Mutational spectrum and genotype-phenotype correlation in Mexican patients with infantile-onset and late-onset Pompe disease.

BACKGROUND: Pompe Disease (PD) is a metabolic myopathy caused by variants in the GAA gene, resulting in deficient enzymatic activity. We aimed to characterize the clinical features and related genetic variants in a series of Mexican patients. METHODS: We performed a retrospective study of clinical records of patients diagnosed with LOPD, IOPD or pseudodeficiency. RESULTS: Twenty-nine patients were included in the study, comprising these three forms. Overall, age of symptom onset was 0.1 to 43 years old. The most frequent variant identified was c.-32-13T>G, which was detected in 14 alleles. Among the 23 different variants identified in the GAA gene, 14 were classified as pathogenic, 5 were likely pathogenic, and 1 was a variant of uncertain significance. Two variants were inherited in cis arrangement and 2 were pseudodeficiency-related benign alleles. We identified two novel variants (c.1615 G>A and c.1076-20_1076-4delAAGTCGGCGTTGGCCTG). CONCLUSION: To the best of our knowledge, this series represent the largest phenotypic and genotypic characterization of patients with PD in Mexico. Patients within our series exhibited a combination of LOPD and IOPD associated variants, which may be related to genetic diversity within Mexican population. Further population-wide studies are required to better characterize the incidence of this disease in Mexican population.

Resveratrol Reduces Neuroinflammation and Hippocampal Microglia Activation and Protects Against Impairment of Memory and Anxiety-Like Behavior in Experimental Cerebral Palsy.

Cerebral palsy (CP) is a neurodevelopmental disorder characterized by motor and postural impairments. However, early brain injury can promote deleterious effects on the hippocampus, impairing memory. This study aims to investigate the effects of resveratrol treatment on memory, anxiety-like behavior, and neuroinflammation markers in rats with CP. Male Wistar rats were subjected to perinatal anoxia (P0-P1) and sensory-motor restriction (P2-P28). They were treated with resveratrol (10 mg/kg, 0.1 ml/100 g) or saline from P3-P21, being divided into four experimental groups: CS (n = 15), CR (n = 15), CPS (n = 15), and CPR (n = 15). They were evaluated in the tests of novel object recognition (NORT), T-Maze, Light-Dark Box (LDB), and Elevated Plus Maze (EPM). Compared to the CS group, the CPS group has demonstrated a reduced discrimination index on the NORT (p < 0.0001) and alternation on the T-Maze (p < 0.01). In addition, the CPS group showed an increase in permanence time on the dark side in LDB (p < 0.0001) and on the close arms of the EPM (p < 0.001). The CPR group demonstrated an increase in the object discrimination index (p < 0.001), on the alternation (p < 0.001), on the permanence time on the light side (p < 0.0001), and on the open arms (p < 0.001). The CPR group showed a reduction in gene expression of IL-6 (p = 0.0175) and TNF-α (p = 0.0007) and an increase in Creb-1 levels (p = 0.0020). The CPS group showed an increase in the activated microglia and a reduction in cell proliferation in the hippocampus, while CPR animals showed a reduction of activated microglia and an increase in cell proliferation. These results demonstrate promising effects of resveratrol in cerebral palsy behavior impairment through reduced neuroinflammation in the hippocampus.

Dietary flavonoid kaempferol reduces obesity-associated hypothalamic microglia activation and promotes body weight loss in mice with obesity.

BACKGROUND: Obesity results from an unbalance in the ingested and burned calories. Energy balance (EB) is critically regulated by the hypothalamic arcuate nucleus (ARC) by promoting appetite or anorectic actions. Hypothalamic inflammation, driven by high activation of the microglia, has been reported as a key mechanism involved in the development of diet-induced obesity. Kaempferol (KF), a flavonoid-type polyphenol present in a large number of fruits and vegetables, was shown to regulate both energy metabolism and inflammation. OBJECTIVES: In this work, we studied the effects of both the central and peripheral treatment with KF on hypothalamic inflammation and EB regulation in mice with obesity. METHODS: Obese adult mice were chronically (40 days) treated with KF (0.5 mg/kg/day, intraperitoneally). During the treatment, body weight, food intake (FI), feed efficiency (FE), glucose tolerance, and insulin sensitivity were determined. Analysis of microglia activation in the ARC of the hypothalamus at the end of the treatment was also performed. Body weight, FI, and FE changes were also evaluated in response to 5µg KF, centrally administrated. RESULTS: Chronic administration of KF decreased ∼43% of the density, and ∼30% of the ratio, of activated microglia in the arcuate nucleus. These changes were accompanied by body weight loss, decreased FE, reduced fasting blood glucose, and a tendency to improve insulin sensitivity. Finally, acute central administration of KF reproduced the effects on EB triggered by peripheral administration. CONCLUSION: These findings suggest that KF might fight obesity by regulating central processes related to EB regulation and hypothalamic inflammation.

A systematic review of neurogenesis in animal models of early brain damage: Implications for cerebral palsy.

Brain damage during early life is the main factor in the development of cerebral palsy (CP), which is one of the leading neurodevelopmental disorders in childhood. Few studies, however, have focused on the mechanisms of cell proliferation, migration, and differentiation in the brain of individuals with CP. We thus conducted a systematic review of preclinical evidence of structural neurogenesis in early brain damage and the underlying mechanisms involved in the pathogenesis of CP. Studies were obtained from Embase, Pubmed, Scopus, and Web of Science. After screening 2329 studies, 29 studies, covering a total of 751 animals, were included. Prenatal models based on oxygen deprivation, inflammatory response and infection, postnatal models based on oxygen deprivation or hypoxic-ischemia, and intraventricular hemorrhage models showed varying neurogenesis responses according to the nature of the brain damage, the time period during which the brain injury occurred, proliferative capacity, pattern of migration, and differentiation profile in neurogenic niches. Results mainly from rodent studies suggest that prenatal brain damage impacts neurogenesis and curbs generation of neural stem cells, while postnatal models show increased proliferation of neural precursor cells, improper migration, and reduced survival of new neurons.

Consenso para el diagnóstico y tratamiento de la esclerosis múltiple en pacientes del ISSSTE / Consensus for the diagnosis and treatment of multiple sclerosis in ISSSTE patients

Resumen: La esclerosis múltiple es una de las principales enfermedades desmielinizantes del sistema nervioso central, que repercute no solo en lo económico, sino también en lo social. El Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado (ISSSTE) dispone de la mayor parte de los tratamientos que modifican la evolución de esta enfermedad y para optimizar su uso, un grupo de neurólogos de la institución se reunió para la realización de un documento sobre aspectos generales de diagnóstico y tratamiento denominado Consenso para el Diagnóstico y Tratamiento de la Esclerosis múltiple en pacientes del ISSSTE. El objetivo de este documento es dar recomendaciones de las diferentes alternativas terapéuticas contra la esclerosis múltiple.

Abstract: Multiple sclerosis is one of the main demyelinating diseases of the central nervous system, which impacts not only economically but also socially. The Mexican Institute of Security and Social Services of State Workers (ISSSTE) has most of the disease modifying treatments for this disease and to optimize its use, a group of neurologists from the institution met to make a document on general aspects of diagnosis and treatment called: Consensus for the diagnosis and treatment of multiple sclerosis in ISSSTE patients. The objective of this consensus is to give recommendations on the different therapeutic alternatives against multiple scle- rosis for adults and children.

Agriculture erases climate-driven ß-diversity in Neotropical bird communities.

Earth is experiencing multiple global changes that will, together, determine the fate of many species. Yet, how biological communities respond to concurrent stressors at local-to-regional scales remains largely unknown. In particular, understanding how local habitat conversion interacts with regional climate change to shape patterns in ß-diversity-differences among sites in their species compositions-is critical to forecast communities in the Anthropocene. Here, we study patterns in bird ß-diversity across land-use and precipitation gradients in Costa Rica. We mapped forest cover, modeled regional precipitation, and collected data on bird community composition, vegetation structure, and tree diversity across 120 sites on 20 farms to answer three questions. First, do bird communities respond more strongly to changes in land use or climate in northwest Costa Rica? Second, does habitat conversion eliminate ß-diversity across climate gradients? Third, does regional climate control how communities respond to habitat conversion and, if so, how? After correcting for imperfect detection, we found that local land-use determined community shifts along the climate gradient. In forests, bird communities were distinct between sites that differed in vegetation structure or precipitation. In agriculture, however, vegetation structure was more uniform, contributing to 7%-11% less bird turnover than in forests. In addition, bird responses to agriculture and climate were linked: agricultural communities across the precipitation gradient shared more species with dry than wet forest communities. These findings suggest that habitat conversion and anticipated climate drying will act together to exacerbate biotic homogenization.

Blown by the wind: the ecology of male courtship display behavior in orchid bees.

Many insects rely on chemical signals to transmit precise information on the location, identity, and quality of potential mates. Chemical signals are often broadcasted at sites with physical properties that maximize signal propagation and signal transmission. Male neotropical orchid bees (Euglossini) perch and display on vertical branches and tree trunks in the forest to expose volatile blends (perfumes) that they previously collected from their environment. Previous studies have shown that the chemical composition of perfume blends is highly differentiated even between closely related species. However, variation in behavioral components of perfume exposure and male display remain poorly understood. We conducted a four-year study on orchid bee display sites (8 species) in pacific Costa Rica, using field observations along with chemical analysis and cage experiments to assess display niche partitioning among sympatric species. We evaluated the influence of physical factors (terrain, wind, light) on the distribution of perch sites and on display behavior, and tested a prediction of the sex pheromone-analogue hypothesis, i.e., that displaying males have above-average quantities or qualities of acquired perfumes. Males of different species displayed in the same general area and sometimes in close proximity to each other, but partitioned the display niche by selecting different perch diameters, display heights, and by displaying at different times of the day. Most perch sites were located inside the forest on elevated ground, especially along ridges, where stronger winds may help disperse perfume signals. Furthermore, the angular position of displaying males on perches was narrowly determined by wind direction, with males being positioned on the downwind side of the perch, where they would be most conspicuous to conspecifics approaching on an odor trail. Although our results generally support the hypothesis that perfumes serve as pheromone analogues, we did not find differences in the perfume composition of males caught at display perches and males captured at chemical baits. This suggests that, while chemical communication is an integral part of orchid bee display, male display activity is not determined by the history of, and success in, volatile acquisition.

Urgencia y emergencia hipertensiva / Hypertensive emergency and urgency

La crisis hipertensiva puede manifestarse de dos formas: la emergencia y la urgencia hipertensivas. Si bien las dos están incluidas en las llamadas crisis hipertensivas, durante la emergencia las complicaciones aparecen de manera brusca y se instalan con rapidez, por lo cual deben disminuirse, al término de unas cuantas horas, las cifras de tensión arterial, con el fin de reducir la morbilidad y mortalidad que este padecimiento ocasiona. Durante las urgencias, en cambio, los episodios ocurren en un lapso mayor y, por lo tanto, la tensión arterial puede controlarse incluso durante las primeras 24 horas, con el mismo objetivo de reducir los riesgos para el paciente. La crisis hipertensiva incluye diversos síndromes clínicos, que son la expresión del daño ocasionado por las cifras elevadas de la tensión arterial sobre los vasos sanguíneos y los órganos fundamentales. La clasificación que más se utiliza se basa en la elevación tensional y la aparición de las manifestaciones clínicas que expresan daño a los órganos. En la actualidad, a pesar de tener una terapéutica farmacológica efectiva contra estos padecimientos, la mortalidad debida a la emergencia hipertensiva sigue elevada (70-90 por ciento). Las causas más comunes de la muerte de estos pacientes son la uremia, el infarto agudo de miocardio y los accidentes cerebrovasculares. Sin embargo, es importante utilizar con precisión el concepto de crisis hipertensiva, en especial porque ésta requiere una terapéutica rápida y agresiva que no está exenta de efectos colaterales, incluso graves, y sólo se justifica si existe una meticulosa valoración clínica que confirme su diagnóstico.

Granuloma inflamatorio secundario a la ingestion de espina de pescado: presentación de un caso y revisión de la literatura / Inflammatory granuloma following a fish bone swallowing

La ingestión de objetos extraños ocurre ocasionalmente en los adultos, especialmente en aquéllos que utilizan prótesis dentales. La mayoría de esos objetos transitan por el tracto gastrointestinal sin causar síntomas, aunque algunas veces se pueden presentar complicaciones como perforación, absceso, obstrucción, tumoración, peritonitis localizada o generalizada. Se informa el caso de una paciente que desarrolló una tumoración abdominal dependiente de intestino secundaria a la perforación de éste, como consecuencia de la ingestión de una espina de pescado. Se comunican los síntomas presentados y la dificultad diagnóstica, pues fue valorada por diferentes especialista sin logara llega a un diagnóstico de certeza. Cabe hacer notar la importancia del aspecto macroscópico de la tumoración, que sugería un proceso tumoral de características malignas, y que histopatológicamanete fue señalado como un granuloma inflamatorio libre de células malignas secundario a cuerpo extraño (espina de pescado), caso raro de acuerdo a la bibliografía revisada.