Pb(NO3 )2 induces cell apoptosis through triggering of reactive oxygen species accumulation and disruption of mitochondrial function via SIRT3/SOD2 pathways.

Lead (Pb) is nonbiodegradable and toxic to the lungs. To investigate the potential mechanisms of Pb-induced reactive oxygen species (ROS) accumulation and cell death in the lungs, human non-small lung carcinoma H460 cells were stimulated with Pb(NO3 )2 in this study. The results showed that Pb(NO3 )2 stimulation increased cell death by inducing cell apoptosis which showed a reduced Bcl-2 expression and an enhanced caspase 3 activation. Pb(NO3 )2 also caused the production of H2 O2 in H460 cells that triggering the buildup of ROS and mitochondrial membrane potential loss. We found that Pb(NO3 )2 modulates oxidoreductive activity through reduced the glutathione-disulfide reductase and glutathione levels in Pb(NO3 )2 -exposed H460 cells. Furthermore, the superoxide dismutase (SOD) upstream molecule sirtuin 3 (SIRT3) was increased with Pb(NO3 )2 dose. Collectively, these results demonstrate that Pb(NO3 )2 promotes lung cell death through SIRT3/SOD-mediated ROS accumulation and mitochondrial dysfunction.

Patient-Reported Variables Affecting Self-Perceived Overall Recovery Among People With Subacute Stroke.

IMPORTANCE: Patients' perception of overall recovery is a critical outcome for stroke rehabilitation. However, the perception of overall recovery cannot be obtained using multidimensional measures, because satisfaction in most domains of life does not guarantee satisfaction in overall recovery. A single overall recovery score seems a straightforward measure. However, the clinical implications of overall scores are restricted, because factors affecting patients' overall recovery are unclear, which can be prioritized to optimize the effectiveness of rehabilitation. OBJECTIVE: To examine patient-reported variables affecting overall recovery scores in patients with differing stroke severity. DESIGN: The 59 items of the Stroke Impact Scale 3.0 were selected using regression analysis with a forward selection to explain the overall recovery score (0% = no recovery; 100% = full recovery). Stroke severity was determined with the National Institutes of Health Stroke Scale. SETTING: Hospitals. PARTICIPANTS: Data of 950 patients collected 90 days after stroke. RESULTS: The models explained about 55% of the variance of the overall recovery scores with five to nine variables, but merely 16% of the variance was explained for patients with moderate stroke. As stroke severity increased, the number of identified variables decreased. Most identified variables were related to social participation and self-care activities (e.g., ability to help others, control the bowels, and dress the torso). Differences in the remaining variables depended on stroke severity. CONCLUSIONS AND RELEVANCE: Patients' priorities differ depending on stroke severity. The identified variables may be set as treatment goals to optimize patients' self-perceived overall recovery. Plain-Language Summary: How patients perceive their overall recovery after a stroke is a critical outcome for their stroke rehabilitation. This study demonstrated that patients with different stroke severity may have different priorities that influence their self-perceived levels of overall recovery. The variables identified in this study may help occupational therapy practitioners identify meaningful goals to optimize patients' self-perceived overall recovery.

Development of a Berg Balance Scale Short-Form Using a Machine Learning Approach in Patients With Stroke.

BACKGROUND AND PURPOSE: The Berg Balance Scale (BBS) is frequently used in routine clinical care and research settings and has good psychometric properties. This study was conducted to develop a short form of the BBS using a machine learning approach (BBS-ML). METHODS: Data of 408 individuals poststroke were extracted from a published database. The initial (ie, 4-, 5-, 6-, 7-, and 8-item) versions were constructed by selecting top-ranked items based on the feature selection algorithm in the artificial neural network model. The final version of the BBS-ML was chosen by selecting the short form that used a smaller number of items to achieve a higher predictive power R2 , a lower 95% limit of agreement (LoA), and an adequate possible scoring point (PSP). An independent sample of 226 persons with stroke was used for external validation. RESULTS: The R2 values for the initial 4-, 5-, 6-, 7-, and 8-item short forms were 0.93, 0.95, 0.97, 0.97, and 0.97, respectively. The 95% LoAs were 14.2, 12.2, 9.7, 9.6, and 8.9, respectively. The PSPs were 25, 35, 34, 35, and 36, respectively. The 6-item version was selected as the final BBS-ML. Preliminary external validation supported its performance in an independent sample of persons with stroke ( R2 = 0.99, LoA = 10.6, PSP = 37). DISCUSSION AND CONCLUSIONS: The BBS-ML seems to be a promising short-form alternative to improve administrative efficiency. Future research is needed to examine the psychometric properties and clinical usage of the 6-item BBS-ML in various settings and samples.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A402 ).

Development of a 13-item Short Form for Fugl-Meyer Assessment of Upper Extremity Scale Using a Machine Learning Approach.

OBJECTIVE: To develop and validate a short form of the Fugl-Meyer Assessment of Upper Extremity Scale (FMA-UE) using a machine learning approach (FMA-UE-ML). In addition, scores of items not included in the FMA-UE-ML were predicted. DESIGN: Secondary data from a previous study, which assessed individuals post-stroke using the FMA-UE at 4 time points: 5-30 days post-stroke screen, 2-month post-stroke baseline assessment, 6-month post-stroke assessment, and 12-month post-stroke assessment. SETTING: Rehabilitation units in hospitals. PARTICIPANTS: A total of 408 individuals post-stroke (N=408). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The 30-item FMA-UE. RESULTS: We established 29 candidate versions of the FMA-UE-ML with different numbers of items, from 1 to 29, and examined their concurrent validity and responsiveness. We found that the responsiveness of the candidate versions obviously declined when the number of items was less than 13. Thus, the 13-item version was selected as the FMA-UE-ML. The concurrent validity was good (intra-class correlation coefficients ≥0.99). The standardized response means of the FMA-UE-ML and FMA-UE were 0.54-0.88 and 0.52-0.91, respectively. The Pearson's rs between the change scores of the FMA-UE-ML and those of the FMA-UE were 0.96-0.98. The predicted item scores had acceptable to good accuracy (Kappa=0.50-0.92). CONCLUSIONS: The FMA-UE-ML seems a promising short form to improve administrative efficiency while retaining good concurrent validity and responsiveness. In addition, the FAM-UE-ML can provide all item scores of the FMA-UE for users.

Evaluating Different Measures of Low Back Pain Among U.S. Manual Materials Handling Workers: Comparisons of Demographic, Psychosocial, and Job Physical Exposure.

OBJECTIVE: To examine differences in demographic, psychosocial, and job physical exposure risk factors between multiple low back pain (LBP) outcomes in a prospective cohort of industrial workers. BACKGROUND: LBP remains a leading cause of lost industrial productivity. Different case definitions involving pain (general LBP), medication use (M-LBP), seeking healthcare (H-LBP), and lost time (L-LBP) are often used to study LBP outcomes. However, the relationship between these outcomes remains unclear. METHOD: Demographic, health status, psychosocial, and job physical exposure risk factors were quantified for 635 incident-eligible industrial workers. Incident cases of LBP outcomes and pain symptoms were quantified and compared across the four outcomes. RESULTS: Differences in age, gender, medical history, and LBP history were found between the four outcomes. Most incident-eligible workers (67%) suffered an LBP outcome during follow-up. Cases decreased from 420 for LBP (25.4 cases/100 person-years) to 303 for M-LBP (22.0 cases/100 person-years), to 151 for H-LBP (15.6 cases/100 person-years), and finally to 56 for L-LBP (8.7 cases/100 person-years). Conversely, pain intensity and duration increased from LBP to H-LBP. However, pain duration was relatively lower for L-LBP than for H-LBP. CONCLUSION: Patterns of cases, pain intensity, and pain duration suggest the influence of the four outcomes. However, few differences in apparent risk factors were observed between the outcomes. Further research is needed to establish consistent case definitions. APPLICATION: Knowledge of patterns between different LBP outcomes can improve interpretation of research and guide future research and intervention studies in industry.

Predicting the handgrip strength across the age span: Cross-validating reference equations from the 2011 NIH toolbox norming study.

STUDY DESIGN: This is a cross-sectional observational study. BACKGROUND: Reference equations for describing hand-grip strength across the age span were derived from the 2011 NIH Toolbox norming study. PURPOSE: The purpose of this study was to cross-validate reference equations by evaluating its predicting power on a separate, independent data set from the 2011-2014 National Health and Nutrition Examination Survey (NHANES) study METHODS: Observed hand-grip strength data from 13,676 noninstitutionalized participants were obtained from the NHANES study. Best values (best from 3 trials) and the mean values (averaged from 3 trials) were determined for each hand. Using the age (yr), height (m), and weight (kg), we computed predicted grip strength values for dominant and nondominant hands using the reference equations. For validation, three predictability measures: the correlation coefficient, residuals, and accuracy, were used along with the Bland-Altman plot. RESULTS: The predicted values highly correlated with observed values (r = 0.90, ICC = 0.89). In predicting best values, means (SD) of residuals were 1.41 (5.57) and 1.03 (5.44) kg for dominant and nondominant hands, respectively. In predicting mean values, means (SD) of residuals were -0.23 (5.42) and -0.54 (5.31) kg for dominant and nondominant hands, respectively. Root mean square error ranged from 4.10 (female's nondominant mean values) to 6.74 (male's dominant best values). About 5.56% fell outside of the 95% confidence interval of the prediction. CONCLUSIONS: We acknowledged that the two studies' hand-grip protocols (NIH Toolbox, NHANES) were different. Results provided the preliminary predicting performance of the reference equations derived from the NIH Toolbox study.

Rasch Analysis of the Stroke Impact Scale-16.

IMPORTANCE: Because the psychometric evidence supporting the use of the Stroke Impact Scale-16 (SIS-16) is limited, an examination of its psychometric properties is warranted. OBJECTIVE: To evaluate the psychometric properties of the SIS-16 using Rasch analysis. DESIGN: Secondary data analysis of responses to the SIS-16 from the published Field Administration of Stroke Therapy-Magnesium Trial database. SETTING: Emergency medical system agencies and acute care receiving hospitals. PARTICIPANTS: A total of 1,010 people with stroke. OUTCOMES AND MEASURES: We examined the item difficulty hierarchy, item fit, person-item match, separation index, person reliability coefficient, and ceiling and floor effect of the SIS-16. RESULTS: The item "climb a flight of stairs" was the most difficult, and "sit without losing balance" was the easiest. Four items misfit the Rasch partial-credit measurement model. Overall, the average patient ability estimate of 2.1 logits (SD = 2.0) was higher than the average item difficulty estimate of 0.0 logits (SD = 1.1). With a separation index of 2.85, the SIS-16 can differentiate people into 4.1 statistically distinct strata. The person reliability coefficient was .89. Given that 24.2% (n = 244) obtained the maximum score and 0.2% (n = 2) obtained the minimum score, the SIS-16 had a ceiling effect in this patient sample. CONCLUSIONS AND RELEVANCE: Results partially support the validity and clinical use of the SIS-16 in subacute stroke clinical settings. Further research is warranted to examine the psychometric properties of the SIS-16 in patients with chronic stroke. What This Article Adds: Our results partially support the use of the SIS-16 in clinical and research settings.

Development of a Short-Form Stroke Impact Scale Using a Machine Learning Algorithm for Patients at the Subacute Stage.

IMPORTANCE: Several short forms of the Stroke Impact Scale Version 3.0 (SIS 3.0) have been proposed in order to decrease its administration time of about 20 min. However, none of the short-form scores are comparable to those of the original measure. OBJECTIVE: To develop a short-form SIS 3.0 using a machine learning algorithm (ML-SIS). DESIGN: We developed the ML-SIS in three stages. First, we calculated the frequencies of items having the highest contribution to predicting the original domain scores across 50 deep neural networks. Second, we iteratively selected the items showing the highest frequency until the coefficient of determination (R2) of each domain was ≥.90. Third, we examined the comparability and concurrent and convergent validity of the ML-SIS. SETTING: Hospitals. PARTICIPANTS: We extracted complete data for 1,010 patients from an existing data set. RESULTS: Twenty-eight items were selected for the ML-SIS. High average R2s (.90-.96) and small average residuals (mean absolute errors and root-mean-square errors = 0.49-2.84) indicate good comparability. High correlations (rs = .95-.98) between the eight domain scores of the ML-SIS and the SIS 3.0 indicate sufficient concurrent validity. Similar interdomain correlations between the two measures indicate satisfactory convergent validity. CONCLUSIONS AND RELEVANCE: The ML-SIS uses about half of the items in the SIS 3.0, has an estimated administration time of 10 min, and provides valid scores comparable to those of the original measure. Thus, the ML-SIS may be an efficient alternative to the SIS 3.0. What This Article Adds: The ML-SIS, a short form of the SIS 3.0 developed using a machine learning algorithm, shows good potential to be an efficient and informative measure for clinical settings, providing scores that are valid and comparable to those of the original measure.

Eye-gaze control of a wheelchair mounted 6DOF assistive robot for activities of daily living.

BACKGROUND: Building control architecture that balances the assistive manipulation systems with the benefits of direct human control is a crucial challenge of human-robot collaboration. It promises to help people with disabilities more efficiently control wheelchair and wheelchair-mounted robot arms to accomplish activities of daily living. METHODS: In this study, our research objective is to design an eye-tracking assistive robot control system capable of providing targeted engagement and motivating individuals with a disability to use the developed method for self-assistance activities of daily living. The graphical user interface is designed and integrated with the developed control architecture to achieve the goal. RESULTS: We evaluated the system by conducting a user study. Ten healthy participants performed five trials of three manipulation tasks using the graphical user interface and the developed control framework. The 100% success rate on task performance demonstrates the effectiveness of our system for individuals with motor impairments to control wheelchair and wheelchair-mounted assistive robotic manipulators. CONCLUSIONS: We demonstrated the usability of using this eye-gaze system to control a robotic arm mounted on a wheelchair in activities of daily living for people with disabilities. We found high levels of acceptance with higher ratings in the evaluation of the system with healthy participants.

Psychometric evaluation of the disabilities of the arm, shoulder and hand (DASH) in patients with orthopedic shoulder impairments seeking outpatient rehabilitation.

STUDY DESIGN: This is a cross-sectional, observational study. INTRODUCTION: The disability of the arm, shoulder and hand (DASH) questionnaire is an upper-extremity specific outcome measure commonly used in routine clinical care and clinical trials. PURPOSE OF THE STUDY: Our purposes were to: (1) examine the psychometric properties of the DASH questionnaire using factor analysis, one- and two-parameter item response theory models, and (2) develop a functional staging map illustrating the relationships between the item difficulty hierarchy of the DASH items and the patient's DASH total score. METHODS: Data from 2724 patients with orthopedic shoulder impairments seeking outpatient physical therapy in 79 clinics in the US were analyzed. RESULTS: Factor analysis supported a general factor, explaining 62.2% of the total variance. The coverage of DASH items was suitable for patients with shoulder impairments with no ceiling or floor effect. Endorsed items representing the most difficult items were related to feeling less capable, executing recreational activities with force or impact, and performing recreational activities in which you move your arm freely. Items with higher discriminating abilities were those related to do heavy household chores, garden/yard work, and change a light bulb overhead. With a separation index equaled to 4.94, the DASH can differentiate persons into at least 6 statistically distinct person strata. None of the DASH items exhibited differential item functioning by gender or symptom acuity, except two items by age group. DISCUSSION: Besides a total (summed) final score obtained from a specific measure, the keyform and functional staging plots/maps can be used to assist clinicians in clinical interpretation of the scores. CONCLUSIONS: Results supported the clinical usage of the DASH questionnaire in patients with orthopedic shoulder impairments seeking outpatient rehabilitation.

Measurement of finger tapping performance using a smartphone application: a pilot study.

[Purpose] Describe the measurement, reliability and validity of finger tapping repetitions recorded using a commercially available smartphone application (app). [Participants and Methods] We tested a convenience sample of 12 young right-handed participants who completed unilateral index finger tapping and peg board completion tasks with each hand. [Results] Measurement of finger tapping performance was practicable and was shown to be acceptably reliable and able to distinguish between performance of the dominant versus nondominant hand. Finger tapping was not correlated with pegboard performance. [Conclusion] A small sample of young adults showed that measures of finger tapping were easily obtained using a smartphone app. The measures demonstrated acceptable reliability and known groups validity. They, however, may not reflect performance at other measures of voluntary movement functions.

Design and development of a sensored glove for home-based rehabilitation.

STUDY DESIGN: Descriptive. INTRODUCTION: Rehabilitation programs that focus on motor recovery of the upper limb require long-term commitment from the clinicians/therapists, require one-to-one caring, and are usually labor-intensive. PURPOSE OF THE STUDY: To contribute to this area, we have developed a sensored hand glove integrated with a computer game (Flappy Bird) to engage patients playing a game where the subject's single/multiple fingers are involved, representing fine motor skill occupational therapeutic exercises. METHODS: We described the sensored rehab glove, its hardware design, electrical and electronic design and instrumentation, software design, and pilot testing results. RESULTS: Experimental results supported that the developed rehab glove system can be effectively used to engage a patient playing a computer game (or a mobile phone game) that can record the data (ie, game score, finger flexion/extension angle, time spent in a therapeutic session, etc.) and put it in a format that could be easily read by a therapist or displayed to the therapists/patients in different graph formats. CONCLUSIONS: We introduced a sensored rehab glove for home-based therapy. The exercise training using the glove is repetitious, functional, and easy to follow and comply with.

Reliability and concurrent validity of the Active Movement Scale (AMS) in adults with musculoskeletal disorders.

BACKGROUND: The Active Movement Scale (AMS) is a brief screen for identifying movement impairments affecting functional task performance. OBJECTIVE: To assess inter-rater reliability, test-retest reliability, floor and ceiling effects, and concurrent validity of the AMS in adults with musculoskeletal disorders. METHODS: Fifty-five subjects (mean age: 61.3±15.3 years) transitioning from physical therapy attended two sessions. The 14-item AMS was assessed by two therapists, resulting in a total score (AMST) and two sub-scores: upper body (AMSU) and lower body (AMSL). Moreover, subjects completed PROMIS Physical Function-10a (PPF), Lifestyle Physical Function (LPF), Cardio Activity Level (CAL) surveys, Two Square Agility Test (TSAT), WorkAbility Rate of Manipulation Turning (WRMT) and Placing (WRMP), Grip Strength (GS), 10-Meter Walk Usual (GSU) and Fast (GSF) pace, and Grooved Pegboard Placing (GPP) and Remove (GPR) tests. RESULTS: Inter-rater reliability coefficients for AMST, AMSU, and AMSL were 0.96, 0.92, and 0.96, respectively, with individual item reliability ranging from 0.58 to 1.0. Test-retest reliability for these assessments yielded coefficients of 0.93, 0.84, and 0.94, with individual item reliability ranging from 0.47 to 0.88. No floor effects were observed, but mild ceiling effects were noted. AMST showed a high correlation with LPF (r = 0.72) and moderate correlation with PPF (r = 0.64) surveys. AMSU had moderate correlations with GPP (r = 0.61) and WRMP (r = 0.57) tests, while AMSL correlated moderately with GSF (r = 0.55) and TSAT (r = 0.50) tests. CONCLUSIONS: This study provides evidence of the reliability and validity of AMS in adults with musculoskeletal disorders to support transitions between rehabilitation and fitness programs.

Motor Imagery Performance through Embodied Digital Twins in a Virtual Reality-Enabled Brain-Computer Interface Environment.

This study introduces an innovative framework for neurological rehabilitation by integrating brain-computer interfaces (BCI) and virtual reality (VR) technologies with the customization of three-dimensional (3D) avatars. Traditional approaches to rehabilitation often fail to fully engage patients, primarily due to their inability to provide a deeply immersive and interactive experience. This research endeavors to fill this gap by utilizing motor imagery (MI) techniques, where participants visualize physical movements without actual execution. This method capitalizes on the brain's neural mechanisms, activating areas involved in movement execution when imagining movements, thereby facilitating the recovery process. The integration of VR's immersive capabilities with the precision of electroencephalography (EEG) to capture and interpret brain activity associated with imagined movements forms the core of this system. Digital Twins in the form of personalized 3D avatars are employed to significantly enhance the sense of immersion within the virtual environment. This heightened sense of embodiment is crucial for effective rehabilitation, aiming to bolster the connection between the patient and their virtual counterpart. By doing so, the system not only aims to improve motor imagery performance but also seeks to provide a more engaging and efficacious rehabilitation experience. Through the real-time application of BCI, the system allows for the direct translation of imagined movements into virtual actions performed by the 3D avatar, offering immediate feedback to the user. This feedback loop is essential for reinforcing the neural pathways involved in motor control and recovery. The ultimate goal of the developed system is to significantly enhance the effectiveness of motor imagery exercises by making them more interactive and responsive to the user's cognitive processes, thereby paving a new path in the field of neurological rehabilitation.

Developing a tablet-based brain-computer interface and robotic prototype for upper limb rehabilitation.

Background: The current study explores the integration of a motor imagery (MI)-based BCI system with robotic rehabilitation designed for upper limb function recovery in stroke patients. Methods: We developed a tablet deployable BCI control of the virtual iTbot for ease of use. Twelve right-handed healthy adults participated in this study, which involved a novel BCI training approach incorporating tactile vibration stimulation during MI tasks. The experiment utilized EEG signals captured via a gel-free cap, processed through various stages including signal verification, training, and testing. The training involved MI tasks with concurrent vibrotactile stimulation, utilizing common spatial pattern (CSP) training and linear discriminant analysis (LDA) for signal classification. The testing stage introduced a real-time feedback system and a virtual game environment where participants controlled a virtual iTbot robot. Results: Results showed varying accuracies in motor intention detection across participants, with an average true positive rate of 63.33% in classifying MI signals. Discussion: The study highlights the potential of MI-based BCI in robotic rehabilitation, particularly in terms of engagement and personalization. The findings underscore the feasibility of BCI technology in rehabilitation and its potential use for stroke survivors with upper limb dysfunctions.

Developing an Accumulative Assessment System of Upper Extremity Motor Function in Patients With Stroke Using Deep Learning.

OBJECTIVE: The Fugl-Meyer assessment for upper extremity (FMA-UE) is a measure for assessing upper extremity motor function in patients with stroke. However, the considerable administration time of the assessment decreases its feasibility. This study aimed to develop an accumulative assessment system of upper extremity motor function (AAS-UE) based on the FMA-UE to improve administrative efficiency while retaining sufficient psychometric properties. METHODS: The study used secondary data from 3 previous studies having FMA-UE datasets, including 2 follow-up studies for subacute stroke individuals and 1 test-retest study for individuals with chronic stroke. The AAS-UE adopted deep learning algorithms to use patients' prior information (ie, the FMA-UE scores in previous assessments, time interval of adjacent assessments, and chronicity of stroke) to select a short and personalized item set for the following assessment items and reproduce their FMA-UE scores. RESULTS: Our data included a total of 682 patients after stroke. The AAS-UE administered 10 different items for each patient. The AAS-UE demonstrated good concurrent validity (r = 0.97-0.99 with the FMA-UE), high test-retest reliability (intra-class correlation coefficient = 0.96), low random measurement error (percentage of minimal detectable change = 15.6%), good group-level responsiveness (standardized response mean = 0.65-1.07), and good individual-level responsiveness (30.5%-53.2% of patients showed significant improvement). These psychometric properties were comparable to those of the FMA-UE. CONCLUSION: The AAS-UE uses an innovative assessment method, which makes good use of patients' prior information to achieve administrative efficiency with good psychometric properties. IMPACT: This study demonstrates a new assessment method to improve administrative efficiency while retaining psychometric properties, especially individual-level responsiveness and random measurement error, by making good use of patients' basic information and medical records.

The minimal important difference for the Postural Assessment Scale for Stroke Patients in the subacute stage.

BACKGROUND: The minimal important difference (MID) of the Postural Assessment Scale for Stroke Patients (PASS) remains unknown, limiting the interpretation of change scores. OBJECTIVES: To estimate the MID of the PASS in patients with subacute stroke. METHODS: Data at admission and discharge for 240 participants were retrieved from a longitudinal study. The "mobility" item of the Barthel Index was used as the anchor for indicating the improvement of posture control. Receiver operating characteristic (ROC) method was used to estimate the anchor-based MID of the PASS. RESULTS: The ROC method identified a MID of 3.0 points, with a sensitivity of 81.0 % and a specificity of 75.6 %. CONCLUSION: The MID of the PASS was 3.0 points, indicating that if a patient achieves an improvement of 3.0 or more points on the PASS, they have a clinically important improvement in posture control. Our results can help in interpreting change scores and aid in understanding the clinical values of treatment outcomes.

Lemon Peel Water Extract: A Novel Material for Retinal Health, Protecting Retinal Pigment Epithelial Cells against Dynamin-Related Protein 1-Mediated Mitochondrial Fission by Blocking ROS-Stimulated Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Pathway.

Previous studies showed that NaIO3 can induce oxidative stress-mediated retinal pigment epithelium (RPE) damage to simulate age-related macular degeneration (AMD). Lemon peel is rich in antioxidants and components that can penetrate the blood-retinal barrier, but their role in retinal oxidative damage remains unexplored. Here, we explore the protection of lemon peel ultrasonic-assisted water extract (LUWE), containing large amounts of flavonoids and polyphenols, against NaIO3-induced retinal degeneration. We initially demonstrated that LUWE, orally administered, prevented retinal distortion and thinning on the inner and outer nuclei layers, downregulating cleaved caspase-3 protein expression in RPE cells in NaIO3-induced mice. The effect of LUWE was achieved through the suppression of apoptosis and the associated proteins, such as cleaved PARP and cleaved caspase-3, as suggested by NaIO3-induced ARPE-19 cell models. This is because LUWE reduced reactive oxygen species-mediated mitochondrial fission via regulating p-Drp-1 and Fis1 expression. We further confirmed that LUWE suppresses the expression of p-MEK-1/2 and p-ERK-1/2 in NaIO3-induced ARPE-19 cells, thereby providing the protection described above, which was confirmed using PD98059 and U0126. These results indicated that LUWE prevents mitochondrial oxidative stress-mediated RPE damage via the MEK/ERK pathway. Elucidation of the molecular mechanism may provide a new protective strategy against retinal degeneration.

Assessing the Practical Differences in LDL-C Estimates Calculated by Friedewald, Martin/Hopkins, or NIH Equation 2: An Observation Cross-Sectional Study.

Objective: Low-density lipoprotein-cholesterol (LDL-C) remains a clinically important cholesterol target in primary prevention of atherosclerotic cardiovascular disease. The present study aimed to assess the practical differences among three equations utilized for the estimation of LDL-C: the Friedewald, the Martin/Hopkins, and the NIH equation 2. Methods: Blood lipid measurements from 4,556 noninstitutionalized participants, aged 12 to 80, were obtained from the 2017-2020 National Health and Nutrition Examination Survey study. We 1) assessed the differences between three calculated LDL-C estimates, 2) examined the correlations between LDL-C estimates using correlation coefficients and regression, and 3) investigated the degree of agreement in classifying individuals into the LDL-C category using weighted Kappa and percentage of agreement. Results: The differences in LDL-C estimates between equations varied by sex and triglyceride levels (p<0.001). Overall, the mean of absolute differences between Friedewald and Martin/Hopkins was 3.17 mg/dL (median=2.0, 95% confidence interval [CI] [3.07-3.27]). The mean of absolute differences between Friedewald and NIH Equation 2 was 2.08 mg/dL (median=2.0, 95% CI [2.03-2.14]). Friedewald correlated highly with Martin/Hopkins (r=0.991, rho=0.989) and NIH Equation 2 (r=0.998, rho=0.997). Cohen's weighted Kappa=0.92 between Friedewald and Martin/Hopkins, and 0.95 between Friedewald and NIH equation 2. The percentage of agreement in classifying individuals into the same LDL-C category was 93.0% between Friedewald and Martin/Hopkins, and 95.4% between Friedewald and NIH equation 2. Conclusion: Understanding the practical differences in LDL-C calculations can be helpful in facilitating decision-making during a paradigm shift.

More Problems, More Pain: The Role of Chronic Life Stressors and Racial/Ethnic Identity on Chronic Pain Among Middle-Aged and Older Adults in the United States.

There is a high prevalence of chronic pain among middle-aged and older adults in the United States. Chronic life stressors have been shown to have detrimental consequences for myriad health conditions, including chronic pain. However, there is limited evidence on the types of chronic life stressors that affect middle-aged and older adults and how these stressors influence the chronic pain burden in this population. Moreover, the interaction between chronic life stressors and racial/ethnic identity remains poorly understood as it relates to chronic pain. The current analysis used the 2018 Health and Retirement Study to investigate relationships between chronic life stressors and odds to experience any chronic pain and high-impact chronic pain. Chronic life stressors were characterized, overall and by racial/ethnic identity, and the main and interaction effects were calculated to evaluate relationships between chronic life stressors, racial/ethnic identity, and odds of experiencing any chronic pain and high-impact chronic pain. Results indicate that in 2018, the most common chronic life stressor among middle-aged and older adults was dealing with their own health problems (68%), followed by dealing with the physical or emotional issues affecting a spouse or child (46%). Adjusted analyses showed that a higher total of chronic life stressors increased the odds of middle-aged and older adults experiencing any chronic pain and high-impact chronic pain. There were no significant interactions between the overall chronic life stress burden and racial/ethnic identity as a predictor of odds to experience any chronic pain or high-impact chronic pain, but significant interaction effects were found related to specific chronic life stressors. Findings underscore the significant impact of chronic life stressors on the chronic pain burden among middle-aged and older adults in the United States, which cut across racial/ethnic identity.