Early Life Research Articles

Short-term exposure to antibiotics begets long-term disturbance in gut microbial metabolism and molecular ecological networks

BackgroundAntibiotic exposure can occur in medical settings and from environmental sources. Long-term effects of brief antibiotic exposure in early life are largely unknown.ResultsPost a short-term treatment by ceftriaxone to C57BL/6 mice in early life, a 14-month observation was performed using 16S rRNA gene-sequencing technique, metabolomics analysis, and metagenomics analysis on the effects of ceftriaxone exposure. Firstly, the results showed that antibiotic pre-treatment significantly disturbed gut microbial α and β diversities (P < 0.05). Both Chao1 indices and Shannon indices manifested recovery trends over time, but they didn’t entirely recover to the baseline of control throughout the experiment. Secondly, antibiotic pre-treatment reduced the complexity of gut molecular ecological networks (MENs). Various network parameters were affected and manifested recovery trends over time with different degrees, such as nodes (P < 0.001, R2 = 0.6563), links (P < 0.01, R2 = 0.4543), number of modules (P = 0.0672, R2 = 0.2523), relative modularity (P = 0.6714, R2 = 0.0155), number of keystones (P = 0.1003, R2 = 0.2090), robustness_random (P = 0.79, R2 = 0.0063), and vulnerability (P = 0.0528, R2 = 0.28). The network parameters didn't entirely recover. Antibiotic exposure obviously reduced the number of key species in gut MENs. Interestingly, new keystones appeared during the recovery process of network complexity. Changes in network stability might be caused by variations in network complexity, which supports the ecological theory that complexity begets stability. Besides, the metabolism profiles of the antibiotic group and control were significantly different. Correlation analysis showed that antibiotic-induced differences in gut microbial metabolism were related to MEN changes. Antibiotic exposure also caused long-term effects on gut microbial functional networks in mice.ConclusionsThese results suggest that short-term antibiotic exposure in early life will cause long-term negative impacts on gut microbial diversity, MENs, and microbial metabolism. Therefore, great concern should be raised about children’s brief exposure to antibiotics if the results observed in mice are applicable to humans.D3-AZHri_jesG1CHKmDZa1Video

Neonatal immune stimulation results in sex-specific changes in ultrasonic vocalizations but does not affect seizure susceptibility in neonatal mice.

Neuroinflammation during the neonatal period has been linked to disorders such as autism and epilepsy. In this study, we investigated the early life behavioral consequences of a single injection of lipopolysaccharide (LPS) at postnatal day 10 (PD10) in mice. To assess deficits in communication, we performed the isolation-induced ultrasonic vocalizations (USVs) test at PD12. To determine if early life immune stimulus could alter seizure susceptibility, latency to flurothyl-induced generalized seizures was measured at 4 hours(hrs), 2days, or 5days after LPS injections. LPS had a sex-dependent effect on USV number. LPS-treated male mice presented significantly fewer USVs than LPS-treated female mice. However, the number of calls did not significantly differ between control and LPS for either sex. In male mice, we found that downward, short, and composite calls were significantly more prevalent in the LPS treatment group, while upward, chevron, and complex calls were less prevalent than in controls (p< 0.05). Female mice that received LPS presented a significantly higher proportion of short, frequency steps, two-syllable, and composite calls in their repertoire when compared with female control mice (p< 0.05). Seizure latency was not altered by early-life inflammation at any of the time points measured. Our findings suggest that early-life immune stimulation at PD10 disrupts vocal development but does not alter the susceptibility to flurothyl-induced seizures during the neonatal period. Additionally, the effect of inflammation in the disruption of vocalization is sex-dependent.

The effects of exposure to and timing of a choline-deficient diet during pregnancy and early postnatal life on the skeletal muscle transcriptome of the offspring

Nonalcoholic fatty liver disease (NAFLD) is related to muscle loss, but the precise mechanism underlying this association remains unclear. The aim of the present study was thus to determine the influence of maternal fatty liver and dietary choline deficiency during pregnancy and/or lactation periods on the skeletal muscle gene expression profile among 24-day-old male rat offspring. Histological examination of skeletal muscle tissue specimens obtained from offspring of dams suffering from fatty liver, provided with proper choline intake during pregnancy and lactation (NN), fed a choline-deficient diet during both periods (DD), deprived of choline only during pregnancy (DN), or only during lactation (ND), was performed. The global transcriptome pattern was assessed using a microarray approach (Affymetrix® Rat Gene 2.1 ST Array Strip). The relative expression of selected genes was validated by real-time PCR (qPCR). Morphological differences in fat accumulation in skeletal muscle related to choline supply were observed. The global gene expression profile was consistent with abnormal morphological changes. Mettl21c gene was overexpressed in all choline-deficient groups compared to the NN group, while two genes, Cdkn1a and S100a4, were downregulated. Processes of protein biosynthesis were upregulated, and processes related to cell proliferation and lipid metabolism were inhibited in DD, DN, and ND groups compared to the NN group. Prenatal and early postnatal exposure to fatty liver and dietary choline deficiency leads to changes in the transcriptome profile in skeletal muscle of 24-day old male rat offspring and is associated with muscle damage, but the mechanism of it seems to be different at different developmental stages of life. Adequate choline intake during pregnancy and lactation can prevent severe muscle disturbance in the progeny of females suffering from fatty liver.

Intragenic MFSD8 duplication and histopathological findings in a rabbit with neuronal ceroid lipofuscinosis.

Neuronal ceroid lipofuscinoses (NCL) are among the most prevalent neurodegenerative disorders of early life in humans. Disease-causing variants have been described for 13 different NCL genes. In this study, a refined pathological characterization of a female rabbit with progressive neurological signs reminiscent of NCL was performed. Cytoplasmic pigment present in neurons was weakly positive with Sudan black B and autofluorescent. Immunohistology revealed astrogliosis, microgliosis and axonal degeneration. During the subsequent genetic investigation, the genome of the affected rabbit was sequenced and examined for private variants in NCL candidate genes. The analysis revealed a homozygous ~10.7 kb genomic duplication on chromosome 15 comprising parts of the MFSD8 gene, NC_013683.1:g.103,727,963_103,738,667dup. The duplication harbors two internal protein coding exons and is predicted to introduce a premature stop codon into the transcript, truncating ~50% of the wild-type MFSD8 open reading frame encoding the major facilitator superfamily domain containing protein 8, XP_002717309.2:p.(Glu235Leufs*23). Biallelic loss-of-function variants in MFSD8 have been described to cause NCL7 in human patients, dogs and a single cat. The available clinical and pathological data, together with current knowledge about MFSD8 variants and their functional impact in other species, point to the MFSD8 duplication as a likely causative defect for the observed phenotype in the affected rabbit.

Role of Maternal Adverse Childhood Experiences on Infant Neglect: A Multi-Perspective Approach.

We explored the intergenerational transmission effects of maternal adverse childhood experiences (ACEs) and infant neglect from multiple perspectives. The study included a sample of postpartum mothers and infants (N = 550) from the outpatient child health care department of a tertiary hospital in Jinan, Shandong Province, China. Our investigation followed three main lines of inquiry. First, the association of overall maternal ACEs with infant neglect was estimated. Secondly, the cumulative and independent effects of maternal ACEs on infant neglect were explored using the Adverse Childhood Experience Questionnaire-Revised (ACEQ-R) with 14 types of ACEs. Finally, the different patterns of 14 maternal ACEs were identified, and the association between the different patterns and infant neglect was explored. There were three main findings. First, infants born to mothers with ACEs experienced higher levels of neglect compared to those born to mothers without ACEs. Second, infants born to mothers with three or more subtypes of ACEs experienced the greatest levels of neglect, with maternal childhood physical neglect emerging as a particularly influential factor. Third, infants in the "median maternal ACEs" and "high maternal neglect and poor peer relationship" groups experienced more severe neglect than those in the "low maternal ACEs" group. These results suggest that early life experiences substantially shape future parenting behaviors, such as infant neglect.

Activation of GPR55 Ameliorates Maternal Separation-Induced Learning and Memory Deficits by Augmenting 5-HT Synthesis in the Dorsal Raphe Nucleus of Juvenile Mice.

Maternal separation (MS) represents a profound early life stressor with enduring impacts on neuronal development and adult cognitive function in both humans and rodents. MS is associated with persistent dysregulations in neurotransmitter systems, including the serotonin (5-HT) pathway, which is pivotal for mood stabilization and stress-coping mechanisms. Although the novel cannabinoid receptor, GPR55, is recognized for its influence on learning and memory, its implications on the function and synaptic dynamics of 5-HT neurons within the dorsal raphe nucleus (DRN) remain to be elucidated. In this study, we sought to discern the repercussions of GPR55 activation on 5-HT synthesis within the DRN of adult C57BL/6J mice that experienced MS. Concurrently, we analyzed potential alterations in excitatory synaptic transmission, long-term synaptic plasticity, and relevant learning and memory outcomes. Our behavioral assessments indicated a marked amelioration in MS-induced learning and memory deficits following GPR55 activation. In conjunction with this, we noted a substantial decrease in 5-HT levels in the MS model, while GPR55 activation stimulated tryptophan hydroxylase 2 synthesis and fostered the release of 5-HT. Electrophysiological patch-clamp analyses highlighted the ability of GPR55 activation to alleviate MS-induced cognitive deficits by modulating the frequency and magnitude of miniature excitatory postsynaptic currents within the DRN. Notably, this cognitive enhancement was underpinned by the phosphorylation of both NMDA and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. In summary, our findings underscore the capacity of GPR55 to elevate 5-HT synthesis and modify synaptic transmissions within the DRN of juvenile mice, positing GPR55 as a promising therapeutic avenue for ameliorating MS-induced cognitive impairment.

Programmed cell death factor 4-mediated hippocampal synaptic plasticity is involved in early life stress and susceptibility to depression

Early life stress (ELS) increases the risk of depression later in life. Programmed cell death factor 4 (PDCD4), an apoptosis-related molecule, extensively participates in tumorigenesis and inflammatory diseases. However, its involvement in a person’s susceptibility to ELS-related depression is unknown. To examine the effects and underlying mechanisms of PDCD4 on ELS vulnerability, we used a “two-hit” stress mouse model: an intraperitoneal injection of lipopolysaccharide (LPS) into neonatal mice was performed on postnatal days 7–9 (P7-P9) and inescapable foot shock (IFS) administration in adolescent was used as a later-life challenge. Our study shows that compared with mice that were only exposed to the LPS or IFS, the “two-hit” stress mice developed more severe depression/anxiety-like behaviors and social disability. We detected the levels of PDCD4 in the hippocampus of adolescent mice and found that they were significantly increased in “two-hit” stress mice. The results of immunohistochemical staining and Sholl analysis showed that the number of microglia in the hippocampus of “two-hit” stress mice significantly increased, with morphological changes, shortened branches, and decreased numbers. However, knocking down PDCD4 can prevent the number and morphological changes of microglia induced by ELS. In addition, we confirmed through the Golgi staining and immunohistochemical staining results that knocking down PDCD4 can ameliorate ELS-induced synaptic plasticity damage. Mechanically, the knockdown of PDCD4 exerts neuroprotective effects, possibly via the mediation of BDNF/AKT/CREB signaling. Combined, these results suggest that PDCD4 may play an important role in the ELS-induced susceptibility to depression and, thus, may become a therapeutic target for depressive disorders.

Association Between Sociodemographic Status and Physical Functioning of Obese School Going Children- A Cross Sectional Study

Background: Obesity is major non-communicable disease (NCD) all over the world affecting both children &amp; adult. More than 30 million overweight children are living in developing countries &amp; 10 million in developed countries. Childhood obesity leads to a significant reduction in health-related functioning. So, the negative effects of childhood obesity on quality of life (QoL) have to be determined to combat the problem. Objective: To determine the association between sociodemographic status and physical functioning of obese school going children. Methods: This was a cross sectional type of descriptive study conducted at different schools of Rajshahi city from June 2015 to September 2015. Four (4) schools were selected- a) Govt. Laboratory High School, Rajshahi b) Rajshahi Collegiate School c) River view Collectorate School, Rajshahi and d) Rajshahi University School. The study population were 5 to 15 years old obese school children. A total number of 221 children were interviewed. Results: The ages of the respondents were between 4 to 15 years, and the mean age was 7.83±3.058 years. Among the 221 respondents more than half (56.6%) were in 4-7 years of age group, another 24.0% belonged to the age group of 8- 11 years and only 19.5% were 12- 15 years age group. Weight of the respondents was from 20 to 65 kg and mean weight of the respondents was (41.64±10.75). Here, 36.2% weight was from 37-47 kg and 29.0% weight was from 26-36 kg. Another 23.1%, 7.7% and 4.1% weight was from 48-58 kg, 59-69 kg and 15-25 kg respectively. There was no significant relationship with respondent age and sex with physical functioning (p ≥ 0.05). There was a significant relationship with weight and physical functioning (p≤0.05). Conclusions: The sociodemographic status may influence the physical functioning of the obese school going children. Their lifestyle must be modified in this early life otherwise they will be affected by different non communicable disease J Rang Med Col. March 2024; Vol. 9, No. 1: 71-76

Maternal high fat diet programs spatial learning and central leptin signaling in mouse offspring in a sex-specific manner

Environmental factors in early life have been demonstrated to increase the risk of neurodevelopmental disorders in offspring, especially the deficiency of the cognitive ability. Leptin has emerged as a key hormone that conveys information on energy stores, but there is growing appreciation that leptin signaling may also play an important role in neurodevelopment. The present study aimed to investigate whether maternal HFD exposure impairs the offspring learning and memory through the programming of central leptin system. We observed that hippocampus-dependent learning and memory were impaired in male but not female offspring from HFD-fed maternal ancestors (C57BL/6 mice), as assessed by novel object recognition and Morris water maze tests. Moreover, the chromatin immunoprecipitation results revealed the maternal HFD consumption led to the increasement in the binding of the histone marker H3K9me3 in male offspring, which mediates gene silencing in the leptin receptor promoter region. Furthermore, there was an increase in the expression of the histone methylase SUV39H1 in male but not female offspring, which regulates H3K9me3. Additionally, it has been observed that IL-6 and IL-1 also could lead to similar alternations when acting on cultured hippocampal neurons in vitro. Taken together, our data suggest that maternal HFD consumption influences male offspring hippocampal cognitive performance in a sex-specific manner, and central leptin signaling may serve as the cross-talk between maternal diet and cognitive impairment in offspring.

The Potential Impact of the Gut Microbiota on Neonatal Brain Development and Adverse Health Outcomes.

Over the past decade, microbiome research has significantly expanded in both scope and volume, leading to the development of new models and treatments targeting the gut-brain axis to mitigate the effects of various disorders. Related research suggests that interventions during the critical period from birth to three years old may yield the greatest benefits. Investigating the substantial link between the gut and brain during this crucial developmental phase raises fundamental issues about the role of microorganisms in human health and brain development. This underscores the importance of focusing on the prevention rather than the treatment of neurodevelopmental and neuropsychiatric disorders. The present review examines the gut microbiota from birth to age 3, with a particular focus on its potential relationship with neurodevelopment. This review emphasizes the immunological mechanisms underlying this relationship. Additionally, the study investigates the impact of the microbiome on cognitive development and neurobehavioral issues such as anxiety and autism. Importantly, it highlights the need to integrate mechanistic studies of animal models with epidemiological research across diverse cultures to better understand the role of a healthy microbiome in early life and the implications of dysbiosis. Furthermore, this review summarizes factors contributing to the transmission of gut microbiome-targeted therapies and their effects on neurodevelopment. Recent studies on environmental toxins known to impact neurodevelopment are also reviewed, exploring whether the microbiota may mitigate or modulate these effects.

Lipids as biomarkers to assess the nutritional and physiological status of two diadromous fish (Anguilla anguilla and Chelon auratus) at early life stages in a temperate macrotidal estuary.

Estuaries are considered as key habitats for the early life stages of fish. However, in the face of massive destruction of many estuarine intertidal areas, management and conservation measures are needed. Fish condition indicators may be used as a proxy of habitat quality and provide valuable information for management of coastal areas. In this study, the larvae of golden mullet (Chelon auratus) and European glass eels (Anguilla anguilla) were sampled in three sites of the Gironde Estuary. Different lipid classes and fatty acids were quantified: phospholipids (globally, phosphatidylethanolamine and phosphatidylcholine), triglycerides, omega-3 (particularly docosahexaenoic and eicosapentaenoic acids), omega-6 and C18:1. These biomarkers provide information on the nutritional status of the larvae as well as on prey availability and larvae diet between sites. One site significantly differed from the others as it seemed to offer abundant and better-quality prey. The very high levels of omega-3 contained in mullet larvae suggested that this site provided a high amount of diatoms. However, the mullet larvae that colonized this site also showed physiological stress that could be explained by exposure to pollutants through their prey. This work constitutes an essential baseline for developing biomarkers to assess the quality of habitats in a global change context.

Hydroalcoholic Extract of Centella asiatica and Madecassic Acid Reverse Depressive-Like Behaviors, Inflammation and Oxidative Stress in Adult Rats Submitted to Stress in Early Life.

Major depressive disorder (MDD) is a severe disorder that causes enormous loss of quality of life, and among the factors underlying MDD is stress in maternal deprivation (MD). In addition, classic pharmacotherapy has presented severe adverse effects. Centella asiatica (C. asiatica) demonstrates a potential neuroprotective effect but has not yet been evaluated in MD models. This study aimed to evaluate the effect of C. asiatica extract and the active compound madecassic acid on possible depressive-like behavior, inflammation, and oxidative stress in the hippocampus and serum of young rats submitted to MD in the first days of life. Rats (after the first day of birth) were separated from the mother for 3h a day for 10days. When adults, these animals were divided into groups and submitted to treatment for 14days. After subjecting the animals to protocols of locomotor activity in the open field and behavioral despair in the forced swimming test, researchers then euthanized the animals. The hippocampus and serum were collected and analyzed for the inflammatory cytokines and oxidative markers. The C. asiatica extract and active compound reversed or reduced depressive-like behaviors, inflammation in the hippocampus, and oxidative stress in serum and hippocampus. These results suggest that C. asiatica and madecassic acid have potential antidepressant action, at least partially, through anti-inflammatory and antioxidant profiles.

Comprehensive spatial distribution of patients with first-episode psychosis (FEP) and its relation to socio-economic factors.

The functional-cognitive impact of first-episode psychosis (FEP) is extremely relevant and implies dysfunction from early life stages like adolescence and youth. Like other illnesses, FEP incidence is also influenced by environmental factors. It is necessary to attend to this age group with early interventions and to act on the environmental factors that the literature correlates with increased FEP incidence: socio-economic aspects, social adversity, bullying at school or cannabis use. In this context, identifying the areas of cities where FEP patients concentrate is important to perform early interventions. The spatial analysis of patient distribution in a whole city is one way to identify the most vulnerable areas and to propose psycho-social interventions for the possible prevention and/or early detection of FEP by improving urban mental health. An epidemiological study of point patterns to determine the areas of a city with a higher incidence of patients with FEP. To do so, the addresses of FEP cases were georeferenced from 1 January 2016 to 31 October 2022, and 109 FEP patients were analysed. Data from a random sample of 383 controls, comprising their addresses, age, and sex, were randomly obtained from the official city council database. By GIS, the areas with higher FEP incidence were analysed to see if they coincided with the zones where inhabitants with lower incomes lived. The risk ratio of the FEP patients was compatible with the constant risk ratio in Albacete (p = 0.22). When performing the process separately with cases and controls only in men and women, the results were not significant for both distributions (p value: 0.12 and 0.57, respectively). Nonetheless, areas within the city had a significantly higher risk. These groups of cases coincided with those who had lower income and more inequality for women, but this pattern was not clear for men. Classifying city areas per income can help to determine the zones at higher risk of FEP, which would allow early healthcare and preventive measures for these zones.

Functioning and neurocognition in very early and early-life onset bipolar disorders: the moderating role of bipolar disorder type.

Defining homogeneous subgroups of bipolar disorder (BD) is a major goal in personalized psychiatry and research. According to the neurodevelopmental theory, age at onset may be a key variable. As potential trait markers of neurodevelopment, cognitive and functional impairment should be greater in the early form of the disease, particularly type 1 BD (BD I). The age at onset was assessed in a multicenter, observational sample of 4190 outpatients with BD. We used a battery of neuropsychological tests to assess six domains of cognition. Functioning was measured using the Functioning Assessment Short Test (FAST). We studied the potential moderation of the type of BD on the associations between the age at onset and cognitive and functioning in a subsample of 2072 euthymic participants, controlling for potential clinical and socio-demographic covariates. Multivariable analyses showed cognition to not be impaired in individuals with early (21-30years) and very early-life (before 14years) onset of BD. Functioning was equivalent between individuals with early and midlife-onset of BD II and NOS but better for individuals with early onset of BD I. In contrast, functioning was not worse in individuals with very early-onset BD I but worse in those with very early-onset BD II and NOS. Early-life onset BDs were not characterized by poorer cognition and functioning. Our results do not support the neurodevelopmental view that a worse cognitive prognosis characterizes early-life onset BD. This study suggests that functional remediation may be prioritized for individuals with midlife-onset BD I and very early life onset BD 2 and NOS.

Persistent gene expression and DNA methylation alterations linked to carcinogenic effects of dichloroacetic acid.

Mechanistic understanding of transient exposures that lead to adverse health outcomes will enhance our ability to recognize biological signatures of disease. Here, we measured the transcriptomic and epigenomic alterations due to exposure to the metabolic reprogramming agent, dichloroacetic acid (DCA). Previously, we showed that exposure to DCA increased liver tumor incidence in B6C3F1 mice after continuous or early life exposures significantly over background level. Using archived formalin-fixed liver samples, we utilized modern methodologies to measure gene expression and DNA methylation levels to link to previously generated phenotypic measures. Gene expression was measured by targeted RNA sequencing (TempO-seq 1500+ toxicity panel: 2754 total genes) in liver samples collected from 10-, 32-, 57-, and 78-week old mice exposed to deionized water (controls), 3.5 g/L DCA continuously in drinking water ("Direct" group), or DCA for 10-, 32-, or 57-weeks followed by deionized water until sample collection ("Stop" groups). Genome-scaled alterations in DNA methylation were measured by Reduced Representation Bisulfite Sequencing (RRBS) in 78-week liver samples for control, Direct, 10-week Stop DCA exposed mice. Transcriptomic changes were most robust with concurrent or adjacent timepoints after exposure was withdrawn. We observed a similar pattern with DNA methylation alterations where we noted attenuated differentially methylated regions (DMRs) in the 10-week Stop DCA exposure groups compared to the Direct group at 78-weeks. Gene pathway analysis indicated cellular effects linked to increased oxidative metabolism, a primary mechanism of action for DCA, closer to exposure windows especially early in life. Conversely, many gene signatures and pathways reversed patterns later in life and reflected more pro-tumorigenic patterns for both current and prior DCA exposures. DNA methylation patterns correlated to early gene pathway perturbations, such as cellular signaling, regulation and metabolism, suggesting persistence in the epigenome and possible regulatory effects. Liver metabolic reprogramming effects of DCA interacted with normal age mechanisms, increasing tumor burden with both continuous and prior DCA exposure in the male B6C3F1 rodent model.

Early-life exposures and long-term health: adverse gestational environments and the programming of offspring renal and vascular disease.

According to the Developmental Origins of Health and Disease (DOHaD) hypothesis, exposure to certain environmental influences during early life may be a key determinant of fetal development and short- and long-term offspring health. Indeed, adverse conditions encountered during the fetal, perinatal, and early childhood stages can alter normal development and growth, as well as put the offspring at elevated risk of developing long-term health conditions in adulthood, including chronic kidney disease (CKD) and cardiovascular diseases. Of relevance in understanding the mechanistic basis of these long-term health conditions, are previous findings showing low glomerular number in human intrauterine growth restriction and low birth weight - indicators of a sub-optimal intrauterine environment. In different animal models, the main sub-optimal intrauterine conditions studied relate to maternal dietary manipulations, poor micronutrient intake, prenatal ethanol exposure, maternal diabetes, glucocorticoid and chemical exposure, hypoxia, and placental insufficiency. These studies have demonstrated changes in kidney structure, glomerular endowment, and expression of key genes and signalling pathways controlling endocrine, excretion and filtration function of the offspring. This review aims to summarize those studies to uncover the effects and mechanisms by which adverse gestational environments impact offspring renal and vascular health in adulthood. This is important for identifying agents and interventions that can prevent and mitigate the long-term consequences of an adverse intrauterine environment on the subsequent generation.

Novel Perspective on the Regulation of Offspring Food Allergy by Maternal Diet and Nutrients.

There has been a dramatic surge in the prevalence of food allergy (FA) that cannot be explained solely by genetics, identifying mechanisms of sensitization that are driven by environmental factors has become increasingly important. Diet, gut microbiota, and their metabolites have been shown to play an important role in the development of FA. In this review, we discuss the latest epidemiological evidence on the impact of two major dietary patterns and key nutrients in early life on the risk of offspring developing FA. The Western diet typically includes high sugar and high fat, which may affect the immune system of offspring and increase susceptibility to FA. In contrast, the Mediterranean diet is rich in fiber, which may reduce the risk of FA in offspring. Furthermore, we explore the potential mechanisms by which maternal dietary nutrients during a window of opportunity (pregnancy, birth, and lactation) influences the susceptibility of offspring to FA through multi-interface crosstalk. Finally, we discuss the limitations and gaps in the available evidence regarding the relationship between maternal dietary nutrients and the risk of FA in offspring. This review provides novel perspective on the regulation of offspring FA by maternal diet and nutrients.

Short communication: Lifetime musical activity and resting-state functional connectivity in cognitive networks.

Participation in multimodal leisure activities, such as playing a musical instrument, may be protective against brain aging and dementia in older adults (OA). Potential neuroprotective correlates underlying musical activity remain unclear. This cross-sectional study investigated the association between lifetime musical activity and resting-state functional connectivity (RSFC) in three higher-order brain networks: the Default Mode, Fronto-Parietal, and Salience networks. We assessed 130 cognitively unimpaired participants (≥ 60 years) from the baseline cohort of the DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) study. Lifetime musical activity was operationalized by the self-reported participation in musical instrument playing across early, middle, and late life stages using the Lifetime of Experiences Questionnaire (LEQ). Participants who reported musical activity during all life stages (n = 65) were compared to controls who were matched on demographic and reserve characteristics (including education, intelligence, socioeconomic status, self-reported physical activity, age, and sex) and never played a musical instrument (n = 65) in local (seed-to-voxel) and global (within-network and between-network) RSFC patterns using pre-specified network seeds. Older participants with lifetime musical activity showed significantly higher local RSFC between the medial prefrontal cortex (Default Mode Network seed) and temporal as well as frontal regions, namely the right temporal pole and the right precentral gyrus extending into the superior frontal gyrus, compared to matched controls. There were no significant group differences in global RSFC within or between the three networks. We show that playing a musical instrument during life relates to higher RSFC of the medial prefrontal cortex with distant brain regions involved in higher-order cognitive and motor processes. Preserved or enhanced functional connectivity could potentially contribute to better brain health and resilience in OA with a history in musical activity. German Clinical Trials Register (DRKS00007966, 04/05/2015).

Acute toxicity testing of 6PPD-quinone on the estuarine-dependent sport fish, Sciaenops ocellatus.

Recently, large-scale fish kills in the Pacific Northwest were linked to tire wear particles (TWPs) left on roadways, with the lethality attributed to 6PPD-quinone. which has a median lethal concentration of <1 µg/L for selected salmonids. However, there remains a paucity of 6PPD-quinone toxicity values developed for estuarine fish species, which is particularly significant because estuaries receiving inflows from highly urbanized watersheds are especially vulnerable to TWP contamination. Therefore, the present study aimed to determine the toxicity of 6PPD-quinone to an economically and ecologically important estuarine-dependent fish-red drum (Sciaenops ocellatus). Here, we examined the relative sensitivities of three early life stages within red drum: embryonic, larval, and post-settlement for 24-72 hours, depending on the life stage. Exposure concentrations ranged from 10 μg/L to 500 μg/L. We also assessed the sub-lethal impacts of 6PPD-quinone exposure on development during embryonic and larval stages, including body and organ sizes. Our results indicate that red drum are not acutely sensitive to 6PPD-quinone at each early life stage tested. We also found that yolk-sac larvae did not exhibit sub-lethal morphological impacts in a dose-dependent manner, regardless of exposure during embryonic and larval stages. These data are the first to assess the impacts of 6PPD-quinone on estuarine-dependent non-model fishes.

Subtypes of childhood maltreatment and posttraumatic stress disorder symptoms in an adult trauma sample: The mechanistic role of sleep.

Childhood maltreatment is indisputably linked to adverse mental health outcomes, including an increased risk to develop posttraumatic stress disorder (PTSD) in adulthood. The role of childhood maltreatment in the context of recovery from a trauma later in adulthood is not well understood. A variable related to both childhood maltreatment and PTSD symptoms, and a potential link between the two, is sleep. The current study aimed to understand how sleep disturbances may play a mechanistic role in the effect of subtypes of childhood maltreatment on PTSD symptom severity in an adult trauma sample. 160 adults (90 women; Mage = 33.73, SD = 10.86) were recruited from the emergency department at a Level-1 trauma center in southeastern Wisconsin after experiencing a traumatic injury. Experiences of childhood maltreatment and sleep were self-reported at 2-week and 3-month posttrauma, respectively. PTSD symptoms were clinically assessed 6 months later. Sleep disturbances 3-month posttrauma mediated the effect of emotional abuse, physical neglect, and emotional neglect on PTSD symptom 6 months after the traumatic injury. The effect of sexual and physical abuse on PTSD symptoms was not significantly mediated by sleep disturbances. These findings highlight the differential impact of subtypes of childhood maltreatment on PTSD symptoms, the mechanistic role of sleep, and the need to consider early life adversity when assessing adult posttrauma experiences. These results also suggest that interventions aimed at improving sleep quality might improve PTSD symptoms in those who have experienced childhood maltreatment and a subsequent traumatic injury in adulthood. (PsycInfo Database Record (c) 2024 APA, all rights reserved).