Background:Immune fitness refers to the body's capacity to respond to health challenges, such as infections, by activating an appropriate immune response. The aim of the current study was to investigate the relationship between oral and gut microbiota community structure and immune fitness scores. Methods:Stool and saliva samples were collected to assess compositions of both oral and gut microbiota. Immune fitness was assessed with a single-item scale ranging from 0 (very poor) to 10 (excellent). Additionally, saliva samples were analyzed to measure the concentrations (pg/ml) of pro-inflammatory biomarkers interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor-alpha (TNF-α). Spearman's correlations were computed between microbiota abundance, immune fitness, and salivary biomarker levels. Bootstrapping was used to adjust for the relatively small sample size in the correlation analysis. Results:A total of 29 healthy participants (15 males; 14 females) enrolled in the study, with a mean age of 21.1 years old. Analysis of the salivary microbiota revealed significant negative correlations between self-reported immune fitness scores and the relative abundances of putative oral proinflammatory genera Selenomonas (r = -0.610), and Lachnospiraceae uncultured (r = -0.501). In the fecal microbiota, immune fitness scores showed a significant positive correlation with the relative abundance of putative beneficial butyrate-producing genus Lachnoclostridium (r = 0.513), and significant negative correlations with commensal gut bacterial genera Colidextribacter (r = -0.582) and Lachnospiraceae FCS020 group (r = -0.504). Conclusion:Self-reported immune fitness is associated with the oral and gut microbiota community. The findings demonstrate the importance of microbiota in immune function and support the use of self-assessment scales to evaluate immune fitness.

Immune fitness is the body’s capacity to respond to health challenges (such as infections) by activating an appropriate immune response. Adequate immune fitness is crucial to maintaining health and preventing and resolving disease. Control day data from an experimental study among 29 healthy volunteers were evaluated to determine the consistency of immune fitness ratings throughout the day. The single-item immune fitness scale was completed hourly, from 09:30 to 15:30. As a comparison, mood was assessed with the Profiles of Mood States-Short Form, including subscales for vigor, fatigue, tension, depression, and anger. The analyses revealed that single-item immune fitness scores were stable throughout the day. In contrast, as expected, assessments of fatigue and vigor varied throughout the day, showing more energy in the morning assessments and less energy in the afternoon assessments. Tension, depression, and anger scores also remained stable throughout the day. In conclusion, this study demonstrates that single-item immune fitness ratings remain consistent and stable throughout the day. Therefore, the time of day at which participants assess their immune fitness does not influence the outcomes in clinical trials. Future studies in larger, more diverse samples can be conducted to confirm these findings.

ObjectiveUsing benzodiazepines and certain antidepressants is associated with an increased risk of motor vehicle crashes due to impaired driving skills. Hence, several countries prohibit people who use these drugs from driving. Traffic regulations for driving under the influence of these drugs are, however, largely based on single-dose studies with healthy participants. The effects of drugs on chronic users may be different because of potential development of tolerance or by adapting behavior. In this study, we test the effects of anti-depressants, hypnotics, or anxiolytics use on driving performance in patients who use these drugs for different durations and compare the effects to healthy controls' performance.MethodsSixty-six healthy controls and 82 medication users were recruited to perform four drives in a driving simulator. Patients were divided into groups that used anti-depressants, hypnotics, or anxiolytics, for shorter or longer than 3 years (i.e. LT3- or LT3+, respectively). The minimum term of use was 6 months. Driving behavior was measured in terms of longitudinal and lateral control (speed variability and Standard Deviation of Lateral Position: SDLP), brake reaction time, and time headway. Impaired driving performance was defined as performing similar to driving with a Blood Alcohol Concentration of 0.5 parts per thousand or higher, determined by means of non-inferiority analyses.ResultsReaction time analyses revealed inconclusive findings in all groups. No significant performance differences between matched healthy controls, LT3- (n = 2), and LT3+ (n = 8) anxiolytics users were found. LT3+ antidepressants users (n = 12) did not perform inferior to their matched controls in terms of SDLP. LT3- hypnotics users (n = 6) showed more speed variability than their matched healthy controls, while this effect was not found for the LT3+ group (n = 14): the latter did not perform inferior to the healthy controls. Regarding Time Headway, no conclusions about the LT3- hypnotics group could be drawn, while the LT3+ group did not perform inferior compared to the control group.ConclusionsThe small number of anxiolytics users prohibits drawing conclusions about clinical relevance. Although many outcomes were inconclusive, there is evidence that some elements of complex driving performance may not be impaired (anymore) after using antidepressants or hypnotics longer than 3 years.

The combination of negative mental and physical symptoms which can be experienced after a single episode of alcohol consumption, starting when blood alcohol concentration (BAC) approaches zero, are collectively referred to as the alcohol hangover. Previous research revealed that 10 to 20% of drinkers claim not to experience next-day hangovers. Past studies were usually limited to single timepoint assessments. The aim of the current semi-naturalistic study was to compare the next-day effects of an evening of alcohol consumption of self-reported hangover-resistant drinkers (n = 14) with those of a group of self-reported hangover-sensitive drinkers (n = 15) at hourly timepoint throughout the day (09:30 until 15:30). Assessments of 23 hangover symptoms, mood (Profiles of Mood States-Short Form), and daytime sleepiness (Karolinska Sleepiness Scale) were made hourly after both an alcohol day and an alcohol-free control day. Additional morning assessments were made for mood (State-Trait Anxiety Inventory-Y, Beck's Depression Inventory-II), risk-taking behavior (RT-18), past night sleep (Groningen Sleep Quality Scale), alcohol consumption, and activities during the test days. No significant differences were found regarding the amount of alcohol consumed and the total sleep time of the two groups. The hangover-sensitive group reported having a hangover as well as the presence of a variety of hangover-related symptoms, which were most severe in the morning and then gradually decreased during the day. The most frequently reported and most severe symptoms were sleepiness and fatigue, concentration problems, and headache. In contrast, the hangover-resistant group reported the absence of a hangover and the presence and severity of next-day symptoms did not significantly differ from the control day, except for increased fatigue and reduced vigor. The next-day effects on sleepiness-related complaints and vigor were significantly more pronounced among hangover-sensitive drinkers compared to hangover-resistant drinkers. In conclusion, contrary to hangover-resistant drinkers, hangover-sensitive drinkers report a variety of hangover symptoms that gradually ease during the day, but are still present in the afternoon.

Background: Survey research found poorer baseline immune fitness for self-reported hangover-sensitive drinkers compared to hangover-resistant drinkers. However, up to now a limited number of clinical studies revealed mixed results regarding the relationship between the concentrations of biomarkers of systemic inflammation in blood or saliva with hangover severity, and could not differentiate between hangover-sensitive drinkers and hangover-resistant drinkers. The aim of this study was to assess immune fitness and saliva biomarkers of systemic inflammation at multiple timepoints following an alcohol day and alcohol-free control day. Methods: The study had a semi-naturalistic design. In the evening before the test days, participants were not supervised. They could drink ad libitum drinking on the alcohol test day and refrained from drinking alcohol on the control day. Activities and behaviors on the alcohol and control day were reported the follow morning. On both test days, from 09:30 to 15:30, hourly assessments of immune fitness (single-item scale) and overall hangover severity (singleitem scale) were made and saliva samples were collected for biomarker assessments. Results: N = 14 hangoverresistant drinkers and n = 15 hangover-sensitive drinkers participated in the study. The amount of alcohol consumed on the alcohol day did not significantly differ between the hangover-resistant group (mean (SD) of 13.5 (7.9) alcoholic drinks) and the hangover-sensitive group (mean (SD) of 12.4 (4.4) alcoholic drinks). All hangover-sensitive drinkers reported having a hangover following the alcohol day (overall hangover severity score 6.1 (on a 0-10 scale) at 09:30, gradually decreasing to 3.3 at 15:30), whereas the hangover-resistant drinkers reported no hangover. On the control day, immune fitness of the hangover-sensitive group was significantly poorer than the hangover-resistant group. On the alcohol day, both groups showed a significant reduction in immune fitness. The effect was evident throughout the day, but significantly more pronounced in the hangover-sensitive group than the hangover-resistant group. No significant differences between the groups were found at any time point on the two test days for saliva concentrations of Interleukin (IL)-1 & beta;, IL-6, IL-8, and tumor necrosis factor (TNF)-& alpha;. Conclusions: Whereas hangover-sensitive drinkers reported a hangover following an alcohol day and hangover-resistant drinkers did not, both groups reported significantly reduced immune fitness throughout the day. However, the reduction in immune fitness among hangover-sensitive drinkers was significantly more pronounced in comparison to the hangover-resistant group.

Background: Intranasal esketamine demonstrates rapid improvement of depressive symptoms. However, transient adverse effects (dissociation, sedation and dizziness) may occur, which could impact driving performance. Aims: To evaluate the effects of 84 mg intranasal esketamine on driving performance in unipolar major depressive disorder (MDD) or persistent depressive disorder (PDD) patients. Methods: The study consisted of two parts. Part A was a single-blind, double-dummy, randomized three-period, cross-over study to compare effects of esketamine versus placebo on next morning driving, 18 ± 2 h post-treatment. Alcohol was administered to demonstrate assay sensitivity. In Part B, same-day driving, 6 ± 0.5 hours post-treatment, was assessed during twice weekly esketamine administration for 3 weeks. Twenty-seven patients with mild-to-moderate MDD or PDD without psychotic features completed a 100 km on-the-road driving test on a public highway in normal traffic. The primary outcome was standard deviation of lateral position (SDLP; cm; weaving of car). Results: In Part A, alcohol impaired driving performance compared to placebo: Least-square means (95% CI), p-value for delta SDLP (cm) compared with placebo: (ΔSDLP = + 1.83 (1.03; 2.62), p < 0.001), whereas esketamine did not: (ΔSDLP = −0.23 (−1.04; 0.58), p = 0.572). In Part B, weekly driving tests showed no differences between placebo baseline SDLP and after esketamine administration over 3 weeks: Day 11: (ΔSDLP = −0.96 (−3.72; 1.81), p = 0.493), Day 18: (ΔSDLP = −0.56 (−3.33; 2.20), p = 0.686) and Day 25: (ΔSDLP = −1.05 (−3.82; 1.71), p = 0.451). Conclusions: In this study, esketamine did not impair on-road driving performance the next morning following a single dose, or on same day after repeated administration.

This article provides an overview of the design and methodology of the "Corona lockdown: how fit are you?" (CLOFIT) study, including the questionnaires and scales that were included in the online survey. The aim of the CLOFIT study was to investigate the psychosocial and health consequences of the coronavirus disease 2019 (COVID-19) pandemic in the Netherlands. The survey was conducted among the Dutch population to collect data on immune fitness and the psychological and health consequences of the 2019 coronavirus disease (COVID-19) pandemic lockdown in the Netherlands. The CLOFIT dataset contains measures from N = 1910 participants and is broadly representative of the Dutch general population. The dataset represents both sexes, a range of ages including the elderly, different education levels, and ethnic backgrounds. The cohort also includes people with a diverse health status and range of medication use.

This study investigated immunological changes during an alcohol hangover, and the possible difference between hangover-resistant and hangover-sensitive drinkers in terms of immune reactivity. Using a semi-naturalistic design, N = 36 healthy social drinkers (18 to 30 years old) provided saliva samples on a control day (after drinking no alcohol) and on a post-alcohol day. Hangover severity was rated directly after saliva collection. Cytokine concentrations, interleukin (IL)-1β, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α, and hangover severity were compared between both test days and between hangover-sensitive and -resistant drinkers. Data from N = 35 drinkers (17 hangover-sensitive and 18 hangover-resistant) were included in the statistical analyses. Relative to the control day, there were significant increases in saliva IL-6 and IL-10 concentrations on the post-alcohol day. No significant differences in cytokine concentrations were found between hangover-sensitive and hangover-resistant drinkers, nor did any change in cytokine concentration correlate significantly with hangover severity. In line with previous controlled studies assessing cytokines in blood, the current naturalistic study using saliva samples also demonstrated that the immune system responds to high-level alcohol intake. However, further research is warranted, as, in contrast to previous findings in blood samples, changes in saliva cytokine concentrations did not differ significantly between hangover-sensitive and hangover-resistant drinkers, nor did they correlate significantly with hangover severity.

Assessment of the presence and severity of alcohol hangovers relies on the subjective method of self-report. Therefore, there is a need of adequate biomarkers that (1) correlate significantly with hangover severity, and (2) correspond to the level of hangover-related performance impairment objectively. In this naturalistic study, n = 35 social drinkers participated. Urine samples were obtained the morning after alcohol consumption and after an alcohol-free control day. Concentrations of 5-hydroxytryptophol (5-HTOL), 5-hydroxyindoleacetic acid (5-HIAA) and the 5-HTOL/5-HIAA ratio were determined. The results confirm previous findings that 5-HTOL and the 5HTOL/5-HIAA ratio are useful biomarkers of recent alcohol consumption. Significant correlations were found with the amount of alcohol consumed, total drink time, and estimated BAC. However, urine concentrations of 5-HTOL and 5-HIAA (and their ratio 5HTOL/5-HIAA) did not significantly correlate with hangover severity. In conclusion, urine 5-HTOL, 5-HIAA, and the 5HTOL/5-HIAA ratio cannot be considered to be suitable biomarkers of alcohol hangover.

The Western 24 h society poses great psychological and physical demands on people, which may result in complaints such as stress or being overworked, and reduced immune fitness. Having a holiday may be a good way to reduce work-related stress and reduced mood and improve perceived immune fitness. Therefore, the aim of the current study was to assess the impact of having a holiday or work on perceived immune fitness and mood. A survey was held among N = 246 young adults who were on holiday in Fiji, and N = 87 subjects who were in Fiji for work. The sample comprised both students and individuals with a job at home. Past year immune status was assessed with the Immune Status Questionnaire (ISQ). Current perceived immune functioning and mood were rated from 0 (very poor) to 10 (excellent). Assessments were made for two occasions: (1) the current situation (in Fiji), and (2) at home (before traveling). Compared to being at home, both students and working individuals on holiday in Fiji reported significantly improved immune fitness and significantly improved mood. For example, both groups reported reduction of stress of about 60% while in Fiji. In students who came to Fiji for work or spending a holiday, improvements in perceived immune fitness were more pronounced than in working people coming on holiday in Fiji. In contrast, working people on holiday reported greater improvements in mood compared to students. The magnitude of improvements were significantly greater among women than men. In conclusion, the data suggest that both having a holiday or working in Fiji is associated with significant improvements of mood, which were themselves associated with improved immune fitness. The findings are of importance for the tourism industry as they demonstrate that, in addition to leisure (or being active) as a purpose for having a holiday, the observed mental health benefits and improved perceived immune fitness provide an additional motive to have a holiday.

Previous research reported cognitive and psychomotor impairments in long‐term users of benzodiazepine receptor agonists (BZRAs). This article explores the role of acute intoxication and clinical complaints.

Various factors may contribute to alcohol hangover severity. The purpose of the current investigation was to evaluate the possible impact of alcohol consumption patterns, perceived immune status, and baseline fatigue on hangover severity. A survey was completed by a convenience sample of N = 199 Dutch students who reported on their latest past month's heavy drinking occasion, including subjective intoxication (perceived drunkenness) and next-day hangover severity, which were rated on single-item scales ranging from 0 (absent) to 10 (extreme). In addition, perceived (momentary) immune fitness was assessed, and the Checklist Individual Strength (CIS) was completed to assess baseline fatigue. The analysis revealed that instead of the amount of alcohol consumed or estimated blood alcohol concentration, it appeared that subjective intoxication (i.e., level of drunkenness) was the most important determinant of alcohol hangover severity. Especially in men, albeit modest, it was perceived that immune fitness also significantly contributed to the level of hangover severity experienced.

The limited number of available studies that examined the pathology of alcohol hangover focused on biomarkers of alcohol metabolism, oxidative stress and the inflammatory response to alcohol as potentially important determinants of hangover severity. The available literature on alcohol metabolism and oxidative stress is reviewed in this article. The current body of evidence suggests a direct relationship between blood ethanol concentration and hangover severity, whereas this association is not significant for acetaldehyde. The rate of alcohol metabolism seems to be an important determinant of hangover severity. That is, fast elimination of ethanol is associated with experiencing less severe hangovers. An explanation for this observation may be the fact that ethanol—in contrast to acetaldehyde—is capable of crossing the blood–brain barrier. With slower ethanol metabolism, more ethanol is able to reach the brain and elicit hangover symptoms. Hangover severity was also significantly associated with biomarkers of oxidative stress. More oxidative stress in the first hours after alcohol consumption was associated with less severe next-day hangovers (i.e., a significant negative correlation was found between hangover severity and malondialdehyde). On the contrary, more oxidative stress at a later stage after alcohol consumption was associated with having more severe next-day hangovers (i.e., a significant positive correlation was found between hangover severity and 8-isoprostane). In conclusion, assessment of biomarkers of alcohol metabolism suggests that fast elimination of ethanol is associated with experiencing less severe hangovers. More research is needed to further examine the complex interrelationship between alcohol metabolism, the role of acetaldehyde and oxidative stress and antioxidants, and the pathology of the alcohol hangover.

The 2010 Alcohol Hangover Research Group consensus paper defined a cutoff blood alcohol concentration (BAC) of 0.11% as a toxicological threshold indicating that sufficient alcohol had been consumed to develop a hangover. The cutoff was based on previous research and applied mostly in studies comprising student samples. Previously, we showed that sensitivity to hangovers depends on (estimated) BAC during acute intoxication, with a greater percentage of drinkers reporting hangovers at higher BAC levels. However, a substantial number of participants also reported hangovers at comparatively lower BAC levels. This calls the suitability of the 0.11% threshold into question. Recent research has shown that subjective intoxication, i.e., the level of severity of reported drunkenness, and not BAC, is the most important determinant of hangover severity. Non-student samples often have a much lower alcohol intake compared to student samples, and overall BACs often remain below 0.11%. Despite these lower BACs, many non-student participants report having a hangover, especially when their subjective intoxication levels are high. This may be the case when alcohol consumption on the drinking occasion that results in a hangover significantly exceeds their "normal" drinking level, irrespective of whether they meet the 0.11% threshold in any of these conditions. Whereas consumers may have relative tolerance to the adverse effects at their "regular" drinking level, considerably higher alcohol intake-irrespective of the absolute amount-may consequentially result in a next-day hangover. Taken together, these findings suggest that the 0.11% threshold value as a criterion for having a hangover should be abandoned.

Assessments in blood and saliva suggests that the amount of ethanol present in the first hours after alcohol consumption and into the following morning is associated with hangover severity. The current analysis determines how ethanol elimination rate is related to hangover severity reported throughout the day.n= 8 subjects participated in two studies. The first was a naturalistic study comprising an evening of alcohol consumption. Hangover severity was assessed hourly from 10 a.m. to 4 p.m., using a 1-item hangover severity scale ranging from 0 (absent) to 10 (extreme). The second study comprised a highly controlled alcohol challenge to reach a breath alcohol concentration (BrAC) of 0.05%. Breathalyzer tests were conducted every 5 min until BrAC reached zero. The ethanol elimination rate, expressed in BrAC%/hour, was computed by dividing the peak BrAC (%) by the time to BrAC of zero (h). At 11:00, 13:00, and 14:00, there were significant negative partial correlations, controlling for estimated BrAC, between ethanol elimination rate and hangover severity. The findings suggest that drinkers with a faster ethanol elimination rate experience less severe hangovers. The observations should be confirmed in a larger sample of subjects who participate in a single study that assesses both hangover severity and ethanol elimination rate.

Objective To assess driving performance and neurocognitive skills of long-term users of sedating antidepressants, in comparison to healthy controls. Methods Thirty-eight long-term (>6 months) users of amitriptyline (n= 13) and mirtazapine (n= 25) were compared to 65 healthy controls. Driving performance was assessed using a 1-h standardised highway driving test in actual traffic, with road-tracking error (standard deviation of lateral position [SDLP]) being the primary measure. Secondary measures included neurocognitive tasks related to driving. Performance differences between groups were compared to those of blood alcohol concentrations of 0.5 mg/ml to determine clinical relevance. Results Compared to controls, mean increase in SDLP of all antidepressant users was not significant, nor clinically relevant (+0.75 cm, 95% CI: -0.83 cm; +2.33 cm). However, users treated less than 3 years (n= 20) did show a significant and clinically relevant increase in SDLP (+2.05 cm). No significant effects were observed on neurocognitive tasks for any user group, although large individual differences were present. Most results from neurocognitive tests were inconclusive, while a few parameters confirmed non-inferiority for users treated longer than 3 years. Conclusion The impairing effects of antidepressant treatment on driving performance and neurocognition mitigate over time following long-term use of 3 years.