Astaxanthin Supplementation Does Not Affect Markers of Muscle Damage or Inflammation After an Exercise-Induced Muscle Damage Protocol in Resistance-Trained Males.

ABSTRACT: Waldman, HS, Bryant, AR, Parten, AL, Grozier, CD, and McAllister, MJ. Astaxanthin supplementation does not affect markers of muscle damage or inflammation after an exercise-induced muscle damage protocol in resistance-trained males. J Strength Cond Res 37(7): e413-e421, 2023-It is well documented that exercise-induced muscle damage (EIMD) decreases exercise performance by elevated inflammation and subjective discomfort. Due to its potent antioxidative properties, astaxanthin (AX) may serve as a potential dietary supplement strategy for mitigating delayed-onset muscle soreness (DOMS) and enhancing recovery and performance. This study aimed to investigate the effects of AX on markers of muscle damage, inflammation, DOMS, and anaerobic performance and substrate metabolism. Thirteen resistance-trained men (mean ± SD , age, 23.4 ± 2.1 years) completed a double-blind, counterbalanced, and crossover design with a 1-week washout period between 2, 4-week supplementation periods at 12 mg·d -1 of AX or placebo. After each supplementation period, subjects completed 2 trials, with trial 1 including a graded exercise test (GXT) and a 30-second Wingate and trial 2 including an EIMD protocol followed by the collection of fasting blood samples (pre-post) to measure creatine kinase, advanced oxidative protein products, C-reactive protein, interleukin-6, insulin, and cortisol. Astaxanthin supplementation had no statistical effects on markers of substrate metabolism during the GXT, Wingate variables, or markers of muscle damage, inflammation, or DOMS when compared with placebo (all p > 0.05). However, 4 weeks of AX supplementation did significantly lower oxygen consumption during the final stage of the GXT (12%, p = 0.02), as well as lowered systolic blood pressure (∼7%, p = 0.04), and significantly lowered baseline insulin values (∼24%, p = 0.05) when compared with placebo. Collectively, these data suggest that 4 weeks of AX supplementation at 12 mg·d -1 did not affect markers of muscle damage, inflammation, or DOMS after an EIMD protocol in a resistance-trained male cohort.

Effects of Betaine Supplementation on Markers of Metabolic Flexibility, Body Composition, and Anaerobic Performance in Active College-Age Females.

Betaine (BET) has shown to be effective in improving body composition and performance, although research in women is lacking. This study investigated the effects of BET supplementation on markers of metabolic flexibility, body composition, and anaerobic performance in college females. Twenty-three active subjects with 21.8 ± 3.0 years of age, 66.6 ± 8.8 kg body mass, 1.6 ± 0.1 m height, and 23.2 ± 5.3% body fat performed a graded exercise test on a cycle ergometer consisting of 4 incremental, 3 min stages for collection of fat and carbohydrate oxidation rates. Three 10 s sprint tests were then completed against a resistance of 7.5% of body mass, separated by 2.5 min of recovery. The study comprised 3 phases: (a) pre-supplementation, (b) randomization to supplement for 2-weeks with either 2.4 g/day BET or placebo (parallel design), and (c) post-supplementation. Repeated-measures analysis of variance were conducted to determine interactions or main effects. There were no group differences for substrate oxidation rates (p > 0.05). Although body composition improved pre-post for both groups (p < 0.05), only the BET group experienced a significant increase in fat free mass (p < 0.01; ∼3%). Further, only the BET group experienced improvements to performance such as a higher mean power output during the final sprint (p = 0.02; ∼3%) and a lower RPE during the final stage of the graded exercise test (p = 0.02). Results from this study suggest BET supplementation may improve body composition and some markers of performance during exercise in collegiate women.

Assessment of Metabolic Flexibility by Substrate Oxidation Responses and Blood Lactate in Women Expressing Varying Levels of Aerobic Fitness and Body Fat.

ABSTRACT: Waldman, HS, Bryant, AR, Knight, SN, Killen, LG, Davis, BA, Robinson, MA, and O'Neal, EK. Assessment of metabolic flexibility by substrate oxidation responses and blood lactate in women expressing varying levels of aerobic fitness and body fat. J Strength Cond Res 37(3): 581-588, 2023-Collection of substrate oxidation responses during exercise is proposed as a noninvasive means for assessing metabolic flexibility in male subjects. However, because of hormonal and metabolic differences between sexes, this method may not be applicable to female subjects. This study assessed metabolic flexibility through indirect calorimetry across female subjects with different maximal oxidative capacities. Thirty-eight (18-45 years) eumenorrheic female subjects were stratified ( p < 0.05) based on V̇ o2 peak (mL·kg -1 ·min -1 ) into (1) endurance-trained (ET, n = 12, 42.6 ± 5.3), (2) recreationally active (RA, n = 13, 32.3 ± 1.6), or (3) overweight female subjects (OW, n = 13, 21.0 ± 4.0). Subjects completed the same 5-stage graded exercise test with intensities of 30, 45, 60, 75, and 90 W. Lactate [La - ], carbohydrate (CHOox), and fat (FATox) oxidation rates were assessed during the last min of each 5-minute stage. Subjects then cycled to exhaustion to determine V̇ o2 peak. Endurance-trained and RA female subjects expressed significantly ( p ≤ 0.05) higher absolute rates and rates scaled to fat-free mass of CHOox and FATox compared with OW female subjects during multiple stages. [La - ] failed to consistently differentiate the 3 groups with higher [La - ] for OW only found during stage 4; however, RER differed by 0.09 units or more at each stage for OW vs. ET. It seems that RER was more sensitive to cohort characteristics than [La - ] contrasting recent findings in male cohorts. In conclusion, indirect calorimetry is a practical and noninvasive method for assessing metabolic flexibility in eumenorrheic female subjects of varying aerobic fitness levels.

No Effect of a Ketone Monoester on Markers of Stress and Performance in a Live-Burn Search and Rescue in Firefighters.

ABSTRACT: Waldman, HS, Bryant, AR, Shepherd, BD, Egan, B, and McAllister, MJ. No effect of a ketone monoester on markers of stress and performance in a live-burn search and rescue in firefighters. J Strength Cond Res 36(3): 763-771, 2022-Firefighters experience a range of stressors that impair performance and elevate the risk for developing cardiometabolic diseases. ß-Hydroxybutyrate (ßHB) has been shown to mitigate markers of oxidative stress and inflammation and serve as an alternative fuel with implications to physical performance. On 2 occasions in a double-blind, counterbalanced, and crossover design, 14 professional firefighters performed a live-burn, search and rescue (S&R) 30 minutes after ingestion of a ketone monoester (KME; 0.5 g·kg-1) or a placebo (PLA). Dependent variables collected before and after the S&R included salivary markers of stress and inflammation (cortisol, α-amylase, interleukin-1 beta, uric acid), perceptual markers (profile of mood state [POMS]), gastrointestinal distress (GI), rating of perceived exertion [RPE]), time to completion, and capillary blood measurement of ßHB and glucose. KME resulted in capillary ßHB concentrations of approximately 2.1-3.2 mM throughout the protocol. Capillary glucose concentrations were lower for the KME compared with PLA (∼7%) (interaction effect, p < 0.001). Salivary markers of stress, GI, and time to complete the S&R (∼10 minutes) did not differ between trials, although KME ingestion resulted in significantly higher RPE after the live-burn S&R (KME,6 ± 1; PLA, 4 ± 1). However, POMS data showed the KME also lowered subjective states of nervousness (KME, 0.0 ± 0.0; PLA, 0.6 ± 0.8) and anxiety (KME, 0.0 ± 0.0; PLA, 0.6 ± 0.7) before the S&R (all p < 0.05; large effect sizes). Compared with PLA, ingestion of a KME by firefighters did not mitigate the rise in various markers of salivary stress or impact physical performance during a live-burn S&R. However, differences in RPE and POMS variables were observed, suggesting a possible cognitive role for ßHB.

From natural disaster to pandemic: A health-system pharmacy rises to the challenge.

PURPOSE: This report describes a health-system pharmacy's response to a natural disaster while staff members simultaneously prepared for the coronavirus disease 2019 (COVID-19) pandemic. By detailing our experience, we hope to help other institutions that are current facing or could encounter similar crises. SUMMARY: In early March 2020, a tornado destroyed the health system's warehouse for storage of most clinical supplies, including personal protective equipment and fluids. The pharmacy purchasing team collaborated with suppliers and manufacturers to recover losses and establish alternative storage areas. Days later, the pharmacy department was forced to address the impending COVID-19 pandemic. Key elements of the COVID-19 response included reducing the potential for virus exposure for patients and staff; overcoming challenges in sourcing of staff, personal protective equipment, and medications; and changing care delivery practices to maintain high-quality patient care while maximizing social distancing. The pharmacy department also created distance learning opportunities for 70 pharmacy students on rotations. After an initial plan, ongoing needs include adjustment in patient care activities if significant staff losses occur, when and how to resume clinical activities, and how to best utilize the resources accumulated. Elements of practice changes implemented to reduce COVID-19 threats to patients and pharmacy personnel have proven beneficial and will be further evaluated for potential continuation. CONCLUSION: The pharmacy department's efforts to respond to a natural disaster and unprecedented pandemic have proven successful to this point and have illuminated several lessons, including the necessity of cohesive department communication, staff flexibility, prioritization of teamwork, and external collaboration.

Deletion and gene expression analyses define the paxilline biosynthetic gene cluster in Penicillium paxilli.

The indole-diterpene paxilline is an abundant secondary metabolite synthesized by Penicillium paxilli. In total, 21 genes have been identified at the PAX locus of which six have been previously confirmed to have a functional role in paxilline biosynthesis. A combination of bioinformatics, gene expression and targeted gene replacement analyses were used to define the boundaries of the PAX gene cluster. Targeted gene replacement identified seven genes, paxG, paxA, paxM, paxB, paxC, paxP and paxQ that were all required for paxilline production, with one additional gene, paxD, required for regular prenylation of the indole ring post paxilline synthesis. The two putative transcription factors, PP104 and PP105, were not co-regulated with the pax genes and based on targeted gene replacement, including the double knockout, did not have a role in paxilline production. The relationship of indole dimethylallyl transferases involved in prenylation of indole-diterpenes such as paxilline or lolitrem B, can be found as two disparate clades, not supported by prenylation type (e.g., regular or reverse). This paper provides insight into the P. paxilli indole-diterpene locus and reviews the recent advances identified in paxilline biosynthesis.

Pathologic mechanisms of type 1 VWD mutations R1205H and Y1584C through in vitro and in vivo mouse models.

Type 1 VWD is the mild to moderate reduction of VWF levels. This study examined the mechanisms underlying 2 common type 1 VWD mutations, the severe R1205H and more moderate Y1584C. In vitro biosynthesis was reduced for both mutations in human and mouse VWF, with the effect being more severe in R1205H. VWF knockout mice received hydrodynamic injections of mouse Vwf cDNA. Lower VWF antigen levels were demonstrated in both homozygous and heterozygous forms for both type 1 mutations from days 14-42. Recombinant protein infusions and hydrodynamic-expressed VWF propeptide to antigen ratios demonstrate that R1205H mouse VWF has an increased clearance rate, while Y1584C is normal. Recombinant ADAMTS13 digestions of Y1584C demonstrated enhanced cleavage of both human and mouse VWF115 substrates. Hydrodynamic-expressed VWF shows a loss of high molecular weight multimers for Y1584C compared with wild-type and R1205H. At normal physiologic levels of VWF, Y1584C showed reduced thrombus formation in a ferric chloride injury model while R1205H demonstrated similar thrombogenic activity to wild-type VWF. This study has elucidated several novel mechanisms for these mutations and highlights that the type 1 VWD phenotype can be recapitulated in the VWF knockout hydrodynamic injection model.

Ag(+)-mediated assembly of 5'-guanosine monophosphate.

Polymorphic forms of nucleic acids provide platforms for new nanomaterials, and transition metal cations give access to alternative arrangements of nucleobases by coordinating with electron-rich functional groups. Interaction of Ag(+) with 5'-guanosine monophosphate (5'-GMP) is considered in this work. Ag(+) promotes nucleotide stacking and aggregation, as indicated by the increased viscosity of 5'-GMP solutions with Ag(+), magnification of the circular dichroism response of guanine by Ag(+), and exothermic reactions between Ag(+) and guanine derivatives. Isothermal titration calorimetry studies show that the reaction is favored starting at 10 microM 5'-GMP. Utilizing the exothermic heat change associated with reaction of Ag(+) with 5'-GMP, local structure within the aggregate was assessed. On the basis of the salt dependence of the reaction and comparison with the corresponding nucleoside, the dianionic phosphate of 5'-GMP is one binding site for Ag(+), although this electrostatic interaction is not a dominant contribution to the overall heat change. Another binding site is the N7 on the nucleobase, as determined via studies with 7-deazaguanosine. Besides this binding site, Ag(+) also associates with the O6, as earlier studies deduced from the shift in the carbonyl stretching frequency associated with adduct formation. With these two binding sites on the nucleobase, the empirical stoichiometry of approximately 1 Ag(+):nucleobase derived from the calorimetry studies indicates that Ag(+) coordinates two nucleobases. The proposed structural model is a Ag(+)-mediated guanine dimer within a base stacked aggregate.

Hydration changes accompanying the binding of minor groove ligands with DNA.

4',6-diamidino-2-phenylindole (DAPI), netropsin, and pentamidine are minor groove binders that have terminal -C(NH2)2+ groups. The hydration changes that accompany their binding to the minor groove of the (AATT)2 sequence have been studied using the osmotic stress technique with fluorescence spectroscopy. The affinity of DAPI for the binding site decreases with the increasing osmolality of the solution, resulting in acquisition of 35+/-1 waters upon binding. A competition fluorescence assay was utilized to measure the binding constants and hydration changes of the other two ligands, using the DNA-DAPI complex as the fluorescence reporter. Upon their association to the (AATT)2 binding site, netropsin and pentamidine acquire 26+/-3 and 34+/-2 additional waters of hydration, respectively. The hydration changes are discussed in the context of the terminal functional groups of the ligands and conformational changes in the DNA.