Effects of CYP1A2 and ADORA2A Genotypes on the Ergogenic Response to Caffeine in Professional Handball Players.

Previous investigations have found that several genes may be associated with the interindividual variability to the ergogenic response to caffeine. The aim of this study is to analyze the influence of the genetic variations in CYP1A2 (−163C  > A, rs762551; characterized such as “fast” (AA genotype) and “slow” caffeine metabolizers (C-carriers)) and ADORA2A (1976T  > C; rs5751876; characterized by “high” (TT genotype) or “low” sensitivity to caffeine (C-carriers)) on the ergogenic response to acute caffeine intake in professional handball players. Thirty-one professional handball players (sixteen men and fifteen women; daily caffeine intake = 60 ± 25 mg·d−1) ingested 3 mg·kg−1·body mass (bm) of caffeine or placebo 60 min before undergoing a battery of performance tests consisting of a countermovement jump (CMJ), a sprint test, an agility test, an isometric handgrip test, and several ball throws. Afterwards, the handball players performed a simulated handball match (2 × 20 min) while movements were recorded using inertial units. Saliva samples were analyzed to determine the genotype of each player for the −163C  > A polymorphism in the CYP1A2 gene (rs762551) and for the 1976T  > C polymorphism in the ADORA2A gene (rs5751876). In the CYP1A2, C-allele carriers (54.8%) were compared to AA homozygotes (45.2%). In the ADORA2A, C-allele carriers (80.6%) were compared to TT homozygotes (19.4%). There was only a genotype x treatment interaction for the ball throwing from 7 m (p = 0.037) indicating that the ergogenic effect of caffeine on this test was higher in CYP1A2 AA homozygotes than in C-allele carriers. In the remaining variables, there were no genotype x treatment interactions for CYP1A2 or for ADORA2A. As a whole group, caffeine increased CMJ height, performance in the sprint velocity test, and ball throwing velocity from 9 m (2.8–4.3%, p = 0.001–0.022, effect size = 0.17–0.31). Thus, pre-exercise caffeine supplementation at a dose of 3 mg·kg−1·bm can be considered as an ergogenic strategy to enhance some neuromuscular aspects of handball performance in professional handball players with low daily caffeine consumption. However, the ergogenic response to acute caffeine intake was not modulated by CYP1A2 or ADORA2A genotypes.post-print617 K

Effects of Caffeine Ingestion on Physical Performance in Elite Women Handball Players: A Randomized, Controlled Study.

Purpose: To investigate the effects of acute caffeine (CAFF) intake on physical performance in elite women handball players. Methods: A total of 15 elite women handball players participated in a randomized, double-blind study. In 2 different trials, participants ingested either a placebo (cellulose) or 3 mg of CAFF per kilogram of body mass (mg/kg bm) before undergoing a battery of neuromuscular tests consisting of handball throws, an isometric handgrip strength test, a countermovement jump, a 30-m sprint test (SV) and a modified version of the agility T test. Then, participants performed a simulated handball game (2 × 20 min), and movement patterns were recorded with a local positioning system. Results: Compared with the placebo, CAFF increased ball velocity in all ball throws (P = .021–.044; effect size [ES] = 0.39–0.49), strength in isometric handgrip strength test (350.8 [41.2] vs 361.6 [46.1] N, P = .034; ES = 0.35), and countermovement-jump height (28.5 [5.5] vs 29.8 [5.5] cm; P = .006; ES = 0.22). In addition, CAFF decreased running time in the SV (4.9 [0.2] vs 4.8 [0.3] s; P = .042; ES = −0.34). In the simulated game, CAFF increased the frequency of accelerations (18.1 [1.2] vs 18.8 [1.0] number/min; P = .044; ES = 0.54), decelerations (18.0 [1.2] vs 18.7 [1.0] number/min; P = .032; ES = 0.56), and body impacts (20 [8] vs 22 [10] impacts/min; P = .032; ES = 0.30). However, postexercise surveys about self-reported feelings of performance indicate that players did not feel increased performance with CAFF. Conclusion: Preexercise ingestion of 3 mg/kg bm of CAFF improved ball-throwing velocity, jump, and sprint performance and the frequency of in-game accelerations and decelerations in elite women handball players.pre-print676 K

Déjà vu: on the use of meat resources by sabretooth cats, hominins, and hyaenas in the Early Pleistocene site of Fuente Nueva 3 (Guadix‑Baza Depression, SE Spain)

The late Early Pleistocene archaeological site of Fuente Nueva 3 (Orce, Guadix-Baza Depression, SE Spain), dated to ~1.4 Ma, provides evidence on the subsistence strategies of the first hominin population that dispersed in Western Europe. The site preserves Oldowan tool assemblages associated with abundant remains of large mammals. A small proportion of these remains show cut marks and percussion marks resulting from defleshing and bone fracturing, and a small proportion of bones also show tooth marks. Previous taphonomic studies of FN3 suggested that the hominins had secondary access to the prey leftovers abandoned by sabretooth cats and other primary predators. However, a recent analysis by Yravedra et al. (2021) of the frequency of anthropogenic marks and tooth marks has concluded that the hominins had primary access to the carcasses of a wide variety of ungulate prey, even though the frequency of evisceration marks is strikingly low. In this rebuttal, we analyse the patterns of bone preservation in FN3, which show that the exploitation of bone marrow by the hominins after hammerstone breakage was a usual activity at the site. Our study also reviews the evidence available on the lesser abilities of sabretooth cats for carcass processing compared to pantherine felids. This reinforces the hypothesis that primary predators provided the hominins the opportunity to scavenge sizeable chunks of meat and bone marrow of their prey carcasses before the arrival of hyaenas. Finally, we also provide new inferences on resource availability and competition intensity among the members of the carnivore guild in FN3, which reinforce our interpretation that a secondary access by the Oldowan hominins to the prey leftovers of sabretooth cats was an optimal foraging strategy in the Guadix-Baza Depression.Funding for open access publishing: Universidad Málaga/CBUA This work has been granted by projects CGL-2016-78577-P, CGL-2016-80975-P, and PID2019-111185GB-I00 of the Spanish Ministry of Science, Innovation and University, “Junta de Andalucía” (FEDER) project UMA18-FEDERJA-188, “Generalitat de Catalunya” grant GENCAT 2017SGR 859, and by Research Group RNM-146 from “Junta de Andalucía.” Funding for open access charge: Universidad de Málaga / CBU

El desarrollo municipal, factor estratégico en el posicionamiento de México en los escenarios políticos y sociales del siglo XXI

LA DEMOCRACIA COMO GOBERNABILIDAD IMPLICA, EN UN PRIMER MOMENTO, establecer una revisión periódica del papel interventor del Estado, por ser éste el principal factor de estabilidad y desarrollo democrático. En un segundo punto, de forma simultánea al estudio del papel del Estado en la conformación de un ambiente de estabilidad, crecimiento, desarrollo, orden y gobernabilidad, merece especial atención el papel y funciones cumplidas tradicionalmente por sus ámbitos de gobierno, como instancias que son fundamentales para la transición, democratización, liberalización y para la propia gobernabilidad

Déjà vu: a reappraisal of the taphonomy of quarry VM4 of the Early Pleistocene site of Venta Micena (Baza Basin, SE Spain)

Venta Micena, an Early Pleistocene site of the Baza Basin (SE Spain), preserves a rich and diverse assemblage of large mammals. VM3, the main excavation quarry of the site, has been interpreted as a den of the giant hyaena Pachycrocuta brevirostris in the plain that surrounded the Baza palaeolake. Taphonomic analysis of VM3 has shown that the hyaenas scavenged the prey previously hunted by the hypercarnivores, transported their remains to the communal den, and consumed the skeletal parts according to their marrow contents and mineral density. In a recent paper (Luzón et al. in Sci Rep 11:13977, https://doi.org/10.1038/s41598-021-93261-1, 2021), a small sample of remains unearthed from VM4, an excavation quarry ~ 350 m distant from VM3, is analysed. The authors indicate several differences in the taphonomic features of this assemblage with VM3, and even suggest that a different carnivore could have been the agent involved in the bone accumulation process. Here, we make a comparative analysis of both quarries and analyse more skeletal remains from VM4. Our results indicate that the assemblages are broadly similar in composition, except for slight differences in the frequency of megaherbivores, carnivores and equids according to NISP values (but not to MNI counts), the degree of bone weathering, and the intensity of bone processing by the hyaenas. Given that VM4 and VM3 were not coeval denning areas of P. brevirostris, these differences suggest that during the years when the skeletal remains were accumulated by the hyaenas at VM3, the rise of the water table of the Baza palaeolake that capped with limestone the bones was delayed compared to VM4, which resulted in their more in-depth consumption by the hyaenas

Cumulative antitumor effect of bismuth lipophilic nanoparticles and cetylpyridinium chloride in inhibiting the growth of lung cancer

Objective: To determine the combined antitumor effect of bismuth lipophilic nanoparticles (BisBAL NP) and cetylpyridinium chloride (CPC) on human lung tumor cells. Material and methods: The human lung tumor cells A549 were exposed to 1–100 µM BisBAL NP or CPC, either separately or in a 1:1 combination. Cell viability was measured with the PrestoBlue assay, the LIVE/DEAD assay, and fluorescence microscopy. The integrity and morphology of cellular microtubules were analyzed by immunofluorescence. Results: A 24-h exposure to 1 µM solutions reduced A549 growth with 21.5% for BisBAL NP, 70.5% for CPC, and 92.4% for the combination ( p < 0.0001), while a 50 µM BisBAL NP/CPC mixture inhibited cell growth with 99% ( p < 0.0001). BisBAL NP-curcumin conjugates were internalized within 30 min of exposure and could be traced within the nucleus of tumor cells within 2 h. BisBAL NP, but not CPC, interfered with microtubule organization, thus interrupting cell replication, similar to the action mechanism of docetaxel. Conclusion: The growth inhibition of A549 human tumor cells by BisBAL NP and CPC was cumulative as of 1 µM. The BisBAL NP/CPC combination may constitute an innovative and cost-effective alternative for treating human lung cancer

Twitter as a Tool for Teaching and Communicating Microbiology: The #microMOOCSEM Initiative

Online social networks are increasingly used by the population on a daily basis. They are considered a powerful tool for science communication and their potential as educational tools is emerging. However, their usefulness in academic practice is still a matter of debate. Here, we present the results of our pioneering experience teaching a full Basic Microbiology course via Twitter (#microMOOCSEM), consisting of 28 lessons of 40-45 minutes duration each, at a tweet per minute rate during 10 weeks. Lessons were prepared by 30 different lecturers, covering most basic areas in Microbiology and some monographic topics of general interest (malaria, HIV, tuberculosis, etc.). Data analysis on the impact and acceptance of the course were largely affirmative, promoting a 330% enhancement in the followers and a >350-fold increase of the number of visits per month to the Twitter account of the host institution, the Spanish Society for Microbiology. Almost one third of the course followers were located overseas. Our study indicates that Massive Online Open Courses (MOOC) via Twitter are highly dynamic, interactive, and accessible to great audiences, providing a valuable tool for social learning and communicating science. This strategy attracts the interest of students towards particular topics in the field, efficiently complementing customary academic activities, especially in multidisciplinary areas like Microbiology.Versión del edito

Next Generation Flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma

[EN]Flow cytometry has become a highly valuable method to monitor minimal residual disease (MRD) and evaluate the depth of complete response (CR) in bone marrow (BM) of multiple myeloma (MM) after therapy. However, current flow-MRD has lower sensitivity than molecular methods and lacks standardization. Here we report on a novel next generation flow (NGF) approach for highly sensitive and standardized MRD detection in MM. An optimized 2-tube 8-color antibody panel was constructed in five cycles of design-evaluation-redesign. In addition, a bulk-lysis procedure was established for acquisition of ⩾107 cells/sample, and novel software tools were constructed for automatic plasma cell gating. Multicenter evaluation of 110 follow-up BM from MM patients in very good partial response (VGPR) or CR showed a higher sensitivity for NGF-MRD vs conventional 8-color flow-MRD -MRD-positive rate of 47 vs 34% (P=0.003)-. Thus, 25% of patients classified as MRD-negative by conventional 8-color flow were MRD-positive by NGF, translating into a significantly longer progression-free survival for MRD-negative vs MRD-positive CR patients by NGF (75% progression-free survival not reached vs 7 months; P=0.02). This study establishes EuroFlow-based NGF as a highly sensitive, fully standardized approach for MRD detection in MM which overcomes the major limitations of conventional flow-MRD methods and is ready for implementation in routine diagnostics.This work has been supported by the International Myeloma Foundation-Black Swan Research Initiative, the Red Temática de Investigación Cooperativa en Cáncer (RTICC); grant SA079U14 from the Consejería de Educación, Junta de Castilla y León, Valladolid, Spain and; grant DTS15/00119 from Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain

Compromising between European and US allergen immunotherapy schools: Discussions from GUIMIT, the Mexican immunotherapy guidelines

Background: Allergen immunotherapy (AIT) has a longstanding history and still remains the only disease-changing treatment for allergic rhinitis and asthma. Over the years 2 different schools have developed their strategies: the United States (US) and the European. Allergen extracts available in these regions are adapted to local practice. In other parts of the world, extracts from both regions and local ones are commercialized, as in Mexico. Here, local experts developed a national AIT guideline (GUIMIT 2019) searching for compromises between both schools. Methods: Using ADAPTE methodology for transculturizing guidelines and AGREE-II for evaluating guideline quality, GUIMIT selected 3 high-quality Main Reference Guidelines (MRGs): the European Academy of Allergy, Asthma and Immunology (EAACI) guideines, the S2k guideline of various German-speaking medical societies (2014), and the US Practice Parameters on Allergen Immunotherapy 2011. We formulated clinical questions and based responses on the fused evidence available in the MRGs, combined with local possibilities, patient's preference, and costs. We came across several issues on which the MRGs disagreed. These are presented here along with arguments of GUIMIT members to resolve them. GUIMIT (for a complete English version, see Supplementary data) concluded the following: Results: Related to the diagnosis of IgE-mediated respiratory allergy, apart from skin prick testing complementary tests (challenges, in vitro testing and molecular such as species-specific allergens) might be useful in selected cases to inform AIT composition. AIT is indicated in allergic rhinitis and suggested in allergic asthma (once controlled) and IgE-mediated atopic dermatitis. Concerning the correct subcutaneous AIT dose for compounding vials according to the US school: dosing tables and formula are given; up to 4 non-related allergens can be mixed, refraining from mixing high with low protease extracts. When using European extracts: the manufacturer's indications should be followed; in multi-allergic patients 2 simultaneous injections can be given (100% consensus); mixing is discouraged. In Mexico only allergoid tablets are available; based on doses used in all sublingual immunotherapy (SLIT) publications referenced in MRGs, GUIMIT suggests a probable effective dose related to subcutaneous immunotherapy (SCIT) might be: 50–200% of the monthly SCIT dose given daily, maximum mixing 4 allergens. Also, a table with practical suggestions on non-evidence-existing issues, developed with a simplified Delphi method, is added. Finally, dissemination and implementation of guidelines is briefly discussed, explaining how we used online tools for this in Mexico. Conclusions: Countries where European and American AIT extracts are available should adjust AIT according to which school is followed

Predictive Power of the "Trigger Tool" for the detection of adverse events in general surgery: a multicenter observational validation study

Background In spite of the global implementation of standardized surgical safety checklists and evidence-based practices, general surgery remains associated with a high residual risk of preventable perioperative complications and adverse events. This study was designed to validate the hypothesis that a new “Trigger Tool” represents a sensitive predictor of adverse events in general surgery. Methods An observational multicenter validation study was performed among 31 hospitals in Spain. The previously described “Trigger Tool” based on 40 specific triggers was applied to validate the predictive power of predicting adverse events in the perioperative care of surgical patients. A prediction model was used by means of a binary logistic regression analysis. Results The prevalence of adverse events among a total of 1,132 surgical cases included in this study was 31.53%. The “Trigger Tool” had a sensitivity and specificity of 86.27% and 79.55% respectively for predicting these adverse events. A total of 12 selected triggers of overall 40 triggers were identified for optimizing the predictive power of the “Trigger Tool”. Conclusions The “Trigger Tool” has a high predictive capacity for predicting adverse events in surgical procedures. We recommend a revision of the original 40 triggers to 12 selected triggers to optimize the predictive power of this tool, which will have to be validated in future studies