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1.
Ecotoxicol Environ Saf ; 284: 116908, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39260219

RESUMO

Deltamethrin (DLM), in combination with the synergist piperonyl butoxide (PBO), is extensively used in pest control programs due to its potent pesticidal properties and appreciable safety margin. However, various research studies report their adverse effects on non-target organisms. In this study, we investigated the toxicity of DLM, PBO, and a DLM-PBO (3:1) combination on Labeo rohita (L. rohita) fish fingerlings. Fish behavior and mortality rates were recorded at different time intervals up to 96 h for concentrations of 0.003, 0.007, 0.015, 0.031, and 0.062 µg/mL, respectively. Biochemical, hematological, and histopathological studies were carried out. High-performance liquid chromatography (HPLC) was used to detect and quantify residues in fish samples. The LC50 values after 48 h for DLM, PBO, and DLM-PBO exposed fish fingerlings were found to be 0.028, 0.066, and 0.007 µg/mL, respectively. At a concentration of 0.003 µg/mL of DLM, PBO, and DLM-PBO, the treated fish fingerlings exhibited similar behavior to the control group. Hematological parameters, such as red blood cell (RBC) and white blood cell (WBC) counts, were reduced in the treated groups compared to the control. Biochemical parameters showed increased levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), while total serum protein levels decreased in DLM, PBO, and DLM-PBO treated fingerlings. Histopathological examination of liver, gill, and heart tissues revealed lesions with hydropic degeneration in the liver and fusions of gill lamellae in the treated tissues. Fish fingerlings exposed to the DLM-PBO combination appeared highly prone to toxicity compared to those treated with DLM and PBO separately.

2.
Future Microbiol ; : 1-15, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39235058

RESUMO

Aim: To assess the functional relevance of a putative Major Facilitator Superfamily protein (PF3D7_0210300; 'PfMFSDT') as a drug transporter, using Candida glabrata for orthologous protein expression.Methods: Complementary Determining Sequence encoding PfMFSDT was integrated into the genome of genetically engineered C. glabrata strain MSY8 via homologous recombination, followed by assessing its functional relevance as a drug transporter.Results & conclusion: The modified C. glabrata strain exhibited plasma membrane localization of PfMFSDT and characteristics of an Major Facilitator Superfamily transporter, conferring resistance to antifungals, ketoconazole and itraconazole. The nanomolar inhibitory effects of the drugs on the intra-erythrocytic growth of Plasmodium falciparum highlight their antimalarial properties. This study proposes PfMFSDT as a drug transporter, expanding the repertoire of the currently known antimalarial 'resistome'.


[Box: see text].

3.
Nanoscale ; 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39253761

RESUMO

Conventional ferroelectric polarization-driven temperature sensors, like pyroelectric sensors, often face challenges such as slow response times, limited compatibility with conventional nanoelectronics, and inability to operate under constant temperature conditions. These shortcomings hinder their adaptability to a broad range of applications, especially when compared to thermal and optical sensors. To address these challenges, we introduce a proof-of-concept methodology that enables ferroelectric-based pyroelectric sensors to measure absolute temperatures with high accuracy and speed. Specifically, we demonstrate that a perturbation pulse (+0.8 V, duration = 180 ns) can serve as an effective probe for quantifying both absolute and dynamic temperatures across ferroelectric hafnium zirconium oxide (HZO) nanolaminates. The device demonstrates an ultrafast response time of ∼50 nanoseconds, offering one million readings per second and a temperature sensing accuracy comparable to the state-of-the-art temperature sensing accuracy of 1.0 K. The observed performance is attributed to the temperature-dependent change of transient negative differential capacitance and effective ferroelectric polarization of HZO. For potential applications, we successfully integrated the sensor with a commercially available universal serial bus interface, thereby demonstrating real-time temperature monitoring during data transfer and environmental heating activities. Our research significantly broadens the range of applications for pyroelectric sensors for both steady-state and rapid dynamic temperature measurements.

4.
Nanomaterials (Basel) ; 14(17)2024 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-39269048

RESUMO

In this study, the effect of annealing and substrate conditions on the ferroelectricity of undoped hafnium oxide (HfO2) was analyzed. Hafnium oxide was deposited on various substrates such as platinum, titanium nitride, and silicon (Pt, TiN, Si) through RF magnetron sputtering. Annealing was performed in a nitrogen atmosphere at temperatures ranging from 400 to 600 °C, and the process lasted anywhere from 1 to 30 min. As a result, it was confirmed that the orthorhombic phase, the main cause of ferroelectricity, was dominant after a post-anneal at 600 °C for 30 min. Additionally, it was observed that interface mixing between hafnium oxide and the substrate may degrade ferroelectricity. Accordingly, the highest remanent polarization, measured at 14.24 µC/cm2, was observed with the Pt electrode. This finding was further corroborated by piezo force microscopy and endurance tests, with the results being significant compared to previously reported values. This analysis demonstrates that optimizing substrate and annealing conditions, rather than doping, can enhance the ferroelectricity of hafnium oxide, laying the foundation for the future development of ferroelectric-based transistors.

5.
Adv Mater ; : e2406607, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39171775

RESUMO

The increasing demand for energy-efficient, sophisticated optical sensing technologies in various applications, from machine vision to optical communication, highlights the necessity for innovations in spatiotemporal information sensing and processing at a nearly single-pixel scale. Traditional methods, including multi-pixel photodetector arrays and event-based camera systems, often fail to provide rapid, real-time detection and processing of dynamic events within the sensor. This shortcoming is particularly notable in handling high-dimensional spatiotemporal data, where the dependency on sequential data input and external processing tools leads to latency, reduced throughput, and heightened energy consumption, thereby impeding real-time parallel data processing capabilities. Here, a carrier-selective, single-pixel, position-sensitive planar photoactive device that integrates spatiotemporal event sensing with inherent short-term memory capabilities is introduced. The proof-of-concept single-pixel event photoactive device enables in-sensor spatiotemporal parallel optical information processing, efficiently managing multibit (>4 bit) data simultaneously and facilitating ultrafast (≈0.4 µs) recognition of input patterns with low energy consumption (25 femtojoules). Additionally, by adjusting the operating speed from continuous to pulsed light illumination, the sensor array can detect trajectories and absolute position of events, offering in-sensor optical flow detection. This single-pixel event photodetector marks significant advancement toward developing compact, energy-efficient, ultrafast sensors suitable for a wide range of in sensor-based photonic applications.

6.
Philos Trans A Math Phys Eng Sci ; 382(2279): 20230357, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39129407

RESUMO

The geometric phase provides important mathematical insights to understand the fundamental nature and evolution of the dynamic response in a wide spectrum of systems ranging from quantum to classical mechanics. While the concept of geometric phase, which is an additional phase factor occurring in dynamical systems, holds the same meaning across different fields of application, its use and interpretation can acquire important nuances specific to the system of interest. In recent years, the development of quantum topological materials and its extension to classical mechanical systems have renewed the interest in the concept of geometric phase. This review revisits the concept of geometric phase and discusses, by means of either established or original results, its critical role in the design and dynamic behaviour of elastic waveguides. Concepts of differential geometry and topology are put forward to provide a theoretical understanding of the geometric phase and its connection to the physical properties of the system. Then, the concept of geometric phase is applied to different types of elastic waveguides to explain how either topologically trivial or non-trivial behaviour can emerge based on the geometric features of the waveguide. This article is part of the theme issue 'Current developments in elastic and acoustic metamaterials science (Part 2)'.

8.
Sci Rep ; 14(1): 19239, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39164363

RESUMO

The geometric features and operational parameters of rotary blades on rotary tillers significantly impact their performance characteristics. The sweepback angle is a geometric feature of the 'L'-shaped rotary blade that has remained unexplored in previous studies. This study aimed to analyze the effect of geometrical and operational parameters on the performance dynamics of the 'L'-shaped rotary blade. The investigation was conducted using the discrete element method (DEM) and further validated through experiments conducted in a soil bin. The simulation experiment was conducted by dividing the particle bed into horizontal particle zones. The effect of the geometrical (sweepback angle) and operational parameters (forward speed, rotational speed, and depth) on the power requirement, disturbance intensity, and mixing index was studied. The novel method was adopted to determine the mixing capability of rotary blades in terms of sub-domain mixing index (SMI) and overall mixing index (OMI). The results revealed that the power requirements for a sweepback angle of 18° were 26.39% and 16.50% lower than those for sweepback angles of 6° and 12°, respectively. The sweepback angle tends to have the least effect on the overall mixing index compared to operational parameters. The average particle velocity decreased by 22.19% and 29.60% with sweepback angles of 12° and 18°, respectively, compared to the sweepback angle of 6°. The relative error during the experiment varied between 1.29% and 13.51%. It was concluded that the sweepback angle was found to be a feasible option for reducing the power requirement with good mixing indices.

9.
J Orthop Case Rep ; 14(8): 10-15, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39157478

RESUMO

Introduction: Osteochondromas are a unique group of benign bone tumors that are characterized by bony outgrowth covered by Cartilage. It has a peculiar micro-architecture as its cortices are extensions of those of parent bone and there is a continuity of medullary cavity; this is akin to branching in plants, rightly earning the name "Exostosis." Case Report: We report a case of a 21-year-old male who presented with complaints of swelling on the upper back associated with mild discomfort. Examination confirmed a bony mass on the dorsal aspect of the scapula without any restricted range of motion of the shoulder joint. On the confirmation of diagnosis, en bloc excision was performed. Conclusion: In conclusion, dorsal scapular osteochondromas are a rarity, and excision of the lesion is an effective management for symptomatic lesions.

10.
Front Hum Neurosci ; 18: 1386168, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39055535

RESUMO

The visual scrutinization process for detecting epileptic seizures (ictal patterns) is time-consuming and prone to manual errors, which can have serious consequences, including drug abuse and life-threatening situations. To address these challenges, expert systems for automated detection of ictal patterns have been developed, yet feature engineering remains problematic due to variability within and between subjects. Single-objective optimization approaches yield less reliable results. This study proposes a novel expert system using the non-dominated sorting genetic algorithm (NSGA)-II to detect ictal patterns in brain signals. Employing an evolutionary multi-objective optimization (EMO) approach, the classifier minimizes both the number of features and the error rate simultaneously. Input features include statistical features derived from phase space transformations, singular values, and energy values of time-frequency domain wavelet packet transform coefficients. Through evolutionary transfer optimization (ETO), the optimal feature set is determined from training datasets and passed through a generalized regression neural network (GRNN) model for pattern detection of testing datasets. The results demonstrate high accuracy with minimal computation time (<0.5 s), and EMO reduces the feature set matrix by more than half, suggesting reliability for clinical applications. In conclusion, the proposed model offers promising advancements in automating ictal pattern recognition in EEG data, with potential implications for improving epilepsy diagnosis and treatment. Further research is warranted to validate its performance across diverse datasets and investigate potential limitations.

11.
Cells ; 13(14)2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-39056755

RESUMO

As per the National Survey on Drug Use and Health, 10.5% of Americans aged 12 years and older are suffering from alcohol use disorder, with a wide range of neurological disorders. Alcohol-mediated neurological disorders can be linked to Alzheimer's-like pathology, which has not been well studied. We hypothesize that alcohol exposure can induce astrocytic amyloidosis, which can be corroborated by the neurological disorders observed in alcohol use disorder. In this study, we demonstrated that the exposure of astrocytes to ethanol resulted in an increase in Alzheimer's disease markers-the amyloid precursor protein, Aß1-42, and the ß-site-cleaving enzyme; an oxidative stress marker-4HNE; proinflammatory cytokines-TNF-α, IL1ß, and IL6; lncRNA BACE1-AS; and alcohol-metabolizing enzymes-alcohol dehydrogenase, aldehyde dehydrogenase-2, and cytochrome P450 2E1. A gene-silencing approach confirmed the regulatory role of lncRNA BACE1-AS in amyloid generation, alcohol metabolism, and neuroinflammation. This report is the first to suggest the involvement of lncRNA BACE1-AS in alcohol-induced astrocytic amyloid generation and alcohol metabolism. These findings will aid in developing therapies targeting astrocyte-mediated neurological disorders and cognitive deficits in alcohol users.


Assuntos
Astrócitos , Etanol , Astrócitos/metabolismo , Astrócitos/efeitos dos fármacos , Etanol/metabolismo , Etanol/farmacologia , Animais , Humanos , Doenças do Sistema Nervoso/metabolismo , Peptídeos beta-Amiloides/metabolismo , Amiloide/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Secretases da Proteína Precursora do Amiloide/metabolismo , Secretases da Proteína Precursora do Amiloide/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/genética , Citocinas/metabolismo , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Ácido Aspártico Endopeptidases/metabolismo , Ácido Aspártico Endopeptidases/genética
12.
J Neuroimmune Pharmacol ; 19(1): 35, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39042253

RESUMO

Brain glucose deprivation is a component of the pathophysiology of ischemia, glucose transporter1 (GLUT1) deficiency, neurological disorders and occurs transiently in diabetes. Microglia, the neuroimmune cells must function effectively to offer immune defence and debris removal in low-energy settings. Brain glucose deprivation may compromise microglial functions further escalating the disease pathology and deteriorating the overall mental health. In the current study, HMC3 human microglia-like cells were cultured in vitro and exposed to glucose deprivation to investigate the effects of glucose deprivation on phenotypic state, redox status, secretion of cytokines and phagocytic capabilities of HMC3 cells. However, HMC3 cells were able to proliferate in the absence of glucose but showed signs of redox imbalance and mitochondrial dysfunction, as demonstrated by decreased MTT reduction and Mito Tracker™ staining of cells, along with a concomitant reduction in NOX2 protein, superoxide, and nitrite levels. Reduced levels of secreted TNF and IL-1ß were the signs of compromised cytokine secretion by glucose-deprived HMC3 microglia-like cells. Moreover, glucose-deprived HMC3 cells also showed reduced phagocytic activity as assessed by fluorescently labelled latex beads-based functional phagocytosis assay. ß-hydroxybutyrate (BHB) supplementation restored the redox status, mitochondrial health, cytokine secretion, and phagocytic activity of glucose-deprived HMC3 microglia-like cells. Overall, impaired brain glucose metabolism may hinder microglia's capacity to release diffusible immune factors and perform phagocytosis. This could escalate the mental health issues in neurological diseases where brain glucose metabolism is compromised. Moreover, nutritional ketosis or exogenous ketone supplementation such as BHB may be utilized as a potential metabolic therapies for these conditions.


Assuntos
Ácido 3-Hidroxibutírico , Citocinas , Glucose , Microglia , Oxirredução , Fagocitose , Humanos , Glucose/metabolismo , Oxirredução/efeitos dos fármacos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Citocinas/metabolismo , Fagocitose/efeitos dos fármacos , Ácido 3-Hidroxibutírico/farmacologia , Linhagem Celular
13.
J Stomatol Oral Maxillofac Surg ; : 101993, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39084561

RESUMO

BACKGROUND: Maxillofacial trauma often results in visible facial disfigurements and can lead to psychological complications such as post-traumatic stress disorder (PTSD). However, PTSD often remains unrecognized and un/undertreated. The goal of the current systematic review was to determine the incidence of PTSD after maxillofacial trauma, associated risk factors, assessment tools employed, and management. METHODS: A literature search was conducted in PubMed, Google Scholar, Semantic Scholar, and Cochrane Library databases following PRISMA guidelines up to March 2024. Collected variables included the number of patients included, PSTD assessment tool, PTSD incidence, and risk factors and management. The meta-analysis was conducted using random effect models in STATA 16. RESULTS: The review included 14 studies (1633 patients, male=1025, female=230, not mentioned=378). Assessment tools varied widely among studies. Meta-analysis revealed a pooled incidence of PTSD of 27 % (n = 14, 95 % CI, 24 %-30 %) at 1-3 months post-trauma and 10 % (n = 3, 95 % CI, 3 %-17 %) at the 6-12 months follow-up, with a statistically significant 60 % reduction between these periods. CONCLUSION: The overall incidence of PTSD following maxillofacial trauma was 27 % at 1-3 months and decreased to 10 % after 6 months. The emphasis should be given to the importance of early intervention strategies and awareness among the treating surgeon to prevent PTSD.

14.
Sci Rep ; 14(1): 17254, 2024 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-39060290

RESUMO

In many Indian regions, paddy wheat is the main crop rotation and facing the problem of straw incorporation for seed bed preparation in short period. The handling of straw in combine harvested paddy fields is a significant issue in the paddy wheat rotation. In order to solve this issue, efforts were carried out to cut paddy straw into small pieces by the newly proposed counter-rotating blades, followed by the simultaneous incorporation of a rotary tiller into the soil. Therefore, a tractor operated chopping cum tilling mixing machine was developed. In the study, three different blades (straw management system (SMS) Serrated, cutter bar and SMS plain) were tested in the terms of torque and required to chop the straw. SMS serrated blade was best suitable for the chopping mechanism as it required minimum cutting torque for the straw bunches. The developed chopping cum tilling mixing machine was tested at three different levels of forward speed (1.77, 2.3, and 3 km h-1), moisture content at three levels (35 ± 3.4, 24 ± 2.2 and 17 ± 2.6%) with fix rotary tiller rotational speed of 810 rev min-1. Optimum operating condition of the machine was obtained at a forward speed of 1.9 km h-1 and a moisture of 24%. At these optimized values, the mixing index (96%), mean weight diameter (7.9 mm), bulk density (1230 g cc-1) and fuel consumption (3 l h-1) were 96%, 7.9 mm, 1230 g cc-1 and 3.0 l h-1 respectively. The developed machine performs three operations i.e., chopping, tilling, and mixing in single pass for effective in-situ straw management.


Assuntos
Triticum , Agricultura/métodos , Desenho de Equipamento , Solo/química , Produção Agrícola/métodos
15.
Heliyon ; 10(12): e32776, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38975083

RESUMO

The goal of the current study was to create and assess the effectiveness of a hand-pulled ergonomically designed flame weeder. The developed weeder was tested in the field at three operating pressures (20, 30 and 40 Psi) and forward speeds (1.00, 1.25 and 1.50 km/h) to study their effects on plant damage, survival rates, weight preservation rates, weed management effectiveness, soil temperatures, and gas and energy consumption. Thereafter, at optimized values of forward speed and operating pressure, a comparative assessment of flame weeding with traditional methods (mechanical and manual weeding) was done in terms of weed control effectiveness, operational time, energy consumption, and cost of operation. Results showed that the optimal performance of the designed flame weeder was achieved when operated at a speed of 1 km/h and an operating pressure of 40 psi. The survival rate, weight preservation rate, weed control efficiency, change in soil temperature, recovery rate, plant damage, gas consumption, and energy consumption were observed to be 27.3 %, 32.5 %, 91.1 %, 40.74 °C, 8.5 %, 2.2 %, 4.05 kg/h, and 2500.24 MJ/ha, respectively, at optimized values of forward speed (1.00 km/h) and operating pressure (40 Psi). The actual field capacity, field efficiency and operating cost of the flame weeder were 0.0755 ha/h, 94.94 %, and 3620.81 ₹/ha, respectively. Hand weeding had the best level of weed control effectiveness, but it was a laborious, time-consuming process. When compared to manual weeding, flame weeding was 50.42 % cheaper and 94.82 % faster.

16.
J Pharm Sci ; 113(9): 2795-2807, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38992795

RESUMO

Burn injuries worldwide pose significant health risks due to frequent microbial infections, which worsen complications and increase mortality rates. The conventional antimicrobial formulations are available in the form of ointments and creams. These formulations are very greasy and stick to the clothes. The applications of these formulations by finger or applicator produce pain in the affected area and incur the possibility of microbial infection. To overcome these hurdles, authors developed a novel non-propellent foam (NPF) based formulation containing chlorhexidine for effective topical delivery. Initially, NPF containing Labrasol® (26.7%), sodium lauryl sulfate (1.2%), hydroxy propyl methyl cellulose (0.56%), butylated hydroxytoluene (0.1%), ethanol (1%), and distilled water was prepared and assessed for its consistency, and ability to form foam. The NPF was statistically optimized using the Box-Behnken design to determine the effect of polymer and surfactants on the critical foam properties. The optimized formulation showed a collapse time of 45 s with a unique nature of collapsing upon slight touch which is highly beneficial for burn patients with microbial infection. The diffusion study showed that more than 90% of the drug was released within 6 h. The skin permeation study showed that 23% of the total drug permeated through the skin after 6 h with 7.64 µg/cm2/h permeation flux. The developed formulation showed good antibacterial activity. The minimum inhibitory concentration of prepared NPF was found to be 2.5 µg/mL, 2.5 µg/mL, and 5.0 µg/mL against E. coli (MTCC-1687), P. aeruginosa (MTCC-1688), and S aureus (MTCC-737) respectively. The developed NPF formulation showed quick collapse time, excellent spreadability, good anti-bacterial activity, and a non-sticky nature representing a promising avenue for burn wound treatment without using any applicator.


Assuntos
Queimaduras , Queimaduras/tratamento farmacológico , Animais , Clorexidina/administração & dosagem , Clorexidina/química , Química Farmacêutica/métodos , Anti-Infecciosos Locais/administração & dosagem , Anti-Infecciosos Locais/farmacologia , Anti-Infecciosos Locais/química , Testes de Sensibilidade Microbiana , Composição de Medicamentos/métodos , Pele/metabolismo , Pele/efeitos dos fármacos , Pele/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Tensoativos/química , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Antibacterianos/química , Pseudomonas aeruginosa/efeitos dos fármacos , Administração Cutânea , Humanos
17.
J Mater Chem B ; 12(30): 7292-7297, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39016812

RESUMO

Chirality is one of the hallmarks of biomolecules. Herein, we utilize heparin, a chiral biomolecule and potent drug, to induce chiral organization into the assembly of an achiral molecule. Polyanionic heparin binds with a dicationic perylenediimide derivative to induce supramolecular helical organization in aqueous medium as well as in a highly competitive cell culture medium.


Assuntos
Heparina , Imidas , Perileno , Heparina/química , Imidas/química , Perileno/química , Perileno/análogos & derivados , Estereoisomerismo , Humanos , Estrutura Molecular , Substâncias Macromoleculares/química , Substâncias Macromoleculares/síntese química
18.
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.

19.
J Paediatr Child Health ; 60(8): 375-383, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39051449

RESUMO

AIM: To describe the clinical profile of acute rheumatic fever (ARF) presentations to paediatric cardiology tertiary services in Western Australia (WA). METHODS: A retrospective clinical audit of individuals with confirmed ARF referred to the only paediatric tertiary cardiac service in WA (1 January 1987 to 31 December 2020). Comparisons between inpatient, outpatient, remote and non-remote groups were assessed. RESULTS: Four hundred seventy-one episodes of ARF in 457 individuals (235 male; median age = 8 years) met clinical criteria. The majority were Aboriginal and Torres Strait Islander children (91.2%), with 62.1% living in remote areas. The number of ARF and rheumatic heart disease (RHD) diagnoses per year increased from 1987 to 2017 with notable peaks in 2013 and 2017. The average annual incidence of tertiary-referred ARF in WA of 4-15-year-olds from 1987 to 2020 was 4.96 per 100 000. ARF features included carditis (59.9%), chorea (31%), polyarthritis (30%) and polyarthralgia (24.2%). RHD was evident in 61.8% of cases and predominantly manifested as mitral regurgitation (55.7%). Thirty-four children (7.4%) with severe RHD underwent valvular surgery. 12% had at least one recurrent ARF episode. Remote individuals had more than double the rate of recurrence compared to non-remote individuals (P = 0.0058). Compared to non-remote episodes, remote presentations had less polyarthritis (P = 0.0022) but greater proportions of raised ESR (P = 0.01), ASOT titres (P = 0.0073), erythema marginatum (P = 0.0218) and severe RHD (P = 0.0133). CONCLUSION: The high proportion of Aboriginal and Torres Strait Islander Australians affected by ARF/RHD in WA reflects the significant burden of disease within this population. Children from remote communities were more likely to present with concurrent severe RHD. Our study reinforces the persisting need to improve primary and secondary ARF initiatives in rural and remote communities.


Assuntos
Febre Reumática , Cardiopatia Reumática , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Incidência , Estudos Retrospectivos , Febre Reumática/epidemiologia , Cardiopatia Reumática/epidemiologia , Austrália Ocidental/epidemiologia , Povos Aborígenes Australianos e Ilhéus do Estreito de Torres
20.
Plant Cell Environ ; 2024 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-38825969

RESUMO

Molecular communication between macromolecules dictates extracellular matrix (ECM) dynamics during pathogen recognition and disease development. Extensive research has shed light on how plant immune components are activated, regulated and function in response to pathogen attack. However, two key questions remain largely unresolved: (i) how does ECM dynamics govern susceptibility and disease resistance, (ii) what are the components that underpin these phenomena? Rice blast, caused by Magnaporthe oryzae adversely affects rice productivity. To understand ECM regulated genotype-phenotype plasticity in blast disease, we temporally profiled two contrasting rice genotypes in disease and immune state. Morpho-histological, biochemical and electron microscopy analyses revealed that increased necrotic lesions accompanied by electrolyte leakage governs disease state. Wall carbohydrate quantification showed changes in pectin level was more significant in blast susceptible compared to blast resistant cultivar. Temporally resolved quantitative disease- and immune-responsive ECM proteomes identified 308 and 334 proteins, respectively involved in wall remodelling and integrity, signalling and disease/immune response. Pairwise comparisons between time and treatment, messenger ribonucleic acid expression, diseasome and immunome networks revealed novel blast-related functional modules. Data demonstrated accumulation of α-galactosidase and phosphatase were associated with disease state, while reactive oxygen species, induction of Lysin motif proteins, CAZymes and extracellular Ca-receptor protein govern immune state.

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