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1.
Int J Psychol ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38576093

RESUMO

Longitudinal studies suggest the psychological difficulties precipitated by the COVID-19 pandemic have gradually declined, but our understanding of the factors that predict change in mental health is limited. We evaluated the mental health of Mexican college students during the early stage of the pandemic and 4 months later, as well as predictors of change in students' mental health. Participants were 648 students (71% women, Mage = 21.46) from a private University in Northern Mexico who completed online surveys from May 2020 to September 2020. Students' self-reported levels of mental health symptoms (depression, anxiety and post-traumatic stress disorder) significantly decreased from May to September. Poor physical health, more COVID-related worry and higher initial levels of peer social support predicted less change in psychological symptoms. On the other hand, more hours of sleep per night and a pre-existing mental health diagnosis predicted steeper decreases in symptoms. Findings suggest reductions in mental health difficulties that are consistent with theoretical frameworks of resilience among Mexican college students. In addition, results underscore the interplay between physical, psychological and social functioning, and the need for continued monitoring of mental health and intervention efforts that address physical health, sleep and pandemic-related worry in University settings.

2.
Front Oncol ; 14: 1304690, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38634051

RESUMO

The main objective of the National Project for Research and Incidence of Childhood Leukemias is to reduce early mortality rates for these neoplasms in the vulnerable regions of Mexico. This project was conducted in the states of Oaxaca, Puebla, and Tlaxcala. A key strategy of the project is the implementation of an effective roadmap to ensure that leukemia patients are the target of maximum benefit of interdisciplinary collaboration between researchers, clinicians, surveyors, and laboratories. This strategy guarantees the comprehensive management of diagnosis and follow-up samples of pediatric patients with leukemia, centralizing, managing, and analyzing the information collected. Additionally, it allows for a precise diagnosis and monitoring of the disease through immunophenotype and measurable residual disease (MRD) studies, enhancing research and supporting informed clinical decisions for the first time in these regions through a population-based study. This initiative has significantly improved the diagnostic capacity of leukemia in girls, boys, and adolescents in the regions of Oaxaca, Puebla, and Tlaxcala, providing comprehensive, high-quality care with full coverage in the region. Likewise, it has strengthened collaboration between health institutions, researchers, and professionals in the sector, which contributes to reducing the impact of the disease on the community.

3.
Pap. psicol ; 45(1): 48-55, Ene-Abr, 2024. tab, ilus
Artigo em Inglês | IBECS | ID: ibc-229716

RESUMO

Borderline personality (BPD) features and intimate partner violence (IPV) have been seen associated, focusing the research specially into perpetrators. The achievement of this systematic review is to analyze this relation in both victims and perpetrators, using 17 scientific articles published between 2017 and 2021 from different data bases. Most studies were focused on perpetrators, in which both men and women were equally represented as perpetrators. Instead, studies about victims were focused on women. Throughout this review, different factors observed in people with BPD traits who are victims or perpetrators of IPV are mentioned, finding particularities in each profile. These findings allow increase knowledge about the relationship between BPD and IPV, promoting a greater understanding that impacts positively on clinical intervention in this population.(AU)


Los rasgos límites de personalidad (TLP) se han visto asociados a violencia en la pareja, con investigaciones centradas especialmente en quienes la ejercen. El objetivo de esta revisión sistemática es analizar esta relación tanto en víctimas como en perpetradores, utilizando 17 artículos científicos publicados entre 2017 y 2021 en distintas bases de datos. Los estudios analizados se centraron mayoritariamente en perpetradores, encontrándose tanto hombres como mujeres igualmente representadas. En cambio, los estudios sobre víctimas atendían por lo general a mujeres. A lo largo de esta revisión, se mencionan distintos factores observados en personas que presentan rasgos TLP y ejercen o son víctimas de violencia de pareja, encontrando particularidades en cada perfil. Este trabajo permite incrementar el conocimiento sobre la relación existente entre TLP y violencia de pareja, fomentando una mayor comprensión que repercuta positivamente en la intervención clínica de esta población.(AU)


Assuntos
Humanos , Masculino , Feminino , Saúde Mental , Vítimas de Crime , Violência por Parceiro Íntimo , Transtorno da Personalidade Borderline , Psicologia , Psiquiatria
4.
Plant Cell ; 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38518291
5.
Sci Data ; 11(1): 274, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448454

RESUMO

Forest biomass is an essential resource in relation to the green transition and its assessment is key for the sustainable management of forest resources. Here, we present a forest biomass dataset for Europe based on the best available inventory and satellite data, with a higher level of harmonisation and spatial resolution than other existing data. This database provides statistics and maps of the forest area, biomass stock and their share available for wood supply in the year 2020, and statistics on gross and net volume increment in 2010-2020, for 38 European countries. The statistics of most countries are available at a sub-national scale and are derived from National Forest Inventory data, harmonised using common reference definitions and estimation methodology, and updated to a common year using a modelling approach. For those counties without harmonised statistics, data were derived from the State of Europe's Forest 2020 Report at the national scale. The maps are coherent with the statistics and depict the spatial distribution of the forest variables at 100 m resolution.


Assuntos
Florestas , Madeira , Biomassa , Bases de Dados Factuais , Europa (Continente)
6.
Appl Environ Microbiol ; 90(4): e0227223, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38501669

RESUMO

Wastewater-based epidemiology has emerged as a valuable tool for monitoring respiratory viral diseases within communities by analyzing concentrations of viral nucleic-acids in wastewater. However, little is known about the fate of respiratory virus nucleic-acids in wastewater. Two important fate processes that may modulate their concentrations in wastewater as they move from household drains to the point of collection include sorption or partitioning to wastewater solids and degradation. This study investigated the decay kinetics of genomic nucleic-acids of seven human respiratory viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), respiratory syncytial virus (RSV), human coronavirus (HCoV)-OC43, HCoV-229E, HCoV-NL63, human rhinovirus (HRV), and influenza A virus (IAV), as well as pepper mild mottle virus (PMMoV) in wastewater solids. Viruses (except for PMMoV) were spiked into wastewater solids and their concentrations were followed for 50 days at three different temperatures (4°C, 22°C, and 37°C). Viral genomic RNA decayed following first-order kinetics with decay rate constants k from 0 to 0.219 per day. Decay rate constants k were not different from 0 for all targets in solids incubated at 4°C; k values were largest at 37°C and at this temperature, k values were similar across nucleic-acid targets. Regardless of temperature, there was limited viral RNA decay, with an estimated 0% to 20% reduction, over the typical residence times of sewage in the piped systems between input and collection point (<1 day). The k values reported herein can be used directly in fate and transport models to inform the interpretation of measurements made during wastewater surveillance.IMPORTANCEUnderstanding whether or not the RNA targets quantified for wastewater-based epidemiology (WBE) efforts decay during transport between drains and the point of sample collection is critical for data interpretation. Here we show limited decay of viral RNA targets typically measured for respiratory disease WBE.


Assuntos
Ácidos Nucleicos , Infecções Respiratórias , Tobamovirus , Vírus , Humanos , Águas Residuárias , Vigilância Epidemiológica Baseada em Águas Residuárias , SARS-CoV-2 , RNA Viral/genética
7.
Plant Cell ; 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38466226

RESUMO

Flowering plant genomes encode four or five DICER-LIKE (DCL) enzymes that produce small interfering RNAs (siRNAs) and microRNAs which function in RNA interference (RNAi). Different RNAi pathways in plants effect transposon silencing, antiviral defense and endogenous gene regulation. DCL2 acts genetically redundantly with DCL4 to confer basal antiviral defense. However, DCL2 may also counteract DCL4, since knockout of DCL4 causes growth defects that are suppressed by DCL2 inactivation. Current models maintain that RNAi via DCL2-dependent siRNAs is the biochemical basis of both effects. Here, we report that DCL2-mediated antiviral resistance and growth defects cannot be explained by the silencing effects of DCL2-dependent siRNAs. Both functions are defective in genetic backgrounds that maintain high levels of DCL2-dependent siRNAs, either with specific point mutations in DCL2 or with reduced DCL2 dosage because of heterozygosity for dcl2 knockout alleles. Intriguingly, all DCL2 functions require its catalytic activity, and the penetrance of DCL2-dependent growth phenotypes in dcl4 mutants correlates with DCL2 protein levels, but not with levels of major DCL2-dependent siRNAs. We discuss this requirement and correlation with catalytic activity, but not with resulting siRNAs, in light of other findings that reveal a DCL2 function in innate immunity activation triggered by cytoplasmic double-stranded RNA.

9.
bioRxiv ; 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38328138

RESUMO

Human type-II topoisomerases, TOP2A and TOP2B, remove transcription associated DNA supercoiling, thereby affecting gene-expression programs, and have recently been associated with 3D genome architecture. Here, we study the regulatory roles of TOP2 paralogs in response to estrogen, which triggers an acute transcriptional induction that involves rewiring of genome organization. We find that, whereas TOP2A facilitates transcription, as expected for a topoisomerase, TOP2B limits the estrogen response. Consistent with this, TOP2B activity is locally downregulated upon estrogen treatment to favor the establishment and stabilization of regulatory chromatin contacts, likely through an accumulation of DNA supercoiling. We show that estrogen-mediated inhibition of TOP2B requires estrogen receptor α (ERα), a non-catalytic function of TOP2A, and the action of the atypical SUMO-ligase ZATT. This mechanism of topological transcriptional-control, which may be shared by additional gene-expression circuits, highlights the relevance of DNA topoisomerases as central actors of genome dynamics.

10.
Ther Adv Urol ; 16: 17562872241229250, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38333072

RESUMO

Background: Pretreatment assessment of patients diagnosed with localized prostate cancer (PCa) is essential for therapeutic decision-making. Currently available staging systems based on prostate-specific antigen (PSA), Gleason score, and clinical stage allow for determining the prognostic characteristics of these patients. Several studies have evaluated the preoperative use of prostate-specific antigen density (PSAD) as a prognostic factor for further risk stratification. To date, the role of PSAD in this setting is still an object of debate. Objectives: The present analysis aimed to assess the predictive potential of PSAD for adverse oncological outcomes after robot-assisted radical prostatectomy (RARP) and to compare its accuracy to preoperative PSA (pPSA). Design and methods: We retrospectively reviewed 427 patients diagnosed with localized PCa who underwent RARP at a single institution between January 2015 and January 2020. Generating receiver operator characteristic (ROC) curves, calculating areas under the curves (AUCs), and using a linear regression model, we analyzed the association of PSAD and pPSA with postoperative positive surgical margins (PSM), Gleason score ⩾ 7, persistent PSA, and biochemical recurrence (BCR), with a median follow-up of 47 months. Results: PSAD showed a significant association with PSM (p < 0.0001), PSA persistence (p < 0.0001), and Gleason ⩾ 7 (p < 0.0001), without being statistically significant in predicting BCR (p = 0.098). The predictive value of PSAD was comparable to pPSA for outcomes of PSA persistence (AUC 0.727 versus 0.771) and Gleason ⩾ 7 (AUC 0.683 versus 0.649). Conclusion: PSAD is a predictive factor for postoperative oncological outcomes of PSM, Gleason score ⩾ 7, and persistence of PSA. Despite the need for further studies, PSAD could be useful as a prognostic parameter in conjunction with established staging systems.


Oncological outcomes in robot-assisted radical prostatectomy: the value of PSA density as a preoperative predictive factor Prostate-specific antigen density (PSAD) has an established role in the diagnostic process of prostate cancer (PCa). However, controversy remains on the assessment of its value as a pretreatment prognostic factor. The aim of our study was to evaluate the predictive ability of PSAD for oncological outcomes in PCa patients treated with robot-assisted radical prostatectomy (RARP) and to compare with the value of preoperative PSA (pPSA). The present analysis showed a significant association of PSAD with positive surgical margins (PSM), Gleason Score >=7 and prostate-specific antigen (PSA) persistence after RARP. Moreover, PSAD demonstrated to perform comparably to pPSA in predicting the outcomes of clinically significant PCa (csPCa) and post-RARP PSA persistence. Therefore, PSAD is considered a preoperative predictive factor potentially useful in conjunction with other previously established prognostic criteria and clinical features.

11.
Front Oncol ; 14: 1304633, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38420017

RESUMO

Background: A heterogeneous geographic distribution of childhood acute lymphoblastic leukemia (ALL) cases has been described, possibly, related to the presence of different environmental factors. The aim of the present study was to explore the geographical distribution of childhood ALL cases in Greater Mexico City (GMC). Methods: A population-based case-control study was conducted. Children <18 years old, newly diagnosed with ALL and residents of GMC were included. Controls were patients without leukemia recruited from second-level public hospitals, frequency-matched by sex, age, and health institution with the cases. The residence address where the patients lived during the last year before diagnosis (cases) or the interview (controls) was used for geolocation. Kulldorff's spatial scan statistic was used to detect spatial clusters (SCs). Relative risks (RR), associated p-value and number of cases included for each cluster were obtained. Results: A total of 1054 cases with ALL were analyzed. Of these, 408 (38.7%) were distributed across eight SCs detected. A relative risk of 1.61 (p<0.0001) was observed for the main cluster. Similar results were noted for the remaining seven ones. Additionally, a proximity between SCs, electrical installations and petrochemical facilities was observed. Conclusions: The identification of SCs in certain regions of GMC suggest the possible role of environmental factors in the etiology of childhood ALL.

13.
Sci Rep ; 14(1): 241, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167966

RESUMO

We present an extensive study of the joint effects of heterogeneous social agents and their heterogeneous social links in a bounded confidence opinion dynamics model. The full phase diagram of the model is explored for two different network's topologies and compared to two opposed extreme cases: on one hand, the heterogeneous agents constitute a mixed population and on the other, their interactions are modeled by a lattice. The results show that when agents prone to compromise coexist with close-minded ones, the steady state of the dynamics shows coexistent phases. In particular, unlike the case of homogeneous agents in networks, or heterogeneous agents in a fully mixed population, it is possible that the society ends up in consensus around one extreme opinion. Moreover, during the dynamics, the consensus may be overturned from one extreme to the other of the opinion space. We also show that the standard order parameter, the normalized average size of the largest opinion cluster, may be misleading in this case, as it hides the existence of these phases. The phase where the opinion of the society is overturned does not require the presence of agents with special characteristics, (stubborn, extremists, etc.); it results from the interplay of agents which have agreed on an extreme opinion with the remaining group that holds the opposite one. Among the former, some may be prone to compromise with other agents which are out of the majority group, these agents, according to their location in the network, may act like bridges between the two groups and slowly attract the whole society to the other extreme.

14.
Viruses ; 16(1)2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38275975

RESUMO

BACKGROUND: The inovirus Pf4 is a lysogenic bacteriophage of Pseudomonas aeruginosa (Pa). People with Cystic Fibrosis (pwCF) experience chronic airway infection with Pa and a significant proportion have high numbers of Pf4 in their airway secretions. Given the known severe damage in the airways of Pa-infected pwCF, we hypothesized a high Pf4 burden can affect airway healing and inflammatory responses. In the airway, basal epithelial cells (BCs) are a multipotent stem cell population critical to epithelium homeostasis and repair. We sought to investigate the transcriptional responses of BCs under conditions that emulate infection with Pa and exposure to high Pf4 burden. METHODS: Primary BCs isolated from pwCF and wild-type (WT) donors were cultured in vitro and exposed to Pf4 or bacterial Lipopolysaccharide (LPS) followed by transcriptomic and functional assays. RESULTS: We found that BCs internalized Pf4 and this elicits a strong antiviral response as well as neutrophil chemokine production. Further, we found that BCs that take up Pf4 demonstrate defective migration and proliferation. CONCLUSIONS: Our findings are highly suggestive of Pf4 playing a role in the pathogenicity of Pa in the airways. These findings provide additional evidence for the ability of inoviruses to interact with mammalian cells and disrupt cell function.


Assuntos
Fibrose Cística , Infecções por Pseudomonas , Animais , Humanos , Sistema Respiratório , Células Epiteliais , Epitélio , Proliferação de Células , Antivirais , Pseudomonas aeruginosa/fisiologia , Infecções por Pseudomonas/microbiologia , Mamíferos
15.
Ophthalmic Plast Reconstr Surg ; 40(2): 206-211, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37972978

RESUMO

PURPOSE: Lacrimal gland adenoid cystic carcinoma (LGACC) is a rare orbital malignancy with devastating lethality. Neoadjuvant intra-arterial chemotherapy (IACC) has demonstrated cytoreductive effects on LGACC macroscopically, but limited studies have examined cellular and molecular determinants of the cytoreductive effect. This post hoc study assessed apoptotic marker expression on excised tumor specimens after neoadjuvant IACC and globe-sparing resection, emphasizing the examination of tumor margins. METHODS: This retrospective study identified LGACC specimens resected in a globe-sparing technique after neoadjuvant IACC by reviewing the Florida Lions Ocular Pathology database at Bascom Palmer Eye Institute. Histopathology slides of the specimens were re-examined to confirm the diagnosis and identify the tumor margin. Immunofluorescent staining was performed for apoptotic markers, including P53, cleaved caspase-3, cleaved PARP-1, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Positive expression was determined by comparison to the negative control. RESULTS: Tumor specimens from 5 patients met inclusion criteria. All 5 cases were positive at the center and the margin for TUNEL, p53, and cleaved caspase-3. One case did not show positive expression of cleaved PARP-1 at the margin but was positive for the other apoptotic markers. CONCLUSIONS: This post hoc study demonstrated positive staining for multiple apoptotic markers in post-IACC tumor specimens at the tumor center and margin. Apoptotic marker expression along the margins of post-treatment specimens is important, as it may offer surrogate information to speculate on the state of residual cancer cells adjacent to the excision margin inadvertently remaining in the orbit.


Assuntos
Carcinoma Adenoide Cístico , Neoplasias Oculares , Aparelho Lacrimal , Humanos , Carcinoma Adenoide Cístico/tratamento farmacológico , Carcinoma Adenoide Cístico/cirurgia , Caspase 3 , Margens de Excisão , Inibidores de Poli(ADP-Ribose) Polimerases , Estudos Retrospectivos , Proteína Supressora de Tumor p53 , Neoplasias Oculares/tratamento farmacológico
16.
Dev Psychobiol ; 66(1): e22441, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38131241

RESUMO

Perinatal mood disorders are a tremendous burden to childbearing families and treatment with selective serotonin reuptake inhibitor (SSRI) antidepressants is increasingly common. Exposure to SSRIs may affect serotonin signaling and ultimately, microbes that live in the gut. Health of the gut microbiome during pregnancy, lactation, and early infancy is critical, yet there is limited evidence to describe the relationship between SSRI exposure and gut microbiome status in this population. The purpose of this Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA)-compliant scoping review is to assess evidence and describe key concepts regarding whether SSRI exposure affects the maternal and infant gut microbiome. Sources were collected from PubMed, Web of Science, and Scopus databases, and an additional gray literature search was performed. Our search criteria returned only three sources, two rodent models and one human subjects research study. Results suggest that fluoxetine (SSRI) exposure may affect maternal gut microbiome dynamics during pregnancy and lactation. There were no available sources to describe the relationship between perinatal SSRI exposure and the infant gut microbiome. There is a significant gap in the literature regarding whether SSRI antidepressants affect the maternal and infant gut microbiome. Future studies are required to better understand how SSRI antidepressant exposure affects perinatal health.


Assuntos
Microbioma Gastrointestinal , Efeitos Tardios da Exposição Pré-Natal , Lactente , Gravidez , Feminino , Humanos , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Antidepressivos/farmacologia , Lactação
17.
J Dairy Sci ; 107(5): 3306-3318, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38101740

RESUMO

In dairy cows, the lactating mammary glands synthesize serotonin, which acts in an autocrine-paracrine manner in the glands and is secreted into the periphery. Serotonin signaling during lactation modulates nutrient metabolism in peripheral tissues such as adipose and liver. We hypothesized that the elevation of circulating serotonin during lactation would increase nutrient partitioning to the mammary glands, thereby promoting milk production. Our objective was to elevate circulating serotonin via intravenous infusion of the serotonin precursor 5-hydroxytryptophan (5-HTP) to determine its effects on mammary supply and extraction efficiency of AA, and milk components production. Twenty-two multiparous mid-lactation Holstein cows were intravenously infused with 5-HTP (1 mg/kg body weight) or saline, in a crossover design with two 21-d periods. Treatments were infused via jugular catheters for 1 h/d, on d 1 to 3, 8 to 10, and 15 to 17 of each period, to maintain consistent elevation of peripheral serotonin throughout the period. Milk and blood samples were collected in the last 96 h of each period. Whole-blood serotonin concentration was elevated above saline control for 96 h after the last 5-HTP infusion. Dry matter intake was decreased for cows receiving 5-HTP, and on average they lost body weight over the 21-d period, in contrast to saline cows who gained body weight. Milk production and milk protein yield were lower in cows receiving 5-HTP during the 3 infusion days, but both recovered to saline cow yields in the days after. Although milk fat yield exhibited a day-by-treatment interaction, no significant difference occurred on any given day. Milk urea nitrogen concentration was lower in 5-HTP cows on the days following the end of infusions, but not different from saline cows on infusion days. Meanwhile, plasma urea nitrogen was not affected by 5-HTP infusion. Circulating concentrations of AA were overall transiently decreased by 5-HTP, with concentrations mostly returning to baseline within 7 h after the end of 5-HTP infusion. Mammary extraction efficiency of AA was unaffected by 5-HTP infusion. Overall, both lactation performance and circulating AA were transiently reduced in cows infused with 5-HTP, despite sustained elevation of circulating serotonin concentration.


Assuntos
5-Hidroxitriptofano , Lactação , Feminino , Bovinos , Animais , Aminoácidos/metabolismo , Serotonina , Infusões Intravenosas/veterinária , Proteínas do Leite , Ureia/análise , Peso Corporal , Dieta/veterinária
18.
Front Pharmacol ; 14: 1244580, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38074149

RESUMO

Postpartum depression affects many individuals after parturition, and selective serotonin reuptake inhibitors (SSRIs) are often used as the first-line treatment; however, both SSRIs and lactation are independently associated with bone loss due to the role of serotonin in bone remodeling. Previously, we have established that administration of the SSRI fluoxetine during the peripartal period results in alterations in long-term skeletal characteristics. In the present study, we treated mice with either a low or high dose of fluoxetine during lactation to determine the consequences of the perturbation of serotonin signaling during this time period on the dam skeleton. We found that lactational fluoxetine exposure affected both cortical and trabecular parameters, altered gene expression and circulating markers of bone turnover, and affected mammary gland characteristics, and that these effects were more pronounced in the dams that were exposed to the low dose of fluoxetine in comparison to the high dose. Fluoxetine treatment during the postpartum period in rodents had short term effects on bone that were largely resolved 3 months post-weaning. Despite the overall lack of long-term insult to bone, the alterations in serotonin-driven lactational bone remodeling raises the question of whether fluoxetine is a safe option for the treatment of postpartum depression.

19.
Epilepsia ; 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38088023

RESUMO

OBJECTIVE: Epilepsy with eyelid myoclonia (EEM) spectrum is a generalized form of epilepsy characterized by eyelid myoclonia with or without absences, eye closure-induced seizures with electroencephalographic paroxysms, and photosensitivity. Based on the specific clinical features, age at onset, and familial occurrence, a genetic cause has been postulated. Pathogenic variants in CHD2, SYNGAP1, NEXMIF, RORB, and GABRA1 have been reported in individuals with photosensitivity and eyelid myoclonia, but whether other genes are also involved, or a single gene is uniquely linked with EEM, or its subtypes, is not yet known. We aimed to dissect the genetic etiology of EEM. METHODS: We studied a cohort of 105 individuals by using whole exome sequencing. Individuals were divided into two groups: EEM- (isolated EEM) and EEM+ (EEM accompanied by intellectual disability [ID] or any other neurodevelopmental/psychiatric disorder). RESULTS: We identified nine variants classified as pathogenic/likely pathogenic in the entire cohort (8.57%); among these, eight (five in CHD2, one in NEXMIF, one in SYNGAP1, and one in TRIM8) were found in the EEM+ subcohort (28.57%). Only one variant (IFIH1) was found in the EEM- subcohort (1.29%); however, because the phenotype of the proband did not fit with published data, additional evidence is needed before considering IFIH1 variants and EEM- an established association. Burden analysis did not identify any single burdened gene or gene set. SIGNIFICANCE: Our results suggest that for EEM, as for many other epilepsies, the identification of a genetic cause is more likely with comorbid ID and/or other neurodevelopmental disorders. Pathogenic variants were mostly found in CHD2, and the association of CHD2 with EEM+ can now be considered a reasonable gene-disease association. We provide further evidence to strengthen the association of EEM+ with NEXMIF and SYNGAP1. Possible new associations between EEM+ and TRIM8, and EEM- and IFIH1, are also reported. Although we provide robust evidence for gene variants associated with EEM+, the core genetic etiology of EEM- remains to be elucidated.

20.
Sci Rep ; 13(1): 21832, 2023 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-38071334

RESUMO

Antidepressant use is two-fold greater in women compared to men; however, most studies have been performed in male subjects. We aimed to understand the impact of selective serotonin reuptake inhibitors (SSRI, most used antidepressants) on calcium homeostasis and steroid metabolism during the peripartum period. Pregnant sheep (n = 10/group) were treated with vehicle or fluoxetine (most common SSRI) during the last month of gestation. Fluoxetine treatment decreased circulating calcium prior to parturition (8.7 ± 0.1 mg/dL vs 8.2 ± 0.1 mg/dL; P = 0.07). In the control group, total calcium decreased after parturition corresponding to the onset of lactogenesis followed by increase in calcium by day 2 postpartum. Interestingly, this normal transient decrease in circulating calcium was absent in fluoxetine-treated ewes. The steroids cortisol and progesterone were not altered by fluoxetine treatment whereas estradiol was decreased after the onset of treatment (12.4 ± 1.3 vs 9.1 ± 1.2 pg/mL, P = 0.05) and prior to parturition (38.1 ± 8.1 vs 22.3 ± 4.2 pg/mL, P = 0.03). Our hypothesis was supported that fluoxetine treatment alters circulating concentrations of calcium in the peripartum period; however, we surprisingly observed a decrease in estradiol concentrations contrary to reports in in vitro studies.


Assuntos
Cálcio , Fluoxetina , Gravidez , Feminino , Masculino , Animais , Ovinos , Humanos , Fluoxetina/farmacologia , Cálcio/metabolismo , Serotonina/metabolismo , Período Periparto , Antidepressivos/farmacologia , Estradiol , Homeostase
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