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1.
J Mol Cell Cardiol ; 181: 57-66, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37315764

RESUMO

m6A mRNA methylation controls cardiomyocyte function and increased overall m6A levels are a stereotyping finding in heart failure independent of the underlying etiology. However, it is largely unknown how the information is read by m6A reader proteins in heart failure. Here we show that the m6A reader protein Ythdf2 controls cardiac function and identified a novel mechanism how reader proteins control gene expression and cardiac function. Deletion of Ythdf2 in cardiomyocytes in vivo leads to mild cardiac hypertrophy, reduced heart function, and increased fibrosis during pressure overload as well as during aging. Similarly, in vitro the knockdown of Ythdf2 results in cardiomyocyte growth and remodeling. Mechanistically, we identified the eucaryotic elongation factor 2 as post-transcriptionally regulated by Ythdf2 using cell type specific Ribo-seq data. Our study expands our understanding on the regulatory functions of m6A methylation in cardiomyocytes and how cardiac function is controlled by the m6A reader protein Ythdf2.


Assuntos
Insuficiência Cardíaca , Remodelação Ventricular , Humanos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Remodelação Ventricular/genética , Metilação , Miócitos Cardíacos/metabolismo , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/metabolismo
2.
Expert Rev Mol Med ; 24: e29, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35912691

RESUMO

Immune system aging, a process known as immunosenescence, involves a striking rearrangement affecting all immune cells, resulting in an increased rate of infections and a major incidence of autoimmune diseases and cancer. Nonetheless, differences in how individuals of the same chronological age carry out this immunosenescence establishment and thus the aging rate have been reported. In the context of neuroimmunoendocrine communication and its role in the response to stress situations, growing evidence suggests that social environments profoundly influence all physiological responses, especially those linked to immunity. Accordingly, negative contexts (loneliness in humans/social isolation in rodents) were associated with immune impairments and decreased lifespan. However, positive social environments have been correlated with adequate immunity and increased lifespan. Therefore, the social context in which an individual lives is proposed as a decisive modulator of the immunosenescence process and, consequently, of the rate of aging. In this review, the most important findings regarding how different social environments (negative and positive) modulate immunosenescence and therefore the aging rate, as well as the role of stress responses, hormesis, and resilience in these environments will be explained. Finally, several possible molecular mechanisms underlying the effects of negative and positive environments on immunosenescence will be suggested.


Assuntos
Imunossenescência , Envelhecimento , Humanos , Sistema Imunitário , Imunossenescência/fisiologia , Longevidade , Meio Social
3.
Aust Crit Care ; 35(3): 302-308, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34419341

RESUMO

BACKGROUND: Acute respiratory failure (ARF) has become one of the most prevalent serious pathologies encountered in the emergency medical service (EMS). In hospital settings, noninvasive ventilation (NIV) therapy prevents complications from more aggressive treatments for that condition. However, the scarce evidence on the benefits of NIV in prehospital EMS (i.e., during transport to the hospital) is inconclusive. OBJECTIVES: To determine whether the administration of NIV during prehospital EMS in cases of ARF reduces in-hospital mortality compared with starting NIV on arrival to in-patient EMS. METHODS: This is a multicentre, observational, prospective cohort study. We recruited a total of 317 patients from the Madrid region (Spain) who were prescribed NIV for their ARF using a nonprobabilistic consecutive sampling method. Analyses of the main outcome (in-hospital mortality) and secondary outcomes (length of hospital stay, readmissions, percentage of intensive care unit admissions, and cost-effectiveness) will include descriptive analyses of patients' characteristics, as well as bivariate and multivariate analyses and cost-effectiveness analysis. DISCUSSION: This study will provide data on NIV management in prehospital and in-patient EMS in patients with ARF. Results will contribute to the existing evidence on the benefits of NIV in the context of prehospital EMS while underlining the importance of a standardized formal training for physicians and nurses working in prehospital and in-patient EMSs. CONCLUSION: The VentilaMadrid study will provide valuable data on the clinical factors of patients receiving NIV in prehospital EMS. Further, were our hypothesis to be confirmed, our results would strongly suggest that the administration of NIV in prehospital EMS by medical and nursing profesionals formally trained in the technique reduces mortality and improves prognoses.


Assuntos
Serviços Médicos de Emergência , Ventilação não Invasiva , Síndrome do Desconforto Respiratório , Estudos de Coortes , Serviços Médicos de Emergência/métodos , Humanos , Estudos Multicêntricos como Assunto , Ventilação não Invasiva/métodos , Estudos Observacionais como Assunto , Estudos Prospectivos , Espanha
4.
Eur J Neurol ; 27(4): 644-652, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31725927

RESUMO

BACKGROUND AND PURPOSE: Cholinergic dysfunction appears to play a role in the cognitive impairment observed in Parkinson's disease and dementia with Lewy bodies. The occurrence of cholinergic dysfunction in the early stages of these conditions, however, has not been investigated. The objective of this study was to investigate cholinergic function in patients with idiopathic rapid eye movement sleep behaviour disorder (iRBD), a disorder recognized to be an early stage of both Parkinson's disease and dementia with Lewy bodies. METHODS: A total of 21 patients with polysomnography-confirmed iRBD with no evidence of parkinsonism and cognitive impairment and 10 controls underwent positron emission tomography (PET) to assess brain acetylcholinesterase levels (11 C-donepezil PET) and nigrostriatal dopaminergic function (18 F-DOPA PET). Clinical examination included the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III, Mini Mental State Examination and Montreal Cognitive Assessment. RESULTS: The 11 C-donepezil PET was successfully performed in 17 patients with iRBD and nine controls. Compared with controls, patients with iRBD showed a mean 7.65% reduction in neocortical 11 C-donepezil levels (P = 0.005). Bilateral superior temporal cortex, occipital cortex, cingulate cortex and dorsolateral prefrontal cortex showed the most significant reductions at voxel level. CONCLUSION: Reduced neocortical 11 C-donepezil binding in our patients indicates cholinergic denervation and suggests that the projections from the nucleus basalis of Meynert, which supplies cholinergic innervation to the neocortex, are dysfunctional in iRBD. Longitudinal studies will clarify if these changes are predictive of future cognitive impairment in these patients.


Assuntos
Encéfalo/diagnóstico por imagem , Colinesterases/metabolismo , Transtorno do Comportamento do Sono REM/diagnóstico por imagem , Idoso , Encéfalo/metabolismo , Denervação , Di-Hidroxifenilalanina/análogos & derivados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Tomografia por Emissão de Pósitrons/métodos , Transtorno do Comportamento do Sono REM/metabolismo
5.
J Helminthol ; 94: e189, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32907643

RESUMO

Fascioliasis is a zoonotic disease caused by liver flukes transmitted by freshwater lymnaeid snails. Donkey and horse reservoir roles have been highlighted in human endemic areas. Liver fluke infection in mules has received very limited research. Their role in disease transmission, epidemiological importance and Fasciola hepatica pathogenicity are studied for the first time. Prevalence was 39.5% in 81 mules from Aconcagua, and 24.4% in 127 from Uspallata, in high-altitude areas of Mendoza province, Argentina. A mean amount of 101,242 eggs/mule/day is estimated. Lymnaeids from Uspallata proved to belong to ribosomal DNA internal transcribed spacer (ITS) markers ITS-1 and ITS-2 combined haplotype 3C of Galba truncatula. These lymnaeids were experimentally susceptible to infection by egg miracidia from mules. Infectivity, number of cercariae/snail and shedding period fit the enhanced F. hepatica/G. truncatula transmission pattern at very high altitude. This indicates that the mule is able to maintain the F. hepatica cycle independently. Individual burdens of 20 and 97 flukes were found. Mule infection susceptibility is intermediate between donkey and horse, although closer to the latter. Anatomo-pathology and histopathology indicate that massive infection may cause mule death. Haematological value decreases of red blood cells, haemoglobin, leucocytes and lymphocytes indicate anaemia and strong immunosuppression. Strongly increased biochemical marker values indicate liver function alterations. The mule probably played a role in the past exchanges with Chile and Bolivia through Mendoza province. Evidence suggests that mules could contribute to the spread of both F. hepatica and G. truncatula to human fascioliasis-endemic areas in these countries.


Assuntos
Reservatórios de Doenças/veterinária , Equidae/parasitologia , Fasciola hepatica/patogenicidade , Fasciolíase/transmissão , Fasciolíase/veterinária , Zoonoses/transmissão , Animais , Argentina/epidemiologia , Reservatórios de Doenças/parasitologia , Fasciola hepatica/genética , Fasciola hepatica/isolamento & purificação , Fasciolíase/epidemiologia , Fezes/parasitologia , Feminino , Humanos , Masculino , Contagem de Ovos de Parasitas , Prevalência , Virulência , Zoonoses/epidemiologia , Zoonoses/parasitologia
6.
J Microsc ; 275(3): 133-148, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31271444

RESUMO

Many metallurgical processes produce characteristic dislocation accumulation, with heterogeneous spatial and orientation distributions and further development of microstructures after heat treatment. Recovery and recrystallisation behaviours are direct consequences of those uneven dislocation distributions. The Electron BackScatter Diffraction (EBSD) technique can be used for the characterisation of such microstructural features, including: Density of Geometrically Necessary Dislocations (GND), Kernel Average Misorientations (KAM), Grain Orientation Spread (GOS), Grain Average Misorientation (GAM), Grain Reference Orientation Deviation (GROD - Angle) and GOS/D, where D is an assumed characteristic grain length. Production of Fe3%Si alloys with a Goss texture, essential step in the manufacture of electrical transformers, requires several different processing stages, including the one called primary recrystallisation, a key process preceding abnormal grain growth. The structure of grains and different microstructural aspects of the recrystallisation stage will provide the conditions for development of the Goss orientation during abnormal grain growth. In the present work we use GOS, GAM, GROD, GOS/D, GND and KAM, calculated from EBSD scans performed on cold rolled Fe3%Si alloys subject to increasing heat treatment times, to characterise the kinetics of recovery and primary recrystallisation in an Fe3%Si alloy. Difficulties in the interpretation of these results may arise from the interactive competition between various microstructural features. Hardness measurements were also performed in order to validate recovery and recrystallisation evolution by classical methods. It was found that the global GOS (i.e. including grains of all orientations) shows changes which can be related to those observed in the hardness for high annealing temperatures but it is not sensitive to microstructure evolution occurring at low temperatures. Meanwhile, GND undergoes changes at all annealing temperatures and, remarkably, it responds to the recovery that GOS cannot detect at low temperatures. The GAM parameter seems to follow better the microhardness results. When grains belonging to different texture components are analysed, gamma fibre grains are the first to recrystallise and alpha fibre grains the last. LAY DESCRIPTION: Many metallurgical processes produce characteristic dislocation accumulation, with heterogeneous spatial and orientation distributions. Further development of such microstructures occurs with subsequent heat treatments. Recovery and recrystallisation behaviours are directly affected by consequences of those uneven dislocation distributions. The Electron Back Scatter Diffraction (EBSD) technique can be used for the characterisation of such microstructural features using different magnitudes that describe locally or globally misorientations between various locations in the material. In search of the best parameters [among them: Density of Geometrically Necessary Dislocations (GND), Kernel Average Misorientations (KAM), Grain Orientation Spread (GOS), Grain Average Misorientation (GAM), Grain Reference Orientation Deviation (GROD - Angle) and GOS/D, where D is an assumed characteristic grain length], we characterised the kinetics of the recovery during the 1st recrystallisation in an Fe3%Si alloy. It was found that the global GOS (i.e. including grains of all orientations) shows changes that can be related to the advance of recrystallisation on the other hand, the GND (KAM, GAM etc.) parameter seems to better follow the progress of recovery phenomenon. When grains belonging to different texture components are analysed, gamma fibre grains are the first to recrystallise and alpha fibre grains the last.

7.
BMC Geriatr ; 19(1): 25, 2019 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-30691405

RESUMO

BACKGROUND: Physical activity may reverse frailty in the elderly, but we encounter barriers to the implementation of exercise programs in this population. Our main aim is to evaluate the effect of a multicomponent physical activity program, versus regular medical practice, on reverting pre-frailty status among the elderly, 12 months post-intervention. METHODS: Randomized parallel group multicenter clinical trial located in primary care setting, among non-dependent and pre-frail patients > 70 years old, including 190 patients (95 intervention, 95 control group). INTERVENTION: Multicomponent physical activity program (MEFAP, for its acronym in Spanish) with twelve 1.5 h-weekly sessions comprised of: 1. Informative session; 2. Exercises for improving aerobic resistance, muscle strength, propioception-balance and flexibility; and 3. Handing out of at-home exercise chart (twice/week). Main variable: pre-frailty according to the Fried phenotype. Secondary variables: sociodemographic, clinical and functional variables; exercise program adherence, patient satisfaction with the program and quality of life. We will perform an intention-to-treat analysis by comparing the retrogression from pre-frailty (1 or 2 Fried criteria) to robust status (0 Fried criteria) by the end of the intervention, 6 months and 12 months post-intervention. The accumulated incidence in each group will be calculated, as well as the relative risk (RR) and the number needed to treat (NNT) with their corresponding 95% confidence intervals. Protocol was approved by the Ethics Committee Hospital la Paz. DISCUSSION: Within the context of regular clinical practice, our results will provide evidence regarding the effects of exercise interventions on frailty among pre-frail older adults, a key population given their significant potential for functional, physical, and mental health improvement. TRIAL REGISTRATION: NCT03568084 . Registered 26 June 2018. Date of enrollment of the first participant to the trial: July 2nd 2018.


Assuntos
Terapia por Exercício/métodos , Exercício Físico/fisiologia , Idoso Fragilizado , Fragilidade/terapia , Força Muscular/fisiologia , Atenção Primária à Saúde/métodos , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada/métodos , Exercício Físico/psicologia , Feminino , Idoso Fragilizado/psicologia , Fragilidade/psicologia , Humanos , Masculino , Satisfação do Paciente , Qualidade de Vida/psicologia , Projetos de Pesquisa , Resultado do Tratamento
8.
Brain Behav Immun ; 69: 440-455, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29341892

RESUMO

Aging is accompanied by impairment in the nervous, immune, and endocrine systems as well as in neuroimmunoendocrine communication. In this context, there is an age-related alteration of the physiological response to acute stress, which is modulated by catecholamine (CA), final products of the sympathetic-adreno-medullary axis. The involvement of CA in essential functions of the nervous system is consistent with the neuropsychological deficits found in mice with haploinsufficiency (hemizygous; HZ) of tyrosine hydroxylase (TH) enzyme (TH-HZ). However, other possible alterations in regulatory systems have not been studied in these animals. The aim of the present work was to analyze whether adult TH-HZ female mice presented the impairment of behavioral traits and immunological responses that occurs with aging and whether they had affected their mean lifespan. ICR-CD1 female TH-HZ and wild type (WT) mice were used in a longitudinal study. Behavioral tests were performed on adult and old mice in order to evaluate their sensorimotor abilities and exploratory capacity, as well as anxiety-like behaviors. At the ages of 2 ±â€¯1, 4 ±â€¯1, 9 ±â€¯1, 13 ±â€¯1 and 20 ±â€¯1 months, peritoneal leukocytes were extracted and several immune functions were assessed (phagocytic capacity, Natural Killer (NK) cytotoxicity, and lymphoproliferative response to lipopolysaccharide (LPS) and concanavalin A (ConA)). In addition, several oxidative stress parameters (catalase, glutathione reductase and glutathione peroxidase activities, and reduced glutathione (GSH) concentrations as antioxidant compounds as well as xanthine oxidase activity, oxidized glutathione (GSSG) concentrations, and GSSG/GSH ratio as oxidants) were analyzed. As inflammatory stress parameters TNF-alpha and IL-10 concentrations, and TNF-alpha/IL-10 ratios as inflammatory/anti-inflammatory markers, were measured. Animals were maintained in standard conditions until their natural death. The results indicate that adult TH-HZ mice presented worse sensorimotor abilities and exploratory capacity than their WT littermates as well as greater anxiety-like behaviors. With regards to the immune system, adult TH-HZ animals exhibited lower values of phagocytic capacity, NK cytotoxicity, and lymphoproliferative response to LPS and ConA than WT mice. Moreover, immune cells of TH-HZ mice showed higher oxidative and inflammatory stress than those of WT animals. Although these differences between TH-HZ and WT, in general, decreased with aging, this premature immunosenescence and impairment of behavior of TH-HZ mice was accompanied by a shorter mean lifespan in comparison to WT counterparts. In conclusion, haploinsufficiency of th gene in female mice appears to provoke premature aging of the regulatory systems affecting mean lifespan.


Assuntos
Senilidade Prematura/metabolismo , Comportamento Animal/fisiologia , Sistema Imunitário/metabolismo , Longevidade/genética , Tirosina 3-Mono-Oxigenase/metabolismo , Senilidade Prematura/genética , Animais , Modelos Animais de Doenças , Comportamento Exploratório/fisiologia , Feminino , Haploinsuficiência , Camundongos , Atividade Motora/fisiologia , Estresse Oxidativo , Tirosina 3-Mono-Oxigenase/genética
9.
Insectes Soc ; 64(4): 525-533, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29081537

RESUMO

Previous observations have noted that in some species of higher termites the soldier caste lacks pigmented particles in its gut and, instead, is fed worker saliva that imparts a whitish coloration to the abdomen. In order to investigate the occurrence of this trait more thoroughly, we surveyed a broad diversity of termite specimens and taxonomic descriptions from the Old World subfamilies Apicotermitinae, Cubitermitinae, Foraminitermitinae, Macrotermitinae, and Termitinae. We identified 38 genera that have this "white-gutted" soldier (WGS) trait. No termite soldiers from the New World were found to possess a WGS caste. Externally, the WGS is characterized by a uniformly pale abdomen, hyaline gut, and proportionally smaller body-to-head volume ratio compared with their "dark-gutted" soldier (DGS) counterparts found in most termitid genera. The WGS is a fully formed soldier that, unlike soldiers in other higher termite taxa, has a small, narrow, and decompartmentalized digestive tube that lacks particulate food contents. The presumed saliva-nourished WGS have various forms of simplified gut morphologies that have evolved at least six times within the higher termites.

11.
Spinal Cord ; 54(10): 861-865, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26927294

RESUMO

STUDY DESIGN: Cross-sectional study. OBJECTIVES: The main goal of this study was to examine the influence of regular physical activity (PA) on lung volumes and flows. SETTING: The study was conducted in the Vall d'Hebrón Hospital, Barcelona (Spain), and La Fe Hospital, Valencia (Spain). METHODS: Spirometric tests were performed to 67 paraplegics, and differences were established between the active group (AG) (n=37) that performed >60 min per week of moderate-to-vigorous PA (MVPA) and 30 non-AG (NAG). Further, we established the relationship between the spirometric and PA variables and between being active and reaching the lower limit of normal (LLN) of the spirometric variables. RESULTS: AG had greater values than the NAG: FVC (P<0.01), FEV1 (P<0.01) and PEF (P<0.01). Moderate correlations between the MVPA and FVC (r=0.41, P<0.01) and the MVPA and FEV1 (r=0.39, P<0.01) were obtained. The relationship between being physically active and reaching the LLN was statistically significant for FEV1 (χ2=6.184, P<0.05) but not for FVC (P>0.05). CONCLUSIONS: The performance of MVPA for a minimum of 60 min per week can have a beneficial effect, both on lung volumes and on expiratory flow, and led to an achievement of the LLN in FEV1.


Assuntos
Exercício Físico/fisiologia , Pneumopatias/etiologia , Paraplegia/complicações , Adulto , Distribuição de Qui-Quadrado , Estudos Transversais , Feminino , Volume Expiratório Forçado/fisiologia , Humanos , Pneumopatias/diagnóstico , Masculino , Pessoa de Meia-Idade , Espanha , Espirometria , Capacidade Vital
12.
Int Endod J ; 48(8): 814, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25652146

RESUMO

The following article from International Endodontic Journal, 'Micro-computed tomography evaluation of apical transportation and centring ability of Reciproc and WaveOne systems in severely curved root canals' by D. A. de Meireles, T. C. C. A. de Brito, A. A. F. Marques, A. D. B. Garrido, L. F. R. Garcia & E. C. Sponchiado Jr, published online on 5 February 2015 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal Editor in Chief, Prof. Paul Dummer, and John Wiley & Sons Ltd. The retraction has been agreed due to the use of techniques for crucial measurements in canal shaping and a lack of clarity regarding the measuring methodology. The use of inadequate measuring methodologies makes the findings of the paper invalid.

13.
Phys Chem Chem Phys ; 16(7): 2962-70, 2014 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-24390482

RESUMO

The optimization of graphene growth on copper foils using an atmospheric pressure chemical vapor deposition setup is reported. CH4 and H2 were used as precursor gases and Raman spectroscopy as the main graphene characterization technique. Different growth parameters, including temperature and reaction time, the molar ratio of CH4/H2 in the feed and total flow of gases during the reaction step, were studied in detail. It was shown that graphene growth was not homogeneous in the entire sample, multilayer graphene was present in most of the sample, however as the synthesis parameters were optimized, graphene gained better quality, obtaining bilayer graphene over most of the sheet in the final optimized sample. Homemade software was used to analyze the quality of the synthesised graphene, obtaining a more quality graphene according to the synthesis parameters optimized. An optimal bilayer graphene sample was prepared at the lowest growth time (10 min) and the highest synthesis temperature (1050 °C), using a CH4/H2 flow ratio and a total flow rate ratio of precursors of 7% and 60 Nml (CH4 + H4) per min respectively.

14.
Int J Pharm ; 649: 123602, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-37967686

RESUMO

Oxidative stress plays a key role in several systemic and ocular diseases, including hypertensive eye diseases. In this context, we previously showed that oral administration of wild olive (acebuche, ACE) oil from Olea europaea var. sylvestris can counteract ocular damage secondary to arterial hypertension by modulating excess reactive oxygen species (ROS) produced by the enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Therefore, this work describes the development of an ACE oil-based formulation for ocular administration as a local therapy to counteract hypertension-related oxidative damage. Specifically, ACE oil nanoemulsions (NEs) were successfully produced and characterized, exhibiting appropriate features for ophthalmic administration, including a nanometer size (<200 nm), moderate negative ZP, adequate osmolality and pH, and colloidal stability in biorelevant fluids. Likewise, the NEs presented a shear thinning behavior, especially convenient for ocular instillation. In vivo evaluation was performed through either intravitreal injection or topical ophthalmic administration in mice with hypertension induced via administration of Nω-nitro-L-arginine-methyl-ester (L-NAME). Both routes of administration reduced hypertensive morphological alterations and demonstrated a noticeable antioxidant effect thanks to the reduction of the activity/expression of NADPH oxidase in cornea and retina. Thus, an ACE oil ophthalmic formulation represent a promising therapy for ocular pathologies associated with arterial hypertension.


Assuntos
Hipertensão , Olea , Camundongos , Animais , Olea/metabolismo , NG-Nitroarginina Metil Éster/efeitos adversos , Hipertensão/induzido quimicamente , Estresse Oxidativo , Espécies Reativas de Oxigênio , NADPH Oxidases/metabolismo , NADPH Oxidases/farmacologia
15.
Front Vet Sci ; 11: 1360288, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39086765

RESUMO

Introduction: Urinary incontinence (UI) consists of involuntary leakage of urine during the storage phase of urination. Methods: An anonymous survey was given to Spanish and Italian veterinarians about canine UI treated cases, diagnosis, treatment, follow-up, and professional interest. Results and discussion: Most veterinarians treated ≤3 cases/quarter, resulting in the percentage of incontinence males being lower than that of females (1-4% vs 0-24%). The percentage of spayed incontinent females was lower in Spain (0-24%) than in Italy (75-100%). Most diagnoses were based on a diagnostic algorithm (Spain: 88.7%; Italy: 65.3%); patient report and history, blood work, urinalysis and abdominal ultrasound. Urethral/bladder pressure measurement was unusual (Spain: 0.2%; Italy: 2.4%). In Spain, radiology with contrast medium and CT urography (26.3% and 34.4%, respectively) were more frequent than in Italy (11.6% and 22.7%, respectively). When suspecting urethral sphincter mechanism incompetence pharmacological trial (Spain: 93.2%; Italy: 78.9%). The first-choice medical treatment was Phenylpropanolamine, followed by Ephedrine and Deslorelin. When pharmacotherapy failed, the most frequent option was drug change, followed by increased drug dosage/frequency of administration, surgical therapy and colposuspension. A review was completed after the first week of treatment followed by periodic reviews. Most of the respondents participated in continuing education only if UI occurred in their everyday practice (Spain: 63.0%; Italy: 55.4%) and about 30% responders did it regardless of the number of UI cases treated (Spain: 30.5%; Italy: 37.4%). Conclusion: Some recommendations in clinical practice were made. UI can be underestimated by owners; therefore, a complete history should be obtained by veterinarians. Veterinarians should carefully evaluate if spaying is advisable considering it could increase UI risk. A step-by-step approach is recommended and a specific diagnostic-therapeutic algorithm for UI in dogs is provided. Conservative approaches (regular exercise, weight loss in overweight dogs and observing an "incontinence diary" to identify abnormal patterns of urination) are advisable.

16.
Redox Biol ; 75: 103305, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39137583

RESUMO

Extensive efforts have been conducted in the search for new targetable drivers of lung squamous cell carcinoma (LUSC); to date, however, candidates remain mostly unsuccessful. One of the oncogenic pathways frequently found to be active in LUSC is NFE2L2 (NRF2 transcription factor), the levels of which are regulated by KEAP1. Mutations in NFE2L2 or KEAP1 trigger NRF2 activation, an essential protector against reactive oxygen species (ROS). We hypothesized that the frequency of NRF2 activation in LUSC (∼35 %) may reflect a sensitivity of LUSC to ROS. Results from this study reveal that whereas tumors containing active forms of NRF2 were protected, ROS induction in wild-type NFE2L2/KEAP1 LUSC cells triggered ferroptosis. The mechanism of ROS action in normal-NRF2 LUSC cells involved transient NRF2 activation, miR-126-3p/miR-126-5p upregulation, and reduction of p85ß and SETD5 levels. SETD5 levels reduction triggered pentose pathway gene levels increase to toxic values. Simultaneous depletion of p85ßPI3K and SETD5 triggered LUSC cell death, while p85ßPI3K and SETD5 overexpression rescued survival of ROS-treated normal-NRF2 LUSC cells. This shows that the cascade involving NRF2 > miR-126-3p, miR-126-5p > p85ßPI3K and SETD5 is responsible for ROS-induced cell death in normal-NRF2 LUSC. Transient ROS-induced cell death is shown in 3D spheroids, patient-derived organoids, and in xenografts of wild-type NFE2L2/KEAP1 LUSC cells, supporting the potential of acute local ROS induction as a therapeutic strategy for LUSC patients with normal-NRF2.


Assuntos
Carcinoma de Células Escamosas , Proteína 1 Associada a ECH Semelhante a Kelch , Neoplasias Pulmonares , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Espécies Reativas de Oxigênio , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Espécies Reativas de Oxigênio/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Animais , Camundongos , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Ferroptose/genética , MicroRNAs/genética
17.
Rehabilitacion (Madr) ; 58(4): 100862, 2024 Jul 09.
Artigo em Espanhol | MEDLINE | ID: mdl-38986344

RESUMO

INTRODUCTION: Lung transplant (LT) is the ultimate option for end-stage lung diseases. Malnutrition and sarcopenia, common in LT recipients, can be reversible with adequate exercise and nutrition. This study aims to assess changes in physical performance and aerobic capacity after a 10-week rehabilitation program (RP) in LT recipients, as well as to describe the prevalence of sarcopenia and malnutrition before and after RP and their influence on clinically relevant outcomes. MATERIALS AND METHODS: Quasi-experimental study, before and after a 10-week PR in first-time TP recipients, aged over 18 years, from January 2022 to September 2023. Aerobic exercise capacity was assessed through the 6-minute walking test (6MWT) and peak oxygen consumption (VO2peak); and physical performance was measured using the Short Physical Performance Battery (SPPB). Additionally, the prevalence of sarcopenia was described according to the criteria of the European Working Group on Sarcopenia in Older People (EWGSOP2) and malnutrition according to the criteria of the Global Leadership Initiative on Malnutrition (GLIM). RESULTS: Of the 41 patients, 56% had sarcopenia and 80% had malnutrition. After RP, the distance walked in the 6MWT increased by 66.3m (p=0.004) in men and 61m (p=0.001) in women. VO2peak increased in men by a mean of 3.1ml/min/kg (p=0.024). Physical performance improved significantly in both men and women according to the Short Physical Performance Battery (SPPB), with clinically relevant differences of 1.6 pts (p<0.001) and 1.2 pts (p=0.012), respectively. The prevalence of sarcopenia decreased to 24% and malnutrition to 61%. CONCLUSIONS: RP proved to be an effective and safe intervention for LT recipients. In addition to improvements in skeletal muscle strength and exercise capacity, a reduction in the prevalence of sarcopenia and malnutrition was also observed.

18.
Rehabilitacion (Madr) ; 58(3): 100858, 2024.
Artigo em Espanhol | MEDLINE | ID: mdl-38824879

RESUMO

INTRODUCTION: Lung transplant (LT) is one of the therapeutic options for patients with terminal respiratory diseases. It is highly important to incorporate the functional status and frailty assessment into the selection process of candidates for LT. OBJECTIVES: Identify the prevalence of frailty in the LT waiting list. Study the relationship between frailty, functional status, Lung Allocation Score (LAS) and muscular dysfunction. METHODOLOGY: Descriptive transversal study of patients on the waiting list for LT. POPULATION: 74 patients with chronic respiratory diseases assessed by the lung transplant committee and accepted to be transplanted in a university hospital in Barcelona. The outcome variables were frailty status was evaluate for SPPB test, functional capacity was evaluate for the six-minute walking test (6MWT) and muscular dysfunction. The results were analyzed with the statistical package STATA 12. RESULTS: Sample of 48 men and 26 women, with a median age of 56.55 years (SD 10.87. The prevalence of frailty assessed with the SPPB was 33.8% (8.1% are in frailty and 25.7% are in a state of pre-frailty). There is a relationship between the SPPB, 6MWT and maximal inspiratory pressure, but not with others force values. There is a relationship between the risk of frailty (scores below 9 in SPPB) and the meters walked in 6 but not with the LAS. CONCLUSIONS: The risk of frailty in patients with terminal chronic respiratory diseases is high. Frailty is related with functional capacity, but not with LAS.


Assuntos
Fragilidade , Estado Funcional , Transplante de Pulmão , Teste de Caminhada , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Transversais , Listas de Espera , Idoso , Prevalência , Pressões Respiratórias Máximas , Seleção de Pacientes
19.
Radiologia ; 54(2): 149-54, 2012.
Artigo em Espanhol | MEDLINE | ID: mdl-22079139

RESUMO

OBJECTIVE: To calibrate 1.5 tesla magnetic resonance scanners for the quantification of the concentration of iron in the liver. MATERIAL AND METHODS: We analyzed twenty-eight 1.5 tesla magnetic resonance scanners using a phantom with four tubes containing different concentrations of iron (III) chloride and one tube without iron. The phantom represented two typical patients: one with moderate iron overload and one with high iron overload. We measured the signal intensity ratio between each iron-containing tube and the tube without iron; then we calculated the theoretical levels of iron concentration in each scanner according to the model for the two levels of overload. We compared the results of each scanner with those of the reference scanner in which the model and the phantom had been designed, and we calculated the percentage of difference between the two scanners. RESULTS: The mean difference in the ratios compared to the reference center was 11% (0.3-39). The mean concentration of iron was 71 µmol Fe/g for moderate overload and 193 µmol Fe/g for high overload. The mean difference was 6% (1.2- 7%) and 3.4% (0-16%). respectively. In two scanners, we applied a correction factor so that the difference was below 25% in all cases. CONCLUSION: We calibrated twenty-eight 1.5 tesla scanners for the concentration of iron in the liver and achieved variability less than 25%.


Assuntos
Ferro/análise , Fígado/química , Imageamento por Ressonância Magnética/normas , Humanos , Imageamento por Ressonância Magnética/instrumentação , Imagens de Fantasmas , Padrões de Referência
20.
J Contam Hydrol ; 251: 104100, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36347658

RESUMO

This study evaluates the potential toxicity of the soils of the Guadiamar Green Corridor (GGC) affected by the Aznalcóllar mine spill (Andalusia, Spain), one of the most important mining accidents in Europe in recent decades. Twenty years after the accident, although the area is considered to be recovered, residual contamination in soils persists, and the bioavailability of some contaminants, such as As, is showing trends of increasing. Therefore, the potential residual toxicity in 84 soil samples was evaluated by bioassays with lettuce (Latuca sativa L.), earthworms (Eisenia andrei) and determining the microbial activity by basal respiration and metabolic quotient. The selected soils sampled along the GGC were divided into 4 types according to their physicochemical properties. In the closest part of the mine two soil types appear (SS1 and SS2), originally decarbonated and loamy, with a reduction in lettuce root elongation of 57% and 34% compared to the control, as well as a the highest metabolic quotient (23.9 and 18.1 ng CcO2 µg Cmicrob-1 h-1, respectively) with the highest risk of Pb and As toxicity. While, located in the middle and final part of the affected area of the spill (SS3 and SS4), soils presented alkaline pH, finer textures and the lowest metabolic quotient (<9.5 ng CcO2 µg Cmicrob-1 h-1). In addition, due to Pb and As exceeded the Guideline values established in the studied area, the human toxicity risk was determined according to US-EPA methodology. Although the total contents were higher than the Guidelines established, the obtained hazard quotients for both contaminants were less than one, so the risk for human health was discarded. However, monitoring over time of the toxicity risks of the GGC soils would be advisable, especially due to the existence of areas where residual contamination persist, and soil hazard quotient obtained for As in children was higher and close to unity.


Assuntos
Metais Pesados , Poluentes do Solo , Criança , Humanos , Solo/química , Chumbo , Metais Pesados/análise , Poluentes do Solo/análise , Monitoramento Ambiental , Medição de Risco
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