The light-dependent pseudo-capacitive charging of conjugated polymer nanoparticles coupled with the depolarization of the neuronal membrane.

The mechanism underlying visual restoration in blind animal models of retinitis pigmentosa using a liquid retina prosthesis based on semiconductive polymeric nanoparticles is still being debated. Through the application of mathematical models and specific experiments, we developed a coherent understanding of abiotic/biotic coupling, capturing the essential mechanism of photostimulation responsible for nanoparticle-induced retina activation. Our modeling is based on the solution of drift-diffusion and Poisson-Nernst-Planck models in the multi-physics neuron-cleft-nanoparticle-extracellular space domain, accounting for the electro-chemical motion of all the relevant species following photoexcitation. Modeling was coupled with electron microscopy to estimate the size of the neuron-nanoparticle cleft and electrophysiology on retina explants acutely or chronically injected with nanoparticles. Overall, we present a consistent picture of electrostatic depolarization of the bipolar cell driven by the pseudo-capacitive charging of the nanoparticle. We demonstrate that the highly resistive cleft composition, due to filling by adhesion/extracellular matrix proteins, is a crucial ingredient for establishing functional electrostatic coupling. Additionally, we show that the photo-chemical generation of reactive oxygen species (ROS) becomes relevant only at very high light intensities, far exceeding the physiological ones, in agreement with the lack of phototoxicity shown in vivo.

Uninstrumented fusion in cervical kyphosis due to neurofibromatosis type I: report of two paediatric cases.

PURPOSE: Severe cervical kyphosis (CK) in neurofibromatosis type 1 (NF-1) is associated with a high risk for progression and neurologic impairment in children. We present our surgical technique and mid-term outcomes of uninstrumented anterior tibial strut grafting for severe CK secondary to NF-1. METHODS: Case report. The Consensus-based Clinical Case Reporting Guideline Development (CARE) guidelines were followed. RESULTS: Two paediatric patients (8- and 3-year-old) presented with severe CK secondary to NF-1. A halo body jacket (HV) allowed the progressive distraction of the cervical spine, avoiding neurological compromise and deformity progression. Circumferential fusion was obtained with anterior tibial strut autograft and posterior onlay bone graft. Cervical spine fusion was successfully maintained at a minimum 4-year follow-up in both patients. CONCLUSION: In children with severe CK secondary to NF-1, cervical distraction and immobilisation with a HV followed by uninstrumented anterior tibial strut grafting and posterior bone grafting, provided spinal fusion and stability without increasing the risk of neurological injury and donor site morbidity. The reported surgical technique appears to be a valuable tool in the armamentarium of the spinal surgeon.

Validation of an Automated Optical Scanner for a Comprehensive Anthropometric Analysis of the Foot and Ankle.

Background: Our objective was to conduct a comprehensive analysis of the reproducibility of foot and ankle anthropometric measurements with a three-dimensional (3D) optical scanner. Methods: We evaluated thirty-nine different anthropometric parameters obtained with a 3D Laser UPOD-S Full-Foot Scanner in a healthy population of twenty subjects. We determined the variance of the measurements for each foot/ankle, and the average variance among different subjects. Results: For 40 feet and ankles (15 women and 5 men; mean age 35.62 +/- 9.54 years, range 9-75 years), the average variance was 1.4 ± 2 (range 0.1 to 8). Overall, the mean absolute measurement error was <1 mm, with a maximum variance percentage of 8.3%. Forefoot and midfoot circumferences had a low variance <2.5, with variance percentages <1%. Hindfoot circumferences, malleolar heights, and the length of the first and fifth metatarsal to the ground contact points showed the highest variance (range 1 to 7). Conclusions: The UPOD-S Full-Foot optical Scanner achieved a good reproducibility in a large set of foot and ankle anthropometric measurements. It is a valuable tool for clinical and research purposes.

Advantages of ultrasound identification of the distal insertion of the calcaneofibular ligament during ligament reconstructions.

INTRODUCTION: In lateral ankle instability, anatomical ligament reconstructions are generally performed using arthroscopy. The ligament graft is passed through the talar, fibular and calcaneal tunnels, reconstructing the anterior talofibular and calcaneofibular (CFL) bundles. However, the calcaneal insertion of the CFL needs to be performed in an extra-articular fashion, and cannot be carried out under arthroscopy, thus requiring specific anatomical landmarks. For obtaining these landmarks, methods based on radiography or surface anatomy have already been described but can only offer an approximate identification of the actual CFL anatomical insertion point. In contrast, an ultrasound technique allows direct visualization of the insertion point and of the sural nerve that may be injured during surgery. Our study aimed to assess the reliability and accuracy of ultrasound visualization when performing calcaneal insertion of the CFL with specific monitoring of the sural nerve. MATERIALS AND METHODS: Our anatomical study was carried out on 15 ankles available from a body donation program. Ultrasound identification of the sural nerve was obtained first with injection of dye. A needle was positioned at the level of the calcaneal insertion of the CFL. After dissection, in all the ankles, the dye was in contact with the sural nerve and the needle was located in the calcaneal insertion area of the CFL. The mean distance between the sural nerve and the needle was 4.8 mm (range 3-7 mm). DISCUSSION AND CONCLUSION: A pre- or intra-operative ultrasound technique is a simple and reliable means for obtaining anatomical landmarks when drilling the calcaneal tunnel for ligament reconstruction of the lateral plane of the ankle. This tunnel should preferably be drilled obliquely from the heel towards the subtalar joint (1 h-3 h direction on an ultrasound cross section), which preserves a maximum distance from the sural nerve for safety purposes, while allowing an accurate anatomical positioning of the osseous tunnel.

The role of conventional and unconventional adaptive routes in lowering of intraocular pressure: Theoretical model and simulation.

In this article, we propose a theoretical model leveraging the analogy between fluid and electric variables to investigate the relation among aqueous humor (AH) circulation and drainage and intraocular pressure (IOP), the principal established risk factor of severe neuropathologies of the optic nerve such as glaucoma. IOP is the steady-state result of the balance among AH secretion (AHs), circulation (AHc), and drainage (AHd). AHs are modeled as a given volumetric flow rate electrically corresponding to an input current source. AHc is modeled by the series of two linear hydraulic conductances (HCs) representing the posterior and anterior chambers. AHd is modeled by the parallel of three HCs: a linear HC for the conventional adaptive route (ConvAR), a nonlinear HC for the hydraulic component of the unconventional adaptive route (UncAR), and a nonlinear HC for the drug-dependent component of the UncAR. The proposed model is implemented in a computational virtual laboratory to study the value attained by the IOP under physiological and pathological conditions. Simulation results (i) confirm the conjecture that the UncAR acts as a relief valve under pathological conditions, (ii) indicate that the drug-dependent AR is the major opponent to IOP increase in the case of elevated trabecular meshwork resistance, and (iii) support the use of the model as a quantitative tool to complement in vivo studies and help design and optimize medications for ocular diseases.

Assessment of the Efficiency of Measuring Foot and Ankle Edema with a 3D Portable Scanner.

Background: To prospectively evaluate the reliability of a portable optical scanner compared to the water displacement technique for volumetric measurements of the foot and ankle and to compare the acquisition time associated with these two methods. Methods: Foot volume was measured in 29 healthy volunteers (58 feet, 24 females and 5 males) by a 3D scanner (UPOD-S 3D Laser Full-Foot Scanner®) and by water displacement volumetry. Measurements were performed on both feet, up to a height of 10 cm above the ground. The acquisition time for each method was evaluated. The Kolmogorov-Smirnov test, Lin's Concordance Correlation Coefficient, and a Student's t-test were performed. Results: Mean foot volume was 869.7 +/- 165.1 cm3 (3D scanner) versus 867.9 +/- 155.4 cm3 (water-displacement volumetry) (p < 10-5). The concordance of measurements was 0.93, indicative of a high correlation between the two techniques. Volumes were 47.8 cm3 lower when using the 3D scanner versus water volumetry. After statistically correcting this underestimation, the concordance was improved (0.98, residual bias = -0.03 +/- 35.1 cm3). The mean examination time was 4.2 +/- 1.7 min (3D optical scanner) versus 11.1 +/- 2.9 min (water volumeter) (p < 10-4). Conclusions: Ankle/foot volumetric measurements performed using this portable 3D scanner are reliable and fast and can be used in clinical practice and research.

Thoracogenic scoliosis: coronal deformity progression in paediatric patients.

PURPOSE: To assess the risk of developing thoracogenic scoliosis (THS) in paediatric patients, depending on the side of lateral thoracotomy (LT) and of spine deviation in the coronal plane by means of logistic regression and scoliosis-free survival analyses. METHODS: A total of 307 consecutive patients undergoing LT were retrospectively reviewed; 32 patients met the inclusion criteria: 1) underwent LT and developed THS; 2) age < 15 years at LT; 3) clinical and radiographic follow-up ≥ 5 years. Patients were divided into ipsilateral group (convexity ipsilateral to LT) and contralateral group (convexity contralateral to LT). RESULTS: The mean follow-up was 10 ± 4.7 in the ipsilateral group (n = 13) and 12 ± 4.8 years in the contralateral group (n = 19). The contralateral group underwent LT at a younger age (4.4 vs 6.4 years, p = 0.55), developed more severe coronal deformity (27.8° vs 18.9°, p = 0.15), had higher rate of THS > 20° (47.5% vs 38.4%; p = 0.34) and > 45° (21.1% vs 0%; p = 0.99). The mean time from LT to THS diagnosis was 4.2 ± 2.9 in ipsilateral group and 5.5 ± 4.2 years in contralateral group. Left-side LT (p = 0.03) and age > 5 years (p = 0.01) showed a lower risk of THS diagnosis. The group variable had a statistically significant effect on the risk of developing THS > 45° (p = 0.03). CONCLUSION: In this series, children that developed THS with a convexity contralateral to the side of LT had more severe and progressive coronal spine deformity. LEVEL OF EVIDENCE: III.

Interrelations Between the Too-Long Anterior Calcaneal Process, Hind and Mid-tarsal Bone Volumes, Angles and Osteochondral Lesion of the Dome of the Talus: Analysis by Software Slicer of 69 CT Scan of Feet.

Introduction: Although the association between Too-Long Anterior Calcaneal Process (TLACP) and osteochondral lesion of the dome of the talus (OCL) has been hypothesized, no study has investigated the interrelations between TLACP, hind and mid-tarsal volumes and angles and the development of OCL. The main goals of this work are: (1) to measure the volume of the calcaneum, talus, navicular and cuboid in subjects with and without TLACP; (2) to evaluate the angular relationships between talus, calcaneum and navicular in subjects with and without TLACP; (3) to assess whether TLACP has an effect on the volume of OCL. Methods: This is a retrospective study of 69 CT scans of 54 consecutive children aged 11-15 years who had undergone a CT scan due to symptomatology suggestive of TLACP. The 3D Slicer software allowed to calculate the volume of the talus, calcaneum, navicular, cuboid, TLACP and OCL (in cm3). The PACS system was used to perform the angular measurements (in degrees) between talus, calcaneum and navicular in the frontal, axial and sagittal plane. Results: Amid the 69 CT scans, 49 were found to have pathologies related to TLACP (71%, TLACP Group) and 20/69 were normal (29%, Control Group). The mean hind and mid-tarsal bone volumes of the TLACP group were comparable to those of the control group. There were 40 (81.6%) OCLs detected exclusively in pathological feet (TLACP group); 32 lesions were medial (80%), and 8 lesions were lateral (20%). According to Ferkel and Sgaglione CT Staging System, there were 22 (55%) stage 1 lesions, 5 (12.5%) stage 2A, 3 (7.5%) stage 2B and 10 (25%) stage three lesions. Only the angle between the talus and calcaneum in the frontal plane was significantly lower in pathological feet with respect to the control group (p < 0.001). In pathological feet, the talus was supinated, and the calcaneus pronated. Conclusions: TLACP tend to stiffen the foot, modifying its biomechanics and leading to supination of the talus and pronation of the calcaneum. This induces an overpressure at the medial side of the talus where we observed a greater frequency of medial OCL with larger volume than lateral OCL. Level of Evidence: III.

Soft tissue sarcomas of the buttock: A systematic review and meta-analysis.

BACKGROUND: Soft tissue sarcomas of the buttock (BSTS) are historically associated with a poor prognosis. The literature includes retrospective studies with small sample size. It is difficult to estimate the rate of local recurrence (LR), distant metastasis (DM) and overall survival (OS). A systematic review and meta-analysis was deployed to summarize the available information on BSTS patients that underwent surgical treatment. METHODS: The PubMed, EMBASE, Scopus and Google Scholar databases were reviewed for eligible studies following PRISMA guidelines. INCLUSION CRITERIA: (1) primary BSTS confirmed by pathological biopsy (2) indication for surgical treatment (3) reporting either the rate of LR, DM, or OS at 5-year (4) articles published up to December 2021 (5) english language. The Methodological Index for Non-Randomized Studies (MINORS) was applied for the quality appraisal. RESULTS: Six eligible studies with 216 BSTS patients were identified. Most patients underwent surgical resection, associated with radiation therapy. The most represented histological types were liposarcoma (n = 43, 19,9%), rhabdomyosarcoma (n = 27, 12.5%), and undifferentiated pleomorphic sarcoma (n = 23, 10.6%). High-grade tumor rates ranged from 37% to 88.2%, marginal resection rates from 20.3% to 50%, LR rates from 0% to 62.5%, DM rates from 37.5% to 62.5%. The pooled 5-year OS from 1941 to 2002 was 41% (IC95%: 33%-49%). The average MINORS score was 9.3 (range: 6 to 11). CONCLUSIONS: Surgical resection of BSTS had on average dissatisfactory outcomes, and the 5-year overall survival was poor, with high rates of local recurrence and distant metastasis. An effort to collect new data with a higher level of evidence is warranted.

Common carotid artery medialization and fracture dislocation of the cervical spine.

PURPOSE: To describe the management of the discovery of a retropharyngeal carotid artery in the context of a cervical dislocation. DESCRIPTION OF THE CASE: A 68-year-old female presented acute neck pain and incomplete tetraplegia following a fall on the stairs. Radiographs, contrast-enhanced computed tomography scan and magnetic resonance of the cervical spine revealed a C5-C6 bi-articular dislocation. A detailed preoperative assessment of the images discovered a medialization of the left common carotid artery. An external reduction and a left anterior cervical approach allowed a careful management of the vascular variation and an anterior C5-C6 arthrodesis. At six months, a full neurological recovery was assessed and radiographs demonstrated successful fusion of the cervical arthrodesis. DISCUSSION/CONCLUSION: Anatomical features such as medialization of the common carotid artery may affect patients with traumatic cervical spine injuries. The severity of the traumatic bone lesions should not overshadow the preoperative analysis of the adjacent anatomical structures encountered during the surgical approach, even in an emergency situation.

Thoracogenic scoliosis: a retrospective review of 129 pediatric patients with a mean follow-up of 10 years.

PURPOSE: To determine the midterm outcome of lateral thoracotomy (LT) in skeletally immature patients concerning thoracogenic scoliosis development and lung parenchyma resection (LPR) extent. METHODS: In total, 129 children met the inclusion criteria: (1) LT during the study period; (2) skeletally immature at the time of LT; (3) clinical and radiographic follow-up of at least 3 years; and (4) no spinal or thoracic deformity on radiographs before LT. Patients were grouped according to their underlying disease, age at LT, and LPR extent. Radiographic parameters were assessed. Kaplan-Meier survival curves and univariate and multivariate analysis were performed. RESULTS: Of 129, 108 patients underwent pneumonectomy (9; 9.1%), lobectomy (79; 61.2%), segmentectomy (20; 15.5%) and 21 patients LT without LPR. The mean age at LT and at last radiological follow-up was 5.5 years (birth-17.8) and 15.2 years (3.4-33.2). The mean follow-up was 10 years (3-28.1). Scoliosis developed on average 5.3 years after LT. The mean Cobb angle was 22.1° (11-90°); > 10° in 37/129 patients (28.7%), of whom 5/129 (3.9%) had > 45°. The average vertebral rotation was 16.2° (2-43°; grade 0-II). RVAD was 26.5° (8°-33°) and 15.3° (2-43°) in patients with Cobb > 45° and ≤ 45°. Gender, age at surgery, and extent of LPR were not risk factors for post-thoracotomy scoliosis (p > 0.05), although younger patients developed a more severe deformity. CONCLUSION: Although post-thoracotomy scoliosis is not associated with significant rotation, the risk of curve progression > 45° is relatively high. Regular follow-up is required as scoliosis may develop several years after LT with or without LPR.

A multi-scale/multi-physics model for the theoretical study of the vascular configuration of retinal capillary plexuses based on OCTA data.

The retinal tissue is highly metabolically active and is responsible for translating the visual stimuli into electrical signals to be delivered to the brain. A complex vascular structure ensures an adequate supply of blood and oxygen, which is essential for the function and survival of the retinal tissue. To date, a complete understanding of the configuration of the retinal vascular structures is still lacking. Optical coherence tomography angiography has made available a huge amount of imaging data regarding the main retinal capillary plexuses, namely the superficial capillary plexuses (SCP), intermediate capillary plexuses (ICP) and deep capillary plexuses (DCP). However, the interpretation of these data is still controversial. In particular, the question of whether the three capillary plexuses are connected in series or in parallel remains a matter of debate. In this work, we address this question by utilizing a multi-scale/multi-physics mathematical model to quantify the impact of the two hypothesized vascular configurations on retinal hemodynamics and oxygenation. The response to central retinal vein occlusion (CRVO) and intraocular pressure (IOP) elevation is also simulated depending on whether the capillary plexuses are connected in series or in parallel. The simulation results show the following: (i) in the in series configuration, the plexuses exhibit a differential response, with DCP and ICP experiencing larger pressure drops than SCP; and (ii) in the in parallel configuration, the blood flow redistributes uniformly in the three plexuses. The different vascular configurations show different responses also in terms of oxygen profiles: (i) in the in series configuration, the outer nuclear layer, outer plexiform layer and inner nuclear layer (INL) are those most affected by CRVO and IOP elevation; and (ii) in the in parallel configuration the INL and ganglion cell layer are those most affected. The in series results are consistent with studies on paracentral acute middle maculopathy, secondary to CRVO and with studies on IOP elevation, in which DCP and ICP and the retinal tissues surrounding them are those most affected by ischemia. These findings seem to suggest that the in series configuration better describes the physiology of the vascular retinal capillary network in health and disease.

Fluid and protein exchange in microvascular networks: Importance of modelling heterogeneity in geometrical and biophysical properties.

KEY POINTS: Microvascular network architecture defines coupling of fluid and protein exchange. Network arrangements markedly reduce capillary hydrostatic pressures and resting fluid movement at the same time as increasing the capacity for change The presence of vascular remodelling or angiogenesis puts constraints of network behaviour The sites of fluid and protein exchange can be segregated to different portions of the network Although there is a net filtration of fluid from a network of exchange vessels, there are specific areas where fluid moves into the circulation (reabsorption) and, when protein is moving into tissue, the amount is insufficient under basal conditions to result in changes in oncotic pressure. ABSTRACT: Integration of functional results obtained across scales, from chemical signalling to the whole organism, is a daunting task requiring the marriage of experimental data with mathematical modelling. In the present study, a novel coupled computational fluid dynamics model is developed incorporating fluid and protein transport using measurements in an in vivo frog (Rana pipiens) mesenteric microvascular network. The influences of network architecture and exchange are explored systematically under the common assumptions of structurally and functionally identical microvessels (Homogeneous Scenario) or microvessels classified by position in flow (Class Uniform Scenario), which are compared with realistic microvascular network components (Heterogeneous Scenario). The model incorporates ten quantities that vary within a microvessel; pressure boundary conditions are calibrated against experimental measurements. The Homogeneous Scenario standard model showed that assuming a single 'typical' capillary hides the influence of vessels arranged into a network architecture, where capillary hydrostatic pressures (pT ) are reduced, resulting in both a nonuniform distribution of blood flow and reduced volume flow rate (Jf,T ). In the Class Uniform Scenario pT was further attenuated to produce a ∼60% reduction in Jf,T . Finally, the Heterogeneous Scenario, incorporating measures of individual vessel surface area, demonstrates additional lowering of pT from inlet values favouring a >70% reduction of Jf,T in the face of a ∼120% increase in protein movement into the tissues relative to the Homogeneous Scenario. Beyond the impacts of network architecture, an unanticipated finding was the influence of a blind-end microvessel on model convergence, indicating a profound influence of the largely unexplored dynamics of vascular remodelling on tissue perfusion.

Physics-based modeling of Age-related Macular Degeneration-A theoretical approach to quantify retinal and choroidal contributions to macular oxygenation.

We developed a mathematical model to characterize how macular oxygenation may be affected by abnormalities in the retinal and choroidal oxygen supplies. The macular region is modeled as a layered structure including: ganglion cell and nerve fiber layers, inner plexiform layer, inner nuclear layer, outer plexiform layer, outer nuclear layer, inner segment of photoreceptors layer and retinal pigmented epithelium. Each layer is characterized by specific levels of oxygen consumption. The vitreous and the choroid are located at the macula boundary and provide oxygen via boundary conditions of Dirichlet type. The three capillary plexi (superficial, intermediate, and deep) of the retinal circulation pierce the macular layers and provide oxygen via a volumetric source that depends on the retinal blood flow. Oxygen profiles through the macular tissue are calculated by simulating the balance among oxygen supply, consumption and diffusion in: (a) physiological baseline conditions; (b) retinal blood flow reduced by 10%, 30% and 50% with respect to baseline; (c) choroidal oxygen level diminished by 10%, 30% and 50% with respect to baseline. Model simulations predict that: (1) the oxygenation of the foveal avascular zone is not affected by reduction in retinal blood flow; (2) a reduction in choroidal oxygen supply significantly affects the outer layers, especially the photoreceptors and outer nuclear layers; (3) the impact of reduction in choroidal oxygen supply is larger in the region more proximal to the macular center; (4) the impact of reduction in retinal blood flow is larger in the region more proximal to the macular periphery. The proposed mathematical model suggests that changes in retinal and choroidal oxygen supplies impact the oxygenation of the macular tissue differentially. These results may help better understand the pathogenesis of macular degeneration.

Photoelectrochemistry and Drift-Diffusion Simulations in a Polythiophene Film Interfaced with an Electrolyte.

Although the efficiency of organic polymer-based retinal devices has been proved, the interpretation of the working mechanisms that grant photostimulation at the polymer/neuron interface is still a matter of debate. To contribute solving this issue, we focus here on the characterization of the interface between poly(3-hexyltiophene) films and water by the combined use of electrochemistry and mathematical modeling. Simulations well reproduce the buildup of photovoltage (zero current condition) upon illumination of the working electrode made by a polymer film deposited onto an indium tin oxide (ITO) substrate. Due to the essential unipolar transport in the photoexcited film, diffusion leads to a space charge separation that is responsible for the initial photovoltage. Later, electron transfer reactions toward oxygen in the electrolyte extract negative charge from the polymer. In spite of the simple model studied, all of these considerations shed light on the possible coupling mechanisms between the polymeric device and the living cell, supporting the hypothesis of pseudocapacitive coupling.

DDH in the Walking Age: Review of Patients with Long-Term Follow-Up.

INTRODUCTION: The best treatment option in children with late detected DDH is still a subject of much controversy and only few studies have investigated the long-term outcome of treatment in such patients. We performed a systematic review to assess long-term outcome of late detected DDH hips treated after walking age. METHODS: Studies met inclusion criteria if they: (1) reported at least 30 hips treated; (2) included children aged between 9 months and 12 years; (3) treatment indication was late detected DDH after walking age; (4) presented a minimum follow-up of 10 years; (5) reported a clinical or radiological outcome. The Kaplan-Meier method was used to evaluate long-term survival according to clinical and radiological outcomes. The rate of total hip replacement (THR) was retrieved. RESULTS: From a total of 6561 articles, 13 articles with grade IV level of evidence were included in our review. A total of 988 hips in 800 patients with a mean follow-up of 27.9 years (range 10-67) were included. The mean age at surgery was 3.3 years (range, 9 months-12 years). The rate of THR increased according to the length of final follow-up. In particular, all studies reported no case of THR at 23.5 years of follow-up, a rate of 10.2% of THR between 30 and 40 years of follow-up and a rate of 35.6% of THR in patients with follow-up more than 40 years. CONCLUSIONS: In patients with late detected DDH, most THR became necessary more than 30 years after the index procedure and their number increased further after 40 years and more of follow-up. Late detected DDH diagnosed after walking age is a life-long disease.

Neurodegenerative Disorders of the Eye and of the Brain: A Perspective on Their Fluid-Dynamical Connections and the Potential of Mechanism-Driven Modeling.

Neurodegenerative disorders (NDD) such as Alzheimer's and Parkinson's diseases are significant causes of morbidity and mortality worldwide. The pathophysiology of NDD is still debated, and there is an urgent need to understand the mechanisms behind the onset and progression of these heterogenous diseases. The eye represents a unique window to the brain that can be easily assessed via non-invasive ocular imaging. As such, ocular measurements have been recently considered as potential sources of biomarkers for the early detection and management of NDD. However, the current use of ocular biomarkers in the clinical management of NDD patients is particularly challenging. Specifically, many ocular biomarkers are influenced by local and systemic factors that exhibit significant variation among individuals. In addition, there is a lack of methodology available for interpreting the outcomes of ocular examinations in NDD. Recently, mathematical modeling has emerged as an important tool capable of shedding light on the pathophysiology of multifactorial diseases and enhancing analysis and interpretation of clinical results. In this article, we review and discuss the clinical evidence of the relationship between NDD in the brain and in the eye and explore the potential use of mathematical modeling to facilitate NDD diagnosis and management based upon ocular biomarkers.

Corrections to "Cardiovascular Function and Ballistocardiogram: A Relationship Interpreted via Mathematical Modeling" [Oct 19 2906-2917].

Presents a missing funding acknowledgment for Dr. Mihail Popescu in the above named paper.

A Theoretical Approach for the Electrochemical Characterization of Ciliary Epithelium.

The ciliary epithelium (CE) is the primary site of aqueous humor (AH) production, which results from the combined action of ultrafiltration and ionic secretion. Modulation of ionic secretion is a fundamental target for drug therapy in glaucoma, and therefore it is important to identify the main factors contributing to it. As several ion transporters have been hypothesized as relevant players in CE physiology, we propose a theoretical approach to complement experimental methods in characterizing their role in the electrochemical and fluid-dynamical conditions of CE. As a first step, we compare two model configurations that differ by (i) types of transporters included for ion exchange across the epithelial membrane, and by (i) presence or absence of the intracellular production of carbonic acid mediated by the carbonic anhydrase enzyme. The proposed model configurations do not include neurohumoral mechanisms such as P2Y receptor-dependent, cAMP, or calcium-dependent pathways, which occur in the ciliary epithelium bilayer and influence the activity of ion transporters, pumps, and channels present in the cell membrane. Results suggest that one of the two configurations predicts sodium and potassium intracellular concentrations and transmembrane potential much more accurately than the other. Because of its quantitative prediction power, the proposed theoretical approach may help relate phenomena at the cellular scale, that cannot be accessed clinically, with phenomena occurring at the scale of the whole eye, for which clinical assessment is feasible.