A Tailored Approach to Leishmaniases Vaccination: Comparative Evaluation of the Efficacy and Cross-Protection Capacity of DNA vs. Peptide-Based Vaccines in a Murine Model.

Zoonotic leishmaniases are a worldwide public health problem for which the development of effective vaccines remains a challenge. A vaccine against leishmaniases must be safe and affordable and should induce cross-protection against the different disease-causing species. In this context, the DNA vaccine pHisAK70 has been demonstrated to induce, in a murine model, a resistant phenotype against L. major, L. infantum, and L. amazonensis. Moreover, a chimeric multiepitope peptide, HisDTC, has been obtained by in silico analysis from the histone proteins encoded in the DNA vaccine and has showed its ability to activate a potent CD4+ and CD8+ T-cell protective immune response in mice against L. infantum infection. In the present study, we evaluated the plasmid DNA vaccine pHisAK70 in comparison with the peptide HisDTC (with and without saponin) against L. major and L. infantum infection. Our preliminary results showed that both formulations were able to induce a potent cellular response leading to a decrease in parasite load against L. infantum. In addition, the DNA candidate was able to induce better lesion control in mice against L. major. These preliminary results indicate that both strategies are potentially effective candidates for leishmaniases control. Furthermore, it is important to carry out such comparative studies to elucidate which vaccine candidates are the most appropriate for further development.

Neglected Zoonotic Diseases: Advances in the Development of Cell-Penetrating and Antimicrobial Peptides against Leishmaniosis and Chagas Disease.

In 2020, the WHO established the road map for neglected tropical diseases 2021-2030, which aims to control and eradicate 20 diseases, including leishmaniosis and Chagas disease. In addition, since 2015, the WHO has been developing a Global Action Plan on Antimicrobial Resistance. In this context, the achievement of innovative strategies as an alternative to replace conventional therapies is a first-order socio-sanitary priority, especially regarding endemic zoonoses in poor regions, such as those caused by Trypanosoma cruzi and Leishmania spp. infections. In this scenario, it is worth highlighting a group of natural peptide molecules (AMPs and CPPs) that are promising strategies for improving therapeutic efficacy against these neglected zoonoses, as they avoid the development of toxicity and resistance of conventional treatments. This review presents the novelties of these peptide molecules and their ability to cross a whole system of cell membranes as well as stimulate host immune defenses or even serve as vectors of molecules. The efforts of the biotechnological sector will make it possible to overcome the limitations of antimicrobial peptides through encapsulation and functionalization methods to obtain approval for these treatments to be used in clinical programs for the eradication of leishmaniosis and Chagas disease.

Curcuma longa-Based Optical Sensor for Hydrochloric Acid and Ammonia Vapor Detection.

In this research, we present a prototype optical system that offers significant advances in detecting hydrochloric acid (HCl) and ammonia (NH3) vapors. The system utilizes a natural pigment sensor based on Curcuma longa that is securely attached to a glass surface support. Through extensive development and testing with HCl (37% aqueous solution) and NH3 (29% aqueous solution) solutions, we have successfully demonstrated the effectiveness of our sensor. To facilitate the detection process, we have developed an injection system that exposes C. longa pigment films to the targeted vapors. The interaction between the vapors and the pigment films triggers a distinct color change, which is then analyzed by the detection system. By capturing the transmission spectra of the pigment film, our system allows a precise comparison of these spectra at different concentrations of the vapors. Our proposed sensor exhibits remarkable sensitivity, allowing the detection of HCl at a concentration of 0.009 ppm using only 100 µL (2.3 mg) of pigment film. In addition, it can detect NH3 at a concentration of 0.03 ppm with a 400 µL (9.2 mg) pigment film. Integrating C. longa as a natural pigment sensor in an optical system opens up new possibilities for detecting hazardous gases. The simplicity and efficiency of our system, combined with its sensitivity, make it an attractive tool in environmental monitoring and industrial safety applications.

Solid Lipid Nanoparticles Enhancing the Leishmanicidal Activity of Delamanid.

Leishmaniasis, a zoonotic parasitic disease transmitted by infected sandflies, impacts nearly 1 million people yearly and is endemic in many countries across Asia, Africa, the Americas, and the Mediterranean; despite this, it remains a neglected disease with limited effective treatments, particularly in impoverished communities with limited access to healthcare. This study aims to repurpose approved drugs for an affordable leishmaniasis treatment. After the screening of potential drug candidates by reviewing databases and utilizing molecular docking analysis, delamanid was chosen to be incorporated into solid lipid nanoparticles (SLNPs). Both in cellulo and in vivo tests confirmed the successful payload release within macrophages and through the epidermis following topical application on murine skin. The evaluation of macrophages infected with L. infantum amastigotes showed that the encapsulated delamanid exhibited greater leishmanicidal activity compared with the free drug. The process of encapsulating delamanid in SLNPs, as demonstrated in this study, places a strong emphasis on employing minimal technology, ensuring energy efficiency, cost-effectiveness, and reproducibility. It enables consistent, low-cost production of nanomedicines, even on a small scale, offering a promising step toward more accessible and effective leishmaniasis treatments.

Transcriptomic Profile of Canine DH82 Macrophages Infected by Leishmania infantum Promastigotes with Different Virulence Behavior.

Zoonotic visceral leishmaniosis caused by Leishmania infantum is an endemic disease in the Mediterranean Basin affecting mainly humans and dogs, the main reservoir. The leishmaniosis outbreak declared in the Community of Madrid (Spain) led to a significant increase in human disease incidence without enhancing canine leishmaniosis prevalence, suggesting a better adaptation of the outbreak's isolates by other host species. One of the isolates obtained in the focus, IPER/ES/2012/BOS1FL1 (BOS1FL1), has previously demonstrated a different phenotype than the reference strain MCAN/ES/1996/BCN150 (BCN150), characterized by a lower infectivity when interacting with canine macrophages. Nevertheless, not enough changes in the cell defensive response were found to support their different behavior. Thus, we decided to investigate the molecular mechanisms involved in the interaction of both parasites with DH82 canine macrophages by studying their transcriptomic profiles developed after infection using RNA sequencing. The results showed a common regulation induced by both parasites in the phosphoinositide-3-kinase-protein kinase B/Akt and NOD-like receptor signaling pathways. However, other pathways, such as phagocytosis and signal transduction, including tumor necrosis factor, mitogen-activated kinases and nuclear factor-κB, were only regulated after infection with BOS1FL1. These differences could contribute to the reduced infection ability of the outbreak isolates in canine cells. Our results open a new avenue to investigate the true role of adaptation of L. infantum isolates in their interaction with their different hosts.

Validity, Reliability, and Sensitivity to Exercise-Induced Fatigue of a Customer-Friendly Device for the Measurement of the Brain's Direct Current Potential.

ABSTRACT: Valenzuela, PL, Sánchez-Martínez, G, Torrontegi, E, Vázquez-Carrión, J, Montalvo, Z, and Kara, O. Validity, reliability, and sensitivity to exercise-induced fatigue of a customer-friendly device for the measurement of the brain's direct current potential. J Strength Cond Res 36(6): 1605-1609, 2022-This study aimed to determine the validity, reliability, and sensitivity to exercise-induced fatigue of the brain's direct current (DC) potential measured with a commercially available and customer-friendly electroencephalography (EEG) device and Omegawave (OW). The study was composed of 3 different experiments as follows: (a) we compared the DC potential values obtained simultaneously in 31 subjects with both OW and a research-quality EEG system; (b) 3 consecutive DC potential measurements with OW were taken at rest on the same day in 25 subjects for reliability analyses; and (c) sensitivity to fatigue was assessed in 9 elite badminton players through the measurement of the DC potential with OW-as well as other fatigue-related measures (e.g., Hooper's index, heart rate variability, jump ability, and simple and complex reaction times)-24 hours after both a day of rest and of strenuous exercise, which were performed in a crossover and randomized design. The DC potential measured with OW was reliable (intraclass correlation coefficient = 0.97) and significantly correlated to that of EEG (r = 0.55, p = 0.001), although significant differences were observed between systems (p < 0.001). Compared with the rest day, strenuous exercise resulted in an impaired Hooper's index (p = 0.010) and jump ability (p = 0.008), longer simple (p = 0.038) and complex reaction times (p = 0.011), and a trend toward sympathetic dominance (standard deviation of normal to normal R-R intervals, p = 0.042; root mean square of differences between consecutive R-R intervals, p = 0.068). In turn, no significant differences were found between sessions for the DC potential (p = 0.173). In summary, the DC potential measured with OW was reliable and modestly correlated to that measured with EEG, but no differences were observed in response to the delayed fatigue (after 24 hours) elicited by strenuous exercise in elite athletes.

A Framework for Implementing Metaheuristic Algorithms Using Intercellular Communication.

Metaheuristics (MH) are Artificial Intelligence procedures that frequently rely on evolution. MH approximate difficult problem solutions, but are computationally costly as they explore large solution spaces. This work pursues to lay the foundations of general mappings for implementing MH using Synthetic Biology constructs in cell colonies. Two advantages of this approach are: harnessing large scale parallelism capability of cell colonies and, using existing cell processes to implement basic dynamics defined in computational versions. We propose a framework that maps MH elements to synthetic circuits in growing cell colonies to replicate MH behavior in cell colonies. Cell-cell communication mechanisms such as quorum sensing (QS), bacterial conjugation, and environmental signals map to evolution operators in MH techniques to adapt to growing colonies. As a proof-of-concept, we implemented the workflow associated to the framework: automated MH simulation generators for the gro simulator and two classes of algorithms (Simple Genetic Algorithms and Simulated Annealing) encoded as synthetic circuits. Implementation tests show that synthetic counterparts mimicking MH are automatically produced, but also that cell colony parallelism speeds up the execution in terms of generations. Furthermore, we show an example of how our framework is extended by implementing a different computational model: The Cellular Automaton.

Should We Base Training Prescription on the Force-Velocity Profile? Exploratory Study of Its Between-Day Reliability and Differences Between Methods.

PURPOSE: To analyze the differences in the force-velocity (F-v) profile assessed under unconstrained (ie, using free weights) and constrained (ie, on a Smith machine) vertical jumps, as well as to determine the between-day reliability. METHODS: A total of 23 trained participants (18 [1] y) performed an incremental load squat jump test (with ∼35%, 45%, 60%, and 70% of the subjects' body mass) on 2 different days using free weights and a Smith machine. Nine of these participants repeated the tests on 2 other days for an exploratory analysis of between-day reliability. F-v variables (ie, maximum theoretical force [F0], velocity [v0], and power, and the imbalance between the actual and the theoretically optimal F-v profile) were computed from jump height. RESULTS: A poor agreement was observed between the F-v variables assessed under constrained and unconstrained conditions (intraclass correlation coefficient [ICC] < .50 for all). The height attained during each single jump performed under both constrained and unconstrained conditions showed an acceptable reliability (coefficient of variation < 10%, ICC > .70). The F-v variables computed under constrained conditions showed an overall good agreement (ICC = .75-.95 for all variables) and no significant differences between days (P > .05), but a high variability for v0, the imbalance between the actual and the theoretically optimal F-v profile, and maximal theoretical power (coefficient of variation = 17.0%-27.4%). No between-day differences were observed for any F-v variable assessed under unconstrained conditions (P > .05), but all of the variables presented a low between-day reliability (coefficient of variation > 10% and ICC < .70 for all). CONCLUSIONS: F-v variables differed meaningfully when obtained from constrained and unconstrained loaded jumps, and most importantly seemed to present a low between-day reliability.

Properties of virulence emergence of Leishmania infantum isolates from Phlebotomus perniciosus collected during the human leishmaniosis outbreak in Madrid, Spain. Hepatic histopathology and immunological parameters as virulence markers in the mouse model.

Recent anthropic activity related to the construction of the Bosquesur Green Park in a large urban setting in Madrid (Spain) has resulted in the largest reported community outbreak of human leishmaniosis in Europe. Previous phylogenetic and molecular-typing studies of parasite isolates have implicated the Leishmania infantum ITS-Lombardi genotype in this outbreak. In an unusual scenario, visceral leishmaniosis (VL) is affecting a significant number of individuals, suggesting that an increase in parasite virulence has occurred. In this work, using an in vivo BALB/c model of VL, we aimed to investigate the properties of emergent virulence of the L. infantum POL2FL7 and BOS1FL1 isolates obtained from Phlebotomus perniciosus collected in the outbreak area and compare them with those of the well-characterized strain BCN150 MON-1 isolated from a dog. The P. perniciosus specimens were collected during an entomological survey conducted in the transmission season of 2012. We observed a range of virulence phenotypes from moderately to highly aggressive after 5 weeks of infection. IV challenge of mice with outbreak isolates from sand flies induced higher splenic and liver parasite burdens, higher serological titres of specific anti-Leishmania antibodies and impaired capacities to control infection, as revealed by the arginine metabolism and low ratios of Th1/Th2 cytokine profiles analysed, compared with the corresponding measures evaluated in mice infected with the BCN150 strain. The BOS1FL1 isolate showed the highest degree of virulence among the isolates, superior to that of POL2FL7, as evidenced by the analysed biomarkers and the histopathological severity of liver lesions. These results provide insight into how L. infantum isolates from sand flies collected in the outbreak area have been able to affect not only immunosuppressed patients but also middle-aged people with normal immunocompetence in the largest human VL outbreak in Europe.

Raccoons (Procyon lotor) in the Madrid region of Spain are carriers of antimicrobial-resistant Escherichia coli and enteropathogenic E. coli.

The role of wildlife in the epidemiology of antimicrobial resistance is unclear. Raccoons in North America can carry a variety of enteric bacteria, with associated antimicrobial resistance, that could infect humans and livestock. The potential for raccoons to carry these bacteria in Europe, where they are an invasive species, has not been explored. Our objectives were to determine the prevalence of Escherichia coli with associated antimicrobial resistance in raccoons from the Madrid region of Spain and to determine whether they are carriers of potential human pathogens, including verotoxin-producing E. coli (VTEC) and enteropathogenic E. coli (EPEC). In total, we tested 237 E. coli isolates from the faeces of 83 euthanized raccoons for susceptibility to 14 antimicrobial agents and the presence of VTEC and EPEC. Antimicrobial resistance to at least one antimicrobial was detected in the faeces of 51% (42/83; 95% CI, 40.1-61.1) of the raccoons tested. A high percentage of raccoons carried, in their faeces, E. coli isolates resistant to ampicillin (33%), streptomycin (33%), tetracycline (30%), sulphafurazole (31%) and trimethoprim-sulphamethoxazole (23%). We detected one isolate of extended-spectrum ß-lactamase-producing E. coli from the faeces of one raccoon. We detected VTEC in the faeces of one raccoon, and EPEC in the faeces of 12% (10/83) of the raccoons. Of the raccoons that carried EPEC in their faeces, 60% (6/10) carried EPEC isolates that exhibited characteristics associated with pathogenicity in humans. Raccoons in Madrid can carry pathogenic and antimicrobial-resistant E. coli in their faeces and may be a risk to public health because of their potential to contaminate food and the environment with their faeces.

A further investigation of the leishmaniosis outbreak in Madrid (Spain): low-infectivity phenotype of the Leishmania infantum BOS1FL1 isolate to establish infection in canine cells.

Human leishmaniosis caused by Leishmania infantum is a zoonotic disease, with dogs as the main reservoir in Mediterranean Basin countries. The largest European outbreak of human leishmaniosis declared in the southwestern Madrid region (Spain) is characterized by unusual epidemiological and clinical features, such as the emergence of new wild reservoirs (hares and rabbits), whereas the seroprevalence, infection, and severity of canine leishmaniosis have not substantially changed since the first studies conducted in Madrid before the outbreak. Previous studies reported that L. infantum isolates from the Madrid leishmaniosis focus displayed elevated virulence in in vivo models of infection and increased infectivity in murine target cells. With the aim of studying whether changes in the host-parasite interaction and virulence profile have developed, we first assessed the behaviour of one circulating isolate of the outbreak, IPER/ES/2012/BOS1FL1 (BOS1FL1), compared to that of a well-characterized strain from canine leishmaniosis, MCAN/ES/1996/BCN150 (BCN150), in terms of infection capacity (percentage of infected cells, representing infectivity, and number of amastigotes per infected cell, representing the intensity of infection) in canine monocytes and macrophages. BCN150 displayed significantly higher infectivity (76.82 ±â€¯4.40 vs 38.58 ±â€¯2.19; P <  0.0001) and intensity of infection (3.64 ± 0.13 vs 1.83 ±â€¯0.12; P <  0.0001) than BOS1FL1 when interacting with canine cells. Our ROS induction results did not differ significantly between the two isolates or with the responses previously described for other L. infantum isolates. Paradoxically, increased resilience to hydrogen peroxide exposure was observed for BOS1FL1 (% viability 40.62 ±â€¯5.54 vs 26.37 ±â€¯2.93; P = 0.039). Finally, we demonstrated that a decreased intracellular load of BOS1FL1 was associated with increased IFN-γ (261.21 ±â€¯26.29 vs 69.80 ±â€¯9.02; P = 0.0151) and decreased IL-10 production (165.06 ±â€¯23.87 vs 264.41 ±â€¯30.58; P = 0.0002). In this study, we provide the first detailed insight into the differences between the isolate BOS1FL1 from the outbreak in Madrid and the well-characterized strain BCN150 MON-1 obtained from a dog in their response to interacting with canine cells. However, further studies are necessary to shed light on the immune mechanisms resulting in BOS1FL1 exhibiting less virulent behaviour in canine cells than in cells derived from other host species.

Epitope Selection for Fighting Visceral Leishmaniosis: Not All Peptides Function the Same Way.

Visceral leishmaniosis (VL) caused by Leishmania infantum is a disease with an increasing prevalence worldwide. Treatments are expensive, toxic, and ineffective. Therefore, vaccination seems to be a promising approach to control VL. Peptide-based vaccination is a useful method due to its stability, absence of local side effects, and ease of scaling up. In this context, bioinformatics seems to facilitate the use of peptides, as this analysis can predict high binding affinity epitopes to MHC class I and II molecules of different species. We have recently reported the use of HisAK70 DNA immunization in mice to induce a resistant phenotype against L. major, L. infantum, and L. amazonensis infections. In the present study, we used bioinformatics tools to select promising multiepitope peptides (HisDTC and AK) from the polyprotein encoded in the HisAK70 DNA to evaluate their immunogenicity in the murine model of VL by L. infantum. Our results revealed that both multiepitope peptides were able to induce the control of VL in mice. Furthermore, HisDTC was able to induce a better cell-mediated immune response in terms of reduced parasite burden, protective cytokine profile, leishmanicidal enzyme modulation, and specific IgG2a isotype production in immunized mice, before and after infectious challenge. Overall, this study indicates that the HisDTC chimera may be considered a satisfactory tool to control VL because it is able to activate a potent CD4+ and CD8+ T-cell protective immune responses.

Reference power values for the jump squat exercise in elite athletes: A multicenter study.

The present study aimed to provide reference values for lower-limb muscle power assessed during the incremental jump squat (JS) test in elite athletes (i.e., professional athletes competing at international level). We pooled data from all JS tests performed by elite athletes of different sports in two high-performance centres between 2015 and 2019, and computed reference values (i.e., terciles) for mean power (MP), mean propulsive power (MPP), and peak power (PP). Reference values were obtained from 684 elite athletes (458 male and 226 female) of 16 different sports (boxing, judo, karate, fencing, taekwondo, wrestling, basketball, soccer, futsal, handball, rugby union, badminton, tennis, long distance running, triathlon, and sprinting). Significant differences (p < 0.001) were found between male and female athletes for MP (7.47 ± 1.93 and 6.15 ± 1.68 W·Kg-1, respectively), MPP (10.50 ± 2.75 and 8.63 ± 2.43 W·Kg-1), and PP (23.64 ± 6.12 and 19.35 ± 5.49 W·Kg-1). However, the velocity at which these power measures was attained seemed to be independent of sex (~0.95, 1.00 and 2.00 m·s-1 for mean, mean propulsive, and peak velocity, respectively) and homogeneous across different sport disciplines (coefficient of variation <10%). These data can be used to classify athletes' power capabilities, and the optimum velocity ranges provided here could be useful for training purposes.

Cumulative effects of triadic closure and homophily in social networks.

Social network structure has often been attributed to two network evolution mechanisms-triadic closure and choice homophily-which are commonly considered independently or with static models. However, empirical studies suggest that their dynamic interplay generates the observed homophily of real-world social networks. By combining these mechanisms in a dynamic model, we confirm the longheld hypothesis that choice homophily and triadic closure cause induced homophily. We estimate how much observed homophily in friendship and communication networks is amplified due to triadic closure. We find that cumulative effects of homophily amplification can also lead to the widely documented core-periphery structure of networks, and to memory of homophilic constraints (equivalent to hysteresis in physics). The model shows that even small individual bias may prompt network-level changes such as segregation or core group dominance. Our results highlight that individual-level mechanisms should not be analyzed separately without considering the dynamics of society as a whole.

Immunization with the HisAK70 DNA Vaccine Induces Resistance against Leishmania Amazonensis Infection in BALB/c Mice.

Leishmania amazonensis is the aetiological agent of a broad spectrum of leishmaniosis in South America. It can cause not only numerous cases of cutaneous leishmaniosis but also diffuse cutaneous leishmaniosis. Considering the diversity of parasite species causing different forms of the disease that coexist in the same region, it is desirable to develop a vaccine capable of eliciting cross-protection. We have previously described the use of HisAK70 DNA vaccine for immunization of mice to assess the induction of a resistant phenotype against Leishmania major and infantum infections. In this study, we extended its application in the murine model of infection by using L. amazonensis promastigotes. Our data revealed that 14 weeks post-infection, HisAK70-vaccinated mice showed key biomarkers of protection, such as higher iNOS/arginase activity, IFN-γ/IL-10, IFN-γ/IL-4, and GM-CSF/IL-10 ratios, in addition to an IgG2a-type response when compared to the control group. These findings correlated with the presentation of lower footpad swelling and parasite burdens in the immunized compared to the control mice. Overall, this study suggests that immunization with HisAK70 may be considered a suitable tool to combat leishmaniosis as it is able to induce a potent cellular immune response, which allows to control the infection caused by L. amazonensis.

Strength and medium-term impact of HisAK70 immunization in dogs: Vaccine safety and biomarkers of effectiveness for ex vivo Leishmania infantum infection.

HisAK70 candidates have successfully been tested in cutaneous (CL) and visceral leishmaniosis (VL) mouse models. Here, we analyse different biomarkers in dog trials after a heterologous immunization strategy with a HisAK70 candidate (plasmid DNA plus adoptive transfer of peripheral blood-derived dendritic cells (DCs) pulsed with the same pathoantigen and CpG ODN as an adjuvant) to explore the antileishmanial activity in an ex vivo canine co-culture system in the presence of Leishmania infantum parasites. In the canine model, the heterologous HisAK70 vaccine could decrease the infection index in the DC-T cell co-culture system by up to 54% after 30 days and reach almost 67% after 100 days post-immunization, respectively, compared to those obtained in the control group of dogs. The observed security and potential to fight ex vivo L. infantum infection highlight a HisAK70 heterologous immunization strategy as a promising alternative to evaluate its effectiveness against canine VL.

Acute Responses to On-Court Repeated-Sprint Training Performed With Blood Flow Restriction Versus Systemic Hypoxia in Elite Badminton Athletes.

PURPOSE: Repeated-sprint training (RS) is commonly conducted in normoxia, but its completion with localized (blood-flow restriction [BFR]) or systemic hypoxia has been proven effective for performance enhancement. Yet, few studies have applied these types of RS sessions in racket sports. The authors aimed to determine the acute responses to these types of training in elite badminton players. METHODS: Eight male elite badminton players participated in this randomized crossover study. They performed 3 on-court RS sessions, each consisting of 3 sets of 10 repetitions of 10-s badminton-specific movements in normoxia (RSN), systemic normobaric hypoxia (RSH, FiO2 = 14%), or with BFR (RS-BFR, 40% arterial occlusion pressure). Performance, perceptual (ie, rating of perceived exertion), and physiological (ie, pulse saturation, muscle oxygenation, blood lactate, creatine kinase, heart-rate variability) responses were measured after each set and up to 48 h postsession. RESULTS: RS-BFR induced a greater performance impairment (lower distance and accelerations) and a higher local perceived exertion in the legs than RSN and RSH (P < .05), whereas greater overall fatigue was reported with RSH (P < .05). RSH induced a lower saturation (P < .001), but no differences were observed in muscle oxygenation between conditions. No differences in creatine kinase or heart-rate variability were observed at any time point (from baseline up to 48 h after the session). CONCLUSIONS: RS-BFR-and, to a lower extent, RSH-resulted in impaired performance and a higher perceived strain than RSN. However, these 2 hypoxic methods do not seem to induce a long-lasting (post 24-48 h) physiological stress in elite badminton players.

Enhancement of Mood but not Performance in Elite Athletes With Transcranial Direct-Current Stimulation.

PURPOSE: To determine if transcranial direct-current stimulation (tDCS) could be effective for the enhancement of swimming performance or mood state in elite athletes. METHODS: Eight male elite triathletes (age = 20 [2] y, maximal oxygen uptake = 71 [4] mL·kg-1·min-1) participated in this crossover, counterbalanced, sham-controlled, double-blind study. Participants received either actual (20 min of anodal stimulation of the motor cortex at 2 mA) or sham tDCS and performed an 800-m swimming test in which rating of perceived exertion and blood lactate response were measured. Mood state (Brunel Mood Scale) was assessed before and after each tDCS session and after the swimming test. Heart-rate variability and central nervous system readiness were assessed before and after each tDCS session. The chances of finding differences between conditions were determined using magnitude-based inferences. RESULTS: A significant and very likely higher Brunel Mood Scale-determined vigor self-perception was found with actual tDCS after the stimulation session (-0.1 [1.2] and 2.0 [2.3] for sham and actual tDCS, respectively; P = .018, effect size = 1.14) and after exercise (-4.1 [2.9] and -0.9 [3.6] for sham and actual tDCS, respectively; P = .022, effect size = 0.98). However, likely trivial and nonsignificant (P > .05) differences were found between conditions in performance (599 [38] s and 596 [39] s, respectively). Unclear and nonsignificant differences were observed between conditions for the rest of the study end points. CONCLUSIONS: tDCS elicited a marked increase in vigor self-perception that was maintained after exercise but failed to improve swimming performance in elite triathletes.

Pharmacogenetic Variation in Over 100 Genes in Patients Receiving Acenocumarol.

Coumarins are widely prescribed worldwide, and in Mexico acenocumarol is the preferred form. It is well known that despite its efficacy, coumarins show a high variability for dose requirements. We investigated the pharmacogenetic variation of 110 genes in patients receiving acenocumarol using a targeted NGS approach. We report relevant population differentiation for variants on CYP2C8, CYP2C19, CYP4F11, CYP4F2, PROS, and GGCX, VKORC1, CYP2C18, NQO1. A higher proportion of novel-to-known variants for 10 genes was identified on 41 core pharmacogenomics genes related to the PK (29), PD (3), of coumarins, and coagulation proteins (9) including, CYP1A1, CYP3A4, CYP3A5, and F8, and a low proportion of novel-to-known variants on CYP2E1, VKORC1, and SULT1A1/2. Using a Bayesian approach, we identified variants influencing acenocumarol dosing on, VKORC1 (2), SULT1A1 (1), and CYP2D8P (1) explaining 40-55% of dose variability. A collection of pharmacogenetic variation on 110 genes related to the PK/PD of coumarins is also presented. Our results offer an initial insight into the use of a targeted NGS approach in the pharmacogenomics of coumarins in Mexican Mestizos.