Calcium-activated potassium channels as amplifiers of TRPV4-mediated pulmonary edema formation in male mice.

BACKGROUND: As a mechanosensitive cation channel and key regulator of vascular barrier function, endothelial transient receptor potential vanilloid-type 4 (TRPV4) contributes critically to ventilator-induced lung injury (VILI) and edema formation. Ca2+ influx via TRPV4 can activate Ca2+-activated K + (KCa) channels, categorized into small (SK1-3), intermediate (IK1), and big (BK) KCa, which may in turn amplify Ca2+ influx by increasing the electrochemical Ca2+ gradient and thus, promote lung injury. We therefore hypothesized that endothelial KCa channels may contribute to the progression of TRPV4-mediated VILI. METHODS: Male C57Bl/6J mice were ventilated for 2 h with low or high tidal volumes in the presence or absence of the non-selective KCa antagonists apamin, charybdotoxin, or the selective IK1 antagonist TRAM34. Lung injury was similarly assessed in overventilated, endothelial-specific TRPV4-deficient mice or TRAM34-treated C57Bl/6J mice challenged with intratracheal acid installation. Changes in endothelial Ca2+ concentration ([Ca2+]i) were monitored by real-time imaging in isolated-perfused lungs in response to airway pressure elevation or in human pulmonary microvascular endothelial cells (HPMECs) in response to TRPV4 activation with or without inhibition of KCa channels. Analogously, changes in intracellular potassium concentration ([K+]i) and membrane potential (Vm) were imaged in vitro. RESULTS: Endothelial TRPV4 deficiency or inhibition of KCa channels, and most prominently inhibition of IK1 by TRAM34 attenuated VILI as demonstrated by reduced lung edema, protein leak, and by quantitative lung histology. All KCa antagonists reduced the [Ca2+]i response to mechanical stimulation or direct TRPV4 activation in isolated lungs. TRAM34 and charybdotoxin, yet not apamin prevented TRPV4-induced K+ efflux and membrane hyperpolarization in HPMECs. TRAM34 also attenuated the TRPV4 agonist-induced Ca2+ influx in vitro and reduced acid-induced lung injury in vivo. CONCLUSIONS: KCa channels, specifically IK1, act as amplifiers of TRPV4-mediated Ca2+ influx and establish a detrimental feedback that promotes barrier failure and drives the progression of VILI.

Regenerative Peripheral Nerve Interfaces (RPNIs) in Animal Models and Their Applications: A Systematic Review.

Regenerative Peripheral Nerve Interfaces (RPNIs) encompass neurotized muscle grafts employed for the purpose of amplifying peripheral nerve electrical signaling. The aim of this investigation was to undertake an analysis of the extant literature concerning animal models utilized in the context of RPNIs. A systematic review of the literature of RPNI techniques in animal models was performed in line with the PRISMA statement using the MEDLINE/PubMed and Embase databases from January 1970 to September 2023. Within the compilation of one hundred and four articles employing the RPNI technique, a subset of thirty-five were conducted using animal models across six distinct institutions. The majority (91%) of these studies were performed on murine models, while the remaining (9%) were conducted employing macaque models. The most frequently employed anatomical components in the construction of the RPNIs were the common peroneal nerve and the extensor digitorum longus (EDL) muscle. Through various histological techniques, robust neoangiogenesis and axonal regeneration were evidenced. Functionally, the RPNIs demonstrated the capability to discern, record, and amplify action potentials, a competence that exhibited commendable long-term stability. Different RPNI animal models have been replicated across different studies. Histological, neurophysiological, and functional analyses are summarized to be used in future studies.

Can a voice assistant help bystanders save lives? A feasibility pilot study chatbot in beta version to assist OHCA bystanders.

OBJECTIVE: Evaluating the usefulness of a chat bot as an assistant during CPR care by laypersons. METHODS: Twenty-one university graduates and university students naive in basic life support participated in this quasi-experimental simulation pilot trial. A version beta chatbot was designed to guide potential bystanders who need help in caring for cardiac arrest victims. Through a Question-Answering (Q&A) flowchart, the chatbot uses Voice Recognition Techniques to transform the user's audio into text. After the transformation, it generates the answer to provide the necessary help through machine and deep learning algorithms. A simulation test with a Laerdal Little Anne manikin was performed. Participants initiated the chatbot, which guided them through the recognition of a cardiac arrest event. After recognizing the cardiac arrest, the chatbot indicated the start of chest compressions for 2 min. Evaluation of the cardiac arrest recognition sequence was done via a checklist and the quality of CPR was collected with the Laerdal Instructor App. RESULTS: 91% of participants were able to perform the entire sequence correctly. All participants checked the safety of the scene and made sure to call 112. 62% place their hands on the correct compression point. A media time of 158 s (IQR: 146-189) was needed for the whole process. 33% of participants achieved high-quality CPR with a median of 60% in QCPR (IQR: 9-86). Compression depth had a median of 42 mm (IQR: 33-53) and compression rate had a median of 100 compressions/min (IQR: 97-100). CONCLUSION: The use of a voice assistant could be useful for people with no previous training to perform de out-of-hospital cardiac arrest recognition sequence. Chatbot was able to guide all participants to call 112 and to perform continuous chest compressions. The first version of the chatbot for potential bystanders naive in basic life support needs to be further developed to reduce response times and be more effective in giving feedback on chest compressions.

[Descriptive analysis of triggers, outcomes and the response of the health systems of child drowning in Galicia (Spain). A 17-year retrospective study.] / Análisis descriptivo de las causas, consecuencias y respuesta de los sistemas de Salud Pública en los ahogamientos pediátricos en Galicia. Un estudio retrospectivo de 17 años.

OBJECTIVE: Drowning is one of major public health problem in childhood. The aim of this paper was to describe the characteristics, locations, interventions and outcomes of child drowning in Galicia over 17 years. METHODS: Retrospective study of 100% of data of drowning amongst children aged 0-14 in the 2004-2020 period who were attended by the 061 emergency services in Galicia (Spain) was made. The characteristics of the incident, the victim's profile, location, type of medical care given and whether the victim survived or died were analysed using the Chi Square test to compare relative frequencies, and Odds Ratio to estimate the risk. RESULTS: During the period under study, 100 child drownings were recorded. In 55%, the main cause was lack of supervision. Young children (aged 0-4) primarily drowned in pools, and pre-teens and teenagers (aged 10-14) in the sea. In 42% of the incidents, bystanders performed CPR (37% included ventilation). Emergency services took 12 minutes on average to arrive at the scene. 6% died in situ and of the rest, were taken to hospital and admitted in 47% PICU, 26% ward, 8% discharged from Accident and Emergency (43% with pulmonary oedema, 41% with supplemental oxygen, 13% with IMV/NIMV [invasive mechanical ventilation/non-invasive]). Pneumonia was the most common complication and survival to discharge was 77%. CONCLUSIONS: Small children usually drown in pools and water facilities because of lack of supervision, whereas adolescents usually drown in the sea. CPR started by bystanders and the fast response of emergency services contributed to a high rate of survival. A large amount of data was lost during the process: accurate, standardized coding of drowning is necessary.

OBJETIVO: El ahogamiento es un importante problema de Salud Pública en la etapa infantil. El objetivo de este trabajo fue describir las características, localizaciones, intervenciones y resultados del ahogamiento pediátrico en Galicia durante 17 años. METODOS: Se realizó un estudio retrospectivo del 100% de los datos de ahogamiento de personas entre 0 y 14 años de edad del año 2004 a 2020, que fueran atendidos por los servicios de emergencias de Galicia 061. Se analizaron las características del incidente, perfil de la víctima, localización, tipo de asistencia sanitaria recibida y supervivencia respecto a muerte mediante el test Chi Cuadrado para comparar frecuencias relativas, y Odds Ratio para estimar el riesgo. RESULTADOS: Se registraron 100 ahogamientos pediátricos. En el 55% la principal causa fue la falta de supervisión. Los niños y niñas de 0-4 años se ahogaban mayoritariamente en piscinas, mientras que los/las adolescentes (10-14 años) en playas. En el 42% de los incidentes el testigo hizo reanimación cardiopulmonar (un 37% incluyó ventilaciones). Los servicios de emergencia tardaron 12 minutos de media en llegar. Un 6% falleció in situ y el resto fueron trasladados al hospital e ingresaron el 47% en UCI, 26% en planta, y 8% cursaron alta en Urgencias (43% con edema pulmonar, 41% con oxígeno suplementario, 13% con VMI/VMNI [ventilación mecánica invasiva/no invasiva]). La neumonía fue una complicación habitual y la supervivencia al alta fue del 77%. CONCLUSIONES: Los niños/as más pequeños se ahogan habitualmente en instalaciones acuáticas por falta de supervisión mientras que los/las adolescentes se suelen ahogar en playas marítimas. El inicio de la reanimación por parte de testigos y la rápida respuesta de los servicios de emergencias se asocia a una alta tasa de supervivencia. Numerosos datos fueron perdidos durante el proceso por lo que es necesaria una correcta y unificada codificación del ahogamiento.

Análisis descriptivo de las causas, consecuencias y respuesta de los sistemas de Salud Pública en los ahogamientos pediátricos en Galicia. Un estudio retrospectivo de 17 años / Descriptive analysis of triggers, outcomes and the response of the health systems of child drowning in Galicia (Spain). A 17-year retrospective study

FUNDAMENTOS: El ahogamiento es un importante problema de Salud Pública en la etapa infantil. El objetivo de este trabajofue describir las características, localizaciones, intervenciones y resultados del ahogamiento pediátrico en Galicia durante 17 años.MÉTODOS: Se realizó un estudio retrospectivo del 100% de los datos de ahogamiento de personas entre 0 y 14 años de edad delaño 2004 a 2020, que fueran atendidos por los servicios de emergencias de Galicia 061. Se analizaron las características del incidente,perfil de la víctima, localización, tipo de asistencia sanitaria recibida y supervivencia respecto a muerte mediante el test Chi Cuadradopara comparar frecuencias relativas, yOdds Ratio para estimar el riesgo.RESULTADOS: Se registraron 100 ahogamientos pediátricos. En el 55% la principal causa fue la falta de supervisión. Los niños yniñas de 0-4 años se ahogaban mayoritariamente en piscinas, mientras que los/las adolescentes (10-14 años) en playas. En el 42% delos incidentes el testigo hizo reanimación cardiopulmonar (un 37% incluyó ventilaciones). Los servicios de emergencia tardaron 12minutos de media en llegar. Un 6% fallecióin situ y el resto fueron trasladados al hospital e ingresaron el 47% en UCI, 26% en planta, y 8% cursaron alta en Urgencias (43% con edema pulmonar, 41% con oxígeno suplementario, 13% con VMI/VMNI [ventilación mecánicainvasiva/no invasiva]). La neumonía fue una complicación habitual y la supervivencia al alta fue del 77%.CONCLUSIONES: Los niños/as más pequeños se ahogan habitualmente en instalaciones acuáticas por falta de supervisión mien-tras que los/las adolescentes se suelen ahogar en playas marítimas. El inicio de la reanimación por parte de testigos y la rápidarespuesta de los servicios de emergencias se asocia a una alta tasa de supervivencia. Numerosos datos fueron perdidos durante elproceso por lo que es necesaria una correcta y unificada codificación del ahogamiento.(AU)

BACKGROUND: Drowning is one of major public health problem in childhood. The aim of this paper was to describe the characte-ristics, locations, interventions and outcomes of child drowning in Galicia over 17 years. METHODS: Retrospective study of 100% of data of drowning amongst children aged 0-14 in the 2004–2020 period who were attended by the 061 emergency services in Galicia (Spain) was made. The characteristics of the incident, the victim’s profile, location, type ofmedical care given and whether the victim survived or died were analysed using the Chi Square test to compare relative frequencies,and Odds Ratio to estimate the risk.RESULTS: During the period under study, 100 child drownings were recorded. In 55%, the main cause was lack of supervision.Young children (aged 0-4) primarily drowned in pools, and pre-teens and teenagers (aged 10-14) in the sea. In 42% of the incidents, bystanders performed CPR (37% included ventilation). Emergency services took 12 minutes on average to arrive at the scene. 6% diedin situ and of the rest, were taken to hospital and admitted in 47% PICU, 26% ward, 8% discharged from A&E (43% with pulmonaryoedema, 41% with supplemental oxygen, 13% with IMV/NIMV [invasive mechanical ventilation/non-invasive]). Pneumonia was the most common complication and survival to discharge was 77%.CONCLUSIONS: Small children usually drown in pools and water facilities because of lack of supervision, whereas adolescentsusually drown in the sea. CPR started by bystanders and the fast response of emergency services contributed to a high rate of survi-val. A large amount of data was lost during the process: accurate, standardized coding of drowning is necessary.(AU)

Grapevine morphological shade acclimation is mediated by light quality whereas hydraulic shade acclimation is mediated by light intensity.

Plants acclimate to shade by sensing light signals such as low photosynthetic active radiation (PAR), low blue light (BL) levels and low red-to-far red ratios (R:FR) trough plant photoreceptors cross talk. We previously demonstrated that grapevine is irresponsive to variations in R:FR and that BL-attenuation mediates morphological and architectural responses to shade increasing light interception and absorption efficiencies. However, we wondered if grapevine respond to low R:FR when BL is attenuated at the same time. Our objective was to evaluate if morphological, architectural and hydraulic acclimation to shade is mediated by low R:FR ratios and BL attenuation. To test this, we carried out experiments under natural radiation, manipulating light quality by selective sunlight exclusion and light supplementation. We grew grapevines under low PAR (LP) and four high PAR (HP) treatments: HP, HP plus FR supplementation (HP + FR), HP with BL attenuation (HP-B) and HP with BL attenuation plus FR supplementation (HP-B + FR). We found that plants grown under HP-B and HP-B + FR had similar morphological (stem and petiole length, leaf thickness and area), architectural (laminae' angles) and anatomical (stomatal density) traits than plants grown under LP. However, only LP plants presented lower stomata differentiation, lower δ13C and hence lower water use efficiency. Therefore, even under a BL and R:FR attenuated environment, morphological and architectural responses were modulated by BL but not by variation in R:FR. Meanwhile water relations were affected by PAR intensity but not by changes in light quality. Knowing grapevine responses to light quantity and quality are indispensable to adopt tools or design new cultural management practices that manipulate irradiance in the field intending to improve crop performance.

Activation of p21 limits acute lung injury and induces early senescence after acid aspiration and mechanical ventilation.

The p53/p21 pathway is activated in response to cell stress. However, its role in acute lung injury has not been elucidated. Acute lung injury is associated with disruption of the alveolo-capillary barrier leading to acute respiratory distress syndrome (ARDS). Mechanical ventilation may be necessary to support gas exchange in patients with ARDS, however, high positive airway pressures can cause regional overdistension of alveolar units and aggravate lung injury. Here, we report that acute lung injury and alveolar overstretching activate the p53/p21 pathway to maintain homeostasis and avoid massive cell apoptosis. A systematic pooling of transcriptomic data from animal models of lung injury demonstrates the enrichment of specific p53- and p21-dependent gene signatures and a validated senescence profile. In a clinically relevant, murine model of acid aspiration and mechanical ventilation, we observed changes in the nuclear envelope and the underlying chromatin, DNA damage and activation of the Tp53/p21 pathway. Absence of Cdkn1a decreased the senescent response, but worsened lung injury due to increased cell apoptosis. Conversely, treatment with lopinavir and/or ritonavir led to Cdkn1a overexpression and ameliorated cell apoptosis and lung injury. The activation of these mechanisms was associated with early markers of senescence, including expression of senescence-related genes and increases in senescence-associated heterochromatin foci in alveolar cells. Autopsy samples from lungs of patients with ARDS revealed increased senescence-associated heterochromatin foci. Collectively, these results suggest that acute lung injury activates p53/p21 as an antiapoptotic mechanism to ameliorate damage, but with the side effect of induction of senescence.

Epidemiological and clinical characteristics of community-acquired and nosocomial influenza cases and risk factors associated with complications: A four season analysis of all adult patients admitted in a tertiary hospital.

BACKGROUND: Information on the characteristics of patients with nosocomial influenza and associated complications is scarce. This study compared epidemiological and clinical characteristics of patients admitted with hospital-acquired influenza (HAI) to those with community-acquired influenza (CAI) and analyzed risk factors associated with complications. METHODS: This retrospective, observational study included all adult patients with confirmed influenza virus infection admitted to Son Espases University Hospital during the influenza season in Spain (October to May) from 2012-2013 to 2015-2016. Symptom onset before admission was included as CAI, and 2 days after admission or within 48 hours after previous discharge were considered as HAI. RESULTS: Overall, 666 patients with laboratory-confirmed influenza were included; 590 (88.6%) and 76 (11.4%) had CAI and HAI, respectively. Baseline characteristics and vaccination rates were similar in both groups. Patients with HAI had significantly fewer symptoms, less radiological alterations, and earlier microbiological diagnosis than those with CAI. Eighty-five (14.4%) and 20 (27.6%) CAI and HAI patients, respectively, experienced at least one complication, including septic shock, admission to the intensive care unit, mechanical ventilation or evolution to death (any one, P = .003). Univariate and multivariate binary logistic regression was performed to assess independent risk factors associated with the occurrence of complications: nosocomial infection, diabetes, oseltamivir treatment, having received no vaccination, microbiological delay, dyspnea, and the state of confusion were the most important significant factors. CONCLUSIONS: Our study shows the need to implement microbiological diagnostic measures in the first 48 hours to reduce HAI frequency and associated complications.

Non-structural carbohydrates and sugar export in grapevine leaves exposed to different light regimes.

Light is a main environmental factor that determines leaf microclimate within the vine, as well as its photosynthesis and carbohydrate metabolism. This study aimed to examine the relationships between photosynthesis, carbohydrate metabolism, and the expression of related genes in leaves of grapevine grown under different radiation regimes. During the 2014/2015 growing season, an experiment was conducted on a Malbec vineyard (Vitis vinifera L.) in which four radiation exposure treatments were established on the leaves: (1) East, (2) West, (3) Sun, and (4) Shade (i.e., reduction in light intensity). Diurnal dynamics of photosynthesis and non-structural carbohydrates were measured and leaf export rates were calculated. Transcript profiles of leaf sugar transporters (VvHT1, VvHT3, VvSUC27), a sucrose phosphate synthase enzyme (VvSPS), and invertases (VvGIN1, VvCWI) were also examined. We showed that East and Sun leaves had higher daily photosynthetic and export rates than West leaves, which was mainly explained by the environmental conditions (air and leaf temperature, VPDleaf-air ) and leaf water status. Shade leaves accumulated less starch and soluble sugars than exposed leaves, which correlated with a higher expression of hexose transporters and invertases. The hypotheses that these sugars in Shade leaves would play a role as signaling molecules and/or have increased sink strength and phloem unloading are discussed. These results allow us to understand the physiological and molecular behavior of leaves exposed to different radiation regimes, which can be used to design appropriate vineyard management practices.

Mechanisms underlying photosynthetic acclimation to high temperature are different between Vitis vinifera cv. Syrah and Grenache.

Photosynthesis acclimation to high temperature differs among and within species. Grapevine intra-specific variation in photosynthetic acclimation to elevated temperature has been scarcely assessed. Our objectives were to (i) evaluate the mechanisms underlying long-term acclimation of photosynthesis to elevated temperature in grapevine, and (ii) determine whether these responses are similar among two varieties. A warming experiment with well irrigated Grenache and Syrah field-grown plants was performed during two growing seasons comparing plants exposed at ambient temperature (control) with plants in open-top chambers (heating) that increased mean air temperature between 1.5 and 3.6°C. Photosynthetic acclimation was assessed through the response of net assimilation (An), Rubisco carboxylation rate (Vcmax) and electron transport rate (Jmax), at leaf temperatures from 20 to 40°C. Our results evidenced different mechanisms for photosynthetic acclimation to elevated temperature. Compared with control, Grenache heated increased An, maintaining higher Vcmax and Jmax at temperatures above 35°C. By contrast, Syrah heated and control presented similar values of An, Vcmax and Jmax, evidencing an adjustment of photosynthesis without increasing C assimilation. Both varieties increased the optimum temperature for An, but to a lesser extent when growth temperature was higher. Our study provides evidence that grapevine varieties present different acclimation mechanisms to expected warming.

Predictive Ability of Waist Circumference and Waist-to-Height Ratio for Cardiometabolic Risk Screening among Spanish Children.

An excess of fat mass has been associated with adverse cardiometabolic risk factors. Different anthropometric measures have been proposed as alternative non-invasive measures for obesity-related cardiometabolic risk. To evaluate the magnitude of association between waist circumference (WC) and waist-to-height ratio (WtHR) with cardiometabolic risk factors and metabolic syndrome and to determine the WtHR cutoff associated with a more favorable cardiometabolic risk profile in Spanish children, data were taken from a cross-sectional survey conducted in 2010 among 848 schoolchildren aged 8-11 years from 20 public schools in the province of Cuenca (Spain). Anthropometric variables, glucose, insulin, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), systolic (SBP) and diastolic blood pressure (DBP) and metabolic syndrome (MetS) were also analyzed. WtHR and WC had a good accuracy for TG, insulin, and MetS. The diagnostic odds ratio ranged from 2.95 to 9.07 for WtHR and from 5.30 to 27.40 for WC. The main result of the present study suggests that both WtHR and WC could be used as a screening tool to identify children with cardiometabolic abnormalities.

A functional-structural plant model that simulates whole- canopy gas exchange of grapevine plants (Vitis vinifera L.) under different training systems.

BACKGROUND AND AIMS: Scaling from single-leaf to whole-canopy photosynthesis faces several complexities related to variations in light interception and leaf properties. To evaluate the impact of canopy strucuture on gas exchange, we developed a functional-structural plant model to upscale leaf processes to the whole canopy based on leaf N content. The model integrates different models that calculate intercepted radiation, leaf traits and gas exchange for each leaf in the canopy. Our main objectives were (1) to introduce the gas exchange model developed at the plant level by integrating the leaf-level responses related to canopy structure, (2) to test the model against an independent canopy gas exchange dataset recorded on different plant architectures, and (3) to quantify the impact of intra-canopy N distribution on crop photosynthesis. METHODS: The model combined a 3D reconstruction of grapevine (Vitis vinifera) canopy architecture, a light interception model, and a coupled photosynthesis and stomatal conductance model that considers light-driven variations in N distribution. A portable chamber device was constructed to measure whole-plant gas exchange to validate the model outputs with data collected on different training systems. Finally, a sensitivity analysis was performed to evaluate the impact on C assimilation of different N content distributions within the canopy. KEY RESULTS: By considering a non-uniform leaf N distribution within the canopy, our model accurately reproduced the daily pattern of gas exchange of different canopy architectures. The gain in photosynthesis permitted by the non-uniform compared with a theoretical uniform N distribution was about 18 %, thereby contributing to the maximization of C assimilation. By contrast, considering a maximal N content for all leaves in the canopy overestimated net CO2 exchange by 28 % when compared with the non-uniform distribution. CONCLUSIONS: The model reproduced the gas exchange of plants under different training systems with a low error (10 %). It appears to be a reliable tool to evaluate the impact of a grapevine training system on water use efficiency at the plant level.

Effectiveness of a school-based physical activity intervention on adiposity, fitness and blood pressure: MOVI-KIDS study.

OBJECTIVE: To test a physical activity intervention (MOVI-KIDS) on obesity indicators, physical fitness and blood pressure (BP) in children. METHODS: A crossover randomised cluster trial was conducted, which comprised 1434 children (4-7 years old) from 21 schools in the provinces of Cuenca and Ciudad Real in the Castilla-La Mancha region of Spain. The intervention consisted of three 60 min sessions/week on weekdays between October 2013 and May 2014. Changes in anthropometric variables, physical fitness and BP parameters were measured. The analyses used were mixed regression models to adjust for baseline covariates under cluster randomisation. RESULTS: There was no significant improvement in overweight/obesity with the intervention compared with the control group in both sexes. Further, the intervention did not alter other adiposity indicators or BP parameters. Improvements in cardiorespiratory fitness were seen in girls (1.19; 95% CI 0.31 to 2.08; p=0.008), but not in boys. Finally, there was an improvement in velocity/agility in both girls (-2.51 s; 95% CI -3.98 to -1.05; p=0.001) and boys (-2.35 s; 95% CI -3.71 to -0.98; p=0.001), and in muscular strength in both girls (0.66; 95% CI 0.03 to 1.28; p=0.038) and boys (1.26; 95% CI 0.03 to 1.28; p<0.001). CONCLUSION: MOVI-KIDS was not successful in reducing the adiposity and maintained BP levels at previous healthy values in children. The intervention, however, showed significant improvements in cardiorespiratory fitness in girls, and muscular strength and velocity/agility in boys and girls. TRIAL REGISTRATION NUMBER: NCT01971840; Post-results.

Persistent risk for new, subsequent new and recurrent hepatocellular carcinoma despite successful anti-hepatitis B virus therapy and tumor ablation: The need for hepatitis B virus cure.

Hepatitis B virus (HBV) is one of the most significant hepatocarcinogens. The ultimate goal of anti-HBV treatment is to prevent the development of hepatocellular carcinoma (HCC). During the last two decades, with the use of currently available anti-HBV therapies (lamivudine, entecavir and tenofovir disoproxil fumatate), there has been a decrease in the incidence of HBV-associated HCC (HBV-HCC). Furthermore, several studies have demonstrated a reduction in recurrent or new HCC development after initial HCC tumor ablation. However, during an observation period spanning 10 to 20 years, several case reports have demonstrated the development of new, subsequent new and recurrent HCC even in patients with undetectable serum HBV DNA. The persistent risk for HCC is attributed to the presence of covalently closed circular DNA (cccDNA) in the hepatocyte nucleus which continues to work as a template for HBV replication. While a functional cure (loss of hepatitis B surface antigen and undetectable viral DNA) can be attained with nucleos(t)ide analogues, these therapies do not eliminate cccDNA. Of utmost importance is successful eradication of the transcriptionally active HBV cccDNA from hepatocyte nuclei which would be considered a complete cure. The unpredictable nature of HCC development in patients with chronic HBV infection shows the need for a complete cure. Continued support and encouragement for research efforts aimed at developing curative therapies is imperative. The aims of this minireview are to highlight these observations and emphasize the need for a cure for HBV.

Physical fitness reference standards for preschool children: The PREFIT project.

OBJECTIVES: Reference values are necessary for classifying children, for health screening, and for early prevention as many non-communicable diseases aggravate during growth and development. While physical fitness reference standards are available in children aged 6 and older, such information is lacking in preschool children. Therefore, the purposes of this study were (1) to provide sex-and age-specific physical fitness reference standards for Spanish preschool children; and (2) to study sex differences across this age period and to characterise fitness performance throughout the preschool period. DESIGN: Cross-sectional. METHODS: A total of 3179 preschool children (1678 boys) aged 2.8-6.4 years old from Spain were included in the present study. Physical fitness was measured using the PREFIT battery. RESULTS: Age- and sex-specific percentiles for the physical fitness components are provided. Boys performed better than girls in the cardiorespiratory fitness, muscular strength, and speed-agility tests over the whole preschool period studied and for the different percentiles. In contrast, girls performed slightly better than boys in the balance test. Older children had better performance in all fitness tests than their younger counterparts. CONCLUSIONS: Our study provides age- and sex-specific physical fitness reference standards in preschool children allowing interpretation of fitness assessment. Sexual dimorphism in fitness tests exists already at preschool age, and these differences become larger with age. These findings will help health, sport, and school professionals to identify preschool children with a high/very low fitness level, to examine changes in fitness over time, and to analyse those changes obtained due to intervention effects.

The risk of eating disorders and bone health in young adults: the mediating role of body composition and fitness.

PURPOSE: To analyze the independent relationship between the risk of eating disorders and bone health and to examine whether this relationship is mediated by body composition and cardiorespiratory fitness (CRF). METHODS: In this cross-sectional study, bone-related variables, lean mass, fat mass (by DXA), risk of eating disorders (SCOFF questionnaire), height, weight, waist circumference and CRF were measured in 487 university students aged 18-30 years from the University of Castilla-La Mancha, Spain. ANCOVA models were estimated to test mean differences in bone mass categorized by body composition, CRF or risk of eating disorders. Subsequently, linear regression models were fitted according to Baron and Kenny's procedures for mediation analysis. RESULTS: The marginal estimated mean ± SE values of total body bone mineral density for the categories "no risk of eating disorders" and "risk of eating disorders" were 1.239 ± 0.126 < 1.305 ± 0.089, P = 0.021. However, this relationship disappeared after adjustment for any of the parameters of body composition or CRF. Therefore, all body composition parameters (except for lean mass) and CRF turned out to be full mediators in the association between the risk of eating disorders and bone health in young adults. CONCLUSIONS: Body composition and CRF mediate the association between the risk of eating disorders and bone health. These findings highlight the importance of maintaining a healthy weight and good CRF for the prevention of the development of eating disorders and for the maintenance of good bone health in young adults. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

Movement behaviors and cardiometabolic risk in schoolchildren.

Growing evidence has accumulated in recent years showing that movement behaviors have important implications for health in children, especially for cardiovascular health, whose risk factors could track from childhood to adulthood. However, these findings are mixed and inconsistent in children. The aim of this study was to examine the relationship between different movement behaviors (sedentary behavior, physical activity and sleep duration) and cardiometabolic risk in schoolchildren. The study shows cross-sectional results of baseline measurement from 146 Spanish schoolchildren, aged 8-to-11 years old, participating in the MOVI-2 study. Movement behaviors were determined using accelerometry combined with self-reported sleep time. Cardiometabolic risk was assessed using a validated metabolic syndrome index. Logistic regression analysis showed that higher levels of vigorous physical activity (OR = 0.110, p = 0.004) and sleeping more than 9 hours (OR = 0.269, p = 0.015) could be protective factors against metabolic syndrome risk in children. ANCOVA analysis showed associations between vigorous physical activity and waist circumference (p < 0.001), and sleep time with insulin resistance (p = 0.017) and lipid profile (p = 0.035). No association was observed between light and moderate physical activity, sedentary behavior and metabolic syndrome (index and components). No statistically significant differences were found for blood pressure and any of the movement behaviors. Our data suggest that both the amount of vigorous physical activity accumulated and sleep duration are independently associated with higher cardiometabolic risk in children.

No Association Between Active Commuting to School, Adiposity, Fitness, and Cognition in Spanish Children: The MOVI-KIDS Study.

BACKGROUND: Walking and bicycling (active commuting) to school may be a useful strategy to increase the daily amount of physical activity, and, potentially, improve children's health. However, it is unclear whether active commuting to school (ACS) has the potential to improve physical health and cognitive performance in children. Our aim was to examine the relationship between ACS with adiposity indicators, physical fitness, and cognitive performance in 4- to 7-year-old children. METHODS: We conducted a cross-sectional study with 1159 children from the provinces of Cuenca and Ciudad Real, Spain. ACS was self-reported by parents. Adiposity (body mass index, waist circumference, body fat mass, and triceps skinfold thickness) and physical fitness (cardiorespiratory and muscular fitness) were measured by standard procedures. Cognitive performance was assessed using the Battery of General and Differential Aptitudes. Data analysis included analysis of covariance. RESULTS: We found no differences in adiposity, physical fitness, and cognitive performance between active commuters and nonactive commuters. CONCLUSIONS: Walking to school had no positive impact on adiposity, physical fitness, and cognition in 4- to 7-year-old children. Future studies should examine the intensity and duration of walking to school needed to provide benefits in health and cognitive performance.

Preventing loss of mechanosensation by the nuclear membranes of alveolar cells reduces lung injury in mice during mechanical ventilation.

The nuclear membrane acts as a mechanosensor that drives cellular responses following changes in the extracellular environment. Mechanically ventilated lungs are exposed to an abnormally high mechanical load that may result in clinically relevant alveolar damage. We report that mechanical ventilation in mice increased the expression of Lamin-A, a major determinant of nuclear membrane stiffness, in alveolar epithelial cells. Lamin-A expression increased and nuclear membrane compliance decreased in human bronchial epithelial cells after a mechanical stretch stimulus and in a murine model of lung injury after positive-pressure ventilation. Reducing Lamin-A maturation by depletion of the protease-encoding gene Zmpste24 preserved alveolar nuclear membrane compliance after mechanical ventilation in mice. Ventilator-induced proapoptotic gene expression changes and lung injury were reduced in mice lacking Zmpste24 compared to wild-type control animals. Similarly, treatment with the human immunodeficiency virus protease inhibitors lopinavir and ritonavir reduced the accumulation of Lamin-A at nuclear membranes and preserved nuclear membrane compliance after mechanical ventilation, mimicking the protective phenotype of Zmpste24-/- animals. These results show that the pathophysiological response to lung mechanical stretch is sensed by the nuclear membranes of lung alveolar cells, and suggest that protease inhibitors might be effective in preventing ventilator-induced lung injury.

Effects of an exercise program on hepatic metabolism, hepatic fat, and cardiovascular health in overweight/obese adolescents from Bogotá, Colombia (the HEPAFIT study): study protocol for a randomized controlled trial.

BACKGROUND: A considerable proportion of contemporary youth have a high risk of obesity-related disorders such as cardiovascular disease, metabolic syndrome, or non-alcoholic fatty liver disease (NAFLD). Although there is consistent evidence for the positive effects of physical activity on several health aspects, most adolescents in Colombia are sedentary. It is, therefore, important to implement strategies that generate changes in lifestyle. The HEPAFIT study aims to examine whether a 6-month exercise program has benefits for hepatic fat content and cardiovascular health outcomes among overweight/obese adolescents from Bogotá, Colombia. METHODS/DESIGN: Altogether, 100 hundred overweight/obese, sedentary adolescents (aged 11-17 years) attending two public schools in Bogotá, Colombia, will be included in a parallel-group randomized controlled trial. Adolescents will be randomly assigned to an intervention group following one of four curricula: (1) the standard physical education curriculum (60 min per week of physical activity, n = 25) at low-to-moderate intensity; (2) a high-intensity physical education curriculum (HIPE, n = 25), consisting of endurance and resistance games and non-competitive activities, such as running, gymkhanas, lifting, pushing, wrestling, or hauling, for 60-min sessions, three times per week, with an energy expenditure goal of 300 to 500 kcal/session at 75-85% maximum heart rate (HRmax); (3) a low-to-moderate intensity physical education curriculum (LIPE, n = 25) consisting of endurance and resistance games and non-competitive activities (e.g., chasing, sprinting, dribbling, or hopping) for 60-min sessions, three times per week with an energy expenditure goal of 300 kcal/session at 55-75% HRmax; and (4) a combined HIPE and LIPE curriculum (n = 25). The HIPE, LIPE, and combined interventions were performed in addition to the standard physical education curriculum. The primary outcome for effectiveness is liver fat content, as measured by the controlled attenuation parameter 1 week after the end of the intervention program. DISCUSSION: The translational focus may be suitable for collecting new information in a school setting on the possible effects of physical activity interventions to reduce liver fat content and to improve metabolic profiles and the cardiometabolic health of overweight/obese adolescents. This may lead to the more efficient use of school physical education resources. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02753231 . Registered on 21 April 2016.