Negative capacitance in multidomain ferroelectric superlattices.

The stability of spontaneous electrical polarization in ferroelectrics is fundamental to many of their current applications, which range from the simple electric cigarette lighter to non-volatile random access memories. Research on nanoscale ferroelectrics reveals that their behaviour is profoundly different from that in bulk ferroelectrics, which could lead to new phenomena with potential for future devices. As ferroelectrics become thinner, maintaining a stable polarization becomes increasingly challenging. On the other hand, intentionally destabilizing this polarization can cause the effective electric permittivity of a ferroelectric to become negative, enabling it to behave as a negative capacitance when integrated in a heterostructure. Negative capacitance has been proposed as a way of overcoming fundamental limitations on the power consumption of field-effect transistors. However, experimental demonstrations of this phenomenon remain contentious. The prevalent interpretations based on homogeneous polarization models are difficult to reconcile with the expected strong tendency for domain formation, but the effect of domains on negative capacitance has received little attention. Here we report negative capacitance in a model system of multidomain ferroelectric-dielectric superlattices across a wide range of temperatures, in both the ferroelectric and paraelectric phases. Using a phenomenological model, we show that domain-wall motion not only gives rise to negative permittivity, but can also enhance, rather than limit, its temperature range. Our first-principles-based atomistic simulations provide detailed microscopic insight into the origin of this phenomenon, identifying the dominant contribution of near-interface layers and paving the way for its future exploitation.

Two-Photon, Ratiometric, Quantitative Fluorescent Probe Reveals Fluctuation of Peroxynitrite Regulated by Arginase 1.

Peroxynitrite, a transient reactive oxygen species (ROS), is believed to play a deleterious role in physiological processes. Herein, we report a two-photon ratiometric fluorescent probe that selectively reacts with peroxynitrite yielding a >200-fold change upon reaction. The probe effectively visualized fluctuations in peroxynitrite generation by arginase 1 in vivo and in vitro. This provides evidence that arginase 1 is a critical regulator of peroxynitrite.

Predictors of PrEP Uptake Among Patients with Equivalent Access.

Increasing PrEP adoption for eligible individuals is critical, but limited research has examined individual-level factors that might be amenable to educational or behavioral intervention. Using data from a PrEP demonstration project conducted at a community health center, we examined differences in behavioral and psychosocial factors between patients offered PrEP who chose to accept it and those who declined. In a multivariable model, the odds of accepting PrEP were higher among those with an HIV-positive main partner, greater risk behavior in the past 3 months, and higher HIV risk perception. PrEP adoption was positively associated with PrEP adherence self-efficacy and negatively associated with perceived sensitivity to medicines. These psychological variables were associated with measures of PrEP- and HIV-related stigma. In the multivariable model, there were no differences in PrEP adoption by demographic factors or socioeconomic status. Data suggest that patients' decisions about PrEP uptake may be impacted not only by objective and subjective HIV risk, but also by psychological variables such as stigma beliefs, medication beliefs, and self-efficacy.

Single Atomic Layer Ferroelectric on Silicon.

A single atomic layer of ZrO2 exhibits ferroelectric switching behavior when grown with an atomically abrupt interface on silicon. Hysteresis in capacitance-voltage measurements of a ZrO2 gate stack demonstrate that a reversible polarization of the ZrO2 interface structure couples to the carriers in the silicon. First-principles computations confirm the existence of multiple stable polarization states and the energy shift in the semiconductor electron states that result from switching between these states. This monolayer ferroelectric represents a new class of materials for achieving devices that transcend conventional complementary metal oxide semiconductor (CMOS) technology. Significantly, a single atomic layer ferroelectric allows for more aggressively scaled devices than bulk ferroelectrics, which currently need to be thicker than 5-10 nm to exhibit significant hysteretic behavior (Park, et al. Adv. Mater. 2015, 27, 1811).

Domain Wall Orientations in Ferroelectric Superlattices Probed with Synchrotron X-Ray Diffraction.

Ferroelectric domains in PbTiO_{3}/SrTiO_{3} superlattices are studied using synchrotron x-ray diffraction. Macroscopic measurements reveal a change in the preferential domain wall orientation from {100} to {110} crystallographic planes with increasing temperature. The temperature range of this reorientation depends on the ferroelectric layer thickness and domain period. Using a nanofocused beam, local changes in the domain wall orientation within the buried ferroelectric layers are imaged, both in structurally uniform regions of the sample and near defect sites and argon ion-etched patterns. Domain walls are found to exhibit a preferential alignment with the straight edges of the etched patterns as well as with structural features associated with defect sites. The distribution of out-of-plane lattice parameters is mapped around one such feature, showing that it is accompanied by inhomogeneous strain and large strain gradients.

Tuning of the depolarization field and nanodomain structure in ferroelectric thin films.

The screening efficiency of a metal-ferroelectric interface plays a critical role in determining the polarization stability and hence the functional properties of ferroelectric thin films. Imperfect screening leads to strong depolarization fields that reduce the spontaneous polarization or drive the formation of ferroelectric domains. We demonstrate that by modifying the screening at the metal-ferroelectric interface through insertion of ultrathin dielectric spacers, the strength of the depolarization field can be tuned and thus used to control the formation of nanoscale domains. Using piezoresponse force microscopy, we follow the evolution of the domain configurations as well as polarization stability as a function of depolarization field strength.

Stereological Changes in Microvascular Parameters in Hippocampus of a Transgenic Rat Model of Alzheimer's Disease.

BACKGROUND: Microcirculatory factors play an important role in amyloid-ß (Aß)-related neuropathology in Alzheimer's disease (AD). Transgenic (Tg) rat models of mutant Aß deposition can enhance our understanding of this microvascular pathology. OBJECTIVE: Here we report stereology-based quantification and comparisons (between- and within-group) of microvessel length and number and associated parameters in hippocampal subregions in Tg model of AD in Fischer 344 rats and non-Tg littermates. METHODS: Systematic-random samples of tissue sections were processed and laminin immunostained to visualize microvessels through the entire hippocampus in Tg and non-Tg rats. A computer-assisted stereology system was used to quantify microvessel parameters including total number, total length, and associated densities in dentate gyrus (DG) and cornu ammonis (CA) subregions. RESULTS: Thin hair-like capillaries are common near Aß plaques in hippocampal subregions of Tg rats. There are a 53% significant increase in average length per capillary across entire hippocampus (p≤0.04) in Tg compared to non-Tg rats; 49% reduction in capillary length in DG (p≤0.02); and, higher microvessel density in principal cell layers (p≤0.03). Furthermore, within-group comparisons confirm Tg but not non-Tg rats have significant increase in number density (p≤0.01) and potential diffusion distance (p≤0.04) of microvessels in principal cell layers of hippocampal subregions. CONCLUSION: We show the Tg deposition of human Aß mutations in rats disrupts the wild-type microanatomy of hippocampal microvessels. Stereology-based microvascular parameters could promote the development of novel strategies for protection and the therapeutic management of AD.

Early Spatial Memory Impairment in a Double Transgenic Model of Alzheimer's Disease TgF-344 AD.

Before the course of Alzheimer's disease fully manifests itself and largely impairs a patient's cognitive abilities, its progression has already lasted for a considerable time without being noticed. In this project, we mapped the development of spatial orientation impairment in an active place avoidance task-a highly sensitive test for mild hippocampal damage. We tested vision, anxiety and spatial orientation performance at four age levels of 4, 6, 9, and 12 months across male and female TgF-344 AD rats carrying human genes for presenilin-1 and amyloid precursor protein. We found a progressive deterioration of spatial navigation in transgenic animals, beginning already at the age of 4 months, that fully developed at 6 months of age across both male and female groups, compared to their age-matched controls. In addition, we described the gradual vision impairment that was accentuated in females at the age of 12 months. These results indicate a rather early onset of cognitive impairment in the TgF-344 AD Alzheimer's disease model, starting earlier than shown to date, and preceding the reported development of amyloid plaques.

Contrast enhanced X-ray computed tomography imaging of amyloid plaques in Alzheimer disease rat model on lab based micro CT system.

Amyloid plaques are small (~ 50 µm), highly-dense aggregates of amyloid beta (Aß) protein in brain tissue, supposed to play a key role in pathogenesis of Alzheimer's disease (AD). Plaques´ in vivo detection, spatial distribution and quantitative characterization could be an essential marker in diagnostics and evaluation of AD progress. However, current imaging methods in clinics possess substantial limits in sensitivity towards Aß plaques to play a considerable role in AD screening. Contrast enhanced X-ray micro computed tomography (micro CT) is an emerging highly sensitive imaging technique capable of high resolution visualization of rodent brain. In this study we show the absorption based contrast enhanced X-ray micro CT imaging is viable method for detection and 3D analysis of Aß plaques in transgenic rodent models of Alzheimer's disease. Using iodine contrasted brain tissue isolated from the Tg-F344-AD rat model we show the micro CT imaging is capable of precise imaging of Aß plaques, making possible to further analyze various aspects of their 3D spatial distribution and other properties.

Reshaping of the gastrointestinal microbiome alters atherosclerotic plaque inflammation resolution in mice.

Since alterations in the intestinal microbiota may induce systemic inflammation and polarization of macrophages to the M1 state, the microbiome role in atherosclerosis, an M1-driven disease, requires evaluation. We aimed to determine if antibiotic (Abx) induced alterations to the intestinal microbiota interferes with atherosclerotic plaque inflammation resolution after lipid-lowering in mice. Hyperlipidemic Apoe-/- mice were fed a western diet to develop aortic atherosclerosis with aortas then transplanted into normolipidemic wild-type (WT) mice to model clinically aggressive lipid management and promote atherosclerosis inflammation resolution. Gut microbial composition pre and post-transplant was altered via an enteral antibiotic or not. Post aortic transplant, after Abx treatment, while plaque size did not differ, compared to Apoe-/- mice, Abx- WT recipient mice had a 32% reduction in CD68-expressing cells (p = 0.02) vs. a non-significant 12% reduction in Abx+ WT mice. A trend toward an M1 plaque CD68-expresing cell phenotype was noted in Abx+ mice. By 16S rRNA sequence analysis, the Abx+ mice had reduced alpha diversity and increased Firmicutes/Bacteroidetes relative abundance ratio with a correlation between gut Firmicutes abundance and plaque CD68-expressing cell content (p < 0.05). These results indicate that in a murine atherosclerotic plaque inflammation resolution model, antibiotic-induced microbiome perturbation may blunt the effectiveness of lipid-lowering to reduce the content of plaque inflammatory CD68-expressing cells.

Wnt signaling enhances macrophage responses to IL-4 and promotes resolution of atherosclerosis.

Atherosclerosis is a disease of chronic inflammation. We investigated the roles of the cytokines IL-4 and IL-13, the classical activators of STAT6, in the resolution of atherosclerosis inflammation. Using Il4-/-Il13-/- mice, resolution was impaired, and in control mice, in both progressing and resolving plaques, levels of IL-4 were stably low and IL-13 was undetectable. This suggested that IL-4 is required for atherosclerosis resolution, but collaborates with other factors. We had observed increased Wnt signaling in macrophages in resolving plaques, and human genetic data from others showed that a loss-of-function Wnt mutation was associated with premature atherosclerosis. We now find an inverse association between activation of Wnt signaling and disease severity in mice and humans. Wnt enhanced the expression of inflammation resolving factors after treatment with plaque-relevant low concentrations of IL-4. Mechanistically, activation of the Wnt pathway following lipid lowering potentiates IL-4 responsiveness in macrophages via a PGE2/STAT3 axis.

Stress and parenting during the global COVID-19 pandemic.

BACKGROUND: Stress and compromised parenting often place children at risk of abuse and neglect. Child maltreatment has generally been viewed as a highly individualistic problem by focusing on stressors and parenting behaviors that impact individual families. However, because of the global coronavirus disease 2019 (COVID-19), families across the world are experiencing a new range of stressors that threaten their health, safety, and economic well-being. OBJECTIVE: This study examined the impacts of the COVID-19 pandemic in relation to parental perceived stress and child abuse potential. PARTICIPANTS AND SETTING: Participants included parents (N = 183) with a child under the age of 18 years in the western United States. METHOD: Tests of group differences and hierarchical multiple regression analyses were employed to assess the relationships among demographic characteristics, COVID-19 risk factors, mental health risk factors, protective factors, parental perceived stress, and child abuse potential. RESULTS: Greater COVID-19 related stressors and high anxiety and depressive symptoms are associated with higher parental perceived stress. Receipt of financial assistance and high anxiety and depressive symptoms are associated with higher child abuse potential. Conversely, greater parental support and perceived control during the pandemic are associated with lower perceived stress and child abuse potential. Results also indicate racial and ethnic differences in COVID-19 related stressors, but not in mental health risk, protective factors, perceived stress, or child abuse potential. CONCLUSION: Findings suggest that although families experience elevated stressors from COVID-19, providing parental support and increasing perceived control may be promising intervention targets.

Single-Cell RNA Sequencing of Visceral Adipose Tissue Leukocytes Reveals that Caloric Restriction Following Obesity Promotes the Accumulation of a Distinct Macrophage Population with Features of Phagocytic Cells.

Obesity can lead to type 2 diabetes and is an epidemic. A major contributor to its adverse effects is inflammation of the visceral adipose tissue (VAT). Life-long caloric restriction (CR), in contrast, results in extended lifespan, enhanced glucose tolerance/insulin sensitivity, and other favorable phenotypes. The effects of CR following obesity are incompletely established, but studies show multiple benefits. Many leukocyte types, macrophages predominantly, reside in VAT in homeostatic and pathological states. CR following obesity transiently increases VAT macrophage content prior to resolution of inflammation and obesity, suggesting that macrophage content and phenotype play critical roles. Here, we examined the heterogeneity of VAT leukocytes and the effects of obesity and CR. In general, our single-cell RNA-sequencing data demonstrate that macrophages are the most abundant and diverse subpopulation of leukocytes in VAT. Obesity induced significant transcriptional changes in all 15 leukocyte subpopulations, with many genes showing coordinated changes in expression across the leukocyte subpopulations. Additionally, obese VAT displayed expansion of one major macrophage subpopulation, which, in silico, was enriched in lipid binding and metabolic processes. This subpopulation returned from dominance in obesity to lean proportions after only 2 weeks of CR, although the pattern of gene expression overall remained similar. Surprisingly, CR VAT is dominated by a different macrophage subpopulation, which is absent in lean conditions. This subpopulation is enriched in genes related to phagocytosis and we postulate that its function includes clearance of dead cells, as well as excess lipids, contributing to limiting VAT inflammation and restoration of the homeostatic state.

Trauma, Post-Migration Stress, and Mental Health: A Comparative Analysis of Refugees and Immigrants in the United States.

Numerous studies describe mental health effects of pre-migration trauma and post-resettlement stress among refugees, yet less research examines these associations with non-refugee immigrants. Additionally, few studies assess the prevalence and impact of traumatic experiences after settlement in a new country. Using a U.S.-based representative sample of Asian (n = 1637) and Latino (n = 1620) refugees and immigrants, we investigated how traumatic events prior to and after migration, and post-migration stressors, are associated with mental illness and distress. Pre-migration trauma posed risk across a broad range of psychological outcomes for Asian refugees and Latino immigrants. Deleterious effects of post-migration trauma were notable for both groups of refugees and immigrants. Discrimination, acculturative stress, and family conflict increased risk for disorder and distress across groups in complex ways. Findings highlight the importance of examining trauma and stress at pre- and post-migration phases across migrant populations, including those not labeled as refugees.

Heteroaggregation of an enveloped bacteriophage with colloidal sediments and effect on virus viability.

Four sediments in the colloidal size range: goethite, montmorillonite, illite, and kaolinite, were suspended with the bacteriophage φ6, a model enveloped virus, to determine relative rates of heteroaggregation and the effect of aggregation on virus viability. Turbidity was measured on combinations of virus and each sediment type at low concentration to determine aggregation rates. Aggregation of sediment with virus occurred regardless of mineral type, and larger fraction of virus is expected to aggregate with increasing sediment concentration leading to higher deposition rates. The negatively charged sediments, aggregated with φ6 (also negatively charged at neutral pH) at a faster rate than the positively charged sediments, yielding turbidity slopes of 4.94 × 10-3 s-1 and 7.50 × 10-4 s-1 for φ6-montmorillonite and φ6-illite aggregates, respectively, and 2.98 × 10-5 s-1 and 2.84 × 10-5 s-1, for φ6-goethite and φ6-kaolinite, respectively. This indicates that the interaction between sediments and virus is hydrophobic, rather than electrostatic. Large numbers of virions remained viable post-aggregation, despite the fragility of the viral envelope, indicating that small-sized aggregates, which may travel more readily through porous media, may pose an infection risk. The fraction of φ6 that remained viable varied with sediment type, with montmorillonite-φ6 aggregates experiencing the greatest reduction in infectivity at 35%. TEM analyses reveal that in all sediment-φ6 combinations, infectivity loss was likely due to disassembly of the viral envelope as a result of aggregation.

A Cross-National Comparison of Suicide Attempts, Drug Use, and Depressed Mood Among Dominican Youth.

We compared suicide attempts, depressed mood, and drug use of 1,710 Dominican public high school students in New York City (NYC) and 9,573 in the Dominican Republic (DR) in 2009. Compared to DR Dominicans, NYC Dominicans were more likely to have reported lifetime marijuana use (27.6% vs. 1.5%), lifetime inhalant use (11.0% vs. 7.6%), lifetime other drug use (9.9% vs. 3.0%), depressed mood (31.3% vs. 27.2%), and suicide attempt (13.8% vs. 8.8%). The results of this study supported the hypothesis that substantial increases in illicit drug use, especially cocaine, heroin, ecstasy, and methamphetamines, among NYC Dominican youth account for their increased risk for suicide attempts compared to their DR Dominican counterparts. It also identified suicide attempts as a public health problem among NYC Dominicans, the largest NYC Latino immigrant population.

Glucose disturbances in non-diabetic patients receiving acute treatment with methylprednisolone pulses.

OBJECTIVE: Methylprednisolone pulses are used in a variety of disease conditions, both for acute and chronic therapy. Although well tolerated, they increase glucose levels in both non-diabetic and diabetic patients. They may also be considered a significant risk for acute metabolic alterations. The purpose of this report is to determine the metabolic changes in blood glucose levels in non-diabetic patients receiving methylprednisolone pulses and identify the presence of predictive factors for its development. METHODS: Observational, prospective study in 50 non-diabetic patients receiving 1 g intravenous methylprednisolone pulses for three consecutive days as an indication for diverse autoimmune disorders. Demographic, anthropometric, and metabolic variables were analyzed, and glucose, insulin and C-peptide levels after each steroid pulse were identified. Different variables and the magnitude of hyperglycemia were analyzed using Pearson's correlation. RESULTS: 50 patients were included, predominantly women (66%, n = 33). The average age was 41 ± 14 years with a BMI of 26 ± 3 kg/m². Baseline glucose was 83 ± 10 mg/dL. After each steroid pulse, glucose increased to 140 ± 28, 160 ± 38 and 183 ± 44, respectively (p < 0.001). C-peptide and insulin concentrations increased significantly (p < 0.001). The prevalence of fasting hyperglycemia after each pulse was 68%, 94% and 98%, respectively. We found no correlation between the magnitude of hyperglycemia and the studied variables. CONCLUSION: Methylprednisolone pulses produced significant increases in fasting glucose in most patients without diabetes. Further studies are needed to define its role in long-term consequences.

Glucose disturbances in non-diabetic patients receiving acute treatment with methylprednisolone pulses / Distúrbios de glicose em pacientes não diabéticos que recebem tratamento agudo com pulsos de metilprednisolona

OBJECTIVE: Methylprednisolone pulses are used in a variety of disease conditions, both for acute and chronic therapy. Although well tolerated, they increase glucose levels in both non-diabetic and diabetic patients. They may also be considered a significant risk for acute metabolic alterations. The purpose of this report is to determine the metabolic changes in blood glucose levels in non-diabetic patients receiving methylprednisolone pulses and identify the presence of predictive factors for its development. METHODS: Observational, prospective study in 50 non-diabetic patients receiving 1 g intravenous methylprednisolone pulses for three consecutive days as an indication for diverse autoimmune disorders. Demographic, anthropometric, and metabolic variables were analyzed, and glucose, insulin and C-peptide levels after each steroid pulse were identified. Different variables and the magnitude of hyperglycemia were analyzed using Pearson's correlation. RESULTS: 50 patients were included, predominantly women (66 percent, n = 33). The average age was 41 ± 14 years with a BMI of 26 ± 3 kg/m². Baseline glucose was 83 ± 10 mg/dL. After each steroid pulse, glucose increased to 140 ± 28, 160 ± 38 and 183 ± 44, respectively (p < 0.001). C-peptide and insulin concentrations increased significantly (p < 0.001). The prevalence of fasting hyperglycemia after each pulse was 68 percent, 94 percent and 98 percent, respectively. We found no correlation between the magnitude of hyperglycemia and the studied variables. CONCLUSION: Methylprednisolone pulses produced significant increases in fasting glucose in most patients without diabetes. Further studies are needed to define its role in long-term consequences.

OBJETIVO: Pulsos de metilprednisolona são usados em diversas doenças, tanto para tratamento agudo quanto crônico. Embora bem tolerados, eles aumentam os níveis de glicose em ambos os pacientes, não diabéticos e diabéticos. Eles também podem ser considerados um risco significativo para alterações metabólicas agudas. O propósito deste estudo é determinar as alterações metabólicas nos níveis de glicose no sangue de pacientes não diabéticos que recebem pulsos de metilprednisolona e identificar a presença de fatores preditivos para seu desenvolvimento. MÉTODOS: Estudo observacional prospectivo em 50 pacientes não diabéticos que recebem pulsoterapia com 1 g de metilprednisolona intravenosa por três dias consecutivos como tratamento para diversas doenças autoimunes. Variáveis demográficas, antropométricas e metabólicas foram analisadas, e glicose, insulina e níveis de peptídeo C foram identificados após cada pulso de esteroide. Diferentes variáveis e a magnitude da hiperglicemia foram analisadas utilizando a correlação de Pearson. RESULTADOS: 50 pacientes foram incluídos, predominantemente mulheres (66 por cento, n = 33). A idade média foi de 41 ± 14 anos com um IMC de 26 ± 3 kg/m². A glicose de base foi de 83 ± 10 mg/dL. Após cada pulso de esteroide, a glicose aumentou para 140 ± 28, 160 ± 38 e 183 ± 44, respectivamente (p < 0,001). Peptídeo C e concentrações de insulina aumentaram significativamente (p < 0,001). A prevalência de hiperglicemia em jejum após cada pulso foi de 68 por cento, 94 por cento e 98 por cento, respectivamente. Não encontramos nenhuma correlação entre a magnitude da hiperglicemia e as variáveis estudadas. CONCLUSÃO: Os pulsos de metilprednisolona produziram aumentos significativos na glicemia de jejum na maioria dos pacientes sem diabetes. Mais estudos são necessários para definir o seu papel nas consequências em longo prazo.