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Recently, the role of trace elements in the pathophysiology of obesity, insulin resistance (IR), and metabolic diseases has been explored. In this cross-sectional study, we aimed to assess the association of overweight, obesity, and cardiometabolic traits with serum copper (Cu) levels in 346 Mexican adults. Serum Cu level was measured by inductively coupled plasma mass spectrometry (ICP-MS). Anthropometrical data were collected, and biochemical parameters were measured. The triglyceride-glucose (TyG) index was used as a surrogate marker to evaluate IR. Overweight and obesity status was positively associated with the serum Cu level (ß = 19.434 ± 7.309, p = 0.008). Serum Cu level was observed to have a positive association with serum triglycerides level (ß = 0.160 ± 0.045, p < 0.001) and TyG (ß = 0.001 ± 0.001, p < 0.001). Additionally, high serum Cu level was positively associated with overweight and obesity status (odds ratio [OR] = 1.9, 95% confidence interval [95% CI] 1.1-3.4, p = 0.014), hypertriglyceridemia (OR = 3.0, 95% CI 1.7-5.3, p < 0.001), and IR (OR = 2.6, 95% CI 1.4-4.6, p = 0.001). In conclusion, our results suggest that overweight, obesity, hypertriglyceridemia, and IR are positively associated with serum Cu levels in Mexican adults.

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Long-term potentiation (LTP) induced by theta-burst stimulation (TBS) undergoes postweaning developmental changes partially linked to GABAergic circuit maturation. Endogenous vasoactive intestinal peptide (VIP) acting on its VPAC1 receptor strongly influences LTP induced by theta-burst stimulation (TBS), an effect dependent on GABAergic transmission. Although VPAC1 receptor levels are developmentally regulated during embryogenesis, their variation along postweaning development is unknown, as is the VPAC1 modulation of LTP or its relation to hippocampal GABAergic circuit maturation. As such, we investigated how VPAC1 modulation of LTP adjusts from weaning to adulthood along with GABAergic circuit maturation. As described, LTP induced by mild TBS (5 bursts, 4 pulses delivered at 100 Hz) was increasingly greater from weaning to adulthood. The influence of the VPAC1 receptor antagonist PG 97-269 (100 nM) on TBS-induced LTP was much larger in juvenile (3-week-old) than in young adult (6-7-week-old) or adult (12-week-old) rats. This effect was not associated with a developmental decrease in synaptic VPAC1 receptor levels. However, an increase in pre and post-synaptic GABAergic synaptic markers suggests an increase in the number of GABAergic synaptic contacts that is more prominent than the one observed in glutamatergic connections during this period. Conversely, endogenous VPAC2 receptor activation did not significantly influence TBS-induced LTP. VPAC2 receptor levels enhance pronouncedly during postweaning development, but not at synaptic sites. Given the involvement of VIP interneurons in several aspects of hippocampal-dependent learning, neurodevelopmental disorders, and epilepsy, this could provide important insights into the role of VIP modulation of hippocampal synaptic plasticity during normal and altered brain development potentially contributing to epileptogenesis.

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Non-epileptic seizures are identified as a common epileptogenic trigger. Early metaplasticity following seizures may contribute to epileptogenesis by abnormally altering synaptic strength and homeostatic plasticity. We now studied how in vitro epileptiform activity (EA) triggers early changes in CA1 long-term potentiation (LTP) induced by theta-burst stimulation (TBS) in rat hippocampal slices and the involvement of lipid rafts in these early metaplasticity events. Two forms of EA were induced: (1) interictal-like EA evoked by Mg2+ withdrawal and K+ elevation to 6 mM in the superfusion medium or (2) ictal-like EA induced by bicuculline (10 µM). Both EA patterns induced and LTP-like effect on CA1 synaptic transmission prior to LTP induction. LTP induced 30 min post EA was impaired, an effect more pronounced after ictal-like EA. LTP recovered to control levels 60 min post interictal-like EA but was still impaired 60 min after ictal-like EA. The synaptic molecular events underlying this altered LTP were investigated 30 min post EA in synaptosomes isolated from these slices. EA enhanced AMPA GluA1 Ser831 phosphorylation but decreased Ser845 phosphorylation and the GluA1/GluA2 ratio. Flotillin-1 and caveolin-1 were markedly decreased concomitantly with a marked increase in gephyrin levels and a less prominent increase in PSD-95. Altogether, EA differentially influences hippocampal CA1 LTP thorough regulation of GluA1/GluA2 levels and AMPA GluA1 phosphorylation suggesting that altered LTP post-seizures is a relevant target for antiepileptogenic therapies. In addition, this metaplasticity is also associated with marked alterations in classic and synaptic lipid raft markers, suggesting these may also constitute promising targets in epileptogenesis prevention.

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Purpose: To report on a patient with Stargardt disease (STGD1) and with an intronic mutation in the ABCA4 gene. Patients and Methods: A 69-year-old female patient presented to the clinic complaining of progressive vision loss. The ophthalmic evaluation was remarkable for a best corrected visual acuity of counting fingers at 5' in the right eye and 3' in the left eye. Imaging revealed deep extensive atrophy of the central macula, epithelial pigment hyperplasia, and other areas of multifocal atrophy in the right eye. Furthermore, fundus autofluorescence imaging of the macula showed central hypoautofluorescence with bilateral expansion to the periphery in both eyes. A full-field electroretinogram showed a normal rod response, with decreased cone response, bilaterally. Genetic testing was positive for a homozygous intronic mutation in the ABCA4 gene of the variant c.5714+5G>A. Conclusions and Importance: Patients with STGD1 due to presumed mild or moderate mutations in the ABCA4 gene may have a more severe presentation and progression of the disease. Based on this, the first report of a genotype-phenotype correlation in a Puerto Rican patient with STGD1 disease, genotyping all Puerto Rican patients is warranted.

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Objectives: In this study, we identify knowledge, attitudes, and practices (KAPs) of the people of the State of Tabasco (Mexico) as they influence transmission and mitigation of COVID-19. Methods: We used an Internet-based survey (N=1848) from March to July 2021, with a probabilistic sampling stratified by municipalities. Results: Most respondents demonstrated knowledge about the etiology and symptoms of COVID-19 - they assume that anyone can contract the disease, and at least 53.5% knew that the cause is a virus. They believed that it constitutes a problem for their community due to its easy transmission; however, they consider themselves to be only at medium risk. They have adopted preventive measures such as handwashing, staying home, and social distancing; however, when analyzing protecting the community, they refer to other people as having responsibility for preventing disease spread. Conclusions: Interventions focused on social and cultural contexts are required. Sociodemographic and ideological factors influence disinformation, limited interventions, and cognitive dissonance. This type of research contributes to discovering areas of opportunity for government and public health organizations to prioritize practical actions and reduce eventual outbreaks.

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Long-term potentiation (LTP) is a highly studied cellular process, yet determining the transduction and gamma aminobutyric acid (GABAergic) pathways that are the essential versus modulatory for LTP elicited by theta burst stimulation (TBS) in the hippocampal Cornu Ammonis 1 (CA1) area is still elusive, due to the use of different TBS intensities, patterns or different rodent/cellular models. We now characterised the developmental maturation and the transduction and GABAergic pathways required for mild TBS-induced LTP in hippocampal CA1 area in male rats. LTP induced by TBS (5x4) (five bursts of four pulses delivered at 100 Hz) lasted for up to 3 h and was increasingly larger from weaning to adulthood. Stronger TBS patterns - TBS (15x4) or three TBS (15x4) separated by 6 min induced nearly maximal LTP not being the best choice to study the value of LTP-enhancing drugs. LTP induced by TBS (5x4) in young adults was fully dependent on N-methyl D-aspartate (NMDA) receptor and calmodulin-dependent protein kinase II (CaMKII) activity but independent of protein kinase A (PKA) or protein kinase C (PKC) activity. Furthermore, it was partially dependent on GABAB receptor activation and was potentiated by GABAA receptor blockade and less by GAT-1 transporter blockade. AMPA GluA1 phosphorylation on Ser831 (CaMKII target) but not GluA1 Ser845 (PKA target) was essential for LTP expression. The phosphorylation of the Kv4.2 channel was observed at Ser438 (CaMKII target) but not at Thr602 or Thr607 (ERK/MAPK pathway target). This suggests that cellular kinases like PKA, PKC, or kinases of the ERK/MAPK family although important modulators of TBS (5x4)-induced LTP may not be essential for its expression in the CA1 area of the hippocampus.

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OBJECTIVE: To describe the characteristics upon presentation of a cohort of Hispanic patients living in Puerto Rico with ocular mucous membrane pemphigoid (MMP). METHODS: Retrospective chart review of subjects with ocular MMP at one academic institution and one private practice. Patients with clinical evidence of ocular MMP, along with a positive mucous membrane biopsy revealing linear antibody or C3 deposition in the basement membrane zone, or with a positive indirect immunofluorescence assay were included. Descriptive statistical analysis was performed. RESULTS: Eight patients with ocular mucous membrane pemphigoid were identified. The median age upon presentation was 60.5 years; however, 2 patients were in their 4th decade and one in the 5th decade of life. Females constituted 62.5% of the cohort. All patients presented with stage III ocular MMP in at least one eye and 50% had history of trichiasis. Seven out of eight patients (87.5%) had extraocular symptoms for a median duration of 36 months (range 2-144 months). The most common site of extraocular involvement was the oropharynx, present in 87.5% of patients. CONCLUSION: Our results suggest that in Puerto Rico ocular MMP most commonly presents in the seventh decade of life. The presence of symblepharon, trichiasis or oropharyngeal mucosal disease should prompt further evaluation and consideration for immunopathological tissue analysis and an IIF assay.

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AIMS: Myxomas are benign soft tissue tumours resembling primitive mesenchyme. They rarely involve ocular structures, and have been recognized in the conjunctiva, eyelids, cornea, and orbit. The aim of this study was to investigate the clinicopathological features of seven patients with primary conjunctival myxoma seen at Dr Luis Sánchez Bulnes Hospital, an ophthalmological referral centre in Mexico City. METHODS AND RESULTS: We reviewed the clinical, histochemical and immunohistochemical studies of patients with documented myxoma of the conjunctiva diagnosed in our hospital. Seven conjunctival myxomas were retrieved from 5923 conjunctival biopsies (0.1%). The mean age of patients was 40 years, with a range of 27-51 years. Females were more frequently affected, and none of our patients had systemic disease. The left eye was involved in five cases, and most of the lesions were located in the bulbar conjunctiva. Histopathological examination revealed a benign tumour composed of spindle-shaped and stellate-shaped cells immersed within an abundant mucinous matrix with sparse vessels and reticulin fibres. Immunohistochemistry demonstrated positivity for vimentin and negativity for smooth muscle actin, SOX10 and GLUT1 in myxoma cells of all cases. S100 was found to be positive in four cases, and muscle-specific-actin in three cases. CONCLUSIONS: Conjunctival myxomas are uncommon tumours. For accurate diagnosis, histopathological examination is mandatory. The treatment of choice is surgical removal, and the prognosis is excellent.

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Cannabinoid receptor 1 (CB1R) is widely distributed in the central nervous system, in excitatory and inhibitory neurons, and in astrocytes. CB1R agonists impair cognition and prevent long-term potentiation (LTP) of synaptic transmission, but the influence of endogenously formed cannabinoids (eCBs) on hippocampal LTP remains ambiguous. Based on the knowledge that eCBs are released upon high frequency neuronal firing, we hypothesized that the influence of eCBs upon LTP could change according to the paradigm of LTP induction. We thus tested the influence of eCBs on hippocampal LTP using two θ-burst protocols that induce either a weak or a strong LTP. LTP induced by a weak-θ-burst protocol is facilitated while preventing the endogenous activation of CB1Rs. In contrast, the same procedures lead to inhibition of LTP induced by the strong-θ-burst protocol, suggestive of a facilitatory action of eCBs upon strong LTP. Accordingly, an inhibitor of the metabolism of the predominant eCB in the hippocampus, 2-arachidonoyl-glycerol (2-AG), facilitates strong LTP. The facilitatory action of endogenous CB1R activation does not require the activity of inhibitory A1 adenosine receptors, is not affected by inhibition of astrocytic metabolism, but involves inhibitory GABAergic transmission. The continuous activation of CB1Rs via exogenous cannabinoids, or by drugs known to prevent metabolism of the non-prevalent hippocampal eCB, anandamide, inhibited LTP. We conclude that endogenous activation of CB1Rs by physiologically formed eCBs exerts a fine-tune homeostatic control of LTP in the hippocampus, acting as a high-pass filter, therefore likely reducing the signal-to-noise ratio of synaptic strengthening.

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BACKGROUND: Dialysis patients are classified according to their peritoneal permeability as low transporter (LT, low solute permeability) or high transporter (HT, high solute permeability). Tight junction (TJ) proteins are critical to maintain ions, molecules and water paracellular transport through peritoneum. Exposure to peritoneal dialysis solutions causes damage to TJ in human peritoneal mesothelial cells (HPMCs). We analyzed the quantity, distribution and function of TJ proteins: claudin-1, -2 and -8, ZO-1 and occludin, in HPMC cultures from LT and HT patients. Since all-trans retinoic acid (ATRA) might modify the expression of TJ proteins, we studied its effect on HPMCs. METHODS: Control HPMCs were isolated from human omentum, while HT or LT cells were obtained from dialysis effluents. Cells were cultured in presence of ATRA 0, 50 or 100 nM. Transepithelial electrical resistance (TER) measurement, immunostaining and Western blot analyses were performed. RESULTS: HT exhibited lower TER than control and LT monolayers. Immunofluorescence for TJ was weak and discontinuous along the cell contour, in LT and HT. Furthermore, claudin-1, occludin and ZO-1 expressions were decreased. In all groups, claudin-2 was localized at nuclei. We observed that ATRA improved TJ distribution and increased TJ expression in HT. This retinoid did not modify claudin-2 and -8 expressions. All-trans retinoic acid decreased TER in HT, but had no effect in LT. CONCLUSIONS: Tight junctions were altered in HPMCs from dialyzed patients. The HT monolayer has lower TER than LT, which might be associated with the peritoneal permeability in these patients. ATRA might be a therapeutic alternative to maintain mesothelial integrity, since it improved TJ localization and expression.

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Patients undergoing continuous ambulatory peritoneal dialysis are classified according to their peritoneal permeability as low transporter (low solute permeability) or High transporter (high solute permeability). Factors that determine the differences in permeability between them have not been fully disclosed. We investigated morphological features of cultured human peritoneal mesothelial cells from low or high transporter patients and its response to All trans retinoic Acid (ATRA, vitamin A active metabolite), as compared to non-uremic human peritoneal mesothelial cells. Control cells were isolated from human omentum. High or low transporter cells were obtained from dialysis effluents. Cells were cultured in media containing ATRA (0, 50, 100 or 200 nM). We studied length and distribution of microvilli and cilia (scanning electron microscopy), epithelial (cytokeratin, claudin-1, ZO-1 and occludin) and mesenchymal (vimentin and α-smooth muscle actin) transition markers by immunofluorescence and Western blot, and transforming growth factor ß1 expression by Western blot. Low and high transporter exhibited hypertrophic cells, reduction in claudin-1, occludin and ZO-1 expression, cytokeratin and vimentin disorganization and positive α-smooth muscle actin label. Vimentin, α-smooth muscle actin and transforming growth factor-ß1 were overexpressed in low transporter. Ciliated cells were diminished in low and high transporters. Microvilli number and length were severely reduced in high transporter. ATRA reduced hypertrophic cells number in low transporter. It also improved cytokeratin and vimentin organization, decreased vimentin and α-smooth muscle actin expression, and increased claudin 1, occludin and ZO-1 expression, in low and high transporter. In low transporter, ATRA reduced transforming growth factor-ß1 expression. ATRA augmented percentage of ciliated cells in low and high transporter. It also augmented cilia length in high transporter. Alterations in structure, epithelial mesenchymal markers and transforming growth factor-ß1 expression were differential between low and high transporter. Beneficial effects of ATRA were improved human peritoneal mesothelial cells morphology tending to normalize structures.

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Se realizó un estudio experimental con el objetivo de evaluar el efecto analgésico del extracto acuoso liofilizado de las hojas de Bixa orellana L, a dosis de 100 y 150 mgkg-l administrado por vía oraL Para el desarrollo del mismo se utilizaron los Métodos de "Hot-plate" y "Contorsiones abdominales". Los animales seleccionados fueron ratones albinos machos de la cepa Balb/C53, con un peso corporal comprendido entre 23.67+ l.03g. Se utilizaron como controles positivos paracetamol e indometacina a dosis de 400 mgkg-l y 10 mgKg-l, respectivamente. Bixa orellana L. presenta actividad analgésica a nivel periférico, en el modelo de contorsiones abdominales, directamente proporcional a la dosis, bajo las condiciones experimentales.

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Se seleccionó al género Erythroxylum como uno de los más promisorios para estudios de procesos antivirales. Las especies de este género fueron colectadas en diferentes épocas de los años 2000 y 2001 en varias localidades de la provincia de Pinar del Río, Cuba. Se estudió la composición fitoquímica de las hojas y extractos de las especies Erythroxylum confusum Britt, Erythroxylum alaternifolium var. alaternifolium y Erythroxylum minutifolium Griseb var. minutifolium, estos 2 últimos endémicos de Cuba. Tanto para las hojas como para los extractos, se encontró correspondencia en la composición de metabolitos presentes: flavonoides, alcaloides, triterpenos y/o esteroides y fenoles y/o taninos, entre las especies tamizadas y lo informado en la literatura para el género(AU)

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Se seleccionó al género Erythroxylum como uno de los más promisorios para estudios de procesos antivirales. Las especies de este género fueron colectadas en diferentes épocas de los años 2000 y 2001 en varias localidades de la provincia de Pinar del Río, Cuba. Se estudió la composición fitoquímica de las hojas y extractos de las especies Erythroxylum confusum Britt, Erythroxylum alaternifolium var. alaternifolium y Erythroxylum minutifolium Griseb var. minutifolium, estos 2 últimos endémicos de Cuba. Tanto para las hojas como para los extractos, se encontró correspondencia en la composición de metabolitos presentes: flavonoides, alcaloides, triterpenos y/o esteroides y fenoles y/o taninos, entre las especies tamizadas y lo informado en la literatura para el género

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Se describe el tamizaje fitoquímico preliminar de las hojas y ramas de la Helietta cubensis Monach -Moldenke, especie endémica cubana que crece en la cima de los mogotes de Pinar del Río. La detección de los metabolitos secundarios se realizó mediante reactivos de identificación específicos para cada familia de compuestos. En ambas partes de la especie se identificaron en alta abundancia flavonoides y lactonas/coumarinas; en baja concentración se detectaron triterpenos/esteroides, lípidos/aceites esenciales, saponinas y carotenos y no la presencia de aminas y alcaloides. Mediante el análisis por cromatografía de capa fina se pudo corroborar los resultados obtenidos en la identificación de alcaloides, flavonoides y coumarinas. En general, los resultados obtenidos fueron homogéneos para ambas partes de la planta, y constituyen el primer reporte de la composición química para esta especie(AU)

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Se describe el tamizaje fitoquímico preliminar de las hojas y ramas de la Helietta cubensis Monach -Moldenke, especie endémica cubana que crece en la cima de los mogotes de Pinar del Río. La detección de los metabolitos secundarios se realizó mediante reactivos de identificación específicos para cada familia de compuestos. En ambas partes de la especie se identificaron en alta abundancia flavonoides y lactonas/coumarinas; en baja concentración se detectaron triterpenos/esteroides, lípidos/aceites esenciales, saponinas y carotenos y no la presencia de aminas y alcaloides. Mediante el análisis por cromatografía de capa fina se pudo corroborar los resultados obtenidos en la identificación de alcaloides, flavonoides y coumarinas. En general, los resultados obtenidos fueron homogéneos para ambas partes de la planta, y constituyen el primer reporte de la composición química para esta especie

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