Increased Severity of Mycoplasma pneumoniae Infections in Spanish Children.

BACKGROUND: Since the end of 2023, an elevated incidence and severity of Mycoplasma pneumoniae infections among children in Asia has been noted. Subsequently, this trend was observed in several European countries although limited data are currently available. We conducted a national study to delineate the ongoing M. pneumoniae outbreak in our country. METHODS: A multicenter retrospective observational study was conducted across 32 hospitals in Spain, encompassing patients under 18 years old hospitalized for M. pneumoniae infection from January 2023 to March 2024. Infection was confirmed by positive polymerase chain reaction and/or by 2 serological tests. RESULTS: A total of 623 children were included, with 79% of cases diagnosed in the final 3 months of the study period. Pneumonia was the most common diagnosis (87%). Respiratory symptoms were present in 97% of cases, with 62% requiring oxygen supplementation and 14% requiring admission to the pediatric intensive care unit (PICU). Risk factors for PICU admission included the presence of neurological symptoms, hypoxemia and a history of prematurity. Children admitted to the PICU exhibited significantly higher neutrophil counts upon admission. CONCLUSIONS: We have observed a notable increase in hospital admissions, including PICU support by up to 14%, due to M. pneumoniae infection in our country since November 2023, indicative of a more severe clinical course associated with this pathogen.

Healthy Lifestyle Is a Protective Factor from Moderate and Severe Relapses and Steroid Use in Inflammatory Bowel Disease: A Prospective Cohort Study.

BACKGROUND: A healthy lifestyle, including good adherence to a Mediterranean diet (MD) and regular physical exercise, may be an important factor during the course of inflammatory bowel disease (IBD). Our aim is to determine whether adherence to MD, physical activity, and the combination of both can impact on IBD course. METHODS: This prospective cohort study includes 693 IBD outpatients who were in remission with a median follow-up time of 27 months (interquartile range 22-29 months). Each patient completed a survey to assess their adherence to the MD and physical activity. Healthy lifestyle was considered to be a proper adherence to both MD and an active lifestyle. Relapse during follow-up, severity of relapses, need for systemic steroids, and therapy changes were recorded. RESULTS: During the follow-up period, 188 patients (27.1%) experienced relapse, of which 56.1% were moderate or severe. Among patients with relapse, 85 (45%) required treatment with corticosteroids, and 15 (7.9%) were hospitalized. Patients with ulcerative colitis (CU) were more adherent to healthy lifestyle than patients with Crohn's disease (P = .011). Healthy lifestyle was associated with lower risk of moderate and severe relapses (adjusted Hazard ratio [aHR], 0.250; 95% confidence interval [CI], 0.093-0.670) and steroids use (aHR 0.292; 95% CI, 0.103-0.828) in IBD patients and with lower risk of moderate and severe relapses (aHR 0.270; 95% CI, 0.093-0.789) in UC patients. CONCLUSIONS: Healthy lifestyle has a favorable influence on promoting a milder disease course, and thus should be a crucial part of clinical management of patients with IBD.

Healthy lifestyle including adherence to a Mediterranean diet and physical exercise has a favorable influence on promoting a milder disease course and thus should be a crucial part of clinical management of patients with IBD.

Cardiovascular risk assessment in inflammatory bowel disease with metabolic dysfunction-associated steatotic liver disease.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) has been reported to increase the risk of early atherosclerosis even in young patients. Moreover, metabolic dysfunction-associated steatotic liver disease (MASLD), which has been linked to IBD, is a well-recognized but underdiagnosis entity related to cardiovascular risk. We analyze the impact of MASLD in IBD patients' cardiovascular risk through both advanced lipoprotein profile sorted by nuclear magnetic resonance spectroscopy, and carotid artery intima-media thickness (CIMT). METHODS: Cross-sectional cohort study which involves 941 IBD adult outpatients. Of them, 50 patients with IBD who met criteria for MASLD and 50 with IBD without MASLD, matched by sex and age were included. Alterations in CIMT were evaluated considering abnormal measures above the 75th percentile adjusted for sex and age. Specific advanced lipoprotein profile was also carried out. RESULTS: Most of the patients had an abnormal CIMT (58%). MASLD (OR=5.05, CI 95%=1.71-14.92) and female sex (OR=3.32, CI 95%=1.03-10) were significantly associated with CIMT alterations. Dense LDL particles (with high cholesterol composition in general cohort (OR=3.62, 95% CI=1.07-12.19) and high triglycerides density in young subgroup (OR=6.25, 95% CI=1.04-50) but not total LDL cholesterol were associated with CIMT alterations. CONCLUSIONS: MASLD and female sex are associated with early atherosclerosis in IBD patients. Dense LDL particle in combination with vascular imaging findings should be evaluated as non-invasive tools in the management of cardiovascular risk in IBD patients.

Argentatin Content in Guayule Leaves (Parthenium argentatum A. Gray).

Approximately one-third of the waste biomass from the cultivation of guayule (Parthenium argentatum A. Gray) for natural rubber production is leaf tissue; however, whether it can be valorized is not known. Guayulins and argentatins are potential high-value products that can be recovered from guayule resin during rubber/latex processing. Argentatins are highly abundant in guayule stem resin; however, unlike the guayulins, their occurrence in leaves has not been investigated. The present study determined the content of argentatins and isoargentatins A and B in the leaves of a pure guayule accession (R1040) and two hybrids (CAL-1 and AZ-2) under conditions of irrigation and non-irrigation. The resin content in leaves was ~10%, which provides a suitable starting point for economic exploitation. The highest production of argentatins occurred in plants under irrigation, with yields of 4.2 and 3.6 kg ha-1 for R1040 and AZ-2, respectively. The R1040 accession had the highest percentage of resin and the greatest total argentatin content (24.5 g kg-1 dried leaf), principally due to the abundance of argentatin A. Contrastingly, CAL-1 consistently showed the lowest argentatin content based on dried leaf weight and production (0.6 kg ha-1). The substantial abundance of argentatins in guayule leaves suggests the potential for future exploitation.

Lifestyle Can Exert a Significant Impact on the Development of Metabolic Complications and Quality Life in Patients with Inflammatory Bowel Disease.

Inflammatory bowel diseases (IBDs) are associated with an increased risk of metabolic comorbidities. There is a lack of data regarding the relationship between lifestyle and metabolic diseases in IBD patients. A cross-sectional study on consecutive IBD outpatients was conducted. Adherence to the Mediterranean diet (MD) was assessed using a 14-item questionnaire from the PREDIMED study, and physical activity was evaluated using the GODIN-Leisure score. Body composition was studied based on body mass index and waist-hip ratio (WHR), while quality of life was assessed using a nine-item short questionnaire. Among the 688 evaluated IBD patients, 66% were overweight or obese, 72.7% did not lead an active lifestyle and 70.1% did not adhere to the MD. Metabolic syndrome was associated with age (OR = 1.07, p = 0.019), overweight/obesity (OR = 12.987, p < 0.001) and the inflammatory behavior of Crohn's disease (OR = 6.172, p = 0.001). Type 2 diabetes mellitus or prediabetes was associated with age (OR = 1.063 p = 0.016), overweight/obesity (OR = 3.861, p < 0.001) and the inflammatory behavior of Crohn's disease (OR = 4.716, p = 0.001). Overweight /obesity (OR = 5.494, p < 0.001), a high WHR (OR = 2.564, p = 0.005) and a non-active lifestyle (OR = 2.202, p = 0.0003) were associated with metabolic dysfunction-associated steatotic liver disease. Lifestyle, body composition and not solely systemic inflammation might exert a significant influence on the emergence of metabolic comorbidities such as MASLD, type 2 diabetes mellitus and metabolic syndrome in patients with IBD.

New strategies to analyze argentatins A and B in guayule (Parthenium argentatum, A. Gray).

There is considerable interest in the exploitation of compounds belonging to the triterpenoid family from guayule (Parthenium argentatum, A. Gray), as they offer several beneficial effects to human health. The most abundant triterpenoids in guayule resin are the argentatins, which are currently analyzed by labor-intensive and time-consuming techniques. The purpose of the present study was to estimate argentatins and isoargentatins A and B in guayule using near-infrared spectroscopy (NIRS) and flow injection analysis (FIA). Results revealed that the best partial least squares regression model exhibited excellent correlation with the values estimated by NIRS calibration (r2c = 0.99-1.00) and cross-validation (r2cv = 0.94-0.99), and the residual predictive deviation was >3 in all cases. After optimization of the liquid chromatography-mass spectrometry and FIA parameters, the FIA mode could reliably collect data for argentatin A and B after applying a calculated coverage factor. In sum, NIRS and FIA appear to be a robust option for the estimation and routine analysis of argentatins in guayule stems and resin, respectively.

V600EBRAF Inhibition Induces Cytoprotective Autophagy through AMPK in Thyroid Cancer Cells.

The dysregulation of autophagy is important in the development of many cancers, including thyroid cancer, where V600EBRAF is a main oncogene. Here, we analyse the effect of V600EBRAF inhibition on autophagy, the mechanisms involved in this regulation and the role of autophagy in cell survival of thyroid cancer cells. We reveal that the inhibition of V600EBRAF activity with its specific inhibitor PLX4720 or the depletion of its expression by siRNA induces autophagy in thyroid tumour cells. We show that V600EBRAF downregulation increases LKB1-AMPK signalling and decreases mTOR activity through a MEK/ERK-dependent mechanism. Moreover, we demonstrate that PLX4720 activates ULK1 and increases autophagy through the activation of the AMPK-ULK1 pathway, but not by the inhibition of mTOR. In addition, we find that autophagy blockade decreases cell viability and sensitize thyroid cancer cells to V600EBRAF inhibition by PLX4720 treatment. Finally, we generate a thyroid xenograft model to demonstrate that autophagy inhibition synergistically enhances the anti-proliferative and pro-apoptotic effects of V600EBRAF inhibition in vivo. Collectively, we uncover a new role of AMPK in mediating the induction of cytoprotective autophagy by V600EBRAF inhibition. In addition, these data establish a rationale for designing an integrated therapy targeting V600EBRAF and the LKB1-AMPK-ULK1-autophagy axis for the treatment of V600EBRAF-positive thyroid tumours.

Resveratrol promotes apoptosis through the induction of dual specificity phosphatase 1 and sensitizes prostate cancer cells to cisplatin.

Resveratrol is a polyphenol with chemopreventive properties against prostate cancer; however, the mechanisms underlying its actions are not completely understood. Previously, we demonstrated that DUSP1 induces apoptosis in prostate cancer cells; therefore in the present study we investigated the role of this phosphatase on resveratrol effects. Moreover, we analysed the efficiency of combined treatment of resveratrol and the chemotherapeutic drug cisplatin on cellular viability and apoptosis and its relation with DUSP1 in prostate cancer cells. We found that resveratrol up-regulates DUSP1 expression in androgen-independent prostate cancer cells, which in turn, is involved in the inhibition of the NF-κB pathway and Cox-2 expression. This phosphatase is required for the induction of apoptosis achieved by resveratrol, but does not regulate the effects of this compound on cell cycle. Furthermore, we show that resveratrol cooperates with cisplatin both in the up-regulation of DUSP1 levels and in the promotion of apoptosis, suggesting that DUSP1 is a major determinant of cisplatin sensitivity to apoptosis. These results reveal a novel molecular mechanism by which resveratrol induces apoptosis in prostate cancer cells, and highlight the importance of DUSP1 in future therapeutic approaches based in the use of this polyphenol and cisplatin.

Epidemiology of Rare Lung Diseases: The Challenges and Opportunities to Improve Research and Knowledge.

Rare lung diseases encompass a broad spectrum of conditions and affect an estimated 1.2-2.5 million people in North America and 1.5-3 million people in Europe. While individual rare lung diseases affect less than 1 in 2000 individuals, collectively they have a significant impact upon the population at large. Hence it is vital to understand firstly the epidemiology and subsequently the pathogenesis and clinical course of these disorders. Through a greater understanding of these aspects of disease, progress can be made in reducing symptoms, containing healthcare costs and utilizing resources efficiently. Furthermore, a greater understanding of the pathobiology of rare lung diseases can inform both the pathogenesis and management of more common pulmonary disorders.In this chapter we review how epidemiological approaches and the utilization of patient registries has improved the knowledge and management of rare lung diseases. We further focus on the epidemiology of several of the more widely known rare pulmonary disorders, including idiopathic pulmonary fibrosis (IPF), cystic fibrosis (CF) and alpha-1 antitrypsin deficiency (AATD). To conclude we describe how patient advocacy groups and foundations have driven advances in research and management of ultra-rare lung diseases, namely, the major strides made in the management and understanding of lymphangioleiomyomatosis (LAM) and pulmonary alveolar proteinosis (PAP).We conclude that the models used to study some of the rarest of diseases may be successfully adopted by other rare and common disease communities, leading to improved care and the possibility of novel therapeutic options.

Poliserositis en paciente con hepatitis C en tratamiento con los nuevos antivirales / Poliserositis in a patient with hepatitis C under treatment with new antivirals

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Automatic counting of microglial cell activation and its applications.

Glaucoma is a multifactorial optic neuropathy characterized by the damage and death of the retinal ganglion cells. This disease results in vision loss and blindness. Any vision loss resulting from the disease cannot be restored and nowadays there is no available cure for glaucoma; however an early detection and treatment, could offer neuronal protection and avoid later serious damages to the visual function. A full understanding of the etiology of the disease will still require the contribution of many scientific efforts. Glial activation has been observed in glaucoma, being microglial proliferation a hallmark in this neurodegenerative disease. A typical project studying these cellular changes involved in glaucoma often needs thousands of images - from several animals - covering different layers and regions of the retina. The gold standard to evaluate them is the manual count. This method requires a large amount of time from specialized personnel. It is a tedious process and prone to human error. We present here a new method to count microglial cells by using a computer algorithm. It counts in one hour the same number of images that a researcher counts in four weeks, with no loss of reliability.

Retinal Macroglial Responses in Health and Disease.

Due to their permanent and close proximity to neurons, glial cells perform essential tasks for the normal physiology of the retina. Astrocytes and Müller cells (retinal macroglia) provide physical support to neurons and supplement them with several metabolites and growth factors. Macroglia are involved in maintaining the homeostasis of extracellular ions and neurotransmitters, are essential for information processing in neural circuits, participate in retinal glucose metabolism and in removing metabolic waste products, regulate local blood flow, induce the blood-retinal barrier (BRB), play fundamental roles in local immune response, and protect neurons from oxidative damage. In response to polyetiological insults, glia cells react with a process called reactive gliosis, seeking to maintain retinal homeostasis. When malfunctioning, macroglial cells can become primary pathogenic elements. A reactive gliosis has been described in different retinal pathologies, including age-related macular degeneration (AMD), diabetes, glaucoma, retinal detachment, or retinitis pigmentosa. A better understanding of the dual, neuroprotective, or cytotoxic effect of macroglial involvement in retinal pathologies would help in treating the physiopathology of these diseases. The extensive participation of the macroglia in retinal diseases points to these cells as innovative targets for new drug therapies.

Neuroprotective Effects of Low-Dose Statins in the Retinal Ultrastructure of Hypercholesterolemic Rabbits.

To evaluate the pleiotropic effects to statins, we analyze the qualitative and quantitative retinal changes in hypercholesterolemic rabbits after a low-dosage statin treatment. For this purpose, New Zealand rabbits were split into three groups: control (G0; n = 10), fed a standard diet; hypercholesterolemic (G1; n = 8), fed a 0.5% cholesterol-enriched diet for 8 months; and statins (G2; n = 8), fed a 0.5% cholesterol-enriched diet for 8 months, together with the administration of statin (pravastatin or fluvastatin sodium) at a dose of 2 mg / kg / day each diet. The retinas were analyzed by transmission electron microscopy and immunohistochemistry (glial fibrillary acidic protein). The retinal thickness of nuclear and plexiform layers were quantified in semi-thin sections. The results revealed that the low-statin-treated rabbits in comparison with the hypercholesterolemic group showed: i) a more preserved structure in all retinal layers; ii) a significant reduction in retinal thickness; iii) a decrease in cell death in the nuclear-and ganglion-cell layers; iv) a reduction of hydropic degeneration in the plexiform and nerve-fiber layers; v) a preservation of astrocytes and of the retinal area occupied by them; and vi) a better-preserved retinal vascular structure. Our findings indicate that low doses of statins can prevent retinal degeneration, acting on retinal macroglia, neurons and retinal vessels, despite that hypercholesterolemia remained unchanged. Thus, the pleiotropic effects of the statins may help safeguard the retinal ultrastructure.

Somatostatin activates Ras and ERK1/2 via a G protein ßγ-subunit-initiated pathway in thyroid cells.

Somatostatin (SST) is one of the main regulators of thyroid function. It acts by binding to its receptors, which lead to the dissociation of G proteins into Gαi and Gßγ subunits. However, much less is known about the function of Gßγ in thyroid cells. Here, we studied the role of SST and Gßγ dimers released upon SST stimulation on the Ras-ERK1/2 pathway in FTRL-5 thyroid cells. We demonstrate that SST activates Ras through Gi proteins, since SST-induced Ras activation is inhibited by pertussis toxin. Moreover, the specific sequestration of Gßγ dimers decreases Ras-GTP and phosphorylated ERK1/2 levels, and overexpression of Gßγ increases ERK1/2 phosphorylation induced by SST, indicating that Gßγ dimers released after SST treatment mediate activation of Ras and ERK1/2. On the other hand, SST treatment does not modify the expression of the thyroid differentiation marker sodium/iodide symporter (NIS) through ERK1/2 activation. However, SST increases AKT activation and the inhibition of the Src/PI3K/AKT pathway increases NIS levels in SST-treated cells. Thus, we conclude that, in thyroid cells, signalling from SST receptors to ERK1/2 involves a Gßγ-mediated signal acting on a Ras-dependent pathway. Moreover, we demonstrate that SST might regulates NIS expression through a Src/PI3K/AKT-dependent mechanism, but not through ERK1/2 signalling, showing the main role of this hormone in thyroid function.

Automatic Counting of Microglial Cells in Healthy and Glaucomatous Mouse Retinas.

Proliferation of microglial cells has been considered a sign of glial activation and a hallmark of ongoing neurodegenerative diseases. Microglia activation is analyzed in animal models of different eye diseases. Numerous retinal samples are required for each of these studies to obtain relevant data of statistical significance. Because manual quantification of microglial cells is time consuming, the aim of this study was develop an algorithm for automatic identification of retinal microglia. Two groups of adult male Swiss mice were used: age-matched controls (naïve, n = 6) and mice subjected to unilateral laser-induced ocular hypertension (lasered; n = 9). In the latter group, both hypertensive eyes and contralateral untreated retinas were analyzed. Retinal whole mounts were immunostained with anti Iba-1 for detecting microglial cell populations. A new algorithm was developed in MATLAB for microglial quantification; it enabled the quantification of microglial cells in the inner and outer plexiform layers and evaluates the area of the retina occupied by Iba-1+ microglia in the nerve fiber-ganglion cell layer. The automatic method was applied to a set of 6,000 images. To validate the algorithm, mouse retinas were evaluated both manually and computationally; the program correctly assessed the number of cells (Pearson correlation R = 0.94 and R = 0.98 for the inner and outer plexiform layers respectively). Statistically significant differences in glial cell number were found between naïve, lasered eyes and contralateral eyes (P<0.05, naïve versus contralateral eyes; P<0.001, naïve versus lasered eyes and contralateral versus lasered eyes). The algorithm developed is a reliable and fast tool that can evaluate the number of microglial cells in naïve mouse retinas and in retinas exhibiting proliferation. The implementation of this new automatic method can enable faster quantification of microglial cells in retinal pathologies.

Macro- and microglial responses in the fellow eyes contralateral to glaucomatous eyes.

Most studies employing experimental models of unilateral glaucoma have used the normotensive contralateral eye as the normal control. However, some studies have recently reported the activation of the retinal macroglia and microglia in the uninjured eye, suggesting that the eye contralateral to experimental glaucoma should not be used as a control. This review analyzes the studies describing the contralateral findings and discusses some of the routes through which the signals can reach the contralateral eye to initiate the glial reactivation.

Novel biodegradable polyesteramide microspheres for controlled drug delivery in Ophthalmology.

Most of the posterior segment diseases are chronic and multifactorial and require long-term intraocular medication. Conventional treatments of these pathologies consist of successive intraocular injections, which are associated with adverse effects. Successful therapy requires the development of new drug delivery systems able to release the active substance for a long term with a single administration. The present work involves the description of a new generation of microspheres based on poly(ester amide)s (PEA), which are novel polymers with improved biodegradability, processability and good thermal and mechanical properties. We report on the preparation of the PEA polymer, PEA microspheres (PEA Ms) and their characterization. PEA Ms (~15µm) were loaded with a lipophilic drug (dexamethasone) (181.0±2.4µg DX/mg Ms). The in vitro release profile of the drug showed a constant delivery for at least 90days. Based on the data from a performed in vitro release study, a kinetic ocular model to predict in vivo drug concentrations in a rabbit vitreous was built. According to the pharmacokinetic simulations, intravitreal injection of dexamethasone loaded PEA microspheres would provide release of the drug in rabbit eyes up to 3months. Cytotoxicity studies in macrophages and retinal pigment epithelial cells revealed a good in vitro tolerance of the microsystems. After sterilization, PEA Ms were administered in vivo by subtenon and intravitreal injections in male Sprague-Dawley rats and the location of the microspheres in rat eyes was monitored. We conclude that PEA Ms provide an alternative delivery system for controlling the delivery of drugs to the eye, allowing a novel generation of microsphere design.

Registros de enfermedades respiratorias integrados en el Registro Nacional de Enfermedades Raras / Respiratory Diseases Registries in the National Registry of Rare Diseases

En el presente trabajo se describen las características generales, objetivos y aspectos organizativos de los registros de enfermedades respiratorias minoritarias integrados en el Registro Nacional de Enfermedades Raras del Instituto de Investigación de Enfermedades Raras (IIER), con el objetivo de dar a conocer su existencia y fomentar la participación de los profesionales. Se recoge información sobre registros de las siguientes enfermedades: déficit de alfa-1 antitripsina, estenosis traqueal idiopática, histiocitosis pulmonar de células de Langerhans del adulto, linfangioleiomiomatosis, proteinosis alveolar y sarcoidosis

This report describes the general characteristics, objectives, and organizational aspects of the registries of minority respiratory diseases included in the National Registry of Rare Diseases of the Research Institute for Rare Diseases (ISCIII), in order to publicize their existence and encourage the participation of professionals. Information is collected on the following conditions: alpha-1 antitrypsin deficiency, idiopathic tracheal stenosis, adult pulmonary Langerhans’ cell histiocytosis, lymphangioleiomyomatosis, alveolar proteinosis, and sarcoidosis (AU)

Microglia in mouse retina contralateral to experimental glaucoma exhibit multiple signs of activation in all retinal layers.

BACKGROUND: Glaucomatous optic neuropathy, a leading cause of blindness, can progress despite control of intraocular pressure - currently the main risk factor and target for treatment. Glaucoma progression shares mechanisms with neurodegenerative disease, including microglia activation. In the present model of ocular hypertension (OHT), we have recently described morphological signs of retinal microglia activation and MHC-II upregulation in both the untreated contralateral eyes and OHT eyes. By using immunostaining, we sought to analyze and quantify additional signs of microglia activation and differences depending on the retinal layer. METHODS: Two groups of adult Swiss mice were used: age-matched control (naïve, n = 12), and lasered (n = 12). In the lasered animals, both OHT eyes and contralateral eyes were analyzed. Retinal whole-mounts were immunostained with antibodies against Iba-1, MHC-II, CD68, CD86, and Ym1. The Iba-1+ cell number in the plexiform layers (PL) and the photoreceptor outer segment (OS), Iba-1+ arbor area in the PL, and area of the retina occupied by Iba-1+ cells in the nerve fiber layer-ganglion cell layer (NFL-GCL) were quantified. RESULTS: The main findings in contralateral eyes and OHT eyes were: i) ameboid microglia in the NFL-GCL and OS; ii) the retraction of processes in all retinal layers; iii) a higher level of branching in PL and in the OS; iv) soma displacement to the nearest cell layers in the PL and OS; v) the reorientation of processes in the OS; vi) MHC-II upregulation in all retinal layers; vii) increased CD68 immunostaining; and viii) CD86 immunolabeling in ameboid cells. In comparison with the control group, a significant increase in the microglial number in the PL, OS, and in the area occupied by Iba-1+ cells in the NFL-GCL, and significant reduction of the arbor area in the PL. In addition, rounded Iba-1+ CD86+ cells in the NFL-GCL, OS and Ym1+ cells, and rod-like microglia in the NFL-GCL were restricted to OHT eyes. CONCLUSIONS: Several quantitative and qualitative signs of microglia activation are detected both in the contralateral and OHT eyes. Such activation extended beyond the GCL, involving all retinal layers. Differences between the two eyes could help to elucidate glaucoma pathophysiology.