A New Hyaluronic Emulgel of Hesperetin for Topical Application-An In Vitro Evaluation.

The present study aimed to formulate and characterize a hesperetin formulation to achieve adequate deposition and retention of hesperetin in the epidermis as a target for some cosmetic/dermatological actions. To derive the final emulgel, various formulations incorporating different proportions of Polysorbate 80 and hyaluronic acid underwent testing through a Box-Behnken experimental design. Nine formulations were created until the targeted emulgel properties were achieved. This systematic approach, following the principles of a design of experiment (DoE) methodology, adheres to a quality-by-design (QbD) paradigm, ensuring a robust and purposeful formulation and highlighting the commitment to a quality-driven design approach. The emulsions were developed using the phase inversion method, optimizing the emulgel with the incorporation of hyaluronic acid. Physically stable optimized emulgels were evaluated for their globule size, surface charge, viscosity, pH, electrical conductivity, and hesperetin content. These assays, along with the temperature swing test, were used to select the optimal formulation. It was characterized by a droplet size, d[4,3], of 4.02 µm, a Z-potential of -27.8 mV, an O/W sign, a pH of 5.2, and a creamy texture and proved to be stable for at least 2 months at room temperature. Additionally, in vitro release kinetics from the selected emulgel exhibited a sustained release profile of hesperetin. Skin assays revealed adequate retention of hesperetin in the human epidermis with minimum permeation. Altogether, these results corroborate the promising future of the proposed emulgel in cosmetic or dermatological use on healthy or diseased skin.

Damage Detection in FRP-Reinforced Concrete Elements.

Fiber-Reinforced Polymer (FRP) composites have emerged as a promising alternative to conventional steel reinforcements in concrete structures owing to their benefits of corrosion resistance, higher strength-to-weight ratio, reduced maintenance cost, extended service life, and superior durability. However, there has been limited research on non-destructive testing (NDT) methods applicable for identifying damage in FRP-reinforced concrete (FRP-RC) elements. This knowledge gap has often limited its application in the construction industry. Engineers and owners often lack confidence in utilizing this relatively new construction material due to the challenge of assessing its condition. Thus, the main objective of this study is to determine the applicability of two of the most common NDT methods: the Ground-Penetrating Radar (GPR) and Phased Array Ultrasonic (PAU) methods for the detection of damage in FRP-RC elements. Three slab specimens with variations in FRP type (glass-, carbon- and basalt-FRP, i.e., GFRP, CFRP, and BFRP, respectively), bar diameter, bar depths, and defect types were investigated to determine the limitations and detection capabilities of these two NDT methods. The results show that GPR could detect damage in GFRP bars and CFRP strands, but PAU was limited to damage detection in CFRP strands. The findings of this study show the applicability of conventional NDT methods to FRP-RC and at the same time identify the areas with a need for further research.

An evaluation of emotion recognition, emotion reactivity, and emotion dysregulation as prospective predictors of 12-month trajectories of non-suicidal self-injury in an adolescent psychiatric inpatient sample.

BACKGROUND: Little is known about trajectories of NSSI. We aimed to identify NSSI trajectories in adolescent psychiatric inpatients and emotional processes that differentiate between trajectories. METHODS: Participants were 180 adolescents (71.7 % female; mean age of 14.89 years, SD = 1.35) from a psychiatric inpatient facility. NSSI was assessed at their index hospitalization, as well as 6, and 12 months after discharge. Emotion recognition, emotion reactivity, and emotion dysregulation were assessed at baseline. Latent class mixture modeling was used to identify different NSSI trajectories and ANOVAs were used to evaluate predictors of the trajectories. RESULTS: Analyses yielded three NSSI trajectories. These included a stable low-frequency class (90.53 % of sample), a stable moderate-frequency class, and a class characterized by high-frequency NSSI at baseline but that largely resolves by 6-month follow-up. After adjustments for multiple comparisons were made, only emotion regulation at baseline differentiated between the trajectories, with greater overall emotion dysregulation and greater emotional non-acceptance (a facet of emotion dysregulation) characterizing the initially high-frequency class and the stable moderate-frequency class more than the stable low-frequency class (ps < .05). Difficulties engaging in goal-directed behavior when distressed characterized the stable moderate-frequency NSSI class more than the stable low-frequency class (p < .05). Limitations The study sample consists predominantly of female and White adolescents and thus may not generalize to other demographic groups. CONCLUSIONS: The current findings suggest that interventions involving emotion regulation with adolescents who engage in NSSI would particularly benefit from a focus on increasing acceptance of emotional experiences.

Prevalence, and Risk Indicators of Coronal and Root Caries in Mexican Older Adults in Nursing Homes.

Background: Several factors are associated with coronal and root caries in older persons. The purpose of this study was to determine the experience, prevalence, and risk indicators (socioeconomic, sociodemographic, and dental variables) of coronal and root caries in older persons residing in nursing homes in Mexico. Methods: A cross-sectional study was carried out in 227 dentate participants with natural teeth. Convenience sample, where all dentate residents were invited to participate. The dependent variables were coronal caries and root caries, which were determined through an oral clinical examination. The independent variables were sociodemographic factors, location, type of center, surfaces free of dental biofilm and calculus, surfaces with recession, retainers in contact with surfaces with recession, xerostomia, smoking, and the previous use of dental services. The binary logistic regression model was used in the analysis. Results: The mean age of the participants in this study was 77.7±8.8 years, and 69.2% were women. Moreover, 71.8% live in long-term care facilities, and 48.0% live in Mexico City. The prevalence of coronal and root caries was found to be 67.8% and 50.7%, respectively. Being male and living in Mexico City were risk indicators for coronal caries, and with a 1% increase in surfaces with no biofilm, the risk decreased by 2%. Being widowed, having government or no social security, denture retainers, and coronal caries were risk indicators for root caries, while the utilization of dental services indicated lower risk. Conclusion: Several variables that differ in nature were found to be risk indicators for coronal and root caries. Coronal caries increases the risk of root caries. Prevention should be aimed at identifying persons at higher risk, and dental care should be improved for persons living in long-term care institutions.

Control of a Back-Support Exoskeleton to Assist Carrying Activities.

Back-support exoskeletons are commonly used in the workplace to reduce low back pain risk for workers performing demanding activities. However, for the assistance of tasks differing from lifting, back-support exoskeletons potential has not been exploited extensively. This work focuses on the use of an active back-support exoskeleton to assist carrying. A control strategy is designed that modulates the exoskeleton torques to comply with the task assistance requirements. In particular, two gait phase detection frameworks are exploited to adapt the exoskeleton assistance according to the legs' motion. The control strategy is assessed through an experimental analysis on ten subjects. Carrying task is performed without and with the exoskeleton assistance. Results prove the potential of the presented control in assisting the task without hindering the gait movement and improving the usability experienced by users. Moreover, the exoskeleton assistance significantly reduces the lumbar load associated with the task, demonstrating its promising use for risk mitigation in the workplace.

Elbow-sideWINDER (Elbow-side Wearable INDustrial Ergonomic Robot): design, control, and validation of a novel elbow exoskeleton.

Musculoskeletal Disorders associated with the elbow are one of the most common forms of work-related injuries. Exoskeletons have been proposed as an approach to reduce and ideally eliminate these injuries; however, exoskeletons introduce their own problems, especially discomfort due to joint misalignment. The Elbow-sideWINDER with its associated control strategy is a novel elbow exoskeleton to assist elbow flexion/extension during occupational tasks. This study describes the exoskeleton showing how this can minimize discomfort caused by joint misalignment, maximize assistive performance, and provide increased robustness and reliability in real worksites. The proposed medium-level control strategy can provide effective assistive torque using three control units as follows: an arm kinematics estimator, a load estimator, and a friction compensator. The combined hardware/software system of the Elbow-sideWINDER is tested in load-lifting tasks (2 and 7 kg). This experiment focuses on the reduction in the activation level of the biceps brachii and triceps brachii in both arms and the change in the range of motion of the elbow during the task. It is shown that using the Elbow-sideWINDER, the biceps brachii, responsible for the elbow flexion, was significantly less activated (up to 38.8% at 2 kg and 25.7% at 7 kg, on average for both arms). For the triceps brachii, the muscle activation was reduced by up to 37.0% at 2 kg and 35.1% at 7 kg, on average for both arms. When wearing the exoskeleton, the range of motion of the elbow was reduced by up to 13.0° during the task, but it was within a safe range and could be compensated for by other joints such as the waist or knees. There are extremely encouraging results that provide good indicators and important clues for future improvement of the Elbow-sideWINDER and its control strategy.

Quasi-passive lower limbs exosuit: an in-depth assessment of fatigue, kinematic and muscular patterns while comparing assistive strategies on an expert subject's gait analysis.

Wearable robots are becoming a valuable solution that helps injured, and elderly people regain mobility and improve clinical outcomes by speeding up the rehabilitation process. The XoSoft exosuit identified several benefits, including improvement of assistance, usability, and acceptance with a soft, modular, bio-mimetic, and quasi-passive exoskeleton. This study compares two assistive configurations: (i) a bilateral hip flexion (HA, hips-assistance) and (ii) a bilateral hip flexion combined with ankle plantarflexion (HAA, hips-ankles-assistance) with the main goal of evaluating compensatory actions and synergetic effects generated by the human- exoskeleton interaction. A complete description of this complex interaction scenario with this actuated exosuit is evaluated during a treadmill walking task, using several indices to quantify the human-robot interaction in terms of muscular activation and fatigue, metabolic expenditure, and kinematic motion patterns. Evidence shows that the HAA biomimetic controller is synergetic with the musculature and performs better concerning the other control strategy. The experimentation demonstrated a metabolic expenditure reduction of 8% of Metabolic Equivalent of Task (MET), effective assistance of the muscular activation of 12.5%, a decrease of the muscular fatigue of 0.6% of the mean frequency, and a significant reduction of the compensatory actions, as discussed in this work. Compensatory effects are present in both assistive configurations, but the HAA modality provides a 47% reduction of compensatory effects when considering muscle activation.

Intranasal Drug Administration in Alzheimer-Type Dementia: Towards Clinical Applications.

Alzheimer-type dementia (ATD) treatments face limitations in crossing the blood-brain barrier and systemic adverse effects. Intranasal administration offers a direct route to the brain via the nasal cavity's olfactory and trigeminal pathways. However, nasal physiology can hinder drug absorption and limit bioavailability. Therefore, the physicochemical characteristics of formulations must be optimized by means of technological strategies. Among the strategies that have been explored, lipid-based nanosystems, particularly nanostructured lipid carriers, are promising in preclinical investigations with minimal toxicity and therapeutic efficacy due to their ability to overcome challenges associated with other nanocarriers. We review the studies of nanostructured lipid carriers for intranasal administration in the treatment of ATD. Currently, no drugs for intranasal administration in ATD have marketing approval, with only three candidates, insulin, rivastigmine and APH-1105, being clinically investigated. Further studies with different candidates will eventually confirm the potential of the intranasal route of administration in the treatment of ATD.

Unveiling the Stereoselectivity and Regioselectivity of the [3+2] Cycloaddition Reaction between N-methyl-C-4-methylphenyl-nitrone and 2-Propynamide from a MEDT Perspective.

[3+2] cycloaddition reactions play a crucial role in synthesizing complex organic molecules and have significant applications in drug discovery and materials science. In this study, the [3+2] cycloaddition (32CA) reactions of N-methyl-C-4-methyl phenyl-nitrone 1 and 2-propynamide 2, which have not been extensively studied before, were investigated using molecular electron density theory (MEDT) at the B3LYP/6-311++G(d,p) level of theory. According to an electron localization function (ELF) study, N-methyl-C-4-methyl phenyl-nitrone 1 is a zwitterionic species with no pseudoradical or carbenoid centers. Conceptual density functional theory (CDFT) indices were used to predict the global electronic flux from the strong nucleophilic N-methyl-C-4-methyl phenylnitrone 1 to the electrophilic 2-propynamide 2 functions. The 32CA reactions proceeded through two pairs of stereo- and regioisomeric reaction pathways to generate four different products: 3, 4, 5, and 6. The reaction pathways were irreversible owing to their exothermic characters: -136.48, -130.08, -130.99, and -140.81 kJ mol-1, respectively. The enthalpy of the 32CA reaction leading to the formation of cycloadduct 6 was lower compared with the other path owing to a slight increase in its polar character, observed through the global electron density transfer (GEDT) during the transition states and along the reaction path. A bonding evolution theory (BET) analysis showed that these 32CA reactions proceed through the coupling of pseudoradical centers, and the formation of new C-C and C-O covalent bonds did not begin in the transition states.

Tooth Loss and Associated Factors in Mexican Older Adults in Nursing Homes: A Multicenter Cross-Sectional Study.

The objective of this study was to determine the experience of tooth loss and associated factors in older adults and elderly residing in nursing homes. A cross-sectional study was conducted in Mexican older adults and elderly aged ≥60 years living in four nursing homes (two in Mexico City, Mexico: one in Cuernavaca, Morelos, and one in Oaxaca, Oaxaca). The data were collected at the facility (home nursing) by two dentists in 2019. To determine the number of tooth loss and DMFT, a clinical oral examination was performed. In addition, a questionnaire was applied to determine diverse independent variables (demographic, socioeconomic, and behavioral). The analysis was performed using nonparametric tests and negative binomial regression (p < 0.05). 257 subjects were included. The mean age was 81.25 ± 9.02 years, and 60.7% were women. The mean number of lost teeth was 18.78 ± 9.05 (women = 19.43 ± 8.59 and men = 17.77 ± 9.68; p > 0.05). In the multivariate negative binomial regression model, it was found that, for each one-year increase in age, the mean tooth loss increased 0.92% (p < 0.05). In current smokers (p < 0.01) and in those who brush their teeth < 2 times a day (p < 0.01), the average of tooth loss increased 22.04% and 61.46%, respectively. The experience of tooth loss in Mexican older adults and elderly was high. Demographic (age) and habit of behavior (tobacco use and less frequent tooth brushing) were associated with increased tooth loss. It is important to promote oral health programs for institutionalized older adults.

FRP-Reinforced/Strengthened Concrete: State-of-the-Art Review on Durability and Mechanical Effects.

Fiber-reinforced polymer (FRP) composites have gained increasing recognition and application in the field of civil engineering in recent decades due to their notable mechanical properties and chemical resistance. However, FRP composites may also be affected by harsh environmental conditions (e.g., water, alkaline solutions, saline solutions, elevated temperature) and exhibit mechanical phenomena (e.g., creep rupture, fatigue, shrinkage) that could affect the performance of the FRP reinforced/strengthened concrete (FRP-RSC) elements. This paper presents the current state-of-the-art on the key environmental and mechanical conditions affecting the durability and mechanical properties of the main FRP composites used in reinforced concrete (RC) structures (i.e., Glass/vinyl-ester FRP bars and Carbon/epoxy FRP fabrics for internal and external application, respectively). The most likely sources and their effects on the physical/mechanical properties of FRP composites are highlighted herein. In general, no more than 20% tensile strength was reported in the literature for the different exposures without combined effects. Additionally, some provisions for the serviceability design of FRP-RSC elements (e.g., environmental factors, creep reduction factor) are examined and commented upon to understand the implications of the durability and mechanical properties. Furthermore, the differences in serviceability criteria for FRP and steel RC elements are highlighted. Through familiarity with their behavior and effects on enhancing the long-term performance of RSC elements, it is expected that the results of this study will help in the proper use of FRP materials for concrete structures.

Similarity-Based Virtual Screening to Find Antituberculosis Agents Based on Novel Scaffolds: Design, Syntheses and Pharmacological Assays.

A method to identify molecular scaffolds potentially active against the Mycobacterium tuberculosis complex (MTBC) is developed. A set of structurally heterogeneous agents against MTBC was used to obtain a mathematical model based on topological descriptors. This model was statistically validated through a Leave-n-Out test. It successfully discriminated between active or inactive compounds over 86% in database sets. It was also useful to select new potential antituberculosis compounds in external databases. The selection of new substituted pyrimidines, pyrimidones and triazolo[1,5-a]pyrimidines was particularly interesting because these structures could provide new scaffolds in this field. The seven selected candidates were synthesized and six of them showed activity in vitro.

Assessment methodology for human-exoskeleton interactions: Kinetic analysis based on muscle activation.

During the development and assessment of an exoskeleton, many different analyzes need to be performed. The most frequently used evaluate the changes in muscle activations, metabolic consumption, kinematics, and kinetics. Since human-exoskeleton interactions are based on the exchange of forces and torques, the latter of these, kinetic analyzes, are essential and provide indispensable evaluation indices. Kinetic analyzes, however, require access to, and use of, complex experimental apparatus, involving many instruments and implicating lengthy data analysis processes. The proposed methodology in this paper, which is based on data collected via EMG and motion capture systems, considerably reduces this burden by calculating kinetic parameters, such as torque and power, without needing ground reaction force measurements. This considerably reduces the number of instruments used, allows the calculation of kinetic parameters even when the use of force sensors is problematic, does not need any dedicated software, and will be shown to have high statistical validity. The method, in fact, combines data found in the literature with those collected in the laboratory, allowing the analysis to be carried out over a much greater number of cycles than would normally be collected with force plates, thus enabling easy access to statistical analysis. This new approach evaluates the kinetic effects of the exoskeleton with respect to changes induced in the user's kinematics and muscular activation patterns and provides indices that quantify the assistance in terms of torque (AMI) and power (API). Following the User-Center Design approach, which requires driving the development process as feedback from the assessment process, this aspect is critical. Therefore, by enabling easy access to the assessment process, the development of exoskeletons could be positively affected.

Nanoliposomes in Cancer Therapy: Marketed Products and Current Clinical Trials.

The drugs used for cancer treatment have many drawbacks, as they damage both tumor and healthy cells and, in addition, they tend to be poorly soluble drugs. Their transport in nanoparticles can solve these problems as these can release the drug into tumor tissues, as well as improve their solubility, bioavailability, and efficacy, reducing their adverse effects. This article focuses on the advantages that nanotechnology can bring to medicine, with special emphasis on nanoliposomes. For this, a review has been made of the nanoliposomal systems marketed for the treatment of cancer, as well as those that are in the research phase, highlighting the clinical trials being carried out. All marketed liposomes studied are intravenously administered, showing a reduced intensity of side-effects compared with the nonliposomal form. Doxorubicin is the active ingredient most frequently employed. Ongoing clinical trials expand the availability of liposomal medicines with new clinical indications. In conclusion, the introduction of drugs in nanoliposomes means an improvement in their efficacy and the quality of life of patients. The future focus of research could be directed to develop multifunctional targeted nanoliposomes using new anticancer drugs, different types of existing drugs, or new standardized methodologies easily translated into industrial scale.

Antidepressants in children and adolescents with major depressive disorder and the influence of placebo response: A meta-analysis.

BACKGROUND: There are few available antidepressants for pediatric Major Depressive Disorder (MDD). The objective of this systematic review and meta-analysis was to review industry-funded studies of antidepressants in children and adolescents with MDD, and to better understand the contribution of study design and placebo response to the findings of these studies. METHODS: Randomized, double-blind, placebo-controlled clinical trials that compared antidepressant with placebo for the acute treatment of MDD in children and/or adolescents were selected. Estimates of the standardized mean difference (SMD) in change in Children's Depression Rating Scale-Revised scores were pooled, after examining for heterogeneity. A random-effects meta-analysis was completed. RESULTS: Thirty-four antidepressant-placebo comparisons, involving 6161 subjects, were included. The SMD among all studies was 0.12 (CI 0.08, 0.17; p < 0.001), a very small effect size, lower than that seen in studies of adults with MDD. When the meta-analysis was limited to studies with a low mean placebo response, the SMD increased to 0.19 and further increased to 0.22 when studies with at least a 50% chance of receiving placebo were included. LIMITATIONS: Many studies focused on older children and younger adolescents. Our findings may not reflect antidepressant efficacy in older adolescents. CONCLUSIONS: The modest SMD identified in this analysis may reflect study design factors and the application of antidepressants developed for adults to pediatric patients. Given the urgent clinical need for more pediatric MDD treatments, the influence of placebo response and the need for drug development tailored to this population should be considered in pediatric MDD trial design.

Noninvasive Prototype for Type 2 Diabetes Detection.

The present work demonstrates the design and implementation of a human-safe, portable, noninvasive device capable of predicting type 2 diabetes, using electrical bioimpedance and biometric features to train an artificial learning machine using an active learning algorithm based on population selection. In addition, there is an API with a graphical interface that allows the prediction and storage of data when the characteristics of the person are sent. The results obtained show an accuracy higher than 90% with statistical significance (p < 0.05). The Kappa coefficient values were higher than 0.9, showing that the device has a good predictive capacity which would allow the screening process of type 2 diabetes. This development contributes to preventive medicine and makes it possible to determine at a low cost, comfortably, without medical preparation, and in less than 2 minutes whether a person has type 2 diabetes.

µRALP and Beyond: Micro-Technologies and Systems for Robot-Assisted Endoscopic Laser Microsurgery.

Laser microsurgery is the current gold standard surgical technique for the treatment of selected diseases in delicate organs such as the larynx. However, the operations require large surgical expertise and dexterity, and face significant limitations imposed by available technology, such as the requirement for direct line of sight to the surgical field, restricted access, and direct manual control of the surgical instruments. To change this status quo, the European project µRALP pioneered research towards a complete redesign of current laser microsurgery systems, focusing on the development of robotic micro-technologies to enable endoscopic operations. This has fostered awareness and interest in this field, which presents a unique set of needs, requirements and constraints, leading to research and technological developments beyond µRALP and its research consortium. This paper reviews the achievements and key contributions of such research, providing an overview of the current state of the art in robot-assisted endoscopic laser microsurgery. The primary target application considered is phonomicrosurgery, which is a representative use case involving highly challenging microsurgical techniques for the treatment of glottic diseases. The paper starts by presenting the motivations and rationale for endoscopic laser microsurgery, which leads to the introduction of robotics as an enabling technology for improved surgical field accessibility, visualization and management. Then, research goals, achievements, and current state of different technologies that can build-up to an effective robotic system for endoscopic laser microsurgery are presented. This includes research in micro-robotic laser steering, flexible robotic endoscopes, augmented imaging, assistive surgeon-robot interfaces, and cognitive surgical systems. Innovations in each of these areas are shown to provide sizable progress towards more precise, safer and higher quality endoscopic laser microsurgeries. Yet, major impact is really expected from the full integration of such individual contributions into a complete clinical surgical robotic system, as illustrated in the end of this paper with a description of preliminary cadaver trials conducted with the integrated µRALP system. Overall, the contribution of this paper lays in outlining the current state of the art and open challenges in the area of robot-assisted endoscopic laser microsurgery, which has important clinical applications even beyond laryngology.

Adaptation of the Beliefs about Well-Being Scale to the Spanish population / Adaptación de la Escala de Creencias sobre el Bienestar a la población española

The study of happiness and well-being is receiving increased attention in different fields. Recent research into well-being has focused on delving deeper into the individual's conception about the experience of well-being. McMahan and Estes (2011a) created a scale that assesses lay conceptions of well-being based on four dimensions: the experience of pleasure, avoidance of negative experience, self-development and contribution to others. The goal of this study was to adapt this scale, the Beliefs about Well-Being Scale (BWBS), to the Spanish population. The sample consisted of 1,024 participants from the general population ranging in age interval from 17 to 87 years old. The confirmatory factorial analysis results in a structure of four dimensions, similar to the original scale, although in the adaptation of the scale the items decrease from 16 to 12. The results of the reliability analysis reveal indexes similar to those of the original scale. These results confirm the validity of Beliefs about Well-Being Scale with general population in a cultural context different from the original study. This will allow cross-cultural studies to analyze the influence of culture in the perception of well-being

El estudio de la felicidad y el bienestar está recibiendo cada vez más atención en diferentes campos. Las investigaciones recientes sobre el bienestar se han centrado en profundizar en la concepción del individuo sobre la experiencia del bienestar. McMahan y Estes (2011a) crearon una escala que evalúa las concepciones legas del bienestar en base a cuatro dimensiones: la experiencia de placer, la evitación de la experiencia negativa, el autodesarrollo y la contribución a los demás. El objetivo de este estudio fue adaptar esta escala, Beliefs about Well-Being Scale (BWBS), a la población española. La muestra estuvo formada por 1.024 participantes de la población general con un intervalo de edad entre 17 y 87 años. El análisis factorial confirmatorio da como resultado una estructura de cuatro dimensiones, similar a la escala original, aunque en la adaptación de la escala los ítems disminuyen de 16 a 12. Los resultados del análisis de fiabilidad revelan índices similares a los de la escala original. Estos resultados confirman la validez de la Escala de Creencias sobre el Bienestar con población general en un contexto cultural diferente al del estudio original. Esto permitirá realizar estudios transculturales para analizar la influencia de la cultura en la percepción del bienestar