Síndromes neurocutáneos

Fil: Servin, Roxana Estela. Universidad Nacional Del Nordeste. Facultad de Medicina; Argentina.Fil: Ávalos, Manuel. Universidad Nacional Del Nordeste. Facultad de Medicina; Argentina.Fil: Warner, Gabriela. Universidad Nacional Del Nordeste. Facultad de Medicina; Argentina.Los síndromes neurocutáneos (SNC) comprenden un grupo heterogéneo de trastornos hereditarios que comprometen principalmente la piel y el sistema nervioso central, estructuras que tienen un origen común en el ectodermo, cuya formación se inicia en las fases precoces del desarrollo embrionario (1-3). Se caracterizan por la presencia de displasias en distintos tejidos y tendencia a la formación de tumores en diversos órganos. Aunque algunos de estos síndromes comparten elementos comunes, poseen características particulares que los diferencian

Magnetic resonance imaging findings in Kenyans and South Africans with active convulsive epilepsy: an observational study

Objective: Focal epilepsy is common in low- and middle-income countries. The frequency and nature of possible underlying structural brain abnormalities have, however, not been fully assessed. Methods: We evaluated the possible structural causes of epilepsy in 331 people with epilepsy (240 from Kenya and 91 from South Africa) identified from community surveys of active convulsive epilepsy. Magnetic resonance imaging (MRI) scans were acquired on 1.5-Tesla scanners to determine the frequency and nature of any underlying lesions. We estimated the prevalence of these abnormalities using Bayesian priors (from an earlier pilot study) and observed data (from this study). We used a mixed-effect modified Poisson regression approach with the site as a random effect to determine the clinical features associated with neuropathology. Results: MRI abnormalities were found in 140 of 240 (modeled prevalence = 59%, 95% confidence interval [CI]: 53%–64%) of people with epilepsy in Kenya, and in 62 of 91 (modeled prevalence = 65%, 95% CI: 57%–73%) in South Africa, with a pooled modeled prevalence of 61% (95% CI: 56%–66%). Abnormalities were common in those with a history of adverse perinatal events (15/23 [65%, 95% CI: 43%–84%]), exposure to parasitic infections (83/120 [69%, 95% CI: 60%–77%]) and focal electroencephalographic features (97/142 [68%, 95% CI: 60%–76%]), but less frequent in individuals with generalized electroencephalographic features (44/99 [44%, 95% CI: 34%–55%]). Most abnormalities were potentially epileptogenic (167/202, 82%), of which mesial temporal sclerosis (43%) and gliosis (34%) were the most frequent. Abnormalities were associated with co-occurrence of generalized non-convulsive seizures (relative risk [RR] = 1.12, 95% CI: 1.04–1.25), lack of family history of seizures (RR = 0.91, 0.86–0.96), convulsive status epilepticus (RR = 1.14, 1.08–1.21), frequent seizures (RR = 1.12, 1.04–1.20), and reported use of anti-seizure medication (RR = 1.22, 1.18–1.26). Significance: MRI identified pathologies are common in people with epilepsy in Kenya and South Africa. Mesial temporal sclerosis, the most common abnormality, may be amenable to surgical correction. MRI may have a diagnostic value in rural Africa, but future longitudinal studies should examine the prognostic role

Vasculature Remodeling in a Rat Model of Cerebral Ischemia. The Fate of the BrdU-Labeled Cells Prior to Stroke

Despite the clinical significance of post-stroke angiogenesis, a detailed phenotypic analysis of pre-stroke vascular remodeling and post-stroke angiogenesis had not yet been done in a model of focal ischemia. In this study, using BrdU-labeling of proliferating cells and immunofluorescence of pre- and post-stroke rats, we found that, (i) BrdU administered before stroke was incorporated preferentially into the nuclei of endothelial cells lining the lumen of existing blood vessels and newly born neurons in the dentate gyrus but not in the subventricular zone or proliferating microglia, (ii) BrdU injection prior to stroke led to the patchy distribution of the newly incorporated endothelial cells into existing blood vessels of the adult rat brain, (iii) BrdU injection prior to stroke specifically labeled neuronal precursors cells in a region of soft tissue beyond the inhibitory scar, which seems to be permissive to regenerative events, (iv) BrdU injection after stroke led to labeling of endothelial cells crossing or detaching from the disintegrating blood vessels and their incorporation into new blood vessels in the stroke region, scar tissue and the region beyond, (v) BrdU injection after stroke led to specific incorporation of BrdU-positive nuclei into the “pinwheel” architecture of the ventricular epithelium, (vi) blood vessels in remote areas relative to the infarct core and in the contralateral non-lesioned cortex, showed co-labeled BrdU/RECA+ endothelial cells shortly after the BrdU injection, which strongly suggests a bone marrow origin of the endothelial cells. In the damaged cortex, a BrdU/prolyl 4-hydroxylase beta double labeling in the close proximity to collagen IV-labeled basement membrane, suggests that, in addition to bone marrow derived endothelial cells, the disintegrating vascular wall itself could also be a source of proliferating endothelial cells, (vii) By day 28 after stroke, new blood vessels were observed in the perilesional area and the scar tissue region, which is generally considered to be resistant to regenerative events. Finally, (viii) vigorous angiogenesis was also detected in a region of soft tissue, also called “islet of regeneration,” located next to the inhibitory scar.Conclusion: BrdU administered prior to, and after stroke, allows to investigate brain vasculature remodeling in the adult brain

Yeast and its derivatives as ingredients in the food industry

In the last 200 years, and still today, yeast is well known for its application in brewing, alcohol fermentation and wine and bread making. They are an endless source of new food ingredients and additives with excellent functional and nutritional properties, now through the use of innovative elaboration and fractionation techniques that come mainly from biotechnology. The book reviewed here contains fourteen chapters in 246 pages that deal with yeasts employed as food ingredients and their potential as Nutraceutics. It compiles the expertise of three Latin American institutionsthat have given priority to the generation of basic knowledge on yeast and set the grounds for the development of new technologies based on these microorganisms. This is a sample of the alternatives offered by yeast in the fields of food science and technology.Fil: Otero, Miguel A.. Instituto Cubano de Investigaciones de los Derivados de la Caña de Azúcar; CubaFil: Guerrero, Isabel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Investigación en Funcionalidad y Tecnología de Alimentos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Wagner, Jorge Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cabello, Agustín J.. Instituto Cubano de Investigaciones de los Derivados de la Caña de Azúcar; CubaFil: Sceni, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: García, Roxana. Instituto Cubano de Investigaciones de los Derivados de la Caña de Azúcar; CubaFil: Soriano, Jorge. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Investigación en Funcionalidad y Tecnología de Alimentos; ArgentinaFil: Tomasini, Araceli. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Investigación en Funcionalidad y Tecnología de Alimentos; ArgentinaFil: Saura, Gustavo. Instituto Cubano de Investigaciones de los Derivados de la Caña de Azúcar; CubaFil: Almazán, Oscar. Instituto Cubano de Investigaciones de los Derivados de la Caña de Azúcar; Cub

Magnetic resonance imaging findings in Kenyans and South Africans with active convulsive epilepsy: an observational study

Objective: Focal epilepsy is common in low- and middle-income countries. The frequency and nature of possible underlying structural brain abnormalities have, however, not been fully assessed. Methods: We evaluated the possible structural causes of epilepsy in 331 people with epilepsy (240 from Kenya and 91 from South Africa) identified from community surveys of active convulsive epilepsy. Magnetic resonance imaging (MRI) scans were acquired on 1.5-Tesla scanners to determine the frequency and nature of any underlying lesions. We estimated the prevalence of these abnormalities using Bayesian priors (from an earlier pilot study) and observed data (from this study). We used a mixed-effect modified Poisson regression approach with the site as a random effect to determine the clinical features associated with neuropathology. Results: MRI abnormalities were found in 140 of 240 (modeled prevalence = 59%, 95% confidence interval [CI]: 53%–64%) of people with epilepsy in Kenya, and in 62 of 91 (modeled prevalence = 65%, 95% CI: 57%–73%) in South Africa, with a pooled modeled prevalence of 61% (95% CI: 56%–66%). Abnormalities were common in those with a history of adverse perinatal events (15/23 [65%, 95% CI: 43%–84%]), exposure to parasitic infections (83/120 [69%, 95% CI: 60%–77%]) and focal electroencephalographic features (97/142 [68%, 95% CI: 60%–76%]), but less frequent in individuals with generalized electroencephalographic features (44/99 [44%, 95% CI: 34%–55%]). Most abnormalities were potentially epileptogenic (167/202, 82%), of which mesial temporal sclerosis (43%) and gliosis (34%) were the most frequent. Abnormalities were associated with co-occurrence of generalized non-convulsive seizures (relative risk [RR] = 1.12, 95% CI: 1.04–1.25), lack of family history of seizures (RR = 0.91, 0.86–0.96), convulsive status epilepticus (RR = 1.14, 1.08–1.21), frequent seizures (RR = 1.12, 1.04–1.20), and reported use of anti-seizure medication (RR = 1.22, 1.18–1.26). Significance: MRI identified pathologies are common in people with epilepsy in Kenya and South Africa. Mesial temporal sclerosis, the most common abnormality, may be amenable to surgical correction. MRI may have a diagnostic value in rural Africa, but future longitudinal studies should examine the prognostic role

The Clinical Development of Taldefgrobep Alfa: An Anti-Myostatin Adnectin for the Treatment of Duchenne Muscular Dystrophy

INTRODUCTION: Duchenne muscular dystrophy (DMD) is a genetic muscle disorder that manifests during early childhood and is ultimately fatal. Recently approved treatments targeting the genetic cause of DMD are limited to specific subpopulations of patients, highlighting the need for therapies with wider applications. Pharmacologic inhibition of myostatin, an endogenous inhibitor of muscle growth produced almost exclusively in skeletal muscle, has been shown to increase muscle mass in several species, including humans. Taldefgrobep alfa is an anti-myostatin recombinant protein engineered to bind to and block myostatin signaling. Preclinical studies of taldefgrobep alfa demonstrated significant decreases in myostatin and increased lower limb volume in three animal species, including dystrophic mice. METHODS: This manuscript reports the cumulative data from three separate clinical trials of taldefgrobep alfa in DMD: a phase 1 study in healthy adult volunteers (NCT02145234), and two randomized, double-blind, placebo-controlled studies in ambulatory boys with DMD-a phase 1b/2 trial assessing safety (NCT02515669) and a phase 2/3 trial including the North Star Ambulatory Assessment (NSAA) as the primary endpoint (NCT03039686). RESULTS: In healthy adult volunteers, taldefgrobep alfa was generally well tolerated and resulted in a significant increase in thigh muscle volume. Treatment with taldefgrobep alfa was associated with robust dose-dependent suppression of free myostatin. In the phase 1b/2 trial, myostatin suppression was associated with a positive effect on lean body mass, though effects on muscle mass were modest. The phase 2/3 trial found that the effects of treatment did not meet the primary endpoint pre-specified futility analysis threshold (change from baseline of ≥ 1.5 points on the NSAA total score). CONCLUSIONS: The futility analysis demonstrated that taldefgrobep alfa did not result in functional change for boys with DMD. The program was subsequently terminated in 2019. Overall, there were no safety concerns, and no patients were withdrawn from treatment as a result of treatment-related adverse events or serious adverse events. TRIAL REGISTRATION: NCT02145234, NCT02515669, NCT03039686

Grassroots Agency: Participation and Conflict in Buenos Aires Shantytowns seen through the Pilot Plan for Villa 7 (1971–1975)

open access articleIn 1971, after more than a decade of national and municipal policies aimed at the top-down removal of shantytowns, the Buenos Aires City Council approved the Plan Piloto para la Relocalización de Villa 7 (Pilot Plan for the Relocation of Shantytown 7; 1971–1975, referred to as the Pilot Plan hereinafter). This particular plan, which resulted in the construction of the housing complex, Barrio Justo Suárez, endures in the collective memory of Argentines as a landmark project regarding grassroots participation in state housing initiatives addressed at shantytowns. Emerging from a context of a housing shortage for the growing urban poor and intense popular mobilizations during the transition to democracy, the authors of the Pilot Plan sought to empower shantytown residents in novel ways by: 1) maintaining the shantytown’s location as opposed to eradication schemes that relocated the residents elsewhere, 2) formally employing some of the residents for the stage of construction, as opposed to “self-help” housing projects in which the residents contributed with unpaid labor, and 3) including them in the urban and architectural design of the of the new housing. This paper will examine the context in which the Pilot Plan was conceived of as a way of re-assessing the roles of the state, the user, and housing-related professionals, often seen as antagonistic. The paper argues that residents’ fair participation and state intervention in housing schemes are not necessarily incompatible, and can function in specific social and political contexts through multiactor proposals backed by a political will that prioritizes grassroots agency

The Usher 1B protein, MYO7A, is required for normal localization and function of the visual retinoid cycle enzyme, RPE65

Mutations in the MYO7A gene cause a deaf-blindness disorder, known as Usher syndrome 1B.  In the retina, the majority of MYO7A is in the retinal pigmented epithelium (RPE), where many of the reactions of the visual retinoid cycle take place.  We have observed that the retinas of Myo7a-mutant mice are resistant to acute light damage. In exploring the basis of this resistance, we found that Myo7a-mutant mice have lower levels of RPE65, the RPE isomerase that has a key role in the retinoid cycle.  We show for the first time that RPE65 normally undergoes a light-dependent translocation to become more concentrated in the central region of the RPE cells.  This translocation requires MYO7A, so that, in Myo7a-mutant mice, RPE65 is partly mislocalized in the light.  RPE65 is degraded more quickly in Myo7a-mutant mice, perhaps due to its mislocalization, providing a plausible explanation for its lower levels.  Following a 50–60% photobleach, Myo7a-mutant retinas exhibited increased all-trans-retinyl ester levels during the initial stages of dark recovery, consistent with a deficiency in RPE65 activity.  Lastly, MYO7A and RPE65 were co-immunoprecipitated from RPE cell lysate by antibodies against either of the proteins, and the two proteins were partly colocalized, suggesting a direct or indirect interaction.  Together, the results support a role for MYO7A in the translocation of RPE65, illustrating the involvement of a molecular motor in the spatiotemporal organization of the retinoid cycle in vision

Associations between unilateral amblyopia in childhood and cardiometabolic disorders in adult life: a cross-sectional and longitudinal analysis of the UK Biobank

Background Amblyopia is a common neurodevelopmental condition and leading cause of childhood visual impairment. Given the known association between neurodevelopmental impairment and cardiometabolic dysfunction in later life, we investigated whether children with amblyopia have increased risk of cardiometabolic disorders in adult life. Methods This was a cross-sectional and longitudinal analysis of 126,399 United Kingdom Biobank cohort participants who underwent ocular examination. A subset of 67,321 of these received retinal imaging. Data analysis was conducted between November 1st 2021 and October 15th 2022. Our primary objective was to investigate the association between amblyopia and a number of components of metabolic syndrome and individual cardiometabolic diseases. Childhood amblyopia, dichotomised as resolved or persisting by adulthood, cardiometabolic disease and mortality were defined using ophthalmic assessment, self-reported, hospital admissions and death records. Morphological features of the optic nerve and retinal vasculature and sublayers were extracted from retinal photography and optical coherence tomography. Associations between amblyopia and cardiometabolic disorders as well as retinal markers were investigated in multivariable-adjusted regression models. Findings Individuals with persisting amblyopia (n = 2647) were more likely to be obese (adjusted odds ratio (95% confidence interval): 1.16 (1.05; 1.28)), hypertensive (1.25 (1.13; 1.38)) and diabetic (1.29 (1.04; 1.59)) than individuals without amblyopia (controls, (n = 18,481)). Amblyopia was also associated with an increased risk of myocardial infarction (adjusted hazard ratio: 1.38 (1.11; 1.72)) and death (1.36 (1.15; 1.60)). On retinal imaging, amblyopic eyes had significantly increased venular caliber (0.29 units (0.21; 0.36)), increased tortuosity (0.11 units (0.03; 0.19)), but lower fractal dimension (−0.23 units (−0.30; −0.16)) and thinner ganglion cell-inner plexiform layer (mGC-IPL, −2.85 microns (−3.47; −2.22)). Unaffected fellow eyes of individuals with amblyopia also had significantly lower retinal fractal dimension (−0.08 units (−0.15; −0.01)) and thinner mGC-IPL (−1.14 microns (−1.74; −0.54)). Amblyopic eyes with a persisting visual deficit had smaller optic nerve disc height (−0.17 units (−0.25; −0.08)) and width (−0.13 units (−0.21; −0.04)) compared to control eyes. Interpretation Although further research is needed to understand the basis of the observed associations, healthcare professionals should be cognisant of greater cardiometabolic dysfunction in adults who had childhood amblyopia. Differences in retinal features in both the amblyopic eye and the unaffected non-amblyopic suggest generalised versus local processes