Design, control and evaluation of a low-cost active orthosis for the gait of spinal cord injured subjects

Robotic gait training after spinal cord injury is of high priority to maximize independence and improve the living conditions of the patients. Current rehabilitation robots are expensive and heavy, and are generally found only in the clinical environment. To overcome these issues, we present the design of a low-cost, low-weight and personalized robotic orthosis for incomplete spinal cord injured subjects. The paper also presents a preliminary experimental evaluation of the assistive device on one subject with spinal cord injury that can control hip flexion to a certain extent, but lacks control of knee and ankle muscles. Results show that gait velocity, stride length and cadence of walking increased (24,11%, 7,41% and 15,56%, respectively) when wearing active orthoses compared to the case when the subject used the usual passive orthoses.Postprint (published version

Topological Progression in Proliferating Epithelia Is Driven by a Unique Variation in Polygon Distribution

Morphogenesis is consequence of lots of small coordinated variations that occur during development. In proliferating stages, tissue growth is coupled to changes in shape and organization. A number of studies have analyzed the topological properties of proliferating epithelia using the Drosophila wing disc as a model. These works are based in the existence of a fixed distribution of these epithelial cells according to their number of sides. Cell division, cell rearrangements or a combination of both mechanisms have been proposed to be responsible for this polygonal assembling. Here, we have used different system biology methods to compare images from two close proliferative stages that present high morphological similarity. This approach enables us to search for traces of epithelial organization. First, we show that geometrical and network characteristics of individual cells are mainly dependent on their number of sides. Second, we find a significant divergence between the distribution of polygons in epithelia from mid-third instar larva versus early prepupa. We show that this alteration propagates into changes in epithelial organization. Remarkably, only the variation in polygon distribution driven by morphogenesis leads to progression in epithelial organization. In addition, we identify the relevant features that characterize these rearrangements. Our results reveal signs of epithelial homogenization during the growing phase, before the planar cell polarity pathway leads to the hexagonal packing of the epithelium during pupal stages.España, Ministero de Ciencia BFU2011-2573

Rules of tissue packing involving different cell types: human muscle organization

Natural packed tissues are assembled as tessellations of polygonal cells. These include skeletal muscles and epithelial sheets. Skeletal muscles appear as a mosaic composed of two different types of cells: the “slow” and “fast” fibres. Their relative distribution is important for the muscle function but little is known about how the fibre arrangement is established and maintained. In this work we capture the organizational pattern in two different healthy muscles: biceps brachii and quadriceps. Here we show that the biceps brachii muscle presents a particular arrangement, based on the different sizes of slow and fast fibres. By contrast, in the quadriceps muscle an unbiased distribution exists. Our results indicate that the relative size of each cellular type imposes an intrinsic organization into natural tessellations. These findings establish a new framework for the analysis of any packed tissue where two or more cell types exist.España, Gobierno BFU2011-2573

Fundamental physical cellular constraints drive self-organization of tissues

Morphogenesis is driven by small cell shape changes that modulate tissue organization. Apical surfaces of proliferating epithelial sheets have been particularly well studied. Currently, it is accepted that a stereotyped distribution of cellular polygons is conserved in proliferating tissues among metazoans. In this work, we challenge these previous findings showing that diverse natural packed tissues have very different polygon distributions. We use Voronoi tessellations as a mathematical framework that predicts this diversity. We demonstrate that Voronoi tessellations and the very different tissues analysed share an overriding restriction: the frequency of polygon types correlates with the distribution of cell areas. By altering the balance of tensions and pressures within the packed tissues using disease, genetic or computer model perturbations, we show that as long as packed cells present a balance of forces within tissue, they will be under a physical constraint that limits its organization. Our discoveries establish a new framework to understand tissue architecture in development and disease. Synopsis Cell shapes in naturally packed tissues have different polygon distributions. Voronoi tessellations-based analysis suggests that polygon frequencies are restricted by the distribution of cell areas, and that this restriction emanates from the balance of forces within the tissue. Cell shapes in natural packed tissues present very different polygon distributions. These patterns can be reproduced by Voronoi tessellations. Natural tissues and Voronoi diagrams share some geometrical properties. There is a physical constraint that limits the organization of natural tissues. Unbalance of forces within the natural tissue breaks this restriction. Cell shapes in naturally packed tissues have different polygon distributions. Voronoi tessellations-based analysis suggests that polygon frequencies are restricted by the distribution of cell areas, and that this restriction emanates from the balance of forces within the tissue.Ministerio de Ciencia e Innovación BFU2011-2573

Design, control, and pilot study of a lightweight and modular robotic exoskeleton for walking assistance after spinal cord injury

Walking rehabilitation using exoskeletons is of high importance to maximize independence and improve the general well-being of spinal cord injured subjects. We present the design and control of a lightweight and modular robotic exoskeleton to assist walking in spinal cord injured subjects who can control hip flexion, but lack control of knee and ankle muscles. The developed prototype consists of two robotic orthoses, which are powered by a motor-harmonic drive actuation system that controls knee flexion–extension. This actuation module is assembled on standard passive orthoses. Regarding the control, the stance-to-swing transition is detected using two inertial measurement units mounted on the tibial supports, and then the corresponding motor performs a predefined flexion–extension cycle that is personalized to the specific patient’s motor function. The system is portable by means of a backpack that contains an embedded computer board, the motor drivers, and the battery. A preliminary biomechanical evaluation of the gait-assistive device used by a female patient with incomplete spinal cord injury at T11 is presented. Results show an increase of gait speed (+24.11%), stride length (+7.41%), and cadence (+15.56%) when wearing the robotic orthoses compared with the case with passive orthoses. Conversely, a decrease of lateral displacement of the center of mass (-19.31%) and step width (-13.37% right step, -8.81% left step) are also observed, indicating gain of balance. The biomechanical assessment also reports an overall increase of gait symmetry when wearing the developed assistive device.Peer ReviewedPostprint (published version

ATM specifically mediates repair of double-strand breaks with blocked DNA ends

Ataxia telangiectasia is caused by mutations in ATM and represents a paradigm for cancer predisposition and neurodegenerative syndromes linked to deficiencies in the DNA-damage response. The role of ATM as a key regulator of signalling following DNA double-strand breaks (DSBs) has been dissected in extraordinary detail, but the impact of this process on DSB repair still remains controversial. Here we develop novel genetic and molecular tools to modify the structure of DSB ends and demonstrate that ATM is indeed required for efficient and accurate DSB repair, preventing cell death and genome instability, but exclusively when the ends are irreversibly blocked. We therefore identify the nature of ATM involvement in DSB repair, presenting blocked DNA ends as a possible pathogenic trigger of ataxia telangiectasia and related disorders

ATM specifically mediates repair of double-strand breaks with blocked DNA ends

Ataxia telangiectasia is caused by mutations in ATM and represents a paradigm for cancer predisposition and neurodegenerative syndromes linked to deficiencies in the DNA-damage response. The role of ATM as a key regulator of signalling following DNA double-strand breaks (DSBs) has been dissected in extraordinary detail, but the impact of this process on DSB repair still remains controversial. Here we develop novel genetic and molecular tools to modify the structure of DSB ends and demonstrate that ATM is indeed required for efficient and accurate DSB repair, preventing cell death and genome instability, but exclusively when the ends are irreversibly blocked. We therefore identify the nature of ATM involvement in DSB repair, presenting blocked DNA ends as a possible pathogenic trigger of ataxia telangiectasia and related disorders

ABLE: assistive biorobotic low-cost exoskeleton

Robotic gait training after spinal cord injury is of high priority to maximize independence and improve the health condition of these patients. Current rehabilitation robots are expensive and heavy, and are generally found only in the clinic. To overcome these issues, we present the design of a low-cost, low-weight, personalized and easy-to-use robotic exoskeleton for incomplete spinal cord injured subjects based on simple modular components that are assembled on the current passive orthopedic supports. The paper also presents a preliminary experimental assessment of the assistive device on one subject with spinal cord injury that can control hip flexion, but lacks control of knee and ankle muscles. Results show that gait velocity, stride length and cadence of walking increased (24,11%, 7,41% and 15,56%, respectively) when wearing the robotic exoskeleton compared to the case when the subject used the usual passive supports.Postprint (author's final draft

Mobile based surveillance platform for detecting Zika virus among Spanish Delegates attending the Rio de Janeiro Olympic Games

Background: Zika virus has created a major epidemic in Central and South America, especially in Brazil, during 2015-16. The infection is strongly associated with fetal malformations, mainly microcephaly, and neurological symptoms in adults. During the preparation of the Rio de Janeiro Olympic Games in 2016, members of Olympic Delegations worldwide expressed their concern about the health consequences of being infected with Zika virus. A major risk highlighted by the scientific community was the impact on the spreading of the virus into new territories immediately after the Games. Objectives: To detect real-time incidence of symptoms compatible with arboviral diseases and other tropical imported diseases among the Spanish Olympic Delegation (SOD) attending the Rio Olympic Games in 2016. Methods: We developed a surveillance platform based on a mobile application installed in participant's smartphones that monitored the health status of the SOD through a daily interactive check of the user health status including geo-localization data. The results were evaluated by a study physician on-call through a web-based platform monitoring system. Participants presenting severe symptoms or those compatible with Zika infection prompted an alarm in the system triggering specialized medical assistance and allowing early detection and control of the introduction of arboviral diseases in Spain. Summary of the results: The system was downloaded by 189 participants and used by 143 of them (76%). Median age was 38 years (IQR 16), and 134 (71%) were male. Mean duration of travel was 19 days (+/-9SD). During the Games the highest accumulated incidence observed was for headache: 6.06% cough: 5.30% and conjunctivitis: 3.03%. The incidence rate of cough during the Olympic Games was 1.1% per day per person, followed by headache 0.8% and 0.4% conjunctivitis or diarrhea. In our cohort we observed that non-athletes experienced more incidence of symptoms, except for incidence of cough which was the same in the two groups (1.1%). No participants reported symptoms fulfilling Zika definition case. Conclusion: Our system did not find cases fulfilling Zika definition amongst participants of the SOD during the Games, consistent with limited cases of Zika in Rio during the Games. The app showed good usability and the web based monitoring platform allowed to manage infectious cases in real-time. The overall system has proven to serve as a real-time surveillance platform for detecting symptoms that could be present in tropical imported diseases, especially arboviral diseases, contributing to the preparedness for the introduction of vector borne-diseases in non-endemic countries

Real-time incidence of travel-related symptoms through a smartphone-based app remote monitoring system: a pilot study

Trip Doctor(R), a Smartphone-based app monitoring system, was developed to detect infections among travelers in real-time. For testing, 106 participants were recruited (62.2% male, mean age 36 years (SD = 11)). Majority of trips were for tourism and main destinations were in South East Asia. Mean travel duration was 14 days (SD = 10). Diarrhea was the most frequently reported symptom (15.5%). The system demonstrated adequate usability and is ready to be used on a larger scale