Purpose:To examine the effects of a school-based karate intervention on academic achievement,psychosocial functioning,and physical fitness in children aged 7-8 years.Methods:Twenty schools in 5 different European coun...Purpose:To examine the effects of a school-based karate intervention on academic achievement,psychosocial functioning,and physical fitness in children aged 7-8 years.Methods:Twenty schools in 5 different European countries(2 second-grade classrooms per school)participated in a cluster randomized controlled trial(Sport at School trial).Participants were assigned to either a control group,which continued with their habitual physical education lessons,or to an intervention group,which replaced these lessons with a 1-year karate intervention(Karate Mind and Movement program).A total of 721 children(344 girls and 377 boys,7.4±0.5 years old,mean±SD)completed the study,of which 333 and 388 were assigned to the control group and intervention group,respectively.Outcomes included academic performance(average grade),psychosocial functioning(Strengths and Difficulties Questionnaire for parents),and different markers of physical fitness(cardiorespiratory fitness,balance,and flexibility).Results:The intervention provided small but significant benefits compared to the control group for academic achievement(d=0.16;p=0.003),conduct problems(d=-0.28;p=0.003),cardiorespiratory fitness(d=0.36;p<0.001),and balance(d=0.24;p=0.015).There was a trend towards significant benefits for flexibility(d=0.24;p=0.056).No significant benefits were observed for other variables,including psychosocial difficulties,emotional symptoms,hyperactivity/inattention,peer problems,or prosocial behaviour(all p>0.05).Conclusion:A 1-year school-based karate intervention was effective in improving academic achievement,conduct problems,and physical fitness in primary school children.The results support the inclusion of karate during physical education lessons.展开更多
BACKGROUND The quality-adjusted life year(QALY)is a metric that is increasingly used today in the field of health economics to evaluate the value of different medical treatments and procedures.Surgical waiting lists(S...BACKGROUND The quality-adjusted life year(QALY)is a metric that is increasingly used today in the field of health economics to evaluate the value of different medical treatments and procedures.Surgical waiting lists(SWLs)represent a pressing problem in public healthcare.The QALY measure has rarely been used in the context of surgery.It would be interesting to know how many QALYs are lost by patients on SWLs.AIM To investigate the relationship between QALYs and SWLs in a systematic review of the scientific literature.METHODS The study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement.An unlimited search was carried out in PubMed,updated on January 19,2024.Data on the following variables were investigated and analyzed:Specialty,country of study,procedure under study,scale used to measure QALYs,the use of a theoretical or real-life model,objectives of the study and items measured,the economic value assigned to the QALY in the country in question,and the results and conclusions published.RESULTS Forty-eight articles were selected for the study.No data were found regarding QALYs lost on SWLs.The specialties in which QALYs were studied the most in relation to the waiting list were urology and general surgery,with 15 articles each.The country in which the most studies of QALYs were carried out was the United States(n=21),followed by the United Kingdom(n=9)and Canada(n=7).The most studied procedure was organ transplantation(n=39),including 15 kidney,14 liver,5 heart,4 lung,and 1 intestinal.Arthroplasty(n=4),cataract surgery(n=2),bariatric surgery(n=1),mosaicplasty(n=1),and septoplasty(n=1)completed the surgical interventions included.Thirty-nine of the models used were theoretical(the most frequently applied being the Markov model,n=34),and nine were real-life.The survey used to measure quality of life in 11 articles was the European Quality of Life-5 dimensions,but in 32 articles the survey was not specified.The willingness-to-pay per QALY gained ranged from$100000 in the United States to€20000 in Spain.CONCLUSION The relationship between QALYs and SWLs has only rarely been studied in the literature.The rate of QALYs lost on SWLs has not been determined.Future research is warranted to address this issue.展开更多
Objective Incidences of post-transurethral resection of the prostate(post-TURP)strictures are between 2.2%and 9.8%.Stricture commonly occurs within the first 6 months.Our objective was to assess the outcomes of patien...Objective Incidences of post-transurethral resection of the prostate(post-TURP)strictures are between 2.2%and 9.8%.Stricture commonly occurs within the first 6 months.Our objective was to assess the outcomes of patients with obliterative strictures post-TURP that underwent a double-face urethroplasty.Methods This is a single-center prospective study of 17 patients with obliterative proximal bulbar stricture post-TURP who underwent double-face graft urethroplasty by two surgeons between January 2014 and January 2020.We defined post-TURP obliterative strictures as those patients who presented with complete or almost complete obstruction of the urethral lumen and who have had a history of acute urine retention.We have excluded patients with bladder neck contracture.Primary outcome was treatment success,defined as the no need for further treatments.Secondary outcome was post-urethroplasty continent rate.Results Seventeen patients were included in the study with median age of 66(interquartile range 40-77)years;median time of follow-up was 24(interquartile range 12-84)months;median stricture length was 4(interquartile range 2-6)cm.Of the 17 patients,15(88.2%)were successful.All patients were continent after urethroplasty.Conclusion With mid-term follow-up,treatment of obliterative proximal bulbar strictures with double-face buccal mucosa graft is a safe and effective procedure.Obliterative proximal bulbar strictures merit double-face urethroplasty with high-rate success and functional outcomes.展开更多
Hepatocellular carcinoma (HCC), chronic hepatitis B (CHB) and chronic hepatitis C (CHC) are characterized by exhaustion of the specific CD8<sup>+</sup> T cell response. This process involves enhancement of...Hepatocellular carcinoma (HCC), chronic hepatitis B (CHB) and chronic hepatitis C (CHC) are characterized by exhaustion of the specific CD8<sup>+</sup> T cell response. This process involves enhancement of negative co-stimulatory molecules, such as programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte antigen-4 (CTLA-4), 2B4, Tim-3, CD160 and LAG-3, which is linked to intrahepatic overexpression of some of the cognate ligands, such as PD-L1, on antigen presenting cells and thereby favouring a tolerogenic environment. Therapies that disrupt these negative signalling mechanisms represent promising therapeutic tools with the potential to restore reactivity of the specific CD8<sup>+</sup> T cell response. In this review we discuss the impressive in vitro and in vivo results that have been recently achieved in HCC, CHB and CHC by blocking these negative receptors with monoclonal antibodies against these immune checkpoint modulators. The article mainly focuses on the role of CTLA-4 and PD-1 blocking monoclonal antibodies, the first ones to have reached clinical practice. The humanized monoclonal antibodies against CTLA-4 (tremelimumab and ipilimumab) and PD-1 (nivolumab and pembrolizumab) have yielded good results in testing of HCC and chronic viral hepatitis patients. Trelimumab, in particular, has shown a significant increase in the time to progression in HCC, while nivolumab has shown a remarkable effect on hepatitis C viral load reduction. The research on the role of ipilimumab, nivolumab and pembrolizumab on HCC is currently underway.展开更多
Chemokines produced in the liver during hepatitis C virus(HCV) infection induce migration of activated T cells from the periphery to infected parenchyma.The milieu of chemokines secreted by infected hepatocytes is pre...Chemokines produced in the liver during hepatitis C virus(HCV) infection induce migration of activated T cells from the periphery to infected parenchyma.The milieu of chemokines secreted by infected hepatocytes is predominantly associated with the T-helper cell/Tc1 T cell(Th1/Tc1) response.These chemokines consist of CCL3(macrophage inflammatory protein-1α;MIP-1α),CCL4(MIP-1β),CCL5(regulated on activation normal T cell expressed and secreted;RANTES),CXCL10(interferon-γ-inducible protein-10;IP-10),CXCL11(interferon-inducible T-cell α chemoattractant;I-TAC),and CXCL9(monokine induced by interferon γ;Mig) and they recruit T cells expressing either CCR5 or CXCR3 chemokine receptors.Intrahepatic and peripheral blood levels of these chemokines are increased during chronic hepatitis C.The interaction between chemokines and their receptors is essential in recruiting HCV-specific T cells to control the infection.When the adaptive immune response fails in this task,non-specific T cells without the capacity to control the infection are also recruited to the liver,and these are ultimately responsible for the persistent hepatic damage.The modulation of chemokine receptor expression and chemokine secretion could be a viral escape mechanism to avoid specific T cell migration to the liver during the early phase of infection,and to maintain liver viability during the chronic phase,by impairing non-specific T cell migration.Some chemokines and their receptors correlate with liver damage,and CXCL10(IP-10) and CXCR3 levels have shown a clinical utility as predictors of treatment response outcome.The regulation of chemokines and their receptors could be a future potential therapeutic target to decrease liver inflammation and to increase specific T cell migration to the infected liver.展开更多
During the course of cirrhosis, there is a progressive deterioration of cardiac function manifested by the disappearance of the hyperdynamic circulation due to afailure in heart function with decreased cardiac output....During the course of cirrhosis, there is a progressive deterioration of cardiac function manifested by the disappearance of the hyperdynamic circulation due to afailure in heart function with decreased cardiac output. This is due to a deterioration in inotropic and chronotropic function which takes place in parallel with a diastolic dysfunction and cardiac hypertrophy in the absence of other known cardiac disease. Other findings of this specific cardiomyopathy include impaired contractile responsiveness to stress stimuli and electrophysiological abnormalities with prolonged QT interval. The pathogenic mechanisms of cirrhotic cardiomyopathy include impairment of the b-adrenergic receptor signalling, abnormal cardiomyocyte membrane lipid composition and biophysical properties, ion channel defects and overactivity of humoral cardiodepressant factors. Cirrhotic cardiomyopathy may be difficult to determine due to the lack of a specific diagnosis test. However, an echocardiogram allows the detection of the diastolic dysfunction and the E/e′ ratio may be used in the followup progression of the illness. Cirrhotic cardiomyopathy plays an important role in the pathogenesis of the impairment of effective arterial blood volume and correlates with the degree of liver failure. A clinical consequence of cardiac dysfunction is an inadequate cardiac response in the setting of vascular stress that may result in renal hypoperfusion leading to renal failure. The prognosis is difficult to establish but the severity of diastolic dysfunction may be a marker of mortality risk. Treatment is non-specific and liver transplantation may normalize the cardiac function.展开更多
Hepatitis B virus (HBV) infection is a global public health problem that concerns 350 million people worldwide. Individuals with chronic hepatitis B (CriB) are at increased risk of developing liver cirrhosis, hepa...Hepatitis B virus (HBV) infection is a global public health problem that concerns 350 million people worldwide. Individuals with chronic hepatitis B (CriB) are at increased risk of developing liver cirrhosis, hepatic de-compensation and hepatocellular carcinoma. To maintain undetectable viral load reduces chronic infection complications. There is no treatment that eradicates HBV infection. Current drugs are expensive, are associated with adverse events, and are of limited efficacy. Current guidelines try to standardize the clinical practice. Nevertheless, controversy remains about management of asymptomatic patients with CriB who are hepatitis B e antigen (HBeAg)-positive with normal alanine aminotransferase, and what is the cut-off value of viral load to distinguish HBeAg- negative CriB patients and inactive carriers. We discuss in detail why DNA level alone is not sufficient to begin treatment of CriB.展开更多
Chronic hepatitis B(CHB) remains a challenging global health problem, with nearly one million related deaths per year. Nucleos(t)ide analogue(NA) treatment suppresses viral replication but does not provide complete cu...Chronic hepatitis B(CHB) remains a challenging global health problem, with nearly one million related deaths per year. Nucleos(t)ide analogue(NA) treatment suppresses viral replication but does not provide complete cure of the hepatitis B virus(HBV) infection. The accepted endpoint for therapy is the loss of hepatitis B surface antigen(HBs Ag), but this is hardly ever achieved. Therefore, indefinite treatment is usually required. Many different studies have evaluated NA therapy discontinuation after several years of NA treatment and before HBs Ag loss. The results have indicated that the majority of patients can remain off therapy, with some even reaching HBs Ag seroconversion. Fortunately, this strategy has proved to be safe, but it is essential to consider the risk of liver damage and other comorbidities and to ensure aclose follow-up of the candidates before considering this strategy. Unanswered questions remain, namely in which patients could this strategy be effective and what is the optimal time point at which to perform it. To solve this enigma, we should keep in mind that the outcome will ultimately depend on the equilibrium between HBV and the host's immune system. Viral parameters that have been described as good predictors of response in HBe Ag(+) cases, have proven useless in HBe Ag(-) ones. Since antiviral immunity plays an essential role in the control of HBV infection, we sought to review and explain potential immunological biomarkers to predict safe NA discontinuation in both groups.展开更多
· AIM: To determine the effect of topical 0.05% cyclosporine A (CsA) on corneal endothelium in patients with dry eye disease. · METHODS: Observational, prospective, case series study. Fifty-five eyes of 29 c...· AIM: To determine the effect of topical 0.05% cyclosporine A (CsA) on corneal endothelium in patients with dry eye disease. · METHODS: Observational, prospective, case series study. Fifty-five eyes of 29 consecutive patients (9 males and 20 females; median age: 66.8 years, interquartile range: 61 -73.2 years) with moderate -severe dry eye disease were evaluated. All patients were treated with topical 0.05% CsA ophthalmic emulsion twice a day in addition to lubricant eyedrops 5 times a day. The follow- up period was 12 months. Before treatment and at 3 and 12 months post -treatment central corneal specular microscopy was performed. The endothelial cell density (ECD), coefficient of variation of cell size (CoV), and percentage of hexagonal cells (Hex %) were analyzed. ·RESULTS: The median ECDs pre-treatment and at 3 and 12 months post-treatment were 2 352.5/mm 2 (inter- quartile range, 2 178 -2548.5), 2 364/mm 2 (interquartile range, 2 174.25 -2 657.5), and 2 366 cells/mm 2 (inter - quartile range, 2 174.75-2 539.75), respectively (P=0.927, one way ANOVA). The median CoVs pre-treatment and at 3 and 12 months post -treatment were 34.5 (interquartile range, 30 -37), 35 (interquartile range, 30 -38), and 34 (interquartile range, 30.75-38.25), respectively (P=0.7193, one way ANOVA). The median Hex % values pre - treatment and at 3 and 12 months post -treatment were 53 (interquartile range, 47 -58), 54 (interquartile range, 45.75 -59), and 50.5 (interquartile range, 45.75 -58), respectively (P=0.824, one way ANOVA). · CONCLUSION: Treatment of patients with dry eye disease for 12 months with topical 0.05% CsA does not seem to cause substantial changes on corneal endothelium.展开更多
Occult hepatitis B virus(HBV) infection is a world-wide entity,following the geographical distribution of detectable hepatitis B.This entity is defined as the persistence of viral genomes in the liver tissue and in so...Occult hepatitis B virus(HBV) infection is a world-wide entity,following the geographical distribution of detectable hepatitis B.This entity is defined as the persistence of viral genomes in the liver tissue and in some instances also in the serum,associated to negative HBV surface antigen serology.The molecular basis of the occult infection is related to the life cycle of HBV,which produces a covalently closed circular DNA that persists in the cell nuclei as an episome,and serves as a template for gene transcription.The mechanism responsible for the HBsAg negative status in occult HBV carriers is a strong suppression of viral replication,probably due to the host’s immune response,co-infection with other infectious agents and epigenetic factors.There is emerging evidence of the potential clinical relevance of occult HBV infection,since this could be involved in occult HBV transmission through orthotopic liver transplant and blood transfusion,reactivation of HBV infection during immunosuppression,impairing chronic liver disease outcome and acting as a risk factor for hepatocellular carcinoma.Therefore it is important to bear in mind this entity in cryptogenetic liver diseases,hepatitis C virus/ HIV infected patients and immunosupressed individuals.It is also necessary to increase our knowledge in this fascinating field to define better strategies to diagnose and treat this infection.展开更多
Hepatitis C virus(HCV)-specific CD8^+ T cells play an important role in the resolution of HCV infection. Nevertheless, during chronic hepatitis C these cells lack their effector functions and fail to control the vi...Hepatitis C virus(HCV)-specific CD8^+ T cells play an important role in the resolution of HCV infection. Nevertheless, during chronic hepatitis C these cells lack their effector functions and fail to control the virus. HCV has developed several mechanisms to escape immune control. One of these strategies is the upregulation of negative co-stimulatory molecules such us programmed death-1 (PD-1). This molecule is upregulated on intrahepatic and peripheral HCV-specific cytotoxic T cells during acute and chronic phases of the disease, whereas PD-1 expression is low in resolved infection. PD-1 expressing HCV-specific CD8^+ T cells are exhausted with impairment of several effector mechanisms, such as: type-1 cytokine production, expansion ability after antigen encounter and cytotoxic ability. However, PD-1 associated exhaustion can be restored by blocking the interaction between PD-1 and its ligand (PD-L1). After this blockade, HCV-specific CD8^+ T cells reacquire their functionality. Nevertheless, functional restoration depends on PD-1 expression level. High PD-l-expressing intrahepatic HCV-specific CD8^+ T cells do not restore their effector abilities after PD-1/ PD-L1 blockade. The mechanisms by which HCV is able to induce PD-1 up-regulation to escape immune control are unknown. Persistent TCR stimulation by a high level of HCV antigens could favour early PD-1 induction, but the interaction between HCV core protein and gClq receptor could also participate in this process. The PD-1/PD-L1 pathway modulation could be a therapeutic strategy, in conjunction with the regulation of others co-stimulatory pathways, in order to restore immune response aclainst HCV to succeed in clearing the infection.展开更多
Hepatitis C virus(HCV)-specific cytotoxic T cell(CTL) response plays a major role in viral control during spontaneous infection resolution. These cells develop an exhausted and pro-apoptotic status during chronic onse...Hepatitis C virus(HCV)-specific cytotoxic T cell(CTL) response plays a major role in viral control during spontaneous infection resolution. These cells develop an exhausted and pro-apoptotic status during chronic onset, being unable to get rid of HCV. The role of this response in contributing to sustained viral response(SVR) after anti-HCV is controversial. Recent studies show that after successful interferon-based anti-HCV treatment, HCV traces are still detectable and this correlates with a peak of HCV-specific CTL response activation, probably responsible for maintaining SVR by subsequent complete HCV clearing. Moreover, SVR patients' serum is still able to induce HCV infection in na?ve chimpanzees, suggesting that the infection could be under the control of the immune system after a successful treatment, being transmissible in absence of this adaptive response. At least theoretically, treatmentinduced viral load decrease could allow an effective HCV-specific CTL response reestablishment. This effect has been recently described with anti-HCV interferonfree regimes, based on direct-acting antivirals. Nevertheless, this is to some extent controversial with interferon-based therapies, due to the detrimental immunoregulatory α-interferon effect on T cells. Moreover, HCV-specific CTL response features during anti-HCV treatment could be a predictive factor of SVR that could have clinical implications in patient management. In this review, the recent knowledge about the role of HCV-specific CTL response in the development of SVR after anti-HCV treatment is discussed.展开更多
Virus-specific T cells play an important role in the resolution of hepatic infection. However, during chronic hepatitis infection these cells lack their effector functions and fail to control the virus. Hepatitis B vi...Virus-specific T cells play an important role in the resolution of hepatic infection. However, during chronic hepatitis infection these cells lack their effector functions and fail to control the virus. Hepatitis B virus and hepatitis C virus have developed several mechanisms to generate immune tolerance. One of these strategies is the depletion of virus-specific T cells by apoptosis. The immunotolerogenic liver has unique property to retain and activate na ve T cell to avoid the over reactivation of immune response against antigens which is exploited by hepatotropic viruses to persist. The deletion of the virus-specific T cells occurs by intrinsic (passive) apoptotic mechanism. The pro-apoptotic molecule Bcl-2 interacting mediator (Bim) has attracted increasing attention as a pivotal involvement in apoptosis, as a regulator of tissue homeostasis and an enhancer for the viral persistence. Here, we reviewed our current knowledge on the evidence showing critical role of Bim in viral-specific T cell death by apoptotic pathways and helps in the immune tolerance.展开更多
This paper describes a vision-based system for blind spot detection (BSD) in intelligent vehicle applications. A camera is mounted in the lateral mirror of a car with the intention of visually detecting cars that are ...This paper describes a vision-based system for blind spot detection (BSD) in intelligent vehicle applications. A camera is mounted in the lateral mirror of a car with the intention of visually detecting cars that are located in the so-called blind spot and cannot be perceived by the vehicle driver. The detection of cars in the blind spot is carried out using computer vision techniques, based on optical flow and a double-stage data clustering technique for robust vehicle detection.展开更多
Estimating the global position of a road vehicle without using GPS is a challenge that many scientists look forward to solving in the near future. Normally, inertial and odometry sensors are used to complement GPS mea...Estimating the global position of a road vehicle without using GPS is a challenge that many scientists look forward to solving in the near future. Normally, inertial and odometry sensors are used to complement GPS measures in an attempt to provide a means for maintaining vehicle odometry during GPS outage. Nonetheless, recent experiments have demonstrated that computer vision can also be used as a valuable source to provide what can be denoted as visual odometry. For this purpose, vehicle motion can be estimated using a non-linear, photogrametric approach based on RAndom SAmple Consensus (RANSAC). The results prove that the detection and selection of relevant feature points is a crucial factor in the global performance of the visual odometry algorithm. The key issues for further improvement are discussed in this letter.展开更多
Multifocal intraocular lenses(IOLs) are currently usually implanted for the treatment of cataracts because they have been proved to be superior to monofocal IOLs with respect to spectacle independence. In turn, they a...Multifocal intraocular lenses(IOLs) are currently usually implanted for the treatment of cataracts because they have been proved to be superior to monofocal IOLs with respect to spectacle independence. In turn, they are associated with a higher prevalence of dysphotopsia symptoms that is one of the most common causes of patient dissatisfaction. Neuroadaptation seems to play a major role in the optimal adaptation to multifocal IOLs. In this context, the development of strategies that facilitate the neuroadaptation process to multifocality might be an effective strategy to reduce patients' dissatisfaction. Video games have been proved to be effective for the improvement of visual acuity and for the promotion of neuroplasticity in elderly subjects and other populations with cortical-related visual impairment. This narrative review highlights the physiological potential of video games as a perceptual strategy to improve visual acuity and promote neuroplasticity in patients using multifocalIOLs, although research is still needed to confirm these benefits in this specific population, with only one comparative study to this date providing evidence of them.展开更多
AIM: To evaluate the effect of age on visual and refractive results after laser in situ keratomileusis(LASIK) obtained with a mechanical microkeratome or a femtosecond laser.METHODS: Retrospective, nonrandomized, coho...AIM: To evaluate the effect of age on visual and refractive results after laser in situ keratomileusis(LASIK) obtained with a mechanical microkeratome or a femtosecond laser.METHODS: Retrospective, nonrandomized, cohort study. A total of 3826 eyes were included in the study(1725 eyes treated with mechanical LASIK and 2101 eyes treated with femtosecond LASIK). The relationship between patient age and the 3-month postoperative visual and refractive results of both procedures were analyzed by linear regression analysis.RESULTS: Three months postoperatively, we found a significant correlation between age and the postoperative spherical equivalent(SE; r2=0.004, P=0.006), efficacy(r2=0.006, P=0.001), and safety indexes(r2=0.05, P=0.0001) in the mechanical LASIK group. On the other hand, we found a significant correlation between age and the postoperative SE(r2=0.02, P=0.0001) and the efficacy index(r2=0.01, P=0.0001) but not the safety index in the femtosecond laser group. Mechanical LASIK provided slightly but significantly better efficacy and predictability in patients 18 to 40 years of age and femtosecond LASIK did so in patients older than 40 years of age. The femtosecond laser provided better safety results than the mechanical microkeratome in both age groups. CONCLUSION: A tendency toward undercorrection and less predictability is found with aging after myopic LASIK regardless of whether the flap was created with a mechanical microkeratome or a femtosecond laser. However, femtosecond laser provides significantly betteroutcomes in terms of efficacy, safety and predictability compared to mechanical microkeratome for the correction of myopia in patients over 40 y.展开更多
AIM: To evaluate the efficacy and the safety of azathioprine (AZA) and buthionine sulfoximine (BSO) bylocalized application into HepG2 tumor in vivo.METHODS: Different hepatoma and colon carcinoma cell lines (HepG2, H...AIM: To evaluate the efficacy and the safety of azathioprine (AZA) and buthionine sulfoximine (BSO) bylocalized application into HepG2 tumor in vivo.METHODS: Different hepatoma and colon carcinoma cell lines (HepG2, HuH7, Chang liver, LoVo, RKO, SW-48, SW-480) were grown in minimal essencial medium supplemented with 10% fetal bovine serum and 1% antibiotic/antimycotic solution and maintained in a humidified 37 ℃ incubator with 5% CO2. These cells were pretreated with BSO for 24 h and then with AZA for different times. We examined the effects of this combination on some proteins and on cellular death. We also studied the eff icacy and the safety of AZA (6 mg/kg per day) and BSO (90 mg/kg per day) in HepG2 tumor growth in vivo using athymic mice. We measured safety by serological markers such as aminotransferases and creatine kinase.RESULTS: The in vitro studies revealed a new mechanism of action for the AZA plus BSO combination in the cancer cells compared with other thiopurines (6-mercaptopurine, 6-methylmercaptopurine, 6-thioguanine and 6-methylthioguanine) in combination with BSO. The cytotoxic effect of AZA plus BSO in HepG2 cells resulted from necroptosis induction in a mitochondrial-dependent manner. From kinetic studies we suggest that glutathione (GSH) depletion stimulates c-Jun amino-terminal kinase and Bax translocation in HepG2 cells with subsequent deregulation of mitochondria (cytochrome c release, loss of membrane potential), and proteolysis activation leading to loss of membrane integrity, release of lactate dehydrogenase and DNA degradation. Some of this biochemical and cellular changes could be reversed by N-acetylcysteine (a GSH replenisher). In vivo studies showed that HepG2 tumor growth was inhibited when AZA was combined with BSO.CONCLUSION: Our studies suggest that a combination of AZA plus BSO could be useful for localizedtreatment of hepatocellular carcinoma as in the currently used transarterial chemoembolization method.展开更多
This work aims to develop simulation models that allow locating adequate areas for forest plantations in the state of Mexico. It combines multi-criteria evaluation (MCE) techniques and geographic information systems (...This work aims to develop simulation models that allow locating adequate areas for forest plantations in the state of Mexico. It combines multi-criteria evaluation (MCE) techniques and geographic information systems (GIS) to analyze and simulate future scenarios for forest plantations under three major objectives: commercial production, restoration and protection, and agroforestry. Results demonstrate the potential of this method to integrate different variables of social, economic and environmental nature, and for solve some problems of forest activities and management by locating the most suitable areas for this forestal activity.展开更多
Web applications represent one of the principal vehicles by which attackers gain access to an organization’s network or resources.Thus,different approaches to protect web applications have been proposed to date.Of th...Web applications represent one of the principal vehicles by which attackers gain access to an organization’s network or resources.Thus,different approaches to protect web applications have been proposed to date.Of them,the two major approaches are Web Application Firewalls(WAF)and Runtime Application Self Protection(RASP).It is,thus,essential to understand the differences and relative effectiveness of both these approaches for effective decisionmaking regarding the security of web applications.Here we present a comparative study between WAF and RASP simulated settings,with the aim to compare their effectiveness and efficiency against different categories of attacks.For this,we used computation of different metrics and sorted their results using F-Score index.We found that RASP tools scored better than WAF tools.In this study,we also developed a new experimental methodology for the objective evaluation ofweb protection tools since,to the best of our knowledge,nomethod specifically evaluates web protection tools.展开更多
基金supported by the Erasmus+program of the European Union(567201-EPP-1-2015-2-IT-SPO-SCP)supported by the University of Alcala(FPI2016)。
文摘Purpose:To examine the effects of a school-based karate intervention on academic achievement,psychosocial functioning,and physical fitness in children aged 7-8 years.Methods:Twenty schools in 5 different European countries(2 second-grade classrooms per school)participated in a cluster randomized controlled trial(Sport at School trial).Participants were assigned to either a control group,which continued with their habitual physical education lessons,or to an intervention group,which replaced these lessons with a 1-year karate intervention(Karate Mind and Movement program).A total of 721 children(344 girls and 377 boys,7.4±0.5 years old,mean±SD)completed the study,of which 333 and 388 were assigned to the control group and intervention group,respectively.Outcomes included academic performance(average grade),psychosocial functioning(Strengths and Difficulties Questionnaire for parents),and different markers of physical fitness(cardiorespiratory fitness,balance,and flexibility).Results:The intervention provided small but significant benefits compared to the control group for academic achievement(d=0.16;p=0.003),conduct problems(d=-0.28;p=0.003),cardiorespiratory fitness(d=0.36;p<0.001),and balance(d=0.24;p=0.015).There was a trend towards significant benefits for flexibility(d=0.24;p=0.056).No significant benefits were observed for other variables,including psychosocial difficulties,emotional symptoms,hyperactivity/inattention,peer problems,or prosocial behaviour(all p>0.05).Conclusion:A 1-year school-based karate intervention was effective in improving academic achievement,conduct problems,and physical fitness in primary school children.The results support the inclusion of karate during physical education lessons.
文摘BACKGROUND The quality-adjusted life year(QALY)is a metric that is increasingly used today in the field of health economics to evaluate the value of different medical treatments and procedures.Surgical waiting lists(SWLs)represent a pressing problem in public healthcare.The QALY measure has rarely been used in the context of surgery.It would be interesting to know how many QALYs are lost by patients on SWLs.AIM To investigate the relationship between QALYs and SWLs in a systematic review of the scientific literature.METHODS The study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement.An unlimited search was carried out in PubMed,updated on January 19,2024.Data on the following variables were investigated and analyzed:Specialty,country of study,procedure under study,scale used to measure QALYs,the use of a theoretical or real-life model,objectives of the study and items measured,the economic value assigned to the QALY in the country in question,and the results and conclusions published.RESULTS Forty-eight articles were selected for the study.No data were found regarding QALYs lost on SWLs.The specialties in which QALYs were studied the most in relation to the waiting list were urology and general surgery,with 15 articles each.The country in which the most studies of QALYs were carried out was the United States(n=21),followed by the United Kingdom(n=9)and Canada(n=7).The most studied procedure was organ transplantation(n=39),including 15 kidney,14 liver,5 heart,4 lung,and 1 intestinal.Arthroplasty(n=4),cataract surgery(n=2),bariatric surgery(n=1),mosaicplasty(n=1),and septoplasty(n=1)completed the surgical interventions included.Thirty-nine of the models used were theoretical(the most frequently applied being the Markov model,n=34),and nine were real-life.The survey used to measure quality of life in 11 articles was the European Quality of Life-5 dimensions,but in 32 articles the survey was not specified.The willingness-to-pay per QALY gained ranged from$100000 in the United States to€20000 in Spain.CONCLUSION The relationship between QALYs and SWLs has only rarely been studied in the literature.The rate of QALYs lost on SWLs has not been determined.Future research is warranted to address this issue.
文摘Objective Incidences of post-transurethral resection of the prostate(post-TURP)strictures are between 2.2%and 9.8%.Stricture commonly occurs within the first 6 months.Our objective was to assess the outcomes of patients with obliterative strictures post-TURP that underwent a double-face urethroplasty.Methods This is a single-center prospective study of 17 patients with obliterative proximal bulbar stricture post-TURP who underwent double-face graft urethroplasty by two surgeons between January 2014 and January 2020.We defined post-TURP obliterative strictures as those patients who presented with complete or almost complete obstruction of the urethral lumen and who have had a history of acute urine retention.We have excluded patients with bladder neck contracture.Primary outcome was treatment success,defined as the no need for further treatments.Secondary outcome was post-urethroplasty continent rate.Results Seventeen patients were included in the study with median age of 66(interquartile range 40-77)years;median time of follow-up was 24(interquartile range 12-84)months;median stricture length was 4(interquartile range 2-6)cm.Of the 17 patients,15(88.2%)were successful.All patients were continent after urethroplasty.Conclusion With mid-term follow-up,treatment of obliterative proximal bulbar strictures with double-face buccal mucosa graft is a safe and effective procedure.Obliterative proximal bulbar strictures merit double-face urethroplasty with high-rate success and functional outcomes.
基金Supported by "Instituto de Salud Carlos Ⅲ",Spain& "European Regional Development Fund(ERDF)a way of making Europe",No.PI12/00130 and No.PI15/00074and"Gilead Spain&Instituto de Salud Carlos Ⅲ",No.GLD14_00217
文摘Hepatocellular carcinoma (HCC), chronic hepatitis B (CHB) and chronic hepatitis C (CHC) are characterized by exhaustion of the specific CD8<sup>+</sup> T cell response. This process involves enhancement of negative co-stimulatory molecules, such as programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte antigen-4 (CTLA-4), 2B4, Tim-3, CD160 and LAG-3, which is linked to intrahepatic overexpression of some of the cognate ligands, such as PD-L1, on antigen presenting cells and thereby favouring a tolerogenic environment. Therapies that disrupt these negative signalling mechanisms represent promising therapeutic tools with the potential to restore reactivity of the specific CD8<sup>+</sup> T cell response. In this review we discuss the impressive in vitro and in vivo results that have been recently achieved in HCC, CHB and CHC by blocking these negative receptors with monoclonal antibodies against these immune checkpoint modulators. The article mainly focuses on the role of CTLA-4 and PD-1 blocking monoclonal antibodies, the first ones to have reached clinical practice. The humanized monoclonal antibodies against CTLA-4 (tremelimumab and ipilimumab) and PD-1 (nivolumab and pembrolizumab) have yielded good results in testing of HCC and chronic viral hepatitis patients. Trelimumab, in particular, has shown a significant increase in the time to progression in HCC, while nivolumab has shown a remarkable effect on hepatitis C viral load reduction. The research on the role of ipilimumab, nivolumab and pembrolizumab on HCC is currently underway.
基金Supported by Grants from "Fiscam" J.C.C.M (Ayuda paraproyectos de investigación en saludPI-2007/32)+7 种基金"AsociaciónCastellana de Aparato Digestivo" (Beca ACADACAD/06)"Fundación de Investigación Médica Mutua Madrilea"(Beca Ayudas a la Investigación FMMM2548/2008),Spainsupported by a research grantfrom "Fiscam" J.C.C.M ("Perfeccionamiento y movilidad deinvestigadores" MOV-2007_JI/18), Spainsupported by a research grant from "Instituto de SaludCarlos Ⅲ" (Contrato de apoyo a la investigación en el SNS"CA07/00157),Spain
文摘Chemokines produced in the liver during hepatitis C virus(HCV) infection induce migration of activated T cells from the periphery to infected parenchyma.The milieu of chemokines secreted by infected hepatocytes is predominantly associated with the T-helper cell/Tc1 T cell(Th1/Tc1) response.These chemokines consist of CCL3(macrophage inflammatory protein-1α;MIP-1α),CCL4(MIP-1β),CCL5(regulated on activation normal T cell expressed and secreted;RANTES),CXCL10(interferon-γ-inducible protein-10;IP-10),CXCL11(interferon-inducible T-cell α chemoattractant;I-TAC),and CXCL9(monokine induced by interferon γ;Mig) and they recruit T cells expressing either CCR5 or CXCR3 chemokine receptors.Intrahepatic and peripheral blood levels of these chemokines are increased during chronic hepatitis C.The interaction between chemokines and their receptors is essential in recruiting HCV-specific T cells to control the infection.When the adaptive immune response fails in this task,non-specific T cells without the capacity to control the infection are also recruited to the liver,and these are ultimately responsible for the persistent hepatic damage.The modulation of chemokine receptor expression and chemokine secretion could be a viral escape mechanism to avoid specific T cell migration to the liver during the early phase of infection,and to maintain liver viability during the chronic phase,by impairing non-specific T cell migration.Some chemokines and their receptors correlate with liver damage,and CXCL10(IP-10) and CXCR3 levels have shown a clinical utility as predictors of treatment response outcome.The regulation of chemokines and their receptors could be a future potential therapeutic target to decrease liver inflammation and to increase specific T cell migration to the infected liver.
基金Supported by Grants from Fondo de Investigaciones Sanitarias(FIS 06/1082,in part)
文摘During the course of cirrhosis, there is a progressive deterioration of cardiac function manifested by the disappearance of the hyperdynamic circulation due to afailure in heart function with decreased cardiac output. This is due to a deterioration in inotropic and chronotropic function which takes place in parallel with a diastolic dysfunction and cardiac hypertrophy in the absence of other known cardiac disease. Other findings of this specific cardiomyopathy include impaired contractile responsiveness to stress stimuli and electrophysiological abnormalities with prolonged QT interval. The pathogenic mechanisms of cirrhotic cardiomyopathy include impairment of the b-adrenergic receptor signalling, abnormal cardiomyocyte membrane lipid composition and biophysical properties, ion channel defects and overactivity of humoral cardiodepressant factors. Cirrhotic cardiomyopathy may be difficult to determine due to the lack of a specific diagnosis test. However, an echocardiogram allows the detection of the diastolic dysfunction and the E/e′ ratio may be used in the followup progression of the illness. Cirrhotic cardiomyopathy plays an important role in the pathogenesis of the impairment of effective arterial blood volume and correlates with the degree of liver failure. A clinical consequence of cardiac dysfunction is an inadequate cardiac response in the setting of vascular stress that may result in renal hypoperfusion leading to renal failure. The prognosis is difficult to establish but the severity of diastolic dysfunction may be a marker of mortality risk. Treatment is non-specific and liver transplantation may normalize the cardiac function.
文摘Hepatitis B virus (HBV) infection is a global public health problem that concerns 350 million people worldwide. Individuals with chronic hepatitis B (CriB) are at increased risk of developing liver cirrhosis, hepatic de-compensation and hepatocellular carcinoma. To maintain undetectable viral load reduces chronic infection complications. There is no treatment that eradicates HBV infection. Current drugs are expensive, are associated with adverse events, and are of limited efficacy. Current guidelines try to standardize the clinical practice. Nevertheless, controversy remains about management of asymptomatic patients with CriB who are hepatitis B e antigen (HBeAg)-positive with normal alanine aminotransferase, and what is the cut-off value of viral load to distinguish HBeAg- negative CriB patients and inactive carriers. We discuss in detail why DNA level alone is not sufficient to begin treatment of CriB.
基金Supported by grants from the “Instituto de Salud Carlos Ⅲ”,Spain and the “European Regional Development Fund(ERDF),a way of making Europe”,No.PI12/00130 and No.PI15/00074the “Gilead Spain & Instituto de Salud Carlos Ⅲ”,No.GLD14_00217 and No.GLD16_00014
文摘Chronic hepatitis B(CHB) remains a challenging global health problem, with nearly one million related deaths per year. Nucleos(t)ide analogue(NA) treatment suppresses viral replication but does not provide complete cure of the hepatitis B virus(HBV) infection. The accepted endpoint for therapy is the loss of hepatitis B surface antigen(HBs Ag), but this is hardly ever achieved. Therefore, indefinite treatment is usually required. Many different studies have evaluated NA therapy discontinuation after several years of NA treatment and before HBs Ag loss. The results have indicated that the majority of patients can remain off therapy, with some even reaching HBs Ag seroconversion. Fortunately, this strategy has proved to be safe, but it is essential to consider the risk of liver damage and other comorbidities and to ensure aclose follow-up of the candidates before considering this strategy. Unanswered questions remain, namely in which patients could this strategy be effective and what is the optimal time point at which to perform it. To solve this enigma, we should keep in mind that the outcome will ultimately depend on the equilibrium between HBV and the host's immune system. Viral parameters that have been described as good predictors of response in HBe Ag(+) cases, have proven useless in HBe Ag(-) ones. Since antiviral immunity plays an essential role in the control of HBV infection, we sought to review and explain potential immunological biomarkers to predict safe NA discontinuation in both groups.
文摘· AIM: To determine the effect of topical 0.05% cyclosporine A (CsA) on corneal endothelium in patients with dry eye disease. · METHODS: Observational, prospective, case series study. Fifty-five eyes of 29 consecutive patients (9 males and 20 females; median age: 66.8 years, interquartile range: 61 -73.2 years) with moderate -severe dry eye disease were evaluated. All patients were treated with topical 0.05% CsA ophthalmic emulsion twice a day in addition to lubricant eyedrops 5 times a day. The follow- up period was 12 months. Before treatment and at 3 and 12 months post -treatment central corneal specular microscopy was performed. The endothelial cell density (ECD), coefficient of variation of cell size (CoV), and percentage of hexagonal cells (Hex %) were analyzed. ·RESULTS: The median ECDs pre-treatment and at 3 and 12 months post-treatment were 2 352.5/mm 2 (inter- quartile range, 2 178 -2548.5), 2 364/mm 2 (interquartile range, 2 174.25 -2 657.5), and 2 366 cells/mm 2 (inter - quartile range, 2 174.75-2 539.75), respectively (P=0.927, one way ANOVA). The median CoVs pre-treatment and at 3 and 12 months post -treatment were 34.5 (interquartile range, 30 -37), 35 (interquartile range, 30 -38), and 34 (interquartile range, 30.75-38.25), respectively (P=0.7193, one way ANOVA). The median Hex % values pre - treatment and at 3 and 12 months post -treatment were 53 (interquartile range, 47 -58), 54 (interquartile range, 45.75 -59), and 50.5 (interquartile range, 45.75 -58), respectively (P=0.824, one way ANOVA). · CONCLUSION: Treatment of patients with dry eye disease for 12 months with topical 0.05% CsA does not seem to cause substantial changes on corneal endothelium.
基金Grants from "Fiscam"J.C.C.M(Ayuda para proyectos de investigación en saludPI-2007/32)+1 种基金"Fundación de Investigación Médica Mutua Madrilea"(Beca Ayudas a la Investigación FMMM2548/2008)from Spain
文摘Occult hepatitis B virus(HBV) infection is a world-wide entity,following the geographical distribution of detectable hepatitis B.This entity is defined as the persistence of viral genomes in the liver tissue and in some instances also in the serum,associated to negative HBV surface antigen serology.The molecular basis of the occult infection is related to the life cycle of HBV,which produces a covalently closed circular DNA that persists in the cell nuclei as an episome,and serves as a template for gene transcription.The mechanism responsible for the HBsAg negative status in occult HBV carriers is a strong suppression of viral replication,probably due to the host’s immune response,co-infection with other infectious agents and epigenetic factors.There is emerging evidence of the potential clinical relevance of occult HBV infection,since this could be involved in occult HBV transmission through orthotopic liver transplant and blood transfusion,reactivation of HBV infection during immunosuppression,impairing chronic liver disease outcome and acting as a risk factor for hepatocellular carcinoma.Therefore it is important to bear in mind this entity in cryptogenetic liver diseases,hepatitis C virus/ HIV infected patients and immunosupressed individuals.It is also necessary to increase our knowledge in this fascinating field to define better strategies to diagnose and treat this infection.
基金Supported by Grants from "Fiscam" J.C.C.M (Ayuda para proyectos de investigación en salud PI-2007/32)+5 种基金"Fundación de Investigación Médica Mutua Madrileń a" (Beca Ayudas a la Investigación FMMM 2548/2008) from SpainBenito-Martínez S was supported by a research grant from "Fiscam" J.C.C.M ("Perfeccionamiento y movilidad de investigadores" MOV-2007_JI/18), SpainCalvino M was supported by a research grant from "Instituto de Salud Carlos III" (Contrato de apoyo a la investigación en el SNS’’ CA07/00157), Spain
文摘Hepatitis C virus(HCV)-specific CD8^+ T cells play an important role in the resolution of HCV infection. Nevertheless, during chronic hepatitis C these cells lack their effector functions and fail to control the virus. HCV has developed several mechanisms to escape immune control. One of these strategies is the upregulation of negative co-stimulatory molecules such us programmed death-1 (PD-1). This molecule is upregulated on intrahepatic and peripheral HCV-specific cytotoxic T cells during acute and chronic phases of the disease, whereas PD-1 expression is low in resolved infection. PD-1 expressing HCV-specific CD8^+ T cells are exhausted with impairment of several effector mechanisms, such as: type-1 cytokine production, expansion ability after antigen encounter and cytotoxic ability. However, PD-1 associated exhaustion can be restored by blocking the interaction between PD-1 and its ligand (PD-L1). After this blockade, HCV-specific CD8^+ T cells reacquire their functionality. Nevertheless, functional restoration depends on PD-1 expression level. High PD-l-expressing intrahepatic HCV-specific CD8^+ T cells do not restore their effector abilities after PD-1/ PD-L1 blockade. The mechanisms by which HCV is able to induce PD-1 up-regulation to escape immune control are unknown. Persistent TCR stimulation by a high level of HCV antigens could favour early PD-1 induction, but the interaction between HCV core protein and gClq receptor could also participate in this process. The PD-1/PD-L1 pathway modulation could be a therapeutic strategy, in conjunction with the regulation of others co-stimulatory pathways, in order to restore immune response aclainst HCV to succeed in clearing the infection.
基金Supported by"Instituto de Salud Carlos III",Spain and"European Regional Development Fund,a way of making Europe",E.U.(PI12/00130)Moreno-Cubero E was funded by a research award from"Asociación de Hepatología Translacional"(AHT Research Award 2014),Spain
文摘Hepatitis C virus(HCV)-specific cytotoxic T cell(CTL) response plays a major role in viral control during spontaneous infection resolution. These cells develop an exhausted and pro-apoptotic status during chronic onset, being unable to get rid of HCV. The role of this response in contributing to sustained viral response(SVR) after anti-HCV is controversial. Recent studies show that after successful interferon-based anti-HCV treatment, HCV traces are still detectable and this correlates with a peak of HCV-specific CTL response activation, probably responsible for maintaining SVR by subsequent complete HCV clearing. Moreover, SVR patients' serum is still able to induce HCV infection in na?ve chimpanzees, suggesting that the infection could be under the control of the immune system after a successful treatment, being transmissible in absence of this adaptive response. At least theoretically, treatmentinduced viral load decrease could allow an effective HCV-specific CTL response reestablishment. This effect has been recently described with anti-HCV interferonfree regimes, based on direct-acting antivirals. Nevertheless, this is to some extent controversial with interferon-based therapies, due to the detrimental immunoregulatory α-interferon effect on T cells. Moreover, HCV-specific CTL response features during anti-HCV treatment could be a predictive factor of SVR that could have clinical implications in patient management. In this review, the recent knowledge about the role of HCV-specific CTL response in the development of SVR after anti-HCV treatment is discussed.
基金Supported by Grants from "Fiscam" JCCM, Ayuda para proyectos de investigación en salud, PI-2010/022"Fundación de Investigación Médica Mutua Madrilea", Beca Ayudas a la Investigación FMMM, 8922/2011A research grant from "Asociación de Hepatología Translacional", No. AHT 2010-01, to Lokhande MU
文摘Virus-specific T cells play an important role in the resolution of hepatic infection. However, during chronic hepatitis infection these cells lack their effector functions and fail to control the virus. Hepatitis B virus and hepatitis C virus have developed several mechanisms to generate immune tolerance. One of these strategies is the depletion of virus-specific T cells by apoptosis. The immunotolerogenic liver has unique property to retain and activate na ve T cell to avoid the over reactivation of immune response against antigens which is exploited by hepatotropic viruses to persist. The deletion of the virus-specific T cells occurs by intrinsic (passive) apoptotic mechanism. The pro-apoptotic molecule Bcl-2 interacting mediator (Bim) has attracted increasing attention as a pivotal involvement in apoptosis, as a regulator of tissue homeostasis and an enhancer for the viral persistence. Here, we reviewed our current knowledge on the evidence showing critical role of Bim in viral-specific T cell death by apoptotic pathways and helps in the immune tolerance.
文摘This paper describes a vision-based system for blind spot detection (BSD) in intelligent vehicle applications. A camera is mounted in the lateral mirror of a car with the intention of visually detecting cars that are located in the so-called blind spot and cannot be perceived by the vehicle driver. The detection of cars in the blind spot is carried out using computer vision techniques, based on optical flow and a double-stage data clustering technique for robust vehicle detection.
文摘Estimating the global position of a road vehicle without using GPS is a challenge that many scientists look forward to solving in the near future. Normally, inertial and odometry sensors are used to complement GPS measures in an attempt to provide a means for maintaining vehicle odometry during GPS outage. Nonetheless, recent experiments have demonstrated that computer vision can also be used as a valuable source to provide what can be denoted as visual odometry. For this purpose, vehicle motion can be estimated using a non-linear, photogrametric approach based on RAndom SAmple Consensus (RANSAC). The results prove that the detection and selection of relevant feature points is a crucial factor in the global performance of the visual odometry algorithm. The key issues for further improvement are discussed in this letter.
基金Coco-Martin MB,Maldonado-López MJ,Molina-Martín A and Pi?ero DP are supported by CDTI(Centro para el Desarrollo Tecnológico Industrial,Ministry of Economy and Competitiveness of Spain)by means of the program PID(“Proyectos de Investigación y Desarrollo”)The author Pi?ero DP has been also supported by the Ministry of Economy,Industry and Competitiveness of Spain within the program Ramón y Cajal(RYC-2016-20471)Valenzuela PL is supported by a contract granted by University of Alcalá(FPI2016)
文摘Multifocal intraocular lenses(IOLs) are currently usually implanted for the treatment of cataracts because they have been proved to be superior to monofocal IOLs with respect to spectacle independence. In turn, they are associated with a higher prevalence of dysphotopsia symptoms that is one of the most common causes of patient dissatisfaction. Neuroadaptation seems to play a major role in the optimal adaptation to multifocal IOLs. In this context, the development of strategies that facilitate the neuroadaptation process to multifocality might be an effective strategy to reduce patients' dissatisfaction. Video games have been proved to be effective for the improvement of visual acuity and for the promotion of neuroplasticity in elderly subjects and other populations with cortical-related visual impairment. This narrative review highlights the physiological potential of video games as a perceptual strategy to improve visual acuity and promote neuroplasticity in patients using multifocalIOLs, although research is still needed to confirm these benefits in this specific population, with only one comparative study to this date providing evidence of them.
文摘AIM: To evaluate the effect of age on visual and refractive results after laser in situ keratomileusis(LASIK) obtained with a mechanical microkeratome or a femtosecond laser.METHODS: Retrospective, nonrandomized, cohort study. A total of 3826 eyes were included in the study(1725 eyes treated with mechanical LASIK and 2101 eyes treated with femtosecond LASIK). The relationship between patient age and the 3-month postoperative visual and refractive results of both procedures were analyzed by linear regression analysis.RESULTS: Three months postoperatively, we found a significant correlation between age and the postoperative spherical equivalent(SE; r2=0.004, P=0.006), efficacy(r2=0.006, P=0.001), and safety indexes(r2=0.05, P=0.0001) in the mechanical LASIK group. On the other hand, we found a significant correlation between age and the postoperative SE(r2=0.02, P=0.0001) and the efficacy index(r2=0.01, P=0.0001) but not the safety index in the femtosecond laser group. Mechanical LASIK provided slightly but significantly better efficacy and predictability in patients 18 to 40 years of age and femtosecond LASIK did so in patients older than 40 years of age. The femtosecond laser provided better safety results than the mechanical microkeratome in both age groups. CONCLUSION: A tendency toward undercorrection and less predictability is found with aging after myopic LASIK regardless of whether the flap was created with a mechanical microkeratome or a femtosecond laser. However, femtosecond laser provides significantly betteroutcomes in terms of efficacy, safety and predictability compared to mechanical microkeratome for the correction of myopia in patients over 40 y.
基金Supported by Grants from SAF2008-05355CCG07-UAH/BIO-2085
文摘AIM: To evaluate the efficacy and the safety of azathioprine (AZA) and buthionine sulfoximine (BSO) bylocalized application into HepG2 tumor in vivo.METHODS: Different hepatoma and colon carcinoma cell lines (HepG2, HuH7, Chang liver, LoVo, RKO, SW-48, SW-480) were grown in minimal essencial medium supplemented with 10% fetal bovine serum and 1% antibiotic/antimycotic solution and maintained in a humidified 37 ℃ incubator with 5% CO2. These cells were pretreated with BSO for 24 h and then with AZA for different times. We examined the effects of this combination on some proteins and on cellular death. We also studied the eff icacy and the safety of AZA (6 mg/kg per day) and BSO (90 mg/kg per day) in HepG2 tumor growth in vivo using athymic mice. We measured safety by serological markers such as aminotransferases and creatine kinase.RESULTS: The in vitro studies revealed a new mechanism of action for the AZA plus BSO combination in the cancer cells compared with other thiopurines (6-mercaptopurine, 6-methylmercaptopurine, 6-thioguanine and 6-methylthioguanine) in combination with BSO. The cytotoxic effect of AZA plus BSO in HepG2 cells resulted from necroptosis induction in a mitochondrial-dependent manner. From kinetic studies we suggest that glutathione (GSH) depletion stimulates c-Jun amino-terminal kinase and Bax translocation in HepG2 cells with subsequent deregulation of mitochondria (cytochrome c release, loss of membrane potential), and proteolysis activation leading to loss of membrane integrity, release of lactate dehydrogenase and DNA degradation. Some of this biochemical and cellular changes could be reversed by N-acetylcysteine (a GSH replenisher). In vivo studies showed that HepG2 tumor growth was inhibited when AZA was combined with BSO.CONCLUSION: Our studies suggest that a combination of AZA plus BSO could be useful for localizedtreatment of hepatocellular carcinoma as in the currently used transarterial chemoembolization method.
文摘This work aims to develop simulation models that allow locating adequate areas for forest plantations in the state of Mexico. It combines multi-criteria evaluation (MCE) techniques and geographic information systems (GIS) to analyze and simulate future scenarios for forest plantations under three major objectives: commercial production, restoration and protection, and agroforestry. Results demonstrate the potential of this method to integrate different variables of social, economic and environmental nature, and for solve some problems of forest activities and management by locating the most suitable areas for this forestal activity.
文摘Web applications represent one of the principal vehicles by which attackers gain access to an organization’s network or resources.Thus,different approaches to protect web applications have been proposed to date.Of them,the two major approaches are Web Application Firewalls(WAF)and Runtime Application Self Protection(RASP).It is,thus,essential to understand the differences and relative effectiveness of both these approaches for effective decisionmaking regarding the security of web applications.Here we present a comparative study between WAF and RASP simulated settings,with the aim to compare their effectiveness and efficiency against different categories of attacks.For this,we used computation of different metrics and sorted their results using F-Score index.We found that RASP tools scored better than WAF tools.In this study,we also developed a new experimental methodology for the objective evaluation ofweb protection tools since,to the best of our knowledge,nomethod specifically evaluates web protection tools.