61 research outputs found
An anti-interleukin-2 receptor drug attenuates thelper 1 lymphocytes-mediated inflammation in an acute model of endotoxin-induced uveitis
The aim of the present study was to evaluate the anti-inflammatory efficacy of Daclizumab, an anti-interleukin-2 receptor
drug, in an experimental uveitis model upon a subcutaneous injection of lipopolysaccharide into Lewis rats, a valuable
model for ocular acute inflammatory processes. The integrity of the blood-aqueous barrier was assessed 24 h after
endotoxin-induced uveitis by evaluating two parameters: cell count and protein concentration in aqueous humors. The
histopathology of all the ocular structures (cornea, lens, sclera, choroid, retina, uvea, and anterior and posterior chambers)
was also considered. Enzyme-linked immunosorbent assays of the aqueous humor samples were performed to quantify the
levels of the different chemokine and cytokine proteins. Similarly, a biochemical analysis of oxidative stress-related markers
was also assessed. The inflammation observed in the anterior chamber of the eyes when Daclizumab was administered with
endotoxin was largely prevented since the aqueous humor protein concentration substantially lowered concomitantly with
a significant reduction in the uveal and vitreous histopathological grading. Th1 lymphocytes-related cytokines, such as
Interleukin-2 and Interferon-c, also significantly reduced with related anti-oxidant systems recovery. Daclizumab treatment
in endotoxin-induced uveitis reduced Th1 lymphocytes-related cytokines, such as Interleukin-2 and Interferon gamma, by
about 60–70% and presented a preventive role in endotoxin-induced oxidative stress. This antioxidant protective effect of
Daclizumab may be related to several of the observed Daclizumab effects in our study, including IL-6 cytokine regulatory
properties and a substantial concomitant drop in INFc. Concurrently, Daclizumab treatment triggered a significant
reduction in both the uveal histopathological grading and protein concentration in aqueous humors, but not in cellular
infiltration
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Stroke rehabilitation in urban and rural settings in the Philippines: Protocol for an interview and visual elicitation study.
INTRODUCTION: There is a lack of community-based rehabilitation for stroke in the Philippines, and research on this topic is limited. Different challenges may be encountered in urban and rural settings. The aim of the Tulong, Ugnayan ng Lingap At gabaY (TULAY) project is to develop a context-appropriate, community-based stroke support programme, consisting of self-management and training resources to augment the rehabilitation and recovery process. An important stage in the development of this programme is to qualitatively explore the experiences and needs of all stakeholders. MATERIALS AND METHODS: Using co-designed and evidence-based topic guides, in-depth semi-structured interviews will be conducted with people living with stroke, household carers and care providers. We will aim to gain a representation of different regions (within Luzon, Visayas, and Northern Mindanao), socioeconomic levels, and urban and rural locations. For people with stroke and household carers, interviews will be supplemented by auto-photography and visual elicitation to widen access for those that prefer to share their experiences visually or have communication problems. An interpretivist paradigm will be applied across all interview data and the consolidated criteria for reporting qualitative research (COREQ) will be followed. Thematic analysis will be undertaken using guidance by Braun and Clarke. DISCUSSION: To our knowledge, this study is the first of its kind in the Philippines. It has several methodological strengths, including the capture of perspectives from multiple stakeholders in diverse settings, the inclusion of people with communication difficulties, use of visual methods, and analysis in the native language. The findings will have various applications, including the potential to influence policy, practice and guidelines, and to inform the development of the TULAY stroke support programme
CNNs for automatic glaucoma assessment using fundus images: an extensive validation
Background
Most current algorithms for automatic glaucoma assessment using fundus images rely on handcrafted features based on segmentation, which are affected by the performance of the chosen segmentation method and the extracted features. Among other characteristics, convolutional neural networks (CNNs) are known because of their ability to learn highly discriminative features from raw pixel intensities.
Methods
In this paper, we employed five different ImageNet-trained models (VGG16, VGG19, InceptionV3, ResNet50 and Xception) for automatic glaucoma assessment using fundus images. Results from an extensive validation using cross-validation and cross-testing strategies were compared with previous works in the literature.
Results
Using five public databases (1707 images), an average AUC of 0.9605 with a 95% confidence interval of 95.92–97.07%, an average specificity of 0.8580 and an average sensitivity of 0.9346 were obtained after using the Xception architecture, significantly improving the performance of other state-of-the-art works. Moreover, a new clinical database, ACRIMA, has been made publicly available, containing 705 labelled images. It is composed of 396 glaucomatous images and 309 normal images, which means, the largest public database for glaucoma diagnosis. The high specificity and sensitivity obtained from the proposed approach are supported by an extensive validation using not only the cross-validation strategy but also the cross-testing validation on, to the best of the authors’ knowledge, all publicly available glaucoma-labelled databases.
Conclusions
These results suggest that using ImageNet-trained models is a robust alternative for automatic glaucoma screening system. All images, CNN weights and software used to fine-tune and test the five CNNs are publicly available, which could be used as a testbed for further comparisons
Imbalance Between Oxidative Stress and Growth Factors in Human High Myopia
La miopĂa es una de las patologĂas oculares más comunes que podrĂa afectar a 2.560 millones de personas en
2020. Hoy en dĂa, la alta miopĂa es una de las principales causas de ceguera en todo el mundo debido a las enfermedades asociadas enfermedad ocular. Sin embargo, las bases celulares para que se desarrollen estas enfermedades no están claras en muchas áreas. Realizamos un estudio prospectivo sobre estrĂ©s oxidativo y factores de crecimiento en ojos humanos miopes y no miopes en un intento de aumentar nuestra comprensiĂłn
de las condiciones fisiopatolĂłgicas subyacentes para diagnosticar adecuadamente, prevenir y tratar el problema de retina que deriva de la miopĂa. Se tomaron muestras de humor acuoso obtenido de 41 pacientes operados de cataratas en nuestro hospital. Se registrĂł, la longitud axial, el estado refractivo y el examen oftalmolĂłgico completo. El VEGF y los niveles de HGF se determinaron mediante un kit ELISA. Capacidad antioxidante total y total
Los niveles de nitritos/nitratos se establecieron con un kit de laboratorio. Mostramos por primera vez un aumento de los niveles totales de nitrito en personas con alta miopĂa. TambiĂ©n proponemos por primera vez
la concurrencia de tres factores: miopĂa, estrĂ©s oxidativo y estrĂ©s oxidativo juntos con factores de crecimiento en el mismo grupo de pacientes. De esta manera, no serĂa exacto incluir la miopĂa alta como un tipo de miopĂa normal, pero con más dioptrĂas o más longitud axial
Lipoic acid lessens Th1-mediated inflammation in lipopolysaccharide-induced uveitis reducing selectively Th1 lymphocytes-related cytokines release
Infl ammation results in the production of free radicals. We evaluated the anti-infl ammatory and antioxidant capacity of lipoic acid in an
experimental uveitis model upon a subcutaneous injection of endotoxin into Lewis rats. The role of oxidative stress in the endotoxin-induced
uveitis model is well-known. Besides, the Th1 response classically performs a central part in the immunopathological process of experimental
autoimmune uveitis. Exogenous sources of lipoic acid have been shown to exhibit antioxidant and anti-infl ammatory properties. Our
results show that lipoic acid treatment plays a preventive role in endotoxin-induced oxidative stress at 24 h post-administration and reduced
Th1 lymphocytes-related cytokines by approximately 50 – 60%. Simultaneously, lipoic acid treatment caused a signifi cant reduction in uveal
histopathological grading and in the protein concentration in aqueous humors, but not in cellular infi ltration
The Journal of Physiology
Dendritic spines are the main receptacles of excitatory information in the brain. Their particular morphology, with a small head connected to the dendrite by a slender neck, has inspired theoretical and experimental work to understand how these structural features affect the processing, storage and integration of synaptic inputs in pyramidal neurons (PNs). The activation of glutamate receptors in spines triggers a large voltage change as well as calcium signals at the spine head. Thus, voltage-gated and calcium-activated potassium channels located in the spine head likely play a key role in synaptic transmission. Here we study the presence and function of large conductance calcium-activated potassium (BK) channels in spines from layer 5 PNs. We found that BK channels are localized to dendrites and spines regardless of their size, but their activity can only be detected in spines with small head volumes (≤0.09 μm3), which reduces the amplitude of two-photon uncaging excitatory postsynaptic potentials recorded at the soma. In addition, we found that calcium signals in spines with small head volumes are significantly larger than those observed in spines with larger head volumes. In accordance with our experimental data, numerical simulations predict that synaptic inputs impinging onto spines with small head volumes generate voltage responses and calcium signals within the spine head itself that are significantly larger than those observed in spines with larger head volumes, which are sufficient to activate spine BK channels. These results show that BK channels are selectively activated in small-headed spines, suggesting a new level of dendritic spine-mediated regulation of synaptic processing, integration and plasticity in cortical PNs. Key points BK channels are expressed in the visual cortex and layer 5 pyramidal neuron somata, dendrites and spines regardless of their size. BK channels are selectively activated in small-headed spines (≤0.09 μm3), which reduces the amplitude of two-photon (2P) uncaging excitatory postsynaptic potentials (EPSPs) recorded at the soma. Two-photon imaging revealed that intracellular calcium responses in the head of 2P-activated spines are significantly larger in small-headed spines (≤0.09 μm3) than in spines with larger head volumes. In accordance with our experimental data, numerical simulations showed that synaptic inputs impinging onto spines with small head volumes (≤0.09 μm3) generate voltage responses and calcium signals within the spine head itself that are significantly larger than those observed in spines with larger head volumes, sufficient to activate spine BK channels and suppress EPSPs
Metástasis óseas y compresión medular como debut de carcinoma folicular de tiroides
En el carcinoma de tiroides, las metástasis a distancia son poco frecuentes (10-15% de los folĂculares). Los sitios más comunes son pulmĂłn, huesos (presentaciĂłn en forma de lesiones lĂticas), el cerebro, el hĂgado, la vejiga y la piel. El diagnĂłstico de carcinoma folicular a travĂ©s de una complicaciĂłn de la metástasis es excepcional, pero se debe considerar en el diagnĂłstico diferencial de una fractura patolĂłgica. Presentamos tres casos de apariciĂłn excepcional
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