Cardiovascular Effects of Transcranial Direct Current Stimulation and Bimanual Training in Children With Cerebral Palsy.

PURPOSE: To determine the influence of combined transcranial direct current stimulation (tDCS) to the motor cortex (M1) and bimanual training on cardiovascular function in children with cerebral palsy (CP). METHODS: Mean arterial pressure (MAP), heart rate (HR), and HR variability (HRV) were measured immediately before and after 20 minutes of cathodal tDCS to contralesional M1 and bimanual training on days 1, 6, and 10 of a 10-day trial in 8 participants (5 females, 7-19 years). RESULTS: Baseline MAP and HR were similar across days (93 ± 10 mm Hg and 90 ± 10 bpm, P > .05). MAP was similar from baseline to postintervention across all 3 days. Systolic pressure, diastolic pressure, nor HR significantly changed. HRV was not influenced by the 10-day intervention. CONCLUSIONS: Combined cathodal tDCS to M1 and bimanual training does not influence autonomic and cardiovascular function in children with CP due to perinatal stroke.

Slow-Paced Breathing and Autonomic Function in People Post-stroke.

Purpose: To determine if acute slow breathing at 6 breaths/min would improve baroreflex sensitivity (BRS) and heart rate variability (HRV), and lower blood pressure (BP) in adults after stroke. Methods: Twelve individuals completed two randomized study visits where they performed a 15-min bout of breathing exercises at 6 breaths/min (slow) and at 12 breaths/min (control). Continuous BP and heart rate (HR) were measured throughout, and BRS, BRS response to elevations in blood pressure (BRSup), BRS response to depressions in blood pressure (BRSdown), and HRV were calculated and analyzed before (pre), during, and after (post) breathing exercises. Results: BRS increased from pre to post slow breathing by 10% (p = 0.012), whereas BRSup increased from pre to during slow breathing by 30% (p = 0.04). BRSdown increased from pre to post breathing for both breathing conditions (p < 0.05). HR (control: Δ - 4 ± 4; slow: Δ - 3 ± 4 beats/min, time, p < 0.01) and systolic BP (control: Δ - 0.5 ± 5; slow: Δ - 6.3 ± 8 mmHg, time, p < 0.01) decreased after both breathing conditions. Total power, low frequency power, and standard deviation of normal inter-beat intervals (SDNN) increased during the 6-breaths/min condition (condition × time, p < 0.001), whereas high frequency increased during both breathing conditions (time effect, p = 0.009). Conclusions: This study demonstrated that in people post-stroke, slow breathing may increase BRS, particularly BRSup, more than a typical breathing space; however, paced breathing at either a slow or typical breathing rate appears to be beneficial for acutely decreasing systolic BP and HR and increasing HRV.

VE/VCO2 slope in lean and overweight women and its relationship to lean leg mass.

Ventilation/carbon dioxide production (VE/VCO2slope) is used clinically to determine cardiorespiratory fitness and morbidity in heart failure (HF). Previously, we demonstrated that lower lean leg mass is associated with high VE/VCO2slope during exercise in HF. In healthy individuals, we evaluated 1) whether VE/VCO2slope differed between lean and overweight women and 2) the relationship between lean leg mass and VE/VCO2slope in overweight sedentary (OWS), overweight trained (OWTR) and lean, trained (LTR) women. METHODS: Gas exchange and ventilation were collected during a treadmill peak oxygen uptake test (VO2peak) in 40 women [26 OWS (29 ±â€¯7 yrs., mean ±â€¯SD), 7 OWTR (33 ±â€¯5 yrs) and 7 LTR (26 ±â€¯6 yrs)]. Body composition was measured by dual X-ray absorptiometry. RESULTS: VO2peak was highest in LTR (46.6 ±â€¯8 ml/kg/min) compared with OWTR (38.1 ±â€¯4.9 ml/kg/min) and OWS women (25.3 ±â€¯4.8 ml/kg/min, p < 0.05). Lean leg mass was highest in OWTR and lowest in LTR women (p < 0.05). VE/VCO2slope was similar between groups (p > 0.05). Higher lean leg mass was associated with lower VE/VCO2slope in overweight women (OWS + OWTR: r = -0.55, p < 0.001), contrasting with higher VE/VCO2slope in LTR women (r = 0.86, p < 0.001). CONCLUSIONS: These findings suggest VE/VCO2slope may not differentiate between low and high cardiorespiratory fitness in healthy individuals and muscle mass may play a role in determining the VE/VCO2slope, independent of disease.

Biochemical Characterization of WbkC, an N-Formyltransferase from Brucella melitensis.

It has become increasingly apparent within the last several years that unusual N-formylated sugars are often found on the O-antigens of such Gram negative pathogenic organisms as Francisella tularensis, Campylobacter jejuni, and Providencia alcalifaciens, among others. Indeed, in some species of Brucella, for example, the O-antigen contains 1,2-linked 4-formamido-4,6-dideoxy-α-d-mannosyl groups. These sugars, often referred to as N-formylperosamine, are synthesized in pathways initiating with GDP-mannose. One of the enzymes required for the production of N-formylperosamine, namely, WbkC, was first identified in 2000 and was suggested to function as an N-formyltransferase. Its biochemical activity was never experimentally verified, however. Here we describe a combined structural and functional investigation of WbkC from Brucella melitensis. Four high resolution X-ray structures of WbkC were determined in various complexes to address its active site architecture. Unexpectedly, the quaternary structure of WbkC was shown to be different from that previously observed for other sugar N-formyltransferases. Additionally, the structures revealed a second binding site for a GDP molecule distinct from that required for GDP-perosamine positioning. In keeping with this additional binding site, kinetic data with the wild type enzyme revealed complex patterns. Removal of GDP binding by mutating Phe 142 to an alanine residue resulted in an enzyme variant displaying normal Michaelis-Menten kinetics. These data suggest that this nucleotide binding pocket plays a role in enzyme regulation. Finally, by using an alternative substrate, we demonstrate that WbkC can be utilized to produce a trideoxysugar not found in nature.

The psychological and physiological effects of acute occupational stress in new anesthesiology residents: a pilot trial.

BACKGROUND: Occupational stress in resident physicians has profound implications for wellness, professionalism, and patient care. This observational pilot trial measured psychological and physiological stress biomarkers before, during, and after the start of anesthesia residency. METHODS: Eighteen physician interns scheduled to begin anesthesia residency were recruited for evaluation at three time points: baseline (collected remotely before residency in June 2013); first-month visit 1 (July); and follow-up visit 2 (residency months 3 to 5, September-November). Validated scales were used to measure stress, anxiety, resilience, and wellness at all three time points. During visits 1 and 2, the authors measured resting heart-rate variability, responses to laboratory mental stress (hemodynamic, catecholamine, cortisol, and interleukin-6), and chronic stress indices (C-reactive protein, 24-h ambulatory heart rate and blood pressure, 24-h urinary cortisol and catecholamines, overnight heart-rate variability). RESULTS: Thirteen interns agreed to participate (72% enrollment). There were seven men and six women, aged 27 to 33 yr. The mean ± SD of all study variables are reported. CONCLUSION: The novelty of this report is the prospective design in a defined cohort of residents newly exposed to the similar occupational stress of the operating environment. Because of the paucity of literature specific to the measures and stress conditions in this investigation, no data were available to generate a priori definition of primary outcomes and a data analytic plan. These findings will allow power analysis for future design of trials examining occupational stress and stress-reducing interventions. Given the importance of physician burnout in our country, the impact of chronic stress on resident wellness requires further study.

Structural and biochemical characterization of a bifunctional ketoisomerase/N-acetyltransferase from Shewanella denitrificans.

Unusual N-acetylated sugars have been observed on the O-antigens of some Gram-negative bacteria and on the S-layers of both Gram-positive and Gram-negative bacteria. One such sugar is 3-acetamido-3,6-dideoxy-α-d-galactose or Fuc3NAc. The pathway for its production requires five enzymes with the first step involving the attachment of dTMP to glucose-1-phosphate. Here, we report a structural and biochemical characterization of a bifunctional enzyme from Shewanella denitificans thought to be involved in the biosynthesis of dTDP-Fuc3NAc. On the basis of a bioinformatics analysis, the enzyme, hereafter referred to as FdtD, has been postulated to catalyze the third and fifth steps in the pathway, namely, a 3,4-keto isomerization and an N-acetyltransferase reaction. For the X-ray analysis reported here, the enzyme was crystallized in the presence of dTDP and CoA. The crystal structure shows that FdtD adopts a hexameric quaternary structure with 322 symmetry. Each subunit of the hexamer folds into two distinct domains connected by a flexible loop. The N-terminal domain adopts a left-handed ß-helix motif and is responsible for the N-acetylation reaction. The C-terminal domain folds into an antiparallel flattened ß-barrel that harbors the active site responsible for the isomerization reaction. Biochemical assays verify the two proposed catalytic activities of the enzyme and reveal that the 3,4-keto isomerization event leads to the inversion of configuration about the hexose C-4' carbon.