An improved simple rat model for global cerebral ischaemia by induced cardiac arrest

OBJECTIVES Cerebral hypoxic-ischaemic injury following cardiac arrest is a devastating disease affecting thousands of patients each year. There is a complex interaction between post-resuscitation injury after whole-body ischaemia-reperfusion and cerebral damage which cannot be explored in in vitro systems only; there is a need for animal models. In this study, we describe and evaluate the feasibility and efficiency of our simple rodent cardiac arrest model. METHODS Ten wistar rats were subjected to 9 and 10 minutes of cardiac arrest. Cardiac arrest was introduced with a mixture of the short-acting beta-blocking drug esmolol and potassium chloride. RESULTS All animals could be resuscitated within 1 minute, and survived until day 5.General health score and neurobehavioural testing indicated substantial impairment after cardiac arrest, without differences between groups. Histological examination of the hippocampus CA1 segment, the most vulnerable segment of the cerebrum, demonstrated extensive damage in the cresyl violet staining, as well as in the Fluoro-Jade B staining and in the Iba-1 staining, indicating recruitment of microglia after the hypoxic-ischaemic event. Again, there were no differences between the 9- and 10-minute cardiac arrest groups. DISCUSSION We were able to establish a simple and reproducible 9- and 10-minute rodent cardiac arrest models with a well-defined no-flow-time. Extensive damage can be found in the hippocampus CA1 segment. The lack of difference between 9- and 10-minute cardiac arrest time in the neuropsychological, the open field test and the histological evaluations is mainly due to the small sample size.

Effectiveness of meticillin-resistant Staphylococcus aureus decolonization in long-term haemodialysis patients: a systematic review and meta-analysis.

BACKGROUND Chronic haemodialysis patients are a high-risk population for meticillin-resistant Staphylococcus aureus (MRSA) colonization, which is a precursor of infection. AIM To summarize the effect of nasal (± whole-body wash) MRSA decolonization in haemodialysis patients by means of a systematic review and meta-analysis. METHODS We identified eligible studies using Medline, Embase, the Cochrane database, clinicaltrials.org, and conference abstracts investigating the success of MRSA decolonization in haemodialysis patients. For the statistical analysis, we used Stata 13 to express study-specific proportions with 95% confidence intervals. A likelihood ratio test was used to assess inter-study heterogeneity. FINDINGS Six published prospective cohort studies and one study described in a conference abstract met our inclusion criteria. From 1150 haemodialysis patients enrolled in these studies, MRSA was isolated from nasal swabs of 147 (12.8%) patients. Six of the trials used mupirocin nasal ointment and combined it with chlorhexidine body washes for decolonization. The most widely used protocol was a five-day course of mupirocin nasal ointment application three times a day, and chlorhexidine body wash once daily. The pooled success rate of decolonization was 0.88 (95% confidence interval: 0.75-0.95). A likelihood ratio test of the fixed versus the random-effects model showed significant inter-study heterogeneity (P = 0.047). Four of seven studies determined subsequent MRSA infections in 94 carriers overall, two (2%) of which experienced infection. CONCLUSION The use of mupirocin together with whole-body decolonization is highly effective in eradicating MRSA carriage in haemodialysis patients. The current literature, however, is characterized by a lack of comparative effectiveness studies for this intervention.

Hyperthermia-related clinical trials on cancer treatment within the ClinicalTrials.gov registry

PURPOSE Hyperthermia has been shown to improve the effectiveness of chemotherapy and radiotherapy in the treatment of cancer. This paper summarises all recent clinical trials registered in the ClinicalTrials.gov registry. MATERIALS AND METHODS The records of 175,538 clinical trials registered at ClinicalTrials.gov were downloaded on 29 September 2014 and a database was established. We searched this database for hyperthermia or equivalent words. RESULTS A total of 109 trials were identified in which hyperthermia was part of the treatment regimen. Of these, 49 trials (45%) had hyperthermic intraperitoneal chemotherapy after cytoreductive surgery (HIPEC) as the primary intervention, and 14 other trials (13%) were also testing some form of intraperitoneal hyperthermic chemoperfusion. Seven trials (6%) were testing perfusion attempts to other locations (thoracic/pleural n = 4, limb n = 2, hepatic n = 1). Sixteen trials (15%) were testing regional hyperthermia, 13 trials (12%) whole body hyperthermia, seven trials (6%) superficial hyperthermia and two trials (2%) interstitial hyperthermia. One remaining trial tested laser hyperthermia. CONCLUSIONS In contrast to the general opinion, this analysis shows continuous interest and ongoing clinical research in the field of hyperthermia. Interestingly, the majority of trials focused on some form of intraperitoneal hyperthermic chemoperfusion. Despite the high number of active clinical studies, HIPEC is a topic with limited attention at the annual meetings of the European Society for Hyperthermic Oncology and the Society of Thermal Medicine. The registration of on-going clinical trials is of paramount importance for the achievement of a comprehensive overview of available clinical research activities involving hyperthermia.

Self-motion direction discrimination in the visually impaired

Despite the close interrelation between vestibular and visual processing (e.g., vestibulo-ocular reflex), surprisingly little is known about vestibular function in visually impaired people. In this study, we investigated thresholds of passive whole-body motion discrimination (leftward vs. rightward) in nine visually impaired participants and nine age-matched sighted controls. Participants were rotated in yaw, tilted in roll, and translated along the interaural axis at two different frequencies (0.33 and 2 Hz) by means of a motion platform. Superior performance of visually impaired participants was found in the 0.33 Hz roll tilt condition. No differences were observed in the other motion conditions. Roll tilts stimulate the semicircular canals and otoliths simultaneously. The results could thus reflect a specific improvement in canal–otolith integration in the visually impaired and are consistent with the compensatory hypothesis, which implies that the visually impaired are able to compensate the absence of visual input.

Post-remission treatment with allogeneic stem cell transplantation in patients aged 60 years and older with acute myeloid leukaemia: a time-dependent analysis

BACKGROUND Acute myeloid leukaemia mainly affects elderly people, with a median age at diagnosis of around 70 years. Although about 50-60% of patients enter first complete remission upon intensive induction chemotherapy, relapse remains high and overall outcomes are disappointing. Therefore, effective post-remission therapy is urgently needed. Although often no post-remission therapy is given to elderly patients, it might include chemotherapy or allogeneic haemopoietic stem cell transplantation (HSCT) following reduced-intensity conditioning. We aimed to assess the comparative value of allogeneic HSCT with other approaches, including no post-remission therapy, in patients with acute myeloid leukaemia aged 60 years and older. METHODS For this time-dependent analysis, we used the results from four successive prospective HOVON-SAKK acute myeloid leukaemia trials. Between May 3, 2001, and Feb 5, 2010, a total of 1155 patients aged 60 years and older were entered into these trials, of whom 640 obtained a first complete remission after induction chemotherapy and were included in the analysis. Post-remission therapy consisted of allogeneic HSCT following reduced-intensity conditioning (n=97), gemtuzumab ozogamicin (n=110), chemotherapy (n=44), autologous HSCT (n=23), or no further treatment (n=366). Reduced-intensity conditioning regimens consisted of fludarabine combined with 2 Gy of total body irradiation (n=71), fludarabine with busulfan (n=10), or other regimens (n=16). A time-dependent analysis was done, in which allogeneic HSCT was compared with other types of post-remission therapy. The primary endpoint of the study was 5-year overall survival for all treatment groups, analysed by a time-dependent analysis. FINDINGS 5-year overall survival was 35% (95% CI 25-44) for patients who received an allogeneic HSCT, 21% (17-26) for those who received no additional post-remission therapy, and 26% (19-33) for patients who received either additional chemotherapy or autologous HSCT. Overall survival at 5 years was strongly affected by the European LeukemiaNET acute myeloid leukaemia risk score, with patients in the favourable risk group (n=65) having better 5-year overall survival (56% [95% CI 43-67]) than those with intermediate-risk (n=131; 23% [19-27]) or adverse-risk (n=444; 13% [8-20]) acute myeloid leukaemia. Multivariable analysis with allogeneic HSCT as a time-dependent variable showed that allogeneic HSCT was associated with better 5-year overall survival (HR 0·71 [95% CI 0·53-0·95], p=0·017) compared with non-allogeneic HSCT post-remission therapies or no post-remission therapy, especially in patients with intermediate-risk (0·82 [0·58-1·15]) or adverse-risk (0.39 [0·21-0·73]) acute myeloid leukaemia. INTERPRETATION Collectively, the results from these four trials suggest that allogeneic HSCT might be the preferred treatment approach in patients 60 years of age and older with intermediate-risk and adverse-risk acute myeloid leukaemia in first complete remission, but the comparative value should ideally be shown in a prospective randomised study. FUNDING None.

Transfer and effects of 1,2,3,5,7-pentachloronaphthalene in an experimental food chain.

Polychlorinated naphthalenes are environmentally relevant compounds that are measured in biota at concentrations in the μg/kg lipid range. Despite their widespread occurrence, literature data on the accumulation and effects of these compounds in aquatic ecosystems are sparsely available. The goal of this study was to gain insights into the biomagnification and effects of 1,2,3,5,7-pentachloronaphthalene (PeCN52) in an experimental food chain consisting of benthic worms and juvenile rainbow trout. Worms were contaminated with PeCN52 by passive dosing from polydimethylsiloxane silicone. The contaminated worms were then used to feed the juvenile rainbow trout at 0.12, 0.25 or 0.50 μg/g fish wet weight/day, and the resulting internal whole-body concentrations of the individual fish were linked to biological responses. A possible involvement of the cellular detoxification system was explored by measuring PeCN52-induced expression of the phase I biotransformation enzyme gene cyp1a1 and the ABC transporter gene abcb1a. At the end of the 28-day study, biomagnification factors were similar for all dietary intake levels with values between 0.5 and 0.7 kg lipid(fish)/kg lipid(worm). The average uptake efficiency of 60% indicated that a high amount of PeCN52 was transferred from the worms to the fish. Internal concentrations of up to 175 mg/kg fish lipid in the highest treatment level did not result in effects on survival, behavior, or growth of the juvenile trout, but were associated with the induction of phase I metabolism which was evident from the significant up-regulation of cyp1a1 expression in the liver. In contrast, no changes were seen in abcb1a transcript levels.

AUGMENTATION OF RECONSTITUTION OF GUT ASSOCIATED LYMPHOID TISSUE IN THE SYNGENEIC MURINE BONE MARROW TRANSPLANTATION MODEL

Gut was studied as a prototypical mucosal membrane in the murine BDF-1 syngeneic bone marrow transplant model. Measures of jejunal intraepithelial lymphocytes (IELs) and crypt cells were obtained by standard techniques and a method of quantifying gut lamina propria plasma cells (PCs) was developed. The degree of ablation of gut PCs and IELs after 900 rads total body irradiation with ('60)Co, and their repopulation effected by transplantation with 2.0 x 10('5) or 1.0 x 10('6) bone marrow cells demonstrated a prolonged period of profound depression in population levels of these cells which was not reflected by the extent of damage sustained to the epithelium. Differences in the depopulation and recovery of gut PCs and IELs revealed a tendency towards initial differentiation of effector cells. A positive dose response to high bone marrow cell innocula was obtained. Subsequent studies determined that gut IEL and PC repopulation was potentiated by the addition of IELs or buffy coat cells (BCs) to the bone marrow transplant. A method of isolating 1.4 - 4.0 x 10('7) viable IELs per gram of murine small bowel was devised employing intralumenal hyaluronidase digestion of the epithelial layer and centrifugation of the resulting suspension through discontinuous Percoll gradients. Irradiated mice received 2.0 x 10('5) bone marrow cells along with an equal number of IELs or BCs. The extent and duration of depression of numbers of IELs and PCs was markedly reduced by the addition of the IEL isolate to the transplantation innocula, and to a lesser degree by the addition of BCs. The augmentation of repopuation far exceeded that expected by simple lodging of cells suggesting that the additionally transplanted cells contained a subpopulation of mucosal membrane lymphoid stem cells or helper cells. Correlation analysis of PC versus IEL levels suggests a possible feedback mechanism governing the relative size of their populations. Normal ratios of IgA, IgM, and IgG bearing PCs was maintained post transplantation with all of the regimens. ^

A novel treatment planning methodology for high dose 166Ho-DOTMP therapy in patients with multiple myeloma

Bone marrow ablation, i.e., the complete sterilization of the active bone marrow, followed by bone marrow transplantation (BMT) is a comment treatment of hematological malignancies. The use of targeted bone-seeking radiopharmaceuticals to selectively deliver radiation to the adjacent bone marrow cavities while sparing normal tissues is a promising technique. Current radiopharmaceutical treatment planning methods do not properly compensate for the patient-specific variable distribution of radioactive material within the skeleton. To improve the current method of internal dosimetry, novel methods for measuring the radiopharmaceutical distribution within the skeleton were developed. 99mTc-MDP was proven as an adequate surrogate for measuring 166Ho-DOTMP skeletal uptake and biodistribution, allowing these measures to be obtained faster, safer, and with higher spatial resolution. This translates directly into better measurements of the radiation dose distribution within the bone marrow. The resulting bone marrow dose-volume histograms allow prediction of the patient disease response where conventional organ scale dosimetry failed. They indicate that complete remission is only achieved when greater than 90% of the bone marrow receives at least 30 Gy. ^ Comprehensive treatment planning requires combining target and non-target organ dosimetry. Organs in the urinary tract were of special concern. The kidney dose is primarily dependent upon the mean transit time of 166 Ho-DOTMP through the kidney. Deconvolution analysis of renograms predicted a mean transit time of 2.6 minutes for 166Ho-DOTMP. The radiation dose to the urinary bladder wall is dependent upon numerous factors including patient hydration and void schedule. For beta-emitting isotopes such as 166Ho, reduction of the bladder wall dose is best accomplished through good patient hydration and ensuring a partially full bladder at the time of injection. Encouraging the patient to void frequently, or catheterizing the patient without irrigation, will not significantly reduce the bladder wall dose. ^ The results from this work will produce the most advanced treatment planning methodology for bone marrow ablation therapy using radioisotopes currently available. Treatments can be tailored specifically for each patient, including the addition of concomitant total body irradiation for patients with unfavorable dose distributions, to deliver a desired patient disease response, while minimizing the dose or toxicity to non-target organs. ^

Molecular mechanisms for the insulin sensitizing activity of rexinoids in skeletal muscle of diabetic (Db/Db) mice

Rexinoids are synthetic agonists for the retinoid X receptors (RXRs), a member of the nuclear receptor family of ligand-activated transcription factors. Rexinoids have been shown to lower serum glucose and insulin levels in animal models of type 2 diabetes. However the mechanisms that are responsible for the insulin-sensitizing action of rexinoids are largely unknown. Skeletal muscle accounts for the majority of insulin-regulated whole-body glucose disposal and impaired insulin action in muscle is an important contributor to the pathophysiology of type 2 diabetes. Glucose transport is a rate-limiting step in glucose utilization. The goal of these studies is to examine the mechanisms of the anti-diabetic activity of rexinoids in skeletal muscle of diabetic db/db mice. The results we have obtained showed that treatment of db/db mice with rexinoids for two weeks resulted in a significant increase in insulin-stimulated glucose transport activity in skeletal muscle. Insulin stimulates glucose transport in muscle via the regulation of both the insulin receptor substrate-1 (IRS-1)/Akt pathway and the Cbl-associated protein (CAP)/Cbl pathway. Rexinoids increased the insulin-stimulated IRS-1 tyrosine phosphorylation and Akt phosphorylation without effects on the activity of the CAP/Cbl pathway. The effects of rexinoids on the IRS-1/Akt pathway were associated with a decrease in the level of IRS-1 Serine 307 phosphorylation as well as qualitative and quantitative alterations in the fatty acyl-CoAs present within the muscle cells. In addition, rexinoids increased the expression of uncoupling protein 3 (UCP3) and activation of AMPK in diabetic muscle. This effect may also enhance the IRS-1/Akt signaling. We believe that it is the concerted activation of the IRS-1/Akt and AMPK signaling systems, a pharmacological mechanism that as far as we know, is unique to rexinoids, that results in the anti-diabetic effects of these drugs. Our results also suggest that the glucose-lowering mechanism of rexinoids is distinct from that of the thiazolidinediones (TZDs), peroxisome proliferator-activated receptor γ (PPARγ) agonists with well-characterized anti-diabetic activity. Rexinoids appear to represent a novel class of insulin sensitizers, with potential applications for the treatment of type 2 diabetes. ^

Molecular analysis of a neurovirulent murine leukemia virus, {\it ts\/}1

ts1 is a neurovirulent spontaneous temperature-sensitive mutant of Moloney murine leukemia virus TB (MoMuLV-TB). MoMuLV-TB causes T-cell lymphoma or lymphoid leukemia in mice after a long latency period whereas ts1 causes a progressive hindlimb paralytic disease after a much shorter latency period. In previous studies, it had been shown that the temperature-sensitive defect resided in the $env$ gene. At the restrictive temperature, the envelope precursor polyprotein, gPr80$\sp{env}$, is inefficiently processed intracellularly into a heterodimer consisting of two cleavage products, gp70 and Prp15E. This inefficient processing is correlated with neurovirulence. In this study, the nucleotide sequences of the env genes for both ts1 and MoMuLV-TB were determined, and the encoded amino acid sequences were deduced from the DNA sequences. There were four unique amino acid substitutions in the gPr80$\sp{env}$ of ts1. In order to determine which unique amino acid was responsible for the phenotypic characteristics of ts1, a set of hybrid genomes was constructed by exchanging restriction fragments between ts1 and MoMuLV-TB. NIH 3T3 cells were transfected with the hybrid genomes to obtain infectious hybrid viruses. Assays of the hybrid viruses showed that a Val-25$\to$Ile substitution in gPr80$\sp{env}$ was responsible for the temperature sensitivity, inefficient processing, and neurovirulence of ts1. In further studies, the Ile-25 in gPr80$\sp{env}$ was substituted with Thr, Ala, Leu, Gly, and Glu by site-directed mutagenesis to generate a new set of mutant viruses, i.e., ts1-T, -A, -L, -G, and -E, respectively. The rank order of the mutants for temperature sensitivity was: ts1-E $>$ ts1-G $>$ ts1-L $>$ ts1-A $>$ ts1 $>$ ts1-T. The degree of temperature sensitivity of each of the mutants also correlated with the degree of inefficient processing of gPr80$\sp{env}$. The mutant viruses were assayed for neurovirulence. ts1-T caused whole body tremor, ts1-A caused hindlimb paralysis, ts1-L caused paraparesis, but ts1-G and -E were not neurovirulent. These results show that inefficient processing of gPr80$\sp{env}$ is correlated with neurovirulence, but if processing of gPr80$\sp{env}$ is too inefficient there is no neurovirulence. Furthermore, the disease profile of each of the neurovirulent viruses depends on the degree of inefficient processing of gPr80$\sp{env}$. ^

Shotgun proteomics reveals physiological response to ocean acidification in Crassostrea gigas

Background. Ocean acidification as a result of increased anthropogenic CO2 emissions is occurring in marine and estuarine environments worldwide. The coastal ocean experiences additional daily and seasonal fluctuations in pH that can be lower than projected end of century open ocean pH reductions. Projected and current ocean acidification have wide-ranging effects on many aquatic organisms, however the exact mechanisms of the impacts of ocean acidification on many of these animals remains to be characterized. Methods. In order to assess the impact of ocean acidification on marine invertebrates, Pacific oysters (Crassostrea gigas) were exposed to one of four different pCO2 levels for four weeks: 400 µatm (pH 8.0), 800 µatm (pH 7.7), 1000 µatm (pH 7.6), or 2800 µatm (pH 7.3). At the end of 4 weeks a variety of physiological parameters were measured to assess the impacts of ocean acidification: tissue glycogen content and fatty acid profile, shell micromechanical properties, and response to acute heat shock. To determine the effects of ocean acidification on the underlying molecular physiology of oysters and their stress response, some of the oysters from 400 µatm and 2800 µatm were exposed to an additional mechanical stress and shotgun proteomics were done on oysters from high and low pCO2 and from with and without mechanical stress. Results. At the end of the four week exposure period, oysters in all four pCO2 environments deposited new shell, but growth rate was not different among the treatments. However, micromechanical properties of the new shell were compromised by elevated pCO2. Elevated pCO2 affected neither whole body fatty acid composition, nor glycogen content, nor mortality rate associated with acute heat shock. Shotgun proteomics revealed that several physiological pathways were significantly affected by ocean acidification, including antioxidant response, carbohydrate metabolism, and transcription and translation. Additionally, the proteomic response to a second stress differed with pCO2, with numerous processes significantly affected by mechanical stimulation at high versus low pCO2 (all proteomics data are available in the ProteomeXchange under the identifier PXD000835). Discussion. Oyster physiology is significantly altered by exposure to elevated pCO2, indicating changes in energy resource use. This is especially apparent in the assessment of the effects of pCO2 on the proteomic response to a second stress. The altered stress response illustrates that ocean acidification may impact how oysters respond to other changes in their environment. These data contribute to an integrative view of the effects of ocean acidification on oysters as well as physiological trade-offs during environmental stress.

Time required to stabilize thermographic images at rest

Thermography for scientific research and practical purposes requires a series of procedures to obtain images that should be standardized; one of the most important is the time required for acclimatization in the controlled environment. Thus, the objective of this study was to identify the appropriate acclimatization time in rest to reach a thermal balance on young people skin. Forty-four subjects participated in the study, 18 men (22.3 ± 3.1 years) and 26 women (21.7 ± 2.5 years). Thermographic images were collected using a thermal imager (Fluke ®), totaling 44 images over a period of 20 minutes. The skin temperature (TSK) was measured at the point of examination which included the 0 minute, 2, 4, 6, 8, 10, 12, 14, 16, 18 and 20. The body regions of interest (ROI) analyzed included the hands, forearms, arms, thighs, legs, chest and abdomen. We used the Friedman test with post hoc Dunn?s in order to establish the time at rest required to obtain a TSK balance and the Mann-Whitney test was used to compare age, BMI, body fat percentage and temperature variations between men and women, considering always a significance level of pmenor que0.05. Results showed that women had significantly higher temperature variations than men (pmenor que0.01) along the time. In men, only the body region of the abdomen obtained a significant variance (pmenor que0.05) on the analyzed period, both in the anterior and posterior part. In women, the anterior abdomen and thighs, and the posterior part of the hands, forearms and abdomen showed significant differences (pmenor que0.05). Based on our results, it can be concluded that the time in rest condition required reaching a TSK balance in young men and women is variable, but for whole body analysis it is recommended at least 10 minutes for both sexes.

Reliability and reproductibility of skin temperature of overweight subjects by an infrared thermograpy software designed for human beings

The technical improvement and new applications of Infrared Thermography (IRT) with healthy subjects should be accompanied by results about the reproducibility of IRT measurements in different popula-tion groups. In addition, there is a remarkable necessity of a larger supply on software to analyze IRT images of human beings. Therefore, the objectives of this study were: firstly, to investigate the reproducibility of skin temperature (Tsk) on overweight and obese subjects using IRT in different Regions of Interest (ROI), moments and side-to-side differences (?T); and secondly, to check the reliability of a new software called Termotracker®, specialized on the analysis of IRT images of human beings. Methods: 22 overweight and obese males (11) and females (11) (age: 41,51±7,76 years; height: 1,65±0,09 m; weight: 82,41±11,81 Kg; BMI: 30,17±2,58 kg/m²) were assessed in two consecutive thermograms (5 seconds in-between) by the same observer, using an infrared camera (FLIR T335, Sweden) to get 4 IRT images from the whole body. 11 ROI were selected using Termotracker® to analyze its reproducibility and reliability through Intra-class Correlation Coefficient (ICC) and Coefficient of Variation (CV) values. Results: The reproducibility of the side-to-side differences (?T) between two consecutive thermograms was very high in all ROIs (Mean ICC = 0,989), and excellent between two computers (Mean ICC = 0,998). The re-liability of the software was very high in all the ROIs (Mean ICC = 0,999). Intraexaminer reliability analysing the same subjects in two consecutive thermograms was also very high (Mean ICC = 0,997). CV values of the different ROIs were around 2%. Conclusions: Skin temperature on overweight subjects had an excellent reproducibility for consecutive ther-mograms. The reproducibility of thermal asymmetries (?T) was also good but it had the influence of several factors that should be further investigated. Termotracker® reached excellent reliability results and it is a relia-ble and objective software to analyse IRT images of humans beings.

Real-time Surveillance Application by Multiple Detectors and Compressive Trackers

A real-time surveillance system for IP network cameras is presented. Motion, part-body, and whole-body detectors are efficiently combined to generate robust and fast detections, which feed multiple compressive trackers. The generated trajectories are then improved using a reidentification strategy for long term operation.

Regulación del movimiento y anticipación en el resto del primer servicio en tenis

Aunque se han logrado importantes avances en estudios de laboratorio con diseños experimentales poco representativos (e.g., Farrow y Reid, 2012; Nieminen, Piirainen, Salmi, y Linnamo, 2013), a día de hoy, todavía se desconoce a cabalidad cómo los jugadores de tenis de diferente nivel de pericia calibran o ajustan sus movimientos a las demandas espacio-temporales presentes en la tarea de resto de un primer servicio. ! Escasos trabajos se han llevado a cabo in situ y a la mayoría se les puede cuestionar algún aspecto de la metodología empleada. Así pues, en varios estudios la frecuencia de grabación ha sido limitada (e.g., a 50 Hz en Jackson y Gudgeon, 2004; Triolet, Benguigui, Le Runigo y Williams, 2013), o la velocidad del saque ha sido visiblemente inferior a la habitual (cf. Carboch, Süss y Kocib, 2014; Williams, Singer y Weigelt, 1998). También, en algunos estudios los participantes experimentados no han sido jugadores de nivel internacional (e.g., Avilés, Ruiz, Sanz y Navia, 2014), y el tamaño muestral ha sido muy pequeño (e.g., Gillet, Leroy, Thouvarecq, Mégrot y Stein, 2010). ! Además, en los diferentes trabajos se han utilizado una diversidad de métodos e instrumentos de medida y los criterios de codificación del inicio de los movimientos y de las respuestas han diferido; como consecuencia el lapso visomotor de respuesta (LVMr) ha sido muy dispar variando considerablemente de 198 a 410 ms. Considerando los inconvenientes señalados anteriormente, el presente estudio tuvo como objetivo determinar un modelo técnico de regulación temporal de los movimientos y de la respuesta del restador, tomando en cuenta el flujo continuo de información proporcionado por el sacador. Para ello, se realizó un análisis cronométrico de los restos de doce jugadores de diferente nivel deportivo (seis internacionales y seis nacionales) que respondieron de forma natural enviando sus devoluciones hacia las dianas. Se grabaron las acciones de los restadores y sacadores con una cámara Casio Exilim Pro Ex-F1 de alta velocidad (300 Hz) y luego se realizó un análisis imagen por imagen cada 3.33 ms. Una vez obtenidos los datos de los vídeos se realizaron análisis con las pruebas de ANOVA de un factor, ANCOVA con la velocidad del saque como covariable, U de Mann-Whitney y Chi-cuadrado de Pearson. En cuanto a la regulación del movimiento hasta el momento del despegue, los jugadores internacionales iniciaron sus acciones antes que los jugadores nacionales lo que podría indicar una mejor preparación al ejecutar los movimientos como reflejo del nivel de pericia. Los jugadores internacionales iniciaron la elevación del pie posterior a -293 ms y los jugadores nacionales a -202 ms. Todas estas acciones se fueron enlazando unas con otras y fue en el momento del impacto del sacador donde los restadores demostraron una remarcable coordinación perceptivo-motriz. Por consiguiente, los jugadores internacionales despegaron e iniciaron el vuelo a tan solo -6.5 ms del impacto y los jugadores nacionales lo hicieron más tarde a +19.5 ms. A lo largo de la secuencia temporal, todo parece indicar que las informaciones que utilizan los restadores interactúan entre sí; información más temprana y menos fiable para anticipar o moverse antes e información más tardía y más fiable para regular la temporalización de las acciones. Los restadores de nivel internacional y nacional anticiparon a nivel espacial en un bajo porcentaje (7.7% vs. 13.6%) y en tiempos similares (-127 vs. -118 ms) sugiriendo que la utilización de variables ópticas tempranas y menos fiables solo se produce en contadas ocasiones. Por otra parte, estos datos se relacionan con una gran precisión en la respuesta ya que tanto los jugadores internacionales como los nacionales demostraron un alto porcentaje de acierto al responder (95.4% vs. 96.7%). Se había señalado que los jugadores internacionales y nacionales se diferenciarían en el tiempo de caída (i.e., aterrizaje) del primer pie del salto preparatorio, sin embargo ese efecto no fue encontrado (128 vs. 135 ms). Tampoco se hallaron diferencias en el porcentaje de caída con el pie contrario a la dirección de la pelota (58% vs. 62%). Donde sí ambos grupos se diferenciaron fue en el tiempo de caída del segundo pie (147 vs. 168 ms). Esta diferencia de 21 ms fue crucial y fue una prueba de la mayor rapidez de los jugadores internacionales; sugiriendo que ésta acción se podría relacionar con el momento del inicio de la respuesta. Aunque los jugadores internacionales hayan demostrado ser más rápidos en relación con sus capacidades funcionales, ambos grupos no se diferenciaron en todas las variables relacionadas con el LVMr. Ellos no utilizaron esos valiosos milisegundos ganados en el instante de la caída del segundo pie para responder más pronto, ya que el LVMr del miembro superior fue el mismo para ambos grupos (179 vs. 174 ms). Es como si hubiesen tenido todo el tiempo del mundo para seguir ajustando sus acciones hasta el propio golpeo. Además, estos tiempos largos sugieren que en la gran mayoría de los restos la información clave que determinó la respuesta fue detectada (extraída) en momentos cercanos al golpeo del sacador y en la primera parte del vuelo de la pelota. Asimismo, se constató que en general el LVMr se ve influenciado por el tipo de información utilizada. De esta manera, cuando se tomaron en cuenta los ensayos en los que hubo anticipación espacial reflejados en el LVMr del cuerpo entero los tiempos disminuyeron (152 vs. 136 ms). Por otra parte, existieron ocasiones (13%) en los que tanto los jugadores internacionales como los nacionales respondieron tarde recibiendo saques directos (208 vs. 195 ms). Es muy posible que en estos casos los jugadores hayan tenido problemas para detectar la información respondiendo fuera de los márgenes temporales de acción lo que mermó su rendimiento. Lo mismo pudo haber ocurrido cuando ambos grupos de jugadores corrigieron el movimiento del miembro superior tras el impacto (17% vs. 10%) lo que aumentó el tiempo en responder al redirigir la respuesta hacia el lado correcto (208 vs. 205 ms). Además, los jugadores internacionales obtuvieron tiempos de movimiento menores que el de los jugadores nacionales (509 vs. 531 ms) lo que se reflejó en un tiempo total de actuación menor (683 vs. 703 ms). Por último, en cuanto al rendimiento del resto, los jugadores internacionales obtuvieron valores superiores a los jugadores nacionales (1.3 vs. 0.9). ABSTRACT Although there have been significant advances in laboratory studies with unrepresentative experimental designs (e.g., Farrow y Reid, 2012; Nieminen, Piirainen, Salmi, y Linnamo, 2013), today it is still unknown to full extent how tennis players of different levels of expertise calibrate or adjust their movements to the spatial-temporal demands present in the return of a first serve. Few studies have been carried out in situ and some aspects of the methodology most of them used can be questioned. Thus, in several studies the recording frequency has been limited (e.g., a 50 Hz en Jackson y Gudgeon, 2004; Triolet, Benguigui, Le Runigo y Williams, 2013), or serve speed was visibly lower than the usual one (cf. Carboch, Süss y Kocib, 2014; Williams, Singer y Weigelt, 1998). Also, in some studies, experienced participants have not played at international level (e.g., Avilés, Ruiz, Sanz y Navia, 2014), and the sample size has been very small (e.g., Gillet, Leroy, Thouvarecq, Mégrot y Stein, 2010). Furthermore, different works have used a variety of methods and measurement instruments and coding criteria of the onset of movements and responses have differed; due to this, visuomotor response delay (LVMr) has been very uneven, varying considerably from 198-410 ms. Considering the drawbacks mentioned above, this study aimed to determine a technical model of temporal regulation of movements and returner’s response, taking into account the continuous flow of information provided by the server. For this, a chronometric analysis of the returns of twelve players (six international and six national) of different sports level, that naturally responded by hitting their returns towards the targets, was performed. Actions of servers and returners were recorded with a Casio Exilim Pro Ex-F1 high speed camera (300 Hz) and then every 3.33 ms analysis was made frame by frame. Once the data of the videos were obtained, analyses were performed using one factor ANOVA test, ANCOVA with the speed of the serve as a covariate, U of Mann- Whitney and Pearson’s Chi-square test. As for the regulation of movement until the moment of serve, international players began their actions before national players, which could indicate that they were better prepared to execute movements reflecting the level of their expertise. International players began raising the rear foot at -293 ms and national players at -202 ms. All these actions were being linked to each other and it was at the moment of impact of the server when the receivers demonstrated a remarkable perceptual-motor coordination. Therefore, international players took off and started their flight just -6.5 ms before the serve and national players did the same somewhat later: +19.5 ms after the serve. Along the timeline, everything seems to indicate that the information used by returners interact with each other; early information which is less reliable to anticipate or move before, and later information more reliable appears to regulate the timing of actions. Returners of international and national levels anticipated at spatial level in a low percentage (7.7% vs. 13.6%) and in similar times (-127 vs. -118 ms) suggesting that the use of early and less reliable optical variables is only produced on rare occasions. Moreover, these data relate to a precise response as both international and national players showed a high percentage of success in responding (95.4% vs. 96.7%). It had been noted that international and national players would differ in the time the fall (i.e., landing) of the first foot of the split-step, however, this effect was not found (128 vs. 135 ms). No differences in the percentage of fall with the opposite foot to the direction of the ball (58% vs. 62%) were found. Where the two groups differed was in the time of the fall of the second foot (147 vs. 168 ms). This difference of 21 ms was crucial and it was a proof of mayor speed of international players; suggesting that this action could be related to the onset time of response. Although international players have proven to be faster in relation to their functional capabilities, both groups did not differ in all variables related to LVMr. They did not use those precious milliseconds earned at the time of the fall of the second foot to respond as soon, since the LVMr of the upper limb was the same for both groups (179 vs. 174 ms). It is as if they had all the time in the world to continue to adjust their actions until the return itself. Furthermore, these long times suggest that in the vast majority of the returns, key information that determined the response was detected (pick-up) in moments close to the hit of the server and in the first part of the ball flight. It was also found that in general the LVMr is influenced by the type of information used. Thus, when taking into account the trials during which there was spatial anticipation, reflected in LVMr of the whole body, the times decreased (152 vs. 136 ms). On the other hand, there were occasions (13%) where both international and national players responded late, thus receiving aces (208 vs. 195 ms). It is quite possible that in these cases the players have had trouble to pick-up information, responding out of temporary margins of action, which affected their performance. The same could have occurred when both groups of players corrected upper limb movement after impact (17% vs. 10%), which increased the time to respond and to redirect the return towards the right side (208 vs. 205 ms). Moreover, international players scored lower movement times than the national players (509 vs. 531 ms), which was reflected in a shorter total response time (683 vs. 703 ms). Finally, as far as the performance of return is concerned, international players scored above the national players values (1.3 vs. 0.9).