Therapeutic drugs for Alzheimer’s disease have been extensively studied due to its recurrence and abundance among neurodegenerative diseases. It is thought that the accumulation of amyloid precursor protein (APP) products, a consequence of an up-regulation of the β-site APP-cleaving enzyme 1 (BACE1), is the main triggering mechanism during the early stages of the disease. This study aims to explore the ability of a multifunctional conjugate based on magnetite nanoparticles for the cellular delivery of siRNA against the expression of the BACE1 gene. We immobilized the siRNA strand on PEGylated magnetite nanoparticles and investigated the effects on biocompatibility and efficacy of the conjugation. Similarly, we co-immobilized the translocating protein OmpA on PEGylated nanoparticles to enhance cellular uptake and endosomal escape. BACE1 suppression was statistically significant in HFF-1 cells, without any presence of a cytotoxic effect. The delivery of the nanoconjugate was achieved through endocytosis pathways, where endosome formation was likely escaped due to the proton-sponge effect characteristic of PEGylated nanoparticles or mainly by direct translocation in the case of OmpA/PEGylated nanoparticles.

Background: Following the Riyadh Declaration, digital health technologies were prioritized in many countries to address the challenges of the COVID-19 pandemic. Digital health apps for telemedicine and video consultations help reduce potential disease spread in routine health care, including follow-up care in orthopedic and trauma surgery. In addition to the satisfaction, efficiency, and safety of telemedicine, its economic and environmental effects are highly relevant to decision makers, particularly for the goal of reaching carbon neutrality of health care systems. Objective: This study aims to provide the first comprehensive health economic and environmental analysis of video consultations in follow-up care after knee and shoulder interventions in an orthopedic and trauma surgery department of a German university hospital. The analysis is conducted from a societal perspective. We analyze both economic and environmental impacts of video consultations, taking into account the goal of carbon neutrality for the German health care system by 2030. Methods: We conducted a prospective randomized controlled trial comparing follow-up care with digital health app video consultations (intervention group) to conventional face-to-face consultations in the clinic (control group). Economic impact included the analysis of travel and time costs and production losses. Examination of the environmental impact comprised the emissions of greenhouse gases, carbon monoxide, volatile hydrocarbons, nitrogen oxides, and particulates, and the calculation of environmental costs. Sensitivity analysis included calculations with a higher cost per ton of carbon dioxide equivalent, which gives equal weight to the welfare of present and future generations. Results: Data from 52 patients indicated that, from the patients’ point of view, telemedicine helped reduce travel costs, time costs, and production losses, resulting in mean cost savings of €76.52 per video consultation. In addition, emissions of 11.248 kg of greenhouse gases, 0.070 kg of carbon monoxide, 0.011 kg of volatile hydrocarbons, 0.028 kg of nitrogen oxides, and 0.0004 kg of particulates could be saved per patient through avoided travel. This resulted in savings of environmental costs between €3.73 and €9.53 per patient. Conclusions: We presented the first comprehensive analysis of economic and environmental effects of telemedicine in the follow-up care of patients in orthopedic and trauma surgery in Germany. Video consultations were found to reduce the environmental footprint of follow-up care; saved travel costs, travel time, and time costs for patients; and helped to lower production losses. Our findings can support the decision-making on the use of digital health during and beyond the COVID-19 pandemic, providing decision makers with data for both economic and environmental effects. Thanks to the pragmatic design of our study, our findings can be applied to a wide range of clinical contexts and potential digital health applications that substitute outpatient hospital visits with video consultations. Trial Registration: German Clinical Trials Register DRKS00023445; https://tinyurl.com/4pcvhz4n

This paper presents a new cardiorespiratory model focused on the prediction of the healthy human response under rest and aerobic dynamic exercise conditions. Simulation results of cardiorespiratory variables are compared against experimental data and two of the most current and complete cardiorespiratory models.

Background: The quest for improved diagnosis and treatment in home health care models has led to the development of wearable medical devices for remote vital signs monitoring. An accurate signal and a high diagnostic yield are critical for the cost-effectiveness of wearable health care monitoring systems and their widespread application in resource-constrained environments. Despite technological advances, the information acquired by these devices can be contaminated by motion artifacts (MA) leading to misdiagnosis or repeated procedures with increases in associated costs. This makes it necessary to develop methods to improve the quality of the signal acquired by these devices. Objective: We aimed to present a novel method for electrocardiogram (ECG) signal denoising to reduce MA. We aimed to analyze the method’s performance and to compare its performance to that of existing approaches. Methods: We present the novel Redundant denoising Independent Component Analysis method for ECG signal denoising based on the redundant and simultaneous acquisition of ECG signals and movement information, multichannel processing, and performance assessment considering the information contained in the signal waveform. The method is based on data including ECG signals from the patient’s chest and back, the acquisition of triaxial movement signals from inertial measurement units, a reference signal synthesized from an autoregressive model, and the separation of interest and noise sources through multichannel independent component analysis. Results: The proposed method significantly reduced MA, showing better performance and introducing a smaller distortion in the interest signal compared with other methods. Finally, the performance of the proposed method was compared to that of wavelet shrinkage and wavelet independent component analysis through the assessment of signal-to-noise ratio, dynamic time warping, and a proposed index based on the signal waveform evaluation with an ensemble average ECG. Conclusions: Our novel ECG denoising method is a contribution to converting wearable devices into medical monitoring tools that can be used to support the remote diagnosis and monitoring of cardiovascular diseases. A more accurate signal substantially improves the diagnostic yield of wearable devices. A better yield improves the devices’ cost-effectiveness and contributes to their widespread application.

Lower limb prosthetic alignment is a procedure mostly subjective. A prosthetic misaligned induces gait deviations and long-term joint diseases. The alignment effects for each lower limb and the stump stays uncertain. To identify the effect of the transfemoral alignment prosthesis on ground reaction forces and thermal images of the residual limb. The effect of misalignment and nominal alignment was evaluated in sixteen transfemoral amputees. The nominal alignment was considered as the optimal alignment for each subject. Misalignment included random variations in the anterior-posterior and medial-lateral translation of the prosthetic foot and the angle of flexion-extension, abduction-adduction, and internal-external rotation of the socket and prosthetic foot. The control group consisted of fifteen non-amputee individuals. The ground reaction force parameters and stump temperature were analyzed for each alignment condition. The statistical analysis included the one-way ANOVA, Kruskal-Wallis, and multiple comparison tests. The prosthesis did not produce statistically significant changes in the average temperature of residual limbs. However, the temperature distribution on the stump skin was different (P < 0.05). The transfemoral prosthesis misalignment produced an irregular heat diffusion on the anterior, posterior, and lateral sides of the stump contour compared to the nominal alignment (P < 0.05). The sound limb did not show differences between nominal alignments and misalignments for most ground reaction force parameters. For almost all GRF parameters, significant differences were observed for the prosthetic limb between misalignment and nominal alignment (P < 0.001). The symmetry indices of ground reaction force parameters of transfemoral amputees did not show any kind of significant improvements after aligning the prosthesis nominally. The stump's temperature distribution and the ground reaction force findings for the prosthetic limb provide a better understanding of the alignment procedure of the transfemoral prosthesis and improve the amputees' compliance to the prosthesis.

Background: Presenilin-1 (PSEN1) mutations are the most common cause of familial early onset Alzheimer’s disease (AD). The PSEN1 E280A (E280A) mutation has an autosomal dominant inheritance and is involved in the production of amyloid-β. The largest family group of carriers with E280A mutation is found in Antioquia, Colombia. The study of mutation carriers provides a unique opportunity to identify brain changes in stages previous to AD. Electroencephalography (EEG) is a low cost and minimally invasiveness technique that enables the following of brain changes in AD. Objective: To examine how previous reported differences in EEG for Theta and Alpha-2 rhythms in E280A subjects are related to specific regions in cortex and could be tracked across different ages. Methods: EEG signals were acquired during resting state from non-carriers and carriers, asymptomatic and symptomatic subjects from E280A kindred from Antioquia, Colombia. Independent component analysis (ICA) and inverse solution methods were used to locate brain regions related to differences in Theta and Alpha-2 bands. Results: ICA identified two components, mainly related to the Precuneus, where the differences in Theta and Alpha-2 exist simultaneously at asymptomatic and symptomatic stages. When the ratio between Theta and Alpha-2 is used, significant correlations exist with age and a composite cognitive scale. Conclusion: Theta and Alpha-2 rhythms are altered in E280A subjects. The alterations are possible to track at Precuneus regions using EEG, ICA, and inverse solution methods.