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1.
Trends Cell Biol ; 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38614918

RESUMEN

H3.3 is a highly conserved nonreplicative histone variant. H3.3 is enriched in promoters and enhancers of active genes, but it is also found within suppressed heterochromatin, mostly around telomeres. Accordingly, H3.3 is associated with seemingly contradicting functions: It is involved in development, differentiation, reprogramming, and cell fate, as well as in heterochromatin formation and maintenance, and the silencing of developmental genes. The emerging view is that different cellular contexts and histone modifications can promote opposing functions for H3.3. Here, we aim to provide an update with a focus on H3.3 functions in early mammalian development, considering the context of embryonic stem cell maintenance and differentiation, to finally conclude with emerging roles in cancer development and cell fate transition and maintenance.

2.
Artículo en Inglés | MEDLINE | ID: mdl-38578584

RESUMEN

Anxiety and depressive difficulties can emerge during early childhood and cause impairment in functioning. Anxiety and depressive behaviors and impairment are typically assessed with global questionnaires that require recall of children's behavior over an extended period which could reduce the accuracy of parent report of children's behavior and functioning. The current study compared parents' report of children's anxiety and depressive behaviors and impairment when evaluated with global measures versus a daily diary measure. Participants (N = 901 parents of 3-5-year-old children) completed global and daily measures of children's behavior and impairment during enrollment to the study. Global measures were completed at baseline and the 14 daily diary measures were completed consecutively for two weeks. Across most measures, daily associations between parent-reported anxiety and depressive behaviors and impairment were stronger compared to associations with global measures. These results suggest that daily measures may better capture links between young children's typical behavior and functioning compared to global measures. In addition, daily assessment might be more effective for measuring mild to moderate yet still impairing behaviors that may be missed on global reports that require longer periods of recall.

3.
Cell Genom ; 4(5): 100541, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38663408

RESUMEN

To better understand inter-individual variation in sensitivity of DNA methylation (DNAm) to immune activity, we characterized effects of inflammatory stimuli on primary monocyte DNAm (n = 190). We find that monocyte DNAm is site-dependently sensitive to lipopolysaccharide (LPS), with LPS-induced demethylation occurring following hydroxymethylation. We identify 7,359 high-confidence immune-modulated CpGs (imCpGs) that differ in genomic localization and transcription factor usage according to whether they represent a gain or loss in DNAm. Demethylated imCpGs are profoundly enriched for enhancers and colocalize to genes enriched for disease associations, especially cancer. DNAm is age associated, and we find that 24-h LPS exposure triggers approximately 6 months of gain in epigenetic age, directly linking epigenetic aging with innate immune activity. By integrating LPS-induced changes in DNAm with genetic variation, we identify 234 imCpGs under local genetic control. Exploring shared causal loci between LPS-induced DNAm responses and human disease traits highlights examples of disease-associated loci that modulate imCpG formation.


Asunto(s)
Islas de CpG , Metilación de ADN , Epigénesis Genética , Monocitos , Adulto , Femenino , Humanos , Masculino , Islas de CpG/genética , Metilación de ADN/efectos de los fármacos , Epigénesis Genética/efectos de los fármacos , Lipopolisacáridos/farmacología , Monocitos/efectos de los fármacos , Monocitos/metabolismo , Monocitos/inmunología , Persona de Mediana Edad , Anciano
4.
Int J Methods Psychiatr Res ; 33(1): e2019, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38481064

RESUMEN

OBJECTIVES: Identification of clinically significant irritability in preschool age is important to implement effective interventions. However, varying informant and measurement methods display distinct patterns. These patterns are associated with concurrent and future mental health concerns. Patterns across multi-informant methods in early-childhood irritability may have clinical utility, identifying risk for impaired psychosocial functioning. METHODS: Using data from the Multidimensional Assessment of Preschoolers Study (N = 425), latent profile analysis identified irritability patterns through the parent-reported Multidimensional Assessment Profile Scales-Temper Loss (MAPS-TL), parent-reported interviewer-rated Preschool Age Psychiatric Assessment (PAPA), and observer-rated Disruptive Behavior Diagnostic Observation Schedule (DB-DOS). These profiles were characterized on protective factors, global functioning, and mental health syndromes, concurrently and at early school age and preadolescent follow-up. RESULTS: Fit indices favored a five-class model: Low All, High Observation with Examiner (high DB-DOS Examiner Context), High All, High Parent Report (high MAPS-TL/PAPA), and Very High Parent Report (very high MAPS-TL/PAPA). Whereas Low All and High Observation with Examiner exhibited strong psychosocial functioning, remaining profiles showed impaired psychosocial functioning, with the Very High Parent Report group showing higher impairment at follow-ups, ds = 0.37-1.25. CONCLUSIONS: Multi-informant measurements of irritability may have utility for clinical prediction, and future studies should test utility for diagnostic precision.


Asunto(s)
Déficit de la Atención y Trastornos de Conducta Disruptiva , Problema de Conducta , Humanos , Preescolar , Problema de Conducta/psicología , Genio Irritable , Salud Mental , Psicometría
5.
J Affect Disord ; 354: 611-618, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38494139

RESUMEN

BACKGROUND: Irritability, marked by diminished frustration tolerance, holds significant implications for youth mental health treatment. Despite prior research on irritability trajectories, understanding of individual differences during adolescence remains limited. This study examines the stability and trajectory of irritability across ages 12-18, investigating associations with psychopathology and functioning at age 18. METHODS: A community sample of families with 3-year-old children (N = 518) was recruited via commercial mailing lists. Irritability was assessed at ages 12, 15, and 18 using the Affective Reactivity Index. Psychopathology at age 18 was evaluated with the Kiddie Schedule for Affective Disorders and Schizophrenia, and functioning was assessed through the UCLA Life Stress Interview. Measurement invariance analyses and latent growth curve modeling were conducted within a structural equation modeling (SEM) framework. RESULTS: Configural, metric, and scalar invariance models were supported. Elevated irritability at age 12 predicted adverse outcomes at age 18, including increased psychotropic medication use, mental health treatment, suicidal ideation, self-injury, and psychiatric disorders. Importantly, these associations persisted even after accounting for corresponding variables at age 12. The trajectory of irritability during early adolescence significantly predicted heightened risks for various outcomes at age 18, including suicidal ideation, depression, anxiety, disruptive behavior disorders, and impaired interpersonal functioning. DISCUSSION: Limitations include using only youth-reported data at age 18, limited generalizability from a mostly White, middle-class sample, and insufficient exploration of the broader developmental trajectory of irritability. Nevertheless, the findings emphasize the crucial role of irritability's trajectory in influencing various psychopathological and functional outcomes in late adolescence.


Asunto(s)
Genio Irritable , Psicopatología , Humanos , Adolescente , Preescolar , Niño , Trastornos de Ansiedad/psicología , Ansiedad , Déficit de la Atención y Trastornos de Conducta Disruptiva , Estudios Longitudinales
6.
Artículo en Inglés | MEDLINE | ID: mdl-38478358

RESUMEN

Irritability is a common presenting problem in youth mental health settings that is thought to include two components: tonic (e.g., irritable, touchy mood) and phasic (e.g., temper outbursts), each with unique correlates and outcomes, including later internalizing and externalizing problems, respectively. However, we are unaware of any studies of early predictors of tonic and phasic irritability. We utilized data from a longitudinal study of a community sample of 3-year-old children followed to age 15 (n = 444). We conducted confirmatory factor analysis (CFA) of items from several self-report irritability measures at age 15, including the Affective Reactivity Index, the International Personality Item Pool, the Schedule for Non-Adaptive and Adaptive Personality Youth Version, and the Child Depression Inventory, and examined their early childhood predictors. The CFA identified dimensions consistent with tonic and phasic irritability. Tonic irritability at age 15 was uniquely associated with concurrent internalizing disorders and suicidal behavior while phasic irritability was uniquely associated with concurrent externalizing disorders. When adolescent tonic and phasic irritability were examined together, female sex and parental depressive and substance use disorders at age 3 uniquely predicted adolescent tonic irritability. Additionally, male sex, less parental education, greater laboratory-observed anger and impulsivity, ODD symptoms, higher irritability, and no parental substance use history at age 3 uniquely predicted adolescent phasic irritability. Youth-reported tonic and phasic irritability at age 15 appear to be distinguishable constructs with distinct concurrent correlates and early antecedents. Findings have important implications for research on the etiology of irritability and developing effective treatments.

8.
Am J Psychiatry ; 181(4): 275-290, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38419494

RESUMEN

Irritability, defined as proneness to anger that may impair an individual's functioning, is common in youths. There has been a recent upsurge in relevant research. The authors combine systematic and narrative review approaches to integrate the latest clinical and translational findings and provide suggestions for addressing research gaps. Clinicians and researchers should assess irritability routinely, and specific assessment tools are now available. Informant effects are prominent, are stable, and vary by age and gender. The prevalence of irritability is particularly high among individuals with attention deficit hyperactivity disorder, autism spectrum disorder, and mood and anxiety disorders. Irritability is associated with impairment and suicidality risk independent of co-occurring diagnoses. Developmental trajectories of irritability (which may begin early in life) have been identified and are differentially associated with clinical outcomes. Youth irritability is associated with increased risk of anxiety, depression, behavioral problems, and suicidality later in life. Irritability is moderately heritable, and genetic associations differ based on age and comorbid illnesses. Parent management training is effective for treating psychological problems related to irritability, but its efficacy in treating irritability should be tested rigorously, as should novel mechanism-informed interventions (e.g., those targeting exposure to frustration). Associations between irritability and suicidality and the impact of cultural context are important, underresearched topics. Analyses of large, diverse longitudinal samples that extend into adulthood are needed. Data from both animal and human research indicate that aberrant responses to frustration and threat are central to the pathophysiology of irritability, revealing important translational opportunities.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Trastorno del Espectro Autista , Animales , Humanos , Adolescente , Genio Irritable/fisiología , Trastornos de Ansiedad/terapia , Trastornos de Ansiedad/tratamiento farmacológico , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/genética , Ansiedad/psicología , Trastornos del Humor/terapia , Déficit de la Atención y Trastornos de Conducta Disruptiva
9.
Artículo en Inglés | MEDLINE | ID: mdl-38366750

RESUMEN

BACKGROUND: Depressive moods and behaviors are developmentally normative, yet potentially impairing, in preschool-aged children. In addition to frequency, duration of behavior is an important parameter to consider when characterizing risk for worsening mood dysregulation. The goal of this study was to identify the duration and severity of depressive moods and behaviors and associations with impairment in a large community sample of preschool-aged children using an online parent-report daily diary. METHODS: Primary caregivers (N = 900) of 3-5-year-old children reported the daily duration of each instance of seven depressive moods and behaviors for 14 days. We used item response theory analyses to examine duration item characteristics. RESULTS: Moods and behaviors occurred at specific durations to be considered psychometrically severe/rare; for example, instances of sadness had to last an average total of 32 min per day or more, irritability at least 38 min, tantrums at least 30 min, and tearfulness/sensitivity at least 35 min. Longer durations of mood and behavior were associated with daily impairment, as well as older child age and less parental education. CONCLUSIONS: To our knowledge, this is the first study to delineate specific duration ranges for depressive moods and behaviors in preschool-aged children. These data, coupled with information about the frequency of mood-related behaviors, can assist child practitioners in differentiating normative patterns from less normative mood problems to evaluate which children may be at risk. Future work should identify the duration of depressive moods and behaviors in early childhood that predict clinically significant psychopathology over time.

10.
Clin Psychol Sci ; 12(1): 115-132, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38288008

RESUMEN

Sexual-minority adolescents frequently endure peer rejection, yet scant research has investigated sexual-orientation differences in behavioral and neural reactions to peer rejection and acceptance. In a community sample of adolescents approximately 15 years old (47.2% female; same-sex attracted: n = 36, exclusively other-sex attracted: n = 310), we examined associations among sexual orientation and behavioral and neural reactivity to peer feedback and the moderating role of family support. Participants completed a social-interaction task while electroencephalogram data were recorded in which they voted to accept/reject peers and, in turn, received peer acceptance/rejection feedback. Compared with heterosexual adolescents, sexual-minority adolescents engaged in more behavioral efforts to ingratiate after peer rejection and demonstrated more blunted neural reactivity to peer acceptance at low, but not medium or high, levels of family support. By using a simulated real-world social-interaction task, these results demonstrate that sexual-minority adolescents display distinct behavioral and neural reactions to peer acceptance and rejection.

11.
J Fam Psychol ; 38(2): 201-211, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38227468

RESUMEN

Parents of sexual and gender minority (SGM) youth play an important role in supporting their SGM child's mental health in the face of stigma. Yet, parents of SGM youth may themselves experience stigma, including discrimination/rejection, and its emotional consequences, including vicarious stigma and shame. The present cross-sectional study leveraged a national sample of parents of SGM youth to investigate associations between parents' stigma experiences and self-reported anxiety and depression symptoms. Further, we additionally explored sociodemographic and contextual correlates of parents' stigma experiences. Participants included 264 parents (Mage = 46) who reported having at least one SGM child under age 30 (Mage = 18). The Lesbian, Gay, Bisexual-Affiliate Stigma Measure (LGB-ASM) assessed parents' experiences of discrimination/rejection (e.g., actual and anticipated rejection experiences due to having an SGM child), vicarious stigma (e.g., worry and concern for one's SGM child), and shame (e.g., feeling embarrassed for having an SGM child). Parents indicated their anxiety and depressive symptoms using respective Patient-Reported Outcomes Measurement Information System-short forms. Results showed that vicarious stigma and shame, but not discrimination/rejection, were uniquely associated with parents' increased symptoms of anxiety (vicarious stigma: ß = 1.59, p < .001; shame: ß = 2.15, p < .001) and depression (vicarious stigma: ß = 0.90, p < .01; shame: ß = 2.77, p < .001). Further, parents with more accepting religious, racial, ethnic, and/or cultural communities reported lower stigma experiences. This study advances understanding of how the psychological consequences of stigma extend beyond SGM people themselves and contribute to mental health difficulties in parents of SGM youth. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Asunto(s)
Depresión , Minorías Sexuales y de Género , Femenino , Niño , Humanos , Adolescente , Persona de Mediana Edad , Adulto , Estudios Transversales , Identidad de Género , Conducta Sexual , Ansiedad/etiología , Padres
13.
Cells ; 12(23)2023 12 04.
Artículo en Inglés | MEDLINE | ID: mdl-38067189

RESUMEN

Clinical and pre-clinical studies of neuropsychiatric (NP) disorders show altered astrocyte properties and synaptic networks. These are refined during early postnatal developmental (PND) stages. Thus, investigating early brain maturational trajectories is essential to understand NP disorders. However, animal experiments are highly time-/resource-consuming, thereby calling for alternative methodological approaches. The function of MEGF10 in astrocyte-mediated synapse elimination (pruning) is crucial to refine neuronal networks during development and adulthood. To investigate the impact of MEGF10 during PND in the rat prefrontal cortex (PFC) and its putative role in brain disorders, we established and validated an organotypic brain slice culture (OBSC) system. Using Western blot, we characterized the expression of MEGF10 and the synaptic markers synaptophysin and PSD95 in the cortex of developing pups. We then combined immunofluorescent-immunohistochemistry with Imaris-supported 3D analysis to compare age- and sex-dependent astrocyte-mediated pruning within the PFC in pups and OBSCs. We thereby validated this system to investigate age-dependent astrocyte-mediated changes in pruning during PND. However, further optimizations are required to use OBSCs for revealing sex-dependent differences. In conclusion, OBSCs offer a valid alternative to study physiological astrocyte-mediated synaptic remodeling during PND and might be exploited to investigate the pathomechanisms of brain disorders with aberrant synaptic development.


Asunto(s)
Astrocitos , Encefalopatías , Ratas , Animales , Hipocampo/metabolismo , Sinapsis/metabolismo , Corteza Prefrontal/metabolismo , Encéfalo , Encefalopatías/metabolismo
14.
Cureus ; 15(11): e49136, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38130518

RESUMEN

Pediatric liver transplant recipients are a high-risk group for the development of adenovirus hepatitis and other manifestations of disseminated adenoviral disease. The risk is greatest during periods of increased immunosuppression, including immediately post-transplantation and following treatment for rejection. Manifestations of adenovirus hepatitis are heterogeneous with a wide spectrum of clinical severity, ranging from mild, focal disease to fulminant liver failure. Here we report a case of liver transplantation-associated adenovirus hepatitis presenting with fever and multifocal liver lesions. The diagnosis was not clinically suspected due to atypical imaging findings and pathology. Non-targeted metagenomic sequencing of plasma cell-free DNA facilitated and expedited the diagnosis. Confirmatory conventional testing was obtained, allowing for appropriate initiation of targeted treatment in this patient.

15.
Psychol Med ; 53(12): 5405-5414, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37795688

RESUMEN

BACKGROUND: Preschool psychiatric symptoms significantly increase the risk for long-term negative outcomes. Transdiagnostic hierarchical approaches that capture general ('p') and specific psychopathology dimensions are promising for understanding risk and predicting outcomes, but their predictive utility in young children is not well established. We delineated a hierarchical structure of preschool psychopathology dimensions and tested their ability to predict psychiatric disorders and functional impairment in preadolescence. METHODS: Data for 1253 preschool children (mean age = 4.17, s.d. = 0.81) were drawn from three longitudinal studies using a similar methodology (one community sample, two psychopathology-enriched samples) and followed up into preadolescence, yielding a large and diverse sample. Exploratory factor models derived a hierarchical structure of general and specific factors using symptoms from the Preschool Age Psychiatric Assessment interview. Longitudinal analyses examined the prospective associations of preschool p and specific factors with preadolescent psychiatric disorders and functional impairment. RESULTS: A hierarchical dimensional structure with a p factor at the top and up to six specific factors (distress, fear, separation anxiety, social anxiety, inattention-hyperactivity, oppositionality) emerged at preschool age. The p factor predicted all preadolescent disorders (ΔR2 = 0.04-0.15) and functional impairment (ΔR2 = 0.01-0.07) to a significantly greater extent than preschool psychiatric diagnoses and functioning. Specific dimensions provided additional predictive power for the majority of preadolescent outcomes (disorders: ΔR2 = 0.06-0.15; functional impairment: ΔR2 = 0.05-0.12). CONCLUSIONS: Both general and specific dimensions of preschool psychopathology are useful for predicting clinical and functional outcomes almost a decade later. These findings highlight the value of transdiagnostic dimensions for predicting prognosis and as potential targets for early intervention and prevention.


Asunto(s)
Trastornos Mentales , Psicopatología , Humanos , Preescolar , Trastornos Mentales/diagnóstico , Miedo
16.
J Funct Morphol Kinesiol ; 8(3)2023 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-37754962

RESUMEN

This study aimed to characterize running-related injuries (RRIs), explore their relationship with run and resistance training (RT) parameters, and identify perceived prevention measures among adult recreational runners. An anonymous online survey was designed and distributed via social media and email. Data were analyzed with chi-square, t-test, or analysis of variance (ANOVA), with significance accepted at p ≤ 0.05. Data from 616 participants (76.8% female, age: 42.3 ± 10.5 y) were analyzed. Most runners (84.4%) had an injury history, with 44.6% experiencing one in the past year. The most common RRI sites included the foot/ankle (30.9%) and knee (22.2%). RRI prevalence was higher in those running >19 miles weekly (48.4%, p = 0.05), but there were no differences based on RT participation status. Among those using RT, relatively more RRIs were observed in runners who trained the hip musculature (50.3%, p = 0.005) and did not include the upper body (61.6%, p < 0.001). A disproportionately high RRI prevalence was found for several of the other risk-reduction strategies. RRIs remain a substantial problem, particularly around the ankle/foot and knee. Higher run volume and performance motives were positively associated with RRIs. Most runners incorporated RRI risk-reduction techniques, with over half using RT. The current study did not determine whether preventative strategies were implemented before or after injury; therefore, prospective studies controlling for previous injuries are required to evaluate the effectiveness of RT in preventing future RRIs.

17.
J Child Psychol Psychiatry ; 64(12): 1665-1678, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37644651

RESUMEN

BACKGROUND: Given the robust evidence base for the efficacy of evidence-based treatments targeting youth anxiety, researchers have advanced beyond efficacy outcome analysis to identify mechanisms of change and treatment directionality. Grounded in developmental transactional models, interventions for young children at risk for anxiety by virtue of behaviorally inhibited temperament often target parenting and child factors implicated in the early emergence and maintenance of anxiety. In particular, overcontrolling parenting moderates risk for anxiety among highly inhibited children, just as child inhibition has been shown to elicit overcontrolling parenting. Although longitudinal research has elucidated the temporal unfolding of factors that interact to place inhibited children at risk for anxiety, reciprocal transactions between these child and parent factors in the context of early interventions remain unknown. METHOD: This study addresses these gaps by examining mechanisms of change and treatment directionality (i.e., parent-to-child vs. child-to-parent influences) within a randomized controlled trial comparing two interventions for inhibited preschoolers (N = 151): the multicomponent Turtle Program ('Turtle') and the parent-only Cool Little Kids program ('CLK'). Reciprocal relations between parent-reported child anxiety, observed parenting, and parent-reported accommodation of child anxiety were examined across four timepoints: pre-, mid-, and post-treatment, and one-year follow-up (NCT02308826). RESULTS: Hypotheses were tested via latent curve models with structured residuals (LCM-SR) and latent change score (LCS) models. LCM-SR results were consistent with the child-to-parent influences found in previous research on cognitive behavioral therapy (CBT) for older anxious youth, but only emerged in Turtle. LCS analyses revealed bidirectional effects of changes in parent accommodation and child anxiety during and after intervention, but only in Turtle. CONCLUSION: Our findings coincide with developmental transactional models, suggesting that the development of child anxiety may result from child-to-parent influences rather than the reverse, and highlight the importance of targeting parent and child factors simultaneously in early interventions for young, inhibited children.


Asunto(s)
Terapia Cognitivo-Conductual , Responsabilidad Parental , Adolescente , Humanos , Preescolar , Responsabilidad Parental/psicología , Trastornos de Ansiedad/terapia , Trastornos de Ansiedad/psicología , Ansiedad/terapia , Ansiedad/psicología , Padres/psicología
18.
Artículo en Inglés | MEDLINE | ID: mdl-37652290

RESUMEN

In iteroparous female salmonids, the growth and reproductive endocrine axes interact during the period after spawning. Energy depletion due to pre-spawn fasting, migration, and ovarian development must be restored, and the next reproductive cycle is initiated in consecutively maturing fish. In the natural environment, food availability is often limited during the post-spawn period. To investigate the growth and reproductive endocrinology of the post-spawn period, we sampled female rainbow trout over the 30 weeks following their first spawning. Fish were fasted for 2 months prior to spawning, then fed a standard or a restricted ration. Analysis was confined to reproductive fish. Plasma estradiol-17ß decreased during the 8 weeks following spawning and then began increasing in both ration groups and was lower in feed-restricted versus standard ration fish from 8 weeks onward. Plasma insulin-like growth factor-1 increased over the same period and then remained constant in both ration groups and was lower in feed-restricted versus standard ration fish from week 8 to week 30. Plasma growth hormone decreased following spawning in standard ration fish and became elevated in feed-restricted versus standard ration fish at 20- and 30-weeks post-spawn. Growth rates, condition factor, and muscle lipid levels were higher in standard ration versus feed-restricted fish within 2-4 weeks after spawning. These results suggest that two phases occurred during the post-spawn period: recovery from spawning and restoration of energy reserves over weeks 0 to 8, followed by adjustment of the growth and reproductive endocrine axes to ration level over weeks 8 to 30.


Asunto(s)
Hormona del Crecimiento , Oncorhynchus mykiss , Femenino , Animales , Factor I del Crecimiento Similar a la Insulina , Ambiente , Ayuno
19.
Sci Total Environ ; 900: 165674, 2023 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-37495149

RESUMEN

BACKGROUND: Gestational exposure to environmental chemicals (ECs) is associated with adverse, sex-specific offspring health effects of global concern. As the maternal steroid, cytokine and oxidative stress milieus can have critical effects on pregnancy outcomes and the programming of diseases in offspring, it is important to study the impact of real-life EC exposure, i.e., chronic low levels of mixtures of ECs on these milieus. Sheep exposed to biosolids, derived from human waste, is an impactful model representing the ECs humans are exposed to in real-life. Offspring of sheep grazed on biosolids-treated pasture are characterized by reproductive and metabolic disruptions. OBJECTIVE: To determine if biosolids exposure disrupts the maternal steroid, cytokine and oxidative stress milieus, in a fetal sex-specific manner. METHODS: Ewes were maintained before mating and through gestation on pastures fertilized with biosolids (BTP), or inorganic fertilizer (Control). From maternal plasma collected mid-gestation, 19 steroids, 14 cytokines, 6 oxidative stress markers were quantified. Unpaired t-test and ANOVA were used to test for differences between control and BTP groups (n = 15/group) and between groups based on fetal sex, respectively. Correlation between the different markers was assessed by Spearman correlation. RESULTS: Concentrations of the mineralocorticoids - deoxycorticosterone, corticosterone, the glucocorticoids - deoxycortisol, cortisol, cortisone, the sex steroids - androstenedione, dehydroepiandrosterone, 16-OH-progesterone and reactive oxygen metabolites were higher in the BTP ewes compared to Controls, while the proinflammatory cytokines IL-1ß and IL-17A and anti-inflammatory IL-36RA were decreased in the BTP group. BTP ewes with a female fetus had lower levels of IP-10. DISCUSSION: These findings suggest that pre-conceptional and gestational exposure to ECs in biosolids increases steroids, reactive oxygen metabolites and disrupts cytokines in maternal circulation, likely contributors to the aberrant phenotypic outcomes seen in offspring of BTP sheep - a translationally relevant precocial model.


Asunto(s)
Reproducción , Esteroides , Embarazo , Masculino , Ovinos , Animales , Femenino , Humanos , Biosólidos , Estrés Oxidativo , Oxígeno
20.
Animals (Basel) ; 13(12)2023 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-37370419

RESUMEN

This study aimed at describing the change in echocardiographic variables after high-dose medetomidine and the reversal with atipamezole in six cats undergoing sedation for semen collection. Further cardiac Troponin I (cTnI) concentration and the effect of repeated sedation were assessed. Echocardiography was performed before and 20 min after sedation with 0.1 mg/kg medetomidine intramuscularly (IM) for urethral catheterisation. Prior to epididymectomy, S-ketamine was administered intravenously. Twenty minutes after reversal with 0.5 mg/kg atipamezole IM, the third echocardiography was performed. Sedation with medetomidine and reversal with atipamezole was repeated on day 7, 14, 21 and 28. Heart rate (HR) and rhythm were monitored throughout all sedations. On day 0 and 28 cTnI concentrations were measured before and after the procedure. After normality testing, the values were compared over time. The administration of medetomidine led to a marked reduction in HR, cardiac output and ventricular systolic function and a significant increase in left ventricular dimensions. Rhythm abnormalities, such as ventricular premature complexes and idioventricular rhythm, could be observed. The administration of atipamezole completely reversed sedation and the changes in haemodynamic variables. No significant increase in cTnI concentrations could be detected, although two out of six cats showed values above the reference range.

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