Effectiveness of using a meditation app in reducing anxiety and improving well-being during the COVID-19 pandemic: A structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: This interventional study will investigate the effect of daily use of a mindfulness app on measures of participant anxiety, well-being, and perceived outlook during the COVID-19 pandemic, by comparing pre-intervention survey responses to post-intervention survey responses. TRIAL DESIGN: Randomized, controlled trial with parallel assignment. Adults will be assigned either to daily use of a meditation app for 30 days or to a control group (no usage of meditation app) with a 1:1 equivalence allocation ratio. PARTICIPANTS: Inclusion Criteria: Participants must be 18 or older, have a smartphone, able to download apps to their smartphone, must be fluent in the English language, able to complete surveys on their own, and must be in the United States for the duration of the study. EXCLUSION CRITERIA: Current regular use of a mindfulness or meditation app, regular practice of mindfulness or meditation, regular therapy sessions, inability to complete surveys independently, or any mental health restrictions that would prevent participation. All data will be collected through the Insight Timer Meditation App and Google Forms. This trial is being conducted through the Lake Erie College of Osteopathic Medicine in Erie, PA, with all data collected digitally. INTERVENTION AND COMPARATOR: Intervention: Participants will be sent a link to a pre-intervention survey prior to first use of the mindfulness app. Participants will be instructed to use the Insight Timer app for 10 minutes daily for 30 days. At the end of the 30-day intervention period, participants will be sent a link for the post-intervention survey. Two months after the conclusion of the 30-day intervention period, participants will be sent a link for another post-intervention survey. Comparator: Participants will receive the same surveys, but will not use any mindfulness app for the 30-day intervention period. After this 30-day period, participants are invited to use the Insight Timer app if they so choose. MAIN OUTCOMES: The main outcomes are (1) anxiety as assessed by survey questions adapted from the GAD7, comparing pre-intervention to post-30-days of app usage and (2) well-being as assessed by survey questions adapted from the WHO-5, comparing pre-intervention and post-30-days of app usage. RANDOMIZATION: Participants will be allocated to interventions via a block random sequence generator with a 1:1 allocation ratio in blocks of 8. BLINDING (MASKING): No masking is being used in this study (open label). NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): Approximately 75 participants will be randomized to each group, with an estimated enrollment of 150 participants. TRIAL STATUS: This study is protocol version number 27-126 and was approved on May 10, 2020. Recruitment began on August 19, 2020 and will end February 28, 2021. The study is estimated to complete on April 30, 2021. TRIAL REGISTRATION: This trial was registered to ClinicalTrials.gov on 30 April 2020. The ClinicalTrials.gov Identifier is NCT04369378 . FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional File 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Increased Skeletal Muscle Fiber Cross-Sectional Area, Muscle Phenotype Shift, and Altered Insulin Signaling in Rat Hindlimb Muscles in a Prenatally Androgenized Rat Model for Polycystic Ovary Syndrome.

Women with polycystic ovary syndrome (PCOS) are reported to have greater lean mass and insulin resistance. To examine muscular changes in a prenatally androgenized (PNA) rat model for PCOS, Sprague-Dawley rats were exposed to 5 mg testosterone or vehicle daily on gestational days 16-19. At 15 weeks of age, endurance on a rota-rod treadmill was measured. At 16 weeks of age, fasting blood glucose and insulin, hindlimb skeletal muscle mass, muscle fiber cross-sectional area (CSA) and composition, and intra- and peri-muscular lipid droplets were examined. Expression of mitochondrial marker ATP synthase and insulin signaling proteins were also investigated. Compared with controls, PNA female rats demonstrated greater total body and hindlimb muscle weights, greater muscle fiber CSA, and trending reduced time on the rota-rod. An increase in fibers co-expressing the slow and fast isoforms of myosin (90 vs. 86%, p < 0.05) and greater expression of ATP synthase (6-fold, p < 0.005) were observed in the gastrocnemius (GN) muscle. More lipid content was observed in GN and tibialis anterior (TA) muscles. PNA rats had elevated fasting serum insulin (1.9 vs. 1.2 ng/mL, p < 0.005) but comparable fasting glucose. Expression of total and Ser636/9-phosphorylated IRS1 were altered in PNA rat hindlimb muscles. Together, skeletal muscle alterations in hindlimb muscles of a PNA rat model for PCOS may represent consequences of, or adaptations to, insulin resistance in this model.

Regular Mindful Yoga Practice as a Method to Improve Androgen Levels in Women With Polycystic Ovary Syndrome: A Randomized, Controlled Trial.

BACKGROUND: Holistic approaches are needed to complement existing therapies for polycystic ovary syndrome (PCOS), a common disorder affecting the health of reproductive-aged females. OBJECTIVE: To determine whether thrice-weekly mindful yoga practice improves endocrine, cardiometabolic, or psychological parameters in women with PCOS. METHODS: Thirty-one women with PCOS between the ages of 23 and 42 years and living in Erie County, Pennsylvania, were recruited for this randomized, controlled study arm, which was part of a larger 3-part investigation. Women were randomly assigned to either a mindful yoga intervention group or no intervention (control) group. Group classes were 1 hour, thrice weekly. Initial endocrine, cardiometabolic, and psychological measurements were compared with measurements taken after the 3-month intervention period. Measurements included free testosterone, dehydroepiandrosterone, androstenedione, body mass index, waist-to-hip ratio, fasting blood glucose and insulin levels, and anxiety and depression scores. RESULTS: Twenty-two women completed the 3-month intervention period, 13 in the mindful yoga group and 9 in the control group. Paired comparisons of pre- and postintervention parameters indicated that women who completed the mindful yoga intervention had significantly lower free testosterone levels (5.96 vs 4.24 pg/mL; P<.05) and dehydroepiandrosterone levels that trended lower. Improved testosterone may persist for several months after completion of a 3-month, thrice-weekly mindful yoga intervention. Additionally, improvements were seen in measures of anxiety and depression. CONCLUSION: The improvements observed suggest that regular mindful yoga practice can be a useful complementary therapeutic option for women with PCOS, particularly for improving serum androgen levels, a hallmark feature of PCOS. This improvement occurred in the absence of weight loss and may persist even if there is a lapse in practice. (ClinicalTrials.gov No. NCT03383484).

Weekly Osteopathic Manipulative Treatment to Improve Measures of Sympathetic Tone in Women With Polycystic Ovary Syndrome: A Randomized, Controlled Pilot Study.

BACKGROUND: Polycystic ovary syndrome (PCOS), a common hormone disorder affecting reproductive and metabolic health of reproductive-age women, was shown in a previous study from these authors to be associated with increased sympathetic tone. Increased sympathetic tone contributes to long-term health risks for cardiovascular disease and promotes PCOS pathogenesis. OBJECTIVE: To determine whether weekly osteopathic manipulative treatment (OMT) improves physiologic measures of sympathetic tone in women with PCOS. METHODS: In the second phase of a larger study from this author group, 25 women with PCOS, aged 22 to 43 years, living in Erie, Pennsylvania, were recruited to participate in a randomized, controlled evaluation of OMT intervention. Participants were randomly assigned to either an OMT intervention or control group. The OMT group received weekly manipulation of Chapman points and rib-raising for viscerosomatic reflexes associated with the ovaries, adrenal glands, and heart for 12 consecutive weeks. Physiologic measures of sympathetic tone were collected, along with metabolic, endocrine, and reproductive measurements, both before the 3-month intervention and within 1 week of completing the intervention. Measurements included heart rate and blood pressure at rest and after 15 minutes of aerobic exercise, heart rate recovery after exercise, resting heart rate variability, serum androgen levels, body mass index, fasting blood glucose and insulin levels, and menstrual cycle length. RESULTS: Nineteen women completed the study. Comparing pre- and postintervention parameters, women with PCOS in the OMT intervention group experienced an improvement in postexercise systolic blood pressure (135.8 vs 129.1 mm Hg) and a trend toward heart rate recovery (23.2 vs 29.4 seconds). No significant improvements were found in the control group or in any other physiologic parameters measured. No significant improvements were found in the endocrine, metabolic, or reproductive parameters measured, although free testosterone was slightly lower after 3 months of weekly OMT (5.69 vs 4.64 pg/mL). CONCLUSION: Improvements in sympathetic tone after OMT suggest that weekly manipulation of Chapman points and viscerosomatic reflexes can be a useful adjunctive therapeutic option for women with PCOS. (ClinicalTrials.gov No. NCT03383484).

Nonpharmacologic Management of Symptoms in Females With Polycystic Ovary Syndrome: A Narrative Review.

Polycystic ovary syndrome is the most common hormone disorder in females of reproductive age, affecting reproductive, metabolic, and cardiovascular health. With an unknown cause and a spectrum of common signs and symptoms, diagnosis is based on consensus criteria, and treatment options often target individual symptoms, with variable effectiveness. Safe, effective complementary and alternative therapies can be used to manage symptoms. The first-line intervention is lifestyle modification, including weight loss when appropriate, with caloric restriction and exercise to maintain a healthy weight. Low-carbohydrate and/or low-glycemic index diets can provide additional benefits, and nutritional supplements may be useful adjuncts. The recommended physical activity regimen should include both aerobic and resistance exercise.

Correlation Between Physiologic and Osteopathic Measures of Sympathetic Activity in Women With Polycystic Ovary Syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common hormone disorder that affects the reproductive, metabolic, and psychological health of reproductive-aged females, with a number of long-term health risks, including type 2 diabetes mellitus and cardiovascular sequelae. Sympathetic hyperactivity in affected persons may be involved in the pathogenesis of the disorder. OBJECTIVE: To determine whether physiologic and osteopathic measures of increased sympathetic tone correlate in a population of women with PCOS. METHODS: For this descriptive observational study, women with PCOS between the ages of 20 and 44 years were recruited. Physiologic measures of sympathetic tone (resting heart rate and blood pressure, resting heart rate variability, and postexercise heart rate recovery and blood pressure) were compared with osteopathic measures of sympathetic tone (Chapman points and viscerosomatic reflexes) for the heart, adrenal glands, and ovaries. RESULTS: Twenty-four women participated in the study. Overall, the participants exhibited both physiologic and osteopathic signs of increased sympathetic tone compared with reference values. In some participants, the number of osteopathic findings were greater than the number of physiologic findings of increased sympathetic tone. CONCLUSIONS: Women with PCOS exhibit increased sympathetic tone by physiologic and osteopathic measures, indicating the utility of assessing sympathetic hyperactivity in these patients by osteopathic methods. Osteopathic structural examination is a valuable diagnostic tool that may allow detection of sympathetic hyperactivity in women with PCOS even before physiologic symptoms manifest. The osteopathic indicators of increased sympathetic tone may represent potential therapeutic targets to improve health in this population. (ClinicalTrials.gov NCT03383484).

Elevated androstenedione in young adult but not early adolescent prenatally androgenized female rats.

BACKGROUND: Elevated testosterone (T) is routinely reported as a marker of hyperandrogenemia in rodent models for polycystic ovary syndrome (PCOS). In women with PCOS, elevated serum androstenedione (A4) is associated with more severe phenotypes, including a positive correlation with serum T, DHEAS, free androgen index (FAI), LH, and LH/FSH ratio. Furthermore, A4, along with calculated free T and FAI, was identified as one of the best predictors of PCOS in adult women of all ages (18 to > 50 y). OBJECTIVE: The objective of this study was to investigate serum A4 levels in early adolescent and young adult prenatally androgenized (PNA) female rats, a model for PCOS. METHODS: Pregnant rats were injected with 5 mg T daily during gestational days 16-19 (PNA rats, experimental group) or an equal volume of vehicle (control group). Female offspring of both groups had tail vein blood drawn for serum analysis at 8 and 16 weeks of age. ELISAs were used to quantify serum A4 and T levels. RESULTS: Serum A4 and T were elevated in 16-week-old PNA rats compared to controls. There was no significant difference in either hormone at 8 weeks of age. CONCLUSIONS: The PNA rats demonstrated elevated serum A4 and T in young adulthood, as has been observed in women with PCOS, further validating this as a model for PCOS and underscoring the importance of serum A4 elevation as a parameter inherent to PCOS and a rodent model for the disorder. Significant A4 elevation develops between early adolescence and early adulthood in this PNA rat model.

Physiological and histological changes in skeletal muscle following in vivo gene transfer by electroporation.

Electroporation (EP) is used to transfect skeletal muscle fibers in vivo, but its effects on the structure and function of skeletal muscle tissue have not yet been documented in detail. We studied the changes in contractile function and histology after EP and the influence of the individual steps involved to determine the mechanism of recovery, the extent of myofiber damage, and the efficiency of expression of a green fluorescent protein (GFP) transgene in the tibialis anterior (TA) muscle of adult male C57Bl/6J mice. Immediately after EP, contractile torque decreased by ∼80% from pre-EP levels. Within 3 h, torque recovered to ∼50% but stayed low until day 3. Functional recovery progressed slowly and was complete at day 28. In muscles that were depleted of satellite cells by X-irradiation, torque remained low after day 3, suggesting that myogenesis is necessary for complete recovery. In unirradiated muscle, myogenic activity after EP was confirmed by an increase in fibers with central nuclei or developmental myosin. Damage after EP was confirmed by the presence of necrotic myofibers infiltrated by CD68+ macrophages, which persisted in electroporated muscle for 42 days. Expression of GFP was detected at day 3 after EP and peaked on day 7, with ∼25% of fibers transfected. The number of fibers expressing green fluorescent protein (GFP), the distribution of GFP+ fibers, and the intensity of fluorescence in GFP+ fibers were highly variable. After intramuscular injection alone, or application of the electroporating current without injection, torque decreased by ∼20% and ∼70%, respectively, but secondary damage at D3 and later was minimal. We conclude that EP of murine TA muscles produces variable and modest levels of transgene expression, causes myofiber damage due to the interaction of intramuscular injection with the permeabilizing current, and that full recovery requires myogenesis.

The rho-guanine nucleotide exchange factor domain of obscurin activates rhoA signaling in skeletal muscle.

Obscurin is a large ( approximately 800-kDa), modular protein of striated muscle that concentrates around the M-bands and Z-disks of each sarcomere, where it is well positioned to sense contractile activity. Obscurin contains several signaling domains, including a rho-guanine nucleotide exchange factor (rhoGEF) domain and tandem pleckstrin homology domain, consistent with a role in rho signaling in muscle. We investigated the ability of obscurin's rhoGEF domain to interact with and activate small GTPases. Using a combination of in vitro and in vivo approaches, we found that the rhoGEF domain of obscurin binds selectively to rhoA, and that rhoA colocalizes with obscurin at the M-band in skeletal muscle. Other small GTPases, including rac1 and cdc42, neither associate with the rhoGEF domain of obscurin nor concentrate at the level of the M-bands. Furthermore, overexpression of the rhoGEF domain of obscurin in adult skeletal muscle selectively increases rhoA expression and activity in this tissue. Overexpression of obscurin's rhoGEF domain and its effects on rhoA alter the expression of rho kinase and citron kinase, both of which can be activated by rhoA in other tissues. Injuries to rodent hindlimb muscles caused by large-strain lengthening contractions increases rhoA activity and displaces it from the M-bands to Z-disks, similar to the effects of overexpression of obscurin's rhoGEF domain. Our results suggest that obscurin's rhoGEF domain signals at least in part by inducing rhoA expression and activation, and altering the expression of downstream kinases in vitro and in vivo.