De novo design of modular peptide-binding proteins by superhelical matching.

General approaches for designing sequence-specific peptide-binding proteins would have wide utility in proteomics and synthetic biology. However, designing peptide-binding proteins is challenging, as most peptides do not have defined structures in isolation, and hydrogen bonds must be made to the buried polar groups in the peptide backbone1-3. Here, inspired by natural and re-engineered protein-peptide systems4-11, we set out to design proteins made out of repeating units that bind peptides with repeating sequences, with a one-to-one correspondence between the repeat units of the protein and those of the peptide. We use geometric hashing to identify protein backbones and peptide-docking arrangements that are compatible with bidentate hydrogen bonds between the side chains of the protein and the peptide backbone12. The remainder of the protein sequence is then optimized for folding and peptide binding. We design repeat proteins to bind to six different tripeptide-repeat sequences in polyproline II conformations. The proteins are hyperstable and bind to four to six tandem repeats of their tripeptide targets with nanomolar to picomolar affinities in vitro and in living cells. Crystal structures reveal repeating interactions between protein and peptide interactions as designed, including ladders of hydrogen bonds from protein side chains to peptide backbones. By redesigning the binding interfaces of individual repeat units, specificity can be achieved for non-repeating peptide sequences and for disordered regions of native proteins.

Design of cell-type-specific hyperstable IL-4 mimetics via modular de novo scaffolds.

The interleukin-4 (IL-4) cytokine plays a critical role in modulating immune homeostasis. Although there is great interest in harnessing this cytokine as a therapeutic in natural or engineered formats, the clinical potential of native IL-4 is limited by its instability and pleiotropic actions. Here, we design IL-4 cytokine mimetics (denoted Neo-4) based on a de novo engineered IL-2 mimetic scaffold and demonstrate that these cytokines can recapitulate physiological functions of IL-4 in cellular and animal models. In contrast with natural IL-4, Neo-4 is hyperstable and signals exclusively through the type I IL-4 receptor complex, providing previously inaccessible insights into differential IL-4 signaling through type I versus type II receptors. Because of their hyperstability, our computationally designed mimetics can directly incorporate into sophisticated biomaterials that require heat processing, such as three-dimensional-printed scaffolds. Neo-4 should be broadly useful for interrogating IL-4 biology, and the design workflow will inform targeted cytokine therapeutic development.

De novo protein design by citizen scientists.

Online citizen science projects such as GalaxyZoo1, Eyewire2 and Phylo3 have proven very successful for data collection, annotation and processing, but for the most part have harnessed human pattern-recognition skills rather than human creativity. An exception is the game EteRNA4, in which game players learn to build new RNA structures by exploring the discrete two-dimensional space of Watson-Crick base pairing possibilities. Building new proteins, however, is a more challenging task to present in a game, as both the representation and evaluation of a protein structure are intrinsically three-dimensional. We posed the challenge of de novo protein design in the online protein-folding game Foldit5. Players were presented with a fully extended peptide chain and challenged to craft a folded protein structure and an amino acid sequence encoding that structure. After many iterations of player design, analysis of the top-scoring solutions and subsequent game improvement, Foldit players can now-starting from an extended polypeptide chain-generate a diversity of protein structures and sequences that encode them in silico. One hundred forty-six Foldit player designs with sequences unrelated to naturally occurring proteins were encoded in synthetic genes; 56 were found to be expressed and soluble in Escherichia coli, and to adopt stable monomeric folded structures in solution. The diversity of these structures is unprecedented in de novo protein design, representing 20 different folds-including a new fold not observed in natural proteins. High-resolution structures were determined for four of the designs, and are nearly identical to the player models. This work makes explicit the considerable implicit knowledge that contributes to success in de novo protein design, and shows that citizen scientists can discover creative new solutions to outstanding scientific challenges such as the protein design problem.

De novo design of potent and selective mimics of IL-2 and IL-15.

We describe a de novo computational approach for designing proteins that recapitulate the binding sites of natural cytokines, but are otherwise unrelated in topology or amino acid sequence. We use this strategy to design mimics of the central immune cytokine interleukin-2 (IL-2) that bind to the IL-2 receptor ßγc heterodimer (IL-2Rßγc) but have no binding site for IL-2Rα (also called CD25) or IL-15Rα (also known as CD215). The designs are hyper-stable, bind human and mouse IL-2Rßγc with higher affinity than the natural cytokines, and elicit downstream cell signalling independently of IL-2Rα and IL-15Rα. Crystal structures of the optimized design neoleukin-2/15 (Neo-2/15), both alone and in complex with IL-2Rßγc, are very similar to the designed model. Neo-2/15 has superior therapeutic activity to IL-2 in mouse models of melanoma and colon cancer, with reduced toxicity and undetectable immunogenicity. Our strategy for building hyper-stable de novo mimetics could be applied generally to signalling proteins, enabling the creation of superior therapeutic candidates.

Genome-wide CRISPR screen reveals CLPTM1L as a lipid scramblase required for efficient glycosylphosphatidylinositol biosynthesis.

SignificanceScramblases translocate lipids across the lipid bilayer without consumption of ATP, thereby regulating lipid distributions in cellular membranes. Cytosol-to-lumen translocation across the endoplasmic reticulum (ER) membrane is a common process among lipid glycoconjugates involved in posttranslational protein modifications in eukaryotes. These translocations are thought to be mediated by specific ER-resident scramblases, but the identity of these proteins and the underlying molecular mechanisms have been elusive. Here, we show that CLPTM1L, an integral membrane protein with eight putative transmembrane domains, is the major lipid scramblase involved in efficient glycosylphosphatidylinositol biosynthesis in the ER membrane. Our results validate the long-standing hypothesis that lipid scramblases ensure the efficient translocations of lipid glycoconjugates across the ER membrane for protein glycosylation pathways.

Racial and Ethnic Differences in Heroin, Methamphetamine, and Cocaine Use, Treatment, and Mortality Trends in 3 National Data Sources-United States, 2010-2019.

BACKGROUND: As overdose deaths continue to rise, public health officials need comprehensive surveillance data to design effective prevention, harm reduction, and treatment strategies. Disparities across race and ethnicity groups, as well as trends in substance use, treatment, or overdose deaths, have been examined individually, but reports rarely compare findings across multiple substances or data sources. OBJECTIVE: To provide a broad assessment of the overdose crisis, we describe trends in substance use, treatment, and overdose mortality across racial and ethnic groups for multiple substances. RESEARCH DESIGN: We conducted a longitudinal, cross-sectional analysis comparing trends. SUBJECTS: We identified self-reported use from the National Survey on Drug Use and Health, substance use treatment admissions from the Treatment Episode Data Set-Admissions, and overdose deaths from the CDC's Multiple Cause of Death files. MEASURES: We measured rates of substance use, treatment, and deaths involving heroin, methamphetamine, and cocaine among United States adults from 2010 to 2019. RESULTS: Heroin, methamphetamine, and cocaine use increased, though not all changes were statistically significant. Treatment admissions indicating heroin and methamphetamine increased while admissions indicating cocaine decreased. Overdose deaths increased among all groups: methamphetamine (257%-1,115%), heroin (211%-577%), and cocaine (88%-259%). Changes in rates of use, treatment, and death for specific substances varied by racial and ethnic group. CONCLUSIONS: Substance use, treatment, and overdose mortality changed considerably, though not always equivalently. Identifying diverging trends in substance-related measures for specific substances and racial and ethnic groups can inform targeted investment in treatment to reduce disparities and respond to emerging changes in the overdose crisis.

Solvate Suite: A Command-Line Interface for Molecular Simulations and Multiscale Microsolvation Modeling.

In this work, we introduce the Solvate Suite, a comprehensive and modular command-line interface designed for molecular simulation and microsolvation modeling. The suite interfaces with widely used scientific software, streamlining computational experiments for liquid systems through the automated creation of simulation boxes and topology with adjustable simulation parameters. Furthermore, it has features for graphical and statistical analysis of simulated properties and extraction of trajectory configurations with various filters. Additionally, it introduces innovative strategies for microsolvation modeling with a multiscale approach, employing equilibrated dynamics to identify favorable solute-solvent interactions and enabling full cluster optimization for free-energy calculations without imaginary frequency contamination.

Unlocking the potential of biosurfactants: Production, applications, market challenges, and opportunities for agro-industrial waste valorization.

Biosurfactants are eco-friendly compounds with unique properties and promising potential as sustainable alternatives to chemical surfactants. The current review explores the multifaceted nature of biosurfactant production and applications, highlighting key fermentative parameters and microorganisms able to convert carbon-containing sources into biosurfactants. A spotlight is given on biosurfactants' obstacles in the global market, focusing on production costs and the challenges of large-scale synthesis. Innovative approaches to valorizing agro-industrial waste were discussed, documenting the utilization of lignocellulosic waste, food waste, oily waste, and agro-industrial wastewater in the segment. This strategy strongly contributes to large-scale, cost-effective, and environmentally friendly biosurfactant production, while the recent advances in waste valorization pave the way for a sustainable society.

Understanding Regional Patterns of Overdose Deaths Related to Opioids and Psychostimulants.

BACKGROUND: As overdose rates increase for multiple substances, policymakers need to identify geographic patterns of substance-specific deaths. In this study, we describe county-level opioid and psychostimulant overdose patterns and how they correlate with county-level social vulnerability measures. METHODS: A cross-sectional observational study, we used nationwide 2016-2018 restricted access Centers for Disease Prevention and Control county-level mortality files for 1,024 counties. We estimated quartiles of opioid and psychostimulant overdose mortality and provided estimates of their association with county-level Social Vulnerability Index (SVI) percentile. RESULTS: There was high opioid and psychostimulant overdose mortality in the Middle Atlantic, South Atlantic, East North Central, and Mountain regions. The Central US had the lowest opioid and psychostimulant overdose mortality rates. Counties with higher SVI scores (i.e. higher social vulnerability) were significantly more likely to experience high opioid and high psychostimulant overdose (high-high) mortality. A 10-percentile increase in SVI score was associated with a 3.1 percentage point increase in the likelihood of being a high-high county (p < 0.001) in unadjusted models and a 1.5 percentage point increase (p < 0.05) in models adjusting for region. CONCLUSION: Our results illustrated the heterogenous geographic distribution of the growing concurrent opioid and psychostimulant overdose crisis. The substantial regional variation we identified highlights the need for local data to guide policymaking and treatment planning. The association of opioid-psychostimulant overdose mortality with social vulnerability demonstrates the critical need in impacted counties for tailored treatment that addresses the complex medical and social needs of people who use both opioids and psychostimulants.

Is there a tolerance for extension of the first metatarsal after the Lapidus procedure? A clinical, functional, and hindfoot radiographic analysis.

PURPOSE: Based on the tripod concept of load distribution, our study aimed to evaluate whether a slight extension of first metatarsal (M1) that may occur after the Lapidus procedure (LP) could alter the radiographic measurements of the hindfoot and influence clinical and functional outcomes. METHODS: Twenty-five patients (27 feet) were reviewed. Hindfoot radiographic analysis was based on seven measurements. Clinical and functional outcomes were evaluated with self-reported questionnaires. Transfer metatarsalgia was also assessed. Correlation analysis was performed according to variations of the studied variables. RESULTS: The average extension of the M1 was 4.26 degrees (p < 0.001). None of the hindfoot radiographic measurements changed significantly (p = 0.13, p = 0.50, p = 0.19, p = 0.70, p = 0.11, p = 0.36, p = 0.83). Patients improved on most questionnaires (p < 0.001). None presented transfer metatarsalgia. No correlation between M1 extension and clinical and functional outcomes was found. CONCLUSION: Possibly there is a tolerance of M1 extension in which it does not alter the radiographic measurements of the hindfoot, overload the lesser metatarsals, or compromise clinical and functional outcomes.

Novel Fe3O4 Nanoparticles with Bioactive Glass-Naproxen Coating: Synthesis, Characterization, and In Vitro Evaluation of Bioactivity.

Immune response to biomaterials, which is intimately related to their surface properties, can produce chronic inflammation and fibrosis, leading to implant failure. This study investigated the development of magnetic nanoparticles coated with silica and incorporating the anti-inflammatory drug naproxen, aimed at multifunctional biomedical applications. The synthesized nanoparticles were characterized using various techniques that confirmed the presence of magnetite and the formation of a silica-rich bioactive glass (BG) layer. In vitro studies demonstrated that the nanoparticles exhibited bioactive properties, forming an apatite surface layer when immersed in simulated body fluid, and biocompatibility with bone cells, with good viability and alkaline phosphatase activity. Naproxen, either free or encapsulated, reduced nitric oxide production, an inflammatory marker, while the BG coating alone did not show anti-inflammatory effects in this study. Overall, the magnetic nanoparticles coated with BG and naproxen showed promise for biomedical applications, especially anti-inflammatory activity in macrophages and in the bone field, due to their biocompatibility, bioactivity, and osteogenic potential.

Biochar obtained from eucalyptus, rice hull, and native bamboo as an alternative to decrease mobility of hexazinone, metribuzin, and quinclorac in a tropical soil.

Mobile herbicides have a high potential for groundwater contamination. An alternative to decrease the mobility of herbicides is to apply materials with high sorbent capacity to the soil, such as biochars. The objective of this research was to evaluate the effect of eucalyptus, rice hull, and native bamboo biochar amendments on sorption and desorption of hexazinone, metribuzin, and quinclorac in a tropical soil. The sorption-desorption was evaluated using the batch equilibrium method at five concentrations of hexazinone, metribuzin, and quinclorac. Soil was amended with eucalyptus, rice hull, and native bamboo biochar at a rate of 0 (control-unamended) and 1% (w w-1), corresponding to 0 and 12 t ha-1, respectively. The amount of sorbed herbicides in the unamended soil followed the decreasing order: quinclorac (65.9%) > metribuzin (21.4%) > hexazinone (16.0%). Native bamboo biochar provided the highest sorption compared to rice hull and eucalyptus biochar-amended soils for the three herbicides. The amount of desorbed herbicides in the unamended soil followed the decreasing order: metribuzin (18.35%) > hexazinone (15.9%) > quinclorac (15.1%). Addition of native bamboo biochar provided the lowest desorption among the biochar amendments for the three herbicides. In conclusion, the biochars differently affect the sorption and desorption of hexazinone, metribuzin, and quinclorac mobile herbicides in a tropical soil. The addition of eucalyptus, rice hull, and native bamboo biochars is a good alternative to increase the sorption of hexazinone, metribuzin, and quinclorac, thus, reducing mobility and availability of these herbicides to nontarget organisms in soil.

De Novo Human Angiotensin-Converting Enzyme 2 Decoy NL-CVX1 Protects Mice From Severe Disease After Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

The emergence of novel variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need to investigate alternative approaches to prevent infection and treat patients with coronavirus disease 2019. Here, we report the preclinical efficacy of NL-CVX1, a de novo decoy that blocks virus entry into cells by binding with nanomolar affinity and high specificity to the receptor-binding domain of the SARS-CoV-2 spike protein. Using a transgenic mouse model of SARS-CoV-2 infection, we showed that a single prophylactic intranasal dose of NL-CVX1 conferred complete protection from severe disease following SARS-CoV-2 infection. Multiple therapeutic administrations of NL-CVX1 also protected mice from succumbing to infection. Finally, we showed that infected mice treated with NL-CVX1 developed both anti-SARS-CoV-2 antibodies and memory T cells and were protected against reinfection a month after treatment. Overall, these observations suggest NL-CVX1 is a promising therapeutic candidate for preventing and treating severe SARS-CoV-2 infections.

TOTAL ANTIOXIDANT CAPACITY MAY NOT BE AN ACCURATE WAY TO PREDICT DENTAL CARIES.

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Salivary biomarkers of oxidative stress in children with dental caries: Systematic review and meta-analysis doi:10.1016/j.archoralbio.2022.105432. SOURCE OF FUNDING: CAPES (Coordination for the improvement of higher education, National Council of Technological and Scientific Development), Finace code 001. TYPE OF STUDY/DESIGN: Systematic review with meta-analysis of data.

Measuring quality STI care among adolescent female primary care patients in Philadelphia.

OBJECTIVES: Engagement in guideline-recommended sexually transmitted infection (STI) care is fundamental to ending the STI epidemic in the USA. However, the US 2021-2025 STI National Strategic Plan and STI surveillance reports do not include a framework to measure quality STI care delivery. This study developed and applied an STI Care Continuum that can be used across settings to improve STI care quality, assess adherence to guideline-recommended care and standardise the measurement of progress towards National Strategic goals. METHODS: Review of the Centers for Disease Control and Prevention STI Treatment guidelines identified seven distinct steps of STI care for gonorrhoea, chlamydia and syphilis: (1) STI testing indication, (2) STI test completion, (3) HIV testing, (4) STI diagnosis, (5) partner services, (6) STI treatment and (7) STI retesting. Steps 1-4, 6 and 7 for gonorrhoea and/or chlamydia (GC/CT) were measured among females aged 16-17 years with a clinic visit at an academic paediatric primary care network in 2019. We used Youth Risk Behavior Surveillance Survey data to estimate step 1, and electronic health record data for steps 2, 3, 4, 6 and 7. RESULTS: Among 5484 female patients aged 16-17 years, an estimated 44% had an STI testing indication. Among those patients, 17% were tested for HIV, of whom none tested positive, and 43% were tested for GC/CT, 19% of whom were diagnosed with GC/CT. Of these patients, 91% received treatment within 2 weeks and 67% were retested within 6 weeks to 1 year after diagnosis. On retesting, 40% were diagnosed with recurrent GC/CT. CONCLUSIONS: Local application of an STI Care Continuum identified STI testing, retesting and HIV testing as areas for improvement. The development of an STI Care Continuum identified novel measures for monitoring progress towards National Strategic indicators. Similar methods can be applied across jurisdictions to target resources, standardise data collection and reporting and improve STI care quality.

Effect of Thiazolidin-4-one Against Lipopolysaccharide-Induced Oxidative Damage, and Alterations in Adenine Nucleotide Hydrolysis and Acetylcholinesterase Activity in Cultured Astrocytes.

Astrocytes play multiple important roles in brain physiology. However, depending on the stimuli, astrocytes may exacerbate inflammatory reactions, contributing to the development and progression of neurological diseases. Therefore, therapies targeting astrocytes represent a promising area for the development of new brain drugs. Thiazolidinones are heterocyclic compounds that have a sulfur and nitrogen atom and a carbonyl group in the ring and represent a class of compounds of great scientific interest due to their pharmacological properties. The aim of this study was to investigate the effect of 3-(3-(diethylamino)propyl)-2-(4-(methylthio)phenyl)thiazolidin-4-one (DS27) on cell proliferation and morphology, oxidative stress parameters, activity of the enzymes ectonucleotidases and acetylcholinesterase (AChE) and interleukin 6 (IL-6) levels in primary astrocyte cultures treated with lipopolysaccharide (LPS), to model neuroinflammation. The astrocyte culture was exposed to LPS (10 µg/ml) for 3 h and subsequently treated with compound DS27 for 24 and 48 h (concentrations ranging to 10-100 µM). LPS induced an increase in astrocyte proliferation, AChE activity, IL-6 levels, oxidative damage, ATP and ADP and a reduction in AMP hydrolysis in rat primary astrocyte cultures. DS27 treatment was effective in reversing these alterations induced by LPS. Our findings demonstrated that DS27 is able to modulate cholinergic and purinergic signaling, redox status, and the levels of pro-inflammatory cytokines in LPS-induced astrocyte damage. These glioprotective effects of DS27 may be very important for improving neuroinflammation, which is associated with many brain diseases.

Effects of hyperprotein diet on anxiety, haemodynamics and morphofunctional aspects of the heart of Wistar rats.

NEW FINDINGS: What is the central question of this study? The consumption of a high-protein diet has been associated with an anxiogenic factor that can influence anxiety and possible cardiovascular changes: does the consumption of a high-protein diet interfere with anxiety, haemodynamics and morphofunctional aspects of the heart of Wistar rats? What is the main finding and its importance? Our study showed that the high-protein diet did not interfere with anxiety and haemodynamics. The animals in the hyperproteic group showed positive heart adaptations characterized by less work and lower heart rate without impairing ejection fraction and systemic blood pressure. ABSTRACT: Anxiety is a mechanism preparatory to a response in situations of threat and danger, involving behavioural, affective and physiological factors. Protein-based foods have a high concentration of amino acids which perform multiple functions, including in the biosynthesis of excitatory transmitters for the central nervous system. In recent years, adherence to high-protein diets has been gaining ground in society, on the basis that it brings benefits to the musculoskeletal system and cardiovascular health. The aim of the present study was to investigate the effect of a high-protein diet in a state of anxiety and to investigate morphofunctional cardiovascular effects of a high-protein diet in Wistar rats. The experiment lasted 8 weeks and two groups of male rats were submitted to either a normoproteic or a hyperproteic diet. Anxiety was assessed using the plus maze test and cardiovascular morphofunctional aspects using transthoracic echocardiography and invasive measurements of femoral blood pressure. There was no statistically significant difference in the anxiety test, but the hyperproteic group was more agitated, with greater displacement during the test. Changes were found in systolic and end-diastolic volume, left ventricular diameter in systole and heart rate, which were significantly lower in the hyperproteic group, and there was an increase in the thickness of the interventricular septum in diastole. The results showed no influence of the higher protein diet on the animals' anxiety, body weight and haemodynamics.

Impact on the ability of healthcare professionals to correctly identify patient-ventilator asynchronies of the simultaneous visualization of estimated muscle pressure curves on the ventilator display: a randomized study (Pmus study).

BACKGROUND: Patient-ventilator asynchronies are usually detected by visual inspection of ventilator waveforms but with low sensitivity, even when performed by experts in the field. Recently, estimation of the inspiratory muscle pressure (Pmus) waveforms through artificial intelligence algorithm has been proposed (Magnamed®, São Paulo, Brazil). We hypothesized that the display of these waveforms could help healthcare providers identify patient-ventilator asynchronies. METHODS: A prospective single-center randomized study with parallel assignment was conducted to assess whether the display of the estimated Pmus waveform would improve the correct identification of asynchronies in simulated clinical scenarios. The primary outcome was the mean asynchrony detection rate (sensitivity). Physicians and respiratory therapists who work in intensive care units were randomized to control or intervention group. In both groups, participants analyzed pressure and flow waveforms of 49 different scenarios elaborated using the ASL-5000 lung simulator. In the intervention group the estimated Pmus waveform was displayed in addition to pressure and flow waveforms. RESULTS: A total of 98 participants were included, 49 per group. The sensitivity per participant in identifying asynchronies was significantly higher in the Pmus group (65.8 ± 16.2 vs. 52.94 ± 8.42, p < 0.001). This effect remained when stratifying asynchronies by type. CONCLUSIONS: We showed that the display of the Pmus waveform improved the ability of healthcare professionals to recognize patient-ventilator asynchronies by visual inspection of ventilator tracings. These findings require clinical validation. TRIAL REGISTRATION: ClinicalTrials.gov: NTC05144607. Retrospectively registered 3 December 2021.

Frequency-resolved microscopic second-order hyperpolarizability of azochromophores: a study on nonlinear all-optical switching applications.

Azochromophores present interesting optical properties for application in all-optical switches (AOSs), such as ultrafast photoisomerization and considerable nonlinear optical response. However, determining the frequency-resolved microscopic second-order hyperpolarizability (real and imaginary parts) related to the pure electronic effects of molecules in solution is a challenging task. In this context, we have used femtosecond-laser induced nonlinear ellipse rotation (NER) measurements to obtain the electronic nonlinear refraction (n2(ω)) and two-photon absorption spectra (α2PA(ω)) of four azochromophores dissolved in methanol and acetone. The measurements ranging from ∼600 up to ∼1300 nm were performed in Disperse Red 1 (DR1), Disperse Red 13 (DR13), Disperse Red 19 (DR19), and Disperse Orange 3 (DO3). Because we carried the solution in a silica cuvette and used a short focal length, we were able to measure the solution's nonlinearities with high precision, as the silica from the cuvette walls worked as a suitable reference medium. Consequently, we precisely determined n2(ω), α2PA(ω), and the second-order hyperpolarizability (γ(ω)) for all molecules and explained the different magnitudes based on the push-pull character. Furthermore, the solvation effect due to the change from methanol to acetone solvent on the n2(ω), α2PA(ω), and γ(ω) is also reported. The results were elucidated using the sum-over-states (SOS) approach within the few-energy-level model and the results were obtained via quantum-chemical calculations using the cubic response function formalism within the density functional theory framework. Finally, we used these results to determine the frequency-resolved figure-of-merit for all-optical switching applications. Our results suggest that chromophores have the potential for applications in AOS based on Fabry-Perot filters.

A hybrid linear discriminant analysis and genetic algorithm to create a linear model of aging when performing motor tasks through inertial sensors positioned on the hand and forearm.

BACKGROUND: During the aging process, cognitive functions and performance of the muscular and neural system show signs of decline, thus making the elderly more susceptible to disease and death. These alterations, which occur with advanced age, affect functional performance in both the lower and upper members, and consequently human motor functions. Objective measurements are important tools to help understand and characterize the dysfunctions and limitations that occur due to neuromuscular changes related to advancing age. Therefore, the objective of this study is to attest to the difference between groups of young and old individuals through manual movements and whether the combination of features can produce a linear correlation concerning the different age groups. METHODS: This study counted on 99 participants, these were divided into 8 groups, which were grouped by age. The data collection was performed using inertial sensors (positioned on the back of the hand and on the back of the forearm). Firstly, the participants were divided into groups of young and elderly to verify if the groups could be distinguished through the features alone. Following this, the features were combined using the linear discriminant analysis (LDA), which gave rise to a singular feature called the LDA-value that aided in verifying the correlation between the different age ranges and the LDA-value. RESULTS: The results demonstrated that 125 features are able to distinguish the difference between the groups of young and elderly individuals. The use of the LDA-value allows for the obtaining of a linear model of the changes that occur with aging in the performance of tasks in line with advancing age, the correlation obtained, using Pearson's coefficient, was 0.86. CONCLUSION: When we compare only the young and elderly groups, the results indicate that there is a difference in the way tasks are performed between young and elderly individuals. When the 8 groups were analyzed, the linear correlation obtained was strong, with the LDA-value being effective in obtaining a linear correlation of the eight groups, demonstrating that although the features alone do not demonstrate gradual changes as a function of age, their combination established these changes.