Differential regulation of gene expression pathways with dexamethasone and ACTH after early life seizures.

Early-life seizures (ELS) are associated with persistent cognitive deficits such as ADHD and memory impairment. These co-morbidities have a dramatic negative impact on the quality of life of patients. Therapies that improve cognitive outcomes have enormous potential to improve patients' quality of life. Our previous work in a rat flurothyl-induction model showed that administration of adrenocorticotropic hormone (ACTH) at time of seizure induction led to improved learning and memory in the animals despite no effect on seizure latency or duration. Administration of dexamethasone (Dex), a corticosteroid, did not have the same positive effect on learning and memory and has even been shown to exacerbate injury in a rat model of temporal lobe epilepsy. We hypothesized that ACTH exerted positive effects on cognitive outcomes through beneficial changes to gene expression and proposed that administration of ACTH at seizure induction would return gene-expression in the brain towards the normal pattern of expression in the Control animals whereas Dex would not. Twenty-six Sprague-Dawley rats were randomized into vehicle- Control, and ACTH-, Dex-, and vehicle- ELS. Rat pups were subjected to 60 flurothyl seizures from P5 to P14. After seizure induction, brains were removed and the hippocampus and PFC were dissected, RNA was extracted and sequenced, and differential expression analysis was performed using generalized estimating equations. Differential expression analysis showed that ACTH pushes gene expression in the brain back to a more normal state of expression through enrichment of pathways involved in supporting homeostatic balance and down-regulating pathways that might contribute to excitotoxic cell-damage post-ELS.

Envisioning the future of colorectal surgery: preclinical assessment and detailed description of an endoluminal robotic system (ColubrisMX ELS).

BACKGROUND: The EndoLuminal Surgical System (ELS) is an emerging non-linear robotic system specifically designed for transanal surgery that allows for excision of colorectal neoplasia and luminal defect closure. METHODS: An evaluation of ELS was conducted by a single surgeon in a preclinical setting at the EndoSurgical Center of Florida in Orlando, between October 1st, 2020 and December 31st, 2020, using porcine colon as a model. Mock lesions measured 2.5 to 3.5 cm were excised partial-thickness. Specimen quality and excision time was assessed and evaluated. RESULTS: Twenty consecutive robotic transanal minimally invasive surgery (TAMIS) operations utilizing the ELS system were successfully performed without fragmentation. The mean and standard deviation procedure time for all 20 cases was 18.41 ± 14.15 min. The latter 10 cases were completed in substantially less time, suggesting that ELS requires at least 10 preclinical cases for a surgeon to become familiar with the technology. A second task, namely suture closure of the partial-thickness defect, was performed in 9 of the 20 cases. Mean time and standard deviation for this task measured 27.89 ± 10.07 min. There were no adverse events. CONCLUSIONS: ELS was successful in performing the tasks of partial-thickness disc excision and closure in a preclinical evaluation. Further study is necessary to determine its clinical applicability.

A Taxonomy of Ethical, Legal and Social Implications of Wearable Robots: An Expert Perspective.

Wearable robots and exoskeletons are relatively new technologies designed for assisting and augmenting human motor functions. Due to their different possible design applications and their intimate connection to the human body, they come with specific ethical, legal, and social issues (ELS), which have not been much explored in the recent ELS literature. This paper draws on expert consultations and a literature review to provide a taxonomy of the most important ethical, legal, and social issues of wearable robots. These issues are categorized in (1) wearable robots and the self, (2) wearable robots and the other, and (3) wearable robots in society.

Implementation of the European Laryngological Society classification for pediatric benign laryngotracheal stenosis: a multicentric study.

PURPOSE: The European Laryngological Society (ELS) has published a revised classification for benign laryngotracheal stenosis (LTS), based on their degree, longitudinal extension, and associated comorbidities. We retrospectively applied this classification to pediatric patients treated in four referral centers to assess its reliability in predicting surgical outcomes. METHODS: We included 191 pediatric LTS patients treated by segmental resection, restaged according to the degree of stenosis (I-IV according to Myer-Cotton grading system), number of subsites involved ("a" to "d" for 1-4 subsites among supraglottis, glottis, subglottis and trachea), and presence of systemic comorbidity ("+" sign). We analyzed the ability of this scoring system in predicting the rates of decannulation and complications, as well as the number of re-treatments. RESULTS: The mean decannulation rate was 88%; a higher rate was observed in patients without comorbidities (95.7% vs. 78.1%, p < 0.001), with two or fewer vs. three or four subsites involved (89% vs. 72%, p < 0.01), and in those with an ELS score of IIIa+ or less vs. patients with IIIb or more (96% vs. 82%, p < 0.001). Surgical complications were not dependent on the degree of stenosis, but rather on the number of affected subsites (p < 0.05), as well as on the presence of associated comorbidities (RR 7.5, p < 0.01). The number of re-treatments was dependent on length of resection (p < 0.05), stage according to the revised ELS classification (p < 0.001), and presence of surgical complications (RR 17, p < 0.001). CONCLUSIONS: The revised ELS classification system is easy to apply in everyday practice and offers a sound contribution in the decision-making process.

3,4-diaminopyridine base effectively treats the weakness of Lambert-Eaton myasthenia.

INTRODUCTION: 3,4-diaminopyridine has been used to treat Lambert-Eaton myasthenia (LEM) for 30 years despite the lack of conclusive evidence of efficacy. METHODS: We conducted a randomized double-blind placebo-controlled withdrawal study in patients with LEM who had been on stable regimens of 3,4-diaminopyridine base (3,4-DAP) for ≥ 3 months. The primary efficacy endpoint was >30% deterioration in triple timed up-and-go (3TUG) times during tapered drug withdrawal. The secondary endpoint was self-assessment of LEM-related weakness (W-SAS). RESULTS: Thirty-two participants were randomized to continuous 3,4-DAP or placebo groups. None of the 14 participants who received continuous 3,4-DAP had > 30% deterioration in 3TUG time versus 72% of the 18 who tapered to placebo (P < 0.0001). W-SAS similarly demonstrated an advantage for continuous treatment over placebo (P < 0.0001). Requirement for rescue and adverse events were more common in the placebo group. DISCUSSION: This trial provides significant evidence of efficacy of 3,4-DAP in the maintenance of strength in LEM. Muscle Nerve 57: 561-568, 2018.

Intergenerational Transmission of DNA Methylation Signatures Associated with Early Life Stress.

Early life stress in humans (i.e. maltreatment, violence exposure, loss of a loved one) and in rodents (i.e. disrupted attachment or nesting, electric shock, restraint, predator odor) occurs during critical steps of neural circuit formation. ELS in humans is associated with increased risk for developmental psychopathology, including anxious and depressive phenotypes. The biological mechanisms underlying these potentially persistent maladaptive changes involve long-term epigenetic modifications, which have been suggested to be potentially transmissible to subsequent generations. DNA methylation is an epigenetic mechanism that modifies gene expression patterns in response to environmental challenges and influences mutation rates. It remains to be seen whether a functionally relevant fraction of DNA methylation marks can escape genome-wide erasures that occur in primordial germ cells and after fertilization within the zygote. Early life-stress-triggered changes in epigenetic mediated transmission of acquired behavioral traits among humans have been assessed mainly by targeting genes involved in the hypothalamic-pituitary-adrenal (HPA) axis, such as NR3C1 and FKBP5. Recently, researchers examining epigenetic transmission have begun to apply genome-wide approaches. In humans, reduced representation bisulfite sequencing (RRBS) was performed on peripheral samples that were obtained from individuals who were prenatally exposed to the "Dutch Hunger Winter", resulting in two Differentially Methylated Regions (DMRs) in INSR and CPTIA genes that were functionally, biologically and technically validated, and significantly associated with birth weights and LDL cholesterol levels in offspring. In rodents, non-genomic intergenerational transmission of anxiety which was associated with differentially methylated enhancers that were putatively involved in lipid signaling and synaptic/neurotransmission in hippocampal granule cells, was discovered also using RRBS. Finally, transgenerational transmission of altered behaviors was associated with sperm-derived microRNAs produced by ELS male mice. The field of epigenetic transmission is just beginning to enter the epigenomic era by using genome-wide analyses. Such approaches remain of strong interest to human studies, first in order to help to assess the relevance of the previous targeted studies, and second to discover new important epigenetic modifications of potential clinical importance. New discoveries may help to assess how transmittable the negative impact of stress may be to offspring. The latter may open doors for future treatments and resilience-promoting interventions, as well as new approaches to treat the effects of childhood trauma before the onset of psychiatric disorder.

New statistical methods for estimation of recombination fractions in F2 population.

BACKGROUND: Dominant markers in an F2 population or a hybrid population have much less linkage information in repulsion phase than in coupling phase. Linkage analysis produces two separate complementary marker linkage maps that have little use in disease association analysis and breeding. There is a need to develop efficient statistical methods and computational algorithms to construct or merge a complete linkage dominant marker maps. The key for doing so is to efficiently estimate recombination fractions between dominant markers in repulsion phases. RESULT: We proposed an expectation least square (ELS) algorithm and binomial analysis of three-point gametes (BAT) for estimating gamete frequencies from F2 dominant and codominant marker data, respectively. The results obtained from simulated and real genotype datasets showed that the ELS algorithm was able to accurately estimate frequencies of gametes and outperformed the EM algorithm in estimating recombination fractions between dominant loci and recovering true linkage maps of 6 dominant loci in coupling and unknown linkage phases. Our BAT method also had smaller variances in estimation of two-point recombination fractions than the EM algorithm. CONCLUSION: ELS is a powerful method for accurate estimation of gamete frequencies in dominant three-locus system in an F2 population and BAT is a computationally efficient and fast method for estimating frequencies of three-point codominant gametes.

A rapid method for analysis of fermentatively produced D-xylonate using ultra-high performance liquid chromatography and evaporative light scattering detection.

An ultra-high performance liquid chromatography (UHPLC) based method for the analysis of d-xylonate was developed using an amide column in combination with an evaporative light scattering (ELS) detector. Separation of d-xylonate from other components of the fermentation medium was achieved. The dynamic range of the method was 0.2-7.0 g/L.

ELS1, a novel MATE transporter related to leaf senescence and iron homeostasis in Arabidopsis thaliana.

The multidrug and toxic compound extrusion (MATE) transporters mediate the coupled exchange of organic substrates and monovalent cations have been recently implicated in various plant biological activities. In this work, we isolated a dominant mutant from an Arabidopsis activation-tagging mutant pool. This mutant exhibits pleiotropic phenotype including early flowering, dwarf and bushy architecture, minified lateral organs and early leaf senescence, and is therefore designated early leaf senescence 1-Dominaint (els1-D). Genotyping assays showed that els1-D is a gain-of-function mutant of a novel MATE transporter gene, ELS1, which encodes a close homolog of the previously reported ADP1, BCD1 and DTX50. Further investigations revealed that the overexpression of ELS1 reduces iron content in els1-D, and the accelerated senescence of the detached els1-D leaves can be recovered by exogenous iron supply. In addition, we also found that ELS1 is an iron responsive gene. Based on these findings, we proposed that ELS1 is related to leaf senescence and iron homeostasis in Arabidopsis.

Multidimensional assessment of neuroendocrine and psychopathological profiles in maltreated youth.

It has been debated whether children who have experienced early life stress (ELS), such as early caregiver separation show elevated risk for stress-related psychiatric disorders and a multi-symptom psychopathological profile that is not fully reflected in categorical assessments. In this study, we investigated dimensional measures of stress-related psychopathology in children in permanent out-of-home care, taking into account potential neuroendocrine interactions. In the current study, 25 children who had been placed in permanent out-of-home care before age 3 (years) and 26 controls (aged 10.6 ± 1.75 years) were investigated with categorical (DSM-IV) and dimensional assessments (CBCL) of psychopathology and diurnal salivary cortisol levels were assessed. Semi-structured interviews (K-DIPS) revealed no significant group differences in full-scale psychiatric diagnoses, whereas dimensional assessment (CBCL) revealed significant group differences in externalizing and total problem behaviours within the clinical range for children with ELS. Only children with ELS showed a combined symptom profile of clinical-range internalizing and externalizing problems. Lower morning cortisol values and subsequent flatter decline was found in subjects with ELS children compared to controls, showing group differences in diurnal cortisol secretion. Lower morning cortisol values were associated with more problem behaviour in the ELS group. Results show that ELS children exhibited increased psychopathological symptom severity and complexity associated with lower morning cortisol levels, which was not fully reflected in categorical assessments. This highlights the importance of incorporating dimensional assessments and neurobiological factors into psychopathological evaluations of children in out-of-home care in order to facilitate early identification of children at high risk for stress-related disorders.

Internal effect concentrations of organic substances for early life development of egg-exposed fish.

The present study investigates the likelihood that early life development of marine fish from contaminated areas is affected by maternally transferred persistent organic substances (POPs). The common sole (Solea solea) was used as model species. Fertilized eggs were exposed via the water until hatching, 6 days post fertilization. The newly hatched larvae were allowed to develop further under unexposed conditions until the end of the metamorphosis. Effects on the larvae were determined for the dioxin-like polychlorinated biphenyl PCB 126, the technical PCB-mixture Arochlor 1254, polybrominated diphenylethers (PBDEs), and hexabromocyclododecane (HBCD), for an artificial mixture of PCBs and PBDEs, and for 'field mixtures' extracted from sole from the North Sea and the contaminated Western Scheldt estuary. Effect levels were expressed as tissue concentrations in the newly hatched larvae at the end of the exposure period. Exposure to PCBs, PBDEs, and the artificial and field mixtures caused mortality that started to occur shortly after the larvae became free-feeding (10 days post fertilization) and continued to increase until the onset of metamorphosis, 15 days later. The effects induced by the field mixtures correlated well with the ΣPCB concentrations in the tissue of the exposed larvae. No indications were found for synergistic effects or for substantial contribution of other (unknown) substances in the field mixtures. HBCD did not induce toxic effects. As lipid normalized POP levels in fish eggs are in general comparable to the levels in the tissue of the female fish, fish tissue concentrations are indicative of the internal exposure of the developing larvae as a result maternally transferred POPs will occur in the field. In sole from the Western Scheldt estuary POP levels are about twenty times lower than the larval tissue concentration that produced 50 percent early life stage mortality. Levels in North Sea sole are an order of a magnitude lower. At more heavily contaminated sites negative effect of PCBs, especially of those with dioxin-like toxicity can be expected.

Early life stress modulates the genetic influence on brain structure and cognitive function in children.

The enduring influence of early life stress (ELS) on brain and cognitive development has been widely acknowledged, yet the precise mechanisms underlying this association remain elusive. We hypothesize that ELS might disrupt the genome-wide influence on brain morphology and connectivity development, consequently exerting a detrimental impact on children's cognitive ability. We analyzed the multimodal data of DNA genotypes, brain imaging (structural and diffusion MRI), and neurocognitive battery (NIH Toolbox) of 4276 children (ages 9-10 years, European ancestry) from the Adolescent Brain Cognitive Development (ABCD) study. The genome-wide influence on cognitive function was estimated using the polygenic score (GPS). By using brain morphometry and tractography, we identified the brain correlates of the cognition GPSs. Statistical analyses revealed relationships for the gene-brain-cognition pathway. The brain structural variance significantly mediated the genetic influence on cognition (indirect effect = 0.016, PFDR < 0.001). Of note, this gene-brain relationship was significantly modulated by abuse, resulting in diminished cognitive capacity (Index of Moderated Mediation = -0.007; 95 % CI = -0.012 âˆ¼ -0.002). Our results support a novel gene-brain-cognition model likely elucidating the long-lasting negative impact of ELS on children's cognitive development.

A single 24 h maternal separation at PND 9 promotes behavioral resilience of female C57BL/6J mice and the possible role of hippocampal Homer1a.

Early life stress (ELS) has been thought to increase vulnerability to developing psychiatric disorders later in life, while some researchers have found that adversity early in life may promote stress resilience. Studies investigating the resilient effect of maternal separation (MS) are still relatively few, and the underlying mechanisms remain unknown. In the current study, the effect of a single 24 h MS paradigm at postnatal day 9 (PND 9) in female C57BL/6J mice was investigated by assessing behavioral performance in middle adolescence. We demonstrated that, mice in MS group displayed decreased anxiety-like behavior and increased exploratory behavior than controls in the open field test and elevated plus maze test. Furthermore, MS mice exhibited improved hippocampal-dependent spatial learning in the Morris water maze test. This performance indicated behavioral resilience to early life stress. The protein expression levels of Homer1 isoforms, which are implicated in a variety of neuropsychiatric disorders, were evaluated using Western blot analysis. A significant increase in hippocampal Homer1a protein expression was observed immediately after MS, which subsequently decreased until adolescence (PND 27-42), when a significant increase was observed again. This distinctive change of hippocampal Homer1a protein expression pattern indicated that hippocampal Homer1a might play a role in behavioral resilience to MS in female C57BL/6J mice. In conclusion, this study demonstrated that exposure to a single 24 h MS at PND 9 promoted behavioral resilience of female C57BL/6J mice in middle adolescence. This behavioral resilience might be related to increased expression of hippocampal Homer1a.

Hemolysis Index Correlations with Plasma-Free Hemoglobin and Plasma Lactate Dehydrogenase in Critically Ill Patients under Extracorporeal Membrane Oxygenation or Mechanical Circulatory Support-A Single-Center Study.

Monitoring for thrombosis and hemolysis is crucial for patients under extracorporeal or mechanical circulatory support, but it can be costly. We investigated correlations between hemolysis index (HI) and plasma-free hemoglobin (PFH) levels on one hand, and between the HI and plasma lactate dehydrogenase (LDH) levels on the other, in critically ill patients with and without extracorporeal or mechanical circulatory support. Additionally, we calculated the cost reductions if monitoring through HI were to replace monitoring through PFH or plasma LDH. In a single-center study, HI was compared with PFH and plasma LDH levels in blood samples taken for routine purposes in critically ill patients with and without extracorporeal or mechanical circulatory support. A cost analysis, restricted to direct costs associated with each measurement, was made for an average 10-bed ICU. This study included 147 patients: 56 patients with extracorporeal or mechanical circulatory support (450 measurements) and 91 patients without extracorporeal or mechanical circulatory support (562 measurements). The HI correlated well with PFH levels (r = 0.96; p < 0.01) and poorly with plasma LDH levels (r = 0.07; p < 0.01) in patients with extracorporeal or mechanical circulatory support. Similarly, HI correlated well with PFH levels (r = 0.97; p < 0.01) and poorly with plasma LDH levels (r = -0.04; p = 0.39) in patients without extracorporeal or mechanical circulatory support. ROC analyses demonstrated a strong performance of HI, with the curve indicating excellent discrimination in the whole cohort (area under the ROC of 0.969) as well as in patients under ECMO or mechanical circulatory support (area under the ROC of 0.988). Although the negative predictive value of HI for predicting PFH levels > 10 mg/dL was high, its positive predictive value was found to be poor at various cutoffs. A simple cost analysis showed substantial cost reduction if HI were to replace PFH or plasma LDH for hemolysis monitoring. In conclusion, in this cohort of critically ill patients with and without extracorporeal or mechanical circulatory support, HI correlated well with PFH levels, but poorly with plasma LDH levels. Given the high correlation and substantial cost reductions, a strategy utilizing HI may be preferable for monitoring for hemolysis compared to monitoring strategies based on PFH or plasma LDH. The PPV of HI, however, is unacceptably low to be used as a diagnostic test.

Mind the gap - Relevant design for laboratory oil exposure of fish as informed by a numerical impact assessment model.

Laboratory experiments provide knowledge of species-specific effects thresholds that are used to parameterize impact assessment models of oil contamination on marine ecosystems. Such experiments typically place individuals of species and life stages in tanks with different contaminant concentrations. Exposure concentrations are usually fixed, and the individuals experience a shock treatment being moved from clean water directly into contaminated water and then back to clean water. In this study, we use a coupled numerical model that simulates ocean currents and state, oil dispersal and fate, and early life stages of fish to quantify oil exposure histories, specifically addressing oil spill scenarios of high rates and long durations. By including uptake modelling we also investigate the potential of buffering transient high peaks in exposure. Our simulation results are the basis for a recommendation on the design of laboratory experiments to improve impact assessment model development and parameterization. We recommend an exposure profile with three main phases: i) a gradual increase in concentration, ii) a transient peak that is well above the subsequent level, and iii) a plateau of fixed concentration lasting ∼3 days. In addition, a fourth phase with a slow decrease may be added.

Early-life stress affects Mongolian gerbil interactions with conspecific vocalizations in a sex-specific manner.

During development, early-life stress (ELS) impairs cognition, learning, and emotional regulation, in part by disrupting neural circuitry in regions underlying these higher-order functions. In addition, our recent work indicates that ELS also alters simple sensory perception: ELS impaired auditory perception and neural encoding of short gaps in sounds, which are essential for vocal communication. The combination of higher-order and basic sensory disruption suggests that ELS is likely to affect both the perception and interpretation of communication signals. We tested this hypothesis by measuring behavioral responses to conspecific vocalizations (those emitted by other gerbils) in ELS and untreated Mongolian gerbils. Because stress effects often differ by sex, we separately examined females and males. To induce ELS, pups were intermittently maternally separated and restrained from post-natal days (P) 9-24, a time window when the auditory cortex is most sensitive to external disruption. We measured the approach responses of juvenile (P31-32) gerbils to two types of conspecific vocalizations: an alarm call, which is emitted to alert other gerbils of a potential threat, and the prosocial contact call, which is emitted near familiar gerbils, especially after separation. Control males, Control females, and ELS females approached a speaker emitting pre-recorded alarm calls, while ELS males avoided this source, suggesting that ELS affects the response to alarm calls in male gerbils. During playback of the pre-recorded contact call, Control females and ELS males avoided the sound source, while Control males neither approached nor avoided, and ELS females approached the sound. These differences cannot be accounted for by changes in locomotion or baseline arousal. However, ELS gerbils slept more during playback, suggesting that ELS may reduce arousal during vocalization playback. Further, male gerbils made more errors than females on a measure of working memory, but the sex difference of cognition in this context may stem from novelty aversion rather than impaired memory. These data indicate that ELS influences behavioral responses to ethologically relevant communication sounds in a sex-specific manner, and are among the first to demonstrate an altered response to auditory stimuli following ELS. Such changes may arise from differences in auditory perception, cognition, or a combination of factors, and suggest that ELS may affect auditory communication in human adolescents.

Transgenerational effects of early-life stress on anxiety behavior in zebrafish (Danio rerio).

Early-life adversity impacts on anxiety-related behaviors in adulthood. The effects of such adversity not only affect the animal itself, but can be passed on transgenerationally. Pervasive effects of experimentally-induced early-life stress (ELS) have been documented in adult zebrafish but it is not clear if this can be passed on via the germline. Here, we investigated the effects of ELS across three generations, by analyzing the responses of adult animals exposed to ELS in two different anxiety-related tasks, as well as in social behavior, memory, and cognition. Animals exposed to ELS (at 7 days-post-fertilization) showed a marked attenuation of specific anxiety-related behaviors (F0) as adults, and these alterations were maintained across two subsequent generations (F1 and F2). This suggest zebrafish may be a useful model organism to study the transgenerational effects of ELS, and how this pertains to (for example) neuropsychiatric disorders. In addition, our data may naturally provoke questions regarding consideration of the environment of laboratory-housed zebrafish at early developmental stages. In particular, more work may be necessary to determine how different environmental stressors could affect data variability across laboratories.

Brief and long maternal separation in C57Bl6J mice: behavioral consequences for the dam and the offspring.

Introduction: Animal models, especially rodents, have become instrumental to experimentally investigate the effects of an adverse post-natal environment on the developing brain. For this purpose, maternal separation (MS) paradigms have been widely used in the last decades. Nonetheless, how MS affects maternal behavior and, ultimately, the offspring depend on multiple variables. Methods: To gain further insights into the consequences of MS, we decided to thoroughly measure and compare the effects of short (15 min, 3 times/day) vs. long (3 h, 1 time/day) separation on multiple maternally-associated behaviors and across the entire post-natal period. Results: Compared to unhandled control litters, our results confirmed previous studies and indicated that SMS enhanced the time and variety of maternal care whereas LMS resulted in poor caregiving. We also showed that SMS-accrued caregiving persisted during the whole post-natal period. In contrast, LMS effects on maternal behavior were restricted to the early life (P2-P10). Finally, we also analyzed the behavioral consequences of these different rearing social environments on the offspring. We found that MS has profound effects in social tasks. We showed that affiliative touch, a type of prosocial behavior that provides comfort to others, is particularly sensitive to the modification of maternal caregiving. Discussion: Our results provide further support to the contention that interactions during the early post-natal period critically contribute to emotional processing and brain co-construction.

Effects of prenatal opioid exposure on synaptic adaptations and behaviors across development.

In this review, we focus on prenatal opioid exposure (POE) given the significant concern for the mental health outcomes of children with parents affected by opioid use disorder (OUD) in the view of the current opioid crisis. We highlight some of the less explored interactions between developmental age and sex on synaptic plasticity and associated behavioral outcomes in preclinical POE research. We begin with an overview of the rich literature on hippocampal related behaviors and plasticity across POE exposure paradigms. We then discuss recent work on reward circuit dysregulation following POE. Additional risk factors such as early life stress (ELS) could further influence synaptic and behavioral outcomes of POE. Therefore, we include an overview on the use of preclinical ELS models where ELS exposure during key critical developmental periods confers considerable vulnerability to addiction and stress psychopathology. Here, we hope to highlight the similarity between POE and ELS on development and maintenance of opioid-induced plasticity and altered opioid-related behaviors where similar enduring plasticity in reward circuits may occur. We conclude the review with some of the limitations that should be considered in future investigations. This article is part of the Special Issue on 'Opioid-induced addiction'.

Lichen Biodiversity and Near-Infrared Metabolomic Fingerprint as Diagnostic and Prognostic Complementary Tools for Biomonitoring: A Case Study in the Eastern Iberian Peninsula.

In the 1990s, a sampling network for the biomonitoring of forests using epiphytic lichen diversity was established in the eastern Iberian Peninsula. This area registered air pollution impacts by winds from the Andorra thermal power plant, as well as from photo-oxidants and nitrogen depositions from local and long-distance transport. In 1997, an assessment of the state of lichen communities was carried out by calculating the Index of Atmospheric Purity. In addition, visible symptoms of morphological injury were recorded in nine macrolichens pre-selected by the speed of symptom evolution and their wide distribution in the territory. The thermal power plant has been closed and inactive since 2020. During 2022, almost 25 years later, seven stations of this previously established biomonitoring were revaluated. To compare the results obtained in 1997 and 2022, the same methodology was used, and data from air quality stations were included. We tested if, by integrating innovative methodologies (NIRS) into biomonitoring tools, it is possible to render an integrated response. The results displayed a general decrease in biodiversity in several of the sampling plots and a generalised increase in damage symptoms in the target lichen species studied in 1997, which seem to be the consequence of a multifactorial response.