Finding Suitable Clinical Endpoints for a Potential Treatment of a Rare Genetic Disease: the Case of ARID1B

Abstract There is a lack of reliable, repeatable, and non-invasive clinical endpoints when investigating treatments for intellectual disability (ID). The aim of this study is to explore a novel approach towards developing new endpoints for neurodevelopmental disorders, in this case for ARID1B-related ID. In this study, twelve subjects with ARID1B-related ID and twelve age-matched controls were included in this observational case–control study. Subjects performed a battery of non-invasive neurobehavioral and neurophysiological assessments on two study days. Test domains included cognition, executive functioning, and eye tracking. Furthermore, several electrophysiological assessments were performed. Subjects wore a smartwatch (Withings® Steel HR) for 6 days. Tests were systematically assessed regarding tolerability, variability, repeatability, difference with control group, and correlation with traditional endpoints. Animal fluency, adaptive tracking, body sway, and smooth pursuit eye movements were assessed as fit-for-purpose regarding all criteria, while physical activity, heart rate, and sleep parameters show promise as well. The event-related potential waveform of the passive oddball and visual evoked potential tasks showed discriminatory ability, but EEG assessments were perceived as extremely burdensome. This approach successfully identified fit-for-purpose candidate endpoints for ARID1B-related ID and possibly for other neurodevelopmental disorders. Next, results could be replicated in different ID populations or the assessments could be included as exploratory endpoint in interventional trials in ARID1B-related ID.

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Effectiveness evaluation of translingual neurostimulation in motor rehabilitation in children with spastic diplegia

Pediatric Traumatology Orthopaedics and Reconstructive Surgery ◽

10.17816/ptors7217-24 ◽

2019 ◽

Vol 7 (2) ◽

pp. 17-24 ◽

Cited By ~ 2

Author(s):

Tatiana S. Ignatova ◽

Galina A. Ikoeva ◽

Victor E. Kolbin ◽

Andrey M. Sarana ◽

Sergey G. Shcherbak ◽

...

Keyword(s):

Cerebral Palsy ◽

Active Group ◽

Control Group ◽

Spastic Diplegia ◽

Restorative Treatment ◽

Non Invasive ◽

Novel Approach ◽

Children With Cerebral Palsy ◽

Therapeutic Procedures ◽

And Control

Introduction. Cerebral palsy is one of the most common non-progressive neurological disorders caused by fetal or infant brain injury. Current rehabilitation for children with cerebral palsy involves a series of measures, including physical training, special massage techniques, physiotherapy, treatment by certain positions and postures, use of supporting orthoses and fixation devices for walking, and special orthopedic suits facilitating verticalization and motor activity of a child. Over the last few decades, computerized stimulators and robotics with virtual reality systems have been actively used in neurorehabilitation. However, most of these systems did not show significant efficiency in rehabilitation of children with cerebral palsy. In the last few years, different non-invasive electrostimulation techniques have been considered innovative and can be applied independently or in combination with existing procedures. One of such techniques is translingual neurostimulation. Aim. This study aimed to evaluate the effectiveness of a combination of translingual neurostimulation and physical rehabilitation for children with cerebral palsy. Materials and methods. In this study, we observed 134 children (63 girls and 71 boys) with spastic diplegia aged 2–17 years (mean age is 7.8 years old ± 0.3). Depending on the type of rehabilitation therapy, the patients were divided into two groups: active (main) and control. Active group consisted of 94 children who received standard restorative treatment in combination with translingual neurostimulation, whereas the control group consisted of 40 children who received only standard rehabilitation treatment without translingual neurostimulation. Results. Both groups of patients showed positive dynamics; however, patients in the active group showed greater improvements as evidenced by all grading scales. Improvements were observed in children of all ages, and the results were mostly stable for 12 months. Conclusion. Translingual neurostimulation is a novel approach to neurorehabilitation that shows promising results, in addition to its proven effectiveness and safety. As a result of neurostimulation, the patient’s brain becomes more susceptible to the applied therapeutic procedures aimed at restoring motor control and formation of new motor skills, thereby markedly increasing the effectiveness of neurorehabilitation. This study broadens the perspectives in the use and further development of translingual neurostimulation in rehabilitation of children with cerebral palsy.

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The Application of ASSRs, P50, and MMN in the Exploration of Cognitive Dysfunction Involving Inputs and Processing in Insomnia Patients

Frontiers in Human Neuroscience ◽

10.3389/fnhum.2021.714302 ◽

2021 ◽

Vol 15 ◽

Author(s):

Hongwei Zhao ◽

Chang Liu ◽

Changming Wang ◽

Xiangyu Zheng ◽

Yanhui Peng ◽

...

Keyword(s):

Gender Difference ◽

Cognitive Dysfunction ◽

Event Related Potential ◽

Control Group ◽

Speed Of Information Processing ◽

Significant Difference ◽

Sleep Parameters ◽

And Gender ◽

Auditory Steady State Responses ◽

And Control

Objective cognitive dysfunction has been commonly found in patients with insomnia, such as attention, memory, speed of information processing, and executive functions. Auditory steady-state responses (ASSRs), P50, mismatch negativity (MMN) can meet varied need and estimate such different cognitive dysfunction. Thus, we can examine whether insomnia is associated with different cognitive dysfunction by such multiple event-related potential (ERP) tasks. Methods we used polysomnography (PSG) to record such objective PSG parameters. ASSR, P50, and MMN were performed in sequence, different ERP components have been analyzed such as latency or amplitude between insomnia group and control group. And we chosed person correlation to make correlation analysis between different ERP components and gender, education, and sleep characteristics. Results there is a significant gender difference of ASSR latency found in insomnia group, and the similar result has been found in suppression ratio of amplitudes (S2:S1) for P50. Additionally, a significant correlation between sleep characteristics and ASSR, P50 has been found. Furthermore, there was a significant difference of MMN latency between insomnia and control group, and between sleep characteristics and varied MMN parameters as latency and amplitude. Discussion our results suggested robust electrophysiological abnormalities as ASSR, P50, and MMN in insomnia patients. Such abnormalities included gender difference, education difference, difference in depressive tendency, and difference in sleep parameters. That results revealed varied cognitive dysfunction involving inputs and processing in insomnia patients. And at the same time, we have also explored the neuropsychological mechanisms underlying the cognitive dysfunction with such different ERP tasks.

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Relationship between Invasive and Non-Invasive Hemodynamic Measures in Experimental Pulmonary Hypertension

Current Respiratory Medicine Reviews ◽

10.2174/1573398x16666200516180118 ◽

2020 ◽

Vol 16 (1) ◽

pp. 47-53

Author(s):

Vicente Benavides-Córdoba ◽

Mauricio Palacios Gómez

Keyword(s):

Heart Rate ◽

Pulmonary Hypertension ◽

Ejection Fraction ◽

Right Ventricle ◽

Correlation Coefficient ◽

Pearson Correlation ◽

Systolic Pressure ◽

Control Group ◽

Pearson Correlation Coefficient ◽

Non Invasive

Introduction: Animal models have been used to understand the pathophysiology of pulmonary hypertension, to describe the mechanisms of action and to evaluate promising active ingredients. The monocrotaline-induced pulmonary hypertension model is the most used animal model. In this model, invasive and non-invasive hemodynamic variables that resemble human measurements have been used. Aim: To define if non-invasive variables can predict hemodynamic measures in the monocrotaline-induced pulmonary hypertension model. Materials and Methods: Twenty 6-week old male Wistar rats weighing between 250-300g from the bioterium of the Universidad del Valle (Cali - Colombia) were used in order to establish that the relationships between invasive and non-invasive variables are sustained in different conditions (healthy, hypertrophy and treated). The animals were organized into three groups, a control group who was given 0.9% saline solution subcutaneously (sc), a group with pulmonary hypertension induced with a single subcutaneous dose of Monocrotaline 30 mg/kg, and a group with pulmonary hypertension with 30 mg/kg of monocrotaline treated with Sildenafil. Right ventricle ejection fraction, heart rate, right ventricle systolic pressure and the extent of hypertrophy were measured. The functional relation between any two variables was evaluated by the Pearson correlation coefficient. Results: It was found that all correlations were statistically significant (p <0.01). The strongest correlation was the inverse one between the RVEF and the Fulton index (r = -0.82). The Fulton index also had a strong correlation with the RVSP (r = 0.79). The Pearson correlation coefficient between the RVEF and the RVSP was -0.81, meaning that the higher the systolic pressure in the right ventricle, the lower the ejection fraction value. Heart rate was significantly correlated to the other three variables studied, although with relatively low correlation. Conclusion: The correlations obtained in this study indicate that the parameters evaluated in the research related to experimental pulmonary hypertension correlate adequately and that the measurements that are currently made are adequate and consistent with each other, that is, they have good predictive capacity.

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Retinal vascular fractal dimensions and their association with macrovascular cardiac disease.

Ophthalmic Research ◽

10.1159/000514442 ◽

2021 ◽

Author(s):

Sebastian Dinesen ◽

Pia Søndergaard Jensen ◽

Maria Bloksgaard ◽

Søren Leer Blindbæk ◽

Jo G.R. De Mey ◽

...

Keyword(s):

Confidence Interval ◽

Cardiac Disease ◽

Artery Bypass ◽

Fractal Dimensions ◽

Macrovascular Disease ◽

Control Group ◽

Vascular Structure ◽

Non Invasive ◽

Automatic Software ◽

Multivariable Regression

Introduction As the only part of the human vasculature, retina is available for direct, non-invasive inspection. Retinal vascular fractal dimension (DF) is a method to measure the structure of the retinal vascular tree, with higher non-integer values between 1 and 2 representing a more complex and dense retinal vasculature. Retinal vascular structure has been associated with a variety of systemic diseases and this study examined the association of DF and macrovascular cardiac disease in a case-control design. Methods Retinal fundus photos were captured with Topcon TRC-50X in 38 persons that had coronary artery bypass grafting (CABG, cases) and 37 cardiovascular healthy controls. The semi-automatic software VAMPIRE was used to measure retinal DF. Results Patients with CABG had lower DF of the retinal main venular vessels compared to the control group (1.15 vs. 1.18, p=0.01). In a multivariable regression model adjusted for gender and age, eyes in the fourth quartile with higher DF were less likely to have CABG compared to patients in the first (OR, 7.20; 95% confidence interval, 1.63 to 31.86; p=0.009) and second quartile (OR, 8.25; 95% confidence interval, 1.70 to 40.01; p=0.009). Conclusions This study demonstrates that lower complexity of main venular vessels associates with higher risk of having CABG. The research supports the hypothesis that the retinal vascular structure can be used to assess non-ocular macrovascular disease.

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Variability of serum IgG sialylation and galactosylation degree in women with advanced endometriosis

Scientific Reports ◽

10.1038/s41598-021-85200-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Katarzyna Sołkiewicz ◽

Hubert Krotkiewski ◽

Marcin Jędryka ◽

Ewa M. Kratz

Keyword(s):

Cluster Analysis ◽

Sialic Acid ◽

Control Group ◽

Clinical Tool ◽

Non Invasive ◽

Healthy Women ◽

Serum Igg ◽

And Cluster Analysis ◽

Invasive Diagnostics ◽

And Control

AbstractEndometriosis is an inflammatory disease which diagnostics is difficult and often invasive, therefore non-invasive diagnostics methods and parameters are needed for endometriosis detection. The aim of our study was to analyse the glycosylation of native serum IgG and IgG isolated from sera of women classified as: with endometriosis, without endometriosis but with some benign ginecological disease, and control group of healthy women, in context of its utility for differentiation of advanced endometriosis from the group of healthy women. IgG sialylation and galactosylation/agalactosylation degree was determined using specific lectins: MAA and SNA detecting sialic acid α2,3- and α2,6-linked, respectively, RCA-I and GSL-II specific to terminal Gal and terminal GlcNAc, respectively. The results of ROC and cluster analysis showed that the serum IgG MAA-reactivity, sialylation and agalactosylation factor may be used as supplementary parameters for endometriosis diagnostics and could be taken into account as a useful clinical tool to elucidate women with high risk of endometriosis development. Additionally, we have shown that the analysis of native serum IgG glycosylation, without the prior time-consuming and expensive isolation of the protein, is sufficient to differentiation endometriosis from a group of healthy women.

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The Effect of a Non-Invasive Positive Pressure Ventilation Simulation Program on General Ward Nurses’ Knowledge and Self-Efficacy

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18062877 ◽

2021 ◽

Vol 18 (6) ◽

pp. 2877

Author(s):

Moon-Sook Kim ◽

Mi-Hee Seo ◽

Jin-Young Jung ◽

Jinhyun Kim

Keyword(s):

Self Efficacy ◽

Qualitative Data ◽

Positive Pressure Ventilation ◽

Intervention Group ◽

General Ward ◽

Simulation Program ◽

Positive Pressure ◽

Control Group ◽

Training Strategy ◽

Non Invasive

The purpose of this study is to develop a simulation-based ventilator training program for general ward nurses and identify its effects. Quantitative data were collected from 29 nurses (intervention group: 15, control group: 14), of which seven were interviewed with focus groups to collect qualitative data. The quantitative results revealed significant differences in ventilator-related knowledge (p = 0.029) and self-efficacy (p = 0.026) between the intervention and control groups. Moreover, three themes were derived from meaningful statements in the qualitative data: understanding psychophysical discomfort of the patient while applying the ventilator; helping in ventilator care; and establishing a future ventilator training strategy. The findings confirmed that the non-invasive positive pressure ventilation (NPPV) simulation program is an effective method for improving the knowledge of ventilator nursing and self-efficacy and will be helpful in developing educational methods and strategies related to ventilator nursing for general ward nurses.

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Effects of multi-domain cognitive training on working memory retrieval in older adults: behavioral and ERP evidence from a Chinese community study

Scientific Reports ◽

10.1038/s41598-020-79784-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Xiangfei Hong ◽

You Chen ◽

Jijun Wang ◽

Yuan Shen ◽

Qingwei Li ◽

...

Keyword(s):

Older Adults ◽

Working Memory ◽

Training Program ◽

Cognitive Training ◽

Local Community ◽

Training Group ◽

Event Related Potential ◽

Control Group ◽

Baseline Session

AbstractWorking memory (WM) is a fundamental cognitive function that typically declines with age. Previous studies have shown that targeted WM training has the potential to improve WM performance in older adults. In the present study, we investigated whether a multi-domain cognitive training program that was not designed to specifically target WM could improve the behavioral performance and affect the neural activity during WM retrieval in healthy older adults. We assigned healthy older participants (70–78 years old) from a local community into a training group who completed a 3-month multi-domain cognitive training and a control group who only attended health education lectures during the same period. Behavioral and electroencephalography (EEG) data were recorded from participants while performing an untrained delayed match or non-match to category task and a control task at a pre-training baseline session and a post-training follow-up session. Behaviorally, we found that participants in the training group showed a trend toward greater WM performance gains than participants in the control group. Event-related potential (ERP) results suggest that the task-related modulation of P3 during WM retrieval was significantly enhanced at the follow-up session compared with the baseline session, and importantly, this enhancement of P3 modulation was only significant in the training group. Furthermore, no training-related effects were observed for the P2 or N2 component during WM retrieval. These results suggest that the multi-domain cognitive training program that was not designed to specifically target WM is a promising approach to improve WM performance in older adults, and that training-related gains in performance are likely mediated by an enhanced modulation of P3 which might reflect the process of WM updating.

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Tethered Lipid Membranes as a Nanoscale Arrangement Towards Non-Invasive Analysis of Acute Pancreatitis

Biomedicines ◽

10.3390/biomedicines9070755 ◽

2021 ◽

Vol 9 (7) ◽

pp. 755

Author(s):

Rima Budvytyte ◽

Akvile Milasiute ◽

Dalius Vitkus ◽

Kestutis Strupas ◽

Aiste Gulla ◽

...

Keyword(s):

Acute Pancreatitis ◽

Lipid Membranes ◽

Electrochemical Impedance ◽

Membrane Integrity ◽

Electrochemical Technique ◽

Label Free ◽

Non Invasive ◽

Novel Approach ◽

Analytical System ◽

Shock Proteins

Extracellular heat shock proteins (HSPs) mediate immunological functions and are involved in pathologies such as infection, stress, and cancer. Here, we demonstrated the dependence of an amount of HSP70 and HSP90 in serum vs. severity of acute pancreatitis (AP) on a cohort of 49 patients. Tethered bilayer lipid membranes (tBLMs) have been developed to investigate HSPs’ interactions with tBLMs that can be probed by electrochemical impedance spectroscopy (EIS). The results revealed that HSP70 and HSP90 interact via different mechanisms. HSP70 shows the damage of the membrane, while HSP90 increases the insulation properties of tBLM. These findings provide evidence that EIS offers a novel approach for the study of the changes in membrane integrity induced by HSPs proteins. Herein, we present an alternative electrochemical technique, without any immunoprobes, that allows for the monitoring of HSPs on nanoscaled tBLM arrangement in biologics samples such us human urine. This study demonstrates the great potential of tBLM to be used as a membrane based biosensor for novel, simple, and non-invasive label-free analytical system for the prediction of AP severity.

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A novel approach to radiographic detection of bucco-palatal/lingual dilacerations: A preliminary study with ImageJ

Proceedings of the Institution of Mechanical Engineers Part H Journal of Engineering in Medicine ◽

10.1177/09544119211030717 ◽

2021 ◽

pp. 095441192110307

Author(s):

Samed Satir ◽

Muhammed Hilmi Buyukcavus ◽

Kaan Orhan

Keyword(s):

Longitudinal Axis ◽

Control Group ◽

Single Root ◽

Novel Approach ◽

Significant Difference ◽

Spectrum Feature ◽

Group 2 ◽

Imagej Software ◽

And Control ◽

Control Group Group

The purpose of our study is to determine whether bucco-palatal/lingual (BPL) root dilacerations (RD), especially in single root teeth, can be determined using the ImageJ program through only one periapical radiography. Extracted teeth without any RD ( n = 8) were determined as the control group (Group 1) and with RD in apical 1/3 part at least 20° with the longitudinal axis in the BPL direction ( n = 8) as the study group (Group 2). With the help of a simple holder system prepared, digital periapical radiographs of all teeth were taken in an anteroposterior position. Histogram analysis of all periapical radiographs was performed using the spectrum feature of ImageJ software. It was aimed to make a dilaceration analysis by comparing the groups using mean, standard deviation, minimum, maximum, and bin width values. As a result of the Mann-Whitney U test, all mean and maximum values showed a statistically significant difference between the study and control groups ( p < 0.05). This pilot study revealed that the ImageJ software can be used to diagnose BPL dilaceration in the apical 1/3 part of the root. It is important for dentists and patients that it can contribute to limiting the radiation dose to which patients will be exposed.

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Capnography and Pulse Oximetry Improve Fast Track Extubation in Patients Undergoing Coronary Artery Bypass Graft Surgery: A Randomized Clinical Trial

10.21203/rs.3.rs-496561/v1 ◽

2021 ◽

Author(s):

Seyed Tayeb Moradian ◽

Fatemah Beitollahi ◽

Mohammad Saeid Ghiasi ◽

Amir vahedian-azimi

Keyword(s):

Clinical Trial ◽

Pulse Oximetry ◽

Fast Track ◽

Artery Bypass ◽

Bypass Graft ◽

Intervention Group ◽

Control Group ◽

Artery Bypass Graft ◽

Cabg Surgery ◽

Non Invasive

Abstract Background Use of capnography as a non-invasive method during the weaning process for fast track extubation (FTE) is controversial. We conducted the present study to determine whether pulse oximetry and capnography could be utilized as alternatives to arterial blood gas (ABG) measurements in patients under mechanical ventilation (MV) following coronary artery bypass graft (CABG) surgery. Methods In this randomized clinical trial, 70 patients, who were candidates for CABG surgery, were randomly assigned into two equal groups (n = 35); the intervention group and the control group. In the intervention group, the ventilator management and weaning from MV was done using Etco2 from capnography and SpO2 from pulse oximetry. Meanwhile, in the control group, weaning was done based on ABG analysis. The length of intensive care unit (ICU) stay, time to extubation, number of manual ventilator setting changes, and alarms were compared between the groups. Results The end-tidal carbon dioxide (ETCO2) levels in the intervention group were completely similar to the partial pressure of carbon dioxide (PaCo2) in the control group (39.5 ± 3.1 vs. 39.4 ± 4.32, P > 0.05). The mean extubation times were significantly shorter in the intervention group compared to those in the control patients (212.2 ± 80.6 vs. 342.7 ± 110.7, P < 0.001). Moreover, the number of changes in the manual ventilator setting and the number of alarms were lower in the intervention group (P < 0.05). However, the differences in the length of stay in ICU between the two groups were not significant (P = 0.219). Conclusion According to our results, the use of non-invasive monitors, including capnography and pulse oximetry, is emphasized in order to utilize FTE after CABG surgery. Furthermore, it is a safe and valuable monitor that could be a good alternative for ABG in this population. Nevertheless, further studies with larger sample sizes and on different disease states and populations are required to assess the accuracy of our findings. Trial registration: IRCT, IRCT201701016778N6, Registered 3 March 2017, https://www.irct.ir/trial/7192

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