Increased prevalence of Kidney cysts in individuals carrying heterozygous COL4A3 or COL4A4 pathogenic variants.

BACKGROUND: Clinical variability among individuals with heterozygous pathogenic/likely pathogenic (P/LP) variants in the COL4A3/COL4A4 genes (also called autosomal dominant Alport syndrome or COL4A3/COL4A4 related disorder) is huge; many individuals are asymptomatic or show microhematuria, while others may develop proteinuria and chronic kidney disease (CKD). The prevalence of simple kidney cysts (KC) in the general population varies according to age, and patients with advanced CKD are prone to have them. A possible association between heterozygous COL4A3, COL4A4, and COL4A5 P/LP variants and KC has been described in small cohorts. The presence of KC in a multicenter cohort of individuals with heterozygous P/LP variants in the COL4A3/COL4A4 genes is assessed in this study. METHODS: We evaluated the presence of KC by ultrasound in 157 individuals with P/LP variants in COL4A3 (40.7%) or COL4A4 (53.5%) without kidney replacement therapy. The association between presence of KC and age, proteinuria, eGFR, and causative gene was analyzed. Prevalence of KC was compared with historical case series in the general population. RESULTS: Half of the individuals with P/LP variants in COL4A3/COL4A4 showed KC, which is a significantly higher percentage than in the general population. Only 3.8% (6/157) had cystic nephromegaly. Age and eGFR showed an association with the presence of KC (p<0.001). No association was found between KC and proteinuria, sex, or causative gene. CONCLUSIONS: Individuals with COL4A3/COL4A4 P/LP variants are prone to develop KC more frequently than the general population, and their presence is related to age and to eGFR. Neither proteinuria, sex nor the causative gene influences the presence of KC in these individuals.

SeamlessGAN: Self-Supervised Synthesis of Tileable Texture Maps.

Real-time graphics applications require high-quality textured materials to convey realism in virtual environments. Generating these textures is challenging as they need to be visually realistic, seamlessly tileable, and have a small impact on the memory consumption of the application. For this reason, they are often created manually by skilled artists. In this work, we present SeamlessGAN, a method capable of automatically generating tileable texture maps from a single input exemplar. In contrast to most existing methods, focused solely on solving the synthesis problem, our work tackles both problems, synthesis and tileability, simultaneously. Our key idea is to realize that tiling a latent space within a generative network trained using adversarial expansion techniques produces outputs with continuity at the seam intersection that can then be turned into tileable images by cropping the central area. Since not every value of the latent space is valid to produce high-quality outputs, we leverage the discriminator as a perceptual error metric capable of identifying artifact-free textures during a sampling process. Further, in contrast to previous work on deep texture synthesis, our model is designed and optimized to work with multi-layered texture representations, enabling textures composed of multiple maps such as albedo, normals, etc. We extensively test our design choices for the network architecture, loss function, and sampling parameters. We show qualitatively and quantitatively that our approach outperforms previous methods and works for textures of different types.

Lower-Limb Medical and Rehabilitation Exoskeletons: A Review of the Current Designs.

Medical and rehabilitation exoskeletons are being increasingly considered by therapists when choosing a treatment for individuals affected by lower limb impairments. Although all such exoskeletons seem to provide similar features and performance, there are, in practice, significant differences among them in terms of maximum walking speed, maximum torque, weight, autonomy, interaction with the user, or even the way to use it. In this review, the state of the art of the main commercial exoskeletons is described, while analyzing their properties, advantages, and disadvantages. Three groups are considered: complete exoskeletons, partial exoskeletons and open lines of research. A comparative analysis between them is performed while considering the main scientific and technical aspects to be improved. In conclusion to this analysis, the balance between feasibility and innovation in exoskeletons development is a design challenge. Commercial exoskeletons must fulfil standards whilst ensuring their safety and robustness. However, achieving a new generation of exoskeletons means a need to implement new hardware paradigms, and to enhance control strategies focused on assist-as-needed scheme. Finally, some aspects to improve current designs of the exoskeleton are presented.

Wearable rehabilitation exoskeletons of the lower limb: analysis of versatility and adaptability.

PURPOSE: To analyse the versatility and adaptability of commercially available exoskeletons for mobility assistance and their adaptation to diverse pathologies through a review of clinical trials in robotic lower limb training. DATA SOURCES: A computer-aided search in bibliographic databases (PubMed and Web of Science) of clinical trials published up to September 2020 was done. METHODS: To be selected for detailed review, clinical trials had to meet the following criteria: (1) a protocol was designed and approved, (2) participants were people with pathologies, and (3) the trials were not a single case study. Clinical trial data were collected, extracted, and analysed, considering: objectives, trial participants, number of sessions, pathologies involved, and conclusions. RESULTS: The search resulted in 312 potentially relevant studies of seven commercial exoskeletons, of which 135 passed the preliminary screening; and 69 studies were finally selected. Of the 69 clinical trials included in the review about 50% involved Spinal Cord Injury participants, while roughly 25% focussed on stroke and two trials corresponded to patients with both disorders. The rest were composed of neurological diseases and trauma disorders. CONCLUSIONS: The use of a single wearable robot for different medical conditions in various diseases is a challenge. Based on this comparative, the properties of the exoskeletons that improve the working ability with different pathologies and patient conditions have been evaluated. Suggestions were made for developing a new lower-limb exoskeleton based on various modules with a distributed control system to improve versatility in wearable technology for different gait pattern progression.Implications for rehabilitationWearable robotic exoskeletons for gait assistance have been analysed from the perspective of adaptation to different diseases.This paper emphasizes the importance of personalized therapies and adaptive assistive technology.Suggestions were made for a new modular exoskeleton capable of addressing the issue of low versatility characterizing currently wearable assistive technology.

Neural Photometry-Guided Visual Attribute Transfer.

We present a deep learning-based method for propagating spatially-varying visual material attributes (e.g., texture maps or image stylizations) to larger samples of the same or similar materials. For training, we leverage images of the material taken under multiple illuminations and a dedicated data augmentation policy, making the transfer robust to novel illumination conditions and affine deformations. Our model relies on a supervised image-to-image translation framework and is agnostic to the transferred domain; we showcase a semantic segmentation, a normal map, and a stylization. Following an image analogies approach, the method only requires the training data to contain the same visual structures as the input guidance. Our approach works at interactive rates, making it suitable for material edit applications. We thoroughly evaluate our learning methodology in a controlled setup providing quantitative measures of performance. Last, we demonstrate that training the model on a single material is enough to generalize to materials of the same type without the need for massive datasets.

Using a robotic exoskeleton at home: An activity tolerance case study of a child with spinal muscular atrophy.

PURPOSE: Spinal Muscular Atrophy (SMA) Type II is a neurodegenerative disease that leads to progressive muscle weakness. It prevents children from walking and affects their respiratory function and their activity tolerance, among other health problems. We aimed to assess the activity tolerance showed by a child with SMA using a pediatric gait exoskeleton at home when walking and performing activities. DESIGN AND METHODS: This study presents the case of a 6-year-old boy with SMA Type II and respiratory failure who used a pediatric gait exoskeleton at home for a period of two months. A nursing assessment was done before and during the use of the device to evaluate the child's activity tolerance during the sessions. Nursing interviews, performance, vital signs, fatigue, field notes, and functional scales were analyzed. RESULTS: The nursing assessment showed a good activity tolerance of the child. Performance using the device improved over time; vital signs did not vary significantly during the sessions; fatigue perception decreased over time; and the child reached a higher score on some functional outcomes. CONCLUSIONS: A first step has been taken to evaluate the impact of exoskeleton technology in children with SMA Type II from the nursing point of view, exposing the potential of this technology for the care of children with neuromuscular diseases, and the need for more research on the topic. PRACTICE IMPLICATIONS: The information in this study will be useful to nurses to know the effects of gait exoskeletons in pediatric care of children with neuromuscular diseases like SMA.

ATLAS2030 Pediatric Gait Exoskeleton: Changes on Range of Motion, Strength and Spasticity in Children With Cerebral Palsy. A Case Series Study.

Background: Cerebral Palsy (CP), the most common motor disability in childhood, affects individual's motor skills, movement and posture. This results in limited activity and a low social participation. The ATLAS2030 exoskeleton is a pediatric device that enables gait rehabilitation for children with neurological or neuromuscular pathologies with gait pathology. Purpose: To study changes in relation to range of motion (ROM), strength and spasticity in children with CP after using the ATLAS2030 gait exoskeleton. Methods and Participants: Three children (mean age 8.0 ± 2.0), two girls and one boy, two of them with GMFCS IV and one with GMFCS III, received robot-assisted gait training (RAGT) with ATLAS2030 for one month. Results: The average time of exoskeleton use was 54.7 ± 10.4 min in all sessions, and all participants were able to perform all exercises. The strength of all muscle groups was increased after the 10 sessions for the participants assessed and the limited ROM in the sagittal plane (hip and knee extension and ankle dorsiflexion) decreased after the use of the exoskeleton compared to the initial state. Spasticity was reduced at the end of the sessions after the use of the exoskeleton compared to their initial state. Conclusion: The ROM, spasticity and strength were improved after RAGT with ATLAS2030 exoskeleton in these children with CP. However, further studies with larger samples should be carried out to confirm our findings.

Tasa de ultrafiltración horaria ajustada a peso corporal y mortalidad en hemodiálisis / Ultrafiltration rate adjusted to body weight and mortality in hemodialysis patients

Antecedentes y objetivo: La mortalidad de los pacientes en hemodiálisis es alta. Una tasa de ultrafiltración horaria ajustada por peso (UFR/W) elevada se ha asociado con episodios de hipotensión arterial y con mayor riesgo de muerte y/o eventos cardiovasculares. Material y métodos: Hemos evaluado la asociación entre UFR/W y mortalidad en 215 pacientes en hemodiálisis prevalentes seguidos durante 28 ± 6,12 meses. Se estimaron características clínicas basales y UFR/W media a lo largo del seguimiento. Resultados: La UFR/W media fue 9,0 ± 2,4 y los terciles 7,1 y 10,1 mL/kg/h. Se categorizó a la población en función del tiempo que habían estado con UFR/W igual o superior a los puntos de corte descritos en la literatura como relacionados con mayor mortalidad (10,0 mL/kg/h y 13,0 mL/kg/h). Los pacientes con mayor UFR/W fueron más jóvenes, con mayor ganancia de peso interdiálisis y porcentaje de reducción de peso, pero con menor peso seco, inicial y final. Durante el seguimiento, fallecieron 46 (21,4%) personas de las cuales la mayoría eran > 70 años, diabéticas o con enfermedad cardiovascular. No hubo diferencias en la mortalidad entre los grupos de UFR/W ni en la UFR/W entre los fallecidos y no fallecidos. En comparación con estudios previos donde describieron la asociación entre UFR/W y mortalidad, en nuestra población había más prevalencia de medicación protectora cardiovascular y no se observaron UFR/W tan altas. Conclusión: En nuestro medio, la UFR/W más elevada se observó en pacientes más jóvenes y de menor peso y no se asoció con mayor mortalidad. (AU)

Background and aims: Mortality among hemodialysis patients remains high. An elevated ultrafiltration rate adjusted by weight (UFR/W) has been associated with hypotension and higher risk of death and/or cardiovascular events. Methods: We evaluated the association between UFR/W and mortality in 215 hemodialysis patients. The mean follow-up was 28 ± 6.12 months. We collected patientś baseline characteristics and mean UFR/W throughout the follow-up. Results: Mean UFR/W was 9.0 ± 2,4 and tertiles 7.1 y 10.1 mL/kg/h. We divided our population according to the percentage of sessions with UFR/W above the limits described in the literature associated with increased mortality (10.0 mL/kg/h and 13.0 mL/kg/h). Patients with higher UFR/W were younger, with higher interdialytic weight gain and weight reduction percentage but lower dry, pre and post dialysis weight. Throughout the follow-up, 46 (21.4%) patients died, the majority over 70 years old, diabetic or with cardiovascular disease. There were neither differences regarding mortality between groups nor differences in UFR/W among patients who died and those who did not. Contrary to previous studies, we did not find an association between UFR/W and mortality, maybe due to a higher prevalence in the use of cardiovascular protection drugs and lower UFR/W. Conclusions: The highest UFR/W were observed in younger patients with lower weight and were not associated with an increased mortality. (AU)

Gait-assisted exoskeletons for children with cerebral palsy or spinal muscular atrophy: A systematic review.

BACKGROUND: Cerebral Palsy (CP) and Spinal Muscular Atrophy (SMA) are common causes of motor disability in childhood. Gait exoskeletons are currently being used as part of rehabilitation for children with walking difficulties. OBJECTIVE: To assess the safety and efficacy and describe the main characteristics of the clinical articles using robot-assisted gait training (RAGT) with exoskeleton for children with CP or SMA. METHODS: A computer search was conducted in five bibliographic databases regarding clinical studies published in the last ten years. In order to be included in this review for further analysis, the studies had to meet the following criteria: (1) assess efficacy or safety of interventions; (2) population had to be children with CP or SMA aged between 3 and 14; (3) exoskeleton must be bilateral and assist lower limbs during walking. RESULTS: Twenty-one articles were selected, of which only five were clinical trials. 108 participants met the inclusion criteria for this study, all with a diagnosis of CP. The evidence level of the selected papers was commonly low. CONCLUSIONS: RAGT therapy seems to be safe for children with CP. However, further investigation is needed to confirm the results related to efficacy. There is no evidence of RAGT therapy for SMA children.

Phosphate, Microbiota and CKD.

Phosphate is a key uremic toxin associated with adverse outcomes. As chronic kidney disease (CKD) progresses, the kidney capacity to excrete excess dietary phosphate decreases, triggering compensatory endocrine responses that drive CKD-mineral and bone disorder (CKD-MBD). Eventually, hyperphosphatemia develops, and low phosphate diet and phosphate binders are prescribed. Recent data have identified a potential role of the gut microbiota in mineral bone disorders. Thus, parathyroid hormone (PTH) only caused bone loss in mice whose microbiota was enriched in the Th17 cell-inducing taxa segmented filamentous bacteria. Furthermore, the microbiota was required for PTH to stimulate bone formation and increase bone mass, and this was dependent on bacterial production of the short-chain fatty acid butyrate. We review current knowledge on the relationship between phosphate, microbiota and CKD-MBD. Topics include microbial bioactive compounds of special interest in CKD, the impact of dietary phosphate and phosphate binders on the gut microbiota, the modulation of CKD-MBD by the microbiota and the potential therapeutic use of microbiota to treat CKD-MBD through the clinical translation of concepts from other fields of science such as the optimization of phosphorus utilization and the use of phosphate-accumulating organisms.

Clinical Features of Asymptomatic SARS-CoV-2 Infection in Hemodialysis Patients.

BACKGROUND: CKD is a risk factor for severe COVID-19. However, the clinical spectrum of COVID-19 in hemodialysis patients is still poorly characterized. OBJECTIVE: To analyze the clinical spectrum of COVID-19 on hemodialysis patients. METHOD: A retrospective observational study was conducted on 66 hemodialysis patients. Nasopharyngeal swab PCR and serology for SARS-CoV-2, blood analysis, chest radiography, treatment, and outcomes were assessed. RESULTS: COVID-19 was diagnosed in 50 patients: 38 (76%) were PCR-positive and 12 (24%) were PCR-negative but developed anti-SARS-CoV-2 antibodies. By contrast, 17% of PCR-positive patients failed to develop detectable antibodies against SARS-CoV-2. Among PCR-positive patients, 5/38 (13%) were asymptomatic, while among PCR-negative patients 7/12 (58%) were asymptomatic (p = 0.005) for a total of 12/50 (24%) asymptomatic patients. No other differences were found between PCR-positive and PCR-negative patients. No differences in potential predisposing factors were found between asymptomatic and symptomatic patients except for a lower use of ACE inhibitors among asymptomatic patients. Asymptomatic patients had laboratory evidence of milder disease such as higher lymphocyte counts and oxygen saturation and lower troponin I and interleukin-6 levels than symptomatic patients. Overall mortality was 7/50 (14%) and occurred only in symptomatic PCR-positive patients in whom mortality was 7/33 (21%). CONCLUSIONS: Asymptomatic SARS-CoV-2 infection is common in hemodialysis patients, especially among patients with initial negative PCR that later seroconvert. Thus COVID-19 mortality in hemodialysis patients may be lower than previously estimated based on PCR tests alone.

Ultrafiltration rate adjusted to body weight and mortality in hemodialysis patients.

BACKGROUND AND AIMS: Mortality among hemodialysis patients remains high. An elevated ultrafiltration rate adjusted by weight (UFR/W) has been associated with hypotension and higher risk of death and/or cardiovascular events. METHODS: We evaluated the association between UFR/W and mortality in 215 hemodialysis patients. The mean follow-up was 28 ±â€¯6.12 months. We collected patients' baseline characteristics and mean UFR/W throughout the follow-up. RESULTS: Mean UFR/W was 9.0 ±â€¯2,4 and tertiles 7.1 y 10.1 mL/kg/h. We divided our population according to the percentage of sessions with UFR/W above the limits described in the literature associated with increased mortality (10.0 ml/kg/h and 13.0 mL/kg/h). Patients with higher UFR/W were younger, with higher interdialytic weight gain and weight reduction percentage but lower dry, pre and post dialysis weight. Throughout the follow-up, 46 (21.4%) patients died, the majority over 70 years old, diabetic or with cardiovascular disease. There were neither differences regarding mortality between groups nor differences in UFR/W among patients who died and those who did not. Contrary to previous studies, we did not find an association between UFR/W and mortality, maybe due to a higher prevalence in the use of cardiovascular protection drugs and lower UFR/W. CONCLUSIONS: The highest UFR/W were observed in younger patients with lower weight and were not associated with an increased mortality.

The Spectrum of Clinical and Serological Features of COVID-19 in Urban Hemodialysis Patients.

INTRODUCTION: The inherent immunosuppression of uremia increases the susceptibility of hemodialysis patients to infection. There is still limited evidence on hemodialysis patients and COVID-19. The clinical and analytical spectrum and treatment responses and mortality are poorly characterized. MATERIAL AND METHODS: Clinical and analytical features, chest X-ray, polymerase chain reaction (PCR) and antibodies for SARS-CoV-2, treatment and outcomes were analyzed in 48 patients diagnosed with COVID-19 during March and April 2020 in two coordinated Spanish hemodialysis units. RESULTS: In 200 haemodialysis patients, COVID-19 was diagnosed in 48, of whom 22 were PCR positive, eight PCR negative but seroconverted and two were diagnosed on typical clinical grounds. Despite a mean age of 72.6 years, the overall mortality rate was 5/48 (10%). Among the PCR positive patients, 21 (55%) required admission and five (13%) died. PCR positive patients were more often symptomatic and hospitalized and had higher troponin I levels than PCR negative patients, but did not differ in lymphocyte counts, D-dimer or interleukin-6 (IL-6) levels. Among PCR negative COVID-19 patients, three out of 10 (30%) required admission, and none died. The most frequent symptom among the 48 patients was fever (31%), followed by asymptomatic patients (23%). A low number of lymphocytes was the only parameter significantly different between hospitalized and ambulatory COVID-19 patients, independently of PCR status. CONCLUSIONS: COVID-19 hemodialysis patients are frequently asymptomatic, and mortality may be lower than previously reported. Diagnosis may be retrospective, based on seroconversion, as PCR may be negative. This information should guide preventive and patient isolation strategies.

Epigenetic Modifiers as Potential Therapeutic Targets in Diabetic Kidney Disease.

Diabetic kidney disease is one of the fastest growing causes of death worldwide. Epigenetic regulators control gene expression and are potential therapeutic targets. There is functional interventional evidence for a role of DNA methylation and the histone post-translational modifications-histone methylation, acetylation and crotonylation-in the pathogenesis of kidney disease, including diabetic kidney disease. Readers of epigenetic marks, such as bromodomain and extra terminal (BET) proteins, are also therapeutic targets. Thus, the BD2 selective BET inhibitor apabetalone was the first epigenetic regulator to undergo phase-3 clinical trials in diabetic kidney disease with an endpoint of kidney function. The direct therapeutic modulation of epigenetic features is possible through pharmacological modulators of the specific enzymes involved and through the therapeutic use of the required substrates. Of further interest is the characterization of potential indirect effects of nephroprotective drugs on epigenetic regulation. Thus, SGLT2 inhibitors increase the circulating and tissue levels of ß-hydroxybutyrate, a molecule that generates a specific histone modification, ß-hydroxybutyrylation, which has been associated with the beneficial health effects of fasting. To what extent this impact on epigenetic regulation may underlie or contribute to the so-far unclear molecular mechanisms of cardio- and nephroprotection offered by SGLT2 inhibitors merits further in-depth studies.

Repeated Look-up Tables.

Efficient hardware implementations routinely approximate mathematical functions with look-up tables, while keeping the error of the approximation under control. For a certain class of commonly occurring 1D functions, namely monotonically increasing or decreasing functions, we found that it is possible to approximate such functions by repeated application of a very low resolution 1D look-up table. There are many advantages to cascading multiple identical LUTs, including the promise of a very simple hardware design and the use of standard linear interpolation. Further, the complexity associated with unequal bin sizes can be avoided. We show that for realistic applications, including gamma correction, high dynamic range encoding and decoding curves, as well as tone mapping and inverse tone mapping applications, multiple cascaded look-up tables can reduce the approximation error by more than 50% compared to a single look-up table with the same total memory footprint.