Fluid balance during physical work in the heat is not modified by the menstrual cycle when fluids are freely available.

We tested the hypothesis that women may be more at risk of becoming dehydrated during physical work in the heat in the early follicular phase (EF), compared with the late follicular (LF) and mid-luteal (ML) phases of the menstrual cycle when allowed free access to drink. Twelve healthy, eumenorrheic, unacclimated women (26 ± 5 yr) completed three trials (EF, LF, and ML phases) involving 4 h of exposure to 33.8 ± 0.8 °C, 54 ± 1% relative humidity. Each hour, participants walked on a treadmill for 30 min at a rate of metabolic heat production of 338 ± 9 W. Participants drank a cool, flavor-preferred non-caloric sport drink ad libitum. Nude body weight was measured pre- and post-exposure, and percent changes in body weight loss were interpreted as an index of changes in total body water. Total fluid intake and urine output were measured and sweat rate was estimated from changes in body mass corrected for fluid intake and urine output. Fluid intake was not different between phases (EF: 1,609 ± 919 mL; LF: 1,902 ± 799 mL; ML: 1,913 ± 671; P = 0.202). Total urine output (P = 0.543) nor sweat rate (P = 0.907) differed between phases. Percent changes in body mass were not different between phases (EF: -0.5 ± 0.9%; LF: -0.3 ± 0.9%; ML: -0.3 ± 0.7%; P = 0.417). This study demonstrates that the normal hormonal fluctuations that occur throughout the menstrual cycle do not alter fluid balance during physical work in the heat.NEW & NOTEWORTHY The effect of the menstrual cycle on fluid balance during physical work in the heat when fluids are freely available is unknown. This study demonstrates that fluid balance is not modified in women across three distinct phases of the menstrual cycle during physical work in the heat These results indicate that when women have free access to cool fluid during physical work in the heat, they respond similarly across all three phases to maintain fluid homeostasis across the menstrual cycle.

High Intraindividual Variability in the Response of Serum Erythropoietin to Multiple Simulated Altitude Exposures.

Baranauskas, Marissa N., Timothy J. Fulton, Alyce D. Fly, Bruce J. Martin, Timothy D. Mickleborough, and Robert F. Chapman. High intraindividual variability in the response of serum erythropoietin to multiple simulated altitude exposures. High Alt Med Biol. 23:85-89, 2022. Purpose: To evaluate within-subject variability in the serum erythropoietin (EPO) response to multiple simulated altitude exposures. Methods: Seven physically active men and women (age 27 ± 3 years, body mass index = 24.6 ± 4.0 kg/m2) were exposed to normobaric hypoxia (fraction of inspired oxygen [FiO2] = 0.14) for 12 hours on three separate occasions. Serum EPO concentrations were measured before exposure (0 hour), after 6 hours, and after 12 hours in hypoxia. The EPO response to hypoxia was calculated as percent change from 0 to 12 hours (ΔEPO0-12). Results: Exposure time had a significant effect on EPO (p < 0.001) with concentrations increasing 3.2 ± 1.3 mIU/ml from 0 to 6 hours (p = 0.034) and 4.7 ± 1.2 mIU/ml from 0 to 12 hours (p = 0.001). Group mean ΔEPO0-12 remained unchanged (p = 0.688) between the three exposures; however, there was considerable intraindividual variability in EPO responses. The intrasubject coefficient of variation for ΔEPO0-12 was 61% ± 28% (range: 17%-103%) with intrasubject associations ranging r = 0.052 to r = 0.651 between repeated exposures. Conclusions: Athletes who routinely supplement training with simulated altitude methods (e.g., hypoxic tents) should expect inconsistent EPO responses to intermittent exposures lasting ≤12 hours.

Influence of Zinc on the Acute Changes in Erythropoietin and Proinflammatory Cytokines with Hypoxia.

Baranauskas, Marissa N., Joseph Powell, Alyce D. Fly, Bruce J. Martin, Timothy D. Mickleborough, Hunter L. Paris, and Robert F. Chapman. Influence of zinc on the acute changes in erythropoietin and proinflammatory cytokines with hypoxia. High Alt Med Biol. 22: 148-156, 2021. Background: Considerable, unexplained, interindividual variability characterizes the erythropoietin (EPO) response to hypoxia, which can impact hematological acclimatization for individuals sojourning to altitude. Zinc supplementation has the potential to alter EPO by attenuating increases in inflammation and oxidative stress. Yet, the application of such an intervention has not been evaluated in humans. In this proof-of-concept study, we aimed to evaluate the EPO and inflammatory responses to acute hypoxia in human participants following chronic zinc supplementation. Methods: Nine physically active participants (men n = 5, women n = 4, age 28 ± 4 years, height 176 ± 11 cm, mass 77 ± 21 kg) were exposed to 12 hours of normobaric hypoxia simulating an altitude of 3,000 m (FiO2 = 0.14) before and after 8 weeks of supplementation with 40 mg/day of elemental zinc from picolinate. Blood samples for subsequent analysis of serum zinc, EPO, superoxide dismutase (extracellular superoxide dismutase [EC-SOD]), C-reactive protein (CRP), and proinflammatory cytokines were obtained pre- and postsupplementation and exposure to hypoxia. Results: After zinc supplementation, EPO increased by 64.9 ± 36.0% (mean ± standard deviation) following 12 hours of hypoxia, but this response was not different from presupplementation (70.8 ± 46.1%). Considerable interindividual (range: -1% to +208%) variability was apparent in the acute EPO response. While most markers of inflammation did not change with hypoxia, interleukin-6 concentrations increased from 1.17 ± 0.05 to 1.97 ± 0.32 pg/ml during the final 6 hours. The acute EPO response at 12 hours was not related to changes in serum zinc, EC-SOD, CRP, or proinflammatory cytokines. Conclusions: Zinc supplementation does not influence the acute EPO or inflammatory response with short-term exposure to moderate levels of normobaric hypoxia (3,000 m) in apparently healthy young adults.

Ventilatory Responsiveness during Exercise and Performance Impairment in Acute Hypoxia.

INTRODUCTION: An adequate increase in minute ventilation to defend arterial oxyhemoglobin saturation (SpO2) during hypoxic exercise is commonly viewed as an important factor contributing to large inter-individual variations in the degree of exercise performance impairment in hypoxia. Although the hypoxic ventilatory response (HVR) could provide insight into the underpinnings of such impairments, it is typically measured at rest under isocapnic conditions. Thus, we aimed to determine whether 1) HVR at rest and during exercise are similar and 2) exercise HVR is related to the degree of impairment in cycling time trial (TT) performance from normoxia to acute hypoxia (∆TT). METHODS: Sixteen endurance-trained men (V˙O2peak, 62.5 ± 5.8 mL·kg-1·min-1) performed two poikilocapnic HVR tests: one during seated rest (HVRREST) and another during submaximal cycling (HVREX). On two separate visits, subjects (n = 12) performed a 10-km cycling TT while breathing either room air (FiO2 = 0.21) or hypoxic gas mixture (FiO2 = 0.16) in a randomized order. RESULTS: HVREX was significantly (P < 0.001) greater than HVRREST (1.52 ± 0.47 and 0.22 ± 0.13 L·min-1·%SpO2-1, respectively), and these measures were not correlated (r = -0.16, P = 0.57). ∆TT was not correlated with HVRREST (P = 0.70) or HVREX (P = 0.54), but differences in ventilation and end-tidal CO2 between hypoxic and normoxic TT and the ventilatory equivalent for CO2 during normoxic TT explained ~85% of the variance in performance impairment in acute hypoxia (P < 0.01). CONCLUSION: We conclude that 1) HVR is not an appropriate measure to predict the exercise ventilatory response or performance impairments in acute hypoxia and 2) an adequate and metabolically matched increase in exercise ventilation, but not the gain in the ventilatory response to hypoxia, is essential for mitigating hypoxia-induced impairments in endurance cycling performance.

Expanding course goals beyond disciplinary boundaries: physiology education in an undergraduate course on psychoactive drugs.

The topic of psychoactive drugs is one of inherent interest to college students. We used this insight to design and implement a multidisciplinary undergraduate course with psychoactive drugs as the central theme. The Medical Science of Psychoactive Drugs examines the biological mechanisms underlying all major effects of psychoactive drugs, including the effects on the brain and other organs and tissues. Physiological principles, molecular mechanisms, and genetic factors involved in drug-induced therapeutic and adverse effects are emphasized. The course is open to undergraduate students at all levels and carries no prerequisites, and enrollment is limited to approximately 50 students. Major teaching modes include lecture, short homework papers on topics related to the previous class meeting, small-group discussions at several points during each class, and whole class discussions. Because of the diversity of students' knowledge of basic science, we employ a variety of methods designed to help students grasp the necessary scientific concepts. Our methods are intended to be inquiry based and highly interactive. Our goals are 1) to foster the development of an organized knowledge base about psychoactive drugs that will have practical applicability in the daily lives of the students; 2) to promote the rational application of this knowledge in thinking about current medical, social, legal, and ethical issues involving psychoactive drugs; and 3) to cultivate science literacy, critical thinking, and communication skills among students.

Total synthesis of myxothiazols, novel bis-thiazole beta-methoxyacrylate-based anti-fungal compounds from myxobacteria.

Convergent total syntheses of myxothiazols A and Z are described. The syntheses are based on elaboration of the (S)-E,E-diene thioamide 22, conversion of 22 into the bis-thiazole 27 and Wittig reactions between 27c and the aldehyde 30. The substituted beta-methoxyacrylate aldehyde 30 was produced via an Evans asymmetric aldol protocol or via the 2H-pyran-2-one 31. An E-selective Wittig reaction between the ylide derived from the phosphonium salt 27c and the (+)-aldehyde 30 led to (+)-myxothiazol Z (1b), and a corresponding reaction with the (+/-)-acrylamide aldehyde 44 gave (+/-)-myxothiazol A (1a). Complementary studies led to synthesis of the ester 47b, corresponding to myxothiazol R and myxothiazol S.