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1.
Ann Bot ; 132(7): 1249-1258, 2023 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-37823772

RESUMO

BACKGROUND AND AIMS: Endoreduplication, the duplication of the nuclear genome without mitosis, is a common process in plants, especially in angiosperms and mosses. Accumulating evidence supports the relationship between endoreduplication and plastic responses to stress factors. Here, we investigated the level of endoreduplication in Ceratodon (Bryophyta), which includes the model organism Ceratodon purpureus. METHODS: We used flow cytometry to estimate the DNA content of 294 samples from 67 localities and found three well-defined cytotypes, two haploids and one diploid, the haploids corresponding to C. purpureus and Ceratodon amazonum, and the diploid to Ceratodon conicus, recombination occurring between the former two. KEY RESULTS: The endoreduplication index (EI) was significantly different for each cytotype, being higher in the two haploids. In addition, the EI of the haploids was higher during the hot and dry periods typical of the Mediterranean summer than during spring, whereas the EI of the diploid cytotype did not differ between seasons. CONCLUSIONS: Endopolyploidy may be essential in haploid mosses to buffer periods of drought and to respond rapidly to desiccation events. Our results also suggest that the EI is closely related to the basic ploidy level, but less so to the nuclear DNA content as previously suggested.


Assuntos
Briófitas , Bryopsida , Diploide , Haploidia , Endorreduplicação/genética , Secas , DNA
2.
Psychopharmacology (Berl) ; 240(1): 203-211, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36538098

RESUMO

RATIONALE: Clozapine has proven to be superior to other antipsychotic drugs in the treatment of schizophrenia but is under-prescribed due to its potentially severe side effects. Clozapine-induced sialorrhea (CIS) is a frequent and extremely uncomfortable side effect, which remains understudied. OBJECTIVES: To examine the prevalence of diurnal and nocturnal CIS in a sample of patients treated with clozapine, and to evaluate its impact on quality of life. METHODS: We conducted a cross-sectional, observational study of 130 patients with schizophrenia spectrum disorders treated with clozapine. The prevalence of CIS was evaluated via specific sialorrhea scales. None of the patients included in the study was receiving a specific treatment for hypersalivation during the study period. Possible associations between sialorrhea and clinical and quality of life variables were analyzed. RESULTS: Of 130 subjects, 120 (92.3%) suffered from CIS. Eighty-one (62.31%) suffered from diurnal CIS, 115 (88.56%) from nocturnal CIS, and 85 (65.38%) suffered from both. Significant positive associations between quality of life and diurnal CIS (B = 0.417; p = 2.1e - 6, R2 = 0.156) and nocturnal CIS (B = 0.411; p = 7.7e - 6, R2 = 0.139) were detected. Thirty per cent of the subjects reported a moderate to severe negative impact of sialorrhea on their quality of life. CONCLUSIONS: The present study suggests that CIS is highly prevalent in patients with schizophrenia and has an important impact on quality of life in one-third of our sample. Therefore, the inclusion of a systematic evaluation and treatment of CIS in standard clinical practice is highly recommended. TRIAL REGISTRATION: Clinical Trials ( https://clinicaltrials.gov ) under reference NCT04197037.


Assuntos
Antipsicóticos , Clozapina , Sialorreia , Humanos , Clozapina/efeitos adversos , Sialorreia/induzido quimicamente , Sialorreia/epidemiologia , Sialorreia/tratamento farmacológico , Prevalência , Qualidade de Vida , Estudos Transversais , Antipsicóticos/efeitos adversos
3.
Med Intensiva (Engl Ed) ; 46(9): 491-500, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36057440

RESUMO

OBJECTIVES: The current official model of training in Intensive Care Medicine (ICM) in Spain is based on exposure to experiences through clinical rotations. The main objective was to determine the level of competency (I novice to V independent practitioner) achieved by the residents at the end of the 3rd year of training (R3) in ICM through a simulation-based OSCE. Secondary objectives were: (1) To identify gaps in performance, and (2) To investigate the reliability and feasibility of conducting simulation-based assessment at multiple sites. DESIGN: Observational multicenter study. SETTING: Thirteen Spanish ICU Departments. PARTICIPANTS: Thirty six R3. INTERVENTION: The participants performed on five, 15-min, high-fidelity crisis scenarios in four simulation centers. The performances were video recorded for later scoring by trained raters. MAIN VARIABLES OF INTEREST: Via a Delphi technique, an independent panel of expert intensivists identified critical essential performance elements (CEPE) for each scenario to define the levels of competency. RESULTS: A total of 176 performances were analyzed. The internal consistency of the check-lists were adequate (KR-20 range 0.64-0.79). Inter-rater reliability was strong [median Intraclass Correlation Coefficient across scenarios: 0.89 (0.65-0.97)]. Competency levels achieved by R3 were: Level I (18.8%), II (35.2%), III (42.6%), IV/V (3.4%). Overall, a great heterogeneity in performance was observed. CONCLUSION: The expected level of competency after one year in the ICU was achieved only in half of the performances. A more evidence-based educational approach is needed. Multiple center simulation-based assessment showed feasibility and reliability as an evaluation method of competency. TRIAL REGISTRATION: COBALIDATION. NCT04278976. (https://register. CLINICALTRIALS: gov).


Assuntos
Medicina de Emergência , Internato e Residência , Competência Clínica , Cuidados Críticos , Medicina de Emergência/educação , Humanos , Reprodutibilidade dos Testes
4.
Psychopharmacology (Berl) ; 239(1): 229-242, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34888704

RESUMO

RATIONALE: Major depressive disorder (MDD) is a leading cause of disability worldwide but currently prescribed treatments do not adequately ameliorate the disorder in a significant portion of patients. Hence, a better appreciation of its aetiology may lead to the development of novel therapies. OBJECTIVES: In the present study, we have built on our previous findings indicating a role for protease-activated receptor-2 (PAR2) in sickness behaviour to determine whether the PAR2 activator, AC264613, induces behavioural changes similar to those observed in depression-like behaviour. METHODS: AC264613-induced behavioural changes were examined using the open field test (OFT), sucrose preference test (SPT), elevated plus maze (EPM), and novel object recognition test (NOR). Whole-cell patch clamping was used to investigate the effects of PAR2 activation in the lateral habenula with peripheral and central cytokine levels determined using ELISA and quantitative PCR. RESULTS: Using a blood-brain barrier (BBB) permeable PAR2 activator, we reveal that AC-264613 (AC) injection leads to reduced locomotor activity and sucrose preference in mice but is without effect in anxiety and memory-related tasks. In addition, we show that AC injection leads to elevated blood sera IL-6 levels and altered cytokine mRNA expression within the brain. However, neither microglia nor peripheral lymphocytes are the source of these altered cytokine profiles. CONCLUSIONS: These data reveal that PAR2 activation results in behavioural changes often associated with depression-like behaviour and an inflammatory profile that resembles that seen in patients with MDD and therefore PAR2 may be a target for novel antidepressant therapies.


Assuntos
Transtorno Depressivo Maior , Microglia , Animais , Citocinas , Depressão , Humanos , Camundongos , Receptor PAR-2
5.
Med. intensiva (Madr., Ed. impr.) ; 45(7): 411-420, Octubre 2021. tab
Artigo em Espanhol | IBECS | ID: ibc-224143

RESUMO

Objetivos: 1) Determinar la satisfacción de tutores y residentes con la metodología utilizada para la implementación de CoBaTrICE, y 2) determinar la validez y la fiabilidad de las escalas de valoración global diseñados ad hoc para analizar el desempeño de los residentes con fines formativos. Diseño: Estudio prospectivo de cohortes. Participantes: Todos los residentes y tutores del Servicio de Medicina Intensiva del Hospital Universitario y Politécnico La Fe de Valencia. Intervención: En marzo del 2016 se inició la implementación de CoBaTrICE sustentada en: 1) formación de los tutores en técnicas de retroalimentación; 2) realización por los residentes de múltiples ejercicios reales de evaluación objetiva y estructurada para adquirir las competencias del programa, y 3) uso de un portafolio electrónico para registrar las evidencias del progreso y estimular la reflexión. Métodos: La satisfacción con CoBaTrICE se evaluó mediante una encuesta realizada tras 9 meses de implementación a los 15 residentes y 5 tutores del servicio. Se preguntó sobre la metodología de las evaluaciones, calidad de la retroalimentación, autorregulación del aprendizaje y utilidad del portafolio. Se determinaron la consistencia interna (alfa de Cronbach), índices de generalizabilidad y fiabilidad interjueces (índice de correlación intraclase) de las escalas de valoración global. Resultados: La aplicación de CoBaTrICE fue satisfactoria en todas las dimensiones estudiadas. Se constataron la validez y la fiabilidad de las escalas de valoración utilizadas. Conclusiones: La metodología utilizada para implementar CoBaTrICE fue valorada positivamente por tutores y residentes. Las escalas de valoración global utilizadas en la evaluación formativa demostraron ser válidas, fiables y reproducibles. (AU)


Objectives; 1. To determine the satisfaction of tutors and residents with a specific methodology used to implement CoBaTrICE; 2. To determine the reliability and validity of the global rating scales designed ad hoc to assess the performance of the residents for training purposes. Design Prospective cohort study Participants All the residents and tutors of the ICU Department of the Hospital Universitario y Politécnico la Fe de Valencia. Intervention CoBaTrICE implementation started in March 2016, it was based on: 1) Training the tutors in feedback techniques; 2) Performing multiple objective and structured work based assessments to achieve the competences of the program; and 3) The use of an electronic portfolio to promote learning reflection and to collect the evidence that learning was taking place. Methods The acceptance of CoBaTrICE was explored through a satisfaction survey conducted after 9 months of implementation of the training program. The 15 residents and 5 tutors of the ICU Department were asked about the methodology of the formative assessments, the quality of the feedback, self-learning regulation and the electronic portfolio usefulness. The validity of the global rating scales was assessed through the tests alfa de Cronbach, reliability and generalizability indexes, and intraclass correlation coefficient. Results The implementation of CoBaTrICE was satisfactory in all the dimensions studied. The global rating scales used for formative purposes showed reliability and validity. Conclusions The methodology used to implement CoBaTrICE was highly valued by tutors and residents. The global rating scales used for formative purposes showed reliability and validity. (AU)


Assuntos
Humanos , Capacitação Profissional , Internato e Residência , Avaliação Educacional , Educação Baseada em Competências , Unidades de Terapia Intensiva , Estudos Retrospectivos , Estudos de Coortes , Espanha , Inquéritos e Questionários , Reprodutibilidade dos Testes
6.
Med Intensiva (Engl Ed) ; 45(7): 411-420, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34563341

RESUMO

OBJECTIVES: 1. To determine the satisfaction of tutors and residents with a specific methodology used to implement CoBaTrICE. 2. To determine the reliability and validity of the global rating scales designed ad hoc to assess the performance of the residents for training purposes. DESIGN: Prospective cohort study. PARTICIPANTS: All the residents and tutors of the ICU Department of the Hospital Universitario y Politécnico la Fe de Valencia. INTERVENTION: CoBaTrICE implementation started in March 2016, it was based on: (1) Training the tutors in feedback techniques; (2) Performing multiple objective and structured work based assessments to achieve the competences of the program; and (3) The use of an electronic portfolio to promote learning reflection and to collect the evidence that learning was taking place. METHODS: The acceptance of CoBaTrICE was explored through a satisfaction survey conducted after 9 months of implementation of the training program. The 15 residents and 5 tutors of the ICU Department were asked about the methodology of the formative assessments, the quality of the feedback, self-learning regulation and the electronic portfolio usefulness. The validity of the global rating scales was assessed through the tests alfa de Cronbach, reliability and generalizability indexes, and intraclass correlation coefficient. RESULTS: The implementation of CoBaTrICE was satisfactory in all the dimensions studied. The global rating scales used for formative purposes showed reliability and validity. CONCLUSIONS: The methodology used to implement CoBaTrICE was highly valued by tutors and residents. The global rating scales used for formative purposes showed reliability and validity.


Assuntos
Educação Médica , Cuidados Críticos , Humanos , Estudos Prospectivos , Encaminhamento e Consulta , Reprodutibilidade dos Testes
7.
Osteoporos Int ; 32(2): 353-362, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32793995

RESUMO

The aim of this study was to evaluate the association of levels of urinary total polyphenols considered as a proxy measure of polyphenol intake, with longitudinal changes of bone properties, in the InCHIANTI study. Dietary intake of polyphenols appears to be associated with future accelerated deterioration of bone health. INTRODUCTION: Polyphenols, micronutrients ingested through plant-based foods, have antioxidant and anti-inflammatory properties and may contribute to osteoporosis prevention. We evaluated associations of high levels of urinary total polyphenols (UTP), a proxy measure of polyphenol intake, with longitudinal changes of bone properties in a representative cohort of free-living participants of the InCHIANTI study. METHODS: The InCHIANTI study enrolled representative samples from the registry list of two towns in Tuscany, Italy. Baseline data were collected in 1998 and follow-up visits in 2001 and 2004. Of the 1453 participants enrolled, 956 consented to donate a 24-h urine sample used to assess UTP, had dietary assessment, a physical examination, and underwent a quantitative computerized tomography (pQCT) of the tibia. From pQCT images, we estimated markers of bone mass (BM), diaphyseal design (DD), and material quality (MQ). Mixed models were used to study the relationship between baseline tertiles of UTP with changes of the bone characteristics over the follow-up. RESULTS: At baseline, higher levels of UTP were positively correlated with markers of BM, DD, and MQ. Compared with lower tertile of UTP, participants in the intermediate and highest tertiles had higher cortical bone area, cortical mineral content, and cortical thickness. However, participants in the intermediate and highest UTP tertiles experienced accelerated deterioration of these same parameters over the follow-up compared with those in the lowest UTP tertile. CONCLUSIONS: Dietary intake of polyphenols estimated by UTP and dietary questionnaire was associated with long-term accelerated deterioration of bone health. Our study does not support the recommendation of increasing polyphenol intake for osteoporosis prevention.


Assuntos
Antioxidantes , Polifenóis , Densidade Óssea , Estudos de Coortes , Dieta , Humanos , Itália/epidemiologia , Polifenóis/farmacologia
8.
Transl Med UniSa ; 22: 50-51, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32523910
9.
J Psychopharmacol ; 34(7): 709-715, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32438848

RESUMO

BACKGROUND: Rodent behavioural assays are widely used to delineate the mechanisms of psychiatric disorders and predict the efficacy of drug candidates. Conventional behavioural paradigms are restricted to short time windows and involve transferring animals from the homecage to unfamiliar apparatus which induces stress. Additionally, factors including environmental perturbations, handling and the presence of an experimenter can impact behaviour and confound data interpretation. To improve welfare and reproducibility these issues must be resolved. Automated homecage monitoring offers a more ethologically relevant approach with reduced experimenter bias. AIM: To evaluate the effectiveness of an automated homecage system at detecting locomotor and social alterations induced by phencyclidine (PCP) in group-housed rats. PCP is an N-methyl-D-aspartate (NMDA) receptor antagonist commonly utilised to model aspects of schizophrenia. METHODS: Rats housed in groups of three were implanted with radio frequency identification (RFID) tags. Each homecage was placed over a RFID reader baseplate for the automated monitoring of the social and locomotor activity of each individual rat. For all rats, we acquired homecage data for 24 h following administration of both saline and PCP (2.5 mg/kg). RESULTS: PCP resulted in significantly increased distance travelled from 15 to 60 min post injection. Furthermore, PCP significantly enhanced time spent isolated from cage mates and this asociality occured from 60 to 105 min post treatment. CONCLUSIONS: Unlike conventional assays, in-cage monitoring captures the temporal duration of drug effects on multiple behaviours in the same group of animals. This approach could benefit psychiatric preclinical drug discovery through improved welfare and increased between-laboratory replicability.


Assuntos
Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Locomoção/efeitos dos fármacos , Fenciclidina/farmacologia , Animais , Transtornos Dissociativos/psicologia , Masculino , Dispositivo de Identificação por Radiofrequência , Ratos , Reprodutibilidade dos Testes , Comportamento Social , Fatores de Tempo
10.
Nurse Educ Today ; 86: 104319, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31926382

RESUMO

PURPOSE: This study aimed to identify which of the standardised Nursing Interventions Classification (NIC) activities should be used in the design of clinical cases with high fidelity simulation for educational preparation of undergraduate nursing students in non-technical skills. DESIGN AND METHODS: A three-round Delphi study was carried out: the first round with taxonomy experts, the second round with academic and clinical lecturers with limited experience in the simulation-based learning methodology, and the third round with academic and clinical lecturers having at least two years of simulation experience. The NIC interventions were grouped into two levels of competence in accordance with the undergraduate nursing degree curriculum (1st- and 2nd-year students, the "novice" level; 3rd- and 4th-year students, the "advanced" level). The NIC allows the description of nurse student competencies in multiple clinical scenarios and throughout various contexts: theory, clinical practice and simulation. FINDINGS: The experts identified 163 interventions in 8 areas as relevant and feasible, selecting 42 for the "novice" students, in Nursing Fundamentals (13) and Adult Nursing Care 1 (29), and 97 for the "advanced" students: Maternity Care and Child Health Nursing (18), Mental Health (13), Nursing Care of Older People (12), Community Health Nursing (20) and Adult Nursing Care 2 (34). In addition, 24 interventions were identified as cross-cutting, with training to be provided across all four years of the degree. CONCLUSION: A total of 163 interventions of the NIC list were selected by experts as being both relevant and feasible to nursing undergraduate education. This creates the favourable framework to design high-fidelity scenarios for the training of non-technical skills according to the competences required and in line with the health care reality. Therefore, enabling an optimal combination of theoretical education by academic lecturers with practical training by clinical lecturers and staff nurses.


Assuntos
Treinamento com Simulação de Alta Fidelidade/métodos , Terminologia Padronizada em Enfermagem , Adulto , Idoso , Competência Clínica/normas , Competência Clínica/estatística & dados numéricos , Currículo/normas , Currículo/tendências , Técnica Delphi , Bacharelado em Enfermagem/métodos , Bacharelado em Enfermagem/normas , Feminino , Treinamento com Simulação de Alta Fidelidade/normas , Treinamento com Simulação de Alta Fidelidade/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade
11.
Eur J Neurosci ; 52(2): 2838-2852, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31989721

RESUMO

Mitogen-activated protein kinases (MAPKs) regulate normal brain functioning, and their dysfunction is implicated in a number of brain disorders. Thus, there is great interest in understanding the signalling systems that control MAPK functioning. One family of proteins that contribute to this process, the mitogen-activated protein kinase phosphatases (MKPs), directly inactivate MAPKs through dephosphorylation. Recent studies have identified novel functions of MKPs in foetal development, the immune system, cancer and synaptic plasticity and memory. In the present study, we performed an unbiased investigation using MKP-2-/- mice to assess whether MKP-2 plays a global role in modulating brain function. Local cerebral glucose utilization is significantly increased in the ventral tegmental area (VTA) of MKP-2-/- mice, with connectivity analysis revealing alterations in VTA functional connectivity, including a significant reduction in connectivity to the nucleus accumbens and hippocampus. In addition, spontaneous excitatory postsynaptic current frequency, but not amplitude, onto putative dopamine neurons in the VTA is increased in MKP-2-/- mice, which indicates that increased excitatory drive may account for the increased VTA glucose utilization. Consistent with modified VTA function and connectivity, in behavioural tests MKP-2-/- mice exhibited increased sucrose preference and impaired amphetamine-induced hyperlocomotion. Overall, these data reveal that MKP-2 plays a role in modulating VTA function and that its dysfunction may contribute to brain disorders in which altered reward processing is present.


Assuntos
Fosfatases da Proteína Quinase Ativada por Mitógeno/genética , Proteínas Tirosina Fosfatases/genética , Área Tegmentar Ventral , Anfetamina , Animais , Deleção de Genes , Camundongos , Camundongos Knockout , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteína Fosfatase 1 , Recompensa , Área Tegmentar Ventral/metabolismo
12.
Nutr Metab Cardiovasc Dis ; 30(2): 167-178, 2020 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-31848052

RESUMO

Diabetic foot syndrome (DFS) is a complex disease. The best outcomes are reported with the multi-disciplinary team (MDT) approach, where each member works collaboratively according to his/her expertise. However, which health provider should act as the team leader (TL) has not been determined. The TL should be familiar with the management of diabetes, related complications and comorbidities. He/she should be able to diagnose and manage foot infections, including prompt surgical treatment of local lesions, such as abscesses or phlegmons, in an emergent way in the first meeting with the patient. According to the Organization for Economic Co-operation and Development (OECD) reports, Italy is one of countries with a low amputation rate in diabetic patients. Many factors might have contributed to this result, including 1)the special attention directed to diabetes by the public health system, which has defined diabetes as a "protected disease", and accordingly, offers diabetic patients, at no charge, the best specialist care, including specific devices, and 2)the presence of a network of diabetic foot (DF) clinics managed by diabetologists with medical and surgical expertise. The health care providers all share a "patient centred model" of care, for which they use their internal medicine background and skills in podiatric surgery to manage acute or chronic needs in a timely manner. Therefore, according to Italian experiences, which are fully reported in this document, we believe that only a skilled diabetologist/endocrinologist should act as a TL. Courses and university master's degree programmes focused on DF should guarantee specific training for physicians to become a TL.


Assuntos
Pé Diabético/terapia , Endocrinologistas/organização & administração , Liderança , Equipe de Assistência ao Paciente/organização & administração , Papel do Médico , Atitude do Pessoal de Saúde , Competência Clínica , Tomada de Decisão Clínica , Consenso , Pé Diabético/diagnóstico , Educação de Pós-Graduação em Medicina , Endocrinologistas/educação , Endocrinologistas/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Itália
13.
Sci Rep ; 9(1): 3178, 2019 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-30816124

RESUMO

To determine the efficacy and safety of the Ologen collagen matrix adjunctive to Ahmed valve surgery. A randomized prospective multicentre clinical trial involving 58 patients that were followed for one year. Conventional surgery with Ahmed valve was performed in 31 eyes (Control group/CG) and in 27 Ologen (Ologen group/OG) was placed over the valve's plate. Baseline data: age, corneal thickness, intraocular pressure(IOP) and antiglaucoma medications.Postoperative data (days 1, 7 and months 1, 3, 6 and 12): IOP, antiglaucoma medications, visual acuity and complications were recorded. Frequency of hypertensive phase, complete and qualified success and survival rate were studied. No differences were found between CG and OG in the baseline data. The only difference between groups was a significantly lower IOP at day 1. No other differences were found in the follow-up between groups. Hypertensive phase (56%CG and 55%OG, p = 0,947), complete success 28,6%CG and 30,4%OG (p = 0,88) and qualified success 96,4% and 95,9%(p = 0,794). Survival rates at 1 year were 76,7%(CG) and 69,2%(OG)(p = 0,531). 38,7% of patients in the CG suffered some complication during follow-up and 61,5% in OG(p = 0,086). Ologen does not increase safety or efficacy in Ahmed valve surgery at one-year follow-up. This is the first study that shows no benefit of Ologen adjunctive to this surgery.


Assuntos
Anti-Hipertensivos/administração & dosagem , Colágeno/administração & dosagem , Implantes para Drenagem de Glaucoma , Glaucoma/tratamento farmacológico , Glicosaminoglicanos/administração & dosagem , Adulto , Idoso , Paquimetria Corneana/métodos , Feminino , Glaucoma/patologia , Glaucoma/cirurgia , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/patologia , Hipertensão/cirurgia , Pressão Intraocular/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Implantação de Prótese/métodos , Tonometria Ocular , Resultado do Tratamento , Acuidade Visual/efeitos dos fármacos
14.
Exp Neurol ; 308: 35-46, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29944857

RESUMO

Protein S-acylation is a widespread post-translational modification that regulates the trafficking and function of a diverse array of proteins. This modification is catalysed by a family of twenty-three zDHHC enzymes that exhibit both specific and overlapping substrate interactions. Mutations in the gene encoding zDHHC9 cause mild-to-moderate intellectual disability, seizures, speech and language impairment, hypoplasia of the corpus callosum and reduced volume of sub-cortical structures. In this study, we have undertaken behavioural phenotyping, magnetic resonance imaging (MRI) and isolation of S-acylated proteins to investigate the effect of disruption of the Zdhhc9 gene in mice in a C57BL/6 genetic background. Zdhhc9 mutant male mice exhibit a range of abnormalities compared with their wild-type littermates: altered behaviour in the open-field test, elevated plus maze and acoustic startle test that is consistent with a reduced anxiety level; a reduced hang time in the hanging wire test that suggests underlying hypotonia but which may also be linked to reduced anxiety; deficits in the Morris water maze test of hippocampal-dependent spatial learning and memory; and a 36% reduction in corpus callosum volume revealed by MRI. Surprisingly, membrane association and S-acylation of H-Ras was not disrupted in either whole brain or hippocampus of Zdhhc9 mutant mice, suggesting that other substrates of this enzyme are linked to the observed changes. Overall, this study highlights a key role for zDHHC9 in brain development and behaviour, and supports the utility of the Zdhhc9 mutant mouse line to investigate molecular and cellular changes linked to intellectual disability and other deficits in the human population.


Assuntos
Aciltransferases/genética , Encéfalo/patologia , Deficiência Intelectual/genética , Animais , Comportamento Animal , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Modelos Animais de Doenças , Masculino , Aprendizagem em Labirinto , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
15.
J Nutr Health Aging ; 20(5): 478-85, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27102783

RESUMO

IMPORTANCE: The decline in physical performance that occurs in many older subjects is a strong predictor of falls, hospitalization, institutionalization and mortality. Polyphenols are bioactive compounds that may play a preventive role against physical performance decline due to their antioxidant and anti-inflammatory properties. OBJECTIVE: To investigate the association between total urinary polyphenols (TUP) and total dietary polyphenols (TDP) and substantial physical performance decline over a nine-year period among older subjects. METHODS: This longitudinal study included 368 participants aged 65 years or older from the InCHIANTI (Invecchiare in Chianti) study, an Italian population-based cohort. TUP and TDP concentrations were assessed at baseline using the Folin-Ciocalteau (F-C) assay and a validated food frequency questionnaire, respectively. Physical performance was objectively measured at baseline and at nine-year follow-up using the Short Physical Performance Battery (SPPB). A substantial decline in physical performance was considered as a decrease of three or more points in the SPPB score. RESULTS: At the nine-year follow-up assessment, 71 participants had suffered a substantial decline in physical performance. In the fully adjusted logistic regression model, participants in the highest TUP tertile had a lower risk of substantial decline in physical performance than those in the lowest tertile (OR, 0.40; 95% CI, 0.17-0.93; P trend=0.033). However, no significant association between TDP intake and physical performance decline was observed. CONCLUSION: This study shows that high TUP concentrations, a biomarker of polyphenol-rich exposure, were associated with lower risk of substantial decline in physical performance in community-dwelling older subjects over a nine-year period. These results suggest that a polyphenol-rich diet may play a role in protecting against physical performance decline in older people.


Assuntos
Polifenóis/urina , Idoso , Estudos de Coortes , Feminino , Seguimentos , Humanos , Itália , Estudos Longitudinais , Masculino , Estudos Prospectivos , Fatores de Tempo
16.
J Neurosci ; 36(8): 2348-54, 2016 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-26911683

RESUMO

Mitogen-activated protein kinases (MAPKs) regulate brain function and their dysfunction is implicated in a number of brain disorders, including Alzheimer's disease. Thus, there is great interest in understanding the signaling systems that control MAPK function. One family of proteins that contribute to this process, the mitogen-activated protein kinase phosphatases (MKPs), directly inactivate MAPKs through dephosphorylation. Recent studies have identified novel functions of MKPs in development, the immune system, and cancer. However, a significant gap in our knowledge remains in relation to their role in brain functioning. Here, using transgenic mice where the Dusp4 gene encoding MKP-2 has been knocked out (MKP-2(-/-) mice), we show that long-term potentiation is impaired in MKP-2(-/-) mice compared with MKP-2(+/+) controls whereas neuronal excitability, evoked synaptic transmission, and paired-pulse facilitation remain unaltered. Furthermore, spontaneous EPSC (sEPSC) frequency was increased in acute slices and primary hippocampal cultures prepared from MKP-2(-/-) mice with no effect on EPSC amplitude observed. An increase in synapse number was evident in primary hippocampal cultures, which may account for the increase in sEPSC frequency. In addition, no change in ERK activity was detected in both brain tissue and primary hippocampal cultures, suggesting that the effects of MKP-2 deletion were MAPK independent. Consistent with these alterations in hippocampal function, MKP-2(-/-) mice show deficits in spatial reference and working memory when investigated using the Morris water maze. These data show that MKP-2 plays a role in regulating hippocampal function and that this effect may be independent of MAPK signaling.


Assuntos
Deleção de Genes , Hipocampo/metabolismo , Memória/fisiologia , Plasticidade Neuronal/fisiologia , Proteínas Tirosina Fosfatases/deficiência , Animais , Potenciais Pós-Sinápticos Excitadores/fisiologia , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Técnicas de Cultura de Órgãos , Proteínas Tirosina Fosfatases/genética
17.
Plant Biol (Stuttg) ; 18(2): 280-8, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26284822

RESUMO

The common cord moss Funaria hygrometrica has a worldwide distribution and thrives in a wide variety of environments. Here, we studied the genetic diversity in F. hygrometrica along an abiotic gradient in the Mediterranean high mountain of Sierra Nevada (Spain) using a genome scan method. Eighty-four samples from 17 locations from 24 to 2700 m were fingerprinted based on their amplified fragment length polymorphism (AFLP) banding pattern. Using PCA and Bayesian inference we found that the genetic diversity was structured in three or four clusters, respectively. Using a genome scan method we identified 13 outlier loci, which showed a signature of positive selection. Partial Mantel tests were performed between the Euclidean distance matrices of geographic and climatic variables, versus the pair-wise genetic distance of the AFLP dataset and AFLP-positive outliers dataset. AFLP-positive outlier data were significantly correlated with the gradient of the climatic variables, suggesting adaptive variation among populations of F. hygrometrica along the Sierra Nevada Mountains. We highlight the additional analyses necessary to identify the nature of these loci, and their biological role in the adaptation process.


Assuntos
Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , Briófitas/genética , Ecossistema , Loci Gênicos , Genoma de Planta , Seleção Genética , Clima , DNA de Plantas/genética , Fluxo Gênico , Geografia , Polimorfismo Genético , Análise de Componente Principal , Espanha
18.
Plant Biol (Stuttg) ; 17(5): 1057-65, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25980839

RESUMO

The distinction between native and introduced biotas presents unique challenges that culminate in organisms with high long-distance dispersal capacities in a rapidly changing world. Bryophytes, in particular, exhibit large distribution ranges, and some species can truly be qualified as cosmopolitan. Cosmopolitan species, however, typically occur in disturbed environments, raising the question of their nativeness throughout their range. Here, we employ genetic data to address the question of the origin of the cosmopolitan, weedy moss Bryum argenteum on the island of Tenerife. The genetic diversity of B. argenteum on Tenerife was comparable to that found in continental areas due to recurrent colonisation events, erasing any signature of a bottleneck that would be expected in the case of a recent colonisation event. The molecular dating analyses indicated that the first colonisation of the island took place more than 100,000 years ago, i.e. well before the first human settlements. Furthermore, the significant signal for isolation-by-distance found in B. argenteum within Tenerife points to the substantial role of genetic drift in establishing the observed patterns of genetic variation. Together, the results support the hypothesis that B. argenteum is native on Tenerife; although the existence of haplotypes shared between Tenerife and continental areas suggests that more recent, potentially man-mediated introduction also took place. While defining nativeness in organisms that are not deliberately introduced, and wherein the fossil record is extremely scarce, is an exceedingly challenging task, our results suggest that population genetic analyses can represent a useful tool to help distinguish native from alien populations.


Assuntos
Bryopsida/genética , Variação Genética , Sequência de Bases , Genética Populacional , Geografia , Haplótipos , Dados de Sequência Molecular , Filogeografia , Análise de Sequência de DNA , Espanha
19.
Plant Sci ; 235: 81-8, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25900568

RESUMO

Formation of mature pollen grain, an essential process for the reproduction of higher plants, is affected in lines that are deficient in the enzymes of the phosphorylated pathway of serine biosynthesis (PPSB). Mutants of phosphoserine phosphatase (PSP), the enzyme that catalyses the last step of PPSB, are embryo-lethal. When they are complemented with a construct carrying PSP1 cDNA under the control of the 35S promoter (psp1.1 35S:PSP1), which is poorly expressed in anther tissues, plants display a wild-type phenotype, but are male-sterile. The pollen from the psp1.1 35S:PSP1 lines are shrunken and unviable. Here we report the morphological alterations that appear in the psp1.1 35S:PSP1 lines during microspore development. We show that the pollen wall from these lines presents a normal exine layer, but a shrunken and collapsed shape. Lack of PSP activity also affects oil bodies formation in the tapetosomes of tapetal cells which, in turn, may influence microspore pollen coat formation. All these results highlight the important role of the PPSB in the normal development of microspores in Arabidopsis thaliana.


Assuntos
Arabidopsis/enzimologia , Flores/crescimento & desenvolvimento , Monoéster Fosfórico Hidrolases/metabolismo , Proteínas de Plantas/metabolismo , Pólen/crescimento & desenvolvimento , Serina/metabolismo , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , DNA Complementar , Óleos de Plantas/metabolismo , Plantas Geneticamente Modificadas , Polinização , Regiões Promotoras Genéticas
20.
ENFURO: Rev. Asoc. Esp. A.T.S. Urol ; (128): 16-21, abr. 2015.
Artigo em Espanhol | IBECS | ID: ibc-149713

RESUMO

El objetivo de esta investigación es identificar las barreras que perciben mujeres con incontinencia urinaria (IU) para emprender una conducta encaminada a la resolución de su problema con la orina. Se trata de un estudio cualitativo con la participación de 34 mujeres de la provincia de Barcelona (España). Los datos se recogieron mediante entrevistas en profundidad y la técnica del grupo focal. La selección de la muestra fue intencional o de conveniencia y el análisis categorial temático se realizó a partir de las transcripciones de los discursos de las participantes. Los resultados muestran que entre las barreras percibidas respecto a la búsqueda de ayuda para su IU, están la falta de conciencia de la IU como enfermedad, unos conocimientos deficientes respecto a la misma y la propia actitud y práctica de algunos médicos. La falta de tiempo y el cansancio las impide autocuidarse. La pereza, la falta de voluntad o de constancia en la realización de los ejercicios del suelo pélvico obstaculizan su ejecución, así como el coste económico de los centros de rehabilitación privados. Se concluye que se debe empoderar a la mujer, apoyarla y ayudarla en la realización de las conductas promotoras de salud para su IU


The objective of this research is to identify the barriers they perceive women with urinary incontinence (UI) for preventing them from undertaking conduct aimed at solving your problem with urine. This is a qualitative study involving 34 women in the province of Barcelona (Spain). Data were collected through in-depth interviews and focus group technique. The sample selection was intentional or convenience categorical and thematic analysis was conducted from the transcripts of the speeches of the participants. The results show that perceived barriers regarding seeking help for UI, is the lack of awareness of the UI as a disease, a deficient knowledge about it and the right attitude and practice of some doctors. The lack of time and fatigue prevents them self-care. Laziness, lack of will or perseverance in performing pelvic floor exercises, impeding its implementation as well as the economic cost of private rehabilitation centers. It is concluded that should empower women, support and assist in the conduct of health promoting behaviors for IU


Assuntos
Humanos , Feminino , Incontinência Urinária/terapia , Técnicas de Exercício e de Movimento , Comportamento de Doença , Grupos Focais , Cooperação do Paciente/estatística & dados numéricos , Fatores de Risco , Diafragma da Pelve/fisiopatologia , Qualidade de Vida , Promoção da Saúde/métodos
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