Oxidative and Nitrosative Stress in Age-Related Macular Degeneration: A Review of Their Role in Different Stages of Disease

Although the exact pathogenetic mechanisms leading to age-related macular degeneration (AMD) have not been clearly identified, oxidative damage in the retina and choroid due to an imbalance between local oxidants/anti-oxidant systems leading to chronic inflammation could represent the trigger event. Different in vitro and in vivo models have demonstrated the involvement of reactive oxygen species generated in a highly oxidative environment in the development of drusen and retinal pigment epithelium (RPE) changes in the initial pathologic processes of AMD; moreover, recent evidence has highlighted the possible association of oxidative stress and neovascular AMD. Nitric oxide (NO), which is known to play a key role in retinal physiological processes and in the regulation of choroidal blood flow, under pathologic conditions could lead to RPE/photoreceptor degeneration due to the generation of peroxynitrite, a potentially cytotoxic tyrosine-nitrating molecule. Furthermore, the altered expression of the different isoforms of NO synthases could be involved in choroidal microvascular changes leading to neovascularization. The purpose of this review was to investigate the different pathways activated by oxidative/nitrosative stress in the pathogenesis of AMD, focusing on the mechanisms leading to neovascularization and on the possible protective role of anti-vascular endothelial growth factor agents in this context

A probabilistic, discriminative and distributed system for the recognition of human actions from multiple views

This paper presents a distributed system for the recognition of human actions using views of the scene grabbed by different cameras. 2D frame descriptors are extracted for each available view to capture the variability in human motion. These descriptors are projected into a lower dimensional space and fed into a probabilistic classifier to output a posterior distribution of the action performed according to the descriptor computed at each camera. Classifier fusion algorithms are then used to merge the posterior distributions into a single distribution. The generated single posterior distribution is fed into a sequence classifier to make the final decision on the performed activity. The system can instantiate different algorithms for the different tasks, as the interfaces between modules are clearly defined. Results on the classification of the actions in the IXMAS dataset are reported. The accuracy of the proposed system is similar to state-of-the-art 3D methods, even though it uses only well-known 2D pattern recognition techniques and does not need to project the data into a 3D space or require camera calibration parameters.This work was supported in part by Projects CICYT TIN 2008-06742-C02-02/TSI, CICYT TEC2008-06732-C02-02/TEC, CAM CONTEXTS (S2009/TIC1485) and DPS2008-07029-C02-02.publicad

Recognizing human activities from sensors using hidden Markov models constructed by feature selection techniques

19 pages, 8 figures.-- This article belongs to the Special Issue "Sensor Algorithms".In this paper a method for selecting features for Human Activity Recognition from sensors is presented. Using a large feature set that contains features that may describe the activities to recognize, Best First Search and Genetic Algorithms are employed to select the feature subset that maximizes the accuracy of a Hidden Markov Model generated from the subset. A comparative of the proposed techniques is presented to demonstrate their performance building Hidden Markov Models to classify different human activities using video sensors.This work was supported in part by Projects CICYT TIN2008-06742-C02-02/TSI, CICYT TEC2008-06732-C02-02/TEC, SINPROB and CAM MADRINET S-0505/TIC/0255.Publicad

Early microvascular and neural changes in patients with type 1 and type 2 diabetes mellitus without clinical signs of diabetic retinopathy

Purpose: To assess and compare early modifications in inner retinal layer thickness and optical coherence tomography angiography parameters in patients with diabetes mellitus (DM) Types 1 and 2 without clinical signs of diabetic retinopathy. Methods: Ninety eyes of 90 subjects (24 Type 1 DM, 36 Type 2 DM, and 30 healthy controls) were prospectively evaluated with spectral domain OCT, swept-source OCT angiography, and color fundus photography (on the same day). Retinal nerve fiber layer, ganglion cell layer (GCL+), and nerve fiber layer + GCL+ (GCL++) thickness were automatically determined by the instrument in the 1, 3, and 6 central mm. On OCT angiography, the following parameters were evaluated: area of foveal avascular zone, number of focally dilated endings of the capillaries (detected only on OCT angiography), presence of regular/irregular foveal avascular zone, capillary loss, and capillary network irregularities in the superficial capillary plexus (SCP) and deep capillary plexus (DCP). Results: Ganglion cell layer+ (P = 0.0099) and GCL++ (P = 0.0367) were significantly thicker in DM Type 1 versus DM Type 2 in 1 central mm, after adjustment for age and DM duration. The area of foveal avascular zone was significantly larger in DM Type 1 versus controls in both SCP and DCP and in DM Type 1 versus Type 2 only in DCP (P , 0.05 for all); the number of focally dilated endings of the capillaries was higher in DM Type 1 versus controls in both SCP and DCP (P , 0.01 for all); and in DM Type 2 versus controls only in DCP (P = 0.007). Perifoveal capillary loss in SCP and inner retinal layer thickness had the highest correlation in both DM types. Conclusion: There are specific neural and microvascular modifications even before clinical signs of diabetic retinopathy in DM Types 1 and 2. Perifoveal capillary loss in the SCP is highly correlated with inner retinal layer. These data may help in characterization of patients at the preclinical stage of diabetic retinopathy

Human metapneumovirus as cause of severe community-acquired pneumonia in adults: insights from a ten-year molecular and epidemiological analysis

Human metapneumovirus; Severe community-acquired pneumonia; BiomarkersMetapneumovirus humano; Neumonía severa adquirida en la comunidad; BiomarcadoresMetapneumovirus humà; Pneumònia greu adquirida a la comunitat; BiomarcadorsBackground Information on the clinical, epidemiological and molecular characterization of human metapneumovirus in critically ill adult patients with severe community-acquired pneumonia (CAP) and the role of biomarkers identifying bacterial coinfection is scarce. Methods This is a retrospective epidemiological study of adult patients with hMPV severe CAP admitted to ICU during a ten-year period with admission PSI score ≥ 3. Results The 92.8% of the 28 patients with severe CAP due to human metapneumovirus were detected during the first half of the year. Median age was 62 years and 60.7% were male. The genotyping of isolated human metapneumovirus showed group B predominance (60.7%). All patients had acute respiratory failure. Median APACHE II and SOFA score were 13 and 6.55, respectively. The 25% were coinfected with Streptococcus pneumoniae. 60.7% of the patients had shock at admission and 50% underwent mechanical ventilation. Seven patients developed ARDS, three of them younger than 60 years and without comorbidities. Mortality in ICU was 14.3%. Among survivors, ICU and hospital stay were 6.5 and 14 days, respectively. Plasma levels of procalcitonin were higher in patients with bacterial coinfection (18.2 vs 0.54; p < 0.05). The levels of C-reactive protein, however, were similar. Conclusion Human metapneumovirus was associated with severe CAP requiring ICU admission among elderly patients or patients with comorbidities, but also in healthy young subjects. These patients often underwent mechanical ventilation with elevated health resource consumption. While one out of four patients showed pneumococcal coinfection, plasma procalcitonin helped to implement antimicrobial stewardship

Climate-Dependent Groundwater Discharge on Semi-Arid Inland Ephemeral Wetlands: Lessons from Holocene Sediments of Lagunas Reales in Central Spain

Wetlands are environments whose water balance is highly sensitive to climate change and human action. This sensitivity has allowed us to explore the relationships between surface water and groundwater in the long term as their sediments record all these changes and go beyond the instrumental/observational period. The Lagunas Reales, in central Spain, is a semi-arid inland wetland endangered by both climate and human activity. The reconstruction of the hydroclimate and water levels from sedimentary facies, as well as the changes in the position of the surface water and groundwater via the record of their geochemical fingerprint in the sediments, has allowed us to establish a conceptual model for the response of the hydrological system (surface water and groundwater) to climate. Arid periods are characterized by low levels of the deeper saline groundwater and by a greater influence of the surface freshwater. A positive water balance during wet periods allows the discharge of the deeper saline groundwater into the wetland, causing an increase in salinity. These results contrast with the classical model where salinity increases were related to greater evaporation rates and this opens up a new way of understanding the evolution of the hydrology of wetlands and their resilience to natural and anthropogenic changes

Aflibercept and Ranibizumab modulate retinal pigment epithelial cells function by acting on their cross talk with vascular endothelial cells

Background/Aims: We performed co-culture experiments between human RPE cells (ARPE-19) and human umbilical vascular endothelial cells (HUVEC) in order to evaluate how anti-VEGF drugs could affect NO release, mitochondrial function, the oxidative status, proliferation and migration of RPE cells through modulation of their cross talk with vascular endothelial cells. Materials: The co-culture HUVEC/RPE, was exposed to Ranibizumab/Aflibercept in the absence/presence of the NO synthase (NOS) inhibitor, the phosphatidylinositol 3\u2032-kinase (PI3K), the extracellular-signal-regulated kinases 1/2 (ERK1/2) and the p38 mitogen-activated protein kinase (p38 MAPK) blockers. Specific kits were used for cell viability, mitochondrial membrane potential, NO, ROS and GSH production. Western blot was performed for apoptosis markers, NOS isoforms, and others kinases detection. Cell migration was analyzed by scratch assay, whereas cell proliferation and cell cycle through xCELLigence and flow cytometry. Results: In RPE cells co-cultured with HUVEC in physiological conditions, Aflibercept/Ranibizumab increased NO release in a dose and time-dependent way. Opposite results were obtained in peroxidative conditions. Both anti-VEGF agents were able to prevent the fall of cell viability and mitochondrial membrane potential, an effect which was reduced by various inhibitors, and increased cell migration. Aflibercept/Ranibizumab counteracted the changes of apoptosis markers, NOS expression/activation, PI3K and ERK1/2 activation caused by peroxidation. These results were confirmed by cell cycle analysis. Conclusion: This study has shown new mechanisms at the basis of protective effects elicited by Aflibercept/Ranibizumab in RPE cells. HUVEC stimulated with Aflibercept/Ranibizumab, could release some paracrine factors that can modulate the RPE cells response in both physiologic and peroxidative conditions

Optical coherence tomography angiography in Purtscher-like retinopathy associated with dermatomyositis : a case report

Purpose: To describe a multimodal imaging diagnosis of retinopathy in dermatomyositis. Case presentation: A 21-year-old white woman with a history of fatigue and a cutaneous rash complained of visual impairment in her left eye. A funduscopic examination showed multiple confluent cotton-wool spots in both eyes. Swept source-optical coherence tomography presented macular edema in both eyes; optical coherence tomography angiography revealed superficial and deep capillary occlusion in all areas affected by cotton-wool spots; and fluorescein angiography showed vascular walls enhancement, veins dilatation, and capillary leakage. After large doses of intravenously administered glucocorticoid therapy, followed by a cyclophosphamide regimen, best corrected visual acuity returned to 20/20 in both eyes. Conclusions: This case report presents optical coherence tomography angiography clinical findings in a rare case of dermatomyositis-associated retinopathy, remarking the importance of a multi-imaging approach for a correct diagnosis and treatment of eye injuries, in order to avoid serious complications and permanent sequelae

Epidemiology and Clinical Features of Listeriosis in Gipuzkoa, Spain, 2010–2020

Background: Listeriosis continues to be one of the most important notifiable foodborne diseases. Nonetheless, in Spain, there are few data on the molecular epidemiology of Listeria monocytogenes infections in recent years. Aim: To describe clinical features and the molecular epidemiology of human listeriosis over an 11-year period (2010–2020) in Gipuzkoa, Northern Spain. Methods: A total of 111 isolates, all but one from invasive disease, were studied. Serotyping (agglutination and multiplex polymerase chain reaction [PCR]) and multilocus sequence typing were performed for all isolates. Antibiotic susceptibility was assessed by the broth microdilution method. Results: The average annual incidence of listeriosis in non-pregnancy-associated cases was 1.55 per 100,000 population, with a 1-month mortality rate of 22.2%. In pregnant women, the average incidence was 0.45 cases per 1,000 pregnancies. Twenty-four sequence types were identified, serotype 4b ST1 (24.3%) being the most frequent followed by 1/2b ST87 (18.9%), which caused two long outbreaks in 2013–2014. A significant association was observed between ST219 and meningitis (p < 0.001). All isolates were susceptible to ampicillin as well as other antibiotics used in listeriosis treatment. Conclusion: Despite current control measures, listeriosis continues to be an important cause of mortality in the elderly, preterm birth, and miscarriages in pregnant women. Improvements in the control and diagnosis of listeriosis are needed to reduce the impact of this infection on vulnerable populations

Surveillance of Helicobacter pylori resistance over 22 Years (2000-2021) in Northern Spain

Objectives Helicobacter pylori gastritis is considered an infectious disease, regardless of symptoms and stage of disease. Most consensus documents recommend empirical therapy based on local antimicrobial susceptibility patterns. We aimed to provide clinically useful information about primary and secondary antimicrobial resistance to antimicrobials commonly prescribed for H. pylori. Methods Overall, 31,406 gastroduodenal biopsies and 2,641 string tests from patients over 15 years of age were plated on selective media, isolating H. pylori in 36.7% of biopsies and 50.7% of string tests. Susceptibility testing could be performed in 96.6% (12,399/12,835) of H. pylori isolates. Polymerase chain reaction (PCR) was also used to detect H. pylori and its resistance to clarithromycin, providing susceptibility data for 112 patients with negative culture results. Results Resistance to amoxicillin and tetracycline was unusual (0.6% and 0.2%, respectively). Rates of primary resistance to clarithromycin and metronidazole remained steady over the 22-year study period, at around 14% for clarithromycin and 30% for metronidazole, while primary resistance to levofloxacin tripled (from 7.6% in 2000 to 21.7% in 2021, P < 0.001) and increased with patient age. Notably, 1.8% of isolates were multiresistant to clarithromycin, metronidazole, and levofloxacin. Overall, secondary resistance rates were higher (P < 0.0001) than primary resistance rates for clarithromycin (42.5% vs 14.1%), metronidazole (40.9% vs 32%), and levofloxacin (21.5% vs 17.1%). Conclusion Determination of susceptibility for H. pylori by culture and/or PCR in patients undergoing endoscopy could facilitate the implementation of tailored therapy and guide the choice of empirical therapy when susceptibility testing cannot be performed, potentially helping limit the emergence of antimicrobial resistance