Atorvastatin-Associated Eosinophilic Spongiosis: A Case Report and a Relevant Literature Review of Dermatological Manifestations.

Atorvastatin, a widely prescribed 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor (HMG-CoA reductase inhibitor), is associated with various adverse effects, including many dermatologic manifestations. We present the case of a 73-year-old man who developed eosinophilic spongiosis shortly after initiating atorvastatin therapy, an adverse effect which to our knowledge has not yet been reported in association with atorvastatin. Our investigation explores the clinical and histopathologic characteristics of eosinophilic spongiosis induced by atorvastatin, delving into potential mechanisms behind statin-induced eosinophilia. A literature review, focusing on atorvastatin's dermatological side effects, revealed a limited number of relevant studies, emphasizing the scarcity of documented cases. Our aim is to raise awareness of eosinophilic spongiosis as a potential side effect of atorvastatin, emphasizing its impact on patients' quality of life. This case prompts further research into the mechanisms underlying such dermatologic reactions, contributing to a better understanding of atorvastatin's diverse adverse effects.

Rare Autoinflammatory Neutrophilic Dermatoses in Pregnancy: Literature Review.

Rare cases of autoinflammatory neutrophilic dermatoses (AINDs) have been reported in patients during pregnancy with associated adverse maternal and fetal outcomes. Due to the rarity and heterogeneous morphology of pregnancy-associated AINDs, clinical diagnosis is often overlooked, and treatment options are limited. In this review, we present the epidemiology, clinical characteristics, therapeutic interventions, maternal and fetal outcomes, and discuss the possible pathophysiology of various pregnancy associated AINDs. Risk factors for the onset and exacerbation of AINDs in pregnancy include older maternal age, disease duration, and specific gestational age. The varied disease courses and conflicting clinical outcomes in both mothers and fetuses demonstrate the importance of symptom recognition and the understanding of the role of pregnancy on AINDs.

Mapping Macrophage Polarization and Origin during the Progression of the Foreign Body Response to a Poly(ethylene glycol) Hydrogel Implant.

Poly(ethylene glycol) (PEG) hydrogels hold promise for in vivo applications but induce a foreign body response (FBR). While macrophages are key in the FBR, many questions remain. This study investigates temporal changes in the transcriptome of implant-associated monocytes and macrophages. Proinflammatory pathways are upregulated in monocytes compared to control monocytes but subside by day 28. Macrophages are initially proinflammatory but shift to a profibrotic state by day 14, coinciding with fibrous capsule emergence. Next, this study assesses the origin of macrophages responsible for fibrous encapsulation using wildtype, C-C Motif Chemokine Receptor 2 (CCR2)-/- mice that lack recruited macrophages, and Macrophage Fas-Induced Apoptosis (MaFIA) mice that enable macrophage ablation. Subpopulations of recruited and tissue-resident macrophages are identified. Fibrous encapsulation proceeds in CCR2-/- mice similar to wildtype mice. However, studies in MaFIA mice indicate that macrophages are necessary for fibrous capsule formation. These findings suggest that macrophage origin impacts the FBR progression and provides evidence that tissue-resident macrophages and not the recruited macrophages may drive fibrosis in the FBR to PEG hydrogels. This study demonstrates that implant-associated monocytes and macrophages have temporally distinct transcriptomes in the FBR and that profibrotic pathways associated with macrophages may be enriched in tissue-resident macrophages.

Do embodiment and fictionality affect young children's learning?

Preschool-aged children can learn from fictional, pretend, and imaginative activities. However, many studies showing this learning involve children as physically passive while consuming fictional narratives rather than as actively, physically engaged. Physical engagement may add to cognitive processes already at play when watching narratives, making children more likely to retain or understand information. Children's natural pretend involves physical movement, role play, and embodiment. To test learning from embodied pretense, we conducted two studies in which we experimentally manipulated whether children were physically passive while consuming narratives or physically actively engaged with them through embodied pretend play using puppets or costumes. In Study 1, children were shown/engaged in television-based narratives, all of which contained fantastical content. In Study 2, children were shown/engaged in lab-created stories, some of which contained fantastical elements. We measured children's learning and perceptions of realism. In Study 1, neither perception of fictionality nor embodiment immediately affected learning, although older preschoolers learned more than younger preschoolers. In Study 2, neither perception nor presence of fantastical content affected learning, but embodiment did. Children learned more from both embodied conditions compared with the physically passive condition. We also included 2-week follow-up tests of recall and found that although children retained very little, embodiment still affected retention in both studies. Overall, children did not use realism judgments to differentiate learning. These findings show the complexity of different elements involved in children's learning from pretense and the need to understand what elements affect learning from fantastical and embodied pretend play and stories.

Effects of Acute Grape Seed Extract Supplementation on Hemodynamics in Normal Body Weight and Obese Males.

Recently, it has been reported that dietary supplementation with grape seed extract (GSE) ameliorates endothelial function and increase nitric oxide (NO) bioavailability. Thus, we investigated if elevated blood pressure and aortic stiffness (AoS) characterized in obese individuals are attenuated following acute GSE supplementation. Twenty men (obese=10; normal body weight (NBW)=10) participated in this study. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR), and AoS were compared 2 h after ingestion of GSE or placebo (PL) on different days, 1 wk apart. Compared with the PL, GSE supplementation significantly decreased SBP (NBW: 103±4 vs. 99±3 mmHg; obese: 118±3 vs. 112±5 mmHg) and MAP (NBW: 75±2 vs. 72±2 mmHg; obese: 86±3 vs. 84±3 mmHg) in both groups, while there were no differences in HR, SV, DBP, TPR, and AoS. GSE supplementation significantly decreased CO in only obese group. In NBW group, TPR tended to be decreased, but there was no significant difference. Our study suggests that acute supplementation with GSE reduced both SBP and MAP via a reduction in CO in obese individuals and decreased peripheral vasoconstriction in NBW group.

Quantifying Strain via Buckling Instabilities in Surface Modified Polymer Brushes.

A compressive strain applied to bilayer films (e.g. thin film adhered to a thick substrate) can lead to buckled or wrinkled morphologies, which has many important applications in stretchable electronics, anti-counterfeit technology, and high-precision micro and nano-metrology. A number of buckling-based metrology methods have been developed to quantify the residual stress and viscoelastic properties of polymer thin films. However, in some systems (e.g. solvent-induced swelling or thermal strain), the compressive strain is unknown or difficult to measure. We present a quantitative method of measuring the compressive strain of wrinkled polymer films and coatings with knowledge of the "skin" thickness, wrinkle wavelength, and wrinkle amplitude. The derived analytical expression is validated with a well-studied model system, e.g., stiff, thin film (PS) bonded to a thick, compliant substrate (PDMS). After validation, we use our expression to quantify the applied swelling strain of previously reported wrinkled poly(styrene-alt-maleic anhydride) brush surfaces. Finally, the applied strain is used to rationalize the observed persistence length of aligned wrinkles created during atomic force microscopy (AFM) lithography and subsequent solvent exposure.

It's All Critical: Acting Teachers' Beliefs About Theater Classes.

Acting classes and theater education have long been framed as activities during which children can learn skills that transfer outside the acting classroom. A growing empirical literature provides evidence for acting classes' efficacy in teaching vocabulary, narrative, empathy, theory of mind, and emotional control. Yet these studies have not been based in what is actually happening in the acting classroom, nor on what acting teachers report as their pedagogical strategies. Instead, previous work has been unsystematic and fragmented in its measured transfer outcomes, and absent mechanistic explanation. Expanding research on this topic requires more grounding in teachers' beliefs about the acting classes they teach, as well as observation of the classes themselves. As a first step, we surveyed 173 acting teachers online, asking them about the activities within acting classes they believed caused change in their students, as well as which outcomes they believed were changed as a result of acting classes. Teachers taught across educational levels (elementary to professional) and had a variety of training in teaching acting. Overall, teachers rated almost every activity within classes as important for and causing impact on students, and almost every outcome as being positively influenced as a result of acting class. When forced to rank-order outcomes, teachers focused on collaboration, communication, creativity, confidence, and empathy as most likely to change. Teachers rated the importance of class activities and outcomes differently depending on what level they taught. This study shows the difficulty of surveying highly motivated teachers, given the globally high rankings, but also proposes candidate psychological skills likely to change as a result of acting classes and the mechanistic behaviors that may cause change.

Children Learn From Both Embodied and Passive Pretense: A Replication and Extension.

Research suggests that children can learn new information via pretense. However, a fundamental problem with existing studies is that children are passive receivers of the pretense rather than active, engaged participants. This preregistered study replicates previous learning from pretense findings (Sutherland & Friedman, 2012, Child Development), in which children are passive observers of pretense, and extends to two additional conditions that require children to partially (with puppets) or fully (with costumes) embody a character. Children (N = 144, 24-79 months) learned equally well, and better than those in the control condition, from all three play scenarios. At a 2-week follow-up, learning was equally retained across embodiment conditions for older, but not younger, preschoolers. Future research should consider embodiment's role for more complex material.

Sequential and one-pot post-polymerization modification reactions of thiolactone-containing polymer brushes.

Thiolactone chemistry has garnered significant attention as a powerful post-polymerization modification (PPM) route to mutlifunctional polymeric materials. Here, we apply this versatile chemistry to the fabrication of ultrathin, multifunctional polymer surfaces via aminolysis and thiol-mediated double modifications of thiolactone-containing polymer brushes. Polymer brush surfaces were synthesized via microwave-assisted surface-initiated polymerization of DL-homocysteine thiolactone acrylamide. Aminolysis and thiol-Michael double modifications of the thiolactone-functional brush were explored using both sequential and one-pot reactions with bromobenzyl amine and 1H,1H-perfluoro-N-decyl acrylate. X-ray photoelectron spectroscopy and argon gas cluster ion sputter depth profiling enabled quantitative comparison of the sequential and one-pot PPM routes with regard to conversion and spatial distribution of functional groups immobilized throughout thickness of the brush. While one-pot conditions proved to be more effective in immobilizing the amine and acrylate within the brush, the sequenital reaction enabled the fabrication of multifunctional, micropattterned brush surfaces using reactive microcontact printing.

Brain-derived neurotrophic factor signaling mitigates the impact of acute social stress.

Brain-derived neurotrophic factor (BDNF) is known to promote fear learning as well as avoidant behavioral responses to chronic social defeat stress, but, conversely, this peptide can also have antidepressant effects and can reduce depressant-like symptoms such as social avoidance. The purpose of this study was to use a variety of approaches to determine whether BDNF acting on tropomyosin receptor kinase B (TrkB) promotes or prevents avoidant phenotypes in hamsters and mice that have experienced acute social defeat stress. We utilized systemic and brain region-dependent manipulation of BDNF signaling before or immediately following social defeat stress in Syrian hamsters, TrkBF616A knock-in mice, and C57Bl/6J mice and measured the subsequent behavioral response to a novel opponent. Systemic TrkB receptor agonists reduced, and TrkB receptor antagonists enhanced, behavioral responses to social defeat in hamsters and mice. In the neural circuit that we have shown mediates defeat-induced behavioral responses, BDNF in the basolateral amygdala, but not the nucleus accumbens, also reduced social avoidant phenotypes. Conversely, knockdown in the basolateral amygdala of TrkB signaling in TrkBF616A mice enhanced defeat-induced social avoidance. These data demonstrate that systemic administration of BDNF-TrkB drugs at the time of social defeat alters the behavioral response to the defeat stressor. These drugs appear to act, at least in part, in the basolateral amygdala and not the nucleus accumbens. These findings were generalizable to two rodent species with very different social structures and, within mice, to a variety of strains providing converging evidence that BDNF-TrkB signaling reduces anxiety- and depression-like symptoms following short-term social stress.

Flibanserin for hypoactive sexual desire disorder in premenopausal women.

Flibanserin is a mixed 5-HT1A agonist and 5-HT2A antagonist for treatment of premenopausal women with hypoactive sexual desire disorder. It is the first FDA-approved treatment for this disorder and can improve the number of satisfying sexual events. The drug has been associated with hypotension and syncope.

Parent-Teacher Agreement on Social Skills and Behavior Problems Among Ethnically Diverse Preschoolers with Autism Spectrum Disorder.

Parents and teachers provide complimentary information in the assessment of preschoolers so it is important to understand parent-teacher agreement, especially for children with autism. Parents and teachers rated an ethnically diverse sample of preschoolers with autism (N = 257; 67% Latino) on the Devereux Early Childhood Assessment (LeBuffe and Naglieri in Devereux Early Childhood Assessment: User's guide, Kaplan Press, Lewisville, 1999). Correlations between parent and teacher ratings were moderate and significant for social skills (r = 0.20-0.37) but near zero for behavioral concerns. Parents rated children as having stronger social skills and fewer behavioral concerns than teachers, unlike prior research with typically developing preschoolers. Both informants rated White/other children more positively than minority children on several subscales, although agreement was similar across groups. Implications for practice are discussed.

Buckling Instabilities in Polymer Brush Surfaces via Postpolymerization Modification.

We report a simple route to engineer ultrathin polymer brush surfaces with wrinkled morphologies using post-polymerization modification (PPM), where the length scale of the buckled features can be tuned from hundreds of nanometers to one micrometer using PPM reaction time. We show that partial crosslinking of the outer layer of the polymer brush under poor solvent conditions is critical to obtain wrinkled morphologies upon swelling. Characterization of the PPM kinetics and swelling behavior via ellipsometry and the through-thickness composition profile via time-of-flight secondary ion mass spectroscopy (ToF-SIMS) provided keys insight into parameters influencing the buckling behavior.

Cancer Mortality Trends in Medically Underserved Counties in Virginia.

CONTEXT: Cancer mortality rates in the United States have improved during the past 40 years. The improvement in mortality rates is not equal for all types of cancer or all geographic locations, however. OBJECTIVE: To compare trends in cancer mortality rates in Virginia counties from 2005 through 2009. METHODS: Publicly available data from the National Cancer Institute, the State Cancer Profile, and the Virginia Department of Health were accessed for this analysis. For all counties in Virginia with all-cancer and lung cancer mortality data available, the authors compared counties considered medically underserved areas (VMUAs) with non-VMUAs to examine trends in cancer mortality rates that increased, remained stable, or decreased from 2005 through 2009. The significance level for all data was set at P≤.05. RESULTS: Of 136 counties in Virginia, 134 had all-cancer and 123 had lung cancer mortality data available. The VMUAs had a 48% lower decreasing all-cancer mortality rate than non-VMUAs (13 [26%] vs 37 [74%], respectively; P=.004). Non-VMUAs had a 33.3% higher stable all-cancer mortality rate than VMUAs (50 [66.6%] vs 25 [33.3%], respectively; P=.004) and a 55.2% higher lung cancer mortality rate (17 [22.4%] vs 59 [77.6%], respectively; P<.001). CONCLUSION: The all-cancer and lung cancer mortality rates were found to either remain stable or, in the case of all-cancer mortality, to increase in VMUAs.

High-fat diet consumption disrupts memory and primes elevations in hippocampal IL-1ß, an effect that can be prevented with dietary reversal or IL-1 receptor antagonism.

High-fat diet (HFD)-induced obesity is reaching worldwide proportions. In addition to causing obesity, HFDs also induce a variety of health disorders, which includes cognitive decline. Hippocampal function may be particularly vulnerable to the negative consequences of HFD, and it is suspected that 'primed' neuroinflammatory processes may mediate this response. To examine the link between diet, hippocampal function and neuroinflammation, male Wistar rats were fed a medium or HFD. Hippocampal memory function was measured using contextual pre-exposure fear conditioning (CPE-FC). Rats fed a HFD demonstrated impaired memory, an effect that was augmented with longer duration of HFD consumption. HFD-induced memory impairments were linked to potentiated levels of interleukin-1 beta (IL-1ß) protein in the hippocampus 2h after the foot-shock that occurs during CPE-FC. Central IL-1 receptor antagonism, with intracisterna magna (ICM) administration of hIL-1RA prior to the foot-shock prevented the diet-induced memory disruption, suggesting a critical role for IL-1ß in this phenomenon. Additionally, obese animals whose diet regimen was reversed from HFD back to standard chow recovered memory function and did not demonstrate a foot-shock-induced hippocampal IL-1ß increase. Interestingly, dietary reversal neutralized the negative impact of HFD on memory and IL-1ß, yet animals maintained physiological evidence of obesity (increased body mass and serum leptin), indicating that dietary components, not body mass, may mediate the negative effects on memory.

IL-1RA injected intra-cisterna magna confers extended prophylaxis against lipopolysaccharide-induced neuroinflammatory and sickness responses.

IL-1RA has been used intra-cerebrally to ameliorate neuroinflammatory responses. The present study explored the possibility that the bioactivity of IL-1RA administered intra-cerebrally may be prolonged in the CNS. hIL-1RA was detected in hippocampus from 2h to 14d post-ICM treatment. hIL-1RA ameliorated both the hippocampal cytokine (TNFα and NFκBIα) and sickness response to peripheral LPS administered 4d after hIL-1RA. Four days post treatment, hIL-1RA reduced the basal expression of IL-1R1, Iba-1, MHCII, and TLR4 and blunted the microglial IL-1ß and IL-6 response to LPS ex vivo. IL-1RA might be administered prophylactically to prevent the neuroinflammatory effects of trauma.

Glucocorticoids mediate stress-induced priming of microglial pro-inflammatory responses.

Acute and chronic stress sensitizes or "primes" the neuroinflammatory response to a subsequent pro-inflammatory challenge. While prior evidence shows that glucocorticoids (GCs) play a pivotal role in stress-induced potentiation of neuroinflammatory responses, it remains unclear whether stress-induced GCs sensitize the response of key CNS immune substrates (i.e. microglia) to pro-inflammatory stimuli. An ex vivo approach was used to address this question. Here, stress-induced GC signaling was manipulated in vivo and hippocampal microglia challenged with the pro-inflammatory stimulus LPS ex vivo. Male Sprague-Dawley rats were either pretreated in vivo with the GC receptor antagonist RU486 or adrenalectomized (ADX). Animals were then exposed to an acute stressor (inescapable tailshock; IS) and 24 h later hippocampal microglia were isolated and challenged with LPS to probe for stress-induced sensitization of pro-inflammatory responses. Prior exposure to IS resulted in a potentiated pro-inflammatory cytokine response (e.g. IL-1ß gene expression) to LPS in isolated microglia. Treatment in vivo with RU486 and ADX inhibited or completely blocked this IS-induced sensitization of the microglial pro-inflammatory response. The present results suggest that stress-induced GCs function to sensitize the microglial pro-inflammatory response (IL-1ß, IL-6, NFκBIα) to immunologic challenges.

Activation of the infralimbic cortex in a fear context enhances extinction learning.

Activation of the infralimbic region (IL) of the medial prefrontal cortex (mPFC) reduces conditioned fear in a variety of situations, and the IL is thought to play an important role in the extinction of conditioned fear. Here we report a series of experiments using contextual fear conditioning in which the IL is activated with the GABAa antagonist picrotoxin (Ptx) during a single extinction session in the fear context. We investigate the impact of this manipulation on subsequent extinction sessions in which Ptx is no longer present. First, we demonstrate that a single treatment with intra-IL Ptx administered in a conditioned fear context greatly accelerates the rate of extinction on the following days. Importantly, IL-Ptx also enhances extinction to a different fear context than the one in which IL-Ptx was administered. Thus, IL-Ptx primes extinction learning regardless of the fear context in which the IL was initially activated. Second, activation of the IL must occur in conjunction with a fear context in order to enhance extinction; the extinction enhancing effect is not observable if IL-Ptx is administered in a neutral context. Finally, this extinction enhancing effect is specific to the IL for it does not occur if Ptx is injected into the prelimbic region (PL) of the mPFC. The results indicate a novel persisting control of fear induced by activation of the IL and suggest that IL activation induces changes in extinction-related circuitry that prime extinction learning.

Beta-endorphin mediates behavioral despair and the effect of ethanol on the tail suspension test in mice.

BACKGROUND: The opioid peptide beta-endorphin (beta-E) is synthesized and released in response to stressful stimuli as well as acute alcohol administration. The release of beta-E following exposure to an inescapable aversive situation may mediate behaviors that contribute to allostasis of the stress response. The present study examines the effects of beta-E on immobility in assays involving inescapable stress, both under basal conditions and after acute administration of EtOH. METHODS: Female and male transgenic mice with varying capacities to translate beta-E were subjected to either the forced swim (FST, Experiment 1) or the tail suspension test (TST, Experiment 2). In Experiment 3, mice were divided into three groups based on hormonal status (male, female-estrous, and female-nonestrous) and injected with either 1 g/kg EtOH or equivolume saline 14 minutes prior to behavioral assessment on the TST. RESULTS: Experiments 1 and 2 demonstrated a direct relationship between beta-E levels and immobility. There were also sex differences in behavior in these tests, with males displaying more immobility than females. A main effect of genotype in Experiment 3 replicated findings in Experiments 1 and 2. There was also an effect of EtOH (increasing immobility) and a significant interaction reflecting a particularly robust effect of the drug in mice with low beta-E. In addition, there were interactions between beta-E, EtOH effects, and hormonal status. CONCLUSIONS: These findings support the contention that beta-E moderates behavioral responses to stressful stimuli and suggest a role for this peptide in coping behavior. Furthermore, the effects of EtOH on the response to stress may be mediated by beta-E. Sex differences in this influence may contribute to sex differences in disease susceptibility and expression.

Medial prefrontal cortical activation modulates the impact of controllable and uncontrollable stressor exposure on a social exploration test of anxiety in the rat.

The presence of behavioral control over a stressor can blunt many of the effects of the stressor. We have recently reported that uncontrollable stress (inescapable electric tailshock, IS) reduces later social exploration of a juvenile whereas controllable stress (escapable shock, ES) does not. Activation of the ventral medial prefrontal cortex (vmPFC) is crucial to blunting the effects of IS on later escape behavior (learned helplessness). The goal of the current study was to test the role of the vmPFC in modulating the effects of stressor controllability on anxiety in the social exploration test. Thus, adult male rats were implanted with cannula guides for drug microinjection into the vmPFC. In Experiment 1, temporary inactivation of the vmPFC with the GABA(A) agonist muscimol before exposure to ES prevented the protective effects of stress control, leading to reduced social exploration. In Experiment 2, excitation of the vmPFC prior to IS with the GABA-activated Cl(( - )) channel antagonist picrotoxin mimicked the stress resistance produced by control and prevented IS-induced reduction in social exploration. These results are consistent with prior work and identify the vmPFC as a critical component of the neural circuitry mediating the effects of stressor control on later behaviors. The relationship between the vmPFC, dorsal raphé nucleus, and other structures mediating stress-induced anxiety are discussed.