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1.
Artigo em Inglês | MEDLINE | ID: mdl-38957358

RESUMO

Type 2 diabetes mellitus (T2DM) is a metabolic disease and comorbidity associated with several conditions, including cardiac dysfunction leading to heart failure with preserved ejection fraction (HFpEF), in turn resulting in T2DM-induced cardiomyopathy (T2DM-CM). However, the molecular mechanisms underlying the development of T2DM-CM are poorly understood. It is hypothesized that molecular alterations in myopathic genes induced by diabetes promote the development of HFpEF, whereas cardiac myosin inhibitors can rescue the resultant T2DM-mediated cardiomyopathy. To test this hypothesis, a Leptin receptor-deficient db/db homozygous (Lepr db/db) mouse model was used to define the pathogenesis of T2DM-CM. Echocardiographic studies at 4 and 6 months revealed that Lepr db/db hearts started developing cardiac dysfunction by four months, and left ventricular hypertrophy with diastolic dysfunction was evident at 6 months. RNA-seq data analysis, followed by functional enrichment, revealed the differential regulation of genes related to cardiac dysfunction in Lepr db/db heart tissues. Strikingly, the level of cardiac myosin binding protein-C phosphorylation was significantly increased in Lepr db/db mouse hearts. Finally, using isolated skinned papillary muscles and freshly isolated cardiomyocytes, CAMZYOS ® (mavacamten, MYK-461), a prescription heart medicine used for symptomatic obstructive hypertrophic cardiomyopathy treatment, was tested for its ability to rescue T2DM-CM. Compared with controls, MYK-461 significantly reduced force generation in papillary muscle fibers and cardiomyocyte contractility in the db/db group. This line of evidence shows that 1) T2DM-CM is associated with hyperphosphorylation of cardiac myosin binding protein-C and 2) MYK-461 significantly lessened disease progression in vitro, suggesting its promise as a treatment for HFpEF.

2.
J Environ Manage ; 362: 121168, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38823302

RESUMO

Targeted grazing to control undesirable plant species is increasingly of interest across a diversity of ecosystems, particularly as an alternative or complement to widely used herbicides. However, there are limited comprehensive evaluations of targeted grazing that evaluate both invasive species management effectiveness and potential negative effects on the ecosystem. Phragmites australis, a tall-statured, dense perennial invasive grass from Eurasia, is a pervasive problem in wetlands across the North American continent. As with many invasive species where management has historically relied on herbicides and resistance is a growing concern, land managers seek viable alternatives that have minimal negative ecosystem impacts. Grazing has been used for millennia to manage native Phragmites in Europe. Similarly, in its invasive range within North America, small-scale studies suggest Phragmites may be suppressed by grazers. Yet, the effectiveness of grazing at large scales and its effects on broader ecosystem properties remain largely unknown. We evaluated the influence of targeted grazing on vegetation, soil nutrients, and water nutrients over two years in large plots (∼300x the size of previous studies). We also tested the effects of mowing, a treatment that can be used to facilitate grazer access to large, dense Phragmites stands. In line with our predictions, we found that cattle grazing effectively suppressed invasive Phragmites over two years. Mowing reduced litter, and moderately reduced standing dead Phragmites, both of which suppress native plant germination in this system. However, these reductions in Phragmites were not accompanied by indications of native plant community recovery, as we had optimistically predicted. Despite the potential for grazing to reduce nutrient sequestration by plants and fertilize soils, we were surprised to find no clear negative effects of grazing on nutrient mobilization to groundwater or floodwater. Taken together, our findings indicate that targeted grazing, when implemented at broad scales over short time frames, is effective at achieving invasive plant management goals without sizable nutrient impacts. However, additional steps will be needed to achieve the restoration of diverse, robust native plant communities.


Assuntos
Espécies Introduzidas , Áreas Alagadas , Animais , Poaceae , Ecossistema , Solo , Herbivoria , Nutrientes
3.
Health Rep ; 35(5): 16-25, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38758724

RESUMO

Background: The availability of measures to operationalize allostatic load - the cumulative toll on the body of responding to stressor demands - in population health surveys may differ across years or surveys, hampering analyses on the entire sampled population. Here, impacts of variable selection and calculation method were evaluated to generate an allostatic load index applicable across all cycles of the Canadian Health Measures Survey (CHMS). Methods: Data from CHMS cycles 1 to 4 were used to compare allostatic load scores when replacing the most prevalent risk factor, waist-to-hip ratio - available in cycles 1 to 4 but not 5 and 6 - with body mass index (BMI), waist circumference, waist circumference within BMI groups (classified as normal, overweight, or obese), or waist-to-height ratio. Indexes were generated using clinical or sex-specific empirically defined risk thresholds and as count-based or continuous scores. Logistic regression models that included age and sex were used to relate each potential index to socioeconomic indicators (educational attainment, household income). Results: Of the variables assessed, waist-to-height ratio and waist circumference were closest to waist-to-hip ratio according to an individual's percentile ranking and in classifying "at risk" using either clinical or empirically defined cut-offs. Allostatic load profiles generated using waist-to-height ratios most closely resembled profiles constructed using waist-to-hip ratios. Sex-dependent associations with educational attainment and household income were maintained across constructs whether indexes were count-based or continuous. Interpretation: Allostatic load profiles and associations with socioeconomic indicators were robust to variable substitution and method of calculation, supporting the use of a harmonized index across survey cycles to assess the cumulative toll on health of stressor exposure.


Assuntos
Alostase , Índice de Massa Corporal , Inquéritos Epidemiológicos , Circunferência da Cintura , Relação Cintura-Quadril , Humanos , Canadá , Masculino , Feminino , Alostase/fisiologia , Adulto , Pessoa de Meia-Idade , Razão Cintura-Estatura , Fatores de Risco , Idoso , Fatores Socioeconômicos
4.
J Psychopharmacol ; 38(6): 532-540, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38647196

RESUMO

BACKGROUND: Dysfunctional sensory gating in anxiety disorders, indexed by the failure to inhibit the P50 event-related potential (ERP) to repeated stimuli, has been linked to deficits in the major inhibitory neurotransmitter γ-aminobutyric acid (GABA). AIMS/METHODS: This study, conducted in 30 healthy volunteers, examined the acute effects of GABAA (lorazepam: 1 mg) and GABAB receptor (baclofen: 10 mg) agonists on P50 measures of auditory sensory gating within a paired-stimulus (S1-S2) paradigm and assessed changes in gating in relation to self-ratings of anxiety. RESULTS: Compared to placebo, lorazepam reduced ERP indices of sensory gating by attenuating response to S1. Although not directly impacting P50 inhibition, baclofen-induced changes in gating (relative to placebo) were negatively correlated with trait but not state anxiety. CONCLUSIONS: These preliminary findings support the involvement of GABA in sensory gating and tentatively suggest a role for GABAB receptor signaling in anxiety-associated gating dysregulation.


Assuntos
Ansiedade , Baclofeno , Agonistas dos Receptores de GABA-B , Lorazepam , Receptores de GABA-B , Filtro Sensorial , Humanos , Masculino , Feminino , Adulto , Baclofeno/farmacologia , Lorazepam/farmacologia , Agonistas dos Receptores de GABA-B/farmacologia , Ansiedade/metabolismo , Adulto Jovem , Filtro Sensorial/efeitos dos fármacos , Receptores de GABA-B/metabolismo , Receptores de GABA-B/efeitos dos fármacos , Agonistas de Receptores de GABA-A/farmacologia , Voluntários Saudáveis , Método Duplo-Cego , Potenciais Evocados Auditivos/efeitos dos fármacos , Potenciais Evocados Auditivos/fisiologia , Receptores de GABA-A/metabolismo , Receptores de GABA-A/efeitos dos fármacos , Adolescente
5.
Clin EEG Neurosci ; 55(3): 329-339, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37306065

RESUMO

Auditory cortical plasticity deficits in schizophrenia are evidenced with electroencephalographic (EEG)-derived biomarkers, including the 40-Hz auditory steady-state response (ASSR). Aiming to understand the underlying oscillatory mechanisms contributing to the 40-Hz ASSR, we examined its response to transcranial alternating current stimulation (tACS) applied bilaterally to the temporal lobe of 23 healthy participants. Although not responding to gamma tACS, the 40-Hz ASSR was modulated by theta tACS (vs sham tACS), with reductions in gamma power and phase locking being accompanied by increases in theta-gamma phase-amplitude cross-frequency coupling. Results reveal that oscillatory changes induced by frequency-tuned tACS may be one approach for targeting and modulating auditory plasticity in normal and diseased brains.


Assuntos
Córtex Auditivo , Esquizofrenia , Estimulação Transcraniana por Corrente Contínua , Humanos , Eletroencefalografia , Estimulação Transcraniana por Corrente Contínua/métodos , Córtex Auditivo/fisiologia , Lobo Temporal , Esquizofrenia/terapia , Esquizofrenia/complicações
6.
Global Spine J ; 12(1): 110-120, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32964731

RESUMO

STUDY DESIGN: Basic science animal research study. OBJECTIVES: Using T10 spinal contused rats, we sought to identify molecular and circulating, metabolic and immune biomarkers during the subchronic and chronic recovery periods that may inform us concerning neurorehabilitation. METHODS: Gene expression of the cord and ELISA were performed in 28 and 100 days in T10 injured rats and compared to sham-injured rats. Hundred-day injured rats were placed on either a low-fat or high-fat diet following the recovery phase. Linear regression analysis was performed between markers and locomotor score, body weight, body composition, and blood cholesterol and triglycerides. RESULTS: Gene expression in the thoracic cord for complement marker, C1QC, dendritic cell marker, ITGAX, and cholesterol biosynthesis genes, FDFT1, HMCGR, LDLR, and SREBP1, were significantly associated with BBB score, body weight, composition, and other metabolic parameters. Circulating levels of these proteins, however, did not vary by injury or predict the level of locomotor recovery. CONCLUSIONS: Identification of reliable circulating biomarkers that are durable and based on level of spinal injury are complicated by immune and metabolic comorbidities. Continued work is necessary to identify stable markers of disease progression.

7.
Front Robot AI ; 8: 719154, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34950706

RESUMO

This article presents an understanding of naive users' perception of the communicative nature of unmanned aerial vehicle (UAV) motions refined through an iterative series of studies. This includes both what people believe the UAV is trying to communicate, and how they expect to respond through physical action or emotional response. Previous work in this area prioritized gestures from participants to the vehicle or augmenting the vehicle with additional communication modalities, rather than communicating without clear definitions of the states attempting to be conveyed. In an attempt to elicit more concrete states and better understand specific motion perception, this work includes multiple iterations of state creation, flight path refinement, and label assignment. The lessons learned in this work will be applicable broadly to those interested in defining flight paths, and within the human-robot interaction community as a whole, as it provides a base for those seeking to communicate using non-anthropomorphic robots. We found that the Negative Attitudes towards Robots Scale (NARS) can be an indicator of how a person is likely to react to a UAV, the emotional content they are likely to perceive from a message being conveyed, and it is an indicator for the personality characteristics they are likely to project upon the UAV. We also see that people commonly associate motions from other non-verbal communication situations onto UAVs. Flight specific recommendations are to use a dynamic retreating motion from a person to encourage following, use a perpendicular motion to their field of view for blocking, simple descending motion for landing, and to use either no motion or large altitude changes to encourage watching. Overall, this research explores the communication from the UAV to the bystander through its motion, to see how people respond physically and emotionally.

8.
Clin Physiol Funct Imaging ; 41(4): 376-384, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33884750

RESUMO

BACKGROUND: Blood flow restricted (BFR) exercise results in transient muscle growth that may be due to metabolite accumulation, hyperaemia and muscle damage, possibly serving as a stimulus for hypertrophy. Understanding the duration of this growth is important for exercise recovery and measurement of hypertrophy. PURPOSE: To measure changes in muscle size via ultrasound throughout a 48-h period after a session of BFR knee extension (KE) exercise. METHODS: Muscle thickness of the vastus lateralis (VL) was measured via ultrasound in 12 participants (six males and six females, age: 20.3 ± 1.1 years) before and immediately, 10 min, 30 min, 1, 3, 8, 24, and 48 h after unilateral exercise. One leg served as a non-exercise control while the other leg performed four sets of unilateral BFR KE at 30% of one-repetition maximum with a pressurized cuff applied to the proximal thigh and inflated to 50% arterial occlusion pressure. RESULTS: Vastus lateralis thickness was 34.9 ± 7.2% higher immediately after exercise, 28.6 ± 7.9% at 10 min, 25.2 ± 6.1% at 30 min, 14.9 ± 4.8% at 1 h and 11.8 ± 5.6% at 3 h (p < 0.05). There were no changes compared to pre-exercise measurements past 3 h, and the control limb did not change (p > 0.05). The muscle thickness of the exercise leg was significantly greater than that of the control leg from immediately after exercise up to 1 h post-exercise (p < 0.05). CONCLUSION: Muscle thickness of the VL increases for 3 h post-BFR exercise and returns to normal within 8 h. This timeframe should be considered when prescribing exercise and planning muscle hypertrophy assessments.


Assuntos
Músculo Quadríceps , Treinamento Resistido , Adulto , Exercício Físico , Feminino , Humanos , Masculino , Músculo Esquelético/diagnóstico por imagem , Músculo Quadríceps/diagnóstico por imagem , Fluxo Sanguíneo Regional , Ultrassonografia , Adulto Jovem
9.
Clin Med (Lond) ; 21(2): e223-e227, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33762390

RESUMO

Hydrogen therapy is a very promising treatment against several diseases due to its mild attributes, high affinity and inherent biosafety. However, there is little elaboration about current hydrogen treatment in liver diseases. This article introduces the administration of hydrogen and mechanisms of hydrogen therapy in vivo, including modulating reactive oxygen species, apoptosis and autophagy, and inflammation, affecting mitochondria, as well as protein transporters. The major focus is clinical hydrogen use and related mechanisms in liver dysfunction or diseases, including non-alcoholic fatty liver disease, hepatitis B, liver dysfunction caused by liver tumour and colorectal tumour chemotherapy. Further, the article reveals ex vivo hydrogen application in liver protection. Finally, the article discusses the current and future challenges of hydrogen therapy in liver diseases, aiming to improve knowledge of hydrogen therapy and provide some insights into this burgeoning field.


Assuntos
Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Apoptose , Humanos , Hidrogênio , Fígado
10.
J Dermatol Sci ; 98(3): 146-151, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32173167

RESUMO

Inflammasomes are large intracellular multi-protein signaling complexes which are responsible for the activation of inflammatory responses. Among multifarious subtypes of inflammasomes, NLRP3 has been associated with a variety of inflammatory and autoimmune skin conditions, including dermatophytosis, psoriasis, acne, urticaria and bullous pemphigoid and other different skin diseases which have been a subject of intensive investigation. NLRP3 is considered to be a sensor of microbial and other danger signals and plays a crucial role in immune responses, dysregulation of NLRP3 inflammasome activation is involved in skin diseases. With the in-depth research, targeting NLRP3 inflammasome and its downstream signaling will provide new insights into the development of future therapeutic strategies. In this review, we summarize the molecular mechanism of NLRP3 inflammasome activation as well as the current knowledge on the contribution of the NLRP3 inflammasome in infection-related, immune-mediated and autoimmune skin diseases.


Assuntos
Anti-Inflamatórios/uso terapêutico , Inflamassomos/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Dermatopatias/imunologia , Animais , Anti-Inflamatórios/farmacologia , Autoimunidade/efeitos dos fármacos , Autoimunidade/genética , Humanos , Inflamassomos/antagonistas & inibidores , Inflamassomos/genética , Camundongos , Mutação , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Polimorfismo de Nucleotídeo Único , Dermatopatias/tratamento farmacológico , Dermatopatias/genética , Dermatopatias/microbiologia
11.
Curr Res Physiol ; 3: 50-58, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33644768

RESUMO

Bariatric surgery produces significant positive benefits to recipients such as significant body fat loss and resolution of the various obesity-related comorbidities, such as reduced reproductive function. Females of childbearing age seek bariatric surgical remedies to improve their chance of successful pregnancy; however, limited knowledge exists on the impact of surgical weight loss to subsequently born offspring. We previously reported that circulating leptin levels were reduced in pregnant females having previously received vertical sleeve gastrectomy (VSG) in comparison to control dams having received Sham surgery. Furthermore, the levels of leptin receptors in the VSG placenta were also reduced in VSG. These data suggest a significant difference in leptin signaling during pregnancy that may produce an altered developmental environment for the offspring. Here, we investigate the adult offspring of dams having received VSG or Sham-VSG prior to pregnancy. Endogenous fasting plasma leptin levels were not different between Sham and VSG offspring. Fasting leptin receptor mRNA in the medial basal hypothalamus (MBH) was elevated in VSG offspring in comparison to Sham. Intraperitoneal administration of exogenous leptin produced reductions in acute food intake in male Sham offspring, but did not reduce food intake at any time point measured in male VSG offspring. Using Western blot, we identified elevated pSTAT3 and pSTAT3/STAT3 ratios in the MBH of post-VSG offspring in comparison to controls. Using immunohistochemistry, we found an increased number of pSTAT positive cells in the arcuate nucleus in the Sham offspring in comparison to VSG. In contrast, within the paraventricular and ventromedial nuclei in the hypothalamus of the VSG offspring had elevated numbers of pSTAT-positive cells in comparison to controls. Collectively, these data support our hypothesis that leptin signaling is dysregulated in VSG offspring and may be partially responsible for the long-term impact of maternal bariatric surgery on the metabolic health of offspring.

12.
Physiol Rep ; 7(16): e14207, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31456327

RESUMO

Within the spinal cord injured (SCI) population, metabolic dysfunction may be exacerbated. Models of cord injury coupled with metabolic stressors have translational relevance to understand disease progression in this population. In the present study, we used a rat model of thoracic SCI at level T10 (tSCI) and administered diets comprised of either 9% or 40% butterfat to create a unique model system to understand the physiology of weight regulation following cord injury. SCI rats that recovered on chow for 28 days had reduced body mass, lean mass, and reduced fat mass but no differences in percentage of lean or fat mass composition. Following 12 weeks on either low-fat diet (LFD) or high-fat diet (HFD), SCI rats maintained on LFD did not gain weight at the same rate as SCI animals maintained on HFD. LFD-SCI had reduced feed conversion efficiency in comparison to Sham-LFD whereas tSCI-HFD were equivalent to Sham-HFD rats. Although SCI rats still maintained lower lean body mass, by the end of the study HFD-fed rats had higher body fat percentage than LFD-fed rats. Macronutrient selection testing demonstrated SCI rats had a significant preference for protein over Sham rats. Analysis of metabolic cage activity showed tSCI rats had elevated energy expenditure, despite reduced locomotor activity. Muscle triglycerides and cholesterol were reduced only in LFD-tSCI rats. These data suggest that consumption of HFD by tSCI rats alters the trajectory of metabolic dysfunction in the context of spinal cord disease progression.


Assuntos
Peso Corporal/fisiologia , Dieta com Restrição de Gorduras , Dieta Hiperlipídica , Metabolismo Energético/fisiologia , Traumatismos da Medula Espinal/metabolismo , Animais , Composição Corporal/fisiologia , Dieta , Modelos Animais de Doenças , Masculino , Ratos , Ratos Long-Evans , Aumento de Peso/fisiologia
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