Study of the Effects of Remote Heavy Group Vibrations on the Temperature Dependence of Hydride Kinetic Isotope Effects of the NADH/NAD+ Model Reactions.

It has recently been observed that the temperature(T)-dependence of KIEs in H-tunneling reactions, characterized by isotopic activation energy difference (ΔEa = EaD - EaH), is correlated to the rigidity of the tunneling ready states (TRSs) in enzymes. A more rigid system with narrowly distributed H-donor-acceptor distances (DADs) at the TRSs gives rise to a weaker T-dependence of KIEs (i.e., a smaller ΔEa). Theoreticians have attempted to develop new H-tunneling models to explain this, but none has been universally accepted. In order to further understand the observations in enzymes and provide useful data to build new theoretical models, we have studied the electronic and solvent effects on ΔEa's for the hydride-tunneling reactions of NADH/NAD+ analogues. We found that a tighter charge-transfer (CT) complex system gives rises to a smaller ΔEa, consistent with the enzyme observations. In this paper, we use the remote heavy group (R) vibrational effects to mediate the system rigidity to study the rigidity-ΔEa relationship. The specific hypothesis is that slower vibrations of a heavier remote group would broaden the DAD distributions and increase the ΔEa value. Four NADH/NAD+ systems were studied in acetonitrile but most of such heavy group vibrations do not appear to significantly increase the ΔEa. The remote heavy group vibrations in these systems may have not affected the CT complexation rigidity to a degree that can significantly increase the DADs, and further, the ΔEa values.

Asthma control in normal weight and overweight/obese asthmatic children following adenotonsillectomy.

OBJECTIVES: Childhood adenotonsillar hypertrophy (ATH) with sleep-disordered breathing (SDB) frequently occurs concomitant with asthma. Adenotonsillectomy and reduction in asthma severity association has been reported. We describe changes in asthma control in nonobese or normal weight and obese/overweight children undergoing adenotonsillectomy for SDB. METHODS: This prospective, nonrandomized cohort trial with 6-month follow-up at a tertiary children's hospital enrolled 41 children with persistent asthma undergoing adenotonsillectomy for SDB. Children with significant chronic medical conditions, premature birth (< 28 weeks), or recent respiratory infection were excluded. Patients were stratified by baseline BMI into nonobese or normal weight (BMI < 85 percentile) and obese/overweight (BMI > 85%). The primary outcome was change in Childhood Asthma Control Test (cACT) scores 3 and 6 months following adenotonsillectomy. Secondary outcome examined improvement in Pediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ) 3 and 6 months following adenotonsillectomy. RESULTS: Baseline characteristics were similar except for anthropometric measures and mean PACQLQ (P = .03). Children with nonobese or normal weight (n = 26) had statistically significant improvement in change in cACT at 3 (22.80 ± 2.33 vs. 17.86 ± 3.53, P < .001) and 6 (20.71±3.29 vs. 18.24 ± 4.16, P = .044) months compared with baseline. PACQLQ scores also improved at 3 (6.20 ± 0.87 vs. 4.56 ± 1.12, P < .001) and 6 (6.36 ± 0.72 vs. 4.93 ± 0.96, P < .001) months. Obese/overweight children (n = 10) had significant improvement in cACT scores at 6 months (20.00 ± 3.90 vs. 15.00 ± 6.90, P = .048). Change of cACT scores at 3 months (17.86 ± 3.53 vs. 14.86 ± 6.31, P = .272) was not significantly different. PACQLQ scores improved at 3 (5.47 ± 1.09 vs. 3.70 ± 0.85, P < .001) and 6 (5.75 ± 2.19 vs. 3.67 ± 1.04, P = .016) months. CONCLUSION: Nonobese or normal-weight children undergoing adenotonsillectomy demonstrated significant improvement in asthma control scores at 3 and 6 and obese/overweight children at 6 months. Using the PACQLQ, caregiver quality of life improved for all children at 3 and 6 months. Surgical management of ATH in children with comorbid SBD and asthma is a good treatment option.

Can Bodybuilding Peak Week Manipulations Favorably Affect Muscle Size, Subcutaneous Thickness, and Related Body Composition Variables? A Case Study.

BACKGROUND: The purpose of this case study was to implement an evidence-based dietary approach to peaking for a bodybuilding competition and monitor its impact on body composition, muscle thickness (MT), intra-to-extra-cellular fluid shifts, subcutaneous thickness (ST), and hydration status. Secondarily, to document any adverse events of this peak week approach in a small, controlled setting. Methods Dietary practices were recorded, and laboratory testing was conducted throughout peak week, including competition morning. Assessments included: dual-energy X-ray absorptiometry (DEXA) for body composition, B-mode ultrasound for MT and ST, bioimpedance spectroscopy (BIS) for total body water (TBW)/intracellular water (ICW)/extracellular water (ECW), and raw BIS data (i.e., resistance, reactance, and phase angle), urine specific gravity (USG) for hydration status, and subjective fullness. Sequential dietary manipulations were made (i.e., CHO depletion/fat loading, CHO/water loading, and a refinement phase) with specific physiological goals. This was reflected in changes observed across all assessments throughout the peak week. RESULTS: From the carbohydrate-depleted state (three days out) to competition day, we observed increases in lean body mass, MT, TBW (primarily ICW), and subjective fullness. Kendall's Tau B revealed a strong relationship between carbohydrate intake and ∑MT (τ = 0.733, p = 0.056). Additionally, novel ST data demonstrated a 10% reduction for the summation of all seven sites, with some drastic changes in specific regions (e.g., -43% for triceps ST) from three days out to competition day. CONCLUSIONS: These data suggest that the prototypical goals of bodybuilders' peak week (i.e., increasing muscle fullness, decreasing subcutaneous thickness) to enhance their aesthetics/muscularity presented can be achieved with a drug-free protocol involving dietary manipulations.

Progressive Resistance Training Volume: Effects on Muscle Thickness, Mass, and Strength Adaptations in Resistance-Trained Individuals.

ABSTRACT: Aube, D, Wadhi, T, Rauch, J, Anand, A, Barakat, C, Pearson, J, Bradshaw, J, Zazzo, S, Ugrinowitsch, C, and De Souza, EO. Progressive resistance training volume: effects on muscle thickness, mass, and strength adaptations in resistance-trained individuals. J Strength Cond Res 36(3): 600-607, 2022-This study investigated the effects of 12-SET, 18-SET, and 24-SET lower-body weekly sets on muscle strength and mass accretion. Thirty-five resistance-trained individuals (one repetition maximum [1RM] squat: body mass ratio [1RM: BM] = 2.09) were randomly divided into 12-SET: n = 13, 18-SET: n = 12, and 24-SET: n = 10. Subjects underwent an 8-week resistance-training (RT) program consisting of 2 weekly sessions. Muscle strength (1RM), repetitions to failure (RTF) at 70% of 1RM, anterior thigh muscle thickness (MT), at the medial MT (MMT) and distal MT (DMT) points, as well as the sum of both sites (ΣMT), along with region of interest for fat-free mass (ROI-FFM) were measured at baseline and post-testing. For the 1RM, there was a main time effect (p ≤ 0.0001). However, there was a strong trend toward significance (p = 0.052) for group-by-time interaction, suggesting that 18-SET increased 1RM back squat to a greater extent compared with 24-SET (24-SET: 9.5 kg, 5.4%; 18-SET: 25.5 kg, 16.2%; 12-SET: 18.3 kg, 11.3%). For RTF, only a main time-effect (p ≤ 0.0003) was observed (24-SET: 5.7 reps, 33.1%; 18-SET: 2.4 reps, 14.5%; 12-SET: 5.0 reps, 34.8%). For the MMT, DMT, ΣMT, and ROI-FFM, there was only main time-effect (p ≤ 0.0001) (MMT: 24-SET: 0.15 cm, 2.7%; 18-SET: 0.32 cm, 5.7%; 12-SET: 0.38 cm, 6.4%-DMT: 24-SET: 0.39 cm, 13.1%; 18-SET: 0.28 cm, 8.9%; 12-SET: 0.34 cm, 9.7%-ΣMT: 24-SET: 0.54 cm, 6.1%; 18-SET: 0.60 cm, 6.7%; 12-SET: 0.72 cm, 7.7%, and ROI-FFM: 24-SET: 0.70 kg, 2.6%; 18-SET: 1.09 kg, 4.2%; 12-SET: 1.20 kg, 4.6%, respectively). Although all of the groups increased maximum strength, our results suggest that the middle dose range may optimize the gains in back squat 1RM. Our findings also support that differences in weekly set number did not impact in MT and ROI-FFM adaptations in subjects who can squat more than twice their body mass.

Kinetics of the hydride reduction of an NAD(+) analogue by isopropyl alcohol in aqueous and acetonitrile solutions: solvent effects, deuterium isotope effects, and mechanism.

The rate constants of the hydride-transfer reactions from isopropyl alcohol (i-PrOH) to an NAD(+) model, 9-phenylxanthylium ion (PhXn(+)), in acetonitrile (AN) and in water containing AN (80% H(2)O/20% AN) were determined over a temperature range from 36 to 67 degrees C. The reactions follow second-order rate laws. In the latter solution, formation of the water adduct of PhXn(+) was observed as a side-equilibrium (K). The observed inverse solvent kinetic isotope effect (k(H(2)O)(obs)/k(D(2)O)(obs) = 0.54), the larger than unity equilibrium isotope effect (K(H(2)O)/K(D(2)O) = 2.69), and the results of acid effect on the observed rate constants of the reactions are consistent with the "side-equilibrium mechanism". Kinetic isotope effects at all three H/D positions of i-PrOH for the net hydride-transfer process were determined in both solutions at 60 degrees C: KIE(alpha-D)(H) = 3.2(AN), 3.2(H(2)O); KIE(beta-D6)(H) = 1.05(AN), 1.16(H(2)O); KIE(OD)(H) = 1.08(AN), 1.04(H(2)O). These KIE values are consistent with the presence of the positively charged alcohol moiety in the transition state (TS) for cleavage of the alpha-C-H bond, the delocalization of the positive charge over the alpha-C-OH group, and the stepwise hydride and proton transfer processes. Comparison of the activation parameters for the reactions in the two solvent systems as well as those in the i-PrOH/AN (1:1 v/v) reported earlier suggests that the AN medium promotes the reaction by activating the ground-state alcohol reactant through weak interactions with the electron pairs on alcohol O, while water and parent alcohol media facilitate the reaction by H-bonding stabilization of the alcohol moiety of the TS. Results suggest that in the alcohol dehydrogenases without a Zn(II) cofactor in the active sites alcohols would be oxidized via hydride transfer to NAD(+) coenzyme followed by the rapid deprotonation to the nearby basic species in the active site of the enzymes.