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Spectral differences in ambient light can affect animal behavior and convey crucial information about an individual's environment. The ability to perceive and respond to differences in ambient light varies widely by taxa and is shaped by a species' ecology. Mexican jumping bean moths, Cydia saltitans, spend their entire larval period encased in fallen host seeds and contend with potentially lethal environmental temperatures when host seeds are in direct sunlight. We investigate if and how C. saltitans larvae in host seeds respond to lighting conditions associated with these thermal risks in their natural environments. In a temperature-controlled experiment, we identified that larvae exhibited distinct behavioral ("jumping") responses corresponding to four lighting treatments (white, red, green, and purple), despite extremely minimal light penetration through host seed walls. Red light induced the highest larval activity (measured by probability of movement and by displacement from origin), suggesting that larvae have mechanisms to perceive low levels of red light and/or to detect subtle increases in heat produced by red/near infrared-biased light spectra, possibly providing them with an early-warning mechanism against thermal stress. Our findings highlight the interplay of environmental lighting, behavior, and potential thermosensory adaptations in a species with a visually constrained environment.
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Motor disability in children is evident in diagnoses such as cerebral palsy, muscular dystrophy, multiple sclerosis, or spinal muscular atrophy, among others, due to altered movement and postural patterns. This becomes more evident as the child grows and can be treated with physical therapy. The effectiveness of early interventions in facilitating an improvement in daily life activities varies depending on the child's condition. In this context, the use of exoskeletons has emerged in recent years as a valuable resource for conducting more efficient therapy processes. This work describes the design (both structural and functional) and preliminary usability and functional validation of a 3D-printed passive upper limb exoskeleton. The goal is to provide clinicians with an efficient, low-cost device that is both easy to manufacture and assemble and, in a gamified environment, serves as an assistive device to physical therapy. The device features 5 degrees of freedom, enabling both a pro-gravity and an anti-gravity mode, controlled by a series of elastic bands. This gives rise to a dual operating mode, offering assistance or resistance to different arm, forearm, and shoulder-dependent movements. Usability validation conducted by exoskeleton users showed average results in all aspects rated above 3.8 out of 5, which implies levels of satisfaction between "quite satisfied" and "very satisfied". The analysis of metrics recorded during therapy, such as the Hand Path Ratio and Success Rate (capturing user movements using an inertial sensor in the gamified environment), as well as the range of motion, reveals quantifiable improvements which can be attributed to the use of the exoskeleton: the Hand Path Ratio tended to approach 1 throughout sessions in almost all the users, the Success Rate remained stable (as users consistently were capable of completing the assigned tasks), and the range of motion showed that all patients achieved improvements of more than 10 degrees in some of the tested movements). These functional validation processes involved the participation of 7 children with varying levels of upper limb neuro-motor impairments.
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Desenho de Equipamento , Exoesqueleto Energizado , Impressão Tridimensional , Extremidade Superior , Humanos , Masculino , Criança , Feminino , Reprodutibilidade dos Testes , Adolescente , Paralisia Cerebral/reabilitação , Paralisia Cerebral/fisiopatologia , Fenômenos Biomecânicos , Modalidades de Fisioterapia/instrumentaçãoRESUMO
Introducción: El programa Team Strategies and Tools to Enhance Performance and Patient Safety (TeamSTEPPS®) ha demostrado mejorar el trabajo interprofesional entre los profesionales sanitarios mejorando el trabajo en equipo. Se formó a profesionales de cuidados intensivos en esta metodología mediante el Curso «Instructor/a en simulación: Mejorando el Trabajo en Equipo a Través de TeamSTEPPS®». Objetivos: Analizar el desempeño del trabajo en equipo y las buenas prácticas en simulación de los profesionales de cuidados intensivos asistentes al curso y explorar sus percepciones sobre la experiencia formativa llevada a cabo durante el mismo. Métodos: Se llevó a cabo un estudio descriptivo transversal y fenomenológico mediante una metodología mixta. Se aplicaron a los 18 asistentes al curso los cuestionarios «TeamSTEPPS 2.0 Team Performance Observation Tool» para evaluar el desempeño del trabajo en equipo y «Educational Practices Questionnaire» para las buenas prácticas en simulación tras los escenarios simulados. Posteriormente se realizó una entrevista grupal a través de un grupo focal a ocho asistentes mediante la plataforma de videoconferencias Zoom. Se realizó un análisis temático y de contenido de los discursos desde el paradigma interpretativo. Los datos cuantitativos y cualitativos se analizaron mediante los programas IBM SPSS Statistics 27.0 y MAXQDA Analytics Pro, respectivamente. Resultados: Tanto el nivel de desempeño del trabajo en equipo (media = 96,25; DT = 8.257) como las buenas prácticas en simulación (media = 75; DT = 1.632) tras los escenarios simulados fueron adecuados. Se identificaron los siguientes temas principales: satisfacción con la metodología TeamSTEPPS®, utilidad de la metodología, barreras de implementación de la misma y habilidades no técnicas mejoradas a través del TeamSTEPPS®. Conclusiones: La metodología TeamSTEPPS® puede ser una buena estrategia de educación interprofesional para la mejora de la comunicación el...(AU)
Introduction: The Team Strategies and Tools to Enhance Performance and Patient Safety (TeamSTEPPS®) programme has been shown to improve interprofessional work among healthcare professionals by enhancing teamwork. Intensive care professionals were trained in this methodology through the course «Simulation Trainer: Improving Teamwork through TeamSTEPPS®». Objectives: To analyse the teamwork performance and good practice in simulation of the intensive care professionals attending the course and to explore their perceptions of the training experience carried out during the course. Methods: A cross-sectional descriptive and phenomenological study was carried out using a mixed methodology. The 18 course participants were administered the questionnaires «TeamSTEPPS 2.0 Team Performance Observation Tool» to evaluate teamwork performance and «Educational Practices Questionnaire» for good practices in simulation after the simulated scenarios. Subsequently, a group interview was conducted through a focus group with 8 attendees using the Zoom videoconferencing platform. A thematic and content analysis of the discourses was carried out using the interpretative paradigm. Quantitative and qualitative data were analysed using IBM SPSS Statistics 27.0 and MAXQDA Analytics Pro, respectively. Results: Both the level of teamwork performance (mean = 96.25; SD = 8.257) and good practice in simulation (mean = 75; SD = 1.632) following the simulated scenarios were adequate. The following main themes were identified: satisfaction with the TeamSTEPPS® methodology, usefulness of the methodology, barriers to methodology implementation and non-technical skills improved through TeamSTEPPS®. Conclusions: TeamSTEPPS® methodology can be a good interprofessional education strategy for the improvement of communication and teamwork in intensive care professionals, both at the care level (through on-site simulation strategies)...(AU)
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Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , 28574 , Treinamento por Simulação , Cuidados de Enfermagem , Cuidados Críticos , Liderança , Treinamento com Simulação de Alta Fidelidade , Enfermagem , Epidemiologia Descritiva , Estudos Transversais , Inquéritos e Questionários , Pesquisa Qualitativa , Educação em EnfermagemRESUMO
This paper describes a procedure for the validation of alpha-particle sources (exempt unsealed sources) to be used in experimental setups with liquefied gases at cryogenic temperatures (down to -196 °C) and high vacuum. These setups are of interest for the development and characterization of neutrino and dark matter detectors based on liquid argon, among others. Due to the high purity requirements, the sources have to withstand high vacuum and cryogenic temperatures for extended periods. The validation procedure has been applied to 241Am sources produced by electrodeposition.
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BACKGROUND: STAT-ON™ is an objective tool that registers ON-OFF fluctuations making possible to know the state of the patient at every moment of the day in normal life. Our aim was to analyze the opinion of different Parkinson's disease experts about the STAT-ON™ tool after using the device in a real clinical practice setting (RCPS). METHODS: STAT-ON™ was provided by the Company Sense4Care to Spanish neurologists for using it in a RCPS. Each neurologist had the device for at least three months and could use it in PD patients at his/her own discretion. In February 2020, a survey with 30 questions was sent to all participants. RESULTS: Two thirds of neurologists (53.8% females; mean age 44.9±9 years old) worked in a Movement Disorders Unit, the average experience in PD was 16±6.9 years, and 40.7% of them had previously used other devices. A total of 119 evaluations were performed in 114 patients (range 2-9 by neurologist; mean 4.5±2.3). STAT-ON™ was considered "quite" to "very useful" by 74% of the neurologists with an overall opinion of 6.9±1.7 (0, worst; 10, best). STAT-ON™ was considered better than diaries by 70.3% of neurologists and a useful tool for the identification of patients with advanced PD by 81.5%. Proper identification of freezing of gait episodes and falls were frequent limitations reported. CONCLUSION: STAT-ON™ could be a useful device for using in PD patients in clinical practice.
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Transtornos Neurológicos da Marcha , Doença de Parkinson , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Prova Pericial , Inquéritos e Questionários , NeurologistasRESUMO
INTRODUCTION: The Team Strategies and Tools to Enhance Performance and Patient Safety (TeamSTEPPS®) programme has been shown to improve interprofessional work among healthcare professionals by enhancing teamwork. Intensive care professionals were trained in this methodology through the course "Simulation Trainer: Improving Teamwork through TeamSTEPPS®". OBJECTIVES: To analyse the teamwork performance and good practice in simulation of the intensive care professionals attending the course and to explore their perceptions of the training experience carried out during the course. METHODS: A cross-sectional descriptive and phenomenological study was carried out using a mixed methodology. The 18 course participants were administered the questionnaires "TeamSTEPPS™ 2.0 Team Performance Observation Tool" to evaluate teamwork performance and "Educational Practices Questionnaire" for good practices in simulation after the simulated scenarios. Subsequently, a group interview was conducted through a focus group with 8 attendees using the Zoom™ videoconferencing platform. A thematic and content analysis of the discourses was carried out using the interpretative paradigm. Quantitative and qualitative data were analysed using IBM SPSS Statistics™ 27.0 and MAXQDA Analytics Pro™ respectively. RESULTS: Both the level of teamwork performance (meanâ¯=â¯96.25; SDâ¯=â¯8.257) and good practice in simulation (meanâ¯=â¯75; SDâ¯=â¯1.632) following the simulated scenarios were adequate. The following main themes were identified: satisfaction with the TeamSTEPPS® methodology, usefulness of the methodology, barriers to methodology implementation and non-technical skills improved through TeamSTEPPS®. CONCLUSIONS: TeamSTEPPS® methodology can be a good interprofessional education strategy for the improvement of communication and teamwork in intensive care professionals, both at the care level (through on-site simulation strategies) and at the teaching level (through its inclusion in the students' curriculum).
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Equipe de Assistência ao Paciente , Treinamento por Simulação , Humanos , Estudos Transversais , Comunicação , Cuidados CríticosRESUMO
Canonical inflammasomes are innate immune protein scaffolds that enable the activation of inflammatory caspase-1, and subsequently the processing and release of interleukin (IL)-1ß, IL-18, and danger signals, as well as the induction of pyroptotic cell death. Inflammasome assembly and activation occurs in response to sensing of infectious, sterile and self-derived molecular patterns by cytosolic pattern recognition receptors, including the Nod-like receptor NLRP3. While these responses are essential for host defense, excessive and uncontrolled NLRP3 inflammasome responses cause and contribute to a wide spectrum of inflammatory diseases, including gout. A key step in NLRP3 inflammasome assembly is the sequentially nucleated polymerization of Pyrin domain (PYD)- and caspase recruitment domain (CARD)-containing inflammasome components. NLRP3 triggers polymerization of the adaptor protein ASC through PYD-PYD interactions, but ASC polymerization then proceeds in a self-perpetuating manner and represents a point of no return, which culminates in the activation of caspase-1 by induced proximity. In humans, small PYD-only proteins (POPs) lacking an effector domain regulate this key process through competitive binding, but limited information exists on their physiological role during health and disease. Here we demonstrate that POP1 expression in macrophages is sufficient to dampen MSU crystal-mediated inflammatory responses in animal models of gout. Whether MSU crystals are administered into a subcutaneous airpouch or into the ankle joint, the presence of POP1 significantly reduces neutrophil infiltration. Also, airpouch exudates have much reduced IL-1ß and ASC, which are typical pro-inflammatory indicators that can also be detected in synovial fluids of gout patients. Exogenous expression of POP1 in mouse and human macrophages also blocks MSU crystal-induced NLRP3 inflammasome assembly, resulting in reduced IL-1ß and IL-18 secretion. Conversely, reduced POP1 expression in human macrophages enhances IL-1ß secretion. We further determined that the mechanism for the POP1-mediated inhibition of NLRP3 inflammasome activation is through its interference with the crucial NLRP3 and ASC interaction within the inflammasome complex. Strikingly, administration of an engineered cell permeable version of POP1 was able to ameliorate MSU crystal-mediated inflammation in vivo, as measured by neutrophil infiltration. Overall, we demonstrate that POP1 may play a crucial role in regulating inflammatory responses in gout.
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Gota , Inflamassomos , Ribonucleoproteínas/metabolismo , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Caspase 1/metabolismo , Gota/metabolismo , Humanos , Inflamassomos/metabolismo , Interleucina-18/metabolismo , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismoRESUMO
Introducción La oclusión venosa retiniana (OVR) se ha relacionado con factores de riesgo vascular y trombofilia. Métodos Se trata de un estudio de cohorte prospectivo de todos los pacientes diagnosticados de OVR y remitidos a una clínica de medicina interna de un hospital universitario terciario durante un período de 10 años. Se analizaron variables clínicas, de laboratorio y ecográficas de troncos supraaórticos y se compararon según la edad. Resultados Se incluyeron unos 309 pacientes diagnosticados de OVR, 25 de ellos menores de 50 años. La prevalencia de hipertensión arterial, dislipidemia, diabetes mellitus, hiperhomocisteinemia y placa carotídea fue significativamente mayor en pacientes > 50 años que en los menores. Sin embargo, la prevalencia de trombofilia hereditaria fue mayor en el grupo más joven (32 vs. 11,4%; p = 0,005). Se observaron enfermedades poco frecuentes relacionadas con la OVR como hepatitis C, talasemia menor, enfermedad de Lyme, vasculitis y perlebitis en pacientes jóvenes sin factores de riesgo vascular. Conclusión Sugerimos realizar un estudio genético de trombofilia en pacientes con OVR menores de 50 años, siendo siempre recomendable un control exhaustivo de los factores de riesgo vascular en todos los pacientes con OVR. Además, sugerimos tener en cuenta las enfermedades poco frecuentes relacionadas con la OVR, especialmente en pacientes jóvenes sin factores de riesgo vascular (AU)
Introduction Retinal vein occlusion (RVO) has been related to vascular risk factors and thrombophilia. Methods This is a prospective cohort study of all patients diagnosed with RVO and referred to an Internal Medicine clinic of a tertiary teaching hospital during a 10-year period. Clinical, laboratory and supra-aortic trunks ultrasound variables were analysed and compared according to age. Results Some 309 patients diagnosed with RVO were included, 25 of them younger than 50 years. The prevalence of high blood pressure, dyslipidaemia, diabetes mellitus, hyperhomocysteinemia, and carotid plaque was significantly higher in patients>50 years than in those below. However, the prevalence of inherited thrombophilia was higher in the younger group (32.0 vs 11.4%; p = 0.005). Uncommon diseases related to RVO such as hepatitis C, thalassemia minor, Lyme disease, vasculitis, and periphlebitis were observed in young patients without vascular risk factors. Conclusion We suggest performing a genetic thrombophilia study in RVO patients younger than 50 years, while an exhaustive control of vascular risk factors is always recommended in all RVO patients. Moreover, we suggest bearing in mind uncommon diseases related to RVO, especially in young patients without vascular risk factors (AU)
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Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Hipertensão/complicações , Oclusão da Artéria Retiniana/etiologia , Trombofilia/complicações , Estudos Prospectivos , Estudos de Coortes , Fatores de RiscoRESUMO
Intracellular sensing of stress and danger signals initiates inflammatory innate immune responses by triggering inflammasome assembly, caspase-1 activation and pyroptotic cell death as well as the release of interleukin 1ß (IL-1ß), IL-18 and danger signals. NLRP3 broadly senses infectious patterns and sterile danger signals, resulting in the tightly coordinated and regulated assembly of the NLRP3 inflammasome, but the precise mechanisms are incompletely understood. Here, we identified NLRP11 as an essential component of the NLRP3 inflammasome in human macrophages. NLRP11 interacted with NLRP3 and ASC, and deletion of NLRP11 specifically prevented NLRP3 inflammasome activation by preventing inflammasome assembly, NLRP3 and ASC polymerization, caspase-1 activation, pyroptosis and cytokine release but did not affect other inflammasomes. Restored expression of NLRP11, but not NLRP11 lacking the PYRIN domain (PYD), restored inflammasome activation. NLRP11 was also necessary for inflammasome responses driven by NLRP3 mutations that cause cryopyrin-associated periodic syndrome (CAPS). Because NLRP11 is not expressed in mice, our observations emphasize the specific complexity of inflammasome regulation in humans.
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Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Caspase 1/genética , Caspases/metabolismo , Humanos , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Licenciamento , Macrófagos , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismoRESUMO
INTRODUTION: Retinal vein occlusion (RVO) has been related to vascular risk factors and thrombophilia. METHODS: This is a prospective cohort study of all patients diagnosed with RVO and referred to an Internal Medicine clinic of a tertiary teaching hospital during a 10-year period. Clinical, laboratory and supra-aortic trunks ultrasound variables were analysed and compared according to age. RESULTS: Some 309 patients diagnosed with RVO were included, 25 of them younger than 50 years. The prevalence of high blood pressure, dyslipidaemia, diabetes mellitus, hyperhomocysteinemia, and carotid plaque was significantly higher in patients >50 years than in those below. However, the prevalence of inherited thrombophilia was higher in the younger group (32.0% vs 11.4%; pâ¯=â¯0.005). Uncommon diseases related to RVO such as hepatitis C, thalassemia minor, Lyme disease, vasculitis, and periphlebitis were observed in young patients without vascular risk factors. CONCLUSION: We suggest performing a genetic thrombophilia study in RVO patients younger than 50 years, while an exhaustive control of vascular risk factors is always recommended in all RVO patients. Moreover, we suggest bearing in mind uncommon diseases related to RVO, especially in young patients without vascular risk factors.
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Hipertensão , Oclusão da Veia Retiniana , Trombofilia , Humanos , Hipertensão/complicações , Estudos Prospectivos , Oclusão da Veia Retiniana/epidemiologia , Oclusão da Veia Retiniana/etiologia , Fatores de Risco , Trombofilia/complicações , Trombofilia/epidemiologiaRESUMO
Exacerbations of symptoms represent an unmet need for people with asthma. Bacterial dysbiosis and opportunistic bacterial infections have been observed in, and may contribute to, more severe asthma. However, the molecular mechanisms driving these exacerbations remain unclear. We show here that bacterial lipopolysaccharide (LPS) induces oncostatin M (OSM) and that airway biopsies from patients with severe asthma present with an OSM-driven transcriptional profile. This profile correlates with activation of inflammatory and mucus-producing pathways. Using primary human lung tissue or human epithelial and mesenchymal cells, we demonstrate that OSM is necessary and sufficient to drive pathophysiological features observed in severe asthma after exposure to LPS or Klebsiella pneumoniae. These findings were further supported through blockade of OSM with an OSM-specific antibody. Single-cell RNA sequencing from human lung biopsies identified macrophages as a source of OSM. Additional studies using Osm-deficient murine macrophages demonstrated that macrophage-derived OSM translates LPS signals into asthma-associated pathologies. Together, these data provide rationale for inhibiting OSM to prevent bacterial-associated progression and exacerbation of severe asthma.
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Asma , Oncostatina M/metabolismo , Animais , Asma/patologia , Humanos , Pulmão/patologia , Macrófagos/metabolismo , Camundongos , Muco , Oncostatina M/genéticaRESUMO
INTRODUCTION: Several scoring systems predict mortality in alcohol-associated hepatitis (AH), including the Maddrey discriminant function (mDF) and model for end-stage liver disease (MELD) score developed in the United States, Glasgow alcoholic hepatitis score in the United Kingdom, and age, bilirubin, international normalized ratio, and creatinine score in Spain. To date, no global studies have examined the utility of these scores, nor has the MELD-sodium been evaluated for outcome prediction in AH. In this study, we assessed the accuracy of different scores to predict short-term mortality in AH and investigated additional factors to improve mortality prediction. METHODS: Patients admitted to hospital with a definite or probable AH were recruited by 85 tertiary centers in 11 countries and across 3 continents. Baseline demographic and laboratory variables were obtained. The primary outcome was all-cause mortality at 28 and 90 days. RESULTS: In total, 3,101 patients were eligible for inclusion. After exclusions (n = 520), 2,581 patients were enrolled (74.4% male, median age 48 years, interquartile range 40.9-55.0 years). The median MELD score was 23.5 (interquartile range 20.5-27.8). Mortality at 28 and 90 days was 20% and 30.9%, respectively. The area under the receiver operating characteristic curve for 28-day mortality ranged from 0.776 for MELD-sodium to 0.701 for mDF, and for 90-day mortality, it ranged from 0.773 for MELD to 0.709 for mDF. The area under the receiver operating characteristic curve for mDF to predict death was significantly lower than all other scores. Age added to MELD obtained only a small improvement of AUC. DISCUSSION: These results suggest that the mDF score should no longer be used to assess AH's prognosis. The MELD score has the best performance in predicting short-term mortality.
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Doença Hepática Terminal/etiologia , Hepatite Alcoólica/mortalidade , Fígado/fisiopatologia , Adulto , Análise Discriminante , Doença Hepática Terminal/mortalidade , Doença Hepática Terminal/fisiopatologia , Feminino , Seguimentos , Saúde Global , Hepatite Alcoólica/complicações , Hepatite Alcoólica/fisiopatologia , Humanos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Fatores de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida/tendências , Fatores de TempoRESUMO
Amyotrophic Lateral Sclerosis (ALS) is a devastating heterogeneous disease with still no convincing therapy. To identify the most strategically significant hallmarks for therapeutic intervention, we have performed a comprehensive transcriptomics analysis of dysregulated pathways, comparing datasets from ALS patients and healthy donors. We have identified crucial alterations in RNA metabolism, intracellular transport, vascular system, redox homeostasis, proteostasis and inflammatory responses. Interestingly, the transcription factor NRF2 (nuclear factor (erythroid-derived 2)-like 2) has significant effects in modulating these pathways. NRF2 has been classically considered as the master regulator of the antioxidant cellular response, although it is currently considered as a key component of the transduction machinery to maintain coordinated control of protein quality, inflammation, and redox homeostasis. Herein, we will summarize the data from NRF2 activators in ALS pre-clinical models as well as those that are being studied in clinical trials. As we will discuss, NRF2 is a promising target to build a coordinated transcriptional response to motor neuron injury, highlighting its therapeutic potential to combat ALS.
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Esclerose Lateral Amiotrófica , Fator 2 Relacionado a NF-E2 , Esclerose Lateral Amiotrófica/tratamento farmacológico , Esclerose Lateral Amiotrófica/genética , Antioxidantes , Regulação da Expressão Gênica , Humanos , Neurônios Motores/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismoRESUMO
The balance between NLRP3 inflammasome activation and mitophagy is essential for homeostasis and cellular health, but this relationship remains poorly understood. Here we found that interleukin-1α (IL-1α)-deficient macrophages have reduced caspase-1 activity and diminished IL-1ß release, concurrent with reduced mitochondrial damage, suggesting a role for IL-1α in regulating this balance. LPS priming of macrophages induced pro-IL-1α translocation to mitochondria, where it directly interacted with mitochondrial cardiolipin (CL). Computational modeling revealed a likely CL binding motif in pro-IL-1α, similar to that found in LC3b. Thus, binding of pro-IL-1α to CL in activated macrophages may interrupt CL-LC3b-dependent mitophagy, leading to enhanced Nlrp3 inflammasome activation and more robust IL-1ß production. Mutation of pro-IL-1α residues predicted to be involved in CL binding resulted in reduced pro-IL-1α-CL interaction, a reduction in NLRP3 inflammasome activity, and increased mitophagy. These data identify a function for pro-IL-1α in regulating mitophagy and the potency of NLRP3 inflammasome activation.
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Cardiolipinas/metabolismo , Interleucina-1alfa/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Animais , Autofagia , Cardiolipinas/fisiologia , Caspase 1/metabolismo , Feminino , Células HEK293 , Humanos , Inflamassomos/metabolismo , Interleucina-1alfa/fisiologia , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Knockout , Proteínas Associadas aos Microtúbulos/metabolismo , Mitocôndrias/metabolismo , Mitofagia/fisiologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/fisiologia , Ligação Proteica/fisiologia , Domínios Proteicos/fisiologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
BACKGROUND: STAT-ON™ is an objective tool that registers ON-OFF fluctuations making possible to know the state of the patient at every moment of the day in normal life. Our aim was to analyze the opinion of different Parkinson's disease experts about the STAT-ON™ tool after using the device in a real clinical practice setting (RCPS). METHODS: STAT-ON™ was provided by the Company Sense4Care to Spanish neurologists for using it in a RCPS. Each neurologist had the device for at least three months and could use it in PD patients at his/her own discretion. In February 2020, a survey with 30 questions was sent to all participants. RESULTS: Two thirds of neurologists (53.8% females; mean age 44.9±9 years old) worked in a Movement Disorders Unit, the average experience in PD was 16±6.9 years, and 40.7% of them had previously used other devices. A total of 119 evaluations were performed in 114 patients (range 2-9 by neurologist; mean 4.5±2.3). STAT-ON™ was considered "quite" to "very useful" by 74% of the neurologists with an overall opinion of 6.9±1.7 (0, worst; 10, best). STAT-ON™ was considered better than diaries by 70.3% of neurologists and a useful tool for the identification of patients with advanced PD by 81.5%. Proper identification of freezing of gait episodes and falls were frequent limitations reported. CONCLUSION: STAT-ON™ could be a useful device for using in PD patients in clinical practice.
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INTRODUCTION: Motor fluctuations are one of the most common complications of Parkinson's disease and their treatment is still a complex matter. Therefore, from the Neurology Movement Disorders Group we present our clinical experience in the treatment of these complications, with the intention of it being useful in decision-making in daily clinical practice. DEVELOPMENT: Nineteen questions were developed based on a literature review and an open survey answered by members of this group. These issues were discussed in two phases, using the Delphi methodology. Considering the results of the survey, levodopa dose adjustment and dopamine agonists are the option with the best efficacy/tolerability ratio in the treatment of motor fluctuations. Rotigotine is useful in the motor fluctuations associated with gastroparesis, and intermittent subcutaneous apomorphine has positive effects in patients with unpredictable off periods. The most relevant adverse effect associated with dopamine agonists is impulse control disorder. Catechol-O-methyltransferase inhibitors are useful in the initial stages of motor fluctuations, especially in wearing off. Monoamine oxidase inhibitors are generally drugs that are well-tolerated and useful in motor fluctuations. If these measures are not effective, second-line treatments should be indicated on a case-by-case basis. CONCLUSION: The clinical profile of patients with Parkinson's disease is paramount in deciding the most appropriate therapy for the treatment of motor fluctuations.
TITLE: Experiencia clínica en el tratamiento de las fluctuaciones motoras en la enfermedad de Parkinson. Consenso Delphi de un grupo de expertos en trastornos del movimiento.Introducción. Las fluctuaciones motoras son una de las complicaciones más frecuentes en la enfermedad de Parkinson y su tratamiento sigue siendo complejo. Por ello, desde el Grupo de Trastornos del Movimiento de la Asociación Madrileña de Neurología presentamos nuestra experiencia clínica en el tratamiento de estas complicaciones, con la intención de que sea de utilidad en la toma de decisiones en la práctica clínica diaria. Desarrollo. Se elaboraron 19 preguntas a partir de una revisión bibliográfica y una encuesta abierta respondida por los miembros de dicho grupo. Dichas cuestiones se debatieron en dos fases, utilizando la metodología Delphi. Considerando los resultados de la encuesta, el ajuste de la dosis de levodopa y los agonistas dopaminérgicos son la opción con mejor relación eficacia/tolerabilidad en el tratamiento de las fluctuaciones motoras. La rotigotina es útil en las fluctuaciones motoras asociadas a gastroparesia, y la apomorfina subcutánea intermitente, en pacientes con off impredecible. El efecto adverso más relevante asociado a los agonistas dopaminérgicos es el trastorno del control de impulsos. Los inhibidores de la catecol-O-metiltransferasa son útiles en las fluctuaciones motoras de inicio, especialmente en el wearing off. Los inhibidores de la monoaminooxidasa son fármacos, en general, bien tolerados y útiles en las fluctuaciones motoras. En caso de que estas medidas no resulten eficaces, se deben indicar terapias de segunda línea de manera individualizada. Conclusión. El perfil clínico del paciente con enfermedad de Parkinson es primordial para decidir la terapia más adecuada en el tratamiento de las fluctuaciones motoras.
Assuntos
Antiparkinsonianos , Atividade Motora , Doença de Parkinson , Antiparkinsonianos/uso terapêutico , Inibidores de Catecol O-Metiltransferase/uso terapêutico , Consenso , Agonistas de Dopamina/uso terapêutico , Humanos , Levodopa/uso terapêutico , Atividade Motora/efeitos dos fármacos , Doença de Parkinson/tratamento farmacológico , Resultado do TratamentoRESUMO
This work presents an overview of the applications of retrospective dosimetry techniques in case of incorporation of radionuclides. The fact that internal exposures are characterized by a spatially inhomogeneous irradiation of the body, which is potentially prolonged over large periods and variable over time, is particularly problematic for biological and electron paramagnetic resonance (EPR) dosimetry methods when compared with external exposures. The paper gives initially specific information about internal dosimetry methods, the most common cytogenetic techniques used in biological dosimetry and EPR dosimetry applied to tooth enamel. Based on real-case scenarios, dose estimates obtained from bioassay data as well as with biological and/or EPR dosimetry are compared and critically discussed. In most of the scenarios presented, concomitant external exposures were responsible for the greater portion of the received dose. As no assay is available which can discriminate between radiation of different types and different LETs on the basis of the type of damage induced, it is not possible to infer from these studies specific conclusions valid for incorporated radionuclides alone. The biological dosimetry assays and EPR techniques proved to be most applicable in cases when the radionuclides are almost homogeneously distributed in the body. No compelling evidence was obtained in other cases of extremely inhomogeneous distribution. Retrospective dosimetry needs to be optimized and further developed in order to be able to deal with real exposure cases, where a mixture of both external and internal exposures will be encountered most of the times.
Assuntos
Radiação Ionizante , Radiometria/métodos , Animais , Espectroscopia de Ressonância de Spin Eletrônica , Humanos , Radioisótopos/farmacocinéticaRESUMO
Lactic acid, psychrophilic, and mesophilic bacteria, Escherichia coli, Salmonella spp. and Staphylococcus aureus were enumerated on chicken breasts after treatment with different high intensity ultrasound (frequency 40â¯kHz, intensity 9.6â¯W/cm-2) application times (0, 30, and 50â¯min) and packaging atmospheres (aerobic and vacuum) after a 7-day storage. The experiment was performed in commercial 7-week-old chicken breasts. Counts were performed prior to and immediately after ultrasonication, and on the 7th day of chill-storage. After sonication and storage, mesophiles, psychrophiles, LAB and S. aureus increased statistically. Psychrophiles decreased significantly under anaerobic packaging. There were no differences among ultrasonication times in terms of mesophiles, psychrophiles, LAB, E. coli and Salmonella spp. S. aureus numbers had a significant reduction after 50â¯min sonication. Under these experimental conditions, high-intensity ultrasound for 50â¯min is a control method of S. aureus and the anaerobic packaging reduces numbers of psychrophiles in chicken breast. The effect of ultrasound is only significant after the storage time.
Assuntos
Contaminação de Alimentos/prevenção & controle , Microbiologia de Alimentos , Carne/microbiologia , Sonicação , Animais , Temperatura Baixa , Contagem de Colônia Microbiana , Escherichia coli , Embalagem de Alimentos , Aves Domésticas , Salmonella , Staphylococcus aureusRESUMO
The aim of the present study was to characterize the dynamics of the bolus formation that take place during mastication of commercial cooked ham samples. In addition, the relationships between these properties and texture perception were studied. Five commercial samples which presented different mechanical properties and moisture contents were studied. Ten participants were asked to chew the cooked ham samples normally and to expectorate the bolus after different chewing periods. Oral activity measurements (chewing time and number of chewing strokes), moisture content, saliva uptake and particle size distribution in the boluses were obtained. Seventeen participants evaluated the sensory perceptions generated over the sample consumption time, using the Temporal Check-All-That-Apply (TCATA) method. The results revealed that the duration of mastication and number of chewing cycles through to swallowing varied significantly among the cooked ham samples and were mainly related to instrumental texture parameters. The pattern of fragmentation under mastication also varied greatly between samples. Sensations of softness and hardness during ham consumption were again linked to instrumental texture parameters (TPA hardness, TPA chewiness and shear force). The perception of fibrousness was related to the degree of fragmentation of the ham in the mouth, and juiciness seemed to be related to the amount of saliva taken up by the product.