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Abstract Congenital aniridia is a rare eye disease characterized by loss of PAX6 protein leading to aniridia-associated keratopathy that significantly reduces vision. The miR-204-5p is a possible regulator of PAX6 function and here we evaluate its effect in multiple in vitro and in vivo models. In vitro, miR-204-5p overexpression suppressed vascular factor ANGPT1 in human limbal stem cells (T-LSC) and Pax6-knockdown LSC (mut-LSC), and in primary human limbal epithelial cells (LEC) at the gene and protein levels and following LPS stimulation. However, miR-204-5p inhibited VEGFA expression only in mut-LSCs and LPS-stimulated LEC. Also, miR-204-5p increased PAX6 expression in mut-LSC and differentiated corneal epithelial cells, but not in LEC. Topical miR-204-5p after LPS-induced keratitis in mice failed to suppress Vegfa, Angpt1, Il-1β, and Tnf-α or rescue Pax6 levels in contrast to in vitro results, although it significantly reduced the inflammatory infiltrate in the cornea. In Pax6 Sey/+ aniridia mice, miR-204-5p did not rescue PAX6 levels or suppress Vegfa, Angpt1, or inhibit the ERK1/2 pathway. While short-term miR-204-5p treatment effectively suppresses VEGFA and ANGPT1 and enhances PAX6 expression in multiple corneal epithelia, effects are variable across primary and immortalized cells. Effects of longer-term in vivo treatment, however, require further study.

Abstract Introduction In congenital aniridia caused by mutations in paired box 6 (PAX6), PAX6 influences the migration and differentiation of limbal epithelial cells (LECs), thereby playing a pivotal role in aniridia-associated keratopathy. The antidepressants ritanserin and duloxetine affect PAX6 expression in LECs. Limbal stromal cells, which support limbal epithelial stem cells, are crucial in the limbal stem cell niche. This study explores how ritanserin and duloxetine influence gene expression in primary human limbal stromal cells from subjects with congenital aniridia and from healthy subjects, in vitro. Methods Primary human limbal stromal cells from corneas affected by aniridia (AN-LSCs) (n = 8) and from healthy corneas (LSCs) (n = 8) were isolated and cultured in either low-glucose serum-free (LGSF) or normal-glucose serum-containing (NGSC) media. Cells were treated with 4 µM ritanserin or duloxetine for 24 h. Quantitative PCR (qPCR) and western blot were used to assess the expression of PAX6, FOSL2, TGF-β1, ACTA2A1, LUM, COL1A1, COL5A1, DSG1, FABP5 and ADH7. Results In AN-LSCs with LGSF-medium, ritanserin increased PAX6 messenger RNA (mRNA) (p = 0.007) and decreased TGF-β1 and FOSL2 mRNA levels (P = 0.005, P = 0.038). In addition, TGF-β1 protein levels decreased with both treatments (P = 0.02, P = 0.007), and FABP5 protein level increased, using ritanserin (P = 0.019). In LSCs with LGSF-medium, ACTA2A1 mRNA levels decreased using ritanserin and duloxetine (P = 0.028; P = 0.031), while FABP5 mRNA levels increased with ritanserin treatment (P = 0.003). Also, duloxetine use reduced α-SMA protein (P = 0.013) and increased FABP5 protein levels (P = 0.029). In LSCs with NGSC-medium, ritanserin elevated LUM, FABP5 and ADH7 mRNA and protein levels (P = 0.025, P = 0.003, P = 0.047, P = 0.024, P = 0.013, P = 0.039). Conclusions The results of our study confirmed that the antipsychotropic drugs ritanserin and duloxetine alter PAX6 and TGF-β1 gene expression in AN-LSCs cultured in LGSF-medium. These drugs were found to have an impact on retinoic acid signaling pathways and keratocyte characteristic markers both in LSCs and AN-LSCs, using different culture media.

In most cases, sensors are the means that enable a computer to get information from a process of interest. This requires that the information generated by the sensor can be processed by the computer in a timely manner. However, if accurate data from the sensor is required, an appropriate transduction process is required. There are sensors that generate a frequency-domain output. Since these sensors typically have a short response time, it is required to get the best approximation to their frequency within the shortest time possible. There are different methods for obtaining the frequency value generated by the sensor. Although such methods can be applied, their functioning characteristics are not suitable for application in sensors. The principle of rational approximations is a method that has proven plenty of improvements in comparison to other frequency measurement methods. In this work, the functioning of the principle of rational approximations is explored when different time references are used. After the computational analysis of the principle of rational approximations, it was found out how the reference frequency value affects the measurement process. It was found that if the magnitude of reference and unknown frequencies have an increment in their difference, then the relative error decreases.

Summary:. We introduce a novel technique using augmented reality (AR) on smartphones and tablets, making it possible for surgeons to review perforator anatomy in three dimensions on the go. Autologous breast reconstruction with abdominal flaps remains challenging due to the highly variable anatomy of the deep inferior epigastric artery. Computed tomography angiography has mitigated some but not all challenges. Previously, volume rendering and different headsets were used to enable better three-dimensional (3D) review for surgeons. However, surgeons have been dependent on others to provide 3D imaging data. Leveraging the ubiquity of Apple devices, our approach permits surgeons to review 3D models of deep inferior epigastric artery anatomy segmented from abdominal computed tomography angiography directly on their iPhone/iPad. Segmentation can be performed in common radiology software. The models are converted to the universal scene description zipped format, which allows immediate use on Apple devices without third-party software. They can be easily shared using secure, Health Insurance Portability and Accountability Act–compliant sharing services already provided by most hospitals. Surgeons can simply open the file on their mobile device to explore the images in 3D using “object mode” natively without additional applications or can switch to AR mode to pin the model in their real-world surroundings for intuitive exploration. We believe patient-specific 3D anatomy models are a powerful tool for intuitive understanding and communication of complex perforator anatomy and would be a valuable addition in routine clinical practice and education. Using this one-click solution on existing devices that is simple to implement, we hope to streamline the adoption of AR models by plastic surgeons.

Summary:. Preoperative vascular imaging has become standard practice in the planning of microsurgical breast reconstruction. Currently, translating perforator locations from radiological findings to a patient’s abdomen is often not easy or intuitive. Techniques using three-dimensional printing or patient-specific guides have been introduced to superimpose anatomy onto the abdomen for reference. Augmented and mixed reality is currently actively investigated for perforator mapping by superimposing virtual models directly onto the patient. Most techniques have found only limited adoption due to complexity and price. Additionally, a critical step is aligning virtual models to patients. We propose repurposing suture packaging as an image tracking marker. Tracking markers allow quick and easy alignment of virtual models to the individual patient’s anatomy. Current techniques are often complicated or expensive and limit intraoperative use of augmented reality models. Suture packs are sterile, readily available, and can be used to align abdominal models on the patients. Using an iPad, the augmented reality models automatically align in the correct position by using a suture pack as a tracking marker. Given the ubiquity of iPads, the combination of these devices with readily available suture packs will predictably lower the barrier to entry and utilization of this technology. Here, our workflow is presented along with its intraoperative utilization. Additionally, we investigated the accuracy of this technology.

Zeolites are porous materials that have cavities interconnected by channels. These crystalline materials are composed of Si-O tetrahedral structures, and according to the assembly of such tetrahedral structures, specific crystalline structures are obtained. Until now, it has been said that there are more than 245 different zeolitic frameworks, and since each one has a specific distribution of pores and cavities, each kind of zeolite has a specific area-to-volume ratio. As a result of the type of zeolite structure, the zeolite can exhibit specific properties, i.e., electrical or optical. Moreover, the physical properties of zeolites can be modified after the inclusion of another chemical species in their structure or in their voids, which can result in tuning a zeolite for specific applications. In this work, synthetic zeolites of types LTA, FAU and MFI are characterized by a number of methods. In particular, the data from UV-Vis spectroscopy are analyzed, and the effect of crystalline structure on properties such as optical bandgap, refractive index, absorption coefficient, incident photon frequency, and extinction coefficient is studied.

This paper introduces an autonomous robot designed for in-pipe structural health monitoring of oil/gas pipelines. This system employs a 3D Optical Laser Scanning Technical Vision System (TVS) to continuously scan the internal surface of the pipeline. This paper elaborates on the mathematical methodology of 3D laser surface scanning based on dynamic triangulation. This paper presents the mathematical framework governing the combined kinematics of the Mobile Robot (MR) and TVS. It discusses the custom design of the MR, adjusting it to use of robustized mathematics, and incorporating a laser scanner produced using a 3D printer. Both experimental and theoretical approaches are utilized to illustrate the formation of point clouds during surface scanning. This paper details the application of the simple and robust mathematical algorithm RANSAC for the preliminary processing of the measured point clouds. Furthermore, it contributes two distinct and simplified criteria for detecting defects in pipelines, specifically tailored for computer processing. In conclusion, this paper assesses the effectiveness of the proposed mathematical and physical method through experimental tests conducted under varying light conditions.

Long-duration spaceflight can have adverse effects on human health. One of the most common ocular conditions experienced by astronauts is dry eye disease (DED). Symptoms of DED include feelings of eye irritation, eye strain, foreign body sensation and blurred vision. Over 30% of International Space Station expedition crew members reported irritation and foreign body sensation. We reviewed the current literature on the prevalence and mechanisms of DED in astronauts and its potential implications for long-duration spaceflight, including the influence of environmental factors, such as microgravity and fluid shift on tear film physiology in space. DED has negative effects on astronaut performance, which is why there is a need for further research into the pathophysiology and countermeasures. As an in-flight countermeasure, neurostimulation seems to be among the most promising options.

The foot is considered a wonder of biological engineering due to its structure, formed by bones, ligaments, and tendons that collaborate to ensure stability and mobility. A key area often examined by medical professionals in patients with diabetic feet is the plantar surface, due to the risk of ulcer development. If left untreated, these ulcers can lead to severe complications, including amputation of the toe, foot, or even the limb. Interpolation methods are used to find areas with overloads in a system of sensor maps that are based on capacitive, load cells, or force-sensitive resistors (FSRs). This manuscript presents the assessment of linear, nearest neighbors, and bicubic methods in comparison with ground truth to calculate the root mean square error (RMSE) in two assessments using a dataset of eight healthy subjects, four men and four women, with an average age of 25 years, height of 1.63 m, and weight of 72 kg with shoe sizes from 7.3 USA using FSR map with 48 sensors. Additionally, this paper describes the conditioning circuit development to implement a plantar surface system that enables interpolating loads on the plantar surface. The proposed system's results show that the first assessment indicates an RMSE of 0.089, 0.126, and 0.089 for linear, nearest neighbor, and bicubic methods, while the second assessment shows a mean RMSE for linear, nearest neighbor, and bicubic methods of 0.114, 0.159, and 0.112. [ABSTRACT FROM AUTHOR]

Individuals' lifestyles are affected by valgus and varus deformities in the rearfoot, causing pain in the joints and plantar surface due to the misalignment between the tibial and calcaneus. In orthopedics, medical professionals measure this misalignment by using X-ray systems and goniometers. The X-ray emits ionizing radiation that can cause damage through cumulative exposure over a lifetime, whereas the goniometer will produce measurement errors. This patent review conducted a technological search of systems and methods across various databases using inclusion and exclusion criteria. These thirty-five obtained patents provide valuable information about mechanical, electronic, and mechatronic technologies and non-ionizing radiation to evaluate valgus and varus deformities. The patents are classified into stationary mechanisms, stationary electronic devices, dynamic mechanisms, dynamic electronic devices, stationary mechatronic devices, and dynamic mechatronic devices. They are further categorized based on their measurement methods as either visual or automatic. Additionally, the patents are grouped by usage mode into sitting, standing, and walking. This patent review aims to provide medical professionals with little-known techniques for measuring and evaluating the rearfoot alignment. [ABSTRACT FROM AUTHOR]

The study objective was to evaluate the effect of single and/or extra doses of vitamin C (VC) on water-restricted (WR) Xhosa goats, by evaluating their intake, digestibility, nitrogen, and mineral balance during summer. Goats (42) were randomly divided into seven groups: GI (control, received ad libitum water daily), GII (WR-70% of ad lib.), GIII (WR-50% of ad lib.), GIV (WR-70% of ad lib. + VC [3 g/day orally]), GV (WR-50% of ad lib. + VC [3 g/day orally]), GVI (WR-70% of ad lib. + VC [3 g/day orally + 5 g extras every eighth day]), and GVII (WR-50% of ad lib. + VC [3 g/day orally + 5 g extras on every eighth day]). The experiment was a complete randomized design. Data obtained were analysed using the general linear model (PROC GLM) of SAS procedure. The depression in nutrients intake was lessened with VC supplementation. Water-restriction effect was not significant on nutrient intake/metabolic weight. Retained nitrogen increased with water-restriction levels but not influenced by VC. NH3–N significantly decreased as the level of water restriction increases, while the pH was similar across the WR groups. Supplementation of VC failed to significantly influence the depression in apparent digestibility and digestible nutrients induced by water restriction levels. The retained Ca, K, and Mg increased with levels of water restriction.

This paper introduces an autonomous robot designed for in-pipe structural health monitoring of oil/gas pipelines. This system employs a 3D Optical Laser Scanning Technical Vision System (TVS) to continuously scan the internal surface of the pipeline. This paper elaborates on the mathematical methodology of 3D laser surface scanning based on dynamic triangulation. This paper presents the mathematical framework governing the combined kinematics of the Mobile Robot (MR) and TVS. It discusses the custom design of the MR, adjusting it to use of robustized mathematics, and incorporating a laser scanner produced using a 3D printer. Both experimental and theoretical approaches are utilized to illustrate the formation of point clouds during surface scanning. This paper details the application of the simple and robust mathematical algorithm RANSAC for the preliminary processing of the measured point clouds. Furthermore, it contributes two distinct and simplified criteria for detecting defects in pipelines, specifically tailored for computer processing. In conclusion, this paper assesses the effectiveness of the proposed mathematical and physical method through experimental tests conducted under varying light conditions. [ABSTRACT FROM AUTHOR]

Purpose: Congenital aniridia is a rare disease, which is in most cases related to PAX6 haploinsufficiency. Aniridia associated keratopathy (AAK) also belongs to ocular signs of congenital aniridia. In AAK, there is corneal epithelial thinning, corneal inflammation, vascularization and scarring. In advanced stage AAK, typically, conjunctival epithelial cells slowly replace the corneal epithelium. Based on previous results we hypothesize that alterations of the conjunctival cells in congenital aniridia may also support the corneal conjunctivalization process. The aim of this study was to identify deregulated proteins in conjunctival impression cytology samples of congenital aniridia subjects. Methods: Conjunctival impression cytology samples of eight patients with congenital aniridia [age 34.5 ± 9.9 (17–51) years, 50% female] and eight healthy subjects [age 34.1 ± 11.9 (15–54) years, 50% female] were collected and analysed using mass spectrometry. Proteomic profiles were analysed in terms of molecular functions, biological processes, cellular components and pathway enrichment using the protein annotation of the evolutionary relationship (PANTHER) classification system. Results: In total, 3323 proteins could be verified and there were 127 deregulated proteins (p < 0.01) in congenital aniridia. From the 127 deregulated proteins (DEPs), 82 altered biological processes, 63 deregulated cellular components, 27 significantly altered molecular functions and 31 enriched signalling pathways were identified. Pathological alteration of the biological processes and molecular functions of retinol binding and retinoic acid biosynthesis, as well as lipid metabolism and apoptosis related pathways could be demonstrated. Conclusions: Protein profile of conjunctival impression cytology samples of aniridia subjects identifies alterations of retinol binding, retinoic acid biosynthesis, lipid metabolism and apoptosis related pathways. Whether these changes are directly related to PAX6 haploinsufficiency, must be investigated in further studies. These new findings offer the possibility to identify potential new drug targets. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a highly prevalent multifactorial disease for which Diabetes Mellitus (DM) is a risk factor. Abnormal phosphorylation and aggregation of tau is a key hallmark of AD. In animal models, DM induces or exacerbates the phosphorylation of tau, suggesting that DM may influence the risk at AD by directly facilitating tau pathology. Previously we reported that tau phosphorylation induced in response to metabolic stress is reversible. Since identification and understanding of early players in tau pathology is pivotal for therapeutic intervention, we here investigated the mechanism underlying tau phosphorylation in the diabetic brain and its potential for reversibility. To model DM we used streptozotocin-treatment to induce insulin deficiency in rats. Insulin depletion leads to increased tau phosphorylation in the brain and we investigated the activation status of known tau kinases and phosphatases in this model. We identified protein kinase A (PKA) as a tau kinase activated by DM in the brain. The potential relevance of this signaling pathway to AD pathogenesis is indicated by the increased level of active PKA in temporal cortex of early stage AD patients. Our data indicate that activation of PKA and tau phosphorylation are associated with insulin deficiency per se, rather than the downstream energy deprivation. In vitro studies confirm that insulin deficiency results in PKA activation and tau phosphorylation. Strikingly, both active PKA and induced tau phosphorylation are reversed upon insulin treatment in the steptozotocin animal model. Our data identify insulin deficiency as a direct trigger that induces the activity of the tau kinase PKA and results in tau phosphorylation. The reversibility upon insulin treatment underscores the potential of insulin as an early disease-modifying intervention in AD and other tauopathies.

When a frequency domain sensor is under the effect of an input stimulus, there is a frequency shift at its output. One of the most important advantages of such sensors is their converting a physical input parameter into time variations. In consequence, changes of an input stimulus can be quantified very precisely, provided that a proper frequency counter/meter is used. Unfortunately, it is well known in the time-frequency metrology that if a higher accuracy in measurements is needed, a longer time for measuring is required. The principle of rational approximations is a method to measure a signal frequency. One of its main properties is that the time required for measuring decreases when the order of an unknown frequency increases. In particular, this work shows a new measurement technique, which is devoted to measuring the frequency shifts that occur in frequency domain sensors. The presented research result is a modification of the principle of rational approximations. In this work a mathematical analysis is presented, and the theory of this new measurement method is analysed in detail. As a result, a new formalism for frequency measurement is proposed, which improves resolution and reduces the measurement time.

The use of sensors is a primary need in robotic systems. There are sensors that generate a signal whose frequency depends on input stimulus. The application of such sensors is desirable due to their short response time, accuracy, and resolution. For proper use of these sensors, adequate frequency measurement is required. The principle of rational approximations is a method for frequency estimation that has advantages over other measurement methods. Some of them include not a fixed sampling time, insensitivity to jitter, and accuracy limited by the reference stability. Nevertheless, there are some measurement parameters with a not well-researched effect in measurement process. The objective of this work is to elucidate how the phase of input signals (measurand and reference) affects the frequency measurement process.