miRNAs in Heart Development and Disease.

Cardiovascular diseases (CVD) are a group of disorders that affect the heart and blood vessels. They include conditions such as myocardial infarction, coronary artery disease, heart failure, arrhythmia, and congenital heart defects. CVDs are the leading cause of death worldwide. Therefore, new medical interventions that aim to prevent, treat, or manage CVDs are of prime importance. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the posttranscriptional level and play important roles in various biological processes, including cardiac development, function, and disease. Moreover, miRNAs can also act as biomarkers and therapeutic targets. In order to identify and characterize miRNAs and their target genes, scientists take advantage of computational tools such as bioinformatic algorithms, which can also assist in analyzing miRNA expression profiles, functions, and interactions in different cardiac conditions. Indeed, the combination of miRNA research and bioinformatic algorithms has opened new avenues for understanding and treating CVDs. In this review, we summarize the current knowledge on the roles of miRNAs in cardiac development and CVDs, discuss the challenges and opportunities, and provide some examples of recent bioinformatics for miRNA research in cardiovascular biology and medicine.

Pilot study of newborn screening for six lysosomal diseases in Brazil.

BACKGROUND: Lysosomal diseases (LDs) are progressive life-threatening disorders that are usually asymptomatic at birth. Specific treatments are available for several LDs, and early intervention improves patient's outcomes. Thus, these diseases benefit from newborn screening (NBS). We have performed a pilot study for six LDs in Brazil by tandem mass spectrometry. METHODS: Dried blood spot (DBS) samples of unselected newborns were analyzed by the Neo-LSD™ kit (Perkin-Elmer) by MS/MS. Samples with low enzyme activity were submitted to the evaluation of specific biomarkers by ultra-performance liquid chromatography tandem-mass spectrometry as the second-tier, and were analyzed by a next-generation sequencing (NGS) multi-gene panel as the third-tier. All tests were performed in the same DBS sample. RESULTS: In 20,066 newborns analyzed, 15 samples showed activity of one enzyme below the cutoff. Two newborns had biochemical and molecular results compatible with Fabry disease, and five newborns had biochemical results and pathogenic variants or variants of unknown significance (VUS) in GAA. CONCLUSIONS: This study indicates that the use of enzyme assay as the first-tier test gives an acceptably low number of positive results that requires second/third tier testing. The possibility to run all tests in a DBS sample makes this protocol applicable to large-scale NBS programs.

Fall risk stratification of community-living older people. Commentary on the world guidelines for fall prevention and management.

The Task Force on Global Guidelines for Falls in Older Adults has put forward a fall risk stratification tool for community-dwelling older adults. This tool takes the form of a flowchart and is based on expert opinion and evidence. It divides the population into three risk categories and recommends specific preventive interventions or treatments for each category. In this commentary, we share our insights on the design, validation, usability and potential impact of this fall risk stratification tool with the aim of guiding future research.

Minding your steps: a cross-sectional pilot study using foot-worn inertial sensors and dual-task gait analysis to assess the cognitive status of older adults with mobility limitations.

BACKGROUND: Cognitive impairment is a critical aspect of our aging society. Yet, it receives inadequate intervention due to delayed or missed detection. Dual-task gait analysis is currently considered a solution to improve the early detection of cognitive impairment in clinical settings. Recently, our group proposed a new approach for the gait analysis resorting to inertial sensors placed on the shoes. This pilot study aimed to investigate the potential of this system to capture and differentiate gait performance in the presence of cognitive impairment based on single- and dual-task gait assessments. METHODS: We analyzed demographic and medical data, cognitive tests scores, physical tests scores, and gait metrics acquired from 29 older adults with mobility limitations. Gait metrics were extracted using the newly developed gait analysis approach and recorded in single- and dual-task conditions. Participants were stratified into two groups based on their Montreal Cognitive Assessment (MoCA) global cognitive scores. Statistical analysis was performed to assess differences between groups, discrimination ability, and association of gait metrics with cognitive performance. RESULTS: The addition of the cognitive task influenced gait performance of both groups, but the effect was higher in the group with cognitive impairment. Multiple dual-task costs, dual-task variability, and dual-task asymmetry metrics presented significant differences between groups. Also, several of these metrics provided acceptable discrimination ability and had a significant association with MoCA scores. The dual-task effect on gait speed explained the highest percentage of the variance in MoCA scores. None of the single-task gait metrics presented significant differences between groups. CONCLUSIONS: Our preliminary results show that the newly developed gait analysis solution based on foot-worn inertial sensors is a pertinent tool to evaluate gait metrics affected by the cognitive status of older adults relying on single- and dual-task gait assessments. Further evaluation with a larger and more diverse group is required to establish system feasibility and reliability in clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov (identifier: NCT04587895).

Is the quality of therapeutic collaboration associated with the assimilation of problematic experiences progress? A comparison of two cases.

OBJECTIVE: How are collaborative interactions associated with clients' progress in therapy? This study addressed this question, by assessing the quality of therapeutic collaboration and comparing it passage by passage with the clients' assimilation of problematic experiences in two cases of major depression treated with Cognitive Behavioral Therapy, one recovered and one improved-but-not-recovered. METHOD: We used the Therapeutic Collaboration Coding System to code collaborative work and the Assimilation of Problematic Experiences Scale (APES) to rate clients' progress. In both cases, for the distribution of specific collaborative therapeutic exchanges, we tested for the difference of empirical means between lower and higher APES levels. RESULTS: Both cases progress in APES, but in contrast with Annie (Improved-but-not-recovered), Kate (Recovered) achieved higher levels of change in last sessions. In addition, we found significant differences in the types of collaborative therapeutic exchanges associated with lower and higher APES levels. CONCLUSION: Ambivalent therapeutic exchanges distinguished the recovered case from the not recovered case highlighting a source of difficulties in facilitating therapeutic change in CBT. In addition, observations in these cases supported the theoretical suggestion that supporting interventions would be better accepted at lower APES levels, whereas challenging interventions would be better accepted at higher APES levels.

Clinical and cost effectiveness of a system for turning and positioning intensive care unit patients, when compared to usual care turning and positioning devices, for the prevention of hospital-acquired pressure injuries. A randomised controlled trial.

Pressure injuries affect 13.1% to 45.5% of patients in the intensive care unit and lead to pain and discomfort for patients, burden on healthcare providers, and unnecessary cost to the health system. Turning and positioning systems offer improvements on usual care devices, however the evidence of the effectiveness of such systems is still emerging. We conducted an investigator initiated, prospective, single centre, two group, non-blinded, randomised controlled trial to determine the effectiveness of a system for turning and positioning intensive care unit patients, when compared to usual care turning and positioning devices, for preventing PIs. The trial was prematurely discontinued after enrolment of 78 participants due to COVID-19 pandemic related challenges and lower than expected enrolment rate. The study groups were comparable on baseline characteristics and adherence to the interventions was high. Four participants developed a PI (in the sacral, ischial tuberosity or buttock region), n = 2 each in the intervention and control group. Each participant developed one PI. As the trial is underpowered, these findings do not provide an indication of the clinical effectiveness of the interventions. There was no participant drop-out or withdrawal and there were no adverse events, device deficiencies, or adverse device effects identified or reported. The results of our study (in particular those pertaining to enrolment, intervention adherence and safety) provide considerations for future trials that seek to investigate how to prevent PIs among ICU patients.

Ambivalence Resolution in Meaning Reconstruction Grief Therapy: An Exploratory Study.

In psychotherapy, ambivalence may be conceptualized as a conflict between two distinct motivations: one that is favorable to change (pro-change) and another that favors the maintenance of a problematic pattern (pro status quo). Previous studies identified two processes by which clients resolve this conflict: imposing the innovative part and silencing the problematic one (dominance), and establishing negotiations between the innovative and the pro status quo parts (negotiation). The present exploratory study examined ambivalence resolution in a sample of clients diagnosed with complicated grief. Results revealed that, in recovered cases, negotiation increases and dominance decreases from the beginning until the middle sessions of therapy and the opposite tendency is observed from the middle to the final sessions. Unchanged cases reveal an overall high proportion of dominance and an overall low proportion of negotiation. These results are partially divergent from those reported in previous studies with samples of clients diagnosed with major depression.

Premature termination of the unified protocol for the transdiagnostic treatment of emotional disorders: The role of ambivalence towards change.

Ambivalence towards change is an expected, recurrent process in psychological change. However, the prolonged experience of ambivalence in psychotherapy contributes to client disengagement, which could result in treatment dropout. Considering the negative effects of premature termination of therapy and the convenience of the identification of clients who are at risk of dropping out before achieving good-outcome, the current study explored the predictive power of ambivalence for premature therapy termination using a multilevel time-backwards model (i.e., considering the session of the dropout as session zero and then modelling what occurred from the dropout until session 1). Participants included a total of 96 psychotherapy clients (38 dropouts) treated in a university-based clinic following the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders. Multilevel modelling using a time-backwards model to analyse dropout data provided evidence of the predictive power of ambivalence evolution throughout treatment on the decision to prematurely discontinue treatment (p < .0001; R2 adj = .29). Specifically, good-outcome dropouts presented a decreasing ambivalence trend throughout treatment, whereas poor-outcome dropouts tended to experience the same levels of ambivalence before deciding to drop out (time × dropout; ß11 = .64, p = .014). Additionally, poor-outcome dropouts presented higher levels of ambivalence (ß01 = 9.92, p < .0001) in the last session. The results suggest that the pattern of client ambivalence towards change is a predictor of premature termination of therapy. Implications for clinical and research contexts are discussed.

Can increased load carriage affect lower limbs kinematics during military gait?

The aim of this study was to investigate if increased load carriage, in male military personnel, can affect the lower limbs kinematics. Twelve male military volunteers from the Portuguese Army were recruited and evaluated in an unloaded and loaded gait condition. Linear kinematics and lower limbs joint angle at heel strike, midstance and toe off were calculated. The stance, swing and double support times were found to be different between load conditions (p < 0.05). There was an interaction between load and limb (p < 0.05) for joint angles, during midstance, with limbs performing different movements in the frontal plane during loaded gait. Load increase had a different effect on the right knee, with a reduction in the abduction (valgus). This study may be beneficial in offering suggestion to improve the performance of gait with load and in an attempt to help prevent possible injuries. Practitioner summary: Increased load can affect lower limbs of male soldiers at the pelvic, hip and knee angles on the frontal plane, which can alter the joint force distribution. While these alterations may indicate protective mechanics, load management procedures should be implemented along with gait monitoring to avoid negative effects in performance.

Ambivalence resolution in the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders: An exploratory case study.

Patient ambivalence towards change is a central therapeutic target in the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP). However, we do not know if and how patients resolve ambivalence across the sessions and modules of the UP. Previous studies have identified two types of ambivalence resolution-dominance and negotiation-and different patterns of resolution for recovered and unchanged cases. Objectives: This exploratory single case study aimed to describe the frequency of observed ambivalence resolution strategies across UP sessions and evaluate the impact of distinct ambivalence resolution strategies on ambivalence. Method: Sixteen sessions of a recovered case were coded with observational measures of ambivalence and ambivalence resolution. Results: Observed ambivalence significantly decreased; dominance remained highly frequent across sessions, and negotiation increased from the beginning to the middle phase of treatment but not from the middle to the final phase. Negotiation was significantly associated with ambivalence reduction. Conclusion: The progression of ambivalence resolution strategies differed from previous studies with distinct therapeutic approaches; promoting negotiation between the different parts of the client's inner conflict across the whole therapy may be valuable in dealing with patient ambivalence in UP treatment.

Innovative moments in recovered cases treated with the unified protocol for transdiagnostic treatment of emotional disorders.

OBJECTIVE: Innovative moments (IMs) are moments in which the previous problematic pattern of meaning is challenged. Studies have shown that IMs are associated with good psychotherapy outcomes. A three-level hierarchy of IMs was observed in recent studies, with level 1 IMs being more elementary and levels 2 and 3 being more complex and associated with treatment success. However, studies with manualized protocol treatments are thus far lacking. This study analyzed the longitudinal progression of IMs in the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP) and explored its associations with changes in psychological distress. METHODS: Data were collected from a Portuguese university-based outpatient clinic and included 18 cases with positive outcomes. Nine sessions of each case were coded with the IM coding system (N=162). RESULTS: Multilevel analyses showed a significant increase in all IM levels across treatments. The decrease in psychological distress predicted an increase in level 2 IMs in the same session. CONCLUSION: The evolution of IMs is similar to what was found previously in other studies. Contrary to what was found in previous studies, IMs did not predict outcomes in the following session, whereas the reduction in psychological distress predicted the emergence of level 2 IMs.

Improving B1+ parametric estimation in the brain from multispin-echo sequences using a fusion bootstrap moves solver.

PURPOSE: To simultaneously estimate the B1+ field (along with the T2 ) in the brain with multispin-echo (MSE) sequences and dictionary matching. METHODS: T2 mapping provides clinically relevant information such as in the assessment of brain degenerative diseases. It is commonly obtained with MSE sequences, and accuracy can be further improved by matching the MSE signal to a precomputed dictionary of echo-modulation curves. For additional T1 quantification, transmit B1+ field knowledge is also required. Preliminary work has shown that although simultaneous brain B1+ estimation along with T2 is possible, it presents a bimodal distribution with the main peak coinciding with the true value. By taking advantage of this, the B1+ maps are expected to be spatially smooth by applying an iterative method that takes into account each pixel neighborhood known as the fusion bootstrap moves solver (FBMS). The effect of the FBMS on B1+ accuracy and piecewise smoothness is investigated and different spatial regularization levels are compared. Total variation regularization was used for both B1+ and T2 simultaneous estimation because of its simplicity as an initial proof-of-concept; future work could explore non edge-preserving regularization independently for B1+ . RESULTS: Improvements in B1+ accuracy (up to 45.37% and 16.81% B1+ error decrease) and recovery of spatially homogeneous maps are shown in simulations and in vivo 3.0T brain data, respectively. CONCLUSION: Accurate B1+ estimated values can be obtained from widely available MSE sequences while jointly estimating T2 maps with the use of echo-modulation curve matching and FBMS at no further cost.

tRNA-modifying enzyme mutations induce codon-specific mistranslation and protein aggregation in yeast.

Protein synthesis rate and accuracy are tightly controlled by the cell and are essential for proteome homoeostasis (proteostasis); however, the full picture of how mRNA translational factors maintain protein synthesis accuracy and co-translational protein folding are far from being fully understood. To address this question, we evaluated the role of 70 yeast tRNA-modifying enzyme genes on protein aggregation and used mass spectrometry to identify the aggregated proteins. We show that modification of uridine at anticodon position 34 (U34) by the tRNA-modifying enzymes Elp1, Elp3, Sml3 and Trm9 is critical for proteostasis, the mitochondrial tRNA-modifying enzyme Slm3 plays a fundamental role in general proteostasis and that stress response proteins whose genes are enriched in codons decoded by tRNAs lacking mcm5U34, mcm5s2U34, ncm5U34, ncm5Um34, modifications are overrepresented in protein aggregates of the ELP1, SLM3 and TRM9 KO strains. Increased rates of amino acid misincorporation were also detected in these strains at protein sites that specifically mapped to the codons sites that are decoded by the hypomodified tRNAs, demonstrating that U34 tRNA modifications safeguard the proteome from translational errors, protein misfolding and proteotoxic stress.

A Deep Learning Approach for Foot Trajectory Estimation in Gait Analysis Using Inertial Sensors.

Gait performance is an important marker of motor and cognitive decline in older adults. An instrumented gait analysis resorting to inertial sensors allows the complete evaluation of spatiotemporal gait parameters, offering an alternative to laboratory-based assessments. To estimate gait parameters, foot trajectories are typically obtained by integrating acceleration two times. However, to deal with cumulative integration errors, additional error handling strategies are required. In this study, we propose an alternative approach based on a deep recurrent neural network to estimate heel and toe trajectories. We propose a coordinate frame transformation for stride trajectories that eliminates the dependency from previous strides and external inputs. Predicted trajectories are used to estimate an extensive set of spatiotemporal gait parameters. We evaluate the results in a dataset comprising foot-worn inertial sensor data acquired from a group of young adults, using an optical motion capture system as a reference. Heel and toe trajectories are predicted with low errors, in line with reference trajectories. A good agreement is also achieved between the reference and estimated gait parameters, in particular when turning strides are excluded from the analysis. The performance of the method is shown to be robust to imperfect sensor-foot alignment conditions.

Orientation-Invariant Spatio-Temporal Gait Analysis Using Foot-Worn Inertial Sensors.

Inertial sensors can potentially assist clinical decision making in gait-related disorders. Methods for objective spatio-temporal gait analysis usually assume the careful alignment of the sensors on the body, so that sensor data can be evaluated using the body coordinate system. Some studies infer sensor orientation by exploring the cyclic characteristics of walking. In addition to being unrealistic to assume that the sensor can be aligned perfectly with the body, the robustness of gait analysis with respect to differences in sensor orientation has not yet been investigated-potentially hindering use in clinical settings. To address this gap in the literature, we introduce an orientation-invariant gait analysis approach and propose a method to quantitatively assess robustness to changes in sensor orientation. We validate our results in a group of young adults, using an optical motion capture system as reference. Overall, good agreement between systems is achieved considering an extensive set of gait metrics. Gait speed is evaluated with a relative error of -3.1±9.2 cm/s, but precision improves when turning strides are excluded from the analysis, resulting in a relative error of -3.4±6.9 cm/s. We demonstrate the invariance of our approach by simulating rotations of the sensor on the foot.

Enhancing knowledge on low-value fishing species: the distinct reproductive strategy of two gurnard species.

The depletion and overexploitation of several fish stock demands for a valorisation of non-target and discarded species. Nonetheless, such species are often poorly studied, and information on their biological parameters must be gathered for effective population management. For 1 year, the reproductive strategy of the piper gurnard Trigla lyra and the red gurnard Chelidonichthys cuculus was studied by monthly samples obtained from commercial boats operating on western Portuguese coast. Both species showed a biased sex ratio towards females, especially for larger length classes. Length at first maturity could be estimated only for red gurnard (22.1 and 19.9 cm for females and males, respectively) because all piper gurnard individuals caught were mature. Piper gurnard showed determinate fecundity and a short spawning season, from November to February with a peak in January, whereas red gurnard showed indeterminate fecundity and a wide spawning season, from late December to May. The relative annual fecundity estimated for red gurnard (1893 ± 728 oocytes × g-1 eviscerated weight [EW]) was higher than the one estimated for piper gurnard (1018 ± 250 oocytes×g-1 EW). Although important information for understanding the species dynamics is presented in this study, additional information on other life-history parameters and of species landings is required.

What is the effect of emotional processing on depression? A longitudinal study.

Emotional processing is an empirically established predictor of pre-post therapy improvement in depression. However, its relationship to symptom alleviation over time requires clarification. To clarify the contribution of emotional processing to gradual symptom improvement, we explored both (1) the effect of emotional processing on pre-post therapy changes in depressive symptoms (final outcome) and (2) its association with the intensity of clinical symptoms across sessions (session-by-session outcome). These relationships were estimated in a sample of 50 depressed clients treated with cognitive-behavioral therapy (CBT) or emotion-focused therapy (EFT). Emotional processing was measured by the Experiencing Scale during Emotion Episodes in five sessions taken across therapy. As expected, we found that a greater increase in emotional processing during treatment predicted a greater pre-post therapy improvement in depressive symptoms. Higher levels of emotional processing predicted next-session lower intensity on clinical symptoms, but the intensity of symptoms contributed to explaining the subsequent level of emotional processing achieved. Our observations suggest that clients' capabilities to process their emotions may both facilitate and be promoted by gradual improvement in symptoms. These results suggest the reciprocal predictive influence of emotional processing and symptoms on the therapeutic change in depression.

Positioning immobile critically ill patients who are at risk of pressure injuries using a purpose-designed positioning device and usual care equipment: An observational feasibility study.

The prevalence of pressure injuries in the intensive care unit (ICU) setting is high with rates ranging from 13.1% to 45.5%. Evaluation of interventions to prevent pressure injuries should be informed by preliminary research to identify factors that should be considered during the design of future trials. The study objectives were to evaluate the process of participant recruitment and monitoring in the ICU; measure the maintenance of body angle (in the side-lying lateral tilt position) and head and neck alignment angle (in the supine position) among immobile critically ill patients when using a purpose-designed positioning device and usual care equipment, and; ascertain the time required to position patients with the purpose-designed positioning device and the usual care equipment. A prospective, observational, feasibility study was conducted in an ICU in Victoria, Australia. The sample was immobile critically ill adults at high-risk of developing pressure injuries. The usual care interventions were pillows, foam wedges, and rolled towels, and the intervention device was the Z-Flo Fluidized Positioner. The body angle and head and neck alignment were measured on six occasions (at baseline, 1 hour, and 2 hours). The time required for positioning was also measured. The sample was predominately male (n = 5, 62%) with a mean age of 59 years. The majority of patients (n = 106, 92.2%) were not immobile and therefore were ineligible to participate. A total of 48 turning and positioning interventions were observed. For the side-lying lateral tilt position, the degree of difference from baseline to 2 hours was no more than three degrees for all the devices (the Fluidized Positioner 25°-26°, the foam wedge 29°-27°, and the pillow 23°-21°). For the head and neck position, the degree of difference from baseline to 2 hours was the greatest for the pillow and rolled towel (78°-71°, a difference of 7°) and the pillow alone (79°-74°, a difference of 5°). The degree of difference was the lowest for the Fluidized Positioner (84°-86°, a difference of 2°). Future research to evaluate positioning equipment in the ICU should consider patient eligibility characteristics, particularly immobility. The conduct of preliminary studies to inform the design of larger pressure injury prevention trials is recommended.

Real-Time Drink Trigger Detection in Free-living Conditions Using Inertial Sensors.

Despite the importance of maintaining an adequate hydration status, water intake is frequently neglected due to the fast pace of people's lives. For the elderly, poor water intake can be even more concerning, not only due to the damaging impact of dehydration, but also since seniors' hydration regulation mechanisms tend to be less efficient. This work focuses on the recognition of the pre-drinking hand-to-mouth movement (a drink trigger) with two main objectives: predict the occurrence of drinking events in real-time and free-living conditions, and assess the potential of using this method to trigger an external component for estimating the amount of fluid intake. This shall contribute towards the efficiency of more robust multimodal approaches addressing the problem of water intake monitoring. The system, based on a single inertial measurement unit placed on the forearm, is unobtrusive, user-independent, and lightweight enough for real-time mobile processing. Drinking events outside meal periods were detected with an F-score of 97% in an offline validation with data from 12 users, and 85% in a real-time free-living validation with five other subjects, using a random forest classifier. Our results also reveal that the algorithm first detects the hand-to-mouth movement 0.70 s before the occurrence of the actual sip of the drink, proving that this approach can have further applications and enable more robust and complete fluid intake monitoring solutions.

Wearable Embedded Intelligence for Detection of Falls Independently of on-Body Location.

Falls are one of the most common problems in the elderly population. Therefore, each year more solutions for automatic fall detection are emerging. This paper proposes a single accelerometer algorithm for wearable devices that works for three different body locations: chest, waist and pocket, without a calibration step being required. This algorithm is able to be fully executed on a wearable device and no external devices are necessary for data processing. Additionally, a study of the accelerometer sampling rate, that allows the algorithm to achieve a better performance, was performed. The algorithm was validated with a continuous dataset with daily living activities and 272 simulated falls. Considering the trade-off between sensitivity and the number of false alarms the most suitable sampling rate found was 50 Hz. The proposed algorithm was able to achieve a trade-off of no false alarms and 89.5% of fall detection rate when wearing the sensor on the user's waist with a medium sensitivity level of the algorithm. In conclusion, this paper presents a reliable solution for automatic fall detection that can be adapted to different usages and conditions, since it can be used in different body locations and its sensitivity can be adapted to different subjects according to their physical activity level.