Effects of 36 hours of sleep deprivation on military-related tasks: Can ammonium inhalants maintain performance?

INTRODUCTION: A lack of sleep can pose a risk during military operations due to the associated decreases in physical and cognitive performance. However, fast-acting ergogenic aids, such as ammonia inhalants (AI), may temporarily mitigate those adverse effects of total sleep deprivation (TSD). Therefore, the present study aimed to investigate the acute effect of AI on cognitive and physical performance throughout 36 hours of TSD in military personnel. METHODS: Eighteen male military cadets (24.1 ± 3.0 y; 79.3 ± 8.3 kg) performed 5 identical testing sessions during 36 hours of TSD (after 0 [0], 12 [-12], 24 [-24], and 36 [-36] hours of TSD), and after 8 [+8] hours of recovery sleep. During each testing session, the following assessments were conducted: Epworth sleepiness scale (ESS), simple reaction time (SRT), shooting accuracy (SA), rifle disassembling and reassembling (DAS), and countermovement jump height (JH). Heart rate (HR) was continuously monitored during the SA task, and a rating of perceived exertion (RPE) was obtained during the JH task. At each time point, tests were performed twice, either with AI or without AI as control (CON), in a counterbalanced order. RESULTS: There was faster SRT (1.6%; p < 0.01) without increasing the number of errors, higher JH (1.5%; p < 0.01), lower RPE (9.4%; p < 0.001), and higher HR (5.0%; p < 0.001) after using AI compared to CON regardless of TSD. However, neither SA nor DAS were affected by AI or TSD (p > 0.05). Independent of AI, the SRT was slower (3.2-9.3%; p < 0.001) in the mornings (-24, +8) than in the evening (-12), JH was higher (3.0-4.7%, p < 0.001) in the evenings (-12, -36) than in the mornings (0, -24, +8), and RPE was higher (20.0-40.1%; p < 0.001) in the sleep-deprived morning (-24) than all other timepoints (0, -12, -36, +8). Furthermore, higher ESS (59.5-193.4%; p < 0.001) was reported at -24 and -36 than the rest of the time points (0, -12, and + 8). CONCLUSION: Although there were detrimental effects of TSD, the usage of AI did not reduce those adverse effects. However, regardless of TSD, AI did result in a short-term increase in HR, improved SRT without affecting the number of errors, and improved JH while concurrently decreasing the RPE. No changes, yet, were observed in SA and DAS. These results suggest that AI could potentially be useful in some military scenarios, regardless of sleep deprivation.

Glycolytic and Krebs cycle enzymes activity in rat prefrontal cortex, hippocampus, and striatum after single and repeated NMDA inhibition by MK-801.

Psychosis is a state of altered thoughts which often accompanies schizophrenia. It was suggested that changes in energetic metabolism accompany psychosis and post-psychosis states. Here, we use the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 to experimentally induce psychosis-like behavior in rats. We addressed an effect of single and repeated (5×) MK-801 application (0.3 mg/kg; i.p.) on the energy metabolism in homogenates and crude mitochondrial fraction (CMF) of the striatum (STR), prefrontal cortex (PFC), and the hippocampus (HIP) of the adult male Wistar rat (n = 39). In each brain region, we assessed activity of glycolytic (hexokinase (HK) and lactate dehydrogenase (LDH)) and Krebs cycle enzymes (citrate synthase (CS) and malate dehydrogenase (MDH)) 2 h and 3 days (3d) after the last MK-801 application together with relative respiratory rates assessment in tissue homogenate. In STR, a single MK-801 application led to a decrease in the LDH (p = 0.0035) and the increase of the MDH (p = 0.0043) activities following 3d. Therein, repeated MK-801 doses evoked increased LDH (p = 0.0204) and CS (p = 0.0019) activities in the homogenate 2 h and increased HK (p = 0.0007) 3d after the last application. Elevated HK activity within CMF was observed after 3d (p = 0.0054). In PFC, repeated MK-801 application decreased HK activity in the homogenate 3d after the final application (p = 0.0234). Correspondingly, PFC HK activity in CMF of repeated administration samples dropped (p = 0.003). In HIP, repeated MK-801 administration led to increased respiration of SDH (p = 0.0475) only 2 h after the last application and decreased CS activity (p = 0.0160) was observed 3d after the last application. Our results indicate a progressive metabolic dysregulation of glycolytic and Krebs cycle enzymes following repeated inhibition of NMDA receptors activity in a region-specific manner. Energetic alterations may form a basis for persisting cognitive problems during and following a psychosis in schizophrenia patients.

Diurnal and seasonal differences in cardiopulmonary response to exercise in morning and evening chronotypes.

Circadian clocks regulate multiple physiological domains from molecular to behavioral levels and adjust bodily physiology to seasonal changes in day length. Circadian regulation of cellular bioenergy and immunity in the cardiovascular and muscle systems may underpin the individual diurnal differences in performance capacity during exercise. Several studies have shown diurnal differences in cardiopulmonary parameters at maximal and submaximal workloads in morning and evening circadian human phenotypes. However, the effect of seasons on these changes was not elucidated. In this study, we recruited subjects with Morningness-Eveningness Questionnaire scores corresponding to morning and evening types. Subjects underwent morning (7:00-9:00) and evening (20:00-22:00) maximal workload spiroergometry in both winter and summer seasons. We analyzed their performance time, anaerobic threshold, heart rate, and respiratory parameters. Our results suggest that evening types manifest diurnal variations in physical performance, particularly in winter. They also have slower heart rate recovery than morning types, irrespective of the time of day or season. Compared to winter, the chronotype effect on the magnitude of morning-evening differences in performance time, maximal heart rate, and anaerobic threshold onset was more significant in summer. Our data are in concordance with previous observations and confirm the difference between morning and evening types in the timing of maximum performance capacity.

The Effect of a Common Daily Schedule on Human Circadian Rhythms During the Polar Day in Svalbard: A Field Study.

All Arctic visitors have to deal with extreme conditions, including a constant high light intensity during the summer season or constant darkness during winter. The light/dark cycle serves as the most potent synchronizing signal for the biological clock, and any Arctic visitor attending those regions during winter or summer would struggle with the absence of those entraining signals. However, the inner clock can be synchronized by other zeitgebers such as physical activity, food intake, or social interactions. Here, we investigated the effect of the polar day on the circadian clock of 10 researchers attending the polar base station in the Svalbard region during the summer season. The data collected in Svalbard was compared with data obtained just before leaving for the expedition (in the Czech Republic 49.8175°N, 15.4730°E). To determine the circadian functions, we monitored activity/rest rhythm with wrist actigraphy followed by sleep diaries, melatonin rhythm in saliva, and clock gene expression (Per1, Bmal1, and Nr1D1) in buccal mucosa samples. Our data shows that the two-week stay in Svalbard delayed melatonin onset but did not affect its rhythmic secretion, and delayed the activity/rest rhythm. Furthermore, the clock gene expression displayed a higher amplitude in Svalbard compared to the amplitude detected in the Czech Republic. We hypothesize that the common daily schedule at the Svalbard expedition strengthens circadian rhythmicity even in conditions of compromised light/dark cycles. To our knowledge, this is the first study to demonstrate peripheral clock gene expression during a polar expedition.

Circadian rhythms of melatonin and peripheral clock gene expression in idiopathic REM sleep behavior disorder.

OBJECTIVE: To evaluate changes in the expression of clock genes and melatonin levels in patients with idiopathic REM sleep behavior disorder (RBD) as a potential early stage of synucleinopathies. METHODS: We assessed the rhythmicity of circadian clock genes using real time-quantitative polymerase chain reaction and 24-h blood melatonin profiles using radio-immunoassay in 10 RBD patients and nine age-matched controls. RESULTS: The RBD patients did not show circadian rhythmicity for clock genes Per2, Bmal1, and Nr1d1 but the rhythmicity of Per 1 remained, and the amplitude of Per3 was diminished. The 24-h melatonin rhythm did not differ between RBD patients and healthy control subjects. Melatonin profile in RBD patients was delayed by 2 h compared to controls, the habitual sleep phases were phase delayed by about 1 h, however no phase shift occurred in any of the clock genes studied. The control group had stable acrophases of melatonin rhythms of approximately 5 h whereas the RBD patients had a more dispersed range over 11 h. CONCLUSIONS: Our results suggest that RBD could be associated with altered expression of clock genes and delayed melatonin secretion. Thus, we argue that circadian system dysregulation could play a role in RBD.

Serum Levels of IGF-1 and IGFBP-3 in Relation to Clinical and Pathobiological Aspects of Head and Neck Squamous Cell Carcinomas.

BACKGROUND/AIM: Head and neck squamous cell carcinoma (HNSCC) includes tumors of various anatomical sites sharing multifactorial etiopathogenesis and generally dismal response to conventional treatment. The objective of this study was to determine the clinical significance of serum levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) in HNSCC. PATIENTS AND METHODS: A total of 46 patients, with histologically-confirmed diagnosis of HNSCC (21 oropharyngeal, 21 laryngeal, and 4 hypopharyngeal cancers) were enrolled in this study. IGF-1 and IGFBP-3 serum levels were measured by an immunoradiometric assay using commercial kits. The adjustment of serum levels at 60 years of age was performed. RESULTS: Significant differences were found in IGF-1 serum concentrations between patients with p16 positive and p16 negative HNSCC (p=0.0062), with higher IGF-1 levels in p16 positive tumors, between low-grade and high-grade cancers (p=0.0323) only in larynx, with elevated IGF-1 concentrations associated with high-grade and between recurrent and non-recurrent HNSCC (p=0.0354), with lower IGF-1 levels in recurrent tumors. CONCLUSION: The conflicting results of this study may reflect some abnormality of IGF axis regulation in HNSCC, as well as the influence of other etiological factors (e.g. smoking, HPV infection).

Human myeloid dendritic cells for cancer therapy: does maturation matter?

Dendritic cells form the connection between innate and adoptive mechanisms of the immune system. As antigen-presenting cells, dendritic cells are capable of presenting tumour antigen and effectively stimulating immune response targeted against a tumour. A number of preclinical and clinical studies document dendritic cells' potential in anti-cancer treatment. Increasing knowledge of dendritic cell biology is leading to improved methods for their preparation for clinical application. Unfortunately, there is to date no consensus specifying optimal conditions for dendritic cell preparation in vitro. This review summarizes the methods used for preparing myeloid dendritic cells derived from monocytic precursors while focusing on cytokine cocktails used for their growth, maturation, and functional adjustment.