Biomarkers in Contrast-Induced Acute Kidney Injury: Towards A New Perspective.

Contrast-Induced Acute Kidney Injury (CI-AKI) remains a frequent iatrogenic condition since radiological procedures using intra-vascular iodinated contrast media (CM) are being widely administered for diagnostic and therapeutic purposes. Despite the improvement of the medical healthcare system worldwide, CI-AKI is still associated with direct short-term and indirect long-term outcomes including increased morbidity and mortality, especially in patients with underlying pre-existing renal function impairment, cardiovascular disease, or diabetes that could rapidly progress into Chronic Kidney Disease. Although the RIFLE (Risk, Injury, Failure, Loss, End-Stage Kidney Disease), AKIN (Acute Kidney Injury Network), and KDIGO (Kidney Disease Improving Global Outcomes) clinical criteria and recommendation guidelines are based on traditional "gold standard" biomarkers known as serum creatinine, glomerular filtration rate, and urinary output, new reliable serum and urinary biomarkers are still needed for an effective unified diagnostic strategy for AKI. Starting from previous and recent publications on the benefits and limitations of validated biomarkers responding to kidney injury, glomerular filtration, and inflammation among others, this review unravels the role of new emerging biomarkers used alone or in combination as reliable tools for early diagnosis and prognosis of CI-AKI, taking into account patients and procedures-risk factors towards a new clinical perspective.

Cilastatin as a Potential Anti-Inflammatory and Neuroprotective Treatment in the Management of Glaucoma.

Glaucoma is a neurodegenerative disease that causes blindness. In this study, we aimed to evaluate the protective role of cilastatin (CIL), generally used in the treatment of nephropathologies associated with inflammation, in an experimental mouse model based on unilateral (left) laser-induced ocular hypertension (OHT). Male Swiss mice were administered CIL daily (300 mg/kg, i.p.) two days before OHT surgery until sacrifice 3 or 7 days later. Intraocular Pressure (IOP), as well as retinal ganglion cell (RGC) survival, was registered, and the inflammatory responses of macroglial and microglial cells were studied via immunohistochemical techniques. Results from OHT eyes were compared to normotensive contralateral (CONTRA) and naïve control eyes considering nine retinal areas and all retinal layers. OHT successfully increased IOP values in OHT eyes but not in CONTRA eyes; CIL did not affect IOP values. Surgery induced a higher loss of RGCs in OHT eyes than in CONTRA eyes, while CIL attenuated this loss. Similarly, surgery increased macroglial and microglial activation in OHT eyes and to a lesser extent in CONTRA eyes; CIL prevented both macroglial and microglial activation in OHT and CONTRA eyes. Therefore, CIL arises as a potential effective strategy to reduce OHT-associated damage in the retina of experimental mice.

Novel Experimental Mouse Model to Study Malaria-Associated Acute Kidney Injury.

The impact of malaria-associated acute kidney injury (MAKI), one of the strongest predictors of death in children with severe malaria (SM), has been largely underestimated and research in this area has been neglected. Consequently, a standard experimental mouse model to research this pathology is still lacking. The purpose of this study was to develop an in vivo model that resembles the pathology in MAKI patients. In this study, unilateral nephrectomies were performed on wild-type mice prior to infection with Plasmodium berghei NK65. The removal of one kidney has shown to be an effective approach to replicating the most common findings in humans with MAKI. Infection of nephrectomized mice, compared to their non-nephrectomized counterparts, resulted in the development of kidney injury, evident by histopathological analysis and elevated levels of acute kidney injury (AKI) biomarkers, including urinary neutrophil gelatinase-associated lipocalin, serum Cystatin C, and blood urea nitrogen. Establishment of this in vivo model of MAKI is critical to the scientific community, as it can be used to elucidate the molecular pathways implicated in MAKI, delineate the development of the disease, identify biomarkers for early diagnosis and prognosis, and test potential adjunctive therapies.

Tendencias en la hospitalización por infección del tracto urinario en la población pediátrica de España en el período 2000-2015 / Trends in hospitalization for urinary tract infection in the paediatric age group in the 2000–2015 period in Spain

Objetivo: Analizar las tendencias en la hospitalización por infección del tracto urinario (ITU) en menores de 0-14 años en España en el período 2000-2015. Métodos: Estudio retrospectivo observacional realizado por medio del conjunto mínimo básico de datos hospitalario con códigos de la Clasificación Internacional de Enfermedades (CIE-9). Se incluyeron todos los ingresos por cistitis, pielonefritis e ITU de localización no especificada en niños menores de 15 años. Se recogieron datos sobre el sexo, edad, tipo de alta, diagnóstico principal, comorbilidades, estancia hospitalaria y coste total. Se calcularon tasas crudas de hospitalización por 1000 habitantes menores de 15 años y se llevó a cabo un análisis de regresión segmentada para identificar tendencias temporales. Resultados: En el período 2000-2015, hubo 124.696 ingresos en niños menores de 15 años. De este total, el 72,97% tenían de 0 a 1 año y el 60,12% recibió un diagnóstico de ITU no especificada, el 39,27% de pielonefritis, y el 0,52% de cistitis. La tasa bruta de hospitalización por ITU osciló entre 1,24 en 2000 y 0,98 en 2015. La tasa de hospitalización por ITU fue mayor en niñas que en niños. El análisis de regresión segmentada mostró una tendencia decreciente en la tasa de hospitalización por ITU, con un porcentaje de cambio anual medio (PCAM) del −1,5% (IC 95%: −2,4 a −0,6). Los cambios observados fueron mayores en niñas (PCAM −1,8; IC 95%: −2,5 a −1,0) y en el grupo de 7 a 10 años (PCAM −5,9; IC 95%: −6,7 a −5,2). Conclusiones: La tasa de hospitalización asociada a infección urinaria en pacientes menores de 15 años en España descendió durante el período 2000-2015. Las mayores tasas se dieron en niñas y en menores de 2 años. (AU)

Objective: To analyse the trends in hospital admissions related to urinary tract infection among children aged 0–14 years in Spain in the 2000–2015 period. Methods: We conducted a retrospective observational study using the minimum basic hospital discharge dataset system of Spain, which applies the International Classification of Diseases, version 9 (ICD-9) coding system. We included every hospitalization due to cystitis, pyelonephritis and unspecified UTI among children aged less than 15 years. We collected data on patient sex and age, type of discharge, main diagnosis, comorbidities, length of stay and overall cost. We calculated crude hospitalization rates per 1000 inhabitants aged less than 15 years and performed a joinpoint regression analysis to identify temporal trends. Results: In the 2000–2015 period, there were 124696 hospitalizations in children under 15 years. Of these patients, 72.97% were aged 0–1 year and 60.12% had a diagnosis of unspecified UTI, 39.27% of pyelonephritis, and 0.52% of cystitis. The crude rate of hospitalization due to UTI ranged from 1.24 in year 2000 to 0.98 in 2015. The rate of hospitalization was higher in female versus male patients. The joinpoint analysis found a decreasing trend in the rate of hospitalization due to UTI, with an average annual percent change (AAPC) of −1.5% (95% confidence interval [CI], −2.4 to −0.6). The largest decreases occurred in female patients (AAPC, −1.8; 95% CI, −2.5 to −1.0) and children aged 7–10 years (AAPC −5.9; 95% CI, −6.7 to −5.2). Conclusions: The rate of hospitalization related to UTI in Spain in patients aged up to 14 years decreased during the 2000–2015 period. The highest hospitalization rates occurred in female patients and in the 0-to-1 year age group. (AU)

Trends in hospitalization for urinary tract infection in the paediatric age group in the 2000-2015 period in Spain.

OBJECTIVE: To analyse the trends in hospital admissions related to urinary tract infection among children aged 0-14 years in Spain in the 2000-2015 period. METHODS: We conducted a retrospective observational study using the minimum basic hospital discharge dataset system of Spain, which applies the International Classification of Diseases, version 9 (ICD-9) coding system. We included every hospitalisation due to cystitis, pyelonephritis and unspecified UTI among children aged less than 15 years. We collected data on patient sex and age, type of discharge, main diagnosis, comorbidities, length of stay and overall cost. We calculated crude hospitalization rates per 1000 inhabitants aged less than 15 years and performed a joinpoint regression analysis to identify temporal trends. RESULTS: In the 2000-2015 period, there were 124 696 hospitalizations in children under 15 years. Of these patients, 72.97% were aged 0-1 year and 60.12% had a diagnosis of unspecified UTI, 39.27% of pyelonephritis, and 0.52% of cystitis. The crude rate of hospitalization due to UTI ranged from 1.24 in year 2000 to 0.98 in 2015. The rate of hospitalization was higher in female versus male patients. The joinpoint analysis found a decreasing trend in the rate of hospitalization due to UTI, with an average annual percent change (AAPC) of -1.5% (95% confidence interval [CI], -2.4 a -0.6). The largest decreases occurred in female patients (AAPC, -1.8; 95% CI, -2.5 a -1.0) and children aged 7-10 years (AAPC - 5.9; 95% CI, -6.7 a -5.2). CONCLUSIONS: The rate of hospitalization related to UTI in Spain in patients aged up to 14 years decreased during the 2000-2015 period. The highest hospitalization rates occurred in female patients and in the 0-to-1 year age group.

Immune response and reactogenicity after immunization with two-doses of an experimental COVID-19 vaccine (CVnCOV) followed by a third-fourth shot with a standard mRNA vaccine (BNT162b2): RescueVacs multicenter cohort study.

Background: There is no evidence to date on immunogenic response among individuals who participated in clinical trials of COVID-19 experimental vaccines redirected to standard national vaccination regimens. Methods: This multicentre, prospective controlled cohort study included subjects who received a COVID-19 experimental vaccine (CVnCoV)(test group, TG) - and unvaccinated subjects (control group, CG), selected among individuals to be vaccinated according to the Spanish vaccination program. All study subjects received BNT162b2 as a standard national vaccination schedule, except 8 (from CG) who received mRNA-1273 and were excluded from immunogenicity analyses. Anti-RBD antibodies level and neutralising titres (NT50) against G614, Beta, Mu, Delta and Omicron variants were analysed. Reactogenicity was also assessed. Findings: 130 participants (TG:92; CG:38) completed standard vaccination. In TG, median (IQR) of anti-RBD antibodies after first BNT162b2 dose were 10740·0 BAU/mL (4466·0-12500) compared to 29·8 BAU/mL (14·5-47·8) in CG (p <0·0001). Median NT50 (IQR) of G614 was 2674·0 (1865·0-3997·0) in TG and 63·0 (16·0-123·1) in CG (p <0·0001). After second BNT162b2 dose, anti-RBD levels increased to ≥12500 BAU/mL (11625·0-12500) in TG compared to 1859·0 BAU/mL (915·4-3820·0) in CG (p <0·0001). NT50 was 2626·5 (1756·0-5472·0) and 850·4 (525·1-1608·0), respectively (p <0·0001). Variant-specific (Beta, Mu, Omicron) response was also assessed. Most frequent adverse reactions were headache, myalgia, and local pain. No severe AEs were reported. Interpretation: Heterologous BNT162b2 as third and fourth doses in previously suboptimal immunized individuals elicit stronger immune response than that obtained with two doses of BNT162b2. This apparent benefit was also observed in variant-specific response. No safety concerns arose. Funding: Partly funded by the Institute of Health Carlos-III and COVID-19 Fund, co-financed by the European Regional Development Fund (FEDER) "A way to make Europe".

FKBP51, AmotL2 and IQGAP1 Involvement in Cilastatin Prevention of Cisplatin-Induced Tubular Nephrotoxicity in Rats.

The immunophilin FKBP51, the angiomotin AmotL2, and the scaffoldin IQGAP1 are overexpressed in many types of cancer, with the highest increase in leucocytes from patients undergoing oxaliplatin chemotherapy. Inflammation is involved in the pathogenesis of nephrotoxicity induced by platinum analogs. Cilastatin prevents renal damage caused by cisplatin. This functional and confocal microscopy study shows the renal focal-segmental expression of TNFα after cisplatin administration in rats, predominantly of tubular localization and mostly prevented by co-administration of cilastatin. FKBP51, AmotL2 and IQGAP1 protein expression increases slightly with cilastatin administration and to a much higher extent with cisplatin, in a cellular- and subcellular-specific manner. Kidney tubule cells expressing FKBP51 show either very low or no expression of TNFα, while cells expressing TNFα have low levels of FKBP51. AmotL2 and TNFα seem to colocalize and their expression is increased in tubular cells. IQGAP1 fluorescence increases with cilastatin, cisplatin and joint cilastatin-cisplatin treatment, and does not correlate with TNFα expression or localization. These data suggest a role for FKBP51, AmotL2 and IQGAP1 in cisplatin toxicity in kidney tubules and in the protective effect of cilastatin through inhibition of dehydropeptidase-I.

Role of Glucocorticoid Signaling and HDAC4 Activation in Diaphragm and Gastrocnemius Proteolytic Activity in Septic Rats.

Sepsis increases glucocorticoid and decreases IGF-1, leading to skeletal muscle wasting and cachexia. Muscle atrophy mainly takes place in locomotor muscles rather than in respiratory ones. Our study aimed to elucidate the mechanism responsible for this difference in muscle proteolysis, focusing on local inflammation and IGF-1 as well as on their glucocorticoid response and HDAC4-myogenin activation. Sepsis was induced in adult male rats by lipopolysaccharide (LPS) injection (10 mg/kg), and 24 h afterwards, rats were euthanized. LPS increased TNFα and IL-10 expression in both muscles studied, the diaphragm and gastrocnemius, whereas IL-6 and SOCS3 mRNA increased only in diaphragm. In comparison with gastrocnemius, diaphragm showed a lower increase in proteolytic marker expression (atrogin-1 and LC3b) and in LC3b protein lipidation after LPS administration. LPS increased the expression of glucocorticoid induced factors, KLF15 and REDD1, and decreased that of IGF-1 in gastrocnemius but not in the diaphragm. In addition, an increase in HDAC4 and myogenin expression was induced by LPS in gastrocnemius, but not in the diaphragm. In conclusion, the lower activation of both glucocorticoid signaling and HDAC4-myogenin pathways by sepsis can be one of the causes of lower sepsis-induced proteolysis in the diaphragm compared to gastrocnemius.

Lipidomics Reveals Cisplatin-Induced Renal Lipid Alterations during Acute Kidney Injury and Their Attenuation by Cilastatin.

Nephrotoxicity is a major complication of cisplatin-based chemotherapy, leading to acute kidney injury in ca. 30% of patients, with no preventive intervention or treatment available for clinical use. Cilastatin has proved to exert a nephroprotective effect for cisplatin therapies in in vitro and in vivo models, having recently entered clinical trials. A deeper understanding at the molecular level of cisplatin-induced renal damage and the effect of potential protective agents could be key to develop successful nephroprotective therapies and to establish new biomarkers of renal damage and nephroprotection. A targeted lipidomics approach, using LC-MS/MS, was employed for the quantification of 108 lipid species (comprising phospholipids, sphingolipids, and free and esterified cholesterol) in kidney cortex and medulla extracts from rats treated with cisplatin and/or cilastatin. Up to 56 and 63 lipid species were found to be altered in the cortex and medulla, respectively, after cisplatin treatment. Co-treatment with cilastatin attenuated many of these lipid changes, either totally or partially with respect to control levels. Multivariate analysis revealed that lipid species can be used to discriminate renal damage and nephroprotection, with cholesterol esters being the most discriminating species, along with sulfatides and phospholipids. Potential diagnostic biomarkers of cisplatin-induced renal damage and cilastatin nephroprotection were also found.

Ejercicios para mejorar la efectividad del Tokui-Waza en el Tachi Waza / Exercícios para melhorar a eficácia do Tokui-Waza em Tachi Waza / Exercises to improve the effectiveness of Tokui-Waza in Tachi Waza

RESUMEN En el judo actual, el dominio del Tokui-Waza o técnica favorita es imprescindible para vencer al contrario y alzarse con la victoria; no obstante, ello requiere de una adecuada preparación técnico táctica y su sistematización en el proceso de entrenamiento. A partir de la existencia de una serie de insuficiencias relacionadas con el proceder didáctico de los entrenadores para la enseñanza-aprendizaje de las acciones técnico tácticas del Tokui Waza y en aras de posibilitarle a las atletas, una adecuada formación en el proceso de preparación técnica, fundamentado en nuevas y mejores formas de afrontar y perfeccionar este proceso, la presente investigación tuvo como objetivo implementar un conjunto de ejercicios para el mejoramiento de la efectividad del Tokui Waza en el Tachi Waza del equipo femenino de judo, categoría 15-16 años de la Escuela Integral Deportiva de Pinar del Río, en correspondencia con las diferentes manifestaciones dentro del combate. Para ello, se trabajó con una muestra de 12 atletas integrantes de este equipo. Se emplearon los métodos y técnicas de investigación científica como: la observación, entrevista estandarizada e individual y el análisis de documentos. Como resultado se aporta un conjunto de ejercicios estructurados, que incluyen situaciones simplificadas y complejas que actúan didácticamente sobre los componentes de la preparación técnico-táctica además que constituyen una herramienta de utilidad para los entrenadores en el perfeccionamiento de su labor en la preparación deportiva de los atletas.

RESUMO No judô actual, o domínio do Tokui-Waza ou técnica favorita é essencial para derrotar o adversário e ganhar a vitória; contudo, isto requer uma preparação técnico-táctica adequada e a sua sistematização no processo de treino. Da existência de uma série de insuficiências relacionadas com o procedimento didáctico dos treinadores para o ensino-aprendizagem das acções técnico-tácticas de Tokui Waza e a fim de permitir aos atletas, um treino adequado no processo de preparação técnica, baseado em novas e melhores formas de abordar e melhorar este processo, o objectivo desta investigação era implementar um conjunto de exercícios para melhorar a eficácia de Tokui Waza no Tachi Waza da equipa feminina de judô, categoria 15-16 anos da Escuela Integral Deportiva de Pinar del Río, em correspondência com as diferentes manifestações no âmbito do combate. Para este efeito, trabalhou se com uma amostra de 12 atletas membros desta equipa. Foram utilizados métodos e técnicas de investigação científica, tais como: observação, entrevista padronizada e individualizada e análise de documentos. Como resultado, é fornecido um conjunto de exercícios estruturados, que incluem situações simplificadas e complexas que actuam didaticamente sobre os componentes da preparação técnico-táctica e que constituem uma ferramenta útil para os treinadores na melhoria do seu trabalho na preparação desportiva dos atletas.

ABSTRACT In the current sport of Judo, the mastery of the Tokui-Waza or favorite technique is essential to defeat the opponent and win the victory, however this requires an adequate technical-tactical preparation and its systematization in the training process. From the existence of a series of inadequacies related to the didactic procedure of the coaches for the teaching-learning of the technical-tactical actions of Tokui Waza, in order to enable the athletes an adequate training in the process of technical preparation, based on new and better ways to address and improve this process, the objective of this research is to implement a set of exercises to improve the effectiveness of Tokui Waza in the Tachi Waza of the women's Judo team, category 15-16 years old, of the Integral Sports School in Pinar del Río, in correspondence with the different manifestations within the combat. For this purpose, a sample of 12 athletes, members of this team, was used. Scientific research methods and techniques were used, such as: observation, standardized and individual interview, as well as document analysis. As a result, a set of structured exercises is provided, which include simplified and complex situations, which act didactically on the components of the technical-tactical preparation, constituting a useful tool for coaches in the improvement of their work in the sports preparation of athletes.

Effect of Cilastatin on Cisplatin-Induced Nephrotoxicity in Patients Undergoing Hyperthermic Intraperitoneal Chemotherapy.

Cisplatin is one of the most widely used chemotherapeutic agents in oncology, although its nephrotoxicity limits application and dosage. We present the results of a clinical study on prophylaxis of cisplatin-induced nephrotoxicity in patients with peritoneal carcinomatosis undergoing cytoreduction and hyperthermic intraperitoneal intraoperative chemotherapy (HIPEC-cisplatin). Prophylaxis was with imipenem/cilastatin. Cilastatin is a selective inhibitor of renal dehydropeptidase I in the proximal renal tubule cells that can reduce the nephrotoxicity of cisplatin. Unfortunately, cilastatin is not currently marketed alone, and can only be administered in combination with imipenem. The study has a retrospective part that serves as a control (n = 99 patients receiving standard surgical prophylaxis) and a prospective part with imipenem/cilastatin prophylaxis corresponding to the study group (n = 85 patients). In both groups, we collected specific data on preoperative risk factors of renal damage, fluid management, hemodynamic control, and urine volume during surgery (including the hyperthermic chemotherapy perfusion), as well as data on hemodynamic and renal function during the first seven days after surgery. The main finding of the study is that cilastatin may exert a nephroprotective effect in patients with peritoneal carcinomatosis undergoing cytoreduction and hyperthermic intraperitoneal cisplatin perfusion. Creatinine values remained lower than in the control group (ANOVA test, p = 0.037). This translates into easier management of these patients in the postoperative period, with significantly shorter intensive care unit (ICU) and hospital stay.

Ejercicios especiales para mejorar la ejecución de técnicas de piernas en judocas escolares / Exercícios especiais para melhorar a execução de técnicas de pernas em judocas escolares / Special exercises to improve the execution of leg techniques in school judo

Resumen Insuficiencias detectadas en la realización de técnicas de piernas de los judocas escolares de Pinar del Río motivaron la realización de esta investigación que tiene como objetivo: elaborar un conjunto de ejercicios especiales que contribuyan al desarrollo del trabajo de los entrenadores con este grupo de técnicas para mejorar la ejecución de los 14 atletas de esta categoría. Al inicio de este estudio, se realizaron observaciones a sesiones de entrenamiento, topes de control y competencias preparatorias para obtener información directa sobre el modo en que se manifiestan estas acciones. También se utilizó una entrevista a los entrenadores para conocer sus conocimientos, criterios y desempeño en el trabajo con estas técnicas y la encuesta para valorar el conocimiento de los atletas acerca de la importancia de la preparación técnica en estas acciones. Además, se practicó una medición mediante una prueba técnica para conocer el comportamiento de la ejecución de estas en los atletas motivo de investigación, en la cual las variables analizadas fueron: puntuación obtenida, total de acciones y forma de realización (directa, combinación o como contraataque). Este estudio permitió el conocimiento de las deficiencias presentadas por estos atletas en la ejecución de las técnicas de piernas, las cuales influyen de forma negativa en los resultados competitivos ya que estas se realizan con gran frecuencia durante el combate por su vinculación con otras técnicas en la realización de combinaciones y contraataques. Este trabajo es una herramienta valiosa para la labor de los entrenadores, dirigida a la preparación técnica del judoca.

Resumo As insuficiências detectadas no desempenho das técnicas de perna das judocas escolares de Pinar del Río motivaram a realização desta investigação que tem como objetivo: elaborar um conjunto de exercícios especiais que contribuam para o desenvolvimento do trabalho dos treinadores com este grupo de técnicas para melhorar o desempenho dos 14 atletas desta categoria. No início deste estudo, foram feitas observações a sessões de formação, paragens de controlo e concursos preparatórios para obter informações diretas sobre a forma como estas ações se manifestam. Uma entrevista com os treinadores foi também utilizada para descobrir os seus conhecimentos, critérios e desempenho no trabalho com estas técnicas e o inquérito foi utilizado para avaliar os conhecimentos dos atletas sobre a importância da preparação técnica nestas ações. Além disso, foi feita uma medição através de um teste técnico para conhecer o comportamento da execução destes nos atletas sob investigação, no qual as variáveis analisadas foram: pontuação obtida, total de ações e forma de execução (direta, combinada ou como contra-ataque). Este estudo permitiu o conhecimento das deficiências apresentadas por estes atletas na execução das técnicas de pernas, que influenciam de forma negativa nos resultados competitivos, uma vez que estes são feitos com grande frequência durante o combate pela sua implicação com outras técnicas na realização de combinações e contra-ataques. Este trabalho é um instrumento valioso para o trabalho dos treinadores, destinado à preparação técnica do judoca.

Abstract Insufficiencies detected in the performance of leg techniques of the school judokas of Pinar del Río motivated the realization of this research, which aims to develop a set of special exercises that contribute to the development of the work of coaches with this group of techniques to improve the performance of the 14 athletes in this category. At the beginning of this study, observations were made of training sessions, control stops and preparatory competitions to obtain direct information on how these actions are manifested. An interview with the coaches was also used to find out their knowledge, criteria, and performance at work with these techniques, and the survey was used to assess the athletes' knowledge about the importance of technical preparation in these actions. In addition, a measurement was carried out by means of a technical test, to know the behavior of the execution of these in the athletes reason for research, in which the variables analyzed were: score obtained, total of actions and form of performance (direct, combination or as a counterattack). This study found the knowledge of the deficiencies presented by these athletes, in the execution of leg techniques, which negatively influence competitive results since these are performed with great frequency during combat due to their link with other techniques in performing combinations and counterattacks. This work is a valuable tool for the work of the coaches aimed at the technical preparation of the judoka.

Nephroprotective Effect of Cilastatin against Gentamicin-Induced Renal Injury In Vitro and In Vivo without Altering Its Bactericidal Efficiency.

Gentamicin is a used antibiotic that causes nephrotoxicity in 10-20% of treatment periods, which limits its use considerably. Our results have shown that cilastatin may be a promising therapeutic alternative in toxin-induced acute kidney injury (AKI). Here, we investigated its potential use as a nephroprotector against gentamicin-induced AKI in vitro and in vivo. Porcine renal cells and rats were treated with gentamicin and/or cilastatin. In vivo nephrotoxicity was analyzed by measuring biochemical markers and renal morphology. Different apoptotic, oxidative and inflammatory parameters were studied at cellular and systemic levels. Megalin, mainly responsible for the entry of gentamicin into the cells, was also analyzed. Results show that cilastatin protects cells from gentamicin-induced AKI. Cilastatin decreased creatinine, BUN, kidney injury molecule-1 (KIM-1) and severe morphological changes previously increased by gentamicin in rats. The interference of cilastatin with lipid rafts cycling leads to decreased expression of megalin, and therefore gentamicin uptake and myeloid bodies, resulting in a decrease of apoptotic, oxidative and inflammatory events. Moreover, cilastatin did not prevent bacterial death by gentamicin. Cilastatin reduced gentamicin-induced AKI by preventing key steps in the amplification of the damage, which is associated to the disruption of megalin-gentamicin endocytosis. Therefore, cilastatin might represent a novel therapeutic tool in the prevention and treatment of gentamicin-induced AKI in the clinical setting.

Chemical speciation, distribution and leaching behavior of chlorides from municipal solid waste incineration bottom ash.

Municipal solid waste incineration (MSWI) bottom ash is an environmentally harmful solid waste that cannot be recycled without pre-treatment. The chloride content in bottom ash (BA) is a major obstacle that restricts its application as secondary building materials. Here, the chemical speciation of the chlorides in BA is systematically studied with multiple analytical techniques, i.e., quantitative XRD, microanalysis and XPS. In addition to halite (NaCl), several chloride-rich minerals are present in BA. These phases are hydrous metal oxides, ettringite, decomposed hydration products (C4A3) and incineration slag with a chloride content of 3.2%, 1.4%, 2.1% and 1.3%, respectively. For the first time, the real-time leaching profiles of chloride (up to 80 h) from BA were obtained with a chloride-ion specific electrode to explain the leaching mechanism. In the initial stage of leaching, highly soluble alkali salts (NaCl) and physisorbed chlorides (especially those adsorbed on hydrous metal oxides) are released, which is controlled by diffusion. Later, the leaching is controlled by the solubility/reactivity of the chloride-containing phases, such as ettringite and incineration slag. The results show that the release of chloride is not only a diffusion-controlled process, as reported in the literature, but also a reaction-controlled phenomenon, during which the chloride-rich phases decompose and release chlorides that are associated with them via sorption/incorporation.

Urinary excretion of parathyroid hormone-related protein correlates with renal function in control rats and rats with cisplatin nephrotoxicity.

Parathyroid hormone-related protein (PTHrP) and its receptor are abundantly expressed throughout the renal parenchyma, where PTHrP exerts a modulatory action on renal function. PTHrP upregulation is a common event associated with the mechanism of renal injury and repair. However, no study has yet explored the putative excretion of PTHrP in urine, including its potential relationship with renal function. In the present study, we tested this hypothesis by studying the well-known rat model of acute renal injury induced by the chemotherapeutic agent cisplatin. Using Western blot analysis, we could detect a single protein band, corresponding to intact PTHrP, in the urine of both control and cisplatin-injected rats, whose levels were significantly higher in the latter group. PTHrP was detected in rat urine by dot blot, and its quantification with two specific ELISA kits showed that, compared with control rats, those treated with cisplatin displayed a significant increase in urinary PTHrP (expressed as the PTHrP-to-creatinine ratio or 24-h excretion). In addition, a positive correlation between urinary PTHrP excretion and serum creatinine was found in these animals. In conclusion, our data demonstrate that PTHrP is excreted in rat urine and that this excretion is higher with the decrease of renal function. This suggests that urinary PTHrP levels might be a renal function marker.

La interconexión de las cargas en la planificación del entrenamiento, en el deporte de boxeo / The interconnection of the loads in the planning of the training, in the sport of boxing

Resumen El presente trabajo se enmarca en el contexto de las alternativas relacionadas con la planificación del entrenamiento deportivo, a partir de los modelos ATR (acumulación- transformación-realización). En correspondencia con las concepciones que hoy se utilizan en materia de planificación del entrenamiento, se evidencia la importancia de la interconexión de los contenidos en la preparación de los boxeadores, a partir de la conjugación de cargas cuyas rutas metabólicas son fundamentalmente la fosfagénica, anaerobia aláctica y la glicolitica, anaerobia láctica. El objetivo de la investigación radica en valorar el estado de la planificación del entrenamiento, en función de las tendencias más actuales, relacionadas con la interconexión de las cargas y el modelo ATR en la preparación de los boxeadores de la Academia Provincial de Pinar del Río. Para el estudio, se utilizó una muestra conformada por 13 atletas y siete entrenadores de la Academia Provincial de boxeo de Pinar del Río. Se emplearon diferentes técnicas y métodos como la entrevista a entrenadores, la observación y la medición. No obstante, los documentos y orientaciones de la Comisión Nacional de boxeo aún no cubren todas las expectativas de los colectivos pedagógicos de entrenadores de la academia, lo que deja un margen a la interpretación, por parte de las Comisiones Técnicas de los territorios en cuanto a las alternativas, a la planificación del entrenamiento y la definición de las direcciones e interconexión de estas. Resulta necesario encontrar un mecanismo que, en el plano didáctico, oriente mejor al entrenador en este sentido.

Abstract The present work is framed in the context of the alternatives related to the planning of the sport training, from the ATR models (accumulation-transformation-realization). In correspondence with the conceptions used today in training planning, the importance of the interconnection of the contents in the preparation of boxers is evident, from the conjugation of loads whose metabolic routes are fundamentally phosphagenic, alactic anaerobic and lactic anaerobic glycolithic. The objective of the research is to assess the situation of the training planning, based on the most current trends related to the interconnection of the loads and the ATR model in the preparation of the boxers of the Provincial Academy of Pinar del Río. For the study it was selected a sample, consisting on 13 athletes and 7 coaches from the Provincial Boxing Academy of Pinar del Río. Different methods and techniques such as the interview, the observation and the measurement were used. This study was carried outin correspondence with the most advanced conceptions regarding training planning. It reveals the importance of the interconnection of the contents in the preparation of the boxers from the combination of lactic anaerobic loads and lactic ones. However, the documents and guidelines of the National Boxing Commission still do not meet all the expectations of the pedagogical groups of trainers of the academy, which leaves a margin for interpretation by the Technical Commissions of the territories as regards alternatives, the planning of training and the definition of the directions and interconnection of these. It is necessary to find a mechanism that, at the didactic level, better orients the trainer in this sense.

Correction: Cisplatin-Induced Non-Oliguric Acute Kidney Injury in a Pediatric Experimental Animal Model in Piglets.

[This corrects the article DOI: 10.1371/journal.pone.0149013.].

Vacunación frente a la gripe estacional en las personas mayores. Evaluación de la vacuna tetravalente. Informe de posicionamie / Seasonal flu vaccination for older people: Evaluation of the quadrivalent vaccine. Positioning repor

La gripe es un importante problema de salud pública, particularmente en las personas susceptibles de presentar complicaciones asociadas, personas mayores, niños menores de 2 años, enfermos crónicos, inmunocomprometidos y embarazadas. Pero, además, la gripe tiene un gran impacto sanitario con un aumento de la demanda asistencial y un espectacular aumento de las visitas ambulatorias, sobrecargando los servicios de urgencias y hospitalarios. Durante los brotes epidémicos, las tasas de hospitalización de las personas mayores de 65 años son máximas y la mortalidad notificada por gripe en la temporada 2017/2018 ha sido de 960 defunciones. La vacunación antigripal estacional es el método con una mayor relación coste-efectividad de prevención primaria de la gripe, reduciendo las enfermedades respiratorias relacionadas, el número de visitas a las consultas médicas, el número de hospitalizaciones y muertes en personas de alto riesgo y el absentismo laboral en adultos. En los últimos años la gripe B ha recibido escasa atención en la literatura científica y, sin embargo, en períodos interepidémicos, la gripe B puede ser una de las principales causas de epidemias de gripe estacional, causando una considerable morbimortalidad y un aumento de costes. La vacuna tetravalente, a diferencia de la trivalente, obtiene una protección inmunológica frente al segundo linaje de la gripe B y, de acuerdo con una revisión crítica de la literatura científica, proporciona una protección más amplia sin afectar a la inmunogenicidad de las otras 3 cepas vacunales comunes a las vacunas trivalente y tetravalente. La vacuna tetravalente es coste-efectiva al disminuir el número de casos de gripe y siempre es una intervención rentable, con un importante ahorro de coste para el sistema de salud y para la sociedad, disminuyendo las tasas de hospitalización y de mortalidad asociadas a las complicaciones de la gripe

Influenza is a significant health problem, particularly in those persons susceptible to having associated complications, older people, children less than 2 years, patients with chronic diseases, immunocompromised patients, and pregnant women. But influenza also has a large impact on the health system, with an increase in the healthcare demand and a spectacular increase in outpatient visits, overloading the emergency and hospital services. During epidemic outbreaks, the hospital admission rates of people over 65 years are at a maximum, and the mortality notified for the 2017/2018 influenza season was 960 deaths. The seasonal anti-influenza vaccine is the method with a better cost-effective ratio of primary prevention of influenza, reducing associated respiratory diseases, the number of hospital admissions, and deaths in high risk individuals, as well as work absenteeism in adults. In the last few years, influenza B has received little attention in the scientific literature, although in the periods between epidemics influenza B can be one of the main causes of seasonal epidemics, causing considerable morbidity and mortality and an increase in costs. The quadrivalent vaccine has a second-line immunological protection against influenza B, and according to a critical review of the scientific literature, it provides wider protection without affecting immunogenicity of the other three vaccine strains common to the trivalent and tetravalent vaccine. The quadrivalent vaccine is cost-effective in reducing the number of influenza cases, and is always a worthwhile intervention, with a significant cost saving for the health system and for society, by reducing the hospital admission rates and mortality associated with the complications of influenza

[Seasonal flu vaccination for older people: Evaluation of the quadrivalent vaccine. Positioning report]. / Vacunación frente a la gripe estacional en las personas mayores. Evaluación de la vacuna tetravalente. Informe de posicionamiento.

Influenza is a significant health problem, particularly in those persons susceptible to having associated complications, older people, children less than 2 years, patients with chronic diseases, immunocompromised patients, and pregnant women. But influenza also has a large impact on the health system, with an increase in the healthcare demand and a spectacular increase in outpatient visits, overloading the emergency and hospital services. During epidemic outbreaks, the hospital admission rates of people over 65 years are at a maximum, and the mortality notified for the 2017/2018 influenza season was 960 deaths. The seasonal anti-influenza vaccine is the method with a better cost-effective ratio of primary prevention of influenza, reducing associated respiratory diseases, the number of hospital admissions, and deaths in high risk individuals, as well as work absenteeism in adults. In the last few years, influenza B has received little attention in the scientific literature, although in the periods between epidemics influenza B can be one of the main causes of seasonal epidemics, causing considerable morbidity and mortality and an increase in costs. The quadrivalent vaccine has a second-line immunological protection against influenza B, and according to a critical review of the scientific literature, it provides wider protection without affecting immunogenicity of the other three vaccine strains common to the trivalent and tetravalent vaccine. The quadrivalent vaccine is cost-effective in reducing the number of influenza cases, and is always a worthwhile intervention, with a significant cost saving for the health system and for society, by reducing the hospital admission rates and mortality associated with the complications of influenza. Supplement information: This article is part of a supplement entitled 'Seasonal flu vaccination for older people: Evaluation of the quadrivalent vaccine' which is sponsored by Sanofi-Aventis, S.A.