H2OAthletes study protocol: effects of hydration changes on neuromuscular function in athletes.

We aim to understand the effects of hydration changes on athletes' neuromuscular performance, on body water compartments, fat-free mass hydration and hydration biomarkers and to test the effects of the intervention on the response of acute dehydration in the hydration indexes. The H2OAthletes study (clinicaltrials.gov ID: NCT05380089) is a randomised controlled trial in thirty-eight national/international athletes of both sexes with low total water intake (WI) (i.e. < 35·0 ml/kg/d). In the intervention, participants will be randomly assigned to the control (CG, n 19) or experimental group (EG, n 19). During the 4-day intervention, WI will be maintained in the CG and increased in the EG (i.e. > 45·0 ml/kg/d). Exercise-induced dehydration protocols with thermal stress will be performed before and after the intervention. Neuromuscular performance (knee extension/flexion with electromyography and handgrip), hydration indexes (serum, urine and saliva osmolality), body water compartments and water flux (dilution techniques, body composition (four-compartment model) and biochemical parameters (vasopressin and Na) will be evaluated. This trial will provide novel evidence about the effects of hydration changes on neuromuscular function and hydration status in athletes with low WI, providing useful information for athletes and sports-related professionals aiming to improve athletic performance.

Interindividual variability in energy intake and expenditure during a weight loss intervention.

INTRODUCTION: Behavioral compensations may occur as a response to a negative energy balance. The aim of this study was to explore the associations between changes in energy intake (EI) and changes in physical activity (PA, min/day; kcal/d) as a response to a weight loss (WL) intervention and to understand if interindividual differences occur in EI and energy expenditure (EE). METHODS: Eighty-one participants [mean (SD): age = 42.8 (9.4)y, BMI = 31.2 (4.4)kg/m2, 37% females] divided in intervention (IG, n = 43) and control group (CG, n = 38) were included. The IG underwent a moderate energy restriction (300-500 kcal/d). EI was measured through the intake-balance method. Non-exercise PA (NEPA) and exercise (through logbook) were assessed by accelerometery. The EE in NEPA (NEAT) and in exercise (EiEE) was calculated by applying the Freedson Combination'98 algorithm over the time spent in these activities. Pearson correlations were performed in IG to examine associations between EE components, EI and body composition. To understand if interindividual differences were observed, the SD of individual response (SDIR) and the smallest worthwhile change (SWC, SDbaselineCG×0.2) were calculated. RESULTS: Changes in EI [Δ EI, (kcal/d)] was negatively associated with Δ exercise (min/d:r = -0.413, p = 0.045; %:r = -0.846, p = 0.008) and with Δ EiEE (kcal/d:r = -0.488, p = 0.016; %:r = -0.859, p = 0.006). A negative correlation was found between Δ sedentary time and Δ NEPA (min/d:r = -0.622, p = 0.002; %:r = -0.487, p = 0.018). An interindividual variability was found for EI(SDIR = 151.6, SWC = 72.3) and EE (SDIR = 165, SWC = 134). CONCLUSIONS: Decreases in EI were not associated to compensatory responses such as decreases in PA and/or increases in sedentary time. Interindividual variability was found for EI and EE. Nevertheless, behavioral compensations and the interindividual variability should be considered when implementing WL interventions, to increase the likelihood of achieving sustainable results. (clinicaltrials.gov ID: NCT03031951).

Methanolic Extract and Brominated Compound from the Brazilian Marine Sponge Aplysina fulva Are Neuroprotective and Modulate Inflammatory Profile of Microglia.

Neurodegenerative diseases involve neuroinflammation and a loss of neurons, leading to disability and death. Hence, the research into new therapies has been focused on the modulation of the inflammatory response mainly by microglia/macrophages. The extracts and metabolites of marine sponges have been presented as anti-inflammatory. This study evaluated the toxicity of an extract and purified compound from the Brazilian marine sponge Aplysina fulva as well as its neuroprotection against inflammatory damage associated with the modulation of microglia response. PC12 neuronal cells and neonatal rat microglia were treated with the methanolic extract of A. fulva (AF-MeOH, 0.1-200 µg/mL) or with its purified dimethyl ketal of 3,5-dibromoverongiaquinol (AF-H1, 0.1-100 µM). Cytotoxicity was determined by MTT tetrazolium, Trypan blue, and propidium iodide; microglia were also treated with the conditioned medium (CM) from PC12 cells in different conditions. The microglia phenotype was determined by the expression of Iba-1 and CD68. AF-MeOH and AF-H1 were not toxic to PC12 or the microglia. Inflammatory damage with Escherichia coli lipopolysaccharide (LPS, 5 µg/mL) was not observed in the PC12 cells treated with AF-MeOH (1-10 µg/mL) or AF-H1 (1-10 µM). Microglia subjected to the CM from PC12 cells treated with LPS and AF-MeOH or AF-H1 showed the control phenotype-like (multipolar, low-CD68), highlighting the anti-neuroinflammatory and neuroprotective effect of components of this marine sponge.

Co-option of immune effectors by the hormonal signalling system triggering metamorphosis in Drosophila melanogaster.

Insect metamorphosis is triggered by the production, secretion and degradation of 20-hydroxyecdysone (ecdysone). In addition to its role in developmental regulation, increasing evidence suggests that ecdysone is involved in innate immunity processes, such as phagocytosis and the induction of antimicrobial peptide (AMP) production. AMP regulation includes systemic responses as well as local responses at surface epithelia that contact with the external environment. At pupariation, Drosophila melanogaster increases dramatically the expression of three AMP genes, drosomycin (drs), drosomycin-like 2 (drsl2) and drosomycin-like 5 (drsl5). We show that the systemic action of drs at pupariation is dependent on ecdysone signalling in the fat body and operates via the ecdysone downstream target, Broad. In parallel, ecdysone also regulates local responses, specifically through the activation of drsl2 expression in the gut. Finally, we confirm the relevance of this ecdysone dependent AMP expression for the control of bacterial load by showing that flies lacking drs expression in the fat body have higher bacterial persistence over metamorphosis. In contrast, local responses may be redundant with the systemic effect of drs since reduction of ecdysone signalling or of drsl2 expression has no measurable negative effect on bacterial load control in the pupa. Together, our data emphasize the importance of the association between ecdysone signalling and immunity using in vivo studies and establish a new role for ecdysone at pupariation, which impacts developmental success by regulating the immune system in a stage-dependent manner. We speculate that this co-option of immune effectors by the hormonal system may constitute an anticipatory mechanism to control bacterial numbers in the pupa, at the core of metamorphosis evolution.

Food reward associations with motivational eating behavior traits and body mass index in Portuguese former elite athletes.

BACKGROUND: Motivational eating behavior traits (i.e. eating motivations and intuitive eating) have an important role in body weight regulation, as do food reward processes. Their associations might help explain different responses to food stimulus in the current environment but have never been explored. This study's primary goal was to investigate food reward associations with eating motivations, intuitive eating dimensions and body mass index in former Portuguese elite athletes with overweight/obesity. As a first step, a cultural adaptation of the Leeds Food Preference Questionnaire (LFPQ) was created and validated in an online-surveyed Portuguese sample. RESULTS: Step 1: Analysis from an online survey (N = 348; 69.8% female) conducted to validate the food images from the cultural adaptation of the LFPQ showed that most food images were properly recognized in terms of their fat and sweet content by the Portuguese population, except for some savory items. Step 2: Regarding our primary analysis in 94 former elite athletes with overweight/obesity, self-determined motivations to regulate eating and (to a lower extent) more body-food congruent choices (both markers for healthier eating behaviors) were associated with more favorable food reward outcomes, as opposed to non-self-determined motivations. Less emotional (more intuitive) eaters presented higher implicit wanting for low-fat sweet foods compared to more emotional eaters. CONCLUSION: These findings suggest LFPQ usefulness to evaluate food preferences and detect relevant associations between food reward and motivational eating behavior traits in former elite athletes with overweight/obesity. Health professionals are encouraged to create need-supportive environments that foster self-determined motivations and help individuals make healthier food choices. © 2023 Society of Chemical Industry.

Athletes with different habitual fluid intakes differ in hydration status but not in body water compartments.

Physiological differences have been reported between individuals who have habitual low (LOW) and high (HIGH) water intake (WI). The aims of this study were to explore body water compartments, hydration status, and fat-free mass (FFM) hydration of elite athletes exposed to different habitual WI. A total of 68 athletes (20.6 ± 5.3 years, 23 females) participated in this observational cross-sectional study. Total WI was assessed by seven-day food diaries and through WI, athletes were categorized as HIGH (n = 28, WI≥40.0 mL/kg/d) and LOW (n = 40, WI≤35.0 mL/kg/d). Total body water (TBW) and extracellular water (ECW) were determined by dilution techniques and intracellular water (ICW) as TBW-ECW. Hydration status was assessed by urine-specific gravity (USG) using a refractometer. Fat (FM) and FFM were assessed by dual-energy X-ray absorptiometry (DXA). The FFM hydration was calculated by TBW/FFM. The USG was statistically different between groups for females (LOW: 1.024 ± 0.003; HIGH: 1.015 ± 0.006; p = 0.005) and males (LOW: 1.024 ± 0.002; HIGH: 1.018 ± 0.005; p < 0.001). No differences between groups were detected in body water compartments and FFM hydration in both sexes (p > 0.05). Multiple regression showed that WI remains a predictor of USG regardless of FFM, age, and sex (ß = -0.0004, p < 0.01). We concluded that LOW athletes were classified as dehydrated through USG although their water compartments were not different from HIGH athletes. These results suggest that LOW athletes may expectedly maintain the body water compartments' homeostasis through endocrine mechanisms. Interventions should be taken to encourage athletes to have sufficient WI to maintain optimal hydration.

Prediction of body water compartments by raw bioelectrical impedance parameters in athletes: Comparison between series and parallel measurements.

BACKGROUND: The aim of this study was to determine the predictive role of series and parallel bioelectrical impedance-derived parameters in predicting total body (TBW), intracellular (ICW), and extracellular water (ECW) in athletes. METHODS: This cross-sectional study analyzed 134 male (21.33 ± 5.11 years) and 64 female (20.45 ± 5.46 years) athletes. Using dilution techniques, TBW and ECW were determined while ICW was the difference between both. Raw and standardized for height (/H) bioelectrical resistance (R), reactance (Xc), and impedance (Z) values were obtained using a phase-sensitive device at a single frequency in a series array (s). These were mathematically transformed in a parallel array (p) and capacitance (CAP). Fat-free mass (FFM) was assessed by dual-energy X-ray absorptiometry. RESULTS: Multiple regressions adjusted for age and FFM show that R/Hs, Z/Hs, R/Hp, and Z/Hp were significant predictors of TBW (p < 0.001 in females and males). While Xc/Hs did not predict ICW, Xc/Hp was a predictor (p < 0.001 in females and Males). In females, R/H and Z/H predicted similarly TBW, ICW, and ECW. In males, R/Hs was considered a better predictor than R/Hp for TBW and ICW, and the Xc/Hp was considered the best predictor for ICW. Another significant predictor of ICW was CAP (p < 0.001 in females and males). CONCLUSION: This study highlights the potential value of parallel bioelectrical impedance values to identify fluid compartments in athletes as an alternative to the regularly used series measurements. Moreover, this study supports Xc in parallel, and ultimately CAP, as valid indicators of cell volume.

Does adaptive thermogenesis occur after weight loss in adults? A systematic review.

Adaptive thermogenesis (AT) has been proposed to be a compensatory response that may resist weight loss (WL) and promote weight regain. This systematic review examined the existence of AT in adults after a period of negative energy balance (EB) with or without a weight stabilisation phase. Studies published until 15 May 2020 were identified from PubMed, Cochrane Library, EMBASE, MEDLINE, SCOPUS and Web of Science. Inclusion criteria included statistically significant WL, observational with follow-up or experimental studies, age > 18y, sample size ≥10 participants, intervention period ≥ 1week, published in English, objective measures of total daily energy expenditure (EE) (TDEE), resting EE (REE) and sleeping EE(SEE). The systematic review was registered at PROSPERO (2020 CRD42020165348). A total of thirty-three studies comprising 2528 participants were included. AT was observed in twenty-seven studies. Twenty-three studies showed significant values for AT for REE (82·8 %), four for TDEE (80·0 %) and two for SEE (100 %). A large heterogeneity in the methods used to quantify AT and between subjects and among studies regarding the magnitude of WL and/or of AT was reported. Well-designed studies reported lower or non-significant values for AT. These findings suggest that although WL may lead to AT in some of the EE components, these values may be small or non-statistically significant when higher-quality methodological designs are used. Furthermore, AT seems to be attenuated, or non-existent, after periods of weight stabilisation/neutral EB. More high-quality studies are warranted not only to disclose the existence of AT but also to understand its clinical implications on weight management outcomes.

Effects of a 4-month active weight loss phase followed by weight loss maintenance on adaptive thermogenesis in resting energy expenditure in former elite athletes.

PURPOSE: Despite adaptive thermogenesis (AT) being studied as a barrier to weight loss (WL), few studies assessed AT in the resting energy expenditure (REE) compartment after WL maintenance. The aim of this study was twofold: (1) to understand if AT occurs after a moderate WL and if AT persists after a period of WL maintenance; and (2) if AT is associated with changes in body composition, hormones and energy intake (EI). METHODS: Ninety-four participants [mean (SD); BMI, 31.1(4.3)kg/m2; 43.0(9.4)y; 34% female] were randomized to intervention (IG, n = 49) or control groups (CG, n = 45). Subjects underwent a 1-year lifestyle intervention, divided in 4 months of an active WL followed by 8 months of WL maintenance. Fat mass (FM) and fat-free mass (FFM) were measured by dual-energy X-ray absorptiometry and REE by indirect calorimetry. Predicted REE (pREE) was estimated through a model using FM, FFM. EI was measured by the "intake-balance" method. RESULTS: For the IG, the weight and FM losses were - 4.8 (4.9) and - 11.3 (10.8)%, respectively (p < 0.001). A time-group interaction was found between groups for AT. After WL, the IG showed an AT of -85(29) kcal.d-1 (p < 0.001), and remained significant after 1 year [AT = - 72(31)kcal.d-1, p = 0.031]. Participants with higher degrees of restriction were those with an increased energy conservation (R = - 0.325, p = 0.036 and R = - 0.308, p = 0.047, respectively). No associations were found between diet adherence and AT. Following a sub-analysis in the IG, the group with a higher energy conservation showed a lower WL and fat loss and a higher initial EI. CONCLUSION: AT in REE occurred after a moderate WL and remained significant after WL maintenance. More studies are needed to better clarify the mechanisms underlying the large variability observed in AT and providing an accurate methodological approach to avoid overstatements. Future studies on AT should consider not only changes in FM and FFM but also the FFM composition.

Adaptive thermogenesis after moderate weight loss: magnitude and methodological issues.

PURPOSE: The aim of this study was (1) to assess AT through 13 different mathematical approaches and to compare their results; and (2) to understand if AT occurs after moderate WL. METHODS: Ninety-four participants [mean (SD); BMI, 31.1 (4.3) kg/m2; age, 43.0 (9.4) years; 34% females] underwent a 1-year lifestyle intervention (clinicaltrials.gov ID: NCT03031951) and were randomized to intervention (IG, n = 49) or control groups (CG, n = 45), and all measurements were made at baseline and after 4 months. Fat mass (FM) and fat-free mass (FFM) were measured by dual-energy X-ray absorptiometry and REE by indirect calorimetry. AT was assessed through 13 different approaches, varying in how REE was predicted and/or how AT was assessed. RESULTS: IG underwent a mean negative energy balance (EB) of 270 (289) kcal/day, p < 0.001), resulting in a WL of - 4.8 (4.9)% and an FM loss of - 11.3 (10.8)%. Regardless of approach, AT occurred in the IG, ranging from ~ - 65 to ~ - 230 kcal/day and three approaches showed significant AT in the CG. CONCLUSIONS: Regardless of approach, AT occurred after moderate WL in the IG. AT assessment should be standardized and comparisons among studies with different methodologies to assess AT must be avoided.

Comparison of two pharmacokinetic-pharmacodynamic models of rocuronium bromide during profound neuromuscular block: analysis of estimated and measured post-tetanic count effect.

BACKGROUND: Profound neuromuscular block (NMB) is important in surgeries where complete immobility is considered essential to improve tracheal intubation and surgical conditions. Rocuronium bromide is a commonly used NMB agent. This work describes a noninvasive approach for estimation of post-tetanic count (PTC) based on two pharmacokinetic (PK) models, the Saldien and the De Haes models. The aim was to investigate the rocuronium bromide PK-pharmacodynamic (PD) relationship in estimating the PTC effect during profound NMB. METHODS: In this prospective, non-randomised, observational study, an induction bolus of rocuronium bromide was administered followed by continuous infusion for maintenance of a PTC of 1-2. measured every 3 min. Measurements were analysed as discrete categorical data and by applying the nonlinear mixed-effect modelling approach. Performance of the selected models was evaluated through simulation model-based diagnostics, further assessing the precision of the parameter estimates and the performance of the models at the individual level. RESULTS: Data from 30 adult patients undergoing elective abdominal or neurosurgical procedures were included. Post-tetanic count response profiles during rocuronium bromide infusion were successfully characterised using the population PD analysis. The models showed a good performance for all PTC categories, albeit with a moderate over-prediction of PTC >6. CONCLUSIONS: Our findings indicate that using plasma concentrations of rocuronium bromide estimated with either of the two models, combined with a PD model, provides equal model performance when predicting PTC. These promising results may provide an important advance in guiding rocuronium bromide administration when profound NMB in routine clinical practice is desired.

Effectiveness of a lifestyle weight-loss intervention targeting inactive former elite athletes: the Champ4Life randomised controlled trial.

OBJECTIVES: Many athletes struggle in managing the end of their career, often gaining weight and adopting unhealthy lifestyles. Lifestyle programmes targeting former athletes who have gained substantial fat mass (FM) postsports career are lacking. We studied the effects of the Champ4Life programme on body composition and other health-related outcomes in former elite athletes with overweight or obesity. METHODS: Ninety-four former athletes(42.4±7.3 y, 34.0% female) were recruited and randomly assigned to either an intervention group (IG; n=49) or a control group (CG; n=45). The IG attended 12 educational sessions addressing physical activity, weight management and nutrition. They also had a nutrition appointment aimed to prescribe a moderate caloric deficit(~300-500 kcal/day). Dual-energy X-ray absorptiometry was used to assess body composition. The Short-Form Health Survey-36 questionnaire was used to measure general health-related quality of life. Blood samples were collected to assess cardiometabolic health parameters. RESULTS: At 12 months, the IG lost more weight (estimated difference (ED)=-5.3 kg; -6.9 to -3.8), total FM (ED=-4.1 kg; -5.4 to -2.8) and abdominal FM (ED=-0.49 kg; -0.64 to -0.33) than did the CG (p's<0.001). Cardiometabolic health markers also improved significantly (p<0.05) more in the IG at 12 months (insulin (ED=-4.9 µU/mL;-8.0 to -1.8); homoeostatic model assessment (ED=-1.2; -2.1 to -0.4); total cholesterol (ED=-21.8 mg/dL; -35.4 to -8.2); low-density lipoprotein (ED=18.2 mg/dL;-29.2 to -7.1)), as did quality-of-life dimensions (physical functioning (ED=11.7; 6.5 to 16.9); physical role (ED=17.6; 2.1 to 33.0); general health (ED=19.4; 11.4 to 27.4); vitality (ED=13.3; 5.3 to 21.3) and mental health (ED=12.3; 4.1 to 20.6)). CONCLUSIONS: The Champ4Life programme was effective in substantially reducing total and abdominal FM while preserving fat-free mass and improving health-related markers. These findings will enable evidence-based decisions when implementing lifestyle interventions targeting retired elite athletes. TRIAL REGISTERATION NUMBER: NCT03031951.

Between-devices agreement in obtaining raw bioelectrical parameters after a lifestyle intervention targeting weight loss in former athletes.

It is unclear if different bioelectrical impedance (BI) devices provide similar results regarding raw parameters [Resistance (R), Reactance (Xc), Phase Angle (PhA), and Impedance (Z)] for the same population/individual undergoing a weight loss intervention. The aim was to evaluate the cross-sectional and longitudinal agreement of raw data obtained by two BI devices in former athletes with overweight/obesity. Fifty-nine participants [mean (SD): 43.5 (9.2) years, 30.5 (4.0) kg/m2, 42% females] were included. All the assessments were performed before and after a 4-months lifestyle intervention targeting weight loss (WL). BI parameters were assessed at 50 kHz by two devices: a BI spectroscopy (Xitron Technologies, 4200B, San Diego, USA) and a phase-sensitive single-frequency device (BIA 101 AKERN, Florence, Italy). Cross-sectionally, BIS provided lower mean values for all parameters (0.4% for R, 1.6% for Xc, 1.0% for PhA and 0.4% for Z, p <0.001) compared to SF-BIA. In individuals with a WL≥2.5% (n =18), no longitudinal differences were found in any of the raw parameters between devices (p≥0.128) and there was no proportional bias (p≥0.408). Despite small baseline differences in raw BI parameters, both devices agreed in tracking changes over time at the group level but interpretation should be careful at the individual level.

Energy Availability Over One Athletic Season: An Observational Study Among Athletes From Different Sports.

During the athletic season, changes in body composition occur due to fluctuations in energy expenditure and energy intake. Literature regarding changes of energy availability (EA) is still scarce. The aim was to estimate EA of athletes from nonweight and weight-sensitive sports during the athletic season (i.e., preparatory and competitive phase). Eighty-eight athletes (19.1 ± 4.2 years, 21.8 ± 2.0 kg/m2, 27% females, self-reported eumenorrheic) from five sports (basketball [n = 29]; handball [n = 7]; volleyball [n = 9]; swimming [n = 18]; and triathlon [n = 25]) were included in this observational study. Energy intake and exercise energy expenditure were measured through doubly labeled water (over 7 days and considering neutral energy balance) and metabolic equivalents of tasks, respectively. Fat-free mass (FFM) was assessed through a four-compartment model. EA was calculated as EA = (energy intake - exercise energy expenditure)/FFM. Linear mixed models, adjusted for sex, were performed to assess EA for the impact of time by sport interaction. Among all sports, EA increased over the season: basketball, estimated mean (SE): 7.2 (1.5) kcal/kg FFM, p < .001; handball, 14.8 (2.9) kcal/kg FFM, p < .001; volleyball, 7.9 (2.8) kcal/kg FFM, p = .006; swimming, 8.7 (2.0) kcal/kg FFM, p < .001; and triathlon, 9.6 (2.0) kcal/kg FFM, p < .001. Eleven athletes (12.5%) had clinical low EA at the preparatory phase and none during the competitive phase. During both assessments, triathletes' EA was below optimal, being lower than basketballers (p < .001), volleyballers (p < .05), and swimmers (p < .001). Although EA increased in all sports, triathlon's EA was below optimal during both assessments. Risk of low EA might be seasonal and resolved throughout the season, with higher risk during the preparatory phase. However, in weight-sensitive sports, namely triathlon, low EA is still present.

Validity of water compartments estimated using bioimpedance spectroscopy in athletes differing in hydration status.

We aimed to validate bioelectrical impedance spectroscopy (BIS), compared with tracer dilution measurements, for assessing total body water (TBW), intracellular water (ICW), and extracellular water (ECW) in athletes differing in hydration status. A total of 201 athletes participated. Reference TBW and ECW were determined by deuterium and bromide dilution methods, respectively; ICW was calculated as TBW-ECW. Water compartments were estimated by BIS. Urine specific gravity (USG) classified athletes into well-hydrated (WH) (USG < 1.023), euhydrated (EH) (USG:1.024-1.026), and dehydrated (DH) (USG>1.027). No significant differences were found between BIS and the reference methods for WH, EH, and DH athletes for TBW, ICW nor ECW (p>0.05). Concordance of TBW and its compartments by method was significant (p < 0.001) with coefficients of determination ranging by hydration classification [EH:52-96%;DH:56-98%;WH:71-96%]. Bland-Altman analyses showed no trend for TBW and its compartments with the exception of ICW in the WH athletes. The 95% confidence BIS intervals for the WH group ranged from -3.08 to 2.68 kg for TBW, -4.28 to 4.14 kg for ICW, and -3.29 to 3.02 kg for ECW. For the EH athletes, the 95% confidence intervals ranged from -2.78 to 2.24 kg for TBW, -4.10 to 3.94 kg for ICW, and -3.44 to 3.06 kg for ECW. In DH group, TBW ranged between -1.99 and 2.01 kg, ICW between -3.78 and 6.34 kg, and ECW between -6.22 and 3.74 kg. These findings show that BIS is useful at a group level in assessing water compartments in athletes differing in hydration status. However, the usefulness of BIS is limited at an individual level, especially in dehydrated athletes.

Electromyographic assessment of blink reflex throughout the transition from responsiveness to unresponsiveness during induction with propofol and remifentanil.

General anesthesia is a reversible drug-induced state of altered arousal characterized by loss of responsiveness due to brainstem inactivation. Precise identification of the moment in which responsiveness is lost during the induction of general anesthesia is extremely important to provide information regarding an individual's anesthetic requirements and help intraoperative drug titration. To characterize the transition from responsiveness to unresponsiveness more objectively, we studied neurophysiologic-derived parameters of electromyographic records of electrically evoked blink reflex as a means of identifying the precise moment of loss of responsiveness. Twenty-five patients received a slow infusion of propofol until loss of corneal reflex while successive blink reflexes were elicited and recorded every 6 s. The level of anesthesia was assessed using an adapted version of the Richmond Agitation-Sedation Scale. Different variables of the blink reflex components were calculated and compared to the adapted version of the Richmond Agitation-Sedation score and the estimated effect-site propofol concentration. Baselines of the blink reflex responses were similar to those in literature. After propofol infusion started, the most susceptible component of the blink reflex to propofol was R2 (EC50 = 1.358 (95% CI 1.321, 1.396) µg/mL) and the most resistant was R1 (EC50 = 3.025 (95% CI 2.960, 3.090) µg/mL). Most of the patients (24 out of 25) lost the R1 component when they were still responsive to shaking and shouting and corneal reflex could be elicited clinically (time = 102.48 ± 33.00 s). Habituation was present in R2 but not in R1. The R1 component of the blink reflex was found to have a strong correlation with the adapted version of the Richmond Agitation-Sedation Scale, with amplitude correlating better than areas (ρ = - 0.721 (0.123) versus ρ = - 0.688 (0.165)). We found a strong correlation between the R1 component with the estimated propofol effect-site concentration, with amplitude correlating better than areas (ρ = - 0.838 (0.113) versus ρ = - 0.823 (0.153)) and between the clinical scale and the propofol concentration (ρ = 0.856 (0.060)). The area and amplitude of the R1 component showed to be indicators of predicting different levels of anesthesia (Pk = 0.672 (0.183) versus Pk = 0.709 (0.134)) and these are connected to the propofol concentrations (Pk = 0.593 (0.10)). Our results suggest that electrically evoked blink reflex could be used during the induction of anesthesia as a surrogate of the Richmond Agitation-Sedation Scale to provide an objective endpoint as far as a - 4. At this point, at the moment of loss of R1, the propofol infusion may be stopped, as overshooting increases slightly the effect-site concentration afterward and eventually reaching loss of responsiveness. If the desired target is not achieved, the infusion can then be resumed.

Foreseeing postoperative pain in neurosurgical patients: pupillometry predicts postoperative pain ratings-an observational study.

Pupillary reflex dilation (PRD) is triggered by noxious stimuli and diminished by opioid administration. In the postoperative period, PRD has been shown to be correlated with pain reporting and a useful tool to guide opioid administration. In this study we assessed whether pupillary measurements taken before extubation were related with the patient's reported pain in the Post-Anesthesia Care Unit (PACU) using the Numerical Rating Scale (NRS). Our objective was to evaluate the correlation of PRD and pupillary variables measured intraoperatively with postoperative pain under the same opioid concentration. This was a prospective observational study of 26 neurosurgical patients undergoing general anesthesia exclusively with propofol and remifentanil. A portable infrared pupillometer was used to provide an objective measure of pupil size and PRD (using the Pupillary Pain Index) before extubation. Pain ratings were obtained from patients after recovery of consciousness, while remifentanil was maintained at 2 ng/mL. A significant correlation was observed between NRS scores and pre-extubation PPI (rS = 0.62; P = 0.002), as well as between NRS scores and pupil diameter before tetanic stimulation PPI (rS = 0.56, P = 0.006). We also found a negative correlation between pupil diameter and age (rS = - 0.42, P = 0.04). The statistically significant correlation between pre-extubation PPI scores and NRS scores, as well as between the pupillary diameter before tetanic stimulation and NRS scores suggest the possibility of titrating analgesia at the end of the intraoperative period based on individual responses. This could allow clinicians to identify the ideal remifentanil concentration for the postoperative period.

Performance of blink reflex in patients during anesthesia induction with propofol and remifentanil: prediction probabilities and multinomial logistic analysis.

BACKGROUND: The amount of propofol needed to induce loss of responsiveness varied widely among patients, and they usually required less than the initial dose recommended by the drug package inserts. Identifying precisely the moment of loss of responsiveness will determine the amount of propofol each patient needs. Currently, methods to decide the exact moment of loss of responsiveness are based on subjective analysis, and the monitors that use objective methods fail in precision. Based on previous studies, we believe that the blink reflex can be useful to characterize, more objectively, the transition from responsiveness to unresponsiveness. The purpose of this study is to investigate the relation between the electrically evoked blink reflex and the level of sedation/anesthesia measured with an adapted version of the Richmond Agitation-Sedation Scale, during the induction phase of general anesthesia with propofol and remifentanil. Adding the blink reflex to other variables may allow a more objective assessment of the exact moment of loss of responsiveness and a more personalized approach to anesthesia induction. RESULTS: The electromyographic-derived features proved to be good predictors to estimate the different levels of sedation/anesthesia. The results of the multinomial analysis showed a reasonable performance of the model, explaining almost 70% of the adapted Richmond Agitation-Sedation Scale variance. The overall predictive accuracy for the model was 73.6%, suggesting that it is useful to predict loss of responsiveness. CONCLUSIONS: Our developed model was based on the information of the electromyographic-derived features from the blink reflex responses. It was able to predict the drug effect in patients undergoing general anesthesia, which can be helpful for the anesthesiologists to reduce the overwhelming variability observed between patients and avoid many cases of overdosing and associated risks. Despite this, future research is needed to account for variabilities in the clinical response of the patients and with the interactions between propofol and remifentanil. Nevertheless, a method that could allow for an automatic prediction/detection of loss of responsiveness is a step forward for personalized medicine.

Antimicrobial therapy in palliative care: an overview.

In the advanced stages of illness, patients often face challenging decisions regarding their treatment and overall medical care. Terminal ill patients are commonly affected by infections. However, in palliative care, the use of antimicrobials can be an ethical dilemma. Deciding whether to treat, withhold, or withdraw the antimicrobial treatment for an infection can be difficult. Antimicrobial administration can lead to adverse outcomes but the two main benefits, longer survival and symptom relief, are the main reasons why physicians prescribe antimicrobial when treating terminally ill patients. For the patient who has an irreversible advanced heart or lung disease, or an advanced dementia, or a metastatic cancer, it is easier the decision of withholding mechanical ventilation, tube feeding, and dialysis than antibiotherapy. To characterize infections, agents, and their treatments in palliative care, we conducted a review of the literature. We also included some tips to help health professionals to guide their clinical approach.

Characterization and Comparison of Nutritional Intake between Preparatory and Competitive Phase of Highly Trained Athletes.

Background and objective: For a high level athlete, it is essential to ensure optimal energy as well as macro- and micro-nutrient and fluid intakes, in order to improve their performance during training and competition. Protein intake should be 1.2⁻2.1 g/kg/d, whereas the requirements for carbohydrate and fat intakes should be >5g/kg/d and 20⁻35% of energy, respectively. The micronutrient and fluid intakes in athletes were compared to the Dietary Reference Intake (DRI) and European Food Safety Authority (EFSA) recommendations, respectively. This study aimed to characterize and compare the nutritional habits of athletes at the preparatory and competitive phase, and to test if their nutritional intakes were in accordance with the recommendations. Materials and methods: A total of 276 professional athletes were assessed. To evaluate their nutritional intake, the athletes completed a 7 days food record. Under reporting was defined using a ratio of energy intake to basal metabolic rate (BMR) of 1.1. Body composition was assessed using dual energy X-ray absorptiometry (DXA). Results: Almost half (49%) of the athletes from the final sample reported lower measured intakes of carbohydrates and 27% reported a higher consumption of proteins than what was recommended. In both the preparatory and competitive phases, the micronutrients with a higher mismatch between the actual and recommended intakes were vitamins D and E, magnesium, folate, calcium, and zinc for both sexes, and iron intake for females. A large proportion of athletes reported a lower water intake. Compared to the recommendations, males reported a higher intake of carbohydrates, lipids, vitamins E, calcium, and magnesium (p <0.05) in the competitive phase, while females reported a lower ingestion of water, vitamins A and D, and calcium (p <0.05) in the preparatory phase. Conclusions: Overall, in the preparatory and competitive phases of the season, athletes reported a macro- and micro-nutrient intake below the recommendations, especially in the female athletic population. Dietary intakes in athletes need to be optimized and adjusted to their requirements, according to sex and sport, so as to avoid compromising health and performance.