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Regenerative medicine (RM) has emerged as a promising and revolutionary solution to address a range of unmet needs in healthcare, including ophthalmology. Moreover, RM takes advantage of the body’s innate ability to repair and replace pathologically affected tissues. On the other hand, despite its immense promise, RM faces challenges such as ethical concerns, host-related immune responses, and the need for additional scientific validation, among others. The primary aim of this review is to present a high-level overview of current strategies in the domain of RM (cell therapy, exosomes, scaffolds, in vivo reprogramming, organoids, and interspecies chimerism), centering around the field of ophthalmology. A search conducted on clinicaltrials.gov unveiled a total of at least 209 interventional trials related to RM within the ophthalmological field. Among these trials, there were numerous early-phase studies, including phase I, I/II, II, II/III, and III trials. Many of these studies demonstrate potential in addressing previously challenging and degenerative eye conditions, spanning from posterior segment pathologies like Age-related Macular Degeneration and Retinitis Pigmentosa to anterior structure diseases such as Dry Eye Disease and Limbal Stem Cell Deficiency. Notably, these therapeutic approaches offer tailored solutions specific to the underlying causes of each pathology, thus allowing for the hopeful possibility of bringing forth a treatment for ocular diseases that previously seemed incurable and significantly enhancing patients’ quality of life. As advancements in research and technology continue to unfold, future objectives should focus on ensuring the safety and prolonged viability of transplanted cells, devising efficient delivery techniques, etc.

Background: Leigh syndrome spectrum (LSS) is a novel nomenclature that encompasses both classical Leigh syndrome and Leigh-like phenotypes. Given the heterogeneity of disease presentation, a new consensus published recently addressed the main issues and proposed general guidelines towards diagnosis. Based on these recommendations, we developed a simple pipeline that can be useful in the diagnosis of LSS. Methods: We combined previously published criteria with our own experience to achieve a diagnostic framework that can provide faster satisfactory results with fewer resources. Results: We suggest adding basic biochemical tests for amino acids, acylcarnitine, and urinary organic acids as parallel investigations, as these results can be obtained in a short time. This approach characterized 80% of our cohort and promoted specific intervention in 10% of confirmed cases. Conclusions: Genetic studies are crucial in the diagnosis of LSS, but they are time-consuming and might delay tailored interventions. Therefore, we suggest adding more affordable and less complex biochemical studies as primary tests when investigating treatable causes of LSS.

The elements of the bidiagonal decomposition (BD) of a totally positive (TP) collocation matrix can be expressed in terms of symmetric functions of the nodes. Making use of this result, and studying the relation between Wronskian and collocation matrices of a given TP basis of functions, we can express the entries of the BD of Wronskian matrices as the values of certain symmetric functions evaluated at a single node. Moreover, in the case of polynomial bases, we obtain compact formulae for the entries of the BD of their Wronskian matrices. Interesting examples illustrate the applications of the obtained formulae.

Advanced materials (AMs) encompass materials that feature improved properties compared to common counterparts [...]

Agricultural stubble burning is the third largest source of air pollution after vehicular and industrial emissions. Fine particulate matter (PM2.5), volatile organic compounds (VOCs), carbon monoxide (CO), nitrogen dioxide (NO2), and black carbon (BC) are some of the pollutants emitted during such burning events. The Lower Rio Grande Valley (RGV) region of South Texas is a major hub of agricultural activity, and sugarcane farming is one of them. Unfortunately, this activity results in episodic events of high air pollution in this low-resourced, Hispanic/Latino majority region of the U.S.–Mexico border. This study presents results from a sugarcane site in La Feria, South Texas, where the air quality was monitored before, during, and after the sugarcane stubble burning. Various parameters were monitored on an hourly basis from 24 February 2022 to 4 April 2022. Our results demonstrate high levels of all the monitored pollutants during the burning phase in contrast to the pre- and post-burning period. The black carbon levels went up to 6.43 µg m−3 on the day of burning activity. An increase of 10%, 11.6%, 25.29%, 55%, and 67.57% was recorded in the PM1, PM2.5, PM10, Black Carbon, and CO levels, respectively, during the burning period in comparison with the total study period. The absorption Ångström exponent value reached a maximum value of 2.03 during the burning activity. ThePM2.5/PM10 ratio was 0.87 during the burning activity. This study also highlights the importance for continuous monitoring of air quality levels due to stubble burning in the Lower Rio Grande Valley Region of South Texas.

With advances in technological sciences, individuals can utilize low-cost air monitoring sensors to record air quality at homes, schools, and businesses. Air quality data collected from LCSs are publicly accessible, informing the community of the air quality around them. It is important to measure local and regional particulate matter (PM) concentrations to keep the public involved, especially those with specific health concerns, such as asthma, wheezing, and seasonal allergies. The number of studies involving the use of LCSs to evaluate PM levels is increasing with more manufacturers producing ‘easy to use’ LCSs targeting the public. The goal of this review is to understand and incorporate the findings from studies using LCSs to analyze PM of various sizes, i.e., PM1, PM2.5, PM4, and PM10. This review integrates analyses from 51 different studies in 14 countries, including the U.S. The findings indicate spatial heterogeneity in the PM concentrations across a region. Some of the low-cost sensor manufacturers mentioned in these studies include Plantower, AQMesh, Alpha-sense, PurpleAir, E-MOTEs, and Shinyei. This review emphasizes the importance of LCSs in the field of PM monitoring and its potential to inform the public about their exposure burden, and to aid state and federal decision makers in formulating policies for mitigating the effects of PM pollution in any urban or rural setting.

The mathematical study known as queueing theory has recently become a major point of interest for many government agencies and private companies for increasing efficiency. One such application is vehicle queueing at an international port-of-entry (POE). When queueing, fumes from idling vehicles negatively affect the overall health and well-being of the community, especially the U.S. Customs and Border Protection (CBP) agents that work at the POEs. As such, there is a need to analyze and optimize the border crossing queuing operations to minimize wait times and number of vehicles in the queue and, thus, reduce the vehicle emissions. For this research, the U.S.–Mexico POE located at The Gateway International Bridge in Brownsville, Texas, is used as a case study. Due to data privacy concerns, the hourly wait times for vehicles arriving at the border had to be extracted manually each day using a live wait time tracker online. The data extraction was performed for the month of March 2022. Using these wait times, a queueing simulation software, SIMIO, was used to develop an interactive simulation model and calibrate the service rates. The output from the SIMIO model was then used to develop an artificial neural network (ANN) to predict hourly particulate matter content with an R2 of 0.402. From the ANN, a predictive equation has been developed, which may be used by CBP to make operational decisions and improve the overall efficiency of this POE. Thus, lowering the average wait times and the emissions from idling vehicles in the queue.

Autonomous mobile robots are essential to the industry, and human–robot interactions are becoming more common nowadays. These interactions require that the robots navigate scenarios with static and dynamic obstacles in a safely manner, avoiding collisions. This paper presents a physical implementation of a method for dynamic obstacle avoidance using a long short-term memory (LSTM) neural network that obtains information from the mobile robot’s LiDAR for it to be capable of navigating through scenarios with static and dynamic obstacles while avoiding collisions and reaching its goal. The model is implemented using a TurtleBot3 mobile robot within an OptiTrack motion capture (MoCap) system for obtaining its position at any given time. The user operates the robot through these scenarios, recording its LiDAR readings, target point, position inside the MoCap system, and its linear and angular velocities, all of which serve as the input for the LSTM network. The model is trained on data from multiple user-operated trajectories across five different scenarios, outputting the linear and angular velocities for the mobile robot. Physical experiments prove that the model is successful in allowing the mobile robot to reach the target point in each scenario while avoiding the dynamic obstacle, with a validation accuracy of 98.02%.

Extensions of Filbert and Lilbert matrices are addressed in this work. They are reciprocal Hankel matrices based on Fibonacci and Lucas numbers, respectively, and both are related to Hilbert matrices. The Neville elimination is applied to provide explicit expressions for their bidiagonal factorization. As a byproduct, formulae for the determinants of these matrices are obtained. Finally, numerical experiments show that several algebraic problems involving these matrices can be solved with outstanding accuracy, in contrast with traditional approaches.

The selection of appropriate probiotic strains is vital for their successful inclusion in foods. These strains must withstand processing to reach consumers with ≥106 CFU/g, ensuring effective probiotic function. Achieving this in commercial products is challenging due to sensitivity to temperature during processing. In this work, Lactobacillus reuteri DSM 17938 was microencapsulated by ionic gelation (with alginate or pectin) followed by polymeric coating (with whey protein concentrate or chitosan). Then, such microcapsules were incorporated into a strawberry puree, which was subsequently dehydrated at three temperatures (40 °C, 45 °C, and 50 °C) by Refractance Window®. The ultimate aim was to demonstrate the efficacy of the proposed methods from a technological point of view. Kinetic curves of the probiotic’s viability showed a high cell loading (>109 CFU/g). Additionally, an average encapsulation efficiency of 91% and a particle size of roughly 200 µm were found. A decrease in the viability of the microorganism was observed as drying temperature and time increased. As a demonstration of the above, in a particular case, drying at 45 °C and 50 °C, viable cells were found up to 165 min and 90 min, respectively; meanwhile, drying at 40 °C, viable cells were reported even after 240 min. The greatest viability preservation was achieved with Refractance Window® drying at 40 °C for 240 min when microcapsules coated with whey protein concentrate were incorporated into puree; this procedure showed great potential to produce dehydrated strawberry snacks with moisture (15%), water activity (aw < 0.6), and viability (≥106 CFU/g) suitable for functional foods. The membrane-stabilizing properties of whey protein concentrate could prevent cell damage. In contrast, probiotics in chitosan-coated capsules showed reduced viability, potentially due to antimicrobial properties and the formation of cracks. These findings signify a breakthrough in the production of dehydrated snacks with the addition of probiotics, addressing challenges in preserving the viability of these probiotics during processing; thus, opening the possibility for the development of a probiotic strawberry snack.

Among the many lysosomal storage disorders (LSDs) that would benefit from the establishment of novel cell models, either patient-derived or genetically engineered, is mucopolysaccharidosis type II (MPS II). Here, we present our results on the establishment and characterization of two MPS II patient-derived stem cell line(s) from deciduous baby teeth. To the best of our knowledge, this is the first time a stem cell population has been isolated from LSD patient samples obtained from the dental pulp. Taking into account our results on the molecular and biochemical characterization of those cells and the fact that they exhibit visible and measurable disease phenotypes, we consider these cells may qualify as a valuable disease model, which may be useful for both pathophysiological assessments and in vitro screenings. Ultimately, we believe that patient-derived dental pulp stem cells (DPSCs), particularly those isolated from human exfoliated deciduous teeth (SHEDs), may represent a feasible alternative to induced pluripotent stem cells (iPSCs) in many labs with standard cell culture conditions and limited (human and economic) resources.

The accumulation of microorganisms, plants, algae, or small animals on wet surfaces that have a mechanical function causes biofouling, which can result in structural or other functional deficiencies. The maritime shipping industry must constantly manage biofouling to optimize operational performance, which is a common and long-lasting problem. It can occur on any metal structure in contact with or submerged in ocean water, which represents additional costs in terms of repairs and maintenance. This study is focused on the production of antifouling coatings, made with nanoparticles of copper selenide (CuSe NPs) modified with gum arabic, within a water-base acrylic polymeric matrix. During the curing of the acrylic resin, the CuSe NPs remain embedded in the resin, but this does not prevent the release of ions. The coatings released copper and selenium ions for up to 80 days, and selenium was the element that was released the most. The adhesion of film coatings to metallic substrates showed good adhesion, scale 5B (ASTM D3359 standard). Antimicrobial activity tests show that the coatings have an inhibitory effect on Escherichia coli and Candida albicans. The effect is more noticeable when the coating is detached from the substrate and placed on a growing medium, compared to the coating on a substrate. Scanning electron microscopy (SEM) observations show that nanostructured CuSe coatings are made up of rod-shaped and spherical particles with an average particle size of 101.6 nm and 50 nm, respectively. The energy dispersive X-ray spectroscopy (EDS) studies showed that the ratio of selenium nanoparticles is greater than that of copper and that their distribution is homogeneous.

Resistance and toxicity associated with current treatments for human cytomegalovirus (HCMV) infection highlight the need for alternatives and immunotherapy has emerged as a promising strategy. This study examined the in vitro immunological effects of co-administration of Thymosin-alpha-1 (Tα1) and polyanionic carbosilane dendrimers (PCDs) on peripheral blood mononuclear cells (PBMCs) during HCMV infection. The biocompatibility of PCDs was assessed via MTT and LDH assays. PBMCs were pre-treated with the co-administered compounds and then exposed to HCMV for 48 h. Morphological alterations in PBMCs were observed using optical microscopy and total dendritic cells (tDCs), myeloid dendritic cells (mDCs), and plasmacytoid dendritic cells (pDCs), along with CD4+/CD8+ T cells and regulatory T cells (Treg), and were characterized using multiparametric flow cytometry. The findings revealed that Tα1 + PCDs treatments increased DC activation and maturation. Furthermore, increased co-receptor expression, intracellular IFNγ production in T cells and elevated Treg functionality and reduced senescence were evident with Tα1 + G2-S24P treatment. Conversely, reduced co-receptor expression, intracellular cytokine production in T cells, lower functionality and higher senescence in Treg were observed with Tα1 + G2S16 treatment. In summary, Tα1 + PCDs treatments demonstrate synergistic effects during early HCMV infection, suggesting their use as an alternative therapeutic for preventing virus infection.

Members of the genus Atropa contain various tropane alkaloids, including atropine ((±)-hyoscyamine) and scopolamine, which possess medicinal properties. Preserving the diverse genetic background of wild populations via optimal plant production from seeds could be essential for avoiding the loss of potential uses. We analyzed the germination ecology of two Atropa species comprising the threatened A. baetica and widespread A. belladonna to determine the: (1) influence of temperature, light, and seed age on germination patterns; (2) effects of cold stratification and gibberellic acid (GA3); (3) phenology of seedling emergence in outdoor conditions; (4) phenology of dormancy break and loss of viability in buried seeds; and (5) ability to form persistent soil seed banks. Freshly matured seeds exhibited conditional physiological dormancy, with germination at high temperatures (32/18 °C) but not at low and cold ones (5, 15/4, 20/7 °C). The germination ability increased with time of dry storage and with GA3, thereby suggesting nondeep physiological dormancy. Under outdoor conditions, no seedlings emerged during the first post-sown autumn, but emergence peaks occurred in late winter–early spring. Both species could form small persistent soil seed banks with short durations (3–5 years). A plant production protocol from seeds was established for both taxa.

This paper proposes a new approach to define two frequency trigonometric spline curves with interesting shape preserving properties. This construction requires the normalized B-basis of the space U4(Iα)=span{1,cost,sint,cos2t,sin2t} defined on compact intervals Iα=[0,α], where α is a global shape parameter. It will be shown that the normalized B-basis can be regarded as the equivalent in the trigonometric space U4(Iα) to the Bernstein polynomial basis and shares its well-known symmetry properties. In fact, the normalized B-basis functions converge to the Bernstein polynomials as α→0. As a consequence, the convergence of the obtained piecewise trigonometric curves to uniform quartic B-Spline curves will be also shown. The proposed trigonometric spline curves can be used for CAM design, trajectory-generation, data fitting on the sphere and even to define new algebraic-trigonometric Pythagorean-Hodograph curves and their piecewise counterparts allowing the resolution of C(3 Hermite interpolation problems.

A new class of matrices defined in terms of r-Stirling numbers is introduced. These r-Stirling matrices are totally positive and determine the linear transformation between monomial and r-Bell polynomial bases. An efficient algorithm for the computation to high relative accuracy of the bidiagonal factorization of r-Stirling matrices is provided and used to achieve computations to high relative accuracy for the resolution of relevant algebraic problems with collocation, Wronskian, and Gramian matrices of r-Bell bases. The numerical experimentation confirms the accuracy of the proposed procedure.

Breast milk (BM) is a constantly changing fluid that represents the primary source of nutrition for newborns. It is widely recognized that breastfeeding provides benefits for both the child and the mother, including a lower risk of ovarian and breast cancer, type 2 diabetes mellitus, decreased blood pressure, and more. In infants, breastfeeding has been correlated with a lower risk of infectious diseases, obesity, lower blood pressure, and decreased incidence of respiratory infections, diabetes, and asthma. Various factors, such as the baby’s sex, the health status of the mother and child, the mother’s diet, and the mode of delivery, can affect the composition of breast milk. This review focuses on the biological impact of the nutrients in BM on the development and functionality of vital organs to promote the benefit of health.

We construct one-frequency trigonometric spline curves with a de Boor-like algorithm for evaluation and analyze their shape-preserving properties. The convergence to quadratic B-spline curves is also analyzed. A fundamental tool is the concept of the normalized B-basis, which has optimal shape-preserving properties and good symmetric properties.

Mucopolysaccharidoses (MPSs) are rare inherited lysosomal storage diseases (LSDs) caused by deficient activity in one of the enzymes responsible for glycosaminoglycans lysosomal degradation. MPS II is caused by pathogenic mutations in the IDS gene, leading to deficient activity of the enzyme iduronate-2-sulfatase, which causes dermatan and heparan sulfate storage in the lysosomes. In MPS VI, there is dermatan sulfate lysosomal accumulation due to pathogenic mutations in the ARSB gene, leading to arylsulfatase B deficiency. Alterations in the immune system of MPS mouse models have already been described, but data concerning MPSs patients is still scarce. Herein, we study different leukocyte populations in MPS II and VI disease patients. MPS VI, but not MPS II patients, have a decrease percentage of natural killer (NK) cells and monocytes when compared with controls. No alterations were identified in the percentage of T, invariant NKT, and B cells in both groups of MPS disease patients. However, we discovered alterations in the naïve versus memory status of both helper and cytotoxic T cells in MPS VI disease patients compared to control group. Indeed, MPS VI disease patients have a higher frequency of naïve T cells and, consequently, lower memory T cell frequency than control subjects. Altogether, these results reveal MPS VI disease-specific alterations in some leukocyte populations, suggesting that the type of substrate accumulated and/or enzyme deficiency in the lysosome may have a particular effect on the normal cellular composition of the immune system.

Chicha gum is a natural polymer obtained from the Sterculia striata plant. The hydroxyl groups of its structure have a chemical affinity to form hydrogels, which favors the association with biologically active molecules, such as nerolidol. This association improves the biological properties and allows the material to be used in drug delivery systems. Chicha gum hydrogels associated with nerolidol were produced at two concentrations: 0.01 and 0.02 g mL−1. Then, the hydrogels were characterized by thermogravimetry (TG), Fourier Transform Infrared spectroscopy (FTIR), and rheological analysis. The antibacterial activity was tested against Staphylococcus aureus and Escherichia coli. The cytotoxicity was evaluated against Artemia salina. Finally, an in vivo healing assay was carried out. The infrared characterization indicated that interactions were formed during the gel reticulation. This implies the presence of nerolidol in the regions at 3100–3550 cm−1. The rheological properties changed with an increasing concentration of nerolidol, which resulted in less viscous materials. An antibacterial 83.6% growth inhibition effect was observed using the hydrogel with 0.02 g mL−1 nerolidol. The in vivo healing assay showed the practical activity of the hydrogels in the wound treatment, as the materials promoted efficient re-epithelialization. Therefore, it was concluded that the chicha hydrogels have the potential to be used as wound-healing products.

Paracetamol is one of the most used pharmaceuticals worldwide, but due to its widespread use it is detected in various environmental matrices, such as surface and ground waters, sediments, soils or even plants, where it is introduced mainly from the discharge of wastewater and the use of sewage sludge as fertilizer in agriculture. Its accumulation in certain organisms can induce reproductive, neurotoxic or endocrine disorders, being therefore considered an emerging pollutant. This study reports on the isolation, from sewage sludge produced in wastewater treatment plants (WWTPs), of bacterial strains capable of degrading paracetamol. Up to 17 bacterial strains were isolated, but only two of them, identified as Pseudomonas stutzeri CSW02 and Pseudomonas extremaustralis CSW01, were able to degrade very high concentrations of paracetamol in solution as a sole carbon and energy source, and none of them had been previously described as paracetamol degraders. These bacteria showed the ability to degrade up to 500 mg L−1 of paracetamol in only 6 and 4 h, respectively, much quicker than any other paracetamol-degrader strain described in the literature. The two main paracetamol metabolites, 4-aminophenol and hydroquinone, which present high toxicity, were detected during the degradation process, although they disappeared very quickly for paracetamol concentrations up to 500 mg L−1. The IC50 of paracetamol for the growth of these two isolates was also calculated, indicating that P. extremaustralis CSW01 was more tolerant than S. stutzeri CSW02 to high concentrations of paracetamol and/or its metabolites in solution, and this is the reason for the much lower paracetamol degradation by S. stutzeri CSW02 at 2000–3000 mg L−1. These findings indicate that both bacteria are very promising candidates for their use in paracetamol bioremediation in water and sewage sludge.

Background: The aim of this study was to summarize evidence on energy metabolism through peak fat oxidation (PFO) and maximum fat oxidation (Fatmax), as well as to analyze the protocols used in people with spinal cord injury (SCI) and to examine the main factors related to fat oxidation ability (i.e., age, sex, level of physical activity, and level and degree of injury). Methods: Studies to determine PFO and Fatmax using indirect calorimetry with an arm exercise protocol for SCI patients were included after a systematic search. Other endpoints included study design, sample size, control group, demographic data, level of injury, physical condition, protocol, outcomes measured, and statistical findings. Results: Eight studies (n = 560) were included. The mean value of VO2peak was 1.86 L∙min−1 (range 0.75–2.60 L∙min−1) (lowest value in the tetraplegic subjects). The PFO ranged between 0.06 and 0.30 g∙min−1 (lowest rates: the non-trained subjects with cervical SCI; highest: the tetraplegic subjects). Two types of exercise protocol were found: arm cycle ergometer, and wheelchair propulsion with a computerized ergometer. Five studies used an incremental protocol (2–3 min/stage, different load increments); the rest performed tests of 20 min/stage at three intensities. Conclusion: There are few existing studies measuring fat oxidation in SCI, many of which used small and heterogeneous samples. PFO was lower in SCI subjects when compared with non-injured people performing lower-limb exercise; however, comparing upper-limb exercise, people with SCI showed higher values.

COVID-19 vaccination leads to lower infection, morbidity, and mortality rates. However, COVID-19 infection leads to the development of coagulopathy-related manifestations in the form of both venous and arterial thromboembolism. This study aimed to assess the severity and mortality predictors of COVID-19 patients with thrombotic events in hospitalized patients in Albania. This is a retrospective study conducted in the “Mother Tereza” University Hospital of Tirana. Data were retrieved from the electronic databases of the hospital and only COVID-19 cases admitted to the infectious department during August–December 2020 were selected. Patients who, at admission, had a C-reactive protein (CRP) (mg/L) more than double and a D-dimer (ng/mL) more than triple according to international standards were included in the study. We performed univariate and multivariable logistic regression analysis, calculating unadjusted and adjusted odds ratios (ORs). A p-value < 0.05 was considered statistically significant. The study population included 60 hospitalized persons with a mean age of 64.4 years. Increased lactate dehydrogenase (LDH) (OR = 2.93; 95% CI = 0.82–10.42, p-value = 0.1) and increased creatine kinase (CK) (OR = 2.17; 95% CI = 0.63–7.46, p-value = 0.22) were related with increased probability of death. Moreover, a decreased number of lymphocytes was associated with increased mortality but with no statistical significance (OR = 0.40; 95% CI = 0.11–1.40, p-value = 0.15). The survival rate was higher for patients without comorbidities (p = 0.045). These results could serve as a baseline and as a reference for healthcare personnel who provides services to hospitalized patients with COVID-19. Further studies should take into consideration the vaccination of the population as well as including more hospitals and patients.

Low-cost sensors have been used considerably to characterize air pollution in the last few years. This study involves the usage of this technology for the first time to assess PM2.5 pollution at four cities on the U.S.–Mexico border. These cities in the Lower Rio Grande Valley Region of South Texas are Brownsville, Edinburg, Weslaco, and Port Isabel. A year-long sampling campaign was undertaken from 1 March 2021 to 31 March 2022. TSI BlueSky™ Air Quality Monitors were deployed concurrently at 11 different locations in these four cities. Twenty-four-hour PM2.5 concentrations from these sensors were then compared with ambient PM2.5 data available at the Texas Commission on Environmental Quality (TCEQ) Continuous Ambient Monitoring Station (CAMS) sites to elucidate spatial and temporal variability in the pollutant concentrations at the neighborhood level. The results indicate low to moderate spatial heterogeneity in the PM2.5 concentrations throughout the region. Our findings suggest that low-cost sensors in combination with CAMS sites have the potential to aid community monitoring for real-time spatiotemporal PM2.5 pollution patterns.

In this paper, an optimal hybrid (wind and grid)-hydrogen energy system (H-HES) is proposed using multi-objective non-dominated sorting algorithm (NSGA-II) optimization. The H-HES consists of the main energy system; wind-energy system (W-ES), which supplies a proton exchange membrane (PEM) electrolyzer via an energy management system (EMS) and a rectifier. In addition, the grid-energy system (G-ES) is available to support the W-ES to meet the PEM electrolyzer’s energy demand, and the EMS facilitates control between the W-ES and G-ES. The W-ES is modelled using wind data from Wind Atlas South Africa (WASA) for six Renewable Energy Development Zones (REDZs) in South Africa and their appropriate wind turbine models. The selection of appropriate wind turbine models is guided by the optimal wind turbine variables obtained from NSGA-II corresponding to the optimal H-HES model. The optimal H-HES model is developed using two objective functions: cost of electricity and efficiency, which are minimized and maximized respectively and evaluated using NSGA-II available in Pymoo framework. NSGA-II successfully converges to a Pareto front, and the best solution for the H-HES cost of electricity and efficiency for each wind REDZ is determined by compromise programming; a multi-criteria decision-making technique available in Pymoo. From the optimal cost of electricity and efficiency solutions, optimal variables are successfully obtained for optimal modelling of the H-HES for each wind REDZ.

Obesity is an excessive accumulation of fat that exacerbates the metabolic and inflammatory processes. Studies associate these processes with conditions and dysregulation in the intestinal tract, increased concentrations of lipopolysaccharides (LPSs) in the blood, differences in the abundance of intestinal microbiota, and the production of secondary metabolites such as short-chain fatty acids. β-Caryophyllene (BCP) is a natural sesquiterpene with anti-inflammatory properties and with the potential purpose of fighting metabolic diseases. A diet-induced obesity model was performed in 16-week-old C57BL/6 mice administered with BCP [50 mg/kg]. A reduction in the expression of Claudin-1 was observed in the group with a high-fat diet (HFD), which was caused by the administration of BCP; besides BCP, the phylaAkkermansia and Bacteroidetes decreased between the groups with a standard diet (STD) vs. HFD. Nevertheless, the use of BCP in the STD increased the expression of these phyla with respect to fatty acids; a similar effect was observed, in the HFD group that had a decreasing concentration that was restored with the use of BCP. The levels of endotoxemia and serum leptin increased in the HFD group, while in the HFD + BCP group, similar values were found to those of the STD group, attributing the ability to reduce these in conditions of obesity.

The removal of chlorpyrifos (CLP) from the environment is a matter of general interest, because it is one of the most widely used insecticides in the world but presents a high toxicity and persistence in the environment. Biological strategies are considered as a good option to remediate different environmental compartments. Assisted natural attenuation was used to find the ability of different kinds of soils to mineralise CLP. In this way, two soils showed the capacity to degrade CLP (R and LL up to 47.3% and 61.4% after 100 d, respectively). Thus, two CLP-degrading strains, Bacillus megaterium CCLP1 and Bacillus safensis CCLP2 were isolated from them, showing the capacity to degrade up to 99.1 and 98.9% of CLP in a solution with an initial concentration of 10 mg L−1 after 60 d. Different strategies were considered for increasing the effectiveness of soil bioremediation: (i) biostimulation, using a nutrients solution (NS); (ii) bioaugmentation, using B. megaterium CCLP1 or B. safensis CCLP2; (iii) bioavailability enhancement, using randomly methylated β-cyclodextrin (RAMEB), a biodegradable compound. When bioaugmentation and RAMEB were jointly inoculated and applied, the best biodegradation results were achieved (around 70%). At the end of the biodegradation assay, a toxicity test was used to check the final state of the bioremediated soil, observing that when the degrading strains studied were individually inoculated into the soil, the toxicity was reduced to undetectable levels.

A series of PFDPP copolymers based on fluorene (F) and diketopyrrolopyrrole (DPP) monomers were synthesized via direct arylation polycondensation using Fagnou conditions which involved palladium acetate as catalyst (a gradual catalyst addition of three different percentages were used), potassium carbonate as the base, and neodecanoic acid in N, N-dimethylacetamide. This synthesis provides a low cost compared with traditional methods of transition-metal-catalyzed polymerization. Among the different amounts of catalyst used in the present work, 12% was optimal because it gave the highest reaction yield (81.5%) and one of the highest molecular weights (Mn = 13.8 KDa). Copolymers’ chemical structures, molecular weight distributions, and optical and thermal properties were analyzed. The linear optical properties of PFDPP copolymers resulted very similarly independently to the catalyst amounts used in the synthesis of the PFDPP copolymers: two absorptions bands distinctive of donor–acceptor copolymers, Stokes shifts of 41 nm, a good quantum yield of fluorescence around 47%, and an optical bandgap of 1.7 eV were determined. Electronic nonlinearities were observed in these copolymers with a relatively high two-photon absorption cross-section of 621 GM at 950 nm. The dynamics of excited states and aggregation effects were studied in solutions, nanoparticles, and films of PFDPP. Theoretical calculations modeled the ground-state structures of the (PFDPP)n copolymers with n = 1 to 4 units, determining the charge distribution by the electrostatic potential and modeling the absorption spectra determining the orbital transitions responsible for the experimentally observed leading bands. Experimental and theoretical structure–properties analysis of these donor–acceptor copolymers allowed finding their best synthesis conditions to use them in optoelectronic applications.

In our previous work, we evaluated the therapeutic effects of 1α,25-Dihydroxyvitamin D3, the biologically active form of vitamin D, in the context of bleomycin-induced lung fibrosis. Contrary to the expected, vitamin D supplementation increased the DNA damage expression and cellular senescence in alveolar epithelial type II cells and aggravated the overall lung pathology induced in mice by bleomycin. These effects were probably due to an alteration in the cellular DNA double-strand breaks’ repair capability. In the present work, we have evaluated the effects of two hypocalcemic vitamin D analogs (calcipotriol and paricalcitol) in the expression of DNA damage in the context of minilungs derived from human embryonic stem cells and in the cell line A549.

Allergen immunotherapy (AIT) is the sole disease-modifying treatment for allergic rhinitis; it prevents rhinitis from progressing to asthma and lowers medication use. AIT against mites, insect venom, and certain kinds of pollen is effective. The mechanism of action of AIT is based on inducing immunological tolerance characterized by increased IL-10, TGF-β, and IgG4 levels and Treg cell counts. However, AIT requires prolonged schemes of administration and is sometimes associated with adverse reactions. Over the last decade, novel forms of AIT have been developed, focused on better allergen identification, structural modifications to preserve epitopes for B or T cells, post-traductional alteration through chemical processes, and the addition of adjuvants. These modified allergens induce clinical-immunological effects similar to those mentioned above, increasing the tolerance to other related allergens but with fewer side effects. Clinical studies have shown that molecular AIT is efficient in treating grass and birch allergies. This article reviews the possibility of a new AIT to improve the treatment of allergic illness.

Bone morphogenetic proteins (BMPs) are a group of multifunctional growth factors that belong to the transforming growth factor-β (TGF-β) superfamily of proteins. Originally identified by their ability to induce bone formation, they are now known as essential signaling molecules that regulate the development and function of the female reproductive system (FRS). Several BMPs play key roles in aspects of reproductive system development. BMPs have also been described to be involved in the differentiation of human pluripotent stem cells (hPSCs) into reproductive system tissues or organoids. The role of BMPs in the reproductive system is still poorly understood and the use of FRS tissue or organoids generated from hPSCs would provide a powerful tool for the study of FRS development and the generation of new therapeutic perspectives for the treatment of FRS diseases. Therefore, the aim of this review is to summarize the current knowledge about BMP signaling in FRS development and function.

Blood phenylalanine (Phe) is used as the primary marker to evaluate metabolic control. Our study aimed to describe the metabolic control of patients with phenylketonuria (PKU) comparing three different treatment recommendations (European guidelines/US guidelines/Portuguese consensus). This was a retrospective, observational, single centre study in patients with PKU collecting data on blood Phe levels from 2017. Nutritional intake data and sapropterin (BH4) prescription were collected at the last appointment of 2017. The final sample studied included 87 patients (48% females) [13 hyperphenylalaninemia; 47 mild PKU; 27 classical PKU] with a median age of 18 y (range: 1–36 y). The median number of blood Phe measurements for patients was 21 (range: 6–89). In patients aged < 12 y, the median blood Phe level was 300 μmol/L (range 168–480) and 474 μmol/L (range 156–1194) for patients ≥ 12 y. Overall, a median of 83% of blood Phe levels were within the European PKU guidelines target range. In patients aged ≥ 12 years, there was a higher median % of blood Phe levels within the European PKU guidelines target range (≥12 y: 84% vs. n = 2), only 34% of blood Phe levels were within target range for all 3 guidelines and 49% with mild PKU (n = 11). Girls had better control than boys (89% vs. 66% median Phe levels within European Guidelines). Although it is clear that 50% or more patients were unable to achieve acceptable metabolic control on current treatment options, a globally agreed upper Phe target associated with optimal outcomes for age groups is necessary. More studies need to examine how clinics with dissimilar resources, different therapeutic Phe targets and frequency of monitoring relate to metabolic control.

We aimed to report the implementation of a phenylketonuria (PKU) transition program and study the effects of follow-up with an adult team on metabolic control, adherence, and loss of follow-up. Fifty-five PKU patients were analysed in the study periods (SP): 2 years before (SP1) and after the beginning of adult care (SP2). Retrospective data on metabolic control and number of clinic appointments were collected for each SP, and protein intakes were analysed. In SP2, three patients (6%) were lost to follow-up. There was a small but statistically significant increase in median number of annual blood spots from SP1 to SP2: 11 (7–15) vs. 14 (7–20); p = 0.002. Mean ± SD of median blood Phe remained stable (525 ± 248 µmol/L vs. 552 ± 225 µmol/L; p = 0.100); median % of blood Phe < 480 µmol/L decreased (51 (4–96)% vs. 37 (5–85)%; p = 0.041) and median number of clinic appointments increased from SP1 to SP2: (5 (4–6) vs. 11 (8–13); p < 0.001). No significant differences were found regarding any parameter of protein intake. Our results suggest that the implementation of an adult service was successful as impact on metabolic control was limited and attendance remained high. Continuous dietetic care likely contributed to these results by keeping patients in follow-up and committed to treatment.

Lysosomal storage diseases (LSDs) are a heterogeneous group of genetic disorders with variable degrees of severity and a broad phenotypic spectrum, which may overlap with a number of other conditions. While individually rare, as a group LSDs affect a significant number of patients, placing an important burden on affected individuals and their families but also on national health care systems worldwide. Here, we present our results on the use of an in-house customized next-generation sequencing (NGS) panel of genes related to lysosome function as a first-line molecular test for the diagnosis of LSDs. Ultimately, our goal is to provide a fast and effective tool to screen for virtually all LSDs in a single run, thus contributing to decrease the diagnostic odyssey, accelerating the time to diagnosis. Our study enrolled a group of 23 patients with variable degrees of clinical and/or biochemical suspicion of LSD. Briefly, NGS analysis data workflow, followed by segregation analysis allowed the characterization of approximately 41% of the analyzed patients and the identification of 10 different pathogenic variants, underlying nine LSDs. Importantly, four of those variants were novel, and, when applicable, their effect over protein structure was evaluated through in silico analysis. One of the novel pathogenic variants was identified in the GM2A gene, which is associated with an ultra-rare (or misdiagnosed) LSD, the AB variant of GM2 Gangliosidosis. Overall, this case series highlights not only the major advantages of NGS-based diagnostic approaches but also, to some extent, its limitations ultimately promoting a reflection on the role of targeted panels as a primary tool for the prompt characterization of LSD patients.

Macrophage infiltration in two subcutaneous adipose tissue depots and systemic low-grade inflammation were studied in post-obese (PO), obese (O), and control (C) subjects. Young males were recruited into PO: (n = 10, weight-loss avg. 26%, BMI: 26.6 ± 0.7, mean ±SEM kg/m2), O: (n = 10, BMI: 33.8 ± 1.0kg/m2) and C: (n = 10, BMI: 26.6 ± 0.6 kg/m2). PO and C were matched by BMI. Blood and abdominal and gluteal subcutaneous adipose tissue were obtained in the overnight fasted state. Plasma concentrations of IL-6 and CRP were higher (p < 0.05) in O than in PO and C, TNF-α was higher (p < 0.05) only in O compared to PO and IL-18 was similar between groups. The number of CD68+ macrophages was higher (p < 0.05) in the gluteal than the abdominal depot, and higher (p < 0.05) in O and PO compared to C in both depots. The content of CD163+ macrophages was similar between depots but was higher (p < 0.05) in PO compared to C and O in the gluteal depot. In post obese men with a long-term sustained weight loss, systemic low-grade inflammation was similar to non-obese controls despite a higher subcutaneous adipose tissue CD68+ macrophage content. Interestingly, the anti-inflammatory CD163+ macrophage adipose tissue content was consistently higher in post obese than obese and controls.

The sensorimotor system (SMS) plays an important role in sports and in every day movement. Several tools for assessment and training have been designed. Many of them are directed to specific populations, and have major shortcomings due to the training effect or safety. The aim of the present study was to design and assess a dynamic sensorimotor test and training device that can be adjusted for all levels of performance. The novel pneumatic-driven mechatronic device can guide the trainee, allow independent movements or disrupt the individual with unpredicted perturbations while standing on a platform. The test-reliability was evaluated using intraclass correlation coefficient (ICC). Subjects were required to balance their center of pressure (COP) in a target circle (TITC). The time in TITC and the COP error (COPe) were recorded for analysis. The results of 22 males and 14 females (23.7 ± 2.6 years) showed good to excellent test–retest reliability. The newly designed Active Balance System (ABS) was then compared with the Biodex Balance System SD® (BBS). The results of 15 females, 14 males (23.4 ± 1.6 years) showed modest correlation in static and acceptable correlation in dynamic conditions, suggesting that ABS could be a reliable and comparable tool for dynamic balance assessments.

Nanotechnology applications demand high accuracy positioning systems. Therefore, in order to achieve sub-micrometer accuracy, positioning uncertainty contributions must be minimized by implementing precision positioning control strategies. The positioning control system accuracy must be analyzed and optimized, especially when the system is required to follow a predefined trajectory. In this line of research, this work studies the contribution of the trajectory definition errors to the final positioning uncertainty of a large-range 2D nanopositioning stage. The curve trajectory is defined by curve fitting using two methods: traditional CAD/CAM systems and novel algorithms for accurate curve fitting. This novel method has an interest in computer-aided geometric design and approximation theory, and allows high relative accuracy (HRA) in the computation of the representations of parametric curves while minimizing the numerical errors. It is verified that the HRA method offers better positioning accuracy than commonly used CAD/CAM methods when defining a trajectory by curve fitting: When fitting a curve by interpolation with the HRA method, fewer data points are required to achieve the precision requirements. Similarly, when fitting a curve by a least-squares approximation, for the same set of given data points, the HRA method is capable of obtaining an accurate approximation curve with fewer control points.

Phenylalanine (Phe) tolerance is highly variable in phenylketonuria (PKU) and rarely described in patients aged ≥12 years. Patients ≥12 years of age with PKU were systematically challenged with additional natural protein (NP) if blood Phe levels remained below 480 µmol/L (i.e., upper target blood Phe level for patients aged ≥12 years using Portuguese PKU guidelines). In PKU patients, NP tolerance was calculated at baseline and a median of 6 months after systematic challenge with NP whilst patients were maintaining a blood Phe ≤480 μmol/L. Anthropometry was assessed at both times. Routine blood Phe levels were collected. We studied 40 well-controlled PKU patients (10 hyperphenylalaninemia (HPA), 23 mild and 7 classic PKU), on a low-Phe diet with a mean age of 17 years (12–29 years). Median daily NP intake significantly increased between assessments (35 vs. 40 g/day, p = 0.01). Twenty-six patients (65%) were able to increase their median NP intake by a median 12 g/day (2–42 g)/day and still maintain blood Phe within target range. Out of the previous 26 patients, 20 (77%) (8 HPA, 11 mild and 1 classical PKU) increased NP from animal sources (e.g., dairy products, fish and meat) and 6 patients (23%) (3 mild and 3 classical PKU) from plant foods (bread, pasta, potatoes). Median protein equivalent intake from Phe-free/low-Phe protein substitute decreased (0.82 vs. 0.75 g/kg, p = 0.01), while median blood Phe levels remained unchanged (279 vs. 288 μmol/L, p = 0.06). Almost two-thirds of patients with PKU tolerated additional NP when challenged and still maintained blood Phe within the national target range. This suggests that some patients with PKU treated by a low-Phe diet only may over restrict their NP intake. In order to minimise the burden of treatment and optimise NP intake, it is important to challenge with additional NP at periodic intervals.

Human respiratory syncytial virus (HRSV) is a major cause of serious pediatric respiratory diseases that lacks effective vaccine or specific therapeutics. Although our understanding about HRSV biology has dramatically increased during the last decades, the need for adequate models of HRSV infection is compelling. We have generated a two-dimensional minilung from human embryonic stem cells (hESCs). The differentiation protocol yielded at least six types of lung and airway cells, although it is biased toward the generation of distal cells. We show evidence of HRSV replication in lung cells, and the induction of innate and proinflammatory responses, thus supporting its use as a model for the study of HRSV–host interactions.