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Background and Objectives: Previous studies have shown that the levodopa treatment of Parkinson's disease (PD) elevates circulating homocysteine levels, which are associated with an increased risk of cardiovascular and neurological disorders, or thrombosis. The present trial aimed to examine whether the intake of vitamin B12, folic acid, and vitamin D3 supplements improved homocysteine level and quality of life (QoL)., Materials and Methods: An interventional prospective trial was conducted in multiple centers across Romania. Participants with clinically established PD taking at least 300 mg/day of levodopa for more than 1 year received a daily tablet of a supplement containing 800 UI of vitamin D3, 1000 µg of folic acid, and 15 µg of vitamin B12. They were followed for 6 months and their serum homocysteine, vitamin B12, vitamin D, and QoL scores were measured at baseline and at 6 months of treatment. QoL was measured using a 15D questionnaire, which assesses mobility, vision, hearing, breathing, sleeping, eating, speech, excretion, usual activities, mental function, discomfort and symptoms, depression, distress, vitality, and sexual activity., Results: Twenty-four PD patients with a mean age of 71 ± 5.04 years (54.2% male and 45.8% female) finished the study. After the intervention, the mean score of speech, mental function, discomfort and symptoms, depression, and QoL significantly increased ( p < 0.05 for all). Also, the serum homocysteine and vitamin D were significantly enhanced ( p < 0.0001 and p = 0.025, respectively). Changes in vitamin B12 were not statistically significant at 6 months of treatment ( p = 0.996). No gender differences were found among the changes that we have demonstrated for homocysteine, vitamin B12, vitamin D, and QoL levels ( p < 0.05 for all)., Conclusions: The findings of this study showed that the dietary intake of vitamin B12, folic acid, and vitamin D3 remarkably decreased the dimensions of homocysteine and finally increased the total score of QoL in PD patients. We have successfully captured the potential benefits of the supplementation regimen over time and provided insights into the broader implications for managing PD with a focus on nutritional support.

Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are aggressive sarcomas that can arise both sporadically and in patients with the genetic syndrome Neurofibromatosis type 1 (NF1). Prognosis is dismal, as large dimensions, risk of relapse, and anatomical localization make surgery poorly effective, and no therapy is known. Hence, the identification of MPNST molecular features that could be hit in an efficient and selective way is mandatory to envision treatment options. Here, we find that MPNSTs express high levels of the glycolytic enzyme Hexokinase 2 (HK2), which is known to shield cancer cells from noxious stimuli when it localizes at MAMs (mitochondria-associated membranes), contact sites between mitochondria and endoplasmic reticulum. A HK2-targeting peptide that dislodges HK2 from MAMs rapidly induces a massive death of MPNST cells. After identifying different matrix metalloproteases (MMPs) expressed in the MPNST microenvironment, we have designed HK2-targeting peptide variants that harbor cleavage sites for these MMPs, making such peptides activatable in the proximity of cancer cells. We find that the peptide carrying the MMP2/9 cleavage site is the most effective, both in inhibiting the in vitro tumorigenicity of MPNST cells and in hampering their growth in mice. Our data indicate that detaching HK2 from MAMs could pave the way for a novel anti-MPNST therapeutic strategy, which could be flexibly adapted to the protease expression features of the tumor microenvironment.

Background: Artificial intelligence (AI) can radically change almost every aspect of the human experience. In the medical field, there are numerous applications of AI and subsequently, in a relatively short time, significant progress has been made. Cardiology is not immune to this trend, this fact being supported by the exponential increase in the number of publications in which the algorithms play an important role in data analysis, pattern discovery, identification of anomalies, and therapeutic decision making. Furthermore, with technological development, there have appeared new models of machine learning (ML) and deep learning (DP) that are capable of exploring various applications of AI in cardiology, including areas such as prevention, cardiovascular imaging, electrophysiology, interventional cardiology, and many others. In this sense, the present article aims to provide a general vision of the current state of AI use in cardiology., Results: We identified and included a subset of 200 papers directly relevant to the current research covering a wide range of applications. Thus, this paper presents AI applications in cardiovascular imaging, arithmology, clinical or emergency cardiology, cardiovascular prevention, and interventional procedures in a summarized manner. Recent studies from the highly scientific literature demonstrate the feasibility and advantages of using AI in different branches of cardiology., Conclusions: The integration of AI in cardiology offers promising perspectives for increasing accuracy by decreasing the error rate and increasing efficiency in cardiovascular practice. From predicting the risk of sudden death or the ability to respond to cardiac resynchronization therapy to the diagnosis of pulmonary embolism or the early detection of valvular diseases, AI algorithms have shown their potential to mitigate human error and provide feasible solutions. At the same time, limits imposed by the small samples studied are highlighted alongside the challenges presented by ethical implementation; these relate to legal implications regarding responsibility and decision making processes, ensuring patient confidentiality and data security. All these constitute future research directions that will allow the integration of AI in the progress of cardiology.

Our purpose is to emphasize the role of botulinum toxin in spasticity therapy and functional recovery in patients following strokes. Our retrospective study compared two groups, namely ischemic and hemorrhagic stroke patients. The study group (BT group) comprised 80 patients who received focal botulinum toxin as therapy for an upper limb with spastic muscle three times every three months. The control group (ES group) comprised 80 patients who received only medical rehabilitation consisting of electrostimulation and radial shockwave therapy for the upper limb, which was applied three times every three months. Both groups received the same stretching program for spastic muscles as a home training program. We evaluated the evolution of the patients using muscle strength, Ashworth, Tardieu, Frenchay, and Barthel scales. The analysis indicated a statistically significant difference between the two groups for all scales, with better results for the BT group ( p < 0.0001 for all scales). In our study, the age at disease onset was an important prediction factor for better recovery in both groups but not in all scales. Better recovery was obtained for younger patients (in the BT group, MRC scale: rho = -0.609, p -value < 0.0001; Tardieu scale: rho = -0.365, p -value = 0.001; in the ES group, MRC scale: rho = -0.445, p -value < 0.0001; Barthel scale: rho = -0.239, p -value = 0.033). Our results demonstrated the effectiveness of botulinum toxin therapy compared with the rehabilitation method, showing a reduction of the recovery time of the upper limb, as well as an improvement of functionality and a reduction of disability. Although all patients followed a specific kinetic program, important improvements were evident in the botulinum toxin group.

The purpose of prosthetic devices is to reproduce the angular-torque profile of a healthy human during locomotion. A lightweight and energy-efficient joint is capable of decreasing the peak actuator power and/or power consumption per gait cycle, while adequately meeting profile-matching constraints. The aim of this study was to highlight the dynamic characteristics of a bionic leg with electric actuators with rotational movement. Three-dimensional (3D)-printing technology was used to create the leg, and servomotors were used for the joints. A stepper motor was used for horizontal movement. For better numerical simulation of the printed model, three mechanical tests were carried out (tension, compression, and bending), based on which the main mechanical characteristics necessary for the numerical simulation were obtained. For the experimental model made, the dynamic stresses could be determined, which highlights the fact that, under the conditions given for the experimental model, the prosthesis resists.

The Internet of Things (IoT) has gained significance in agriculture, using remote sensing and machine learning to help farmers make high-precision management decisions. This technology can be applied in viticulture, making it possible to monitor disease occurrence and prevent them automatically. The study aims to achieve an intelligent grapevine disease detection method, using an IoT sensor network that collects environmental and plant-related data. The focus of this study is the identification of the main parameters which provide early information regarding the grapevine's health. An overview of the sensor network, architecture, and components is provided in this paper. The IoT sensors system is deployed in the experimental plots located within the plantations of the Research Station for Viticulture and Enology (SDV) in Murfatlar, Romania. Classical methods for disease identification are applied in the field as well, in order to compare them with the sensor data, thus improving the algorithm for grapevine disease identification. The data from the sensors are analyzed using Machine Learning (ML) algorithms and correlated with the results obtained using classical methods in order to identify and predict grapevine diseases. The results of the disease occurrence are presented along with the corresponding environmental parameters. The error of the classification system, which uses a feedforward neural network, is 0.05. This study will be continued with the results obtained from the IoT sensors tested in vineyards located in other regions.

Background: Videos have been an important medium for providing health and risk communication to the public during the COVID-19 pandemic. Public health officials, health care professionals, and policy makers have used videos to communicate pandemic-related content to large parts of the population. Evidence regarding the outcomes of such communication, along with their determinants, is however limited., Objective: The aim of this study was to test the impact of nonvisual information factors of video communication on 4 outcomes: trust, comprehension, intentions, and behavior., Methods: Twelve short health communication videos related to pandemics were produced and shown to a large sample of participants, applying a randomized controlled between-subjects design. Three factors were included in the creation of the videos: the topic (exponential growth, handwashing, and burden of pandemics on the health care system), the source (expert and nonexpert), and a call to action (present or absent). Participants were randomly assigned to 1 video intervention, and 1194 valid replies were collected. The data were analyzed using factorial ANOVA., Results: The 3 pandemic-related topics did not affect trust, comprehension, intentions, or behavior. Trust was positively influenced by an expert source (2.5%), whereas a nonexpert source instead had a positive effect on the proxy for behavior (5.7%) compared with the expert source. The inclusion of a call to action had a positive effect on both trust (4.1%) and comprehension (15%)., Conclusions: Trust and comprehension in pandemic-related video communication can be enhanced by using expert sources and by including a call to action, irrespective of the topic being communicated. Intentions and behavior appear to be affected to a small extent by the 3 factors tested in this study., International Registered Report Identifier (irrid): RR2-10.2196/34275., (©Daniel Adrian Lungu, Jo Røislien, Siv Hilde Berg, Ionica Smeets, Marie Therese Shortt, Henriette Thune, Kolbjørn Kallesten Brønnick. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 23.08.2023.)

Background: Genetic and metabolic heterogeneity are well-known features of cancer and tumors can be viewed as an evolving mix of subclonal populations, subjected to selection driven by microenvironmental pressures or drug treatment. In previous studies, anti-VEGF therapy was found to elicit rewiring of tumor metabolism, causing marked alterations in glucose, lactate ad ATP levels in tumors. The aim of this study was to evaluate whether differences in the sensitivity to glucose starvation existed at the clonal level in ovarian cancer cells and to investigate the effects induced by anti-VEGF therapy on this phenotype by multi-omics analysis., Methods: Clonal populations, obtained from both ovarian cancer cell lines (IGROV-1 and SKOV3) and tumor xenografts upon glucose deprivation, were defined as glucose deprivation resistant (GDR) or glucose deprivation sensitive (GDS) clones based on their in vitro behaviour. GDR and GDS clones were characterized using a multi-omics approach, including genetic, transcriptomic and metabolic analysis, and tested for their tumorigenic potential and reaction to anti-angiogenic therapy., Results: Two clonal populations, GDR and GDS, with strikingly different viability following in vitro glucose starvation, were identified in ovarian cancer cell lines. GDR clones survived and overcame glucose starvation-induced stress by enhancing mitochondrial oxidative phosphorylation (OXPHOS) and both pyruvate and lipids uptake, whereas GDS clones were less able to adapt and died. Treatment of ovarian cancer xenografts with the anti-VEGF drug bevacizumab positively selected for GDR clones that disclosed increased tumorigenic properties in NOD/SCID mice. Remarkably, GDR clones were more sensitive than GDS clones to the mitochondrial respiratory chain complex I inhibitor metformin, thus suggesting a potential therapeutic strategy to target the OXPHOS-metabolic dependency of this subpopulation., Conclusion: A glucose-deprivation resistant population of ovarian cancer cells showing druggable OXPHOS-dependent metabolic traits is enriched in experimental tumors treated by anti-VEGF therapy., (© 2023. Italian National Cancer Institute ‘Regina Elena’.)

This review aims to measure the different aspects of summer savory including biological activity, medicinal properties, nutritional value, food application, prospective health benefits, and its use as an additive in broiler feed. Furthermore, toxicity related to this is also overviewed. Summer savory leaves are abundant in total phenolic compounds (rosmarinic acid and flavonoids) that have a powerful antioxidant impact. Rosmarinic (α-O-caffeoyl-3,4-dihydroxy-phenyl lactic) acid has been identified in summer savory as a main component. According to phytochemical investigations, tannins, volatile oils, sterols, acids, gums, pyrocatechol, phenolic compounds, mucilage, and pyrocatechol are the primary compounds of Satureja species. Summer savory extract shows considerable biological potential in antioxidant, cytotoxic, and antibacterial assays. Regarding antioxidant activity, summer savory extract displays an inhibitory effect on lipid peroxidation. Summer savory also has Fe (III) reductive and free radical scavenging properties and contains minerals and vitamins. Summer savory has important biological properties, including antimicrobial activity and antioxidant activity, and protective effects against Jurkat T Cells, Alzheimer's disease, cancer, infection, cardiovascular diseases, diabetes, and cholesterol. The leaves and stems of this plant are employed in the food, feed, and pharmacological industries due to their antioxidant properties and substantial nutritional content. Conclusively, summer savory is widely considered beneficial for human health due to its versatile properties and medicinal use., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ejaz, Waliat, Arshad, Khalid, Khalid, Rasul Suleria, Luca, Mironeasa, Batariuc, Ungureanu-Iuga, Coţovanu and Mironeasa.)

The demand for healthy ready-to-eat foods like snacks is increasing. Physical modification of vegetal food matrices through extrusion generates significant changes in the chemical composition of the final product. There is a great variety of food matrices that can be used in extrusion, most of them being based on cereals, legumes, fruits, vegetables, or seeds. The aim of this review was to summarize the main effects of the extrusion process on the bioactive compounds content, namely phenolics, terpenes, vitamins, minerals, and fibers of vegetal mixes, as well as on their biological activity. The literature reported contradictory results regarding the changes in bioactive compounds after extrusion, mainly due to the differences in the processing conditions, chemical composition, physicochemical properties, and nutritional value of the extruded material and quantification methods. The thermolabile phenolics and vitamins were negatively affected by extrusion, while the fiber content was proved to be enhanced. Further research is needed regarding the interactions between bioactive components during extrusion, as well as a more detailed analysis of the impact of extrusion on the terpenes since there are few papers dealing with this aspect.

Traditional Romanian food products are an integral part of local culture and spirituality. These food traditions have been formed over the centuries and represent a particularly important part ofthe development of a circular economy in rural areas. In order to contribute to the development of this sector of activity we conducted a study on consumer perception of traditional Romanian food products. The purpose of this work was to identify the structure of the studies and the future directions of research related to the image of traditional food products through the bibliometric study, as well as the identification of consumer trends, of these products through a survey based on the questionnaire. The results obtained indicate that traditional Romanian food products are consumed by the majority of respondents participating in the survey and that this sector ofactivity has continuity in its development and presents a clear interest among citizens.

Increasing the biocompatibility of some biological implants through tissue engineering is important for regenerative medicine, which recently has a rapid development dynamic. In this study we used tree different washing protocols, respectively with Sodium Lauryl Sulfate (SLS), with Sodium Deoxycholate (SD), and with saline (Sa) to achieve partial decellularization of 2-3mm thick cross-sections through Wistar rat hearts. Pieces of the heart tissue were either histologically analyzed to evaluate the decellularization processes or implanted for 5 days on 9-day-old chick embryo chorioallantoic membrane (CAM) and then histologically analyzed to evaluate CAM-implant interactions. Histological analysis of SLS or SD washed tissues showed different microscopic features of the decellularization processes, SLS-washing leading to the formation of a completely decellularized ECM layer at the periphery of the heart tissue. Both detergents induced changes in the spatial arrangement of collagen fibers of the heart tissue. Histological analysis of the CAM implants shoved that the peripheral zone with complete decellularization induced by SLS increased the biocompatibility of heart tissue implants by favoring neovascularization and cell migration. These results suggested that the biocompatibility of the heart tissue implant can be modulated by the appropriate use of a SLS-based decellularization protocol., Competing Interests: None to declare., (Copyright © 2023, Medical University Publishing House Craiova.)

Heat treatment of sorghum kernels has the potential to improve their nutritional properties. The goal of this study was to assess the impact of dry heat treatment at two temperatures (121 and 140 °C) and grain fractionation, on the chemical and functional properties of red sorghum flour with three different particle sizes (small, medium, and large), for process optimization. The results showed that the treatment temperature had a positive effect on the water absorption capacity, as well as the fat, ash, moisture and carbohydrate content, whereas the opposite tendency was obtained for oil absorption capacity, swelling power, emulsion activity and protein and fiber content. Sorghum flour particle size had a positive impact on water absorption capacity, emulsion activity and protein, carbohydrate and fiber content, while oil absorption capacity, swelling power and fat, ash and moisture content were adversely affected. The optimization process showed that at the treatment temperature at 133 °C, an increase in fat, ash, fiber and carbohydrate content was experienced in the optimal fraction dimension of red sorghum grains. Moreover, the antioxidant performance showed that this fraction produced the best reducing capability when water was used as an extraction solvent. Starch digestibility revealed a 22.81% rise in resistant starch, while the thermal properties showed that gelatinization enthalpy was 1.90 times higher compared to the control sample. These findings may be helpful for researchers and the food industry in developing various functional foods or gluten-free bakery products.

Whole-organ plastic resin casting is a very useful method for preserving rare pathological specimens for forensic/anatomical studies and for teaching/research purposes. Many techniques have been proposed over time, but most of them use special non-commercially available resin mixtures, lengthy protocols, and are overall not easily implemented in any anatomy/pathology department that might need such a procedure for rapid organ preservation. Here, we utilized anatomical sections of the human brain, heart, kidneys, spleen, large intestine, and lungs from on-display organs that were fixed for more than 1 year in 10% neutral-buffered formalin and from a freshly processed cadaver for teaching purposes in our Human Anatomy Department, and we optimized a fast-processing protocol without the use of any clearing agents, which yields solid, clear, cylindrical resin casting blocks. The resulting protocol, which takes no longer than 4 days, proves that at least three commonly used epoxy resins from hobby shops can be utilized without any restrictions, and the use of resin or glycerin vacuum-forced impregnation even offers two choices of intrinsic contrast, depending on the nature of the preparation. A number of innovations have been included here and compared to existing publications, such as the use of a system of permanent fixation plexiglas rods that maintain the organ in the desired position and become invisible in the final block, the use of UVC sterilization of the tissue to ensure a long shelf life of the block, and the utilization of cheap cylindrical polypropylene food containers as casting molds. Altogether, we present a simple resin-embedding protocol that can be made available to any department/institution without the need for expensive materials and specially trained personnel.

This study explored the effect of substituting wheat flour (WF) with distinctive optimal doses of buckwheat flour (BF) corresponding to large, medium, and small particle sizes (PS), previously established based on an optimization process, on composite flour characteristics, dough rheology, and bread quality. The optimal dose for each PS was established in a previous study. The highest value for protein, lipid, mineral, and amino acids was found in the optimal composite flour with medium PS, with significant differences between those with large and small PS. The addition of BF in WF at doses corresponding to each fraction provides optimum rheological properties, with the large and medium PS providing higher performance compared to the small one. The same tendency was observed for volume and texture parameters of bread made from optimal composite flours with medium and large PS, respectively, but the crust and crumb lightness presented lower values than bread with small PS. Regarding the bread nutritional profile, the sample with medium PS possessed the highest protein, lipid, and ash content. Compared to the wheat bread, a considerably higher amino acid content, up to 21.22%, was found in bread made from optimal composite flours with medium and small PS, respectively. The bread samples with medium and large PS, respectively were superior in minerals, the value being up to 2.63 times higher compared to the control. Sensory characteristics results revealed that the bread samples containing 9.13% large and 10.57% medium PS were the most preferred by panelists. The results of this research make an important base to suitably develop wheat-buckwheat bread applications in the future.

The extracellular matrix (ECM) scaffolds are considered a gold standard for the engineering of appropriate grafts used in regenerative medicine for tissue repair, and decellularization of myocardial tissue is one of the most studied processes for obtaining natural ECM to date. Decellularization methods, agents used, or treatment durations can be varied to optimize cardiac tissue decellularization parameters. In this work we performed a morphological and morphometric analysis of cardiac tissue subjected to decellularization protocols based on Sodium Deoxycholate (SD) or Sodium Lauryl Sulfate (SLS) to identify factors that allow optimization of single-detergent based protocols for cardiac ECM manufacturing. For this, Wistar rat hearts (n=10) were subjected to 5 different decellularization protocols (n=2) and then histologically processed to achieve H&E or Azan trichrome stained sections for the morphological and morphometric analysis of the obtained ECM. The results of this study showed that SLS alters the spatial distribution of cardiac ECM collagen fibers, and SD can be successfully used in tailoring single-based detergent decellularization protocols by appropriately adjusting the application times of hypo/hyperosmotic shocks, which increases the lytic action of the detergent, and the washing times for the efficient elimination of cellular residues., Competing Interests: None to declare, (Copyright © 2023, Medical University Publishing House Craiova.)

One of the food industry's challenges is to enhance bread quality from a nutritional point of view without impacting negatively sensorial characteristics and consumer decisions on product choice. This study aimed to assess the baking characteristics of wheat bread supplemented with quinoa flour (QF) of large, medium and small particle sizes at typical doses previously established based on an optimization process, and to evaluate the optimal bread from a physical, textural, nutritional, and sensorial point of view. The results showed a decrease in the Falling number index, water absorption, dough stability, speed of protein weakening, dough extensibility, and creep-recovery compliances for optimal wheat-quinoa composite samples with large and medium particle sizes; meanwhile, for the samples with small particle sizes an opposite trend was recorded, with the exception of dough extensibility. Dough fermentation parameters and bread volume rose for all optimal formulations, while firmness decreased compared to wheat bread. All optimal bread samples presented an improved nutritional profile depending on the particle size. The protein content was up to 19% higher, ash up to 13.8%, and lipids up to fifteen times higher. A noticeable enrichment in minerals (mainly K, Mg, Na, Zn, up to 2.3 times) and essential amino acids (with 13.53%) was also obtained for all optimal breads. From an acceptability point of view, the highest score (8.70) was recorded for the optimal bread with a QF of medium particle size. These findings offer processors new information which will be useful for diversifying bakery products with an enhanced nutritional profile.

Amaranth is an underutilized pseudocereal that can be used to supplement wheat flour (WF) in order to improve the nutritional quality of bread. Bread digestibility is impacted by particle size which produces different nutritional properties. This research aims to evaluate the baking characteristics of optimal wheat−amaranth composite flour for each studied amaranth flour (AF) particle size at doses previously established based on an optimization process and to characterize from a physical, textural, nutritional, and sensorial point of view the obtained bread. The results revealed that the optimal wheat−amaranth composite flour with medium and small particle size, respectively showed a slightly lower α-amylase activity, while dough development time was significantly higher compared to the WF. A significant (p < 0.05) decrease was observed in the elasticity, deformation energy, and dynamic rheological parameters of the optimal composite dough for all the particle sizes, whereas fermentation parameters showed higher values compared to the control, indicating the ability of the gluten structure in large, medium, and small particle sizes of AF to hold the gas and to expand without collapsing. The physical, textural, and especially nutritional characteristics of the optimal WF-AF bread were enhanced. The sensory evaluation results revealed high scores (8.70) for the acceptability of optimal bread with a medium particle size as compared to wheat bread (8.25). The protein and ash content of the optimal breads with large, medium, and small AF particle sizes, respectively, increased significantly, from 8.92 to 10.58%, and 0.82 to 0.99%, respectively, relative to the wheat flour bread (8.35% and 0.72%, respectively). The mineral content was up to two times higher in the optimal breads compared to wheat flour bread. The findings generated from this study are helpful in bakery industry for designing products with enhanced nutritional properties and for introducing new products to the market.

Parkinson’s disease is a chronic, progressive, and neurodegenerative disease, and yet with an imprecise etiopathogenesis. Although neuroinflammation was initially thought to be a secondary condition, it is now believed that microglia-induced inflammation could also contribute to the degeneration of the nigrostriatal pathway. Here, we aimed to establish the feasibility of basic inflammatory biomarkers as prognostic factors in PD. The study was based on retrospective analyses of blood samples taken from patients diagnosed with PD, as well as from healthy subjects. Complete medical records, total leukocyte count with subpopulations, and erythrocyte sedimentation rate (ESR) were analyzed. We calculated the serum neutrophils-to-lymphocytes ratio (NLR) and platelet-to lymphocytes ratio (PLR), and also compared the laboratory data between the PD group and the control group. Only PLR and NLR showed statistically significant differences (p < 0.001 and 0.04, respectively). In our study, ESR did not show statistically significant correlations with motor score or with disability. In our research, ESR was correlated with the disease duration (p = 0.04), and PLR showed a significant correlation with disease stage (p = 0.027) and disease duration (p = 0.001), but not with motor state. These biomarkers could prove to be effective tools for a primary evaluation of inflammation in PD, but further tests are required to properly investigate the neuroinflammatory status of these patients.

Binding of the mitochondrial chaperone TRAP1 to client proteins shapes bioenergetic and proteostatic adaptations of cells, but the panel of TRAP1 clients is only partially defined. Here we show that TRAP1 interacts with F-ATP synthase, the protein complex that provides most cellular ATP. TRAP1 competes with the peptidyl-prolyl cis-trans isomerase cyclophilin D (CyPD) for binding to the oligomycin sensitivity-conferring protein (OSCP) subunit of F-ATP synthase, increasing its catalytic activity and counteracting the inhibitory effect of CyPD. Electrophysiological measurements indicate that TRAP1 directly inhibits a channel activity of purified F-ATP synthase endowed with the features of the permeability transition pore (PTP) and that it reverses PTP induction by CyPD, antagonizing PTP-dependent mitochondrial depolarization and cell death. Conversely, CyPD outcompetes the TRAP1 inhibitory effect on the channel. Our data identify TRAP1 as an F-ATP synthase regulator that can influence cell bioenergetics and survival and can be targeted in pathological conditions where these processes are dysregulated, such as cancer., (© 2022. The Author(s).)

Neurofibromin loss drives neoplastic growth and a rewiring of mitochondrial metabolism. Here we report that neurofibromin ablation dampens expression and activity of NADH dehydrogenase, the respiratory chain complex I, in an ERK-dependent fashion, decreasing both respiration and intracellular NAD + . Expression of the alternative NADH dehydrogenase NDI1 raises NAD + /NADH ratio, enhances the activity of the NAD + -dependent deacetylase SIRT3 and interferes with tumorigenicity in neurofibromin-deficient cells. The antineoplastic effect of NDI1 is mimicked by administration of NAD + precursors or by rising expression of the NAD + deacetylase SIRT3 and is synergistic with ablation of the mitochondrial chaperone TRAP1, which augments succinate dehydrogenase activity further contributing to block pro-neoplastic metabolic changes. These findings shed light on bioenergetic adaptations of tumors lacking neurofibromin, linking complex I inhibition to mitochondrial NAD + /NADH unbalance and SIRT3 inhibition, as well as to down-regulation of succinate dehydrogenase. This metabolic rewiring could unveil attractive therapeutic targets for neoplasms related to neurofibromin loss., (© 2022. The Author(s).)

Digital marketing has given new life to healthcare services by enhancing their visibility in the online space. People choose online healthcare services because they can receive instant answers and communicate with specialists in their comfortable environment at the right time. The purpose of this study was to understand the impact of virtual communities on the intention to use telemedicine. The model is based on a combination of consumer desire (psychological objective) and loyalty through promotional formats (economic objective), as well as data collected from 442 respondents analyzed using structural equation modeling. The research results show that by analyzing target groups in social networks, content can be individualized, and an accurate measurement of e-patient satisfaction must be conducted in order to improve the experience of future consumers of telemedicine services. The results of this study explain what makes people want to use digital healthcare services and can serve as a guide for people who run virtual communities and help digital healthcare service providers figure out how to market their services.

Misleading graphs are a source of misinformation that worry many experts. Especially people with a low graph literacy are thought to be persuaded by graphs that misrepresent the underlying data. But we know little about how people interpret misleading graphs and how these graphs influence their opinions. In this study we focus on the effect of truncating the y-axis for a line chart which exaggerates an upgoing trend. In a randomized controlled trial, we showed participants either a normal or a misleading chart, and we did so in two different contexts. After they had seen the graphs, we asked participants their opinion on the trend and to give an estimation of the increase. Finally we measured their graph literacy. Our results show that context is the only significant factor in opinion-forming; the misleading graph and graph literacy had no effect. None of these factors had a significant impact on estimations for the increase. These results show that people might be less susceptible to misleading graphs than we thought and that context has more impact than a misleading y-axis., Competing Interests: The authors have declared that no competing interests exist.

The aim of this research is to investigate the molecular features and microstructure of amaranth flour (AF) fractions and their partial replacement effect of wheat flour (WF) on the chemical composition, dough dynamic rheology, technological and sensory characteristics of bread. The microstructure and molecular characteristics of AF were depending on their particle size (PS). When WF replacement increased and PS decreased the composite flour was richest in protein, lipids, and ash, while the moisture and carbohydrates of these flours decreased. Dynamic rheological behavior revealed significant variations depending on PS and replacement level. Bread volume and firmness increased when more than 15% AF from large PS replaced WF, while medium and small PS at 5-15% replacements was increased the loaf porosity. Chroma values decreased and samples became darker when the replacement level increased. Moreover, replacement of WF with various AF fractions impacted bread sensory characteristics, obtaining better acceptance for large and medium PS up to 10%., (© 2022. The Author(s).)

This study aimed to investigate the antioxidant profile and the antimicrobial activity of four different types of monofloral honey (manuka (MH), brassica rapeseed (BH), acacia (AH), and linden honey (LH)) against some bacterial/fungal ATCC strains and some multidrug-resistant strains isolated from chronic otitis in dogs. For the characterisation of the antioxidant profile of each honey, we extracted the honey samples by hydroalcoholic extraction and analysed them in terms of total polyphenols (TPC), total flavonoids (TFC), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) using the spectrophotometric method. The antimicrobial activity was determined using the microdilution method at concentrations of 10%, 15%, and 20%, with the results expressed in OD (optical density) calculated as BIR% (bacterial inhibition rate)/MIR% (mycelial inhibition rate). The antioxidant characterisation of the analysed honey samples showed the highest antioxidant activity and concentrations of TPC and TFC in MH, followed by LH. MH was proven to be the most effective on most clinical isolates concerning the antimicrobial activity in comparison with BH, AH, and LH. Except for B. cepacia and P. vulgaris, all the clinical isolates were sensitive to the antibacterial activity of honey. Regarding the ATCC strains, MH 10% was the most effective in inhibiting all the strains tested except for P. aeruginosa. In conclusion, the efficacy classification in our study was MH > BH > AH > LH.

To raise biodiversity awareness effectively, communicators should be aware of knowledge levels in their audiences. Species identification skills have been used in the past as a measure of what people know about species, yet it is not known whether they serve as good indicators. To study the link between species identification and in-depth species knowledge, we presented an animal knowledge test to an online audience of over 7,000 Dutch adults, and used correlation and regression analyses to determine the extent to which species identification predicts in-depth knowledge about species' origin, habitat, diet, and behavior. We found that in-depth knowledge was higher in those who correctly identified species as compared with those who did not correctly identify species, for all four types of in-depth knowledge. Moreover, as compared to alternative variables (work, age, gender, and educational level), species identification was by far the best predictor for in-depth knowledge about species. However, species identification levels were generally higher than levels of in-depth knowledge, and knowledge gaps and misconceptions were uncovered. The results confirm the value of species identification tests, but also highlight limitations and challenges that should be taken into account when establishing knowledge levels and communicating biodiversity., Competing Interests: The authors have declared that no competing interests exist.

With a simple synthesis and easy engineering of physicochemical properties, iron oxide nanoparticles (IONPs) have become widely used in multiple biomedical applications. The study of IONPs toxicity has become an important issue, especially as the results reported so far are contradictory and range from lack of toxicity to cellular toxicity. The aim of this study was to evaluate the histopathological changes induced in mouse liver by long-term intraperitoneal injection of low doses of IONPs functionalized with salicylic acid (SaIONPs). The study was performed on C57BL/6 mice that received by intraperitoneal injection (IP), every two days, 0.6ml of SaIONPs aqueous suspension (35mg/kg body weight SaIONPs that contained 20mg/kg body weight of Fe3O4) for 28 days. The results of this study showed that the cumulative dose of 105mg/kg body weight SaIONPs (62mg/kg body weight of Fe3O4) induced histopathological changes in the subcapsular region of the mouse liver, possible by the release of salicylic acid into the peritoneal cavity. The cumulative dose of 244mg/kg body weight SaIONPs (145mg/kg body weight of Fe3O4) induced liver centrilobular necrosis, which requires the use of lower doses in biological applications. However, this may prove to be beneficial in the case of targeted accumulation of SaIONPs., Competing Interests: None to declare., (Copyright © 2014, Medical University Publishing House Craiova.)

Basal cell carcinoma (BCC) is a common, locally invasive tumor that arises within sun-damaged skin and rarely develops on the palms and soles or mucous membranes. Men generally have higher rates of BCC than women. Incidence also increases with age and the median age of diagnosis is 68 years old. Mortality from BCC is rare and cases of aggressive, local destructive, metastatic BCCs are more likely from tumors with aggressive histopathological (HP) patterns. The aim of this study was to investigate and correlate the immunohistochemical expression of p53, Ki67, alpha-smooth muscle actin (α-SMA), cluster of differentiation (CD)44 and CD31 with both aggressive and nonaggressive types of BCCs. In our study, we observed a varied staining pattern for p53, with the highest reactivity noticed in the peripheral palisading zone. The staining pattern for Ki67 was similar to p53, with a more pronounced reaction in the periphery of the tumor. We found different Ki67 and p53 expression among the various subtypes of BCC. The CD31 reactivity, mostly seen in the stroma, was positive in all BCCs and varied significantly between its different HP subtypes. Regarding stromal expression of α-SMA, the adenoid and basosquamous types had the most intense reaction in our study. The CD44 tumor expression was correlated in our study to the aggressive pattern of BCCs.

Background: The nonlinear nature of contagious diseases and the potential for exponential growth can be difficult to grasp for the general public. This has strong implications for public health communication, which needs to be both easily accessible and efficient. A pandemic is an extreme situation, and the accompanying strict societal measures are generally easier to accept if one understands the underlying reasoning behind them. Bringing about informed attitude change and achieving compliance to strict restrictions requires explanations of scientific concepts and terminologies that laypersons can understand., Objective: The aim of the project is to develop effective, evidence-based modes of video communication for translating complex, but important, health messages about pandemics to both the general population and decision makers. The study uses COVID-19 as a case to learn and prepare society for handling the ongoing and future pandemics, as well as to provide evidence-based tools for the science communication toolbox., Methods: The project applies a mixed methods design, combining qualitative methods (eg, interviews, observational studies, literature reviews) and quantitative methods (eg, randomized controlled trials [RCTs]). The project brings together researchers from a wide range of academic fields, as well as communication industry professionals., Results: This study has received funding from the Trond Mohn Foundation through the Research Council of Norway's "COVID-19 Emergency Call for Proposals" March 2020. Recruitment and data collection for the exploratory first phase of the project ran from February 2021 to March 2021. Creative communication work started in May 2021, and the production of videos for use in the RCTs in the final phase of the project started in September 2021., Conclusions: The COVCOM project will take on several grand challenges within the field of communicating science and provide evidence-based tools to the science communication toolbox. A long-term goal of the project is to contribute to the creation of a more resilient health care system by developing communication responses tailormade for different audiences, preparing society for any future pandemic., International Registered Report Identifier (irrid): DERR1-10.2196/34275., (©Jo Røislien, Jane K O'Hara, Ionica Smeets, Kolbjørn Brønnick, Siv Hilde Berg, Marie Therese Shortt, Daniel Adrian Lungu, Henriette Thune, Siri Wiig. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 11.03.2022.)

The present study aimed to determine the bacteria isolated from bovine mastitis and their antimicrobial resistance in the western part of Romania. Clinical mastitis was diagnosed based on local inflammation in the udder, changes in milk, and when present, generalized symptoms. Subclinical mastitis was assessed using a rapid test-the California Mastitis Test. The identification of bacterial strains was performed based on biochemical profiles using API system tests (API 20 E, API Staph, API 20 Strep, API Coryne, API 20 NE (bioMerieux, Marcy l'Etoile, France), and MALDI-TOF mass spectrometry (MS). The prevalent isolated bacteria were Staphylococcus spp. (50/116; 43.19%), followed by Streptococcus spp. (26/116; 22.41%), E. coli (16/116; 13.79%), Corynebacterium spp. (9/116; 7.75%), Enterococcus spp. (10/116; 8.62%), and Enterobacter spp. (5/116; 4.31%). Phenotype antimicrobial resistance profiling was performed used the disc diffusion method. Generally, Gram-positive bacteria showed low susceptibility to most of the antimicrobials tested, except cephalothin. Susceptibilities to penicillins and quinolones were fairly high in Gram-negative bacteria, whereas resistance was observed to macrolides, aminoglycosides, and tetracyclines. The highest number of isolates were multidrug resistant (MDR), the resistance pathotypes identified including the most frequently antimicrobials used in cow mastitis treatment in Romania.

The economic development of the tourism in disadvantaged mountain areas has the role of sustaining their development and economic growth. The premise of a successful development of tourism in these areas is given by the authenticity of resources. This paper aims to highlight the strategic perspectives/outlook of tourism in disadvantaged mountain areas through the evaluation of strategic alternatives using the concerted analysis SWOT-AHP. The aim of this study is to support communities and actors involved in the phenomenon of tourism in disadvantaged mountain areas in order to achieve positive results and as much as possible with awareness and avoidance of risks, and prevention or combating negative consequences. During the research and analysis, in accordance with the literature, the issue of entrepreneurship was treated as a dependent variable, and the phenomenon of tourism as an independent variable. The vision of tourism planning in disadvantaged mountain areas must focus on its sustainable development that contributes to increasing entrepreneurial initiatives by diversifying and ensuring the complementarity of tourism services calibrated to the needs of tourists and adapted to new social challenges. The strategic planning in the area of the tourism of disadvantaged mountain areas represents a topical challenge in the context of promoting sustainable tourism. Currently, there is a strategy at national level for developing tourism, but there is no strategy for developing tourism in disadvantaged mountain areas., (© The Author(s), under exclusive licence to Springer Nature B.V. 2021.)

Bacterial contamination of boar semen occurs with some frequency in artificial insemination centers and may have a negative effect on the quality of the semen as well as on the sows' reproductive capacity. Normally, the source of bacterial contamination in pig seminal doses is the own boar. However, distilled water or laboratory equipment used to elaborate the seminal doses can be an important source of bacterial contamination. This study focused on the identification of gram-negative bacteria in boar semen, and impact on the quality of ejaculates obtained from boar, as well as on the establishment of antimicrobial resistance patterns of isolated gram-negative bacteria. Semen samples were collected from 96 boars, ranging in age from 12-36 month, from three artificial insemination centers from the North-West of Romania. Bacterial species were identified by two methods: matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry and API 20 E (BioMerieux, France). The main bacteria isolated from the doses diluted semen were gram-negative bacteria (47.91%), with a majority of the contaminant bacteria belonging to the family Enterobacteriaceae : Seratia marcescens 19.56%, Proteus mirabilis 15.21% and Escherichia coli 10.86% and to the family Pseudomonaceae : Ralstonia picketii 17.39%, Burkholderia cepacia 10.86%, Pseudomonas aeruginosa 8.69%, and Pseudomonas fluorescens 4.34%, respectively. More than half of these isolates (56.52%) were resistant to gentamycin and 58.69% were resistant to penicillin. These antibiotics are very frequently added in sperm diluent in the centers for the processing of sperm from boars in Romania. Regular monitoring for bacterial contamination is an important aspect of a control program.

The present study aimed to investigate the influence of quinoa fractions (QF) on the chemical components of wheat flour (WF), dough rheological properties, and baking performance of wheat bread. The microstructure and molecular conformations of QF fractions were dependent to the particle size. The protein, lipids, and ash contents of composite flours increased with the increase of QF addition level, while particle size (PS) decreased these parameters as follows: Medium ˃ Small ˃ Large, the values being higher compared with the control (WF). QF addition raised dough tenacity from 86.33 to 117.00 mm H 2 O, except for the small fraction, and decreased the extensibility from 94.00 to 26.00 mm, while PS determined an irregular trend. The highest QF addition levels and PS led to the highest dough viscoelastic moduli (55,420 Pa for QL&#95;20, 65245 Pa for QM&#95;20 and 48305 Pa for QS&#95;20, respectively). Gradual increase of QF determined dough hardness increase and adhesiveness decrease. Bread firmness, springiness, and gumminess rises were proportional to the addition level. The volume, elasticity, and porosity of bread decreased with QF addition. Flour and bread crust and crumb color parameters were also influenced by QF addition with different PS.

(1) Background: Helleborus purpurascens Waldst. & Kit. (hellebore) is a plant species found mainly in Balkans and the Carpathians, and it is traditionally used for a variety of ailments since the time of Hippocrates. The aim of this study was to investigate the immunomodulatory effect of hellebore extracts correlated with relevant chemical compounds and the extraction method. (2) Methods: A methanolic (H1) and a hydroalcoholic extract (H2) were prepared by standard methods. Qualitative (HPTLC) and quantitative (HPLC) chemical analysis were conducted to reveal the ecdysones and polyphenolic compounds. In vitro studies were performed using rat macrophages, murine fibroblasts and immortalized human T-lymphocytes, and their viability was determined by MTS assay. In vivo studies involved a rat immunodepression model. (3) Results: In vitro assays revealed the stronger effect of H2 on cellular proliferation, compared to H1. In the in vivo assay, H2 revealed an immunostimulatory effect in the context of experimentally induced immunosuppression with dexamethasone, a superior effect to levamisole treatment according to the same regimen, in two doses every 24 h. There was no correlation between pharmacological effect and the reference compounds evaluated. (4) Conclusions: The immunomodulatory effect of methanolic and hydroalcoholic hellebore extracts is not due to ecdysones and polyphenolic compounds, but other polar substances, possible steroid glycosides.

The objective of this investigation was to evaluate the effects generated by amaranth flour (AF)-of different particle sizes (PS) added to white wheat flour from 0% to 20%-on the proximate composition, dough rheological behavior, and bread technological parameters. The reduction of particle size led to an increased hydration capacity of the wheat-amaranth composite flour, while bulk density decreased. Increasing the amount of AF and decreasing the PS led to a significant increase in protein, lipids, and ash contents, while the moisture and carbohydrates of the composite flour decreased. Increasing AF addition led to an increase in dough tenacity and a decrease in dough extensibility, while the PS had an irregular trend. The large particle size, at 15% and 20% levels of AF in wheat flour, increased significantly ( p < 0.001) the dough tenacity and hardness, bread firmness, but decreased bread volume, porosity, and elasticity, while medium and small particles at 5-15% addition levels improved porosity and elasticity of the composite bread. Significant correlations ( p < 0.05) were found between proximate composition, dough rheological characteristics, and bread quality for the wheat-amaranth composite flours. The results of this study are an important basis for the development of innovative wheat-amaranth bread recipes.

The present study aimed to determine the prevalence of Staphylococcus species, which pose risks for public health, by evaluating skin samples collected from dogs in an animal shelter in Timisoara. Skin samples were taken from 78 dogs, which were either clinically healthy or suffering from dermatological conditions. Staphylococcus spp. was isolated and recognized based on conventional methods based on colony appearance, microscopic morphology, sugar fermentation, and coagulase activity. Following biochemical analysis, Staphylococcus isolates were subject to PCR tests to detect sa-f and sa-r genes to confirm the isolates to genus level. The typical colonies were identified to species level using biochemical methods, namely the VITEK ® 2 ID-GP64 identification card (bioMerieux, France). The phenotypic antimicrobial resistance profiling was performed using the VITEK ® 2 AST GP Gram-positive specific bacteria card (bioMerieux, France). Forty-three samples were confirmed as positive for Staphylococcus spp. Staphylococcus isolates were classified into the following categories: S. aureus , S. pseudintermedius , S. intermedius , S. epidermitis , S. haemolyticus, and S. hyicus . Eight (18.60%, 8/43) out of all the samples harbored the mecA gene, highlighting the distribution among isolated staphylococcal species: Staphylococcus pseudintermedius (4/43, 9.30%), Staphylococcus intermedius (1/43, 2.32%) and Staphylococcus aureus (3/43, 9.30%), respectively. The phenomenon of resistance was present, to the following antimicrobial agents: erythromycin (38/43, 88.37%), benzylpenicillin, kanamycin, and tetracycline with 37 strains (37/43, 86.04%), gentamycin (30/43, 69.76%), chloramphenicol (29/43, 67.44%), trimethoprim/sulfamethoxazole (27/43, 62.79%), ampicillin (26/43, 60,46%), rifampicin (25/43, 58,13%), imipenem (14/43, 32,55%), nitrofurantoin (11/43, 25.58%), oxacillin (8/43, 18.60%), vancomycin (4/43, 9.30%) and clindamycin (3/43, 6.97%), respectively. The presence of multidrug-resistant zoonotic staphylococci in clinically healthy dogs and dogs with skin lesions is an animal health and human health concern.

The mitochondrial paralog of the Hsp90 chaperone family TRAP1 is often induced in tumors, but the mechanisms controlling its expression, as well as its physiological functions remain poorly understood. Here, we find that TRAP1 is highly expressed in the early stages of Zebrafish development, and its ablation delays embryogenesis while increasing mitochondrial respiration of fish larvae. TRAP1 expression is enhanced by hypoxic conditions both in developing embryos and in cancer models of Zebrafish and mammals. The TRAP1 promoter contains evolutionary conserved hypoxic responsive elements, and HIF1α stabilization increases TRAP1 levels. TRAP1 inhibition by selective compounds or by genetic knock-out maintains a high level of respiration in Zebrafish embryos after exposure to hypoxia. Our data identify TRAP1 as a primary regulator of mitochondrial bioenergetics in highly proliferating cells following reduction in oxygen tension and HIF1α stabilization.

Hexokinases are a family of ubiquitous exose-phosphorylating enzymes that prime glucose for intracellular utilization. Hexokinase 2 (HK2) is the most active isozyme of the family, mainly expressed in insulin-sensitive tissues. HK2 induction in most neoplastic cells contributes to their metabolic rewiring towards aerobic glycolysis, and its genetic ablation inhibits malignant growth in mouse models. HK2 can dock to mitochondria, where it performs additional functions in autophagy regulation and cell death inhibition that are independent of its enzymatic activity. The recent definition of HK2 localization to contact points between mitochondria and endoplasmic reticulum called Mitochondria Associated Membranes (MAMs) has unveiled a novel HK2 role in regulating intracellular Ca 2+ fluxes. Here, we propose that HK2 localization in MAMs of tumor cells is key in sustaining neoplastic progression, as it acts as an intersection node between metabolic and survival pathways. Disrupting these functions by targeting HK2 subcellular localization can constitute a promising anti-tumor strategy.

Hepatocellular carcinoma (HCC) is the main primary liver malignancy, being associated with both health and economic burden worldwide. Recently, novel molecular markers and possible therapeutic targets were identified. Different adhesion molecules, as well as possible angiogenesis-associated targets can be prime candidates when investigating novel therapies. Considering these premises, our goal was to study the co-existence of E-cadherin and aquaporin 1 (AQP1) in a series of HCC diagnosed patients. Utilizing archived tissue fragments from 17 patients diagnosed with well-to-moderate and poorly differentiated HCC, as well as four samples of normal liver tissue and using a highly specific biotin-free tyramide amplification technique, we have assessed here the expression of E-cadherin and AQP1 during HCC carcinogenesis. Moreover, as we have observed that some of the AQP1 expression seems membrane-bound, we have sought to evaluate their co-localization. Our data showed, as expected, that E-cadherin decreases from control tissue to low-grade and respectively, high-grade HCC. AQP1 was expressed, also as already known, at the level of endothelial blood vessels and bile ducts epithelia, however, we have showed here for the first time that this water pore is also expressed in the cytoplasm and membranes of hepatocytes, both in control and HCC tissue. Moreover, AQP1 expression parallels the decrease of E-cadherin expression during carcinogenesis, but together with this downregulation, we have also found a spatial decrease in the colocalization of the two proteins. Altogether, utilizing a biotin-free tyramide signal amplification technique, this study shows for the first time that AQP1 is expressed at the level of liver epithelia, in both control and HCC tissue.

To protect the personnel of the intervention units operating in high-risk areas, it is necessary to introduce (autonomous/semi-autonomous) robotic intervention systems. Previous studies have shown that robotic intervention systems should be as versatile as possible. Here, we focused on the idea of a robotic system composed of two vectors: a carrier vector and an operational vector. The proposed system particularly relates to the carrier vector. A simple analytical model was developed to enable the entire robotic assembly to be autonomous. To validate the analytical-numerical model regarding the kinematics and dynamics of the carrier vector, two of the following applications are presented: intervention for extinguishing a fire and performing measurements for monitoring gamma radiation in a public enclosure. The results show that the chosen carrier vector solution, i.e., the ground vehicle with six-wheel drive, satisfies the requirements related to the mobility of the robotic intervention system. In addition, the conclusions present the elements of the kinematics and dynamics of the robot., Competing Interests: The authors declare no conflict of interest.

Tomato peels are used as a valuable material to extract lycopene-rich oleoresins by supercritical CO 2 extraction. The extraction involves continuous circling of CO 2 to the extractor after removing the solute in the separators, S40 and S45, where the solvent power of the CO 2 is reduced by reducing pressure down to 20 MPa in S40 and 5 MPa in S45, respectively, leading to two extracts. Lycopene is found to be the major compound, representing 93% and 76% of the total carotenoids in S40 and S45 extracts, respectively. The two extracts are microencapsulated in whey protein concentrate and acacia gum by complex coacervation and freeze-drying, leading to corresponding P40 and P45 powders, with antioxidant activity of 8.57 ± 0.74 and 9.37 ± 0.48 mMol TEAC/g DW in P40 and P45, respectively. Different structural and morphological patterns are observed, with finer microparticles of 1-2 µm in P45. Both powders show dose and time-dependent antiproliferative activity. The half-maximal inhibitory concentration values are 100 µg/mL for P40 and 750 µg/mL for P45 sample, indicating a higher antiproliferative effect of P40 over P45 in HT-29 cell culture. The powders have an extended range of cytocompatibility, up to 1000 µg/mL, in L929 normal cells, stimulating the cell growth. Lycopene retention is tested, and values of 48% and 29% in P40 and P45 are found after 21 days at 25 °C, with the degradation rate in P45 significantly higher, due to the higher content of the surface lycopene, which favored its degradation.

CK2 is a Ser/Thr protein kinase overexpressed in many cancers. It is usually present in cells as a tetrameric enzyme, composed of two catalytic (α or α') and two regulatory (β) subunits, but it is active also in its monomeric form, and the specific role of the different isoforms is largely unknown. CK2 phosphorylates several substrates related to the uncontrolled proliferation, motility, and survival of cancer cells. As a consequence, tumor cells are addicted to CK2, relying on its activity more than healthy cells for their life, and exploiting it for developing multiple oncological hallmarks. However, little is known about CK2 contribution to the metabolic rewiring of cancer cells. With this study we aimed at shedding some light on it, especially focusing on the CK2 role in the glycolytic onco-phenotype. By analyzing neuroblastoma and osteosarcoma cell lines depleted of either one (α) or the other (α') CK2 catalytic subunit, we also aimed at disclosing possible pro-tumor functions which are specific of a CK2 isoform. Our results suggest that both CK2 α and α' contribute to cell proliferation, survival and tumorigenicity. The analyzed metabolic features disclosed a role of CK2 in tumor metabolism, and suggest prominent functions for CK2 α isoform. Results were also confirmed by CK2 pharmacological inhibition. Overall, our study provides new information on the mechanism of cancer cells addiction to CK2 and on its isoform-specific functions, with fundamental implications for improving future therapeutic strategies based on CK2 targeting.

The purpose of the article is to present a point of view on determining the mass moment of inertia coefficient of a tracked vehicle. This coefficient is very useful to be able to estimate the performance of a tracked vehicle, including slips in the converter. Determining vehicle acceleration plays an important role in assessing vehicle mobility. Additionally, during the transition from the Hydroconverter to the hydro-clutch regime, these estimations become quite difficult due to the complexity of the propulsion aggregate (engine and hydrodynamic transmission) and rolling equipment. The algorithm for determining performance is focused on estimating acceleration performance. To validate the proposed model, tests were performed to determine the equivalent reduced moments of inertia at the drive wheel (gravitational method) and the main components (three-wire pendulum method). The dynamic performances determined during the starting process are necessary for the validation of the general model for simulating the longitudinal dynamics of the vehicle. Finally, the differential and algebraic equations of the virtual model approximate more accurately the actual process of the operation of the vehicle. The virtual model, through the data obtained from the simulation process, allows for the determination, indirectly, of the variation of the mass moment of inertia coefficient and its expression of approximation., Competing Interests: The authors declare no conflict of interest.

Cancer cells undergo changes in metabolic and survival pathways that increase their malignancy. Isoform 2 of the glycolytic enzyme hexokinase (HK2) enhances both glucose metabolism and resistance to death stimuli in many neoplastic cell types. Here, we observe that HK2 locates at mitochondria-endoplasmic reticulum (ER) contact sites called MAMs (mitochondria-associated membranes). HK2 displacement from MAMs with a selective peptide triggers mitochondrial Ca 2+ overload caused by Ca 2+ release from ER via inositol-3-phosphate receptors (IP3Rs) and by Ca 2+ entry through plasma membrane. This results in Ca 2+ -dependent calpain activation, mitochondrial depolarization and cell death. The HK2-targeting peptide causes massive death of chronic lymphocytic leukemia B cells freshly isolated from patients, and an actionable form of the peptide reduces growth of breast and colon cancer cells allografted in mice without noxious effects on healthy tissues. These results identify a signaling pathway primed by HK2 displacement from MAMs that can be activated as anti-neoplastic strategy., (© 2020 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)

Multiple sclerosis (MS) is a chronic, severe disease, characterized by a progressive alteration in neuronal transmission, which decreases personal independence and quality of life (QoL). This study aimed to investigate the relationship between QoL and personal autonomy in patients with MS, as well as its correlation with age, educational level, and diseases severity. Twenty-six MS patients were followed-up for six months. All patients completed the 15D questionnaire two times: at T0, when they started a new treatment, and at T1 after six months of treatment. At the end point, all patients completed the Personal Autonomy Questionnaire. The average patient age was 43 years (SD = 10), and 89% of them were female. The mean severity and duration of MS were 3.5 (SD = 1.75) and 9.5 (SD = 5.1), respectively. The average QoL of MS patients at T0 was 0.66 (SD = 0.18), and that at T1 was 0.71 (SD = 0.16). The scores of patients with different types of MS, i.e., relapsing-remitting MS (RRMS) or secondary progressive MS (SPMS), were compared. SPMS patients were older than RRMS patients (mean age 47.5 vs. 39.7 years; p = 0.032), and more RRMS patients were working (0.014). SPMS patients described the same QoL and personal autonomy as RRMS patients. Results from bivariate correlation analyses showed a significant relationship between QoL and age, education, and severity of MS. Also, the analysis showed no significant correlation between QoL and personal autonomy.