Patients with single large-scale mitochondrial DNA (mtDNA) deletion syndromes (SLSMDs) usually present with multisystemic disease, either as Pearson syndrome in early childhood or as Kearns-Sayre syndrome later in life. No disease-modifying therapies exist for SLSMDs. We have developed a method to enrich hematopoietic cells with exogenous mitochondria, and we treated six patients with SLSMDs through a compassionate use program. Autologous CD34 ⁺ hematopoietic cells were augmented with maternally derived healthy mitochondria, a technology termed mitochondrial augmentation therapy (MAT). All patients had substantial multisystemic disease involvement at baseline, including neurologic, endocrine, or renal impairment. We first assessed safety, finding that the procedure was well tolerated and that all study-related severe adverse events were either leukapheresis-related or related to the baseline disorder. After MAT, heteroplasmy decreased in the peripheral blood in four of the six patients. An increase in mtDNA content of peripheral blood cells was measured in all six patients 6 to 12 months after MAT as compared baseline. We noted some clinical improvement in aerobic function, measured in patients 2 and 3 by sit-to-stand or 6-min walk testing, and an increase in the body weight of five of the six patients suffering from very low body weight before treatment. Quality-of-life measurements as per caregiver assessment and physical examination showed improvement in some parameters. Together, this work lays the ground for clinical trials of MAT for the treatment of patients with mtDNA disorders.

Background: This study aimed to examine the association between frailty and depressive symptoms. Methods: Cross-sectional and five-year longitudinal study. Data were from the population-based Survey of Health, Aging, and Retirement in Europe (SHARE) waves six (2015) and eight (2020). Frailty was assessed using the SHARE-Frailty Instrument. Fatigue, appetite, walking difficulties, and physical activity were self-reported, and grip strength was measured using a handgrip dynamometer. The EURO-D 12-item scale was used to measure depressive symptoms. Results: The sample comprised 25,771 older adults (56.2% female) with a mean age of 66.5 (95% CI 66.4, 66.6) years. The prevalence of frailty was 4.2% (95% CI 3.9, 4.4) in 2015 and 6.7% (95% CI 13.5, 14.3) in 2020. Among frail participants, 72.5% and 69.6% had depression in 2015 and 2020, respectively. Frailty was associated with depression over the 5 years. Those with pre-frailty and those with frailty in 2015 had 1.86 (95% CI 1.71, 2.01) and 2.46 (95% CI 2.14, 2.83) greater odds of having depressive symptoms in 2020. Conclusions: Frailty is a predictor of depression in older adults, and frail participants had greater odds of presenting depressive symptoms.

Telerehabilitation offers a unique solution for continuity of care in pediatric rehabilitation under physical distancing. The major aims of this study were to: (1) describe the development of telerehabilitation usage guidelines in a large hospital in Israel, and to (2) evaluate the implementation of telerehabilitation from the perspectives of healthcare practitioners and families. An expert focus group developed guidelines which were disseminated to multidisciplinary clinicians. Following sessions, clinicians filled The Clinician Evaluation of Telerehabilitation Service (CETS), a custom-built feedback questionnaire on telerehabilitation, and parents completed the client version of the Therapist Presence Inventory (TPI-C) and were asked to rate the effectiveness of sessions on an ordinal scale. Four goals of telerehabilitation sessions were defined: (1) maintenance of therapeutic alliance, (2) provision of parental coping strategies, (3) assistance in maintaining routine, and (4) preventing functional deterioration. Principal Components Analysis was used for the CETS questionnaire and the relationships of CETS and TPI-C with child’s age and the type of session were evaluated using Spearman’s correlations and the Kruskal–Wallis H test. In total, sixty-seven telerehabilitation sessions, with clients aged 11.31 ± 4.8 years, were documented by clinicians. Three components (child, session, parent) explained 71.3% of the variance in CETS. According to therapists, their ability to maintain the therapeutic alliance was generally higher than their ability to achieve other predefined goals (p < 0.01). With younger children, the ability to provide feedback to the child, grade treatment difficulty and provide coping strategies to the parents were diminished. Families perceived the therapist as being highly present in therapy regardless of treatment type. These results demonstrate a potential framework for the dissemination of telerehabilitation services in pediatric rehabilitation.

Background: The step activity monitor (SAM) quantifies steps taken in the home and community by patient populations. Although the SAM has been used to study individuals after stroke, adherence to the use of SAMs has not been addressed. Participants' adherence to wearing the monitor is critical for obtaining accurate assessments. Objective: The purpose of this study was to determine the rate of and predictors for inferred adherence to the use of the SAM after stroke. Design: A cross-sectional design was used. Methods: Community-dwelling individuals (n=408) 2 months after stroke with moderate-to-severe gait impairment (gait speed of ≤0.8 m/s) were studied. Step activity was assessed for 2 days with the SAM. Inferred adherence was established in 3 periods: 6:00 am to 12:00 pm, 12:01 pm to 6:00 pm, and 6:01 pm to 12:00 am. Adherence was defined as activity recorded in all 3 periods. The percentage of participant adherence for the first day, second day, both days, and either day was calculated. Demographic and clinical characteristics of adherers and nonadherers were compared. Independent adherence predictors were identified by means of stepwise logistic regression. Results: Inferred adherence rates for the first day, second day, both days, and either day were 68%, 61%, 53%, and 76%, respectively. Upper and lower extremity impairment, balance control, and endurance were significantly different between adherers and nonadherers. On the other hand, older age, greater balance self-efficacy, and better walking endurance were significant predictors of adherence. Limitations: Participants were individuals with subacute stroke. Therefore, the findings of this study may not be generalized to individuals during the acute and chronic phases of stroke recovery. Conclusions: Strategies to improve adherence are needed when collecting data for more than 1 day and in samples with younger individuals and those with low levels of balance self-efficacy and walking endurance.

We investigated the prevalence of risk behaviors among Israeli adolescents (tobacco smoking, alcohol consumption, drug use) during the COVID-19 pandemic. Associations between different risk behaviors were examined and so was whether specific characteristics could predict risk behaviors in adolescents. The study consisted of 1020 Israeli adolescents aged 15–18. Study subjects completed an online survey between the first and second lockdowns in Israel (April 2020 to September 2020). Participants reported the frequency at which they engaged in four different risky behaviors: general risky behavior, tobacco smoking, alcohol consumption (binge drinking), and cannabis use. The most prevalent risky behavior in the sample was binge drinking (33.8%). The four measured risky behaviors were significantly correlated. Among participants who had previously engaged in a risky behavior assessed, most did not change the behavior frequency during the pandemic. All independent variables (sociodemographic characteristics, family support, and emotional, health excluding friends’ support, physical activity volume, and coronavirus restrictions) were significantly different between participants engaging vs. not engaging in risky behaviors. Our findings suggest that family support is one of the most influential factors in preventing risky behavior during the pandemic, and they emphasize the importance of family-based interventions with children and adolescents from elementary to high school.