Brain health in diverse settings: How age, demographics and cognition shape brain function.

Diversity in brain health is influenced by individual differences in demographics and cognition. However, most studies on brain health and diseases have typically controlled for these factors rather than explored their potential to predict brain signals. Here, we assessed the role of individual differences in demographics (age, sex, and education; n = 1,298) and cognition (n = 725) as predictors of different metrics usually used in case-control studies. These included power spectrum and aperiodic (1/f slope, knee, offset) metrics, as well as complexity (fractal dimension estimation, permutation entropy, Wiener entropy, spectral structure variability) and connectivity (graph-theoretic mutual information, conditional mutual information, organizational information) from the source space resting-state EEG activity in a diverse sample from the global south and north populations. Brain-phenotype models were computed using EEG metrics reflecting local activity (power spectrum and aperiodic components) and brain dynamics and interactions (complexity and graph-theoretic measures). Electrophysiological brain dynamics were modulated by individual differences despite the varied methods of data acquisition and assessments across multiple centers, indicating that results were unlikely to be accounted for by methodological discrepancies. Variations in brain signals were mainly influenced by age and cognition, while education and sex exhibited less importance. Power spectrum activity and graph-theoretic measures were the most sensitive in capturing individual differences. Older age, poorer cognition, and being male were associated with reduced alpha power, whereas older age and less education were associated with reduced network integration and segregation. Findings suggest that basic individual differences impact core metrics of brain function that are used in standard case-control studies. Considering individual variability and diversity in global settings would contribute to a more tailored understanding of brain function.

Biophysical models applied to dementia patients reveal links between geographical origin, gender, disease duration, and loss of neural inhibition.

BACKGROUND: The hypothesis of decreased neural inhibition in dementia has been sparsely studied in functional magnetic resonance imaging (fMRI) data across patients with different dementia subtypes, and the role of social and demographic heterogeneities on this hypothesis remains to be addressed. METHODS: We inferred regional inhibition by fitting a biophysical whole-brain model (dynamic mean field model with realistic inter-areal connectivity) to fMRI data from 414 participants, including patients with Alzheimer's disease, behavioral variant frontotemporal dementia, and controls. We then investigated the effect of disease condition, and demographic and clinical variables on the local inhibitory feedback, a variable related to the maintenance of balanced neural excitation/inhibition. RESULTS: Decreased local inhibitory feedback was inferred from the biophysical modeling results in dementia patients, specific to brain areas presenting neurodegeneration. This loss of local inhibition correlated positively with years with disease, and showed differences regarding the gender and geographical origin of the patients. The model correctly reproduced known disease-related changes in functional connectivity. CONCLUSIONS: Results suggest a critical link between abnormal neural and circuit-level excitability levels, the loss of grey matter observed in dementia, and the reorganization of functional connectivity, while highlighting the sensitivity of the underlying biophysical mechanism to demographic and clinical heterogeneities in the patient population.

Miocardiopatía hipertrófica en la edad pediátrica. Revisión a propósito de una serie de casos

Introducción: La miocardiopatía hipertrófica (MCH) constituye una enfermedad compleja y variable en cuanto a morfología, fisiopatología, pronóstico y sobrevida. Se caracteriza por una hipertrofia del ventrículo izquierdo, aunque en ocasiones puede ser biventricular o ventricular derecha aislada. En la edad pediátrica predominan las causas no sarcoméricas. La ecocardiografía es el método diagnóstico más utilizado para caracterizar la morfología y repercusión hemodinámica, sin embargo, la resonancia magnética cardíaca (RMC) es de elección por aportar mayores ventajas morfológicas y funcionales. Las pruebas genéticas son de gran importancia en la determinación del diagnóstico etiológico, manejo terapéutico y pronóstico. El tratamiento tiene como objetivo principal mejorar la capacidad funcional y aliviar los síntomas. Los betabloqueantes no vasodilatadores son considerados de primera líneay en algunos casos se puede recurrir a terapias avanzadas como disopiramida o terapia de reducción septal (TRS), uso del cardiodesfibrilador implantable (CDI), y en ocasiones se debe considerar trasplante cardiaco en pacientes con síntomas refractarios al tratamiento médico y en MCH del tipo obstructivo. Materiales y métodos: Estudio observacional, descriptivo, corte transversal. Resultados: Se estudiaron 12 pacientes, desde enero de 2020 a diciembre de 2022, con edades comprendidas desde 5 meses hasta 16 años, diagnosticados con MCH de presentación clínica variable y de distintas etiologías. Conclusión: La MCH de causas no sarcoméricas como los síndromes malformativos y errores innatos del metabolismo son las que tienen peor pronóstico y sobrevida. La finalidad de detectar precozmente la MCH es el inicio temprano de la terapia específica, para así retrasar el compromiso cardiovascular y mejorar la sobrevida.

Introduction: Hypertrophic cardiomyopathy (HCM) is a complex and variable disease in terms of morphology, pathophysiology, prognosis and survival. It is characterized by left ventricular hypertrophy, although it can sometimes be biventricular or isolated right ventricular. In the pediatric population, non-sarcomeric causes predominate. Echocardiography is the most widely used diagnostic method to characterize morphology and hemodynamic repercussions; however, cardiac magnetic resonance imaging (CMR) is preferred because it provides greater morphological and functional advantages. Genetic tests are of great importance in determining the etiological diagnosis, therapeutic management and prognosis. The main objective of the treatment is to improve functional capacity and alleviate symptoms. Non-vasodilator beta-blockers are considered first-line treatment and in some cases advanced therapies such as disopyramide or septal reduction therapy (SRT), use of implantable cardioverter-defibrillator (ICD) can be used; heart transplantation should be considered in patients with symptoms refractory to medical treatment and in HCM of the obstructive type. Materials and methods: This was an observational, descriptive, cross-sectional study. Results: 12 patients were studied, from January 2020 to December 2022, with ages ranging from 5 months to 16 years, diagnosed with HCM of variable clinical presentation and of different etiologies. Conclusion: HCM from non-sarcomeric causes such as malformation syndromes and inborn errors of metabolism have the worst prognosis and survival. The purpose of early detection of HCM is the early initiation of specific therapy, in order to delay cardiovascular compromise and improve survival.

Calidad del aire en la ciudad San Francisco de Milagro y su influencia en la salud poblacional / Air quality in the city of San Francisco de Milagros and its influence on population health

atmosférica es responsable de 6.67 millones de muertes al año por accidentes cardiovasculares, enfermedades cardíacas, cáncer de pulmón y enfermedades respiratorias crónicas (HEI, 2020; OMS, 2021). La presente investigación determino la calidad del aire en la ciudad San Francisco de Milagro y su influencia en la salud poblacional. Los esultados expresan, que la concentración promedio de estos gases están dentro delos estándares establecidos por la OMS (2005), OMS (2018); para cada uno de ellos y por ende no son dañinos para la salud de la población en esudio. Sin embargo, actividades de desarrollo local como el caso de obras de construcción, estarían causando molestias en la población, debido a la falta de control y regulación ambiental, como lo demostró el estudio de percepciones(AU)

Environmental pollution is a global health problem with serious negative implications for humans. According to the WHO, air pollution is responsible for 6.67 million deaths per year from cardiovascular accidents, heart disease, lung cancer and chronic respiratory diseases (HEI, 2020; WHO, 2021). This research determined the air quality in the city of San Francisco de Milagro and its influence on population health. The results express that the average concentration of these gases are within the standards established by the WHO (2005), WHO (2018); for each of them and therefore are not harmful to the health of the population under study. However, local development activities such as construction works would be causing inconvenience to the population, due to the lack of environmental control and regulation, as the perceptions study showed(AU)

EFICIENCIA DE POLINIZACIÓN DE COLONIAS HUERFANAS DE Bombus atratus (HYMENOPTERA: APIDAE) EN FRESA (Fragaria x ananassa) BAJO CUBIERTA / Efficiency of Pollination by Orphan Colonies of Bombus atratus (Hymenoptera: Apidae) in Strawberry (Fragaria x ananassa) in Greenhouse

RESUMEN En Colombia la fresa se ha convertido en un cultivo de interés económico debido a la creciente demanda en el mercado extranjero en la última década. La mayoría de plantaciones son a campo abierto y no usan esquemas de polinización para mejorar la calidad de producción. La polinización con abejorros mejora la calidad de los frutos, aunque estos se producen mediante polinización espontánea. La especie nativa Bombus atratus ha sido reconocida como un polinizador eficiente de cultivos hortofrutícolas colombianos bajo invernadero. El presente estudio evaluó la eficiencia de polinización de dos colonias huérfanas en la calidad de los frutos de las variedades camino real y ventana sembrados bajo invernadero en Cajicá-Colombia. Se embolsaron los botones para obtener los frutos producidos espontáneamente y ser comparados con los frutos provenientes de la visita de obreras de B. atratus. Se encontró que la visita de las obreras mejoró la calidad de los frutos en las variables, calibre (35 % y 31 %), longitud (28 % y 19 %), peso fresco (103 % y 90 %), peso seco (126 % y 145 %) y número de semillas (55 % y 81 %) para las variedades Camino Real y Ventana respectivamente. A partir de las observaciones realizadas, se determinó que el recurso floral utilizado por las obreras de B. atratus fue el néctar y se hacen recomendaciones sobre su uso en este cultivo.

ABSTRACT In Colombia the strawberry has become a crop of economic interest due to the growing demand in the foreign market in the last decade. Most plantations are open fields and do not use pollination strategies to improve the production quality. Pollination with bumblebees improves the quality of the fruits, although these are produced by spontaneous pollination. The native species Bombus atratus has been recognized as an efficient pollinator of Colombian horticultural crops under greenhouse. The present study evaluated the pollination efficiency of two orphan colonies in the quality of the fruits of the "Camino real" and "Ventana" cultivars planted under a greenhouse in Cajicá-Colombia. The buttons were excluded to obtain the fruits produced spontaneously and to be compared with the fruits coming from the visit of workers of B. atratus. It was found that the visit of the workers improved fruit quality in the features: caliber (35 % and 31 %), length (28 % and 19 %), fresh weight (103 % and 90 %), dry weight 126 % and 145 %) and number of seeds (55 % and 81 %) for the cultivar "Camino Real" and "Ventana" respectively. From the observations made, it was determined that the floral resource used by the workers of B. atratus was the nectar and recommendations are done about on its use in this crop.

Analysis of somaclonal variation in transgenic and regenerated plants of Arabidopsis thaliana using methylation related metAFLP and TMD markers.

KEY MESSAGE: We provide evidence that nucleotide sequence and methylation status changes occur in the Arabidopsis genome during in vitro tissue culture at a frequency high enough to represent an important source of variation. Somaclonal variation is a general consequence of the tissue culture process that has to be analyzed specifically when regenerated plants are obtained in any plant species. Currently, there are few studies about the variability comprising sequence changes and methylation status at the DNA level, generated by the culture of A. thaliana cells and tissues. In this work, two types of highly reproducible molecular markers, modified methylation sensitive AFLP (metAFLP) and transposon methylation display (TMD) have been used for the first time in this species to analyze the nucleotide and cytosine methylation changes induced by transformation and tissue culture protocols. We found significantly higher average methylation values (7.5%) in regenerated and transgenic plants when compared to values obtained from seed derived plants (3.2%) and that the main component of the somaclonal variation present in Arabidopsis clonal plants is genetic rather than epigenetic. However, we have found that the Arabidopsis regenerated and transgenic plants had a higher number of non-fully methylated sites flanking transposable elements than the control plants, and therefore, their mobilization can be facilitated. These data provide further evidence that changes in nucleotide sequence and methylation status occur in the Arabidopsis genome during in vitro tissue culture frequently enough to be an important source of variation in this species.

Structure and Function of Caltrin (Calcium Transport Inhibitor) Proteins.

Caltrin (calcium transport inhibitor) is a family of small and basic proteins of the mammalian seminal plasma which bind to sperm cells during ejaculation and inhibit the extracellular Ca2+ uptake, preventing the premature acrosomal exocytosis and hyperactivation when sperm cells ascend through the female reproductive tract. The binding of caltrin proteins to specific areas of the sperm surface suggests the existence of caltrin receptors, or precise protein-phospholipid arrangements in the sperm membrane, distributed in the regions where Ca2+ influx may take place. However, the molecular mechanisms of recognition and interaction between caltrin and spermatozoa have not been elucidated. Therefore, the aim of this article is to describe in depth the known structural features and functional properties of caltrin proteins, to find out how they may possibly interact with the sperm membranes to control the intracellular signaling that trigger physiological events required for fertilization.

Structural Prediction and In Silico Physicochemical Characterization for Mouse Caltrin I and Bovine Caltrin Proteins.

It is known that caltrin (calcium transport inhibitor) protein binds to sperm cells during ejaculation and inhibits extracellular Ca2+ uptake. Although the sequence and some biological features of mouse caltrin I and bovine caltrin are known, their physicochemical properties and tertiary structure are mainly unknown. We predicted the 3D structures of mouse caltrin I and bovine caltrin by molecular homology modeling and threading. Surface electrostatic potentials and electric fields were calculated using the Poisson-Boltzmann equation. Several different bioinformatics tools and available web servers were used to thoroughly analyze the physicochemical characteristics of both proteins, such as their Kyte and Doolittle hydropathy scores and helical wheel projections. The results presented in this work significantly aid further understanding of the molecular mechanisms of caltrin proteins modulating physiological processes associated with fertilization.

Rat caltrin protein modulates the acrosomal exocytosis during sperm capacitation.

Caltrin is a small and basic protein of the seminal vesicle secretion that inhibits sperm calcium uptake. The influence of rat caltrin on sperm physiological processes related to fertilizing competence was studied by examining its effect on 1) spontaneous acrosomal exocytosis, 2) protein tyrosine phosphorylation, and 3) sperm-egg interaction. Results show that the presence of caltrin during in vitro capacitation both reduced the rate of spontaneous acrosomal exocytosis without altering the pattern of protein tyrosine phosphorylation, and enhanced the sperm ability to bind to the zona pellucida (ZP). The significantly higher proportion of sperm with intact acrosome observed in the presence of caltrin was accompanied by a strong inhibition in the acrosomal hyaluronidase release. Enhancement of sperm-ZP binding was evident by the increase in the percentage of eggs with bound spermatozoa as well as in the number of bound sperm per egg. Similar results were obtained when the assays were performed using spermatozoa preincubated with caltrin and then washed to remove the unbound protein, indicating that the sperm-bound caltrin was the one involved in both acrosomal exocytosis inhibition and sperm-ZP binding enhancement. Caltrin bound to the sperm head was partially released during the acrosomal exocytosis induced by Ca-ionophore A23187. Indirect immunofluorescence and immunoelectron microscopy studies revealed that caltrin molecules distributed on the dorsal sperm surface disappeared after ionophore exposure, whereas those on the ventral region remained in this localization after the treatment. The present data suggest that rat caltrin molecules bound to the sperm head during ejaculation prevent the occurrence of the spontaneous acrosomal exocytosis along the female reproductive tract. Consequently, more competent spermatozoa with intact and functional acrosome would be available in the oviduct to participate in fertilization.

beta-Microseminoprotein in human spermatozoa and its potential role in male fertility.

beta-Microseminoprotein (MSMB) is one of the most abundant proteins in human seminal plasma. The objectives of this study were: (1) to purify MSMB from seminal plasma (SP) and generate antibodies against the pure protein; (2) to investigate the interaction of MSMB with ejaculated spermatozoa and its possible effect on the spontaneous acrosome reaction (AR); and (3) to quantify MSMB content in SP and examine its relationship with the clinical sperm parameters. MSMB was purified from SP and its presence on the sperm surface was examined by indirect immunofluorescence using a specific polyclonal antibody. The effect of MSMB on the AR was evaluated using guinea pig epididymal spermatozoa as a model. MSMB quantification assay was performed with a two-site binding ELISA using two polyclonal antibodies against MSMB. MSMB was assessed in semen samples from fertile donors (controls) and subfertile patients according to World Health Organization criteria. MSMB was detected on the sperm surface and mainly localized to the acrosomal region of the head and neck. A significant spontaneous AR inhibition was observed when guinea pig epididymal spermatozoa were preincubated with MSMB. Finally, MSMB was significantly increased in subfertile patients when compared with fertile controls (P<0.02). The association of MSMB to the sperm surface, the inhibitor effect on the spontaneous AR and the increased MSMB levels found in SP in subfertile men suggests a relationship between this protein and semen quality and a possible role in the process of fertilization.

The activity of a developmentally regulated cysteine proteinase is required for cyst wall formation in the primitive eukaryote Giardia lamblia.

Giardia is an intestinal parasite that belongs to the earliest diverging branch of the eukaryotic lineage of descent. Giardia undergoes adaptation for survival outside the host's intestine by differentiating into infective cysts. Encystation involves the synthesis and transport of cyst wall constituents to the plasma membrane for release and extracellular organization. Nevertheless, little is known about the molecular events related to cyst wall biogenesis in Giardia. Among the components of the cyst wall there are two proteins that we have previously identified and characterized: CWP1 (26 kDa) and CWP2 (39 kDa). Expression of these proteins is coordinately induced, and both concentrated within encystation-specific secretory vesicles before their extracellular polymerization. Although highly similar to each other at the amino terminus, CWP2 includes a COOH-terminal 121-amino acid extension. Here, we show that this extension, rich in basic residues, is cleaved from CWP2 before cyst wall formation by an intracellular cysteine proteinase activity, which is induced during encystation like CWPs. Specific inhibitors prevent release of cyst wall materials, abolishing cyst wall formation. We also report the purification, cloning, and characterization of the encystation-specific cysteine proteinase responsible for the proteolytic processing of CWP2, which is homologue to lysosomal cathepsin C. Encystation-specific cysteine proteinase ESCP possesses unique characteristics compared with cathepsins from higher eukaryotes, such as a transmembrane domain and a short cytoplasmic tail. These features make this enzyme the most divergent cathepsin C identified to date and provide new insights regarding cyst wall formation in Giardia.