Design of a Remote Multiparametric Tool to Assess Mental Well-Being and Distress in Young People (mHealth Methods in Mental Health Research Project): Protocol for an Observational Study.

BACKGROUND: Mental health conditions have become a substantial cause of disability worldwide, resulting in economic burden and strain on the public health system. Incorporating cognitive and physiological biomarkers using noninvasive sensors combined with self-reported questionnaires can provide a more accurate characterization of the individual's well-being. Biomarkers such as heart rate variability or those extracted from the electrodermal activity signal are commonly considered as indices of autonomic nervous system functioning, providing objective indicators of stress response. A model combining a set of these biomarkers can constitute a comprehensive tool to remotely assess mental well-being and distress. OBJECTIVE: This study aims to design and validate a remote multiparametric tool, including physiological and cognitive variables, to objectively assess mental well-being and distress. METHODS: This ongoing observational study pursues to enroll 60 young participants (aged 18-34 years) in 3 groups, including participants with high mental well-being, participants with mild to moderate psychological distress, and participants diagnosed with depression or anxiety disorder. The inclusion and exclusion criteria are being evaluated through a web-based questionnaire, and for those with a mental health condition, the criteria are identified by psychologists. The assessment consists of collecting mental health self-reported measures and physiological data during a baseline state, the Stroop Color and Word Test as a stress-inducing stage, and a final recovery period. Several variables related to heart rate variability, pulse arrival time, breathing, electrodermal activity, and peripheral temperature are collected using medical and wearable devices. A second assessment is carried out after 1 month. The assessment tool will be developed using self-reported questionnaires assessing well-being (short version of Warwick-Edinburgh Mental Well-being Scale), anxiety (Generalized Anxiety Disorder-7), and depression (Patient Health Questionnaire-9) as the reference. We will perform correlation and principal component analysis to reduce the number of variables, followed by the calculation of multiple regression models. Test-retest reliability, known-group validity, and predictive validity will be assessed. RESULTS: Participant recruitment is being carried out on a university campus and in mental health services. Recruitment commenced in October 2022 and is expected to be completed by June 2024. As of July 2023, we have recruited 41 participants. Most participants correspond to the group with mild to moderate psychological distress (n=20, 49%), followed by the high mental well-being group (n=13, 32%) and those diagnosed with a mental health condition (n=8, 20%). Data preprocessing is currently ongoing, and publication of the first results is expected by September 2024. CONCLUSIONS: This study will establish an initial framework for a comprehensive mental health assessment tool, taking measurements from sophisticated devices, with the goal of progressing toward a remotely accessible and objectively measured approach that maintains an acceptable level of accuracy in clinical practice and epidemiological studies. TRIAL REGISTRATION: OSF Registries N3GCH; https://doi.org/10.17605/OSF.IO/N3GCH. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51298.

Assessing effectiveness of heart rate variability biofeedback to mitigate mental health symptoms: a pilot study.

Introduction: The increasing burden on mental health has become a worldwide concern especially due to its substantial negative social and economic impact. The implementation of prevention actions and psychological interventions is crucial to mitigate these consequences, and evidence supporting its effectiveness would facilitate a more assertive response. Heart rate variability biofeedback (HRV-BF) has been proposed as a potential intervention to improve mental wellbeing through mechanisms in autonomic functioning. The aim of this study is to propose and evaluate the validity of an objective procedure to assess the effectiveness of a HRV-BF protocol in mitigating mental health symptoms in a sample of frontline HCWs (healthcare workers) who worked in the COVID-19 pandemic. Methods: A prospective experimental study applying a HRV-BF protocol was conducted with 21 frontline healthcare workers in 5 weekly sessions. For PRE-POST intervention comparisons, two different approaches were used to evaluate mental health status: applying (a) gold-standard psychometric questionnaires and (b) electrophysiological multiparametric models for chronic and acute stress assessment. Results: After HRV-BF intervention, psychometric questionnaires showed a reduction in mental health symptoms and stress perception. The electrophysiological multiparametric also showed a reduction in chronic stress levels, while the acute stress levels were similar in PRE and POST conditions. A significant reduction in respiratory rate and an increase in some heart rate variability parameters, such as SDNN, LFn, and LF/HF ratio, were also observed after intervention. Conclusion: Our findings suggest that a 5-session HRV-BF protocol is an effective intervention for reducing stress and other mental health symptoms among frontline HCWs who worked during the COVID-19 pandemic. The electrophysiological multiparametric models provide relevant information about the current mental health state, being useful for objectively evaluating the effectiveness of stress-reducing interventions. Further research could replicate the proposed procedure to confirm its feasibility for different samples and specific interventions.

Biopsychosocial Response to the COVID-19 Lockdown in People with Major Depressive Disorder and Multiple Sclerosis.

BACKGROUND: Changes in lifestyle, finances and work status during COVID-19 lockdowns may have led to biopsychosocial changes in people with pre-existing vulnerabilities such as Major Depressive Disorders (MDDs) and Multiple Sclerosis (MS). METHODS: Data were collected as a part of the RADAR-CNS (Remote Assessment of Disease and Relapse-Central Nervous System) program. We analyzed the following data from long-term participants in a decentralized multinational study: symptoms of depression, heart rate (HR) during the day and night; social activity; sedentary state, steps and physical activity of varying intensity. Linear mixed-effects regression analyses with repeated measures were fitted to assess the changes among three time periods (pre, during and post-lockdown) across the groups, adjusting for depression severity before the pandemic and gender. RESULTS: Participants with MDDs (N = 255) and MS (N = 214) were included in the analyses. Overall, depressive symptoms remained stable across the three periods in both groups. A lower mean HR and HR variation were observed between pre and during lockdown during the day for MDDs and during the night for MS. HR variation during rest periods also decreased between pre- and post-lockdown in both clinical conditions. We observed a reduction in physical activity for MDDs and MS upon the introduction of lockdowns. The group with MDDs exhibited a net increase in social interaction via social network apps over the three periods. CONCLUSIONS: Behavioral responses to the lockdown measured by social activity, physical activity and HR may reflect changes in stress in people with MDDs and MS. Remote technology monitoring might promptly activate an early warning of physical and social alterations in these stressful situations. Future studies must explore how stress does or does not impact depression severity.

Psychosomatic response to acute emotional stress in healthy students.

The multidimensionality of the stress response has shown the complexity of this phenomenon and therefore the impossibility of finding a unique biomarker among the physiological variables related to stress. An experimental study was designed and performed to guarantee the correct synchronous and concurrent measure of psychometric tests, biochemical variables and physiological features related to acute emotional stress. The population studied corresponds to a group of 120 university students between 20 and 30 years of age, with healthy habits and without a diagnosis of chronic or psychiatric illnesses. Following the protocol of the experimental pilot, each participant reached a relaxing state and a stress state in two sessions of measurement for equivalent periods. Both states are correctly achieved evidenced by the psychometric test results and the biochemical variables. A Stress Reference Scale is proposed based on these two sets of variables. Then, aiming for a non-invasive and continuous approach, the Acute Stress Model correlated to the previous scale is also proposed, supported only by physiological signals. Preliminary results support the feasibility of measuring/quantifying the stress level. Although the results are limited to the population and stimulus type, the procedure and methodological analysis used for the assessment of acute stress in young people can be extrapolated to other populations and types of stress.

Photoplethysmographic Waveform Analysis for Autonomic Reactivity Assessment in Depression.

OBJECTIVE: In the present study, a photoplethysmographic (PPG) waveform analysis for assessing differences in autonomic reactivity to mental stress between patients with Major Depressive Disorder (MDD) and healthy control (HC) subjects is presented. METHODS: PPG recordings of 40 MDD and 40 HC subjects were acquired at basal conditions, during the execution of cognitive tasks, and at the post-task relaxation period. PPG pulses are decomposed into three waves (a main wave and two reflected waves) using a pulse decomposition analysis. Pulse waveform characteristics such as the time delay between the position of the main wave and reflected waves, the percentage of amplitude loss in the reflected waves, and the heart rate (HR) are calculated among others. The intra-subject difference of a feature value between two conditions is used as an index of autonomic reactivity. RESULTS: Statistically significant individual differences from stress to recovery were found for HR and the percentage of amplitude loss in the second reflected wave ( A13) in both HC and MDD group. However, autonomic reactivity indices related to  A13 reached higher values in HC than in MDD subjects (Cohen's [Formula: see text]), implying that the stress response in depressed patients is reduced. A statistically significant ( ) negative correlation ( r=-0.5) between depression severity scores and A13 was found. CONCLUSION: A decreased autonomic reactivity is associated with higher degree of depression. SIGNIFICANCE: Stress response quantification by dynamic changes in PPG waveform morphology can be an aid for the diagnosis and monitoring of depression.

Marked Presence of Methicillin-Resistant Staphylococcus aureus in Wild Lagomorphs in Valencia, Spain.

The appearance of methicillin-resistant strains of Staphylococcus aureus (MRSA) in several animal species (including rabbits) has set off alarms for their capacity to act as reservoirs for this bacterium. This is especially important in wild animals given its epidemiological implications. The objectives of this study were to identify and characterize S. aureus, specifically MRSA, strains in wild lagomorph high-density areas. Ten hares and 353 wild rabbits from 14 towns with a high rabbit density in the Valencian region (eastern Spanish coast) were sampled. Swabs from the nasal cavity, ears, perineum and lesions (when present) were taken for microbiological studies. The detection of different genes and antibiotic susceptibility studies were also carried out. Of all the animals, 41.3% were positive for S. aureus, of which 63.3% were MRSA. Ears were the anatomical location with more S. aureus and MRSA strains. The more frequently identified MLST type was ST1945 (97.1%, 136/140). The mecA gene was found only in one sample. The rest (n = 139) carried the mecC gene and were included in CC130, except one. Penicillin resistance was detected in 28 mec-negative isolates and, in one case, bacitracin resistance. mecA isolate presented resistance to enrofloxacin and tetracycline, and 10 mecC isolates also showed bacitracin resistance. No MRSA isolate was positive for genes chp, sea, tst and PVL. Two ST1945 isolates contained IEC type E (comprising genes scn and sak). mecA-isolate was positive for blaZ. Of the 28 MSSA strains showing resistance to penicillin, 22 carried the blaZ gene. These surprising results highlight the marked presence of MRSA strains in wild rabbits in high-density areas.

Measuring acute stress response through physiological signals: towards a quantitative assessment of stress.

Social and medical problems associated with stress are increasing globally and seriously affect mental health and well-being. However, an effective stress-level monitoring method is still not available. This paper presents a quantitative method for monitoring acute stress levels in healthy young people using biomarkers from physiological signals that can be unobtrusively monitored. Two states were induced to 40 volunteers, a basal state generated with a relaxation task and an acute stress state generated by applying a standard stress test that includes five different tasks. Standard psychological questionnaires and biochemical markers were utilized as ground truth of stress levels. A multivariable approach to comprehensively measure the physiological stress response is proposed using stress biomarkers derived from skin temperature, heart rate, and pulse wave signals. Acute physiological stress levels (total-range 0-100 au) were continuously estimated every 1 min showing medians of 29.06 au in the relaxation tasks, while rising from 34.58 to 47.55 au in the stress tasks. Moreover, using the proposed method, five statistically different stress levels induced by the performed tasks were also measured. Results obtained show that, in these experimental conditions, stress can be monitored from unobtrusive biomarkers. Thus, a more general stress monitoring method could be derived based on this approach. Graphical abstract Stress measurements of different healthy young people throughout a Stress Session that includes a pre-relax stage (BLs), memory test (ST and MT), stress anticipation time (SA), video display (VD) and arithmetic task.

Unconstrained Estimation of HRV Indices After Removing Respiratory Influences From Heart Rate.

OBJECTIVE: This paper proposes an approach to better estimate the sympathovagal balance (SB) and the respiratory sinus arrhythmia (RSA) after separating respiratory influences from the heart rate (HR). METHODS: The separation is performed using orthogonal subspace projections and the approach is first tested using simulated HR and respiratory signals with different spectral properties. Then, RSA and SB are estimated during autonomic blockade and stress using the proposed approach and the classical heart rate variability (HRV) analysis. Both real- and ECG-derived respiration (EDR) are used and the reliability of the EDR is evaluated. RESULTS: Mean absolute percentage errors lower than [Formula: see text] were obtained after removing previously known respiratory signals from simulated HR. The proposed indices were able to improve the quantification of SB during autonomic withdrawal. In the stress data, differences ( ) among relaxed and stressful phases were found with the proposed approach, using both the real respiration and the EDR, but they disappeared when using the classical HRV. CONCLUSION: A better assessment of the autonomic nervous system' response to pharmacological blockade and stress can be achieved after removing respiratory influences from HR, and this can be done using either the real respiration or the EDR. SIGNIFICANCE: This work can be used to better identify vagal withdrawal and increased sympathetic activation when the classical HRV analysis fails due to the respiratory influences on HR. Furthermore, it can be computed using only the ECG, which is an advantage when developing wearable systems with limited number of sensors.

Effectiveness of patient empowerment over stress related to knee arthroplasty surgery.

OBJECTIVE: This study aims to show evidence of the Empowerment Session's effectiveness through measurements of surgery related emotional stress before and after this session. METHOD: The study was performed on 41 patients with knee arthroplasty surgery prescription by measuring the evolution of their emotional stress generated by surgery expectative, during the empowerment session. Two sets of measurements per patient were performed, before and after the empowerment session. Each set consisted of recording an electrocardiogram for 10min while the patients were seated and then applying two standard psychometric tests: State-Trait Anxiety Inventory test and Visual Analog Stress test. Differences in emotional stress were analyzed using psychometric tests and heart rate variability (HRV) analysis as stress biomarkers. RESULTS: Psychometric stress measurement shows a 17.8% reduction in stress according to the total stress scale value, and a 41.9% reduction in stress between test results before and after the session. Mean heart rate values increased by 7.4% with respect to the initial values, very low frequency power and total power also change in value suggesting more sympathetic and less parasympathetic activity. CONCLUSIONS: Both psychological and physiological measurements suggest the effectiveness of the empowerment session due to a significant increase in the wellness state of patients. Additionally, the correlation between psychometric tests and HRV indices demonstrates that both emotional stress indicators could be used as feedback on the empowerment sessions or as a reference to enhance surgical outcomes.

Evaluation of chronic stress indicators in geriatric and oncologic caregivers: a cross-sectional study.

Caregiving induces chronic stress with physical and psychological impact on informal caregivers health. Therefore, subjective and objective indicators are needed for the early diagnosis of pathologic stress to prevent the risk of developing stress-related diseases in caregivers. Our aim was to assess the self-perceived stress, that is, how and how much the stressor affects the individual, through endocrine, metabolic, and immunologic biomarkers levels in geriatric and oncologic informal caregivers. Informal caregivers and non-caregivers were invited to participate in a cross-sectional study at the Clinic Hospital of Barcelona. Demographic and lifestyle characteristics, self-perceived stress (Perceived Stress Scale, State-Trait Anxiety Inventory and Stress Visual Analogue Scale), and biomarkers (copeptin, glucose, glycated hemoglobin, low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), cholesterol, triglycerides, α-amylase, cortisol, tumor necrosis factor (TNF-α), and Interleukins (IL-6 and IL-10)) were evaluated. Descriptive and non-parametric statistical data analysis were performed. Fifty-six subjects (19 non-caregivers, 17 geriatric caregivers, and 20 oncologic caregivers) participated. Median age (IQR) was 57 years (47-66) and 71.46% were women. Self-perceived stress was higher in oncologic caregivers than geriatric caregivers in all psychometric test analyzed (Wilcoxon Rank Sum test, p value < .05). Glucose concentrations and glycated hemoglobin levels differed statistically among groups (Kruskal-Wallis test (K-W tests), p value < .05), even though the median levels were not clinically relevant. Levels of other biomarkers did not differ significantly (K-W tests, p value > .05). These findings suggest that perceived stress is not homogeneous in the caregivers community and thus these two groups could be differentiated. These results provide the baseline information to initiate social actions addressed to each group of caregivers to increase their wellbeing.

Inclusion of Respiratory Frequency Information in Heart Rate Variability Analysis for Stress Assessment.

Respiratory rate and heart rate variability (HRV) are studied as stress markers in a database of young healthy volunteers subjected to acute emotional stress, induced by a modification of the Trier Social Stress Test. First, instantaneous frequency domain HRV parameters are computed using time-frequency analysis in the classical bands. Then, the respiratory rate is estimated and this information is included in HRV analysis in two ways: 1) redefining the high-frequency (HF) band to be centered at respiratory frequency; 2) excluding from the analysis those instants where respiratory frequency falls within the low-frequency (LF) band. Classical frequency domain HRV indices scarcely show statistical differences during stress. However, when including respiratory frequency information in HRV analysis, the normalized LF power as well as the LF/HF ratio significantly increase during stress ( p-value 0.05 according to the Wilcoxon test), revealing higher sympathetic dominance. The LF power increases during stress, only being significantly different in a stress anticipation stage, while the HF power decreases during stress, only being significantly different during the stress task demanding attention. Our results support that joint analysis of respiration and HRV obtains a more reliable characterization of autonomic nervous response to stress. In addition, the respiratory rate is observed to be higher and less stable during stress than during relax ( p-value 0.05 according to the Wilcoxon test) being the most discriminative index for stress stratification (AUC = 88.2 % ).

Project ES3: attempting to quantify and measure the level of stress.

INTRODUCTION: The WHO has qualified stress as a 'world epidemic' due to its increasingly greater incidence on health. The work described in this paper represents an attempt to objectively quantify the level of stress. AIM: The aim of the method developed here is to measure how close or how far a subject is from a situation that can be considered 'normal' in medical and social terms. SUBJECTS AND METHODS: The literature on the pathophysiology of stress and its methods of study in experiments on both animals and humans was reviewed. Nine prospective observational studies were undertaken with different types of subjects and stressors covering the different types of stress. RESULTS: The results of the literature review made it possible to identify the different types of stress, the indicators that yield significant results, the psychometric tests and the well-documented 'stressors'. This material was then used to design the general method and the details of the nine clinical trials. The preliminary results obtained in some of the studies were used to validate the indicators as well as the efficacy of the techniques used experimentally to diminish stress or to produce it. CONCLUSIONS: The early results obtained in the experimental trials show that we are on the right path towards defining and validating multivariable markers for quantifying levels of stress and also suggest that the method can be applied in a similar way to the study of mental disorders.

TITLE: Proyecto ES3: intentando la cuantificacion y medida del nivel de estres.Introduccion. La Organizacion Mundial de la Salud ha calificado al estres de 'epidemia mundial', debido a su cada vez mayor incidencia en la salud. El trabajo que se presenta en este articulo representa un intento de cuantificar objetivamente el nivel de estres. Objetivo. La metodologia desarrollada tiene como objetivo medir cuan lejos o cuan cerca se encuentra un sujeto de una situacion considerada medica y socialmente como 'normal'. Sujetos y metodos. Se ha realizado un estudio bibliografico de la fisiopatologia del estres y sus metodos de estudio, en experimentacion animal y en humanos. Se han puesto en marcha nueve estudios prospectivos observacionales con distintas tipologias de sujetos y estresores que cubren las diferentes tipologias de estres. Resultados. Como resultado del estudio bibliografico, se han identificado las distintas tipologias de estres, los indicadores que describen resultados significativos, los tests psicometricos y los 'agentes estresantes' bien documentados. Este material ha permitido diseñar la metodologia general y el detalle de los nueve ensayos clinicos. Los resultados preliminares obtenidos en algunos de los estudios han servido para validar los indicadores, asi como la eficacia de las tecnicas utilizadas experimentalmente para disminuir el estres o para producirlo. Conclusiones. Los resultados preliminares obtenidos en los ensayos experimentales muestran que se esta en el camino correcto hacia la definicion y validacion de marcadores multivariable para la cuantificacion de los niveles de estres, y sugieren que la metodologia puede ser aplicada de forma similar al estudio de trastornos mentales.

Cancer prognostics by direct detection of p53-antibodies on gold surfaces by impedance measurements.

The identification and measurement of biomarkers is critical to a broad range of methods that diagnose and monitor many diseases. Serum auto-antibodies are rapidly becoming interesting targets because of their biological and medical relevance. This paper describes a highly sensitive, label-free approach for the detection of p53-antibodies, a prognostic indicator in ovarian cancer as well as a biomarker in the early stages of other cancers. This approach uses impedance measurements on gold microelectrodes to measure antibody concentrations at the picomolar level in undiluted serum samples. The biosensor shows high selectivity as a result of the optimization of the epitopes responsible for the detection of p53-antibodies and was validated by several techniques including microcontact printing, self-assembled-monolayer desorption ionization (SAMDI) mass spectrometry, and adhesion pull-off force by atomic force microscopy (AFM). This transduction method will lead to fast and accurate diagnostic tools for the early detection of cancer and other diseases.

Prototype of a nanostructured sensing contact lens for noninvasive intraocular pressure monitoring.

PURPOSE: To present the application of a new sensor based on a flexible, highly piezoresistive, nanocomposite, all-organic bilayer (BL) adapted to a contact lens (CL) for non-invasive monitoring intraocular pressure (IOP). METHODS: A prototype of a sensing CL, adapted to a pig eyeball, was tested on different enucleated pig eyes. A rigid, gas-permeable CL was designed as a doughnut shape with a 3-mm hole, where the BL film-based sensor was incorporated. The sensor was a polycarbonate film coated with a polycrystalline layer of the highly piezoresistive molecular conductor ß-(ET)2I3, which can detect deformations caused by pressure changes of 1 mm Hg. The pig eyeballs were subjected to controlled-pressure variations (low-pressure transducer) to register the electrical resistance response of the CL sensor to pressure changes. Similarly, a CL sensor was designed according to the anatomic characteristics of the eye of a volunteer on the research team. RESULTS: A good correlation (r² = 0.99) was demonstrated between the sensing CL electrical response, and IOP (mm Hg) changes in pig eyes, with a sensitivity of 0.4 Ω/mm Hg. A human eye test also showed the high potential of this new sensor (IOP variations caused by eye massage, blinking, and eye movements were registered). CONCLUSIONS: A new nanostructured sensing CL for continuous monitoring of IOP was validated in an in vitro model (porcine eyeball) and in a human eye. This prototype has adequate sensitivity to continuously monitor IOP. This device will be useful for glaucoma diagnosis and treatment.

Bioimpedance dispersion width as a parameter to monitor living tissues.

In the case of living tissues, the spectral width of the electrical bioimpedance dispersions (closely related with the alpha parameter in the Cole equation) evolves during the ischemic periods. This parameter is often ignored in favor of other bioimpedance parameters such as the central frequency or the resistivity at low frequencies. The object of this paper is to analyze the significance of this parameter through computer simulations (in the alpha and beta dispersion regions) and to demonstrate its practical importance through experimental studies performed in rat kidneys during cold preservation. The simulations indicate that the dispersion width could be determined by the morphology of the extra-cellular spaces. The experimental studies show that it is a unique parameter able to detect certain conditions such as a warm ischemia period prior to cold preservation or the effect of a drug (Swinholide A) able to disrupt the cytoskeleton. The main conclusion is that, thanks to the alpha parameter in the Cole equation, the bioimpedance is not only useful to monitor the intra/extra-cellular volume imbalances or the inter-cellular junctions resistance but also to detect tissue structural alterations.

Electrical bioimpedance measurement during hypothermic rat kidney preservation for assessing ischemic injury.

Non-heart-beating donors sustain an ischemic insult of unknown severity and duration, which can compromise the viability of the graft. This preliminary study aimed to assess whether electrical bioimpedance monitoring of cold preserved organs could be useful to identify kidneys that have suffered previous warm ischemia (WI). Two rat groups were studied during 24 h of preservation in University of Wisconsin solution (UW): a control cold ischemia group and another group subjected previously to 45 min of WI. Multi-frequency bioimpedance was monitored during preservation by means of a miniaturized silicon probe and the results were modeled according to the Cole equation. Tissular ATP content, lactate dehydrogenase in UW solution and histological injury were assessed. Renal function and cell injury, evaluated during 3 h of ex vivo reperfusion using the isolated perfused rat kidney model, demonstrated differences between groups. Bioimpedance results showed that the time constant and the high frequency resistivity parameters derived from the Cole equation were able to discriminate between groups at the beginning of the preservation (Deltatau approximately 78%, DeltaRinfinity approximately 36%), but these differences tended to converge as preservation time advanced. Nevertheless, another of the Cole parameters, alpha, showed increasing significant differences until 24 h of preservation (Deltaalpha approximately 15%).