term 'Patient Empowerment' (PE) is a growing concept ­ so in popularity as in application ­ covering situations where citizens are encouraged to take an active role in the management of their own health. This concept is serving as engine power for increasing the quality of health systems, but a question is still unanswered, 'how PE will be effectively achieved?' Beyond psychological implications, empowerment of patients in daily practice relies on technology and the way it is used. Unfortunately, the heterogeneity of approaches and technologies makes difficult to have a global vision of how PE is being performed. OBJECTIVE: To clarify how technology is being applied for enhancing patient empowerment as well as to identify current (and future) trends and milestones in this issue. SEARCH STRATEGY: Searches for relevant English language articles using Medline, Scopus, ACM Digital Library, Springer Link, EBSCO host and ScienceDirect databases from the year 2000 until October 2012 were conducted. Among others, a selection criterion was to review articles including terms 'patient' and 'empowerment' in title, abstract or as keywords. MAIN RESULTS AND CONCLUSIONS: Results state that practical approaches to empower patients vary in scope, aim and technology. Health literacy of patients, remote access to health services, and self-care mechanisms are the most valued ways to accomplish PE. Current technology already allows establishing the first steps in the road ahead, but a change of attitude by all stakeholders (i.e. professionals, patients, policy makers, etc.) is required.

Addressing the sources of inter-subject variability in E-field parameters in anodal tDCS stimulation over motor cortical network.

BACKGROUND: Although tDCS constitutes a non-invasive neuromodulation technique with promising results in a great variety of applications, its clinical implementation is compromised by the high inter-subject variability reported. This study aims to analyze the inter-subject variability in electric fields (E-fields) over regions of the cortical motor network under two electrode montages: the classical C3Fp2 and an alternative P3F3, which confines more the Efield over this region. Methods: Computational models of the head of 98 healthy subjects were developed to simulate the E-field under both montages. E-field parameters such as magnitude, focality and orientation were calculated over three regions of interest (ROI): M1S1, SMA and preSMA. The role of anatomical characteristics as a source of inter-subject variability on E-field parameters was addressed using linear mixed-effect models. Results: P3F3 showed a more confined E-field distribution over M1S1 than C3Fp2; the latter elicited higher E-fields over supplementary motor areas. Both montages showed high inter-subject variability, especially for the normal component over C3Fp2. Skin, bone and CSF ROI volumes showed a negative association with E-field magnitude irrespective of montage. Grey matter volume and montage were the main sources of variability for focality. The curvature of gyri was found to be significantly associated with the variability of normal E-fields. Conclusions: Computational modelling proves useful in the assessment of E-field variability. Our simulations predict significant differences in E-field magnitude and focality for C3Fp2 and P3F3. However, anatomical characteristics were also found to be significant sources of E-field variability irrespective of electrode montage. .

Dysregulation of the long non-coding RNA transcriptome in a Rett syndrome mouse model.

Mecp2 is a transcriptional repressor protein that is mutated in Rett syndrome, a neurodevelopmental disorder that is the second most common cause of mental retardation in women. It has been shown that the loss of the Mecp2 protein in Rett syndrome cells alters the transcriptional silencing of coding genes and microRNAs. Herein, we have studied the impact of Mecp2 impairment in a Rett syndrome mouse model on the global transcriptional patterns of long non-coding RNAs (lncRNAs). Using a microarray platform that assesses 41,232 unique lncRNA transcripts, we have identified the aberrant lncRNA transcriptome that is present in the brain of Rett syndrome mice. The study of the most relevant lncRNAs altered in the assay highlighted the upregulation of the AK081227 and AK087060 transcripts in Mecp2-null mice brains. Chromatin immunoprecipitation demonstrated the Mecp2 occupancy in the 5'-end genomic loci of the described lncRNAs and its absence in Rett syndrome mice. Most importantly, we were able to show that the overexpression of AK081227 mediated by the Mecp2 loss was associated with the downregulation of its host coding protein gene, the gamma-aminobutyric acid receptor subunit Rho 2 (Gabrr2). Overall, our findings indicate that the transcriptional dysregulation of lncRNAs upon Mecp2 loss contributes to the neurological phenotype of Rett syndrome and highlights the complex interaction between ncRNAs and coding-RNAs.

Comparative Study of the Impact of Human Leukocyte Antigens on Renal Transplant Survival in Andalusia and the United States.

Renal transplantation is the treatment of choice for patients suffering from chronic renal disease, one of the leading causes of death worldwide. Among the biological barriers that may increase the risk of acute renal graft rejection is the presence of human leukocyte antigen (HLA) incompatibilities between donor and recipient. This work presents a comparative study of the influence of HLA incompatibilities on renal transplantation survival in the Andalusian (South of Spain) and United States (US) population. The main objective is to analyse the extent to which results about the influence of different factors on renal graft survival can be generalised to different populations. The Kaplan-Meier estimator and the Cox model have been used to identify and quantify the impact on the survival probability of HLA incompatibilities, both in isolation and in conjunction with other factors associated with the donor and recipient. According to the results obtained, HLA incompatibilities considered in isolation have negligible impact on renal survival in the Andalusian population and a moderate impact in the US population. Grouping by HLA score presents some similarities for both populations, while the sum of all HLA scores (aHLA) only has an impact on the US population. Finally, the graft survival probability of the two populations differs when aHLA is considered in conjunction with blood type. The results suggest that the disparities in the renal graft survival probability between the two populations under study are due not only to biological and transplantation-associated factors, but also to social-health factors and ethnic heterogeneity between populations.

Functional and technological description of a real-time data management system for telehealthcare.

In health systems, there has been an emergence of new types of data and new technologies that allow continuously monitoring the status of the patients and make easy the achievement of real time information. The storage of all the acquired information makes possible to identify trends in medical data by means of new Clinical Decision Support subsystems. Current knowledge management solutions are specific, proprietary and closed and can not perform real-time analysis to improve the patient's diagnosis or treatment. There are neither solutions that integrate the large amount of heterogeneous information that nowadays are available in health environments. To overcome these objections, this paper proposes a new approach to design a data management system in a telehealthcare system with specific real-time constraints on knowledge acquisition and generation. It is a preliminary study and presents the main features of the system architecture and a preview of the technological solution implemented.

Improving healthcare middleware standards with semantic methods and technologies.

A critical issue in healthcare informatics is to facilitate the integration and interoperability of applications. This goal can be achieved through an open architecture based on a middleware independent from specific applications; useful for working with existing systems, as well as for the integration of new systems. Several standard organizations are making efforts toward this target. This work is based on the EN 12967-1,2,3, developed by CEN, that follows the ODP (Open Distributed Processing) methodology, providing a specification of distributed systems based on the definition of five viewpoints. However, only the three upper viewpoints are used to produce EN 12967, the two lower viewpoints should be considered in the implementation context. We are using Semantic Grid for lower views and Semantic Web and Web Services for the definition of the upper views. We analyze benefits of using these methods and technologies and expose methodology for the development of this semantic healthcare middleware observing European Standards.

A Parametric Computational Analysis Into Galvanic Coupling Intrabody Communication.

Intrabody Communication (IBC) uses the human body tissues as transmission media for electrical signals to interconnect personal health devices in wireless body area networks. The main goal of this work is to conduct a computational analysis covering some bioelectric issues that still have not been fully explained, such as the modeling of skin-electrode impedance, the differences associated with the use of constant voltage, or current excitation modes, or the influence on attenuation of the subject's anthropometrical and bioelectric properties. With this aim, a computational finite element model has been developed, allowing the IBC channel attenuation as well as the electric field and current density through arm tissues to be computed as a function of these parameters. As a conclusion, this parametric analysis has in turn permitted us to disclose some knowledge about the causes and effects of the above-mentioned issues, thus, explaining and complementing previous results reported in the literature.

Inhibition of Gsk3b Reduces Nfkb1 Signaling and Rescues Synaptic Activity to Improve the Rett Syndrome Phenotype in Mecp2-Knockout Mice.

Rett syndrome (RTT) is the second leading cause of mental impairment in girls and is currently untreatable. RTT is caused, in more than 95% of cases, by loss-of-function mutations in the methyl CpG-binding protein 2 gene (MeCP2). We propose here a molecular target involved in RTT: the glycogen synthase kinase-3b (Gsk3b) pathway. Gsk3b activity is deregulated in Mecp2-knockout (KO) mice models, and SB216763, a specific inhibitor, is able to alleviate the clinical symptoms with consequences at the molecular and cellular levels. In vivo, inhibition of Gsk3b prolongs the lifespan of Mecp2-KO mice and reduces motor deficits. At the molecular level, SB216763 rescues dendritic networks and spine density, while inducing changes in the properties of excitatory synapses. Gsk3b inhibition can also decrease the nuclear activity of the Nfkb1 pathway and neuroinflammation. Altogether, our findings indicate that Mecp2 deficiency in the RTT mouse model is partially rescued following treatment with SB216763.

Combining dialysate and blood recirculation to boost uremic toxin removal: theory and simulation study.

Emerging concepts in renal replacement therapies such as daily hemodialysis (HD) and wearable artificial kidney (WAK) meet the challenges derived from the aging of renal disease population. The successful results of blood recirculation to improve the dialysis clearance of medium-high uremic toxins suggest that this technique could be used both in daily HD and WAK. However, blood recirculation induces a reduction of small solutes clearance. This work analyzes the ability of a nonregenerated recirculating dialysate technique to avoid that reduction. The study uses in silico simulations with in vitro data from several commercial dialyzers and very compact dialyzer models derived from them. The resulting combined optimization system (recirculating blood-dialysate system [RBDS]) reached low solute dialysance improvements above 100% in different scenarios. Our outcomes show the RBDS performs best with very compact dialyzers, in agreement with the requirements of daily HD and WAK.

Wearable real-time and adaptive feedback device to face the stuttering: a knowledge-based telehealthcare proposal.

Despite first written references to permanent developmental stuttering occurred more than 2500 years ago, the mechanisms underlying this disorder are still unknown. This paper briefly reviews stuttering causal hypothesis and treatments, and presents the requirements that a new stuttering therapeutic device should verify. As a result of the analysis, an adaptive altered auditory feedback device based on a multimodal intelligent monitor, within the framework of a knowledge-based telehealthcare system, is presented. The subsequent discussion, based partly on the successful outcomes of a similar intelligent monitor, suggests that this novel device is feasible and could help to fill the gap between research and clinic.

Bromodomain inhibition shows antitumoral activity in mice and human luminal breast cancer.

BET bromodomain inhibitors, which have an antitumoral effect against various solid cancer tumor types, have not been studied in detail in luminal breast cancer, despite the prevalence of this subtype of mammary malignancy. Here we demonstrate that the BET bromodomain inhibitor JQ1 exerts growth-inhibitory activity in human luminal breast cancer cell lines associated with a depletion of the C-MYC oncogene, but does not alter the expression levels of the BRD4 bromodomain protein. Interestingly, expression microarray analyses indicate that, upon JQ1 administration, the antitumoral phenotype also involves downregulation of relevant breast cancer oncogenes such as the Breast Carcinoma-Amplified Sequence 1 (BCAS1) and the PDZ Domain-Containing 1 (PDZK1). We have also applied these in vitro findings in an in vivo model by studying a transgenic mouse model representing the luminal B subtype of breast cancer, the MMTV-PyMT, in which the mouse mammary tumor virus promoter is used to drive the expression of the polyoma virus middle T-antigen to the mammary gland. We have observed that the use of the BET bromodomain inhibitor for the treatment of established breast neoplasms developed in the MMTV-PyMT model shows antitumor potential. Most importantly, if JQ1 is given before the expected time of tumor detection in the MMTV-PyMT mice, it retards the onset of the disease and increases the survival of these animals. Thus, our findings indicate that the use of bromodomain inhibitors is of great potential in the treatment of luminal breast cancer and merits further investigation.

Viability study of a personalized and adaptive knowledge-generation telehealthcare system for nephrology (NEFROTEL).

OBJECTIVES: Several important problems in the majority of countries are challenging the centralized and overburdened current model of healthcare. Telehealthcare is presented as a new paradigm that offers high expectations to solve this picture. In this paper we present the major outcomes of the viability study of a novel personalized telehealthcare system for nephrology (NEFROTEL). METHODS: The study evaluates the accuracy and quality of the knowledge generated by two key processing layers, namely, sensor layer and patient physiological image (PPI) layer, in an independent way, thanks to its modular design. The first one was defined by a personalized falling detection monitor, on account of the consequences of falls in chronic renal patients. The second one was analyzed by means of a PPI's prototype based on a urea compartmental pharmacokinetic model. The experimental study of the falling detector monitor has been more extensive than the other because the latter has already been addressed in other works. RESULTS: The outcomes show, firstly, the capability of the PPIs to provide integrated and correlated physiological knowledge adapted to each patient, and secondly, demonstrate the reliability of the impact detection function of the adaptive human movement monitor compliant with the NEFROTEL paradigm. CONCLUSIONS: The study confirms that NEFROTEL is able to provide knowledge concerning a patient in a manner that cannot be accomplished by the ordinary healthcare model at the present time.

Methodological issues for the information model of a knowledge-based telehealthcare system for nephrology (Nefrotel).

Several studies point out the paradox that classic telemedicine by which doctor interacts remotely with patients in real-time is disappearing despite it has not been widely adopted yet. Many cues indicate that health information technologies will be finally adopted because of the growth in health expenditure and the emerging healthcare challenges. Notwithstanding, a detailed analysis of the referred concern has led us to propose a shift in the paradigm of telemedicine systems. This paper presents the major methodological issues of the information model of a novel telehealthcare system for nephrology (Nefrotel) which supports the cited shift in the paradigm. With this objective, we first revise the technological requirements of the database of Nefrotel, and second analyze the current scenario of health information model standards. Our study has shown that it is possible to ensure the compliance and evolution of Nefrotel with information model standards, maximizing its interoperability.

A Machine-to-Machine protocol benchmark for eHealth applications - Use case: Respiratory rehabilitation.

BACKGROUND: M2M (Machine-to-Machine) communications represent one of the main pillars of the new paradigm of the Internet of Things (IoT), and is making possible new opportunities for the eHealth business. Nevertheless, the large number of M2M protocols currently available hinders the election of a suitable solution that satisfies the requirements that can demand eHealth applications. OBJECTIVES: In the first place, to develop a tool that provides a benchmarking analysis in order to objectively select among the most relevant M2M protocols for eHealth solutions. In the second place, to validate the tool with a particular use case: the respiratory rehabilitation. METHODS: A software tool, called Distributed Computing Framework (DFC), has been designed and developed to execute the benchmarking tests and facilitate the deployment in environments with a large number of machines, with independence of the protocol and performance metrics selected. RESULTS: DDS, MQTT, CoAP, JMS, AMQP and XMPP protocols were evaluated considering different specific performance metrics, including CPU usage, memory usage, bandwidth consumption, latency and jitter. The results obtained allowed to validate a case of use: respiratory rehabilitation of chronic obstructive pulmonary disease (COPD) patients in two scenarios with different types of requirement: Home-Based and Ambulatory. CONCLUSIONS: The results of the benchmark comparison can guide eHealth developers in the choice of M2M technologies. In this regard, the framework presented is a simple and powerful tool for the deployment of benchmark tests under specific environments and conditions.