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BACKGROUND: Stress has become a common public health concern, contributing to the rising prevalence of psychiatric disorders. Understanding the impact of stress considering critical variables, such as age, sex, and individual differences, is of the utmost importance for developing effective intervention strategies. METHODS: Stress effects (daily footshocks for 10 days) during adolescence (postnatal day [PND] 31-40) and adulthood (PND 65-74) were investigated on behavioral outcomes and parvalbumin (PV)-expressing GABAergic interneurons and their associated perineuronal nets (PNNs) in the prefrontal cortex of male and female mice 5 weeks post stress. RESULTS: In adulthood, adolescent stress induced behavioral alterations in male mice, including anxiety-like behaviors, social deficits, cognitive impairments, and altered dopamine system responsivity. Applying integrated behavioral z-score analysis, we identified sex-specific differences in response to adolescent stress, with males displaying greater vulnerability than females. Furthermore, adolescent-stressed male mice showed decreased PV+ and PNN+ cell numbers and PV+/PNN+ colocalization, while in females, adolescent stress reduced prefrontal PV+/PNN+ colocalization in the prefrontal cortex. Further analysis identified distinct behavioral clusters, with certain females demonstrating resilience to adolescent stress-induced deficits in sociability and PV+ cell number. Adult stress in male and female mice did not cause long-lasting changes in behavior and PV+ and PNN+ cell number. CONCLUSION: Our findings indicate that the timing of stress, sex, and individual variabilities seem to be determinants for the development of behavioral changes associated with psychiatric disorders, particularly in male mice during adolescence.

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Autism spectrum disorders (ASDs) are characterized by core behavioral symptoms in the domains of sociability, language/communication, and repetitive or stereotyped behaviors. Deficits in the prefrontal and hippocampal excitatory/inhibitory balance due to a functional loss of GABAergic interneurons are proposed to underlie these symptoms. Increasing the postsynaptic effects of GABA with compounds that selectively modulate GABAergic receptors could be a potential target for treating ASD symptoms. In addition, deficits in GABAergic interneurons have been linked to dopamine (DA) system dysregulation, and, despite conflicting evidence, abnormalities in the DA system activity may underly some ASD symptoms. Here, we investigated whether the positive allosteric modulator of α5-containing GABAA receptors (α5-GABAARs) SH-053-2'F-R-CH3 (10 mg/kg) attenuates behavioral abnormalities in rats exposed to valproic acid (VPA) in utero, an established risk factor for autism. We also evaluated if animals exposed to VPA in utero present changes in the ventral tegmental area (VTA) DA system activity using in vivo electrophysiology and if SH-053-2'F-R-CH3 could attenuate these changes. SH-053-2'F-R-CH3 was administered intraperitoneally 30 min before each behavioral test and electrophysiology. In utero VPA exposure caused male and female rats to present increased repetitive behavior (self-grooming) in early adolescence and deficits in social interaction in adulthood. Male, but not female VPA rats, also presented deficits in recognition memory as adults. SH-053-2'F-R-CH3 attenuated the impairments in sociability and cognitive function in male VPA-exposed rats without attenuating the decreased social interaction in females. Adult male and female VPA-exposed rats also showed an increased VTA DA neuron population activity, which was not changed by SH-053-2'F-R-CH3. Despite sex differences, our findings indicate that α5-GABAARs positive allosteric modulators may effectively attenuate some core ASD symptoms.

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Background: Psychiatric disorders often emerge during late adolescence/early adulthood, a period with increased susceptibility to socioenvironmental factors that coincides with incomplete parvalbumin interneuron (PVI) development. Stress during this period causes functional loss of PVIs in the ventral hippocampus (vHip), which has been associated with dopamine system overdrive. This vulnerability persists until the appearance of perineuronal nets (PNNs) around PVIs. We assessed the long-lasting effects of adolescent or adult stress on behavior, ventral tegmental area dopamine neuron activity, and the number of PVIs and their associated PNNs in the vHip. Additionally, we tested whether PNN removal in the vHip of adult rats, proposed to reset PVIs to a juvenile-like state, would recreate an adolescent-like phenotype of stress susceptibility. Methods: Male rats underwent a 10-day stress protocol during adolescence or adulthood. Three to 4 weeks poststress, we evaluated behaviors related to anxiety, sociability, and cognition, ventral tegmental area dopamine neuron activity, and the number of PV+ and PNN+ cells in the vHip. Furthermore, adult animals received intra-vHip infusion of ChABC (chondroitinase ABC) to degrade PNNs before undergoing stress. Results: Unlike adult stress, adolescent stress induced anxiety responses, reduced sociability, cognitive deficits, ventral tegmental area dopamine system overdrive, and decreased PV+ and PNN+ cells in the vHip. However, intra-vHip ChABC infusion caused the adult stress to produce changes similar to the ones observed after adolescent stress. Conclusions: Our findings underscore adolescence as a period of heightened vulnerability to the long-lasting impact of stress and highlight the protective role of PNNs against stress-induced damage in PVIs.

In this work, we aimed to go deeper into understanding perineuronal nets (PNNs), a specialized extracellular matrix that evolves and protects inhibitory neurons in the brain, specifically parvalbumin-positive interneurons (PVIs). PVIs are essential in regulating brain activity. PNNs only reach maturity in adulthood, which leaves these interneurons unprotected during early life. To investigate this vulnerability, we conducted experiments in which we exposed adolescent and adult animals to a stress protocol. We observed that adolescent animals exhibited a higher susceptibility to developing changes associated with psychiatric disorders later in life. This susceptibility may stem from the absence of PNN protection around their PVIs. To explore this possibility further, we administered an enzyme into a specific brain region, the ventral hippocampus, of adult animals to selectively remove PNNs and induce an adolescent-like state. When subjected to stress, these animals displayed abnormalities similar to those observed in animals stressed during adolescence. Our findings have significant implications, suggesting that the presence of PNN protection around PVIs may be critical for mitigating stress-related psychiatric disorders.

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Cannabidiol (CBD) is a major phytocannabinoid in the Cannabis sativa plant. In contrast to Δ9-tetrahydrocannabinol (THC), CBD does not produce the typical psychotomimetic effects of the plant. In addition, CBD has attracted increased interest due to its potential therapeutic effects in various psychiatric disorders, including schizophrenia. Several studies have proposed that CBD has pharmacological properties similar to atypical antipsychotics. Despite accumulating evidence supporting the antipsychotic potential of CBD, the mechanisms of action in which this phytocannabinoid produces antipsychotic effects are still not fully elucidated. Here, we focused on the antipsychotic properties of CBD indicated by a series of preclinical and clinical studies and the evidence currently available about its possible mechanisms. Findings from preclinical studies suggest that CBD effects may depend on the animal model (pharmacological, neurodevelopmental, or genetic models for schizophrenia), dose, treatment schedule (acute vs. repeated) and route of administration (intraperitoneal vs local injection into specific brain regions). Clinical studies suggest a potential role for CBD in the treatment of psychotic disorders. However, future studies with more robust sample sizes are needed to confirm these positive findings. Overall, although more studies are needed, current evidence indicates that CBD may be a promising therapeutic option for the treatment of schizophrenia.

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STATEMENT OF PROBLEM: The gingival zenith (GZ) influences the line angle position in the emergence profile and the axial inclination of the crown. Irregularities in GZ symmetry and contour have a negative impact on dental esthetics. GZ location is not consistently distal to the crown's long axis; instead, it tends to be more distal in anterior teeth. The GZ levelling of the lateral incisor is often described as either level with or slightly above the zenith line connecting the central incisor and canine teeth, but there are also reports of GZ being aligned apically to the zenith line. Controversial reports persist regarding GZ positioning, magnitude, and location, potentially leading to inadequate positioning and levelling of the GZ in esthetic restorative therapy. PURPOSE: The purpose of this systematic review and meta-analysis was to assess the scientific evidence related to GZ level, position, and symmetry in maxillary incisors and canines. MATERIAL AND METHODS: This study adhered to the population, variable, outcome (PVO) criteria and the preferred reporting items for systematic reviews and meta-analysis (PRISMA) checklist. Cross-sectional studies involving healthy adults with complete dentition of the maxillary anterior sextant were subjected to prevalence analysis and quantitative measurement to assess the gingival zenith level and position. Data were extracted, and methodological quality was appraised using the Joanna Briggs Institute critical appraisal checklist for analytical cross-sectional studies. Certainty of evidence was evaluated through the grading of recommendations, assessment, development, and evaluation (GRADE) system. RESULTS: The GZs were distally positioned, coinciding with the tooth axis or mesially positioned in, respectively, 96%, 3%, and 1% on central incisors; 84%, 14%, and 1% on lateral incisors; and 43%, 44%, and 5% on canines. GZ distal positioning was greater in central incisors, followed by lateral incisors and canines. In lateral incisors, the GZ was levelled coronally in 82% of the population. Contralateral symmetry was observed for GZ levelling and positioning. The certainty of the evidence was very low for all comparisons. CONCLUSIONS: The frequency and magnitude of the distal position of the GZ increased the more anterior the tooth. Axially, the GZ was frequently levelled coronally to the zenith line. The contralateral positioning and levelling of the GZ was symmetrical.

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ABSTRACT: The rostral ventromedial medulla (RVM) is a crucial structure in the descending pain modulatory system, playing a key role as a relay for both the facilitation and inhibition of pain. The chronic social defeat stress (CSDS) model has been widely used to study stress-induced behavioral impairments associated with depression in rodents. Several studies suggest that CSDS also causes changes related to chronic pain. In this study, we aimed to investigate the involvement of the RVM in CSDS-induced behavioral impairments, including those associated with chronic pain. We used chemogenetics to activate or inhibit the RVM during stress. The results indicated that the RVM is a vital hub influencing stress outcomes. Rostral ventromedial medulla activation during CSDS ameliorates all the stress outcomes, including social avoidance, allodynia, hyperalgesia, anhedonia, and behavioral despair. In addition, RVM inhibition in animals exposed to a subthreshold social defeat stress protocol induces a susceptible phenotype, facilitating all stress outcomes. Finally, chronic RVM inhibition-without any social stress stimulus-induces chronic pain but not depressive-like behaviors. Our findings provide insights into the comorbidity between chronic pain and depression by indicating the involvement of the RVM in establishing social stress-induced behavioral responses associated with both chronic pain and depression.

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The concept of Ecosystem Services (ES) recognizes the importance of natural ecosystems in supporting human well-being. Hymenoptera, a diverse group of insects including ants, bees, and wasps, play crucial roles in providing ESs. Despite their significance, the provision of ESs by Hymenoptera is often undervalued, leading to ecosystem degradation and loss of important services. This study focuses on the association between Hymenoptera and a rupicolous bromeliad species (Encholirium spectabile) and explores the ESs promoted directly and indirectly by these insects. The study area is located in the Caatinga region of Brazil, characterized by irregular rainfall and a dry season. The results show that Hymenoptera, particularly bees, ants, and wasps, provide a range of ESs including pollination, honey production, pest control, cultural symbolism, and educational value. These services are vital for plant reproduction, food production, and ecosystem functioning in both seasons; there are no differences in species richness between seasons, but rather in species composition. Understanding the importance of Hymenoptera for ESs is crucial for informing conservation and management practices to ensure the sustainability of natural ecosystems. The study highlights the need for conservation actions to protect the intricate ecological relationships between Hymenoptera and bromeliads, which indirectly support ESs by providing habitat and resources, especially during droughts when resources are scarce in the region. By recognizing the importance of bromeliads in supporting Hymenopteran communities, conservation efforts can focus on preserving these critical ecological interactions and maintaining ES provision.

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BACKGROUND AND HYPOTHESIS: Redox dysregulation has been proposed as a convergent point of childhood trauma and the emergence of psychiatric disorders, such as schizophrenia (SCZ). A critical region particularly vulnerable to environmental insults during adolescence is the ventral hippocampus (vHip). However, the impact of severe stress on vHip redox states and their functional consequences, including behavioral and electrophysiological changes related to SCZ, are not entirely understood. STUDY DESIGN: After exposing adolescent animals to physical stress (postnatal day, PND31-40), we explored social and cognitive behaviors (PND47-49), the basal activity of pyramidal glutamate neurons, the number of parvalbumin (PV) interneurons, and the transcriptomic signature of the vHip (PND51). We also evaluated the impact of stress on the redox system, including mitochondrial respiratory function, reactive oxygen species (ROS) production, and glutathione (GSH) levels in the vHip and serum. STUDY RESULTS: Adolescent-stressed animals exhibited loss of sociability, cognitive impairment, and vHip excitatory/inhibitory (E/I) imbalance. Genome-wide transcriptional profiling unveiled the impact of stress on redox system- and synaptic-related genes. Stress impacted mitochondrial respiratory function and changes in ROS levels in the vHip. GSH and glutathione disulfide (GSSG) levels were elevated in the serum of stressed animals, while GSSG was also increased in the vHip and negatively correlated with sociability. Additionally, PV interneuron deficits in the vHip caused by adolescent stress were associated with oxidative stress. CONCLUSIONS: Our results highlight the negative impact of adolescent stress on vHip redox regulation and mitochondrial function, which are partially associated with E/I imbalance and behavioral abnormalities related to SCZ.

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The brain extracellular matrix (ECM) has garnered increasing attention as a fundamental component of brain function in a predominantly "neuron-centric" paradigm. Particularly, the perineuronal nets (PNNs), a specialized net-like structure formed by ECM aggregates, play significant roles in brain development and physiology. PNNs enwrap synaptic junctions in various brain regions, precisely balancing new synaptic formation and long-term stabilization, and are highly dynamic entities that change in response to environmental stimuli, especially during the neurodevelopmental period. They are found mainly surrounding parvalbumin (PV)-expressing GABAergic interneurons, being proposed to promote PV interneuron maturation and protect them against oxidative stress and neurotoxic agents. This structural and functional proximity underscores the crucial role of PNNs in modulating PV interneuron function, which is critical for the excitatory/inhibitory balance and, consequently, higher-level behaviours. This review delves into the molecular underpinnings governing PNNs formation and degradation, elucidating their functional interactions with PV interneurons. In the broader physiological context and brain-related disorders, we also explore their intricate relationship with other molecules, such as reactive oxygen species and metalloproteinases, as well as glial cells. Additionally, we discuss potential therapeutic strategies for modulating PNNs in brain disorders.

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BACKGROUND: Consistent with postmortem findings in patients, most animal models for schizophrenia (SCZ) present abnormal levels of parvalbumin (PV), a marker of fast-spiking GABAergic interneurons, in the prefrontal cortex (PFC) and hippocampus (HIP). However, there are discrepancies in the literature. PV reductions lead to a functional loss of PV interneurons, which is proposed to underly SCZ symptoms. Given its complex etiology, different categories of animal models have been developed to study SCZ, which may distinctly impact PV levels in rodent brain areas. STUDY DESIGN: We performed a quantitative meta-analysis on PV-positive cell number/density and expression levels in the PFC and HIP of animal models for SCZ based on pharmacological, neurodevelopmental, and genetic manipulations. RESULTS: Our results confirmed that PV levels are significantly reduced in the PFC and HIP regardless of the animal model. By categorizing into subgroups, we found that all pharmacological models based on NMDA receptor antagonism decreased PV-positive cell number/density or PV expression levels in both brain areas examined. In neurodevelopmental models, abnormal PV levels were confirmed in both brain areas in maternal immune activation models and HIP of the methylazoxymethanol acetate model. In genetic models, negative effects were found in neuregulin 1 and ERBB4 mutant mice in both brain regions and the PFC of dysbindin mutant mice. Regarding sex differences, male rodents exhibited PV reductions in both brain regions only in pharmacological models, while few studies have been conducted in females. CONCLUSION: Overall, our findings support deficits in prefrontal and hippocampal PV interneurons in animal models for SCZ.

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Coffee is a universal beverage that drives a multi-industry market on a global basis. Today, the sustainability of coffee production is threatened by accelerated climate changes. In this work, we propose the implementation of genomic-assisted breeding for climate-smart coffee in Coffea canephora. This species is adapted to higher temperatures and is more resilient to biotic and abiotic stresses. After evaluating two populations, over multiple harvests, and under severe drought weather condition, we dissected the genetic architecture of yield, disease resistance, and quality-related traits. By integrating genome-wide association studies and diallel analyses, our contribution is four-fold: (i) we identified a set of molecular markers with major effects associated with disease resistance and post-harvest traits, while yield and plant architecture presented a polygenic background; (ii) we demonstrated the relevance of nonadditive gene actions and projected hybrid vigor when genotypes from different geographically botanical groups are crossed; (iii) we computed medium-to-large heritability values for most of the traits, representing potential for fast genetic progress; and (iv) we provided a first step toward implementing molecular breeding to accelerate improvements in C. canephora. Altogether, this work is a blueprint for how quantitative genetics and genomics can assist coffee breeding and support the supply chain in the face of the current global changes.

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Adolescent individuals exhibit great variability in cortical dynamics and behavioral outcomes. The developing adolescent brain is highly sensitive to social experiences and environmental insults, influencing how personality traits emerge. A distinct pattern of mitochondrial gene expression in the prefrontal cortex (PFC) during adolescence underscores the essential role of mitochondria in brain maturation and the development of mental illnesses. Mitochondrial features in certain brain regions account for behavioral differences in adulthood. However, it remains unclear whether distinct adolescent behavioral phenotypes and the behavioral consequences of early adolescent stress exposure in rats are accompanied by changes in PFC mitochondria-related genes and mitochondria respiratory chain capacity. We performed a behavioral characterization during late adolescence (postnatal day, PND 47-50), including naïve animals and a group exposed to stress from PND 31-40 (10 days of footshock and 3 restraint sessions) by z-normalized data from three behavioral domains: anxiety (light-dark box tests), sociability (social interaction test) and cognition (novel-object recognition test). Employing principal component analysis, we identified three clusters: naïve with higher-behavioral z-score (HBZ), naïve with lower-behavioral z-score (LBZ), and stressed animals. Genome-wide transcriptional profiling unveiled differences in the expression of mitochondria-related genes in both naïve LBZ and stressed animals compared to naïve HBZ. Genes encoding subunits of oxidative phosphorylation complexes were significantly down-regulated in both naïve LBZ and stressed animals and positively correlated with behavioral z-score of phenotypes. Our network topology analysis of mitochondria-associated genes found Ndufa10 and Cox6a1 genes as central identifiers for naïve LBZ and stressed animals, respectively. Through high-resolution respirometry analysis, we found that both naïve LBZ and stressed animals exhibited a reduced prefrontal phosphorylation capacity and redox dysregulation. Our findings identify an association between mitochondrial features and distinct adolescent behavioral phenotypes while also underscoring the detrimental functional consequences of adolescent stress on the PFC.

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Bees are the most significant pollinators of flowering plants. This partnership began ca. 120 million years ago, but the uncertainty of how and when bees spread across the planet has greatly obscured investigations of this key mutualism. We present a novel analysis of bee biogeography using extensive new genomic and fossil data to demonstrate that bees originated in Western Gondwana (Africa and South America). Bees likely originated in the Early Cretaceous, shortly before the breakup of Western Gondwana, and the early evolution of any major bee lineage is associated with either the South American or African land masses. Subsequently, bees colonized northern continents via a complex history of vicariance and dispersal. The notable early absences from large landmasses, particularly in Australia and India, have important implications for understanding the assembly of local floras and diverse modes of pollination. How bees spread around the world from their hypothesized Southern Hemisphere origin parallels the histories of numerous flowering plant clades, providing an essential step to studying the evolution of angiosperm pollination syndromes in space and time.

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Multifunctional surfaces may display the potential to accelerate and promote the healing process around dental implants. However, the initial cellular biocompatibility, molecular activity, and the release of functionalized molecules from these novel surfaces require extensive investigation for clinical use. Aiming to develop and compare innovative surfaces for application in dental implants, the present study utilized titanium disks, which were treated and divided into four groups: machined (Macro); acid-etched (Micro); anodized-hydrophilic surface (TNTs); and anodized surface coated with a rifampicin-loaded polymeric layer (poly(lactide-co-glycolide), PLGA) (TNTsRIMP). The samples were characterized regarding their physicochemical properties and the cumulative release of rifampicin (RIMP), investigated at different pH values. Additionally, differentiated osteoblasts from mesenchymal cells were used for cell viability and qRT-PCR analysis. Antibacterial properties of each surface treatment were investigated against Staphylococcus epidermidis. TNTsRIMP demonstrated controlled drug release for up to 7 days in neutral pH environments. Osteogenic cell cultures indicated that all the evaluated surfaces showed biocompatibility. The TNTs group revealed up-regulated values for bone-related gene quantification in 7 days, followed by the TNTsRIMP group. Furthermore, the antibiotic-functionalized surface revealed effectiveness to inhibit S. epidermidis and stimulate promising conditions for osteogenic cell behavior. Characteristics such as nanomorphology and hydrophilicity were determinants for the up-regulated quantification of osteogenic biomarkers related to early bone maturation, encouraging application in intra-osseous implant surfaces; in addition, antibiotic-functionalized surfaces demonstrated significant higher antibacterial properties compared to the other groups. Our findings suggest that polymeric-antibiotic-loaded coating might be applied for the prevention of early infections, favoring its application in multifunctional surfaces for intra- and/or trans-mucosal components of dental implants, while, hydrophilic nanotextured surfaces promoted optimistic properties to stimulate early bone-related cell responses, favoring its application in bone-anchored surfaces.

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The rostral ventromedial medulla (RVM) is a brainstem structure critical for the descending pain modulation system involved in both pain facilitation and inhibition through its projection to the spinal cord. Since the RVM is well connected with pain- and stress-engaged brain structures, such as the anterior cingulate cortex, nucleus accumbens, and amygdala, its involvement in stress responses has become a matter of great interest. While chronic stress has been proposed as a trigger of pain chronification and related psychiatric comorbidities due to maladaptive stress responses, acute stress triggers analgesia and other adaptative responses. Here we reviewed and highlighted the critical role of the RVM in stress responses, mainly in acute stress-induced analgesia (SIA) and chronic stress-induced hyperalgesia (SIH), providing insights into pain chronification processes and comorbidity between chronic pain and psychiatric disorders.

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The misuse of and addiction to opioids are serious public health problems in some countries, such as the USA. Drug addiction is a chronic and relapsing medical condition that involves motivational and memory-related processes due to the strong associations between drugs and consuming-related stimuli. These stimuli usually trigger continuous and compulsive use and are associated with relapses after periods of withdrawal. Several factors contribute to relapse, including withdrawal-induced mood changes. Therefore, drugs attenuating withdrawal-induced affective alterations could be useful alternative treatments for relapse prevention. Cannabidiol (CBD), a non-psychotomimetic component from the Cannabis sativa plant, has anti-anxiety and anti-stress properties and has been investigated as an alternative for the treatment of several mental disorders, including drug addiction. Here, we evaluated if CBD administered 30 min prior to test for a conditioned place aversion (CPA) would attenuate the aversion induced by morphine withdrawal precipitated by the opioid receptor antagonist naloxone in male C57BL/6 mice. We also investigated if this effect involves the activation of 5-HT1A receptors, a mechanism previously associated with CBD anti-aversive effects. As expected, morphine-treated mice spent less time exploring the compartment paired with the naloxone-induced withdrawal, indicating a CPA induced by naloxone-precipitated morphine withdrawal. This effect was not observed in animals treated with CBD, at 30 and 60 mg/kg, prior to the CPA test, indicating that CBD attenuated the expression of CPA induced by naloxone-precipitated morphine withdrawal. Pretreatment with the 5-HT1A receptor antagonist WAY100635 (0.3 mg/kg) blocked CBD effects. Our findings suggest that CBD may reduce the expression of a previously established conditioned aversion induced by morphine withdrawal by a mechanism involving the activation of 5-HT1A receptors. Thus, CBD may be a therapeutic alternative for preventing relapse to opioid addiction by decreasing withdrawal-induced negative affective changes.

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BACKGROUND: The American Academy of Pediatrics (AAP) adolescent blood pressure (BP) percentiles were updated in 2017, and have been used as reference in Brazil since then. However, specific BP percentiles for Brazilian adolescents were recently proposed based on data from the Study of Cardiovascular Risk in Adolescents (ERICA). OBJECTIVES: To compare the prevalence of arterial hypertension according to each reference, as well as to assess the cardiometabolic risk associated with the reclassification by Brazilian BP percentiles. METHODS: Data from 73 399 adolescents aged 12-17 years who participated in the ERICA study were analyzed. To assess cardiometabolic risk, 6185 adolescents who were reclassified upwards by the Brazilian reference were 1 : 1 matched with adolescents that were normotensive by both references and were of the same age, sex and height percentile. The parameters evaluated were: overweight/obesity, waist circumference, total cholesterol, triglycerides, LDL-c, HDL-c, fasting glucose, HbA1c and HOMA-ir. RESULTS: The classification according to Brazilian BP percentiles resulted in a higher prevalence of arterial hypertension (14%, 95% CI 13.2-14.8), when compared with the AAP percentiles (10.6%, 95% CI 10.0-11.2). The use of the Brazilian reference also resulted in higher prevalence of arterial hypertension in girls, teenagers ranging from 12 to 14 years, and those classified with adequate weight, overweight or obesity. In the case-control analysis, cardiometabolic risk factors were present more often in adolescents reclassified with arterial hypertension by the ERICA reference. DISCUSSION: The use of the BP percentiles proposed by ERICA is a sensitive method for tracking Brazilian adolescents with hypertension and higher cardiometabolic risk.

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α-Adrenergic receptors are crucial regulators of vascular hemodynamics and essential pharmacological targets for cardiovascular diseases. With aging, there is an increase in sympathetic activation, which could contribute to the progression of aging-associated cardiovascular dysfunction, including stroke. Nevertheless, there is little information directly associating adrenergic receptor dysfunction in the blood vessels of aged females. This study determined the role of a-adrenergic receptors in carotid dysfunction of senescent female mice (accelerated-senescence prone, SAMP8), compared with a nonsenescent (accelerated-senescence prone, SAMR1). Vasoconstriction to phenylephrine (Phe) was markedly increased in common carotid artery of SAMP8 [area under the curve (AUC), 527 ± 53] compared with SAMR1 (AUC, 334 ± 30, P = 0.006). There were no changes in vascular responses to the vasoconstrictor agent U46619 or the vasodilators acetylcholine (ACh) and sodium nitroprusside (NPS). Hyperactivity to Phe in female SAMP8 was reduced by cyclooxygenase-1 and cyclooxygenase-2 inhibition and associated with augmented ratio of TXA2/PGI2 release (SAMR1, 1.1 ± 0.1 vs. SAMP8, 2.1 ± 0.3, P = 0.007). However, no changes in cyclooxygenase expression were seen in SAMP8 carotids. Selective α1A-receptor antagonism markedly reduced maximal contraction, whereas α1D antagonism induced a minor shift in Phe contraction in SAMP8 carotids. Ligand binding analysis revealed a threefold increase of α-adrenergic receptor density in smooth muscle cells (VSMCs) of SAMP8 vs. SAMR1. Phe rapidly increased intracellular calcium (Cai2+) in VSMCs via the α1A-receptor, with a higher peak in VSMCs from SAMP8. In conclusion, senescence intensifies vasoconstriction mediated by α1A-adrenergic signaling in the carotid of female mice by mechanisms involving increased Cai2+ and release of cyclooxygenase-derived prostanoids.NEW & NOTEWORTHY The present study provides evidence that senescence induces hyperreactivity of α1-adrenoceptor-mediated contraction of the common carotid. Impairment of α1-adrenoceptor responses is linked to increased Ca2+ influx and release of COX-derived vasoconstrictor prostanoids, contributing to carotid dysfunction in the murine model of female senescence (SAMP8). Increased reactivity of the common carotid artery during senescence may lead to morphological and functional changes in arteries of the cerebral microcirculation and contribute to cognitive decline in females. Because the elderly population is growing, elucidating the mechanisms of aging- and sex-associated vascular dysfunction is critical to better direct pharmacological and lifestyle interventions to prevent cardiovascular risk in both sexes.

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Morphological data are a fundamental source of evidence to reconstruct the Tree of Life, and Bayesian phylogenetic methods are increasingly being used for this task. Bayesian phylogenetic analyses require the use of evolutionary models, which have been intensively studied in the past few years, with significant improvements to our knowledge. Notwithstanding, a systematic evaluation of the performance of partitioned models for morphological data has never been performed. Here we evaluate the influence of partitioned models, defined by anatomical criteria, on the precision and accuracy of summary tree topologies considering the effects of model misspecification. We simulated datasets using partitioning schemes, trees, and other properties obtained from two empirical datasets, and conducted Bayesian phylogenetic analyses. Additionally, we reanalyzed 32 empirical datasets for different groups of vertebrates, applying unpartitioned and partitioned models, and, as a focused study case, we reanalyzed a dataset including living and fossil armadillos, testing alternative partitioning hypotheses based on functional and ontogenetic modules. We found that, in general, partitioning by anatomy has little influence on summary topologies analyzed under alternative partitioning schemes with a varying number of partitions. Nevertheless, models with unlinked branch lengths, which account for heterotachy across partitions, improve topological precision at the cost of reducing accuracy. In some instances, more complex partitioning schemes led to topological changes, as tested for armadillos, mostly associated with models with unlinked branch lengths. We compare our results with other empirical evaluations of morphological data and those from empirical and simulation studies of the partitioning of molecular data, considering the adequacy of anatomical partitioning relative to alternative methods of partitioning morphological datasets. [Evolutionary rates; heterogeneity; morphology; Mk model; partition; topology.].

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BACKGROUND AND HYPOTHESIS: Stress during adolescence is a major risk factor for schizophrenia. We have found previously in rats that adolescent stress caused, in adulthood, behavioral changes and enhanced ventral tegmental area (VTA) dopamine system activity, which were associated with dysregulation of the excitatory-inhibitory (E/I) balance in the ventral hippocampus (vHip). Levetiracetam, an anticonvulsant drug, regulates the release of neurotransmitters, including glutamate, via SV2A inhibition. It also modulates parvalbumin interneuron activity via Kv3.1 channels. Therefore, levetiracetam could ameliorate deficits in the E/I balance. We tested whether levetiracetam attenuate the adolescent stress-induced behavioral changes, vHip hyperactivity, and enhanced VTA dopamine system activity in adult rats. STUDY DESIGN: Male Sprague-Dawley rats were subjected to a combination of daily footshock (postnatal day [PD] 31-40), and three 1 h-restraint stress sessions (at PD31, 32, and 40). In adulthood (PD62), animals were tested for anxiety responses (elevated plus-maze and light-dark box), social interaction, and cognitive function (novel object recognition test). The activity of vHip pyramidal neurons and VTA dopamine neurons was also recorded. STUDY RESULTS: Adolescent stress produced anxiety-like responses and impaired sociability and cognitive function. Levetiracetam (10 mg/kg) reversed these changes. Levetiracetam also reversed the increased VTA dopamine neuron population activity and the enhanced firing rate of vHip pyramidal neurons induced by adolescent stress. CONCLUSIONS: These findings suggest that levetiracetam attenuates the adverse outcomes associated with schizophrenia caused by stress during adolescence.

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