Virtual Surgical Planning in Condyle Reconstruction of Posterior Mandibulectomy Defects.

Background: Ameloblastoma is a rare odontogenic tumor most commonly located within the mandible. These tumors can grow to massive proportions and result in malocclusion. Segmental mandibulectomy and reconstruction with an osteocutaneous free flap are frequently required. Virtual surgical planning (VSP) aids the surgeon in creating precise anatomic reconstruction when there is preoperative malocclusion due to tumor size. In this study we seek to further examine reconstruction of posterior mandibulectomy defects inclusive of condylar resection. Methods: Retrospective review of patients treated for giant ameloblastoma (tumor >4 cm) was examined; 3 patients with posterior tumors requiring ramus and condylar resection were included. Reconstruction in all patients was performed using fibula free flaps and VSP custom-made mandibular reconstruction plates. In these patients the reconstructed ramus was shortened and precise contouring done with a burr to recreate the native condylar surface. Intermaxillary fixation was used to maintain occlusion for 1 month postoperatively. Inferior alveolar nerve repair with allograft and nerve connectors was performed for all 3 patients. Results: All patients underwent successful mandibular reconstruction with preservation of mandibular function and improved occlusion postoperatively. Inferior alveolar nerve repair using nerve allograft allowed for neurosensory recovery in the mandibular division of trigeminal nerve distribution in 2 of the 3 patients. Conclusions: Giant ameloblastoma involving the mandibular condyle can be successfully treated with the fibula free flap utilizing mandible reconstruction plates and VSP. This technique allows for excellent restoration of occlusion and neurosensory recovery when paired with reconstruction of the inferior alveolar nerve at time of reconstruction.

Operando Studies of Bismuth Nanoparticles Embedded in N, O-Doped Porous Carbon for High-Performance Potassium-Ion Hybrid Capacitor.

A highly viable alternative to lithium-ion batteries for stationary electrochemical energy-storage systems is the potassium dual-ion hybrid capacitor (PIHC), especially toward fast-charging capability. However, the sluggish reaction kinetics of negative electrode materials seriously impedes their practical implementation. In this paper, a new negative electrode Bi@RPC (Nano-bismuth confined in nitrogen- and oxygen-doped carbon with rationally designed pores, evidenced by advanced characterization) is developed, leading to a remarkable electrochemical performance. PIHCs building with the active carbon YP50F positive electrode result in a high operation voltage (0.1-4 V), and remarkably well-retained energy density at a high-power density (11107 W kg-1 at 98 Wh kg-1 ). After 5000 cycles the proposed PHICs still show a superior capacity retention of 92.6%. Moreover, a reversible mechanism of "absorption-alloying" of the Bi@RPC nanocomposite is revealed by operando synchrotron X-ray diffraction and Raman spectroscopy. With the synergistic potassium ions storage mechanism arising from the presence of well-structured pores and nano-sized bismuth, the Bi@RPC electrode exhibits an astonishingly rapid kinetics and high energy density. The results demonstrate that PIHCs with Bi@RPC-based negative electrode is the promising option for simultaneously high-capacity and fast-charging energy storage devices.

Impacto del confinamiento durante la pandemia de COVID-19 en la prevalencia de la enfermedad tromboembólica venosa / Impact of strict confinement during the COVID-19 pandemic on the prevalence of venous thromboembolic disease

Objetivo: comparar la frecuencia de eventos tromboembólicos agudos en pacientes atendidos en urgencias de un hospital comarcal durante las primeras semanas de la pandemia de COVID-19 del año 2020 respecto al año anterior.Material y métodos: estudio retrospectivo en pacientes mayores de 40 años atendidos en urgencias del Hospital de Riotinto (Huelva) desde el 15 de marzo al 30 de abril de los años 2019 y 2020. La recogida de información se llevó a cabo a partir de una revisión de historias clínicas y el cuestionario de recogida de datos contenía variables clínicas y sociodemográficas.Resultados: se incluyeron 1.245 pacientes. Edad media: 71,2 años (desviación estándar [DE]: 13,7) y un 51,1% eran mujeres. En 2019 se atendieron a 797 mayores de 40 años y en 2020 fueron 448, suponiendo un descenso del 43,79%. La prevalencia de embolismo pulmonar fue superior en 2020 respecto a 2019 (1,6% frente a 0,4%; p = 0,024). La frecuencia de eventos trombóticos venosos fue superior también en 2020 respecto a 2019 (1,35% frente a 0,4%; p = 0,054). La prevalencia global de la enfermedad tromboembólica venosa con variable compuesta (tromboembolismo pulmonar + trombosis venosa) fue significativamente superior en 2020 frente a 2019 (2,9% frente a 0,8%; p = 0,003). Ningún paciente fue diagnosticado de COVID-19 y tromboembolismo.Conclusiones: en el período de confinamiento durante la pandemia hubo un incremento del número de eventos tromboembólicos agudos en adultos, tanto de tromboembolia pulmonar como de trombosis venosa profunda respecto al año previo. (AU)

Aim: to compare the frequency of acute thromboembolic events in patients visited in the casualty department of a regional hospital during the first few weeks of the COVID-19 pandemic in 2020 with the same period of previous year.Material and methods: retrospective study of patients aged over 40 years of age treated in the casualty department of Hospital de Riotinto (Huelva) from 15 March to 30 April 2019 and same period of 2020. The information was collected from a review of medical records. The data collection questionnaire contained clinical and sociodemographic variables.Results: a total of 1245 patients were included. Mean age was 71.2 (SD:13.7) years old and 51.1% were women. In 2019, 797 patients aged over 40 years of age were treated, while in 2020, the patients seen were 448, which represented a decrease of 43.79%. The prevalence of pulmonary embolism was higher in 2020 compared to 2019 (1.6% vs. 0.4%; P=0.024). The frequency of venous thrombotic events was also higher in 2020 compared to 2019 (1.35% vs. 0.4%; P=0.054). The overall prevalence of venous thromboembolic disease with composite variable (pulmonary thromboembolism + venous thrombosis) was statistically significantly higher in 2020 versus 2019 (2.9% versus 0.8%; P=0.003). None of our patients were diagnosed with COVID-19 and thromboembolism.Conclusions: during the period of confinement during the pandemic there was an increase in the number of acute thromboembolic events in adults, both PE and VTE compared to the previous year.(AU)

Cortistatin as a Novel Multimodal Therapy for the Treatment of Parkinson's Disease.

Parkinson's disease (PD) is a complex disorder characterized by the impairment of the dopaminergic nigrostriatal system. PD has duplicated its global burden in the last few years, becoming the leading neurological disability worldwide. Therefore, there is an urgent need to develop innovative approaches that target multifactorial underlying causes to potentially prevent or limit disease progression. Accumulating evidence suggests that neuroinflammatory responses may play a pivotal role in the neurodegenerative processes that occur during the development of PD. Cortistatin is a neuropeptide that has shown potent anti-inflammatory and immunoregulatory effects in preclinical models of autoimmune and neuroinflammatory disorders. The goal of this study was to explore the therapeutic potential of cortistatin in a well-established preclinical mouse model of PD induced by acute exposure to the neurotoxin 1-methil-4-phenyl1-1,2,3,6-tetrahydropyridine (MPTP). We observed that treatment with cortistatin mitigated the MPTP-induced loss of dopaminergic neurons in the substantia nigra and their connections to the striatum. Consequently, cortistatin administration improved the locomotor activity of animals intoxicated with MPTP. In addition, cortistatin diminished the presence and activation of glial cells in the affected brain regions of MPTP-treated mice, reduced the production of immune mediators, and promoted the expression of neurotrophic factors in the striatum. In an in vitro model of PD, treatment with cortistatin also demonstrated a reduction in the cell death of dopaminergic neurons that were exposed to the neurotoxin. Taken together, these findings suggest that cortistatin could emerge as a promising new therapeutic agent that combines anti-inflammatory and neuroprotective properties to regulate the progression of PD at multiple levels.

A Late Pleistocene hominin footprint site on the North African coast of Morocco.

Footprints represent a relevant vestige providing direct information on the biology, locomotion, and behaviour of the individuals who left them. However, the spatiotemporal distribution of hominin footprints is heterogeneous, particularly in North Africa, where no footprint sites were known before the Holocene. This region is important in the evolution of hominins. It notably includes the earliest currently known Homo sapiens (Jebel Irhoud) and the oldest and richest African Middle Stone Age hominin sites. In this fragmented ichnological record, we report the discovery of 85 human footprints on a Late Pleistocene now indurated beach surface of about 2800 m2 at Larache (Northwest coast of Morocco). The wide range of sizes of the footprints suggests that several individuals from different age groups made the tracks while moving landward and seaward across a semi-dissipative bar-trough sandy beach foreshore. A geological investigation and an optically stimulated luminescence dating of a rock sample extracted from the tracksite places this hominin footprint surface at 90.3 ± 7.6 ka (MIS 5, Late Pleistocene). The Larache footprints are, therefore, the oldest attributed to Homo sapiens in Northern Africa and the Southern Mediterranean.

Impact of preoperative pharmaceutical care consultation on medication errors in surgical patients: a comprehensive analysis.

OBJECTIVE: Assessing the impact of introducing preoperative pharmaceutical care consultations by analyzing the severity of prevented medication errors (MEs) and their potential effects on the surgical process. METHODS: Preoperative pharmaceutical care consultation was implemented in our hospital to assess the preoperative medication management of surgical patients between the pre-anesthesia consultation and the day of surgery. Pharmacists evaluated the appropriateness of medication management based on a consensus multidisciplinary institutional protocol. All errors identified between 2016 and 2020 were analyzed, and their severity and potential impact on surgery were standardized. A list of therapeutic groups was created to prioritize patients for consultations. RESULTS: During the study period, 3,105 patients attended the consultations and 1,179 MEs were prevented. According to severity, 30.6% of MEs were classified as category E and 26.2% as D. The Number Needed to Treat to prevent a category E or higher ME (indicating potential harm to patients) was 5 patients. About 14.84% of MEs belonged to the prioritized drug groups. One hundred and thirteen errors would have resulted in a surgery delay of more than 24 h, and 175 errors were classified as G-H (irreversible damage). CONCLUSIONS: This study highlights the effectiveness of pharmaceutical care consultations in preventing MEs and improving surgical outcomes.

LETHE: A Digital Intervention for Cognitive Decline.

Dementia is the main cause of disability in elderly populations. It has been shown that the risk factors of dementia are a mixture of pathological, lifestyle and heritable factors, with some of those being provably modifiable. Early diagnosis of dementia and approaches to slow down its evolution are currently the most prominent management methodologies due to lack of a cure. For that reason, a plethora of home-based assistive technologies for dementia management do exist, with most of them focusing on the improvement of memory and thinking. The main objective of LETHE is prevention in the whole spectrum of cognitive decline in the elderly population at risk reaching from asymptomatic to subjective or mild cognitive impairment to prodromal Dementia. LETHE will provide a Big Data collection platform and analysis system, that will allow prevention, personalized risk detection and intervention on cognitive decline. Through the subsequent 2-year clinical trial, the LETHE system, as well as the respective knowledge gained will be evaluated and validated. The scope of the current paper is to introduce the LETHE study and its respective novel platform as a holistic approach to multidomain lifestyle intervention trial studies. The present work depicts the architectural perspective and extends beyond state-of-the-art guidelines and approaches to health management systems and cloud platform development.Clinical Relevance - Patient Management Systems as well as lifestyle management platforms have significant clinical relevance as they allow for remote and continuous monitoring of patients' health status. LETHE aims to improve patient outcomes by providing predictive models for cognitive decline and patient adherence to the multimodal lifestyle intervention, enabling prompt and appropriate medical decisions.

Fusion of the occipitomastoidal synchondrosis as a developmental marker in the Sima de los Huesos Crania (Atapuerca, Spain).

The basicranium contains multiple synchondroses potentially informative for estimating the developmental stage of individuals. The basilar synchondrosis has been routinely used for this purpose in bioarchaeological, forensic and paleoanthropological research, and studies carried out in modern human populations have shown a close relationship between the fusion of the occipitomastoidal synchondrosis and developmental processes. This synchondrosis articulates the jugular process of the occipital bone with the jugular surface of the temporal bone. As the process of fusion of the synchondrosis progresses, the jugular surface undergoes a series of alterations whose study allows to establish the state of fusion of the synchondrosis when the individual died. The extraordinary preservation of the jugular surface in a large number of individuals represented in the fossil hominin sample from the middle Pleistocene site of the Sima de los Huesos (SH) has made it possible to carry out the first systematic study to assess the usefulness of occipitomastoidal synchondrosis in the establishment of the state of development in fossil hominins. Our results show that the complete closure of the occipitomastoidal synchondrosis occurred toward the end of the growth period in the SH fossils. This result opens up the possibility of using it to determine the developmental stage of fossil hominins for which no other information is available, such as the state of the dentition or the degree of closure of the basilar synchondrosis. This has allowed us to infer a state of development for three SH crania where it could not previously be established with certainty.

IS2aR, a computational tool to transform voxelized reference phantoms into patient-specific whole-body virtual CTs for peripheral dose estimation.

BACKGROUND: The risk of radiogenic cancer induction due to radiotherapy depends on the dose received by the patient's organs. Knowing the position of all organs is needed to assess this dose in a personalized way. However, radiotherapy planning computed tomography (pCT) scans contain truncated patient anatomy, limiting personalized dose evaluation. PURPOSE: To develop a simple and freely available computational tool that adapts an ICRP reference computational phantom to generate a patient-specific whole-body CT for peripheral dose computations. METHODS: Various bone-segmentation methods were explored onto fifteen pCTs, and the one with the highest Sørensen-Dice coefficient was implemented. The reference phantom is registered to the pCT, obtaining a registration transform matrix, which is then applied to create the whole-body virtual CT. Additional validation involved a comparison of absorbed doses to organs delineated on both the pCT and the virtual CT. RESULTS: A dedicated graphical user interface was designed and implemented to house the developed functions for i) selecting a registration region on which automatic bone segmentation and rigid registration will occur, ii) displaying the results of these processes under selectable views, and iii) exporting the final patient-specific whole-body CT. This software was termed IS2aR. The tested whole-body virtual CT generated by IS2aR fulfilled our requirements. CONCLUSIONS: IS2aR is a user-friendly computational software to create a personalized whole-body CT containing the original structures in the reference phantom. The personalized dose deposited in peripheral organs can be estimated further to assess second cancer induction risk in epidemiological studies.

Cortistatin deficiency reveals a dysfunctional brain endothelium with impaired gene pathways, exacerbated immune activation, and disrupted barrier integrity.

BACKGROUND: Brain activity governing cognition and behaviour depends on the fine-tuned microenvironment provided by a tightly controlled blood-brain barrier (BBB). Brain endothelium dysfunction is a hallmark of BBB breakdown in most neurodegenerative/neuroinflammatory disorders. Therefore, the identification of new endogenous molecules involved in endothelial cell disruption is essential to better understand BBB dynamics. Cortistatin is a neuroimmune mediator with anti-inflammatory and neuroprotective properties that exerts beneficial effects on the peripheral endothelium. However, its role in the healthy and injured brain endothelium remains to be evaluated. Herein, this study aimed to investigate the potential function of endogenous and therapeutic cortistatin in regulating brain endothelium dysfunction in a neuroinflammatory/neurodegenerative environment. METHODS: Wild-type and cortistatin-deficient murine brain endothelium and human cells were used for an in vitro barrier model, where a simulated ischemia-like environment was mimicked. Endothelial permeability, junction integrity, and immune response in the presence and absence of cortistatin were evaluated using different size tracers, immunofluorescence labelling, qPCR, and ELISA. Cortistatin molecular mechanisms underlying brain endothelium dynamics were assessed by RNA-sequencing analysis. Cortistatin role in BBB leakage was evaluated in adult mice injected with LPS. RESULTS: The endogenous lack of cortistatin predisposes endothelium weakening with increased permeability, tight-junctions breakdown, and dysregulated immune activity. We demonstrated that both damaged and uninjured brain endothelial cells isolated from cortistatin-deficient mice, present a dysregulated and/or deactivated genetic programming. These pathways, related to basic physiology but also crucial for the repair after damage (e.g., extracellular matrix remodelling, angiogenesis, response to oxygen, signalling, and metabolites transport), are dysfunctional and make brain endothelial barrier lacking cortistatin non-responsive to any further injury. Treatment with cortistatin reversed in vitro hyperpermeability, tight-junctions disruption, inflammatory response, and reduced in vivo BBB leakage. CONCLUSIONS: The neuropeptide cortistatin has a key role in the physiology of the cerebral microvasculature and its presence is crucial to develop a canonical balanced response to damage. The reparative effects of cortistatin in the brain endothelium were accompanied by the modulation of the immune function and the rescue of barrier integrity. Cortistatin-based therapies could emerge as a novel pleiotropic strategy to ameliorate neuroinflammatory/neurodegenerative disorders with disrupted BBB.

Malicious traffic detection on sampled network flow data with novelty-detection-based models.

Cyber-attacks are a major problem for users, businesses, and institutions. Classical anomaly detection techniques can detect malicious traffic generated in a cyber-attack by analyzing individual network packets. However, routers that manage large traffic loads can only examine some packets. These devices often use lightweight flow-based protocols to collect network statistics. Analyzing flow data also allows for detecting malicious network traffic. But even gathering flow data has a high computational cost, so routers usually apply a sampling rate to generate flows. This sampling reduces the computational load on routers, but much information is lost. This work aims to demonstrate that malicious traffic can be detected even on flow data collected with a sampling rate of 1 out of 1,000 packets. To do so, we evaluate anomaly-detection-based models using synthetic sampled flow data and actual sampled flow data from RedCAYLE, the Castilla y León regional subnet of the Spanish academic and research network. The results presented show that detection of malicious traffic on sampled flow data is possible using novelty-detection-based models with a high accuracy score and a low false alarm rate.

Predicting body weight through biometric measurements in growing hair sheep using data mining and machine learning algorithms.

Determination of live weight, which is one of the most important features that determine meat production, is a very important issue for herd management and sustainable livestock. In this context, the necessity of finding alternative methods has emerged, especially in rural conditions, due to the difficulties to be experienced in finding the weighing tool. Especially for conditions with no weighing tool, it has been tried to establish relations between the information obtained from body measurements and live weight. Since these studies will differ from species to species and breed to breed, the need for new studies is extremely high. For this aim, it is to evaluate the body measurement information obtained with the present study using several statistical approaches. To implement this aim, several data mining and machine learning algorithms such as multivariate adaptive regression splines (MARS), classification and regression tree (CART), and support vector machine regression (SVR) algorithms were used for training (70%) and test (30%) sets. To predict final body weight, 280 hair sheep breeds (162 female and 118 male) ranging from 2 months to 3 years were used with different data mining and machine learning approaches. Various goodness-of-fit criteria were used to evaluate the performances of the aforementioned algorithms. Although the MARS and SVR algorithms gave the same and highest results in terms of R2 and r values for both the train and the test sets, the SVR algorithm is one of the methods to be recommended as a result of this study, especially when other goodness-of-fit criteria are evaluated. In conclusion, the usage of SVR algorithms may be a useful tool of machine learning approaches for detecting the hair sheep breed standards and may contribute to increasing the sheep meat quality in Mexico.

Novel Therapeutic Opportunities for Neurodegenerative Diseases with Mesenchymal Stem Cells: The Focus on Modulating the Blood-Brain Barrier.

Neurodegenerative disorders encompass a broad spectrum of profoundly disabling situations that impact millions of individuals globally. While their underlying causes and pathophysiology display considerable diversity and remain incompletely understood, a mounting body of evidence indicates that the disruption of blood-brain barrier (BBB) permeability, resulting in brain damage and neuroinflammation, is a common feature among them. Consequently, targeting the BBB has emerged as an innovative therapeutic strategy for addressing neurological disorders. Within this review, we not only explore the neuroprotective, neurotrophic, and immunomodulatory benefits of mesenchymal stem cells (MSCs) in combating neurodegeneration but also delve into their recent role in modulating the BBB. We will investigate the cellular and molecular mechanisms through which MSC treatment impacts primary age-related neurological conditions like Alzheimer's disease, Parkinson's disease, and stroke, as well as immune-mediated diseases such as multiple sclerosis. Our focus will center on how MSCs participate in the modulation of cell transporters, matrix remodeling, stabilization of cell-junction components, and restoration of BBB network integrity in these pathological contexts.

Índices de fibrosis en el seguimiento de la enfermedad hepática grasa no alcohólica / Fibrosis indices in non-alcoholic fatty liver disease follow-up

Introducción: La enfermedad hepática grasa no alcohólica es una afección clínica- morfológica que se caracteriza por una infiltración grasa del hígado en más de un 5 %; tiene dos estadios: esteatosis simple y esteatohepatitis, la cual puede progresar a: fibrosis, cirrosis y hepatocarcinoma. Objetivo: Determinar la relación entre las variables clínicas y epidemiológicas con esta enfermedad, así como los índices de fibrosis y su relación. Métodos: Se realizó un estudio descriptivo con diseño transversal en los pacientes atendidos en la consulta de hígado y vías biliares del Hospital Universitario « Dr. Celestino Hernández Robau», en la etapa de enero- diciembre de 2017. Se trabajó con una población conformada por 60 pacientes, mayores o igual a 20 años de edad, con diagnóstico de enfermedad hepática grasa no alcohólica primaria, sobrepesos u obesos. Resultados: Predominó el grupo etario entre 50-59 años de edad, del sexo femenino, obesos y con esteatosis grado I. Se constató que el 73,33% de los pacientes tenían síndrome metabólico y en ellos prevaleció el grado II de esteatosis. Al relacionar los riesgos de fibrosis se encontraron 28 pacientes con riesgo indeterminado y alto en las clasificaciones FIB-4 y NFS, respectivamente, y 5 presentaron alto riesgo en ambas variables. Los índices de FIB-4 y NFS tuvieron una correlación significativa, directamente proporcional y considerable. Conclusiones: La correlación detectada entre los índices FIB-4 y NFS reafirmó el valor en la detección de sospecha de fibrosis y orientó, en la práctica clínica, la conducta ante los diferentes pacientes con esta afección.

Introduction: non-alcoholic fatty liver disease is a clinical and morphological condition characterized by fatty infiltration of the liver in more than 5%; it has two stages: simple steatosis and steatohepatitis, which can progress to fibrosis, cirrhosis and hepatocellular carcinoma. Objective: to determine the relationship between clinical and epidemiological variables with this disease, as well as fibrosis indices and their relationship. Methods: a cross-sectional descriptive study was carried out in patients seen in the liver and biliary tract consultation at " Dr. Celestino Hernández Robau" University Hospital from January to December 2017. We worked with a population made up of 60 overweight or obese patients older than or equal to 20 years who were diagnosed with primary non-alcoholic fatty liver disease. Results: the age group between 50-59 years of age, female gender, obese ones and with grade I steatosis prevailed. We found that 73.33% of the patients had metabolic syndrome and grade II steatosis prevailed in them. A number of 28 patients were found with indeterminate and high risk in the FIB-4 and NAFLD classifications, respectively, when relating the risks of fibrosis, as well as 5 had high risk in both variables. The FIB-4 and NAFLD indices had a significant, directly proportional, and considerable correlation. Conclusions: the correlation detected between the FIB-4 and NAFLD indices reaffirmed the value in the detection of suspected fibrosis and guided, in clinical practice, the conduct of different patients with this condition.

Hybrid tungsten-carbon 2D nanostructures viain situgasification of carbon substrates driven by ebeam irradiation of WO2.9microparticles.

Since the transmission electron microscope (TEM) has the capacity to observe the atomic structure of materials,in situTEM synthesis methods are uniquely suited to advance our fundamental understanding of the bottom-up dynamics that drive the formation of nanostructures. E-beam induced fragmentation (potentially identified as a manifestation of Coulomb explosion) and electron stimulated desorption are phenomena that have received attention because they trigger chemical and physical reactions that can lead to the production of various nanostructures. Here we report a simple TEM protocol implemented on WO2.9microparticles supported on thin amorphous carbon substrates. The method produces various nanostructures such as WC nanoparticles, WC supported films and others. Nevertheless, we focus on the gradual graphitization and gasification of the C substrate as it interacts with the material expelled from the WO2.9microparticles. The progressive gasification transforms the substrate from amorphous C down to hybrid graphitic nanoribbons incorporating W nanoparticles. We think these observations open interesting possibilities for the synthesis of 2D nanomaterials in the TEM.

Correction: Label free localization of nanoparticles in live cancer cells using spectroscopic microscopy.

Correction for 'Label free localization of nanoparticles in live cancer cells using spectroscopic microscopy' by Graham L. C. Spicer et al., Nanoscale, 2018, 10, 19125-19130, https://doi.org/10.1039/C8NR07481J.

Combining biophysical models and machine learning to optimize implant geometry and stimulation protocol for intraneural electrodes.

Objective.Peripheral nerve interfaces have the potential to restore sensory, motor, and visceral functions. In particular, intraneural interfaces allow targeting deep neural structures with high selectivity, even if their performance strongly depends upon the implantation procedure and the subject's anatomy. Currently, few alternatives exist for the determination of the target subject structural and functional anatomy, and statistical characterizations from cadaveric samples are limited because of their high cost. We propose an optimization workflow that can guide both the pre-surgical planning and the determination of maximally selective multisite stimulation protocols for implants consisting of several intraneural electrodes, and we characterize its performance in silico. We show that the availability of structural and functional information leads to very high performances and allows taking informed decisions on neuroprosthetic design.Approach.We employ hybrid models (HMs) of neuromodulation in conjunction with a machine learning-based surrogate model to determine fiber activation under electrical stimulation, and two steps of optimization through particle swarm optimization to optimize in silico implant geometry, implantation and stimulation protocols using morphological data from the human median nerve at a reduced computational cost.Main results.Our method allows establishing the optimal geometry of multi-electrode transverse intra-fascicular multichannel electrode implants, the optimal number of electrodes to implant, their optimal insertion, and a set of multipolar stimulation protocols that lead in silico to selective activation of all the muscles innervated by the human median nerve.Significance.We show how to use effectively HMs for optimizing personalized neuroprostheses for motor function restoration. We provide in-silico evidences about the potential of multipolar stimulation to increase greatly selectivity. We also show that the knowledge of structural and functional anatomies of the target subject leads to very high selectivity and motivate the development of methods for theirin vivocharacterization.

Decellularized Graft for Repairing Severe Peripheral Nerve Injuries in Sheep.

BACKGROUND AND OBJECTIVES: Peripheral nerve injuries resulting in a nerve defect require surgical repair. The gold standard of autograft (AG) has several limitations, and therefore, new alternatives must be developed. The main objective of this study was to assess nerve regeneration through a long gap nerve injury (50 mm) in the peroneal nerve of sheep with a decellularized nerve allograft (DCA). METHODS: A 5-cm long nerve gap was made in the peroneal nerve of sheep and repaired using an AG or using a DCA. Functional tests were performed once a month and electrophysiology and echography evaluations at 6.5 and 9 months postsurgery. Nerve grafts were harvested at 9 months for immunohistochemical and morphological analyses. RESULTS: The decellularization protocol completely eliminated the cells while preserving the extracellular matrix of the nerve. No significant differences were observed in functional tests of locomotion and pain response. Reinnervation of the tibialis anterior muscles occurred in all animals, with some delay in the DCA group compared with the AG group. Histology showed a preserved fascicular structure in both AG and DCA; however, the number of axons distal to the nerve graft was higher in AG than in DCA. CONCLUSION: The decellularized graft assayed supported effective axonal regeneration when used to repair a 5-cm long gap in the sheep. As expected, a delay in functional recovery was observed compared with the AG because of the lack of Schwann cells.