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1.
Eur J Med Res ; 29(1): 354, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956703

RESUMO

BACKGROUND: There is sufficient evidence that women with atrial fibrillation (AF) have a greater symptom burden than men with AF and are more likely to experience recurrence after catheter ablation. However, the mechanisms underlying these sex differences are unclear. METHODS: We prospectively enrolled 125 consecutive patients, including 40 non-AF patients and 85 AF patients, who underwent high-density voltage mapping during sinus rhythm and AF patients who underwent first ablation. RESULTS: Overall, 37 (44%) female patients with AF and 24 (60%) female non-AF patients with a mean age of 61.7 ± 11.6 years and 53.6 ± 16.7 years, respectively, were enrolled in this study. The results showed that the atrial voltage of female AF patients was significantly lower than that of male AF patients (1.11 ± 0.58 mV vs. 1.53 ± 0.65 mV; P = 0.003), while there were no significant sex differences in non-AF patients (3.02 ± 0.86 mV vs. 3.21 ± 0.84 mV; P = 0.498). Multiple linear regression analysis revealed that female sex (- 0.29, 95% confidence interval [CI] - 0.64 to - 0.13, P = 0.004) and AF type (- 0.32, 95% CI - 0.69 to - 0.13, P = 0.004) were the only factors independently associated with voltage. Compared with men, women in the paroxysmal AF group had a 3.5-fold greater incidence of recurrence (adjusted hazard ratio 4.49; 95% CI 1.101-18.332, P = 0.036). Both globally and regionally, the results showed that sex-related differences in voltage values occurred prominently in paroxysmal AF patients but not in nonparoxysmal AF patients. CONCLUSION: Sex-related differences in atrial substrates and arrhythmia-free survival were found in paroxysmal AF patients, suggesting the existence of sex-related pathophysiological factors.


Assuntos
Fibrilação Atrial , Átrios do Coração , Humanos , Fibrilação Atrial/fisiopatologia , Feminino , Masculino , Pessoa de Meia-Idade , Átrios do Coração/fisiopatologia , Idoso , Estudos Prospectivos , Ablação por Cateter/métodos , Fatores Sexuais , Adulto , Caracteres Sexuais , Recidiva
2.
CNS Neurosci Ther ; 30(7): e14829, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38961264

RESUMO

AIMS: Paclitaxel (PTX) is extensively utilized in the management of diverse solid tumors, frequently resulting in paclitaxel-induced peripheral neuropathy (PIPN). The present study aimed to investigate sex differences in the behavioral manifestations and underlying pathogenesis of PIPN and search for clinically efficacious interventions. METHODS: Male and female C57BL/6 mice (5-6 weeks and 12 months, weighing 18-30 g) were intraperitoneally (i.p.) administered paclitaxel diluted in saline (NaCl 0.9%) at a dose of 2 mg/kg every other day for a total of 4 injections. Von Frey and hot plate tests were performed before and after administration to confirm the successful establishment of the PIPN model and also to evaluate the pain of PIPN and the analgesic effect of PD-L1. On day 14 after PTX administration, PD-L1 protein (10 ng/pc) was injected into the PIPN via the intrathecal (i.t.) route. To knock down TRPV1 in the spinal cord, adeno-associated virus 9 (AAV9)-Trpv1-RNAi (5 µL, 1 × 1013 vg/mL) was slowly injected via the i.t. route. Four weeks after AAV9 delivery, the downregulation of TRPV1 expression was verified by immunofluorescence staining and Western blotting. The levels of PD-L1, TRPV1 and CGRP were measured via Western blotting, RT-PCR, and immunofluorescence staining. The levels of TNF-α and IL-1ß were measured via RT-PCR. RESULTS: TRPV1 and CGRP protein and mRNA levels were higher in the spinal cords of control female mice than in those of control male mice. PTX-induced nociceptive behaviors in female PIPN mice were greater than those in male PIPN mice, as indicated by increased expression of TRPV1 and CGRP. The analgesic effects of PD-L1 on mechanical hyperalgesia and thermal sensitivity were significantly greater in female mice than in male mice, with calculated relative therapeutic levels increasing by approximately 2.717-fold and 2.303-fold, respectively. PD-L1 and CGRP were partly co-localized with TRPV1 in the dorsal horn of the mouse spinal cord. The analgesic effect of PD-L1 in PIPN mice was observed to be mediated through the downregulation of TRPV1 and CGRP expression following AAV9-mediated spinal cord specific decreased TRPV1 expression. CONCLUSIONS: PTX-induced nociceptive behaviors and the analgesic effect of PD-L1 in PIPN mice were sexually dimorphic, highlighting the significance of incorporating sex as a crucial biological factor in forthcoming mechanistic studies of PIPN and providing insights for potential sex-specific therapeutic approaches.


Assuntos
Antígeno B7-H1 , Peptídeo Relacionado com Gene de Calcitonina , Camundongos Endogâmicos C57BL , Paclitaxel , Doenças do Sistema Nervoso Periférico , Caracteres Sexuais , Canais de Cátion TRPV , Animais , Paclitaxel/toxicidade , Masculino , Feminino , Camundongos , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Canais de Cátion TRPV/metabolismo , Canais de Cátion TRPV/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Antineoplásicos Fitogênicos/toxicidade , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Hiperalgesia/induzido quimicamente , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo
3.
Physiol Meas ; 45(7)2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38959902

RESUMO

Objective.Electrical impedance tomography (EIT) has been used to determine regional lung ventilation distribution in humans for decades, however, the effect of biological sex on the findings has hardly ever been examined. The aim of our study was to determine if the spatial distribution of ventilation assessed by EIT during quiet breathing was influenced by biological sex.Approach.219 adults with no known acute or chronic lung disease were examined in sitting position with the EIT electrodes placed around the lower chest (6th intercostal space). EIT data were recorded at 33 images/s during quiet breathing for 60 s. Regional tidal impedance variation was calculated in all EIT image pixels and the spatial distribution of the values was determined using the established EIT measures of centre of ventilation in ventrodorsal (CoVvd) and right-to-left direction (CoVrl), the dorsal and right fraction of ventilation, and ventilation defect score.Main results.After exclusion of one subject due to insufficient electrode contact, 218 data sets were analysed (120 men, 98 women) (age: 53 ± 18 vs 50 ± 16 yr (p= 0.2607), body mass index: 26.4 ± 4.0 vs 26.4 ± 6.6 kg m-2(p= 0.9158), mean ± SD). Highly significant differences in ventilation distribution were identified between men and women between the right and left chest sides (CoVrl: 47.0 ± 2.9 vs 48.8 ± 3.3% of chest diameter (p< 0.0001), right fraction of ventilation: 0.573 ± 0.067 vs 0.539 ± 0.071 (p= 0.0004)) and less significant in the ventrodorsal direction (CoVvd: 55.6 ± 4.2 vs 54.5 ± 3.6% of chest diameter (p= 0.0364), dorsal fraction of ventilation: 0.650 ± 0.121 vs 0.625 ± 0.104 (p= 0.1155)). Ventilation defect score higher than one was found in 42.5% of men but only in 16.6% of women.Significance.Biological sex needs to be considered when EIT findings acquired in upright subjects in a rather caudal examination plane are interpreted. Sex differences in chest anatomy and thoracoabdominal mechanics may explain the results.


Assuntos
Impedância Elétrica , Caracteres Sexuais , Tórax , Tomografia , Humanos , Masculino , Feminino , Tomografia/métodos , Pessoa de Meia-Idade , Tórax/diagnóstico por imagem , Adulto
4.
Physiol Rep ; 12(13): e16110, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38981849

RESUMO

Pediatric obstructive sleep apnea poses a significant health risk, with potential long-term consequences on cardiovascular health. This study explores the dichotomous nature of neonatal cardiac response to chronic intermittent hypoxia (CIH) between males and females, aiming to fill a critical knowledge gap in the understanding of sex-specific cardiovascular consequences of sleep apnea in early life. Neonates were exposed to CIH until p28 and underwent comprehensive in vivo physiological assessments, including whole-body plethysmography, treadmill stress-tests, and echocardiography. Results indicated that male CIH rats weighed 13.7% less than age-matched control males (p = 0.0365), while females exhibited a mild yet significant increased respiratory drive during sleep (93.94 ± 0.84 vs. 95.31 ± 0.81;p = 0.02). Transcriptomic analysis of left ventricular tissue revealed a substantial sex-based difference in the cardiac response to CIH, with males demonstrating a more pronounced alteration in gene expression compared to females (5986 vs. 3174 genes). The dysregulated miRNAs in males target metabolic genes, potentially predisposing the heart to altered metabolism and substrate utilization. Furthermore, CIH in males was associated with thinner left ventricular walls and dysregulation of genes involved in the cardiac action potential, possibly predisposing males to CIH-related arrhythmia. These findings emphasize the importance of considering sex-specific responses in understanding the cardiovascular implications of pediatric sleep apnea.


Assuntos
Animais Recém-Nascidos , Caracteres Sexuais , Transcriptoma , Masculino , Feminino , Animais , Ratos , Síndromes da Apneia do Sono/genética , Síndromes da Apneia do Sono/metabolismo , Síndromes da Apneia do Sono/fisiopatologia , Ratos Sprague-Dawley , Hipóxia/metabolismo , Hipóxia/genética , Hipóxia/fisiopatologia , MicroRNAs/genética , MicroRNAs/metabolismo , Fatores Sexuais , Coração/fisiopatologia
5.
Nat Commun ; 15(1): 5752, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982135

RESUMO

The early-life organ development and maturation shape the fundamental blueprint for later-life phenotype. However, a multi-organ proteome atlas from infancy to adulthood is currently not available. Herein, we present a comprehensive proteomic analysis of ten mouse organs (brain, heart, lung, liver, kidney, spleen, stomach, intestine, muscle and skin) at three crucial developmental stages (1-, 4- and 8-weeks after birth) acquired using data-independent acquisition mass spectrometry. We detect and quantify 11,533 protein groups across the ten organs and obtain 115 age-related differentially expressed protein groups that are co-expressed in all organs from infancy to adulthood. We find that spliceosome proteins prevalently play crucial regulatory roles in the early-life development of multiple organs, and detect organ-specific expression patterns and sexual dimorphism. This multi-organ proteome atlas provides a fundamental resource for understanding the molecular mechanisms underlying early-life organ development and maturation.


Assuntos
Proteoma , Proteômica , Animais , Proteoma/metabolismo , Camundongos , Feminino , Masculino , Proteômica/métodos , Rim/metabolismo , Rim/crescimento & desenvolvimento , Spliceossomos/metabolismo , Especificidade de Órgãos , Camundongos Endogâmicos C57BL , Encéfalo/metabolismo , Encéfalo/crescimento & desenvolvimento , Fígado/metabolismo , Pulmão/metabolismo , Pulmão/crescimento & desenvolvimento , Regulação da Expressão Gênica no Desenvolvimento , Caracteres Sexuais , Baço/metabolismo , Baço/crescimento & desenvolvimento
6.
Neurosurg Focus ; 57(1): E9, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38950448

RESUMO

OBJECTIVE: Prior studies have investigated associations between gender, symptom resolution, and time to return to play following sport-related concussion (SRC). However, there is a notable gap in research regarding the association between gender and return to learn (RTL) in adolescents. Therefore, this study 1) compared the patterns of RTL between boys and girls who are high school student athletes, and 2) evaluated the possible association between gender and time to RTL after adjusting for covariates. METHODS: A retrospective cohort study of a prospective surveillance program that monitored concussion recovery of athletes in high schools throughout the state of Maine between February 2015 and January 2023 was performed. The primary independent variable was gender, dichotomized as boys and girls. The primary outcome was time to RTL, defined by the number of days for an athlete to return to school without accommodations. Mann-Whitney U-tests were used to compare RTL between the boys and girls. Each athlete's RTL status was dichotomized (i.e., returned vs had not returned) at several time points following injury (i.e., 1, 2, 3, and 4 weeks), and chi-square tests were performed to compare the proportions who achieved RTL between groups. Multivariable linear regression analyses were performed to evaluate the predictive value of gender on RTL. Covariates included age, number of previous concussions, history of learning disability or attention-deficit disorder or attention-deficit/hyperactivity disorder, history of a psychological condition, history of headaches or migraines, initial Sport Concussion Assessment Tool (SCAT3/SCAT5) score, and days to evaluation. RESULTS: Of 895 high school athletes, 488 (54.5%) were boys and 407 (45.5%) were girls. There was no statistically significant difference in median [IQR] days to RTL between genders (6.0 [3.0-11.0] vs 6.0 [3.0-12.0] days; U = 84,365.00, p < 0.375). A greater proportion of boys successfully returned to learn without accommodations by 3 weeks following concussion (93.5% vs 89.4%; χ2 = 4.68, p = 0.030), but no differences were found at 1, 2, or 4 weeks. A multivariable model predicting days to RTL showed that gender was not a significant predictor of RTL (p > 0.05). Longer days to evaluation (ß = 0.10, p = 0.021) and higher initial SCAT3/SCAT5 scores (ß = 0.15, p < 0.001) predicted longer RTL. CONCLUSIONS: In a cohort of high school athletes, RTL did not differ between boys and girls following SRC. Gender was not a significant predictor of RTL. Longer days to evaluation and higher initial symptom scores were associated with longer RTL.


Assuntos
Atletas , Traumatismos em Atletas , Concussão Encefálica , Estudantes , Humanos , Masculino , Feminino , Concussão Encefálica/epidemiologia , Adolescente , Traumatismos em Atletas/epidemiologia , Estudos Retrospectivos , Caracteres Sexuais , Recuperação de Função Fisiológica/fisiologia , Fatores Sexuais , Aprendizagem/fisiologia , Estudos de Coortes , Estudos Prospectivos , Instituições Acadêmicas , Retorno à Escola , Volta ao Esporte
7.
PLoS One ; 19(7): e0285068, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38959265

RESUMO

Sperm whales exhibit sexual dimorphism and sex-specific latitudinal segregation. Females and their young form social groups and are usually found in temperate and tropical latitudes, while males forage at higher latitudes. Historical whaling data and rare sightings of social groups in high latitude regions of the North Pacific, such as the Gulf of Alaska (GOA) and Bering Sea/Aleutian Islands (BSAI), suggest a more complex distribution than previously understood. Sperm whales are the most sighted and recorded cetacean in marine mammal surveys in these regions but capturing their demographic composition and habitat use has proven challenging. This study detects sperm whale presence using passive acoustic data from seven sites in the GOA and BSAI from 2010 to 2019. Differences in click characteristics between males and females (i.e., inter-click and inter-pulse interval) was used as a proxy for animal size/sex to derive time series of animal detections. Generalized additive models with generalized estimation equations demonstrate how spatiotemporal patterns differ between the sexes. Social groups were present at all recording sites with the largest relative proportion at two seamount sites in the GOA and an island site in the BSAI. We found that the seasonal patterns of presence varied for the sexes and between the sites. Male presence was highest in the summer and lowest in the winter, conversely, social group peak presence was in the winter for the BSAI and in the spring for the GOA region, with the lowest presence in the summer months. This study demonstrates that social groups are not restricted to lower latitudes and capture their present-day habitat use in the North Pacific. It highlights that sperm whale distribution is more complex than accounted for in management protocol and underscores the need for improved understanding of sperm whale demographic composition to better understand the impacts of increasing anthropogenic threats, particularly climate change.


Assuntos
Ecossistema , Cachalote , Animais , Cachalote/fisiologia , Feminino , Masculino , Alaska , Vocalização Animal/fisiologia , Estações do Ano , Caracteres Sexuais
8.
Sci Rep ; 14(1): 15039, 2024 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951150

RESUMO

The appropriate structure of the digestive tract is crucial for individual adaptation to ecological conditions. In birds, the length of the small intestine, responsible for food absorption, is generally believed to be positively correlated with body size. In this study, we investigated the variation in small intestine length in the White Stork (Ciconia ciconia), a monomorphic species without visible sexual dimorphism, but characterized by differing parental efforts, which can be reflected by the small intestine lengths between the sexes. We examined the relationship between small intestine length and body size within the sexes. Our findings show that male White Storks have significantly shorter small intestines than females, despite having larger body sizes than the latter. Furthermore, we found a significant relationship between body size and small intestine length, but it was of a different nature in the two sexes. Males exhibited a previously unreported phenomenon, whereby increasing body size was associated with shortening small intestines, whereas females exhibited the opposite pattern. These novel findings shed light on the anatomical adaptations of the digestive tract in birds.


Assuntos
Aves , Tamanho Corporal , Caracteres Sexuais , Animais , Masculino , Feminino , Tamanho Corporal/fisiologia , Aves/anatomia & histologia , Aves/fisiologia , Intestino Delgado/anatomia & histologia , Trato Gastrointestinal/anatomia & histologia , Trato Gastrointestinal/fisiologia
9.
Commun Biol ; 7(1): 774, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951581

RESUMO

Machine learning (ML) newly enables tests for higher inter-species diversity in visible phenotype (disparity) among males versus females, predictions made from Darwinian sexual selection versus Wallacean natural selection, respectively. Here, we use ML to quantify variation across a sample of > 16,000 dorsal and ventral photographs of the sexually dimorphic birdwing butterflies (Lepidoptera: Papilionidae). Validation of image embedding distances, learnt by a triplet-trained, deep convolutional neural network, shows ML can be used for automated reconstruction of phenotypic evolution achieving measures of phylogenetic congruence to genetic species trees within a range sampled among genetic trees themselves. Quantification of sexual disparity difference (male versus female embedding distance), shows sexually and phylogenetically variable inter-species disparity. Ornithoptera exemplify high embedded male image disparity, diversification of selective optima in fitted multi-peak OU models and accelerated divergence, with cases of extreme divergence in allopatry and sympatry. However, genus Troides shows inverted patterns, including comparatively static male embedded phenotype, and higher female than male disparity - though within an inferred selective regime common to these females. Birdwing shapes and colour patterns that are most phenotypically distinctive in ML similarity are generally those of males. However, either sex can contribute majoritively to observed phenotypic diversity among species.


Assuntos
Borboletas , Animais , Feminino , Borboletas/genética , Borboletas/fisiologia , Borboletas/anatomia & histologia , Masculino , Fenótipo , Filogenia , Caracteres Sexuais , Evolução Biológica , Aprendizado de Máquina , Asas de Animais/anatomia & histologia , Asas de Animais/fisiologia
10.
Sci Rep ; 14(1): 15231, 2024 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956189

RESUMO

The 2D:4D digit ratio is commonly used as a surrogate possibly reflecting prenatal testosterone levels. Indirect evidence comes from studies investigating the association between 2D:4D and human characteristics that likely relate to prenatal testosterone. In children, sex-typed play reveals large sex differences early in development and an influence of prenatal testosterone is likely. Findings on the association between 2D:4D and children's sex-typed play are heterogeneous and other influences on the development of sex-typed play have been suggested, most of all social influences like siblings, their sex and birth order. The current study examined the association between right and left 2D:4D, a proposed surrogate for prenatal testosterone exposure, which was assessed in right and left hands of N = 505 6-month-old children, and sex-typed play behavior, which was evaluated 3.5 years later using the Pre-School Activities Inventory (PSAI), and the influence of siblings. To capture differential effects of siblings' sex and birth order, dummy-coded variables were used reflecting having no siblings as well as older or younger sisters or brothers. Multiple regression models were used to investigate the association between PSAI scores and sex, right and left 2D:4D, being a singleton as well as having an older or younger sister or brother. It was shown that sex and having an older brother were significant predictors for sex-typed play. Effects were further disentangled by conducting separate regression analyses in boys and girls. In boys, a significant association between PSAI scores and having an older brother was revealed, in girls, no significant associations were found. Results are discussed highlighting the non-significant association between 2D:4D and children's sex-typed play, which weakens the applicability of 2D:4D as a surrogate reflecting influences of prenatal T. Further, the importance of social factors like siblings on children's sex-typed play is discussed.


Assuntos
Dedos , Jogos e Brinquedos , Irmãos , Humanos , Feminino , Masculino , Dedos/anatomia & histologia , Lactente , Testosterona/metabolismo , Pré-Escolar , Caracteres Sexuais , Gravidez , Criança , Efeitos Tardios da Exposição Pré-Natal
11.
Sci Adv ; 10(28): eadq3079, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38996016

RESUMO

Sex and gender differences exist in the prevalence and clinical manifestation of common brain disorders. Identifying their neural correlates may help improve clinical care.


Assuntos
Encéfalo , Rede Nervosa , Caracteres Sexuais , Humanos , Encéfalo/fisiologia , Masculino , Feminino , Rede Nervosa/fisiologia , Fatores Sexuais , Mapeamento Encefálico
12.
Sci Adv ; 10(28): eadg1421, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38996019

RESUMO

Genomic mechanisms enhancing risk in males may contribute to sex bias in autism. The ubiquitin protein ligase E3A gene (Ube3a) affects cellular homeostasis via control of protein turnover and by acting as transcriptional coactivator with steroid hormone receptors. Overdosage of Ube3a via duplication or triplication of chromosomal region 15q11-13 causes 1 to 2% of autistic cases. Here, we test the hypothesis that increased dosage of Ube3a may influence autism-relevant phenotypes in a sex-biased manner. We show that mice with extra copies of Ube3a exhibit sex-biasing effects on brain connectomics and autism-relevant behaviors. These effects are associated with transcriptional dysregulation of autism-associated genes, as well as genes differentially expressed in 15q duplication and in autistic people. Increased Ube3a dosage also affects expression of genes on the X chromosome, genes influenced by sex steroid hormone, and genes sex-differentially regulated by transcription factors. These results suggest that Ube3a overdosage can contribute to sex bias in neurodevelopmental conditions via influence on sex-differential mechanisms.


Assuntos
Transtorno Autístico , Transcriptoma , Ubiquitina-Proteína Ligases , Animais , Masculino , Feminino , Transtorno Autístico/genética , Camundongos , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Humanos , Comportamento Animal , Caracteres Sexuais , Encéfalo/metabolismo , Modelos Animais de Doenças , Predisposição Genética para Doença
13.
Med Sci Monit ; 30: e944588, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39001576

RESUMO

BACKGROUND This retrospective study from a single center in Cyprus aimed to assess labial (buccal) and palatal bone thickness in 6 anterior maxillary teeth of 120 adults using cone-beam computed tomography (CBCT). MATERIAL AND METHODS The CBCT scans of 120 patients (720 teeth) were examined, with scanning parameters of 90 kvP, 24 s, 4 mA, voxel size 0.3 mm, and field of view of 10×6 cm. All maxillary incisors were categorized into 3 distinct points in terms of buccal (B) and palatal (P) points, with points B1 (buccal) and P1 (palatal) 4 mm below the cementoenamel junction; points B2 and P2 at the midpoint between the labial and palatal alveolar crest plane extending to the root apex; and points B3 and P3 at the root apex. Evaluation was done by measuring the distance from these points to the labial and palatal alveolar bone. RESULTS When the thicknesses were measured between all 6 points and labial and palatal bone, the thickness of point B3 of tooth 13 in men was significantly higher than that in women. At points P1, P2, and P3 for teeth 11 and 13, the palatal bone thickness of men was significantly higher than that of women. At points P2 and P3 of tooth 12, the palatal bone thickness of men was significantly higher than that of women. CONCLUSIONS The study found a correlation between alveolar bone thickness and patient sex in the North Cyprus population. Alveolar bone thickness in the anterior maxillary should be considered in implant treatment and orthodontic techniques.


Assuntos
Processo Alveolar , Tomografia Computadorizada de Feixe Cônico , Incisivo , Maxila , Humanos , Tomografia Computadorizada de Feixe Cônico/métodos , Masculino , Feminino , Incisivo/diagnóstico por imagem , Estudos Retrospectivos , Maxila/diagnóstico por imagem , Maxila/anatomia & histologia , Adulto , Processo Alveolar/diagnóstico por imagem , Processo Alveolar/anatomia & histologia , Pessoa de Meia-Idade , Fatores Sexuais , Chipre , Caracteres Sexuais
14.
J Comp Neurol ; 532(7): e25658, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38987904

RESUMO

Spinal cord injury (SCI) disrupts coordination between the bladder and the external urinary sphincter (EUS), leading to transient or permanent voiding impairment, which is more severe in males. Male versus female differences in spinal circuits related to the EUS as well as post-SCI rewiring are essential for understanding of sex-/gender-specific impairments and possible recovery mechanisms. To quantitatively assess differences between EUS circuits in males versus females and in spinal intact (SI) versus SCI animals, we retrogradely traced and counted EUS-related neurons. In transgenic ChAT-GFP mice, motoneurons (MNs), interneurons (INs), and propriospinal neurons (PPNs) were retrogradely trans-synaptically traced with PRV614-red fluorescent protein (RFP) injected into EUS. EUS-MNs in dorsolateral nucleus (DLN) were separated from other GFP+ MNs by tracing them with FluoroGold (FG). We found two morphologically distinct cell types in DLN: FG+ spindle-shaped bipolar (SB-MNs) and FG- rounded multipolar (RM-MNs) cholinergic cells. Number of MNs of both types in males was twice as large as in females. SCI caused a partial loss of MNs in all spinal nuclei. After SCI, males showed a fourfold rise in the number of RFP-labeled cells in retro-DLN (RDLN) innervating hind limbs. This suggests (a) an existence of direct synaptic interactions between spinal nuclei and (b) a post-SCI increase of non-specific inputs to EUS-MNs from other motor nuclei. Number of INs and PPNs deferred between males and females: In SI males, the numbers of INs and PPNs were ∼10 times larger than in SI females. SCI caused a twofold decrease of INs and PPNs in males but not in females.


Assuntos
Camundongos Transgênicos , Caracteres Sexuais , Traumatismos da Medula Espinal , Uretra , Animais , Feminino , Masculino , Camundongos , Uretra/inervação , Uretra/fisiologia , Medula Espinal , Neurônios Motores/fisiologia , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Vias Neurais/fisiologia
16.
J Clin Invest ; 134(13)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38949020

RESUMO

Cancer risk is modulated by hereditary and somatic mutations, exposures, age, sex, and gender. The mechanisms by which sex and gender work alone and in combination with other cancer risk factors remain underexplored. In general, cancers that occur in both the male and female sexes occur more commonly in XY compared with XX individuals, regardless of genetic ancestry, geographic location, and age. Moreover, XY individuals are less frequently cured of their cancers, highlighting the need for a greater understanding of sex and gender effects in oncology. This will be necessary for optimal laboratory and clinical cancer investigations. To that end, we review the epigenetics of sexual differentiation and its effect on cancer hallmark pathways throughout life. Specifically, we will touch on how sex differences in metabolism, immunity, pluripotency, and tumor suppressor functions are patterned through the epigenetic effects of imprinting, sex chromosome complement, X inactivation, genes escaping X inactivation, sex hormones, and life history.


Assuntos
Epigênese Genética , Neoplasias , Caracteres Sexuais , Humanos , Feminino , Neoplasias/genética , Masculino , Animais , Inativação do Cromossomo X , Hormônios Esteroides Gonadais/metabolismo , Impressão Genômica
17.
J Clin Invest ; 134(13)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38949027

RESUMO

Biological sex is an important modifier of physiology and influences pathobiology in many diseases. While heart disease is the number one cause of death worldwide in both men and women, sex differences exist at the organ and cellular scales, affecting clinical presentation, diagnosis, and treatment. In this Review, we highlight baseline sex differences in cardiac structure, function, and cellular signaling and discuss the contribution of sex hormones and chromosomes to these characteristics. The heart is a remarkably plastic organ and rapidly responds to physiological and pathological cues by modifying form and function. The nature and extent of cardiac remodeling in response to these stimuli are often dependent on biological sex. We discuss organ- and molecular-level sex differences in adaptive physiological remodeling and pathological cardiac remodeling from pressure and volume overload, ischemia, and genetic heart disease. Finally, we offer a perspective on key future directions for research into cardiac sex differences.


Assuntos
Caracteres Sexuais , Remodelação Ventricular , Humanos , Feminino , Masculino , Animais , Cardiopatias/patologia , Cardiopatias/metabolismo , Cardiopatias/fisiopatologia , Cardiopatias/genética , Hormônios Esteroides Gonadais/metabolismo , Coração/fisiopatologia , Coração/fisiologia , Miocárdio/patologia , Miocárdio/metabolismo
18.
Hum Brain Mapp ; 45(10): e26774, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38949599

RESUMO

Testosterone levels sharply rise during the transition from childhood to adolescence and these changes are known to be associated with changes in human brain structure. During this same developmental window, there are also robust changes in the neural oscillatory dynamics serving verbal working memory processing. Surprisingly, whereas many studies have investigated the effects of chronological age on the neural oscillations supporting verbal working memory, none have probed the impact of endogenous testosterone levels during this developmental period. Using a sample of 89 youth aged 6-14 years-old, we collected salivary testosterone samples and recorded magnetoencephalography during a modified Sternberg verbal working memory task. Significant oscillatory responses were identified and imaged using a beamforming approach and the resulting maps were subjected to whole-brain ANCOVAs examining the effects of testosterone and sex, controlling for age, during verbal working memory encoding and maintenance. Our primary results indicated robust testosterone-related effects in theta (4-7 Hz) and alpha (8-14 Hz) oscillatory activity, controlling for age. During encoding, females exhibited weaker theta oscillations than males in right cerebellar cortices and stronger alpha oscillations in left temporal cortices. During maintenance, youth with greater testosterone exhibited weaker alpha oscillations in right parahippocampal and cerebellar cortices, as well as regions across the left-lateralized language network. These results extend the existing literature on the development of verbal working memory processing by showing region and sex-specific effects of testosterone, and are the first results to link endogenous testosterone levels to the neural oscillatory activity serving verbal working memory, above and beyond the effects of chronological age.


Assuntos
Magnetoencefalografia , Memória de Curto Prazo , Testosterona , Humanos , Masculino , Memória de Curto Prazo/fisiologia , Feminino , Adolescente , Criança , Encéfalo/fisiologia , Saliva/química , Saliva/metabolismo , Mapeamento Encefálico , Caracteres Sexuais
19.
Neurobiol Aging ; 141: 160-170, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38964013

RESUMO

Women have a higher incidence of Alzheimer's disease (AD), even after adjusting for increased longevity. Thus, there is an urgent need to identify genes that underpin sex-associated risk of AD. PIN1 is a key regulator of the tau phosphorylation signaling pathway; however, potential differences in PIN1 expression, in males and females, are still unknown. We analyzed brain transcriptomic datasets focusing on sex differences in PIN1 mRNA levels in an aging and AD cohort, which revealed reduced PIN1 levels primarily within females. We validated this observation in an independent dataset (ROS/MAP), which also revealed that PIN1 is negatively correlated with multiregional neurofibrillary tangle density and global cognitive function in females only. Additional analysis revealed a decrease in PIN1 in subjects with mild cognitive impairment (MCI) compared with aged individuals, again driven predominantly by female subjects. Histochemical analysis of PIN1 in AD and control male and female neocortex revealed an overall decrease in axonal PIN1 protein levels in females. These findings emphasize the importance of considering sex differences in AD research.


Assuntos
Doença de Alzheimer , Cognição , Disfunção Cognitiva , Peptidilprolil Isomerase de Interação com NIMA , Neocórtex , Emaranhados Neurofibrilares , Caracteres Sexuais , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Doença de Alzheimer/metabolismo , Peptidilprolil Isomerase de Interação com NIMA/genética , Peptidilprolil Isomerase de Interação com NIMA/metabolismo , Humanos , Feminino , Neocórtex/patologia , Neocórtex/metabolismo , Masculino , Disfunção Cognitiva/genética , Disfunção Cognitiva/patologia , Disfunção Cognitiva/metabolismo , Idoso , Idoso de 80 Anos ou mais , Emaranhados Neurofibrilares/patologia , Emaranhados Neurofibrilares/metabolismo , Fenótipo , Sistema Límbico/patologia , Sistema Límbico/metabolismo , Expressão Gênica , Envelhecimento/patologia , Envelhecimento/genética , Envelhecimento/metabolismo , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Proteínas tau/metabolismo , Proteínas tau/genética , Fosforilação
20.
Cell Rep Med ; 5(7): 101652, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39019008

RESUMO

Based on recent genome-wide association studies, it is theorized that altered regulation of autophagy contributes to the pathophysiology of schizophrenia and bipolar disorder. As activity of autophagy-regulatory pathways is controlled by discrete phosphorylation sites on the relevant proteins, phospho-protein profiling is one of the few approaches available for enabling a quantitative assessment of autophagic activity in the brain. Despite this, a comprehensive phospho-protein assessment in the brains of schizophrenia and bipolar disorder subjects is currently lacking. Using this direction, our broad screening identifies an increase in AMP-activated protein kinase (AMPK)-mediated phospho-activation of the pro-autophagy protein beclin-1 solely in the prefrontal cortex of female, but not male, schizophrenia subjects. Using a reverse translational approach, we surprisingly find that this increase in beclin-1 activity facilitates synapse formation and enhances cognition. These findings are interpreted in the context of human studies demonstrating that female schizophrenia subjects have a lower susceptibility to cognitive dysfunction than males.


Assuntos
Autofagia , Proteína Beclina-1 , Esquizofrenia , Caracteres Sexuais , Esquizofrenia/patologia , Esquizofrenia/metabolismo , Esquizofrenia/genética , Humanos , Feminino , Masculino , Proteína Beclina-1/metabolismo , Proteína Beclina-1/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Fosforilação , Animais , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/patologia , Sinapses/metabolismo , Sinapses/patologia , Transdução de Sinais , Camundongos , Cognição/fisiologia , Adulto
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