Alternative psychopharmacologic treatments for pediatric catatonia: a retrospective analysis.

Introduction: Pediatric catatonia is a highly co-morbid condition with treatment options often limited to electroconvulsive therapy (ECT) or lorazepam. However, lorazepam may not be readily available, and access to ECT is limited by restrictive legislation and stigma. This study aims to provide alternative treatment options for pediatric catatonia. Methods: The study involved a single-site retrospective analysis of a private university hospital in the southern United States. The study included patients under eighteen with catatonia who received psychopharmacologic treatment with an agent other than lorazepam. The patients were evaluated with the Bush-Francis Catatonia Rating Scale (BFCRS), Kanner Catatonia Severity Scale (KCS), and Kanner Catatonia Examination (KCE) at the time of initial evaluation and upon stabilization. A retrospective clinical global impressions-improvement (CGI-I) score was assigned by four authors. Results: 102 pediatric patients diagnosed with catatonia were identified, and 31 met criteria for the study. 20 (65%) were white, 6 (19%) were Black, 4 (13%) were Hispanic, and 1 (3%) were Indian. Most patients (N = 18; 58%) were insured by Medicaid. The mean age at the time of catatonia diagnosis was 13.5 years. All patients were stabilized on either clonazepam or diazepam, with 21 (68%) requiring treatment with an additional medication of either an anti-epileptic, N-methyl-D-aspartate (NMDA) receptor antagonist, and aripiprazole or clozapine. Statistically significant reductions in the BFCRS [t = 11.2, df = 30, std = 6.3, p < 0.001, 95% CI = (7.8, 15.1)], KCS [t = 4.6, df = 38, p < 0.001, 95% CI = (12.0, 31.0)], and KCE [t = 7.8, df = 30, std = 1.8, p < 0.001, 95% CI = (1.9, 3.2)] were observed. For CGI-I the results showed that the estimated probability of observing a score better than no change (>4) is 0.976 [t.s. = 43.2, p < 0.001, 95% CI = (0.931,0.992)], indicating the average subject is expected to experience some improvement. Discussion: In conclusion, all patients responded to these treatments with improvement in their catatonic symptoms. Alternative pharmacologic interventions for catatonia, including benzodiazepines other than lorazepam, valproic acid, NMDA receptor antagonists, and atypical antipsychotics were safe and effective in treating catatonia in this population.

High-Intensity Interval Training in Cardiac Rehabilitation.

Recently, high-intensity interval training (HIIT) has been recognized as a safe and effective alternative to moderate-intensity continuous training for older patients with cardiovascular disease (CVD) in cardiac rehabilitation settings in an effort to improve health outcomes. This brief review considers general principles and suggestions for prescription of HIIT for older patients with CVD, specific challenges pertaining to older adults, the physiologic mechanisms by which HIIT contributes to improvements in peak Vo2, and the effects of HIIT on cardiovascular health in older patients with coronary artery disease and heart failure.

Exercise ventilatory inefficiency in heart failure and chronic obstructive pulmonary disease.

BACKGROUND: Dyspnea on exertion is common to both heart failure (HF) and chronic obstructive pulmonary disease (COPD), and it is important to discriminate whether symptoms are caused by HF or COPD in clinical practice. The ventilatory equivalent for carbon dioxide (V̇E/V̇CO2) slope and V̇E intercept (a reflection of pulmonary dead space) are two candidate non-invasive indices that could be used for this purpose. Thus, we compared non-invasive indexes of ventilatory efficiency in patients with HF and preserved or reduced ejection fraction (HFpEF and HFrEF, respectively) or COPD. METHODS: Patients with HFpEF (n = 21), HFrEF (n = 20), and COPD (n = 22) patients performed cardiopulmonary exercise testing to volitional fatigue. V̇E and gas exchange were measured via breath-by-breath open circuit spirometry. All data from rest to peak exercise were used to calculate V̇E/V̇CO2 slope and V̇E intercept using linear regression. Receiver operating characteristic (ROC) curves were constructed to determine optimized cutoffs for V̇E/V̇CO2 slope and V̇E intercept to discriminate HFpEF and HFrEF from COPD. RESULTS: HFrEF patients had a greater V̇E/V̇CO2 slope than HFpEF and COPD patients (HFrEF: 40 ±â€¯9; HFpEF: 32 ±â€¯7; COPD: 32 ±â€¯7) (p < 0.01). COPD patients had a greater V̇E intercept than HFpEF and HFrEF patients (COPD: 3.32 ±â€¯1.66; HFpEF: 0.77 ±â€¯1.23; HFrEF: 1.28 ±â€¯1.19 L/min) (p < 0.01). A V̇E intercept of 2.64 L/min discriminated COPD from HF patients (AUC: 0.88, p < 0.01), while V̇E/V̇CO2 slope did not (p = 0.11). CONCLUSION: These findings demonstrate that V̇E intercept, not V̇E/V̇CO2 slope, may discriminate COPD from both HFpEF and HFrEF patients.

Effect of dietary nitrate supplementation on conduit artery blood flow, muscle oxygenation, and metabolic rate during handgrip exercise.

Dietary nitrate supplementation has positive effects on mitochondrial and muscle contractile efficiency during large muscle mass exercise in humans and on skeletal muscle blood flow (Q̇) in rats. However, concurrent measurement of these effects has not been performed in humans. Therefore, we assessed the influence of nitrate supplementation on Q̇ and muscle oxygenation characteristics during moderate- (40 %peak) and severe-intensity(85% peak) handgrip exercise in a randomized, double-blind, crossover design. Nine healthy men (age: 25 ± 2 yr) completed four constant-power exercise tests (2/intensity) randomly assigned to condition [nitrate-rich (nitrate) or nitrate-poor (placebo) beetroot supplementation] and intensity (40 or 85% peak). Resting mean arterial pressure was lower after nitrate compared with placebo (84 ± 4 vs. 89 ± 4 mmHg, P < 0.01). All subjects were able to sustain 10 min of exercise at 40% peak in both conditions. Nitrate had no effect on exercise tolerance during 85% peak (nitrate: 358 ± 29; placebo: 341 ± 34 s; P = 0.3). Brachial artery Q̇ was not different after nitrate at rest or any time during exercise. Deoxygenated [hemoglobin + myoglobin] was not different for 40% peak ( P > 0.05) but was elevated throughout 85% peak ( P < 0.05) after nitrate. The metabolic cost (V̇o2) was not different at the end of exercise; however, the V̇o2 primary amplitude at the onset of exercise was elevated after nitrate for the 85% peak work rate (96 ± 20 vs. 72 ± 12 ml/min, P < 0.05) and had a faster response. These findings suggest that an acute dose of nitrate reduces resting blood pressure and speeds V̇o2 kinetics in young adults but does not augment Q̇ or reduce steady-state V̇o2 during small muscle mass handgrip exercise. NEW & NOTEWORTHY We show that acute dietary nitrate supplementation via beetroot juice increases the amplitude and speed of local muscle V̇o2 on kinetics parameters during severe- but not moderate-intensity handgrip exercise. These changes were found in the absence of an increased blood flow response, suggesting that the increased V̇o2 was attained via improvements in fractional O2 extraction and/or spatial distribution of blood flow within the exercising muscle.

Carotenoid Lutein Selectively Inhibits Breast Cancer Cell Growth and Potentiates the Effect of Chemotherapeutic Agents through ROS-Mediated Mechanisms.

Increasing evidence suggests that dietary carotenoids may reduce the risk of breast cancer. However, anti-breast cancer effects of carotenoids have been controversial, albeit understudied. Here, we investigated the effects of specific carotenoids on a wide range of breast cancer cell lines, and found that among several carotenoids (including ß-carotene, lutein, and astaxanthin), lutein significantly inhibits breast cancer cell growth by inducing cell-cycle arrest and caspase-independent cell death, but it has little effect on the growth of primary mammary epithelial cells (PmECs). Moreover, lutein-mediated growth inhibition of breast cancer cells is quantitatively similar to that induced by chemotherapeutic taxanes, paclitaxel and docetaxel, and exposure to lutein plus taxanes additively inhibits breast cancer cell growth. Analysis of mechanisms showed that lutein treatment significantly increases the intracellular reactive oxygen species (ROS) production in triple-negative breast cancer (TNBC) cells, but not in normal PmECs. Lutein-induced growth inhibition is also attenuated by the radical oxygen scavenger N-acetyl cysteine, suggesting a role for ROS generation in the growth inhibitory effect of lutein on TNBC cells. Additionally, we found that the p53 signaling pathway is activated and HSP60 levels are increased by lutein treatment, which may contribute partly to the induction of growth inhibition in TNBC cells. Our findings show that lutein promotes growth inhibition of breast cancer cells through increased cell type-specific ROS generation and alternation of several signaling pathways. Dietary lutein supplementation may be a promising alternative and/or adjunct therapeutic candidate against breast cancer.

Dietary nitrate supplementation opposes the elevated diaphragm blood flow in chronic heart failure during submaximal exercise.

Chronic heart failure (CHF) results in a greater cost of breathing and necessitates an elevated diaphragm blood flow (BF). Dietary nitrate (NO3‾) supplementation lowers the cost of exercise. We hypothesized that dietary NO3‾ supplementation would attenuate the CHF-induced greater cost of breathing and thus the heightened diaphragm BF during exercise. CHF rats received either 5days of NO3‾-rich beetroot (BR) juice (CHF+BR, n=10) or a placebo (CHF, n=10). Respiratory muscle BFs (radiolabeled microspheres) were measured at rest and during submaximal exercise (20m/min, 5% grade). Infarcted left ventricular area and normalized lung weight were not significantly different between groups. During submaximal exercise, diaphragm BF was markedly lower for CHF+BR than CHF (CHF+BR: 195±28; CHF: 309±71mL/min/100g, p=0.04). The change in diaphragm BF from rest to exercise was less (p=0.047) for CHF+BR than CHF. These findings demonstrate that dietary NO3‾ supplementation reduces the elevated diaphragm BF during exercise in CHF rats thus providing additional support for this therapeutic intervention in CHF.

Acute supplementation of N-acetylcysteine does not affect muscle blood flow and oxygenation characteristics during handgrip exercise.

N-acetylcysteine (NAC; antioxidant and thiol donor) supplementation has improved exercise performance and delayed fatigue, but the underlying mechanisms are unknown. One possibility isNACsupplementation increases limb blood flow during severe-intensity exercise. The purpose was to determine ifNACsupplementation affected exercising arm blood flow and muscle oxygenation characteristics. We hypothesized thatNACwould lead to higher limb blood flow and lower muscle deoxygenation characteristics during severe-intensity exercise. Eight healthy nonendurance trained men (21.8 ± 1.2 years) were recruited and completed two constant power handgrip exercise tests at 80% peak power until exhaustion. Subjects orally consumed either placebo (PLA) orNAC(70 mg/kg) 60 min prior to handgrip exercise. Immediately prior to exercise, venous blood samples were collected for determination of plasma redox balance. Brachial artery blood flow (BABF) was measured via Doppler ultrasound and flexor digitorum superficialis oxygenation characteristics were measured via near-infrared spectroscopy. FollowingNACsupplementaiton, plasma cysteine (NAC: 47.2 ± 20.3 µmol/L vs.PLA: 9.6 ± 1.2 µmol/L;P = 0.001) and total cysteine (NAC: 156.2 ± 33.9 µmol/L vs.PLA: 132.2 ± 16.3 µmol/L;P = 0.048) increased. Time to exhaustion was not significantly different (P = 0.55) betweenNAC(473.0 ± 62.1 sec) andPLA(438.7 ± 58.1 sec). RestingBABFwas not different (P = 0.79) withNAC(99.3 ± 31.1 mL/min) andPLA(108.3 ± 46.0 mL/min).BABFwas not different (P = 0.42) during exercise or at end-exercise (NAC: 413 ± 109 mL/min;PLA: 445 ± 147 mL/min). Deoxy-[hemoglobin+myoglobin] and total-[hemoglobin+myoglobin] were not significantly different (P = 0.73 andP = 0.54, respectively) at rest or during exercise between conditions. We conclude that acuteNACsupplementation does not alter oxygen delivery during exercise in men.

Improved lung function following dietary antioxidant supplementation in exercise-induced asthmatics.

INTRODUCTION: Oxidative stress is a characteristic of exercise-induced asthma (EIA), however antioxidant supplementation may attenuate EIA. The purpose of this study was to determine if ascorbic (AsA) and α-tocopherol supplementation would improve airway function in subjects with EIA. METHODS: A single-blind randomized crossover design with eight clinically diagnosed EIA subjects (22.0 ± 0.7 year) and five healthy control subjects (28.2 ± 1.4 year) was used. Subjects consumed vitamins (V) (AsA 500 mg; α-tocopherol 300 IU) or placebo (PLA) daily for three weeks, followed by a three week washout period and then three weeks of the alternative treatment. Ten-minute treadmill tests (90% VO2peak) were performed with pulmonary function testing (forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and between 25 and 75% (FEF25-75%), and peak expiratory flow rates (PEFR)) measured pre-exercise and 1, 5, 15, and 30 min post-exercise. RESULTS: Supplementation led to significant improvements at minute 5 and minute 15 in FVC; FEV1; PERF; FEF25-75% and minute 30 in FEV1 and FEF25-75% post-exercise. CONCLUSION: AsA and α-tocopherol may aid the recovery of pulmonary function in subjects with EIA.

The effects of antioxidant vitamin supplementation on expiratory flow rates at rest and during exercise.

PURPOSE: Previous studies suggest that pulmonary function is associated with fruit and vegetable consumption and plasma concentrations of antioxidant vitamins. Also, expiratory flow limitation (EFL) has been reported to limit ventilation during exercise in healthy individuals. We hypothesized antioxidant vitamin supplementation (AVS) would increase resting expiratory flow rates in healthy subjects and reduce EFL during exercise. METHODS: Ten healthy, nonsmoking subjects (5 M/5 W), consuming <5 servings of fruit and vegetables per day, participated in a randomized, single-blinded crossover design study with subjects receiving a placebo (PLA) or AVS [vitamins C (500 mg), E (400 IU), beta-carotene (15,000 IU), zinc (7.5 mg), selenium (50 mg), copper (1 mg), and manganese (2.5 mg)] for 4 weeks. After a minimum 4-week washout period, subjects received the alternate supplementation. Pulmonary function tests and total antioxidant status (TAS) from plasma were measured pre- and post-supplement period. Subjects completed a pre- and post-supplement treadmill test for 20 min at 70% [Formula: see text] followed by increasing workload until exhaustion. RESULTS: AVS increased (p < 0.05) TAS by ~21% and resting expiratory flow rates (FEF25-75, FEF50) by ~9%. Following AVS, %EFL was significantly reduced by ~15% at minute 15, 20, and end-exercise with no change (p > 0.05) in end-expiratory lung volumes. Breathing frequency and ratings of perceived exertion and dyspnea were also lower (p < 0.05) at min 20 of exercise. No changes (p > 0.05) were evident at rest or during exercise with PLA. CONCLUSIONS: These results suggest that AVS can increase TAS, improve resting expiratory flow rates and reduce EFL during exercise in healthy subjects who are not meeting fruit and vegetable recommendations.