Background Frailty is common and significantly impacts prognosis in heart failure(HF). The Vulnerable Elders Survey-13(VES-13), widely used in oncogeriatrics and public health, remains unexplored as a frailty screenin...Background Frailty is common and significantly impacts prognosis in heart failure(HF). The Vulnerable Elders Survey-13(VES-13), widely used in oncogeriatrics and public health, remains unexplored as a frailty screening tool in HF outpatients. In this study, we prospectively evaluated VES-13 against a multimodal screening assessment in detecting frailty and predicting individual risk of adverse prognosis.Methods Frailty was assessed at the initial visit using both a multimodal approach, incorporating Barthel Index, Older American Resources and Services scale, Pfeiffer Test, abbreviated Geriatric Depression Scale, age > 85 years, lacking support systems,and VES-13. Patients scoring ≥ 3 on VES-13 or meeting at least one multimodal criterion were classified as frail. Endpoints included all-cause mortality, a composite of death or HF hospitalization, and recurrent HF hospitalizations.Results A total of 301 patients were evaluated. VES-13 identified 40.2% as frail and the multimodal assessment 33.2%. In Cox regression analyses, frailty identified by VES-13 showed greater prognostic significance than the multimodal assessment for allcause mortality(HR = 3.70 [2.15–6.33], P < 0.001 vs. 2.40 [1.46–4.0], P = 0.001) and the composite endpoint(HR = 3.13 [2.02–4.84], P< 0.001 vs. 1.96 [1.28–2.99], P = 0.002). Recurrent HF hospitalizations were four times more frequent in VES-13 frail patients while two times in those identified as frail by the multimodal assessment. Additionally, stratifying patients by VES-13 tertiles provided robust risk differentiation.Conclusions VES-13, a simple frailty tool, outperformed a comprehensive multimodal assessment and could be easily integrated into routine HF care, highlighting its clinical utility in identifying patients at risk for poor outcomes.展开更多
Aging is characterized by a progressive decline in physiological function,driven by intrinsic mechanisms(primary aging)and modifiable factors(secondary aging),ultimately leading to multimorbidity,disability,and mortal...Aging is characterized by a progressive decline in physiological function,driven by intrinsic mechanisms(primary aging)and modifiable factors(secondary aging),ultimately leading to multimorbidity,disability,and mortality.Mitochondrial dysfunction,a major hallmark of aging,plays a central role in the loss of muscle mass and strength observed in frailty and sarcopenia.With age,mitochondrial quality control processes,including biogenesis,mitophagy,and dynamics,become dysregulated,impairing energy metabolism and muscle homeostasis.Mitochondrial dysfunction correlates with clinical biomarkers of sarcopenia and frailty,such as the decrease in walking speed and muscle strength,making it a therapeutic target for mitohormesis-based strategies aimed at preserving functional capacity.Mitohormetic agents induce reversible mitochondrial stress,triggering adaptive responses that enhance function.Among these interventions,physical exercise,particularly endurance and resistance training(RT),has been reported to be among the most effective,as it may modulate mitochondrial biogenesis,dynamics,and mitophagy through increases in proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α)and mitochondrial transcription factor A(TFAM)expression,mitochondrial deoxyribonucleic acid(mtDNA)copy number,and mitochondrial content.Chronic RT can also elevate fusion and fission markers,potentially as a compensatory mechanism to mitigate mitochondrial damage.Apart from exercise,mitohormetic compounds such as harmol and piceid are emerging as promising supplements in the aging field.By modulating mitochondrial bioenergetics and dynamics,they may complement lifestyle-based interventions to improve mitochondrial fitness and extend health span.展开更多
The nervous system function requires a precise but plastic neural architecture.The neuronal shape dictates how neurons interact with each other and with other cells,being the morphology of dendrites and axons the cent...The nervous system function requires a precise but plastic neural architecture.The neuronal shape dictates how neurons interact with each other and with other cells,being the morphology of dendrites and axons the central determinant of the functional properties of neurons and neural circuits.The topological and structural morphology of axons and dendrites defines and determines how synapses are conformed.The morphological diversity of axon and dendrite arborization governs the neuron’s inputs,synaptic integration,neuronal computation,signal transmission,and network circuitry,hence defining the particular connectivity and function of the different brain areas.展开更多
In Alzheimer’s disease,microglial phagocytosis is engaged in the pathogenesis as it clears abnormal protein accumulations,debris,and apoptotic cells in the early stages of Alzheimer’s disease,but fuels neuroinflamma...In Alzheimer’s disease,microglial phagocytosis is engaged in the pathogenesis as it clears abnormal protein accumulations,debris,and apoptotic cells in the early stages of Alzheimer’s disease,but fuels neuroinflammation and accelerates disease progression in later stages.In vivo parabiosis experiments in aged animals have demonstrated that blood-born factors modulate synaptic plasticity,neurogenesis,and microglial responses.We hypothesize that peripheral factors can modulate microglial function and thereby possibly influence Alzheimer’s disease pathology.The objective of this study is to investigate the effects of Alzheimer’s disease serum on microglial phagocytosis.Here,we use an immortalized human microglial cell line in an in vitro parabiosis assay to investigate the impact of the serum from individuals diagnosed with Alzheimer’s disease(n=30)and age-matched controls(n=30)(PRODEM study)on microglial phagocytosis.Exposure to Alzheimer’s disease serum increased microglial phagocytic uptake of pH-sensitive fluorescent particles and downregulated expression of the lysosomal master regulator transcription factor EB(TFEB)and of ATPase H^(+)transporting lysosomal V1 subunit B2(ATP6V1B2),a component of the vacuolar ATPase.To identify serum components that may relate to changes in phagocytosis,serum samples of the Three-City Study(3C Study)were used.In the 3C Study,blood samples were collected up to 12 years before the onset of cognitive decline or dementia and their serum metabolome is well-defined.Microglia exposed to the serum of future Alzheimer’s disease patients from the 3C Study displayed an increased phagocytic uptake compared with the serum of matched controls,depending on the presence of the apolipoprotein Eε4 allele in the Alzheimer’s disease patients.Furthermore,microglial phagocytosis correlated inversely with serum levels of the omega-3 fatty acid eicosapentaenoic acid.We confirmed this inverse correlation between eicosapentaenoic acid and phagocytosis in the serum samples of the PRODEM cohort.In addition,in vitro testing of eicosapentaenoic acid on microglial phagocytosis showed a concentration-dependent decrease in phagocytic uptake.In conclusion,following incubation with Alzheimer’s disease blood serum,we observed increased microglial phagocytic uptake and the downregulation of TFEB and ATP6V1B2,possibly indicating lysosomal dysfunction.Furthermore,microglial phagocytosis was inversely correlated with serum eicosapentaenoic acid levels,suggesting an important role for dietary eicosapentaenoic acid in microglial function.展开更多
Background There is scarce data about comparisons between geriatric assessment tools in patients with aortic stenosis(AS).We aimed to describe the geriatric profile of patients with AS undergoing transcatheter aortic ...Background There is scarce data about comparisons between geriatric assessment tools in patients with aortic stenosis(AS).We aimed to describe the geriatric profile of patients with AS undergoing transcatheter aortic valve implantation(TAVI)and to analyze the ability of different tools for predicting clinical outcomes in this context.Methods This was a single center retrospective registry including patients with AS undergoing TAVI and surviving to hospital discharge.The primary endpoint was all-cause mortality or need for urgent readmission one year after TAVI.Results A total of 377 patients were included(mean age of 80.4 years).Most patients were independent or mildly dependent,with an optimal cognitive status.The proportion of frailty ranged from 17.6%to 49.8%.A total of 20 patients(5.3%)died and 110/377 patients(29.2%)died or were readmitted during follow up.Overall,most components of the geriatric assessment showed an association with clinical outcomes.Disability for instrumental activities showed a significant association with mortality and a strong association with the rate of mortality or readmission.The association between frailty and clinical outcomes was higher for short physical performance battery(SPPB),essential frailty toolset(EFT)and the frailty index based on comprehensive geriatric assessment(IF-VIG)and lower for Fried criteria and FRAIL scale.Conclusions AS patients from this series presented a good physical performance,optimal cognitive status and a reasonably low prevalence of frailty.The best predictive ability was observed for disability for instrumental activities and frailty as measured by the EFT,SPPB and the IF-VIG.展开更多
BACKGROUND: Prehospital medication is a reality, and the role of these therapies must be explored to assess their validity, especially for acute respiratory diseases, which are usually associated with increased morbid...BACKGROUND: Prehospital medication is a reality, and the role of these therapies must be explored to assess their validity, especially for acute respiratory diseases, which are usually associated with increased morbidity. The aim of this study was to examine the association of prehospital medication use with mortality in patients with acute respiratory disease.METHODS: A prospective, multicenter, emergency medical service(EMS) delivery cohort study was carried out in adults with unselected respiratory diseases managed by EMS who were transferred to the emergency department. From January 1, 2019, to October 31, 2023, six advanced life support units, thirty-eight basic life support units, and four hospitals in Spain participated in the study. Demographic data, vital signs, use of mechanical ventilation, prehospital respiratory diagnosis, and prehospital medication were collected. The primary outcome was 30-day in-hospital mortality.RESULTS: A total of 961 patients were included, with a mortality rate of 17.5%(168 patients). Age, an increasing number of comorbidities, the use of invasive mechanical ventilation(IMV), the use of major analgesics, hypnotics, and bicarbonate were risk factors. In contrast, elevated systolic blood pressure and Glasgow Coma Scale scores were found to be protective factors against mortality. The predictive capacity of the model reached an area under the curve(AUC) of 0.857(95% confidence interval [95% CI] 0.827–0.888).CONCLUSION: Our data revealed that IMV, major analgesics, hypnotics and bicarbonate administration were associated with elevated mortality. Adding prehospital drug therapy information to demographic variables and vital signs could improve EMS decision-making, allowing a better characterization of patients at risk of clinical worsening.展开更多
BACKGROUND:Oxygen supply is a common procedure performed by emergency medical services(EMS);however,whether prehospital oxygen or fraction of inspired oxygen(FiO2)therapy predict mortality has not been studied to date...BACKGROUND:Oxygen supply is a common procedure performed by emergency medical services(EMS);however,whether prehospital oxygen or fraction of inspired oxygen(FiO2)therapy predict mortality has not been studied to date.This study aims to determine mortality associated with oxygen therapy in unselected patients with acute disease who underwent prehospital care.METHODS:This was a prospective,observational,cohort,multicenter,EMS-delivery,ambulance-based study.Adults with unselected acute disease who were managed by EMS and evacuated with high priority to the emergency department of four hospitals in three Spanish provinces.Epidemiological variables,on-scene vital signs,and prehospital blood analysis data were collected.The primary outcome was short-(2-,7-,and 30-day),medium-(90-and 180-day),and long-term(365-day)all-cause cumulative mortality.The samples were a priori split according to thresholds of their received FiO2(FiO2=0.21,that is without oxygen therapy;FiO2 between 0.22 and 0.49;and FiO2≥0.5).The categorical variables FiO2,epidemiological variables,vital signs,prehospital point-of-care testing(POCT)and patient outcomes were fitted with a logistic regression model.Additionally,a propensity score matching and a survival analysis were used.RESULTS:The final sample included 7,494 patients,70.3%of whom did not receive oxygen therapy,15%with a FiO2 between 0.22 and 0.49,and 14.7%with a FiO2≥0.5.The 2-day mortality was 0.4%,5.3%,and 22.9%respectively(P<0.001).The 365-day mortality was 9.9%,33.1%,and 50.5%respectively(P<0.001).Finally,the FiO2 predictive capacities 2-,30-,and 365-day mortality were AUC=0.870(95%CI:0.840-0.899),0.810(95%CI:0.784-0.837),0.704(95%CI:0.679-0.728),respectively.CONCLUSION:Prehospital oxygen therapy by thresholds of FiO2 was linked to death and allowed mortality prediction.This finding could provide an aid for EMS providers,allowing to assess more individualized patient risk.展开更多
Infective endocarditis(IE) remains a severe and life-t hreatening disease, with rising incidence and a particularly high mortality rate, especially among elderly patients.^([1]) While antibiotics are the mainstay of t...Infective endocarditis(IE) remains a severe and life-t hreatening disease, with rising incidence and a particularly high mortality rate, especially among elderly patients.^([1]) While antibiotics are the mainstay of treatment, the success rate in left-sided IE is often limited,as nearly half of all patients eventually require surgical intervention for definitive management.^([2]) Heart failure is the main indication for surgery, but access to surgery is frequently restricted by several factors, particularly in patients with advanced age, often driven by the presence of comorbidities or hemodynamic instability.^([3,4])展开更多
This study investigated the short-term effects of woody residues and compost on Orange-fleshed sweet potatoes(OFSP)focusing on plant growth,storage root production,and bioactive compounds.Conducted in a commercial orc...This study investigated the short-term effects of woody residues and compost on Orange-fleshed sweet potatoes(OFSP)focusing on plant growth,storage root production,and bioactive compounds.Conducted in a commercial orchard,the experiment compared different organic fertilization treatments with a control.Four treatments were established:Treatment 1(T1)received compost fertilization;Treatment 2,control,(T2)had no fertilization;and Treatments 3(T3)and 4(T4)were fertilized with high(15 kg·m^(-2))and low(7.5 kg·m^(-2))doses of woody plant residues,respectively.Although woody residue application initially hampered plant growth,it ultimately enhanced biological nitrogen fixation,phosphorus availability,and reduced stress and senescence.Agronomic production did not differ between the compost and woody residue treatments but was increased at the high woody residue dose compared to control.At late growth stages,ascorbic acid decreased in all treatments.At this time,the total phenolic content in storage roots remained high in the woody residue treatments.Conversely,compost reduced the bioactive compounds,without affecting growth,potentially due to oxidative stress in late growth stages.The lower crop senescence index and comparable agronomic production to the compost treatment suggest that woody residues were beneficial for OFSP growth and bioactive composition.The superior quality of the tuberous roots produced with woody residues indicates that this is an effective organic fertilization method for sweet potato production that can contribute to its resilience to environmental variations.展开更多
Regular physical activity is associated with lower adult cancer incidence and mortality,1 with this protective association seemingly independent of important risk factors (high body weight, smoking).2 The potential pr...Regular physical activity is associated with lower adult cancer incidence and mortality,1 with this protective association seemingly independent of important risk factors (high body weight, smoking).2 The potential preventive effect of an active lifestyle was presumed a long time ago by some visionary scientists.展开更多
The reduction of CO_(2)toward CO and CH_(4)over Ni-loaded MoS_(2)-like layered nanomaterials is investigated.The mild hydrothermal synthesis induced the formation of a molybdenum oxysulfide(MoO_(x)S_(y))phase,enriched...The reduction of CO_(2)toward CO and CH_(4)over Ni-loaded MoS_(2)-like layered nanomaterials is investigated.The mild hydrothermal synthesis induced the formation of a molybdenum oxysulfide(MoO_(x)S_(y))phase,enriched with sulfur defects and multiple Mo oxidation states that favor the insertion of Ni^(2+)cations via photo-assisted precipitation.The photocatalytic tests under LED irradiation at different wavelengths from 365 to 940 nm at 250℃rendered 1%CO_(2)conversion and continuous CO production up to 0.6 mmol/(gcat h).The incorporation of Ni into the MoO_(x)S_(y)structure boosted the continuous production of CO up to 5.1 mmol/(gcat h)with a CO_(2)conversion of 3.5%.In situ spectroscopic techniques and DFT simulations showed the O-incorporated MoS_(2)structure,in addition to Ni clusters as a supported metal catalyst.The mechanistic study of the CO_(2)reduction reaction over the catalysts revealed that the reverse water-gas shift reaction is favored due to the preferential formation of carboxylic species.展开更多
Deep phenotyping and genetic characterization of individuals are fundamental to assessing the metabolic status and determining nutrition-specific requirements.This study aimed to ascertain the utmost effectiveness of ...Deep phenotyping and genetic characterization of individuals are fundamental to assessing the metabolic status and determining nutrition-specific requirements.This study aimed to ascertain the utmost effectiveness of personalized interventions by aligning dietary adjustments with both the genotype and metabolotype of individuals.Therefore,we assessed here the usefulness of a polygenic score(PGS)characterizing a potential pro-inflammatory profile(PGSi)as a nutrigenetic tool to discern individuals from the Danish PREVENTOMICS cohort that could better respond to precision nutrition(PN)plans,specifically targeted at counteracting the low-grade inflammatory profile typically found in obesity.The cohort followed a PN plan to counteract the pro-inflammatory profile(PNi group)or generic dietary recommendations(Control)for 10 weeks.PGSi was applied for genetic stratification(Low/High).The effects of the intervention on anthropometrics and biomarkers related to inflammatory profile and carbohydrate metabolism were assessed.Around 30%of subjects had a high genetic predisposition to pro-inflammatory status(high-PGSi).These individuals demonstrated the most effective response to the dietary plan,experiencing improved body composition,with significant decreases in body weight(∆:-4.84%;P=0.039)and body fat(∆:-4.86%;P=0.007),and beneficial changes in pro-and anti-inflammatory biomarkers,with significant increases in IL-10(∆:71.3%;P=0.025)and decreases in TNF-α(∆:-3.0%;P=0.048),CRP(∆:-31.1%),ICAM1(∆:-5.8%),and MCP1(∆:-4.2%)circulating levels,compared to low-PGSi individuals.Both phenotypic and genetic stratification contributed to a better understanding of metabolic heterogeneity in response to diet.This approach allows for refinement of the prediction of individual requirements and potentially for better management of obesity.展开更多
目的临床指南需要根据相关研究结果定期审查以确保其可靠性,但在更新临床指南的过程中仍然缺乏对于更新过程表述的优先报告条目。本文旨在介绍更新版指南报告清单(Checklist for the Reporting of Updated Guidelines,Check Up)及其制...目的临床指南需要根据相关研究结果定期审查以确保其可靠性,但在更新临床指南的过程中仍然缺乏对于更新过程表述的优先报告条目。本文旨在介绍更新版指南报告清单(Checklist for the Reporting of Updated Guidelines,Check Up)及其制定过程。方法基于临床指南更新的研究证据的概述,指南研究与评价工具(Appraisal of Guidelines for Research and EvaluationⅡ,AGREEⅡ)和报告清单专家组(33位)的建议开发了初始清单的各条目。然后,使用多个步骤对本清单进行了完善,包括评估10个现有的更新版临床指南,对关键信息提供者进行访谈[应答率为54.2%(13/24)],清单制定专家组内部进行的一个三轮的德尔菲(Delphi)共识调查,以及来自于临床指南方法学专家[应答率为90%(53/59)]和指南使用者[应答率为55.6%(10/18)]的外部评审意见。结果清单最终包括16个条目,主要涉及:(1)更新版指南的呈现;(2)编辑独立性;(3)更新过程采用的方法。结论更新版指南的报告清单作为一个工具可用于评估更新版指南报告的完整性,并为指南制定者提供撰写报告的要求。展开更多
Background:Mammalian cells possess molecular clocks,the adequate functioning of which is decisive for metabolic health.Exercise is known to modulate these clocks,potentially having distinct effects on metabolism depen...Background:Mammalian cells possess molecular clocks,the adequate functioning of which is decisive for metabolic health.Exercise is known to modulate these clocks,potentially having distinct effects on metabolism depending on the time of day.This study aimed to investigate the impact of morning vs.evening moderate-intensity aerobic exercise on glucose regulation and energy metabolism in healthy men and women.It also aimed to elucidate molecular mechanisms within skeletal muscle.Methods:Using a randomized crossover design,healthy men(n=18)and women(n=17)performed a 60-min bout of moderate-intensity aerobic exercise in the morning and evening.Glucose regulation was continuously monitored starting 24 h prior to the exercise day and continuing until 48 h post-exercise for each experimental condition.Energy expenditure and substrate oxidation were measured by indirect calorimetry during exercise and at rest before and after exercise for 30 min.Skeletal muscle biopsies were collected immediately before and after exercise to assess mitochondrial function,transcriptome,and mitochondrial proteome.Results:Results indicated similar systemic glucose,energy expenditure,and substrate oxidation during and after exercise in both sexes.Notably,transcriptional analysis,mitochondrial function,and mitochondrial proteomics revealed marked sexual dimorphism and time of day variations.Conclusion:The sexual dimorphism and time of day variations observed in the skeletal muscle in response to exercise may translate into observable systemic effects with higher exercise-intensity or chronic exercise interventions.This study provides a foundational molecular framework for precise exercise prescription in the clinical setting.展开更多
Introduction Long-term use of benzodiazepines(BZD)triggers health problems.Although Spain leads European use of BZD,the number of long-term users(LTUs)remains unknown.Objective The aim of the study is to estimate the ...Introduction Long-term use of benzodiazepines(BZD)triggers health problems.Although Spain leads European use of BZD,the number of long-term users(LTUs)remains unknown.Objective The aim of the study is to estimate the proportion of primary care(PC)patients who initiate a BDZ prescription that subsequently become LTU and to identify its associated factors.Design Retrospective real-world data cohort.Setting and participant It included the population over 15 years with a new prescription of BZD in PC in Catalonia.Users were considered LTU if they had been dispensed at least three prescriptions within 3 months.Sociodemographic characteristics of patients and prescribers,pathologies,previous BZD use,number and type of visits,and prescription quality standard were considered.We estimated the proportion of LTU among patients with a new prescription,stratified by age and sex,and estimated risk factors by multivariate generalised linear models.Result 100638 users with a new BZD prescription were included.27.1%were LTU at 3 months and 14.5%at 6 months.LTU increases with age and is higher in women.Predictors of LTU are Spanish nationality,living in rural areas,having a mental illness,having used BZD,having virtual visits or not meeting pharmacy-therapeutic quality standards.Conclusion The number of patients who develop LTU is high,especially in the elderly.Exploring the causes of this phenomenon could contribute to the development of future interventions.展开更多
Diabetic retinopathy(DR) has been classically considered to be a microcirculatory disease of the retina caused by the deleterious metabolic effects of hyperglycemia per se and the metabolic pathways triggered by hyper...Diabetic retinopathy(DR) has been classically considered to be a microcirculatory disease of the retina caused by the deleterious metabolic effects of hyperglycemia per se and the metabolic pathways triggered by hyperglycemia.However,retinal neurodegeneration is already present before any microcirculatory abnormalities can be detected in ophthalmoscopic examination.In other words,retinal neurodegeneration is an early event in the pathogenesis of DR which predates and participates in the microcirculatory abnormalities that occur in DR.Therefore,the study of the mechanisms that lead to neurodegeneration will be essential to identify new therapeutic targets in the early stages of DR.Elevated levels of glutamate and the overexpression of the renin-angiotensin-system play an essential role in the neurodegenerative process that occurs in diabetic retina.Among neuroprotective factors,pigment epithelial derived factor,somatostatin and erythropoietin seem to be the most relevant and these will be considered in this review.Nevertheless,it should be noted that the balance between neurotoxic and neuroprotective factors rather than levels of neurotoxic factors alone will determine the presence or absence of retinal neurodegeneration in the diabetic eye.New strategies,based on either the delivery of neuroprotective agents or the blockade of neurotoxic factors,are currently being tested in experimental models and in clinical pilot studies.Whether these novel therapies will eventually supplement or prevent the need for laser photocoagulation or vitrectomy awaits the results of additional clinical research.展开更多
Inflammatory bowel disease (IBD) develops in genetically susceptible individuals due to the influence of environmental factors, leading to an abnormal recognition of microbiota antigens by the innate immune system whi...Inflammatory bowel disease (IBD) develops in genetically susceptible individuals due to the influence of environmental factors, leading to an abnormal recognition of microbiota antigens by the innate immune system which triggers an exaggerated immune response and subsequent bowel tissue damage. IBD has been more frequently found in families, an observation that could be due to either genetic, environmental or both types of factors present in these families. In addition to expanding our knowledge on IBD pathogenesis, defining the specific contribution to familial IBD of each one of these factors might have also clinical usefulness. We review the available evidence on familial IBD pathogenesis.展开更多
Inflammatory bowel disease (IBD) includes two entities, Crohn’s disease and ulcerative colitis. Both are chronic conditions with frequent complications and surgical procedures and a great impact on patient’s quality...Inflammatory bowel disease (IBD) includes two entities, Crohn’s disease and ulcerative colitis. Both are chronic conditions with frequent complications and surgical procedures and a great impact on patient’s quality of life. The thiopurine antimetabolites azathioprine and 6-mercaptopurine are widely used in IBD patients. Current indications include maintenance therapy, steroid-dependant disease, fistula closure, prevention of infliximab immunogenicity and prevention of Crohn’s disease recurrence. Surprisingly, the wide use of immunosuppressants in the last decades has not decreased the need of surgery, probably because these treatments are introduced at too late stages in disease course. An earlier use of immunossupressants is now advocated by some authors. The rational includes: (1) failure to modify IBD natural history of present therapeutic approach, (2) demonstration that azathioprine can induce mucosal healing, a relevant prognostic factor for Crohn’s disease and ulcerative colitis, and (3) demonstration that early immunossupression has a very positive impact on pediatric, recently diagnosed Crohn’s disease patients. We are now awaiting the results of new studies, to clarify the contribution of azathioprine, as compared to infliximab (SONIC Study), and to demonstrate the usefulness of azathioprine in recently diagnosed adult Crohn’s disease patients (AZTEC study).展开更多
Hepatitis C virus(HCV)infection represents a major public health issue.Hepatitis C can be cured bytherapy,but many infected individuals are unaware of their status.Effective HCV screening,fast diagnosis and characteri...Hepatitis C virus(HCV)infection represents a major public health issue.Hepatitis C can be cured bytherapy,but many infected individuals are unaware of their status.Effective HCV screening,fast diagnosis and characterization,and hepatic fibrosis staging are highly relevant for controlling transmission,treating infected patients and,consequently,avoiding end-stage liver disease.Exposure to HCV can be determined with high sensitivity and specificity with currently available third generation serology assays.Additionally,the use of point-of-care tests can increase HCV screening opportunities.However,active HCV infection must be confirmed by direct diagnosis methods.Additionally,HCV genotyping is required prior to starting any treatment.Increasingly,high-volume clinical laboratories use different types of automated platforms,which have simplified sample processing,reduced hands-on-time,minimized contamination risks and human error and ensured full traceability of results.Significant advances have also been made in the field of fibrosis stage assessment with the development of non-invasive methods,such as imaging techniques and serum-based tests.However,no single test is currently available that is able to completely replace liver biopsy.This review focuses on approved commercial tools used to diagnose HCV infection and the recommended hepatic fibrosis staging tests.展开更多
文摘Background Frailty is common and significantly impacts prognosis in heart failure(HF). The Vulnerable Elders Survey-13(VES-13), widely used in oncogeriatrics and public health, remains unexplored as a frailty screening tool in HF outpatients. In this study, we prospectively evaluated VES-13 against a multimodal screening assessment in detecting frailty and predicting individual risk of adverse prognosis.Methods Frailty was assessed at the initial visit using both a multimodal approach, incorporating Barthel Index, Older American Resources and Services scale, Pfeiffer Test, abbreviated Geriatric Depression Scale, age > 85 years, lacking support systems,and VES-13. Patients scoring ≥ 3 on VES-13 or meeting at least one multimodal criterion were classified as frail. Endpoints included all-cause mortality, a composite of death or HF hospitalization, and recurrent HF hospitalizations.Results A total of 301 patients were evaluated. VES-13 identified 40.2% as frail and the multimodal assessment 33.2%. In Cox regression analyses, frailty identified by VES-13 showed greater prognostic significance than the multimodal assessment for allcause mortality(HR = 3.70 [2.15–6.33], P < 0.001 vs. 2.40 [1.46–4.0], P = 0.001) and the composite endpoint(HR = 3.13 [2.02–4.84], P< 0.001 vs. 1.96 [1.28–2.99], P = 0.002). Recurrent HF hospitalizations were four times more frequent in VES-13 frail patients while two times in those identified as frail by the multimodal assessment. Additionally, stratifying patients by VES-13 tertiles provided robust risk differentiation.Conclusions VES-13, a simple frailty tool, outperformed a comprehensive multimodal assessment and could be easily integrated into routine HF care, highlighting its clinical utility in identifying patients at risk for poor outcomes.
基金Instituto de Salud CarlosⅢCB16/10/00435(CIBERFES)(PID2022-142470OB-I00)from the Spanish Ministry of Innovation and Science+3 种基金PROMETEO(CIPROM/2022/56)de"Consellería de Educación,Universidades,y Empleo de la Generalitat Valenciana"EU Funded H2020-DIABFRAIL-LATAM(Ref:825546)Red EXERNET-RED DE EJERCICIO FISICO Y SALUD(RED2022-134800-T)Agencia Estatal de Investigacion(Ministerio de Ciencias e Innovación)funded by Generalitat Valenciana and co-financed with FEDER funds(OP FEDER of Comunitat Valenciana 2014–2020).A.G-G(FPU22/02539)and S.S-R(PREP2022-000563)received a predoctoral grant financed by the Spanish Ministry of Universities.
文摘Aging is characterized by a progressive decline in physiological function,driven by intrinsic mechanisms(primary aging)and modifiable factors(secondary aging),ultimately leading to multimorbidity,disability,and mortality.Mitochondrial dysfunction,a major hallmark of aging,plays a central role in the loss of muscle mass and strength observed in frailty and sarcopenia.With age,mitochondrial quality control processes,including biogenesis,mitophagy,and dynamics,become dysregulated,impairing energy metabolism and muscle homeostasis.Mitochondrial dysfunction correlates with clinical biomarkers of sarcopenia and frailty,such as the decrease in walking speed and muscle strength,making it a therapeutic target for mitohormesis-based strategies aimed at preserving functional capacity.Mitohormetic agents induce reversible mitochondrial stress,triggering adaptive responses that enhance function.Among these interventions,physical exercise,particularly endurance and resistance training(RT),has been reported to be among the most effective,as it may modulate mitochondrial biogenesis,dynamics,and mitophagy through increases in proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α)and mitochondrial transcription factor A(TFAM)expression,mitochondrial deoxyribonucleic acid(mtDNA)copy number,and mitochondrial content.Chronic RT can also elevate fusion and fission markers,potentially as a compensatory mechanism to mitigate mitochondrial damage.Apart from exercise,mitohormetic compounds such as harmol and piceid are emerging as promising supplements in the aging field.By modulating mitochondrial bioenergetics and dynamics,they may complement lifestyle-based interventions to improve mitochondrial fitness and extend health span.
基金supported by the Wellcome Trust(grant No.103852).
文摘The nervous system function requires a precise but plastic neural architecture.The neuronal shape dictates how neurons interact with each other and with other cells,being the morphology of dendrites and axons the central determinant of the functional properties of neurons and neural circuits.The topological and structural morphology of axons and dendrites defines and determines how synapses are conformed.The morphological diversity of axon and dendrite arborization governs the neuron’s inputs,synaptic integration,neuronal computation,signal transmission,and network circuitry,hence defining the particular connectivity and function of the different brain areas.
基金part of the EU consortium DCog Plast ‘Diet Cognition and Plasticity” funded by the Joint Programming Initiative “A Health Diet for a Healthy Life”(JPI-HDHL) via the BMWFW (BMWFW-10.420/0009-WF/V/3c/2015 and the Medical Research Council UK:MR/N030087/1)(to LA and ST)supported by the PMU-FFF Research Fund (A-16/01/019-AIG)+9 种基金BA by the PMU-Research and Innovation Fund (PMU-RIF)(project 2023-PRE-008-Altendorfer)supported by the Center for Urban Mental Healthby Alzheimer Nederlandthe Zon MW Program Mechanisms Of DEMentia (MODEM)by the Gravitation program iCNS of the Dutch Research Council (NWO)supported by Grant PID2020-114921RB-C21Maria de Maeztu Unit of Excellence grant CEX2021-001234-M funded by MCIU/AEI/and CIBERFESCB16/10/00269, from the Instituto de Salud Carlos III all of them by “ERDF A way of making Europe”the Generalitat de Catalunya’s Agency AGAUR of 2021SGR00687ICREA Award
文摘In Alzheimer’s disease,microglial phagocytosis is engaged in the pathogenesis as it clears abnormal protein accumulations,debris,and apoptotic cells in the early stages of Alzheimer’s disease,but fuels neuroinflammation and accelerates disease progression in later stages.In vivo parabiosis experiments in aged animals have demonstrated that blood-born factors modulate synaptic plasticity,neurogenesis,and microglial responses.We hypothesize that peripheral factors can modulate microglial function and thereby possibly influence Alzheimer’s disease pathology.The objective of this study is to investigate the effects of Alzheimer’s disease serum on microglial phagocytosis.Here,we use an immortalized human microglial cell line in an in vitro parabiosis assay to investigate the impact of the serum from individuals diagnosed with Alzheimer’s disease(n=30)and age-matched controls(n=30)(PRODEM study)on microglial phagocytosis.Exposure to Alzheimer’s disease serum increased microglial phagocytic uptake of pH-sensitive fluorescent particles and downregulated expression of the lysosomal master regulator transcription factor EB(TFEB)and of ATPase H^(+)transporting lysosomal V1 subunit B2(ATP6V1B2),a component of the vacuolar ATPase.To identify serum components that may relate to changes in phagocytosis,serum samples of the Three-City Study(3C Study)were used.In the 3C Study,blood samples were collected up to 12 years before the onset of cognitive decline or dementia and their serum metabolome is well-defined.Microglia exposed to the serum of future Alzheimer’s disease patients from the 3C Study displayed an increased phagocytic uptake compared with the serum of matched controls,depending on the presence of the apolipoprotein Eε4 allele in the Alzheimer’s disease patients.Furthermore,microglial phagocytosis correlated inversely with serum levels of the omega-3 fatty acid eicosapentaenoic acid.We confirmed this inverse correlation between eicosapentaenoic acid and phagocytosis in the serum samples of the PRODEM cohort.In addition,in vitro testing of eicosapentaenoic acid on microglial phagocytosis showed a concentration-dependent decrease in phagocytic uptake.In conclusion,following incubation with Alzheimer’s disease blood serum,we observed increased microglial phagocytic uptake and the downregulation of TFEB and ATP6V1B2,possibly indicating lysosomal dysfunction.Furthermore,microglial phagocytosis was inversely correlated with serum eicosapentaenoic acid levels,suggesting an important role for dietary eicosapentaenoic acid in microglial function.
文摘Background There is scarce data about comparisons between geriatric assessment tools in patients with aortic stenosis(AS).We aimed to describe the geriatric profile of patients with AS undergoing transcatheter aortic valve implantation(TAVI)and to analyze the ability of different tools for predicting clinical outcomes in this context.Methods This was a single center retrospective registry including patients with AS undergoing TAVI and surviving to hospital discharge.The primary endpoint was all-cause mortality or need for urgent readmission one year after TAVI.Results A total of 377 patients were included(mean age of 80.4 years).Most patients were independent or mildly dependent,with an optimal cognitive status.The proportion of frailty ranged from 17.6%to 49.8%.A total of 20 patients(5.3%)died and 110/377 patients(29.2%)died or were readmitted during follow up.Overall,most components of the geriatric assessment showed an association with clinical outcomes.Disability for instrumental activities showed a significant association with mortality and a strong association with the rate of mortality or readmission.The association between frailty and clinical outcomes was higher for short physical performance battery(SPPB),essential frailty toolset(EFT)and the frailty index based on comprehensive geriatric assessment(IF-VIG)and lower for Fried criteria and FRAIL scale.Conclusions AS patients from this series presented a good physical performance,optimal cognitive status and a reasonably low prevalence of frailty.The best predictive ability was observed for disability for instrumental activities and frailty as measured by the EFT,SPPB and the IF-VIG.
基金supported by the Institute of Health Carlos Ⅲ (Spain)co-financed by the European Union (DTS23/00010) for FMR。
文摘BACKGROUND: Prehospital medication is a reality, and the role of these therapies must be explored to assess their validity, especially for acute respiratory diseases, which are usually associated with increased morbidity. The aim of this study was to examine the association of prehospital medication use with mortality in patients with acute respiratory disease.METHODS: A prospective, multicenter, emergency medical service(EMS) delivery cohort study was carried out in adults with unselected respiratory diseases managed by EMS who were transferred to the emergency department. From January 1, 2019, to October 31, 2023, six advanced life support units, thirty-eight basic life support units, and four hospitals in Spain participated in the study. Demographic data, vital signs, use of mechanical ventilation, prehospital respiratory diagnosis, and prehospital medication were collected. The primary outcome was 30-day in-hospital mortality.RESULTS: A total of 961 patients were included, with a mortality rate of 17.5%(168 patients). Age, an increasing number of comorbidities, the use of invasive mechanical ventilation(IMV), the use of major analgesics, hypnotics, and bicarbonate were risk factors. In contrast, elevated systolic blood pressure and Glasgow Coma Scale scores were found to be protective factors against mortality. The predictive capacity of the model reached an area under the curve(AUC) of 0.857(95% confidence interval [95% CI] 0.827–0.888).CONCLUSION: Our data revealed that IMV, major analgesics, hypnotics and bicarbonate administration were associated with elevated mortality. Adding prehospital drug therapy information to demographic variables and vital signs could improve EMS decision-making, allowing a better characterization of patients at risk of clinical worsening.
基金supported by the Institute of Health Carlos III(Spain)and co-financed by the European Union[grant numbers DTS23/00010]for FM-R。
文摘BACKGROUND:Oxygen supply is a common procedure performed by emergency medical services(EMS);however,whether prehospital oxygen or fraction of inspired oxygen(FiO2)therapy predict mortality has not been studied to date.This study aims to determine mortality associated with oxygen therapy in unselected patients with acute disease who underwent prehospital care.METHODS:This was a prospective,observational,cohort,multicenter,EMS-delivery,ambulance-based study.Adults with unselected acute disease who were managed by EMS and evacuated with high priority to the emergency department of four hospitals in three Spanish provinces.Epidemiological variables,on-scene vital signs,and prehospital blood analysis data were collected.The primary outcome was short-(2-,7-,and 30-day),medium-(90-and 180-day),and long-term(365-day)all-cause cumulative mortality.The samples were a priori split according to thresholds of their received FiO2(FiO2=0.21,that is without oxygen therapy;FiO2 between 0.22 and 0.49;and FiO2≥0.5).The categorical variables FiO2,epidemiological variables,vital signs,prehospital point-of-care testing(POCT)and patient outcomes were fitted with a logistic regression model.Additionally,a propensity score matching and a survival analysis were used.RESULTS:The final sample included 7,494 patients,70.3%of whom did not receive oxygen therapy,15%with a FiO2 between 0.22 and 0.49,and 14.7%with a FiO2≥0.5.The 2-day mortality was 0.4%,5.3%,and 22.9%respectively(P<0.001).The 365-day mortality was 9.9%,33.1%,and 50.5%respectively(P<0.001).Finally,the FiO2 predictive capacities 2-,30-,and 365-day mortality were AUC=0.870(95%CI:0.840-0.899),0.810(95%CI:0.784-0.837),0.704(95%CI:0.679-0.728),respectively.CONCLUSION:Prehospital oxygen therapy by thresholds of FiO2 was linked to death and allowed mortality prediction.This finding could provide an aid for EMS providers,allowing to assess more individualized patient risk.
文摘Infective endocarditis(IE) remains a severe and life-t hreatening disease, with rising incidence and a particularly high mortality rate, especially among elderly patients.^([1]) While antibiotics are the mainstay of treatment, the success rate in left-sided IE is often limited,as nearly half of all patients eventually require surgical intervention for definitive management.^([2]) Heart failure is the main indication for surgery, but access to surgery is frequently restricted by several factors, particularly in patients with advanced age, often driven by the presence of comorbidities or hemodynamic instability.^([3,4])
基金funded by the Ministry of Science and Innovation and Universities(AEI/FEDER,UE)with the project Hortbiosol(TED2021-130783B-C21)the National Institute of Health CarlosⅢ,ISCⅢ,with the project CIBEROBN+2 种基金the Generalitat de Catalunya(GC)+European Funds of Rural Development 56301262021 P4 Regensol demonstration projectINSA-UB is María de Maeztu Unit of Excellence(Grant CEX2021-001234-M funded by MICIN/AEI/FEDER,UE)the National Scholarship Program of Paraguay“Carlos Antonio Lo pez”(BECAL 183/2021)。
文摘This study investigated the short-term effects of woody residues and compost on Orange-fleshed sweet potatoes(OFSP)focusing on plant growth,storage root production,and bioactive compounds.Conducted in a commercial orchard,the experiment compared different organic fertilization treatments with a control.Four treatments were established:Treatment 1(T1)received compost fertilization;Treatment 2,control,(T2)had no fertilization;and Treatments 3(T3)and 4(T4)were fertilized with high(15 kg·m^(-2))and low(7.5 kg·m^(-2))doses of woody plant residues,respectively.Although woody residue application initially hampered plant growth,it ultimately enhanced biological nitrogen fixation,phosphorus availability,and reduced stress and senescence.Agronomic production did not differ between the compost and woody residue treatments but was increased at the high woody residue dose compared to control.At late growth stages,ascorbic acid decreased in all treatments.At this time,the total phenolic content in storage roots remained high in the woody residue treatments.Conversely,compost reduced the bioactive compounds,without affecting growth,potentially due to oxidative stress in late growth stages.The lower crop senescence index and comparable agronomic production to the compost treatment suggest that woody residues were beneficial for OFSP growth and bioactive composition.The superior quality of the tuberous roots produced with woody residues indicates that this is an effective organic fertilization method for sweet potato production that can contribute to its resilience to environmental variations.
基金supported in part by NIH Grant No. U01 TR002004 (REACH project)Research by TP and CFL is funded by the Spanish Ministry of Science and Innovation and (Fondo de Investigaciones Sanitarias, ISCIII)+3 种基金Fondos FEDER (grant numbers PI22/00201 (TP)PI20/00645 and PI23/00396 (CF-L))Research by CFL is also funded by ISCIII (FORT23/00023)Research by AL and CF-L is funded by Wereld Kanker Onderzoek Fonds (WKOF) as part of the World Cancer Research Fund International grant programme (IIG_FULL_2021_007).
文摘Regular physical activity is associated with lower adult cancer incidence and mortality,1 with this protective association seemingly independent of important risk factors (high body weight, smoking).2 The potential preventive effect of an active lifestyle was presumed a long time ago by some visionary scientists.
基金Financial support from the Spanish Ministry of Science and Universities through CEX2023-001286-S,PID2020-114926RB-I00,and CTQ2016-77144-Rthe MICINN Scholarship.
文摘The reduction of CO_(2)toward CO and CH_(4)over Ni-loaded MoS_(2)-like layered nanomaterials is investigated.The mild hydrothermal synthesis induced the formation of a molybdenum oxysulfide(MoO_(x)S_(y))phase,enriched with sulfur defects and multiple Mo oxidation states that favor the insertion of Ni^(2+)cations via photo-assisted precipitation.The photocatalytic tests under LED irradiation at different wavelengths from 365 to 940 nm at 250℃rendered 1%CO_(2)conversion and continuous CO production up to 0.6 mmol/(gcat h).The incorporation of Ni into the MoO_(x)S_(y)structure boosted the continuous production of CO up to 5.1 mmol/(gcat h)with a CO_(2)conversion of 3.5%.In situ spectroscopic techniques and DFT simulations showed the O-incorporated MoS_(2)structure,in addition to Ni clusters as a supported metal catalyst.The mechanistic study of the CO_(2)reduction reaction over the catalysts revealed that the reverse water-gas shift reaction is favored due to the preferential formation of carboxylic species.
基金supported through the European Union’s Horizon 2020 Research and Innovation Program(818318)。
文摘Deep phenotyping and genetic characterization of individuals are fundamental to assessing the metabolic status and determining nutrition-specific requirements.This study aimed to ascertain the utmost effectiveness of personalized interventions by aligning dietary adjustments with both the genotype and metabolotype of individuals.Therefore,we assessed here the usefulness of a polygenic score(PGS)characterizing a potential pro-inflammatory profile(PGSi)as a nutrigenetic tool to discern individuals from the Danish PREVENTOMICS cohort that could better respond to precision nutrition(PN)plans,specifically targeted at counteracting the low-grade inflammatory profile typically found in obesity.The cohort followed a PN plan to counteract the pro-inflammatory profile(PNi group)or generic dietary recommendations(Control)for 10 weeks.PGSi was applied for genetic stratification(Low/High).The effects of the intervention on anthropometrics and biomarkers related to inflammatory profile and carbohydrate metabolism were assessed.Around 30%of subjects had a high genetic predisposition to pro-inflammatory status(high-PGSi).These individuals demonstrated the most effective response to the dietary plan,experiencing improved body composition,with significant decreases in body weight(∆:-4.84%;P=0.039)and body fat(∆:-4.86%;P=0.007),and beneficial changes in pro-and anti-inflammatory biomarkers,with significant increases in IL-10(∆:71.3%;P=0.025)and decreases in TNF-α(∆:-3.0%;P=0.048),CRP(∆:-31.1%),ICAM1(∆:-5.8%),and MCP1(∆:-4.2%)circulating levels,compared to low-PGSi individuals.Both phenotypic and genetic stratification contributed to a better understanding of metabolic heterogeneity in response to diet.This approach allows for refinement of the prediction of individual requirements and potentially for better management of obesity.
文摘目的临床指南需要根据相关研究结果定期审查以确保其可靠性,但在更新临床指南的过程中仍然缺乏对于更新过程表述的优先报告条目。本文旨在介绍更新版指南报告清单(Checklist for the Reporting of Updated Guidelines,Check Up)及其制定过程。方法基于临床指南更新的研究证据的概述,指南研究与评价工具(Appraisal of Guidelines for Research and EvaluationⅡ,AGREEⅡ)和报告清单专家组(33位)的建议开发了初始清单的各条目。然后,使用多个步骤对本清单进行了完善,包括评估10个现有的更新版临床指南,对关键信息提供者进行访谈[应答率为54.2%(13/24)],清单制定专家组内部进行的一个三轮的德尔菲(Delphi)共识调查,以及来自于临床指南方法学专家[应答率为90%(53/59)]和指南使用者[应答率为55.6%(10/18)]的外部评审意见。结果清单最终包括16个条目,主要涉及:(1)更新版指南的呈现;(2)编辑独立性;(3)更新过程采用的方法。结论更新版指南的报告清单作为一个工具可用于评估更新版指南报告的完整性,并为指南制定者提供撰写报告的要求。
基金funded by the Spanish Ministry of Culture and Sport,Consejo Superior de Deportes,Plan de Recuperación,Transformación y Resiliencia,Unión Europea,Next Generation EUAyudas Europeas a Proyectos de Investigaci on Aplicada a la Actividad Física Beneficiosa para la Salud y la Medicina Deportiva(EXP_77437)+9 种基金by the Spanish Ministry of Science and Innovation(PID2022-141506OB-I00)the European Regional Development Funds(ERDF)by the University of Granada Plan Propio de Investigación-Excellence actions:Unit of Excellence on Exercise Nutrition and Health(UCEENS)supported by the Spanish Ministry of Education,Culture and Sport(FPU19/03745 and FPU20/05530,respectively)supported by the Juan de la Cierva Formación Grant FJC2020-044453-I funded by Ministerio de Ciencia e Innovaci on/Agencia Estatal de Investigaci on MCIN/AEI/10.13039/501100011033European Union Next Generation,Plan de Recuperación,Transformación y Resilencia(EU/PRTR)“Ramón y Cajal fellowship 2013-2017”funded by MCIN/AEI/10.13039/501100011033 and“El Fondo Social Europeo invierte en tu futuro”partially supported by the Grant PID2020-114054RA-I001001100482funded by MCIN/AEI/10.13039/501100011033supported by a grant from the MCIN/AEI/10.13039/501100011033,Spain,and the ERDF(PID2021-126788OB-I00).
文摘Background:Mammalian cells possess molecular clocks,the adequate functioning of which is decisive for metabolic health.Exercise is known to modulate these clocks,potentially having distinct effects on metabolism depending on the time of day.This study aimed to investigate the impact of morning vs.evening moderate-intensity aerobic exercise on glucose regulation and energy metabolism in healthy men and women.It also aimed to elucidate molecular mechanisms within skeletal muscle.Methods:Using a randomized crossover design,healthy men(n=18)and women(n=17)performed a 60-min bout of moderate-intensity aerobic exercise in the morning and evening.Glucose regulation was continuously monitored starting 24 h prior to the exercise day and continuing until 48 h post-exercise for each experimental condition.Energy expenditure and substrate oxidation were measured by indirect calorimetry during exercise and at rest before and after exercise for 30 min.Skeletal muscle biopsies were collected immediately before and after exercise to assess mitochondrial function,transcriptome,and mitochondrial proteome.Results:Results indicated similar systemic glucose,energy expenditure,and substrate oxidation during and after exercise in both sexes.Notably,transcriptional analysis,mitochondrial function,and mitochondrial proteomics revealed marked sexual dimorphism and time of day variations.Conclusion:The sexual dimorphism and time of day variations observed in the skeletal muscle in response to exercise may translate into observable systemic effects with higher exercise-intensity or chronic exercise interventions.This study provides a foundational molecular framework for precise exercise prescription in the clinical setting.
基金supported by the CIBERESP Network Biomedical Research Center for Epidemiology and Public Health(ESP22PI08)Intramural Call for Research Projects 2022The funding entity was not involved in the design or development of the study.IA-L has a Miguel Servet contract(CP22/00029)funded by the Carlos III Health Institute.
文摘Introduction Long-term use of benzodiazepines(BZD)triggers health problems.Although Spain leads European use of BZD,the number of long-term users(LTUs)remains unknown.Objective The aim of the study is to estimate the proportion of primary care(PC)patients who initiate a BDZ prescription that subsequently become LTU and to identify its associated factors.Design Retrospective real-world data cohort.Setting and participant It included the population over 15 years with a new prescription of BZD in PC in Catalonia.Users were considered LTU if they had been dispensed at least three prescriptions within 3 months.Sociodemographic characteristics of patients and prescribers,pathologies,previous BZD use,number and type of visits,and prescription quality standard were considered.We estimated the proportion of LTU among patients with a new prescription,stratified by age and sex,and estimated risk factors by multivariate generalised linear models.Result 100638 users with a new BZD prescription were included.27.1%were LTU at 3 months and 14.5%at 6 months.LTU increases with age and is higher in women.Predictors of LTU are Spanish nationality,living in rural areas,having a mental illness,having used BZD,having virtual visits or not meeting pharmacy-therapeutic quality standards.Conclusion The number of patients who develop LTU is high,especially in the elderly.Exploring the causes of this phenomenon could contribute to the development of future interventions.
基金Supported by Grants from the Ministerio de Cienciae Innovacion,No.SAF2009-07408CIBER de Diabetesy Enfermedades Metabólicas Asociadas and Generaltitat de Catalunya,No. 2009SGR739
文摘Diabetic retinopathy(DR) has been classically considered to be a microcirculatory disease of the retina caused by the deleterious metabolic effects of hyperglycemia per se and the metabolic pathways triggered by hyperglycemia.However,retinal neurodegeneration is already present before any microcirculatory abnormalities can be detected in ophthalmoscopic examination.In other words,retinal neurodegeneration is an early event in the pathogenesis of DR which predates and participates in the microcirculatory abnormalities that occur in DR.Therefore,the study of the mechanisms that lead to neurodegeneration will be essential to identify new therapeutic targets in the early stages of DR.Elevated levels of glutamate and the overexpression of the renin-angiotensin-system play an essential role in the neurodegenerative process that occurs in diabetic retina.Among neuroprotective factors,pigment epithelial derived factor,somatostatin and erythropoietin seem to be the most relevant and these will be considered in this review.Nevertheless,it should be noted that the balance between neurotoxic and neuroprotective factors rather than levels of neurotoxic factors alone will determine the presence or absence of retinal neurodegeneration in the diabetic eye.New strategies,based on either the delivery of neuroprotective agents or the blockade of neurotoxic factors,are currently being tested in experimental models and in clinical pilot studies.Whether these novel therapies will eventually supplement or prevent the need for laser photocoagulation or vitrectomy awaits the results of additional clinical research.
基金Supported by Grants from Ministerio de Ciencia e Innovación(SAF2008/03676) and Fundació Miarnau to Sans M
文摘Inflammatory bowel disease (IBD) develops in genetically susceptible individuals due to the influence of environmental factors, leading to an abnormal recognition of microbiota antigens by the innate immune system which triggers an exaggerated immune response and subsequent bowel tissue damage. IBD has been more frequently found in families, an observation that could be due to either genetic, environmental or both types of factors present in these families. In addition to expanding our knowledge on IBD pathogenesis, defining the specific contribution to familial IBD of each one of these factors might have also clinical usefulness. We review the available evidence on familial IBD pathogenesis.
基金Grants from Ministerio de Educación y Ciencia(SAF2005-00280) to MS
文摘Inflammatory bowel disease (IBD) includes two entities, Crohn’s disease and ulcerative colitis. Both are chronic conditions with frequent complications and surgical procedures and a great impact on patient’s quality of life. The thiopurine antimetabolites azathioprine and 6-mercaptopurine are widely used in IBD patients. Current indications include maintenance therapy, steroid-dependant disease, fistula closure, prevention of infliximab immunogenicity and prevention of Crohn’s disease recurrence. Surprisingly, the wide use of immunosuppressants in the last decades has not decreased the need of surgery, probably because these treatments are introduced at too late stages in disease course. An earlier use of immunossupressants is now advocated by some authors. The rational includes: (1) failure to modify IBD natural history of present therapeutic approach, (2) demonstration that azathioprine can induce mucosal healing, a relevant prognostic factor for Crohn’s disease and ulcerative colitis, and (3) demonstration that early immunossupression has a very positive impact on pediatric, recently diagnosed Crohn’s disease patients. We are now awaiting the results of new studies, to clarify the contribution of azathioprine, as compared to infliximab (SONIC Study), and to demonstrate the usefulness of azathioprine in recently diagnosed adult Crohn’s disease patients (AZTEC study).
基金Supported by A Miguel Servet contract No.MS09/00044 funded by FIS-ISCIII(Spanish Government)to MartróEgrant PI10/01734 within the"Plan Nacional de I+D+I"co-financed by"ISCIII-Subdirección General de Evaluación y el Fondo Eu-ropeo de Desarrollo Regional"(FEDER)to González V,Saludes V,MartróE
文摘Hepatitis C virus(HCV)infection represents a major public health issue.Hepatitis C can be cured bytherapy,but many infected individuals are unaware of their status.Effective HCV screening,fast diagnosis and characterization,and hepatic fibrosis staging are highly relevant for controlling transmission,treating infected patients and,consequently,avoiding end-stage liver disease.Exposure to HCV can be determined with high sensitivity and specificity with currently available third generation serology assays.Additionally,the use of point-of-care tests can increase HCV screening opportunities.However,active HCV infection must be confirmed by direct diagnosis methods.Additionally,HCV genotyping is required prior to starting any treatment.Increasingly,high-volume clinical laboratories use different types of automated platforms,which have simplified sample processing,reduced hands-on-time,minimized contamination risks and human error and ensured full traceability of results.Significant advances have also been made in the field of fibrosis stage assessment with the development of non-invasive methods,such as imaging techniques and serum-based tests.However,no single test is currently available that is able to completely replace liver biopsy.This review focuses on approved commercial tools used to diagnose HCV infection and the recommended hepatic fibrosis staging tests.
