Pharmacologic Management of Aggression in Adults with Intellectual Disability

Introduction: Aggression is a common behavioral problem seen in patients with intellectual disabilities (ID). The safety and efficacy of second generation antipsychotics (SGAs), mood stabilizers and antidepressants in the management of aggression in these individuals have minimally been studied. This review aims to 1) summarize the studies conducted using second generation antipsychotics, mood stabilizers and antidepressants in treating aggressive behaviors in patient with ID and 2) determine based on the existing literature, which medications have been examined in the most rigorous study design that might suggest the most efficacy for use in clinical practice.Methods: Literature searches using PUBMED Central, CINAHL Plus, PsychINFO, and Embase databases were conducted using the following terms: intellectual disability/disabilities, mental retardation, developmental disability/disabilities, aggression, agitation, behavior disorder, adult, treatment, management. Studies predominantly including children with ID, and autism/pervasive developmental disabilities spectrum disorders were excluded. Analyses were done by class of medication: SGAs, mood stabilizers and antidepressants. The primary outcome measure was reduction in aggressive or self injurious behaviors as measured by each individual study.Results: The most rigorous study designs found using these agents were randomized controlled trials (RCT). A total of 10 RCTs were found, the majority being with risperidone (3) and lithium (2). Treatment with risperidone showed reduction in aggression when compared to placebo in most RCTs with the exception of one study in which risperidone was not better than placebo. Both lithium studies showed reduction in aggression when compared to placebo. The most abundant literature exists in retrospective chart reviews. The most commonly studied agent was risperidone which showed reduction in aggression in majority of the studies.Conclusions: Limited data exists for treatment of aggression in adults with ID. There are very few studies examining pharmacologic agents using RCTs. Given that risperidone and lithium were the most commonly studied agents in the most rigorous experimental design, it is suggested that these two agents prove efficacious for treatment of aggression in patients with ID. Limitations to most of these studies included concomitant psychotropic administration with variations in types and dosing, severity of ID, and the idea that a wide variety of aggression scales were used to assess outcome. Further research with more scientific rigor is required in this field

Estimated 2020 CO2 Emission Reductions in Virginia’s Transportation Sector from COVID-19

The initial lockdown phase of the COVID-19 pandemic presented an unfortunate opportunity to observe how abrupt, large-scale changes in traffic volume can reduce greenhouse gas emissions. This study explores how carbon dioxide (CO2) emissions from Virginia’s transportation sector may have been affected by the changes in activity stemming from COVID-19 to inform more carbon-neutral policies as the state recovers from the economic downfall. Emission savings were calculated by multiplying the percent change from 2019 to 2020 in traffic volume from the Virginia Department of Transportation with the business-as-usual 2020 U.S. Environmental Protection Agency estimate of CO2 emissions for Virginia’s transportation sector. We estimate Virginia’s 2020 COVID-19 transportation CO2 emissions reduction is around 15.0% (14.2 to 15.7%), with reduced passenger vehicle traffic making up the bulk of the inferred reduction. This study highlights the utility of reimagining our current transportation sector as a way to implement sustainable, state-level carbon reduction policies, such as the Clean Car Standards

Are Behavioral Effects of Early Experience Mediated by Oxytocin?

Early experiences can alter adaptive emotional responses necessary for social behavior as well as physiological reactivity in the face of challenge. In the highly social prairie vole (Microtus ochrogaster), manipulations in early life or hormonal treatments specifically targeted at the neuropeptides oxytocin (OT) and arginine vasopressin (AVP), have long-lasting, often sexually dimorphic, consequences for social behavior. Here we examine the hypothesis that behavioral changes associated with differential early experience, in this case handling the family during the first week of life, may be mediated by changes in OT or AVP or their brain receptors. Four early treatment groups were used, differing only in the amount of manipulation received during the first week of life. MAN1 animals were handled once on post-natal day 1; MAN1 treatment produces a pattern of behavior usually considered typical of this species, against which other groups were compared. MAN1–7 animals were handled once a day for post-natal days 1–7, MAN 7 animals were handled once on post-natal day 7, and MAN0 animals received no handling during the first week of life. When tested following weaning, males in groups that had received manipulation during the first few days of life (MAN1 and MAN1–7) displayed higher alloparenting than other groups. Neuroendocrine measures, including OT receptor binding and OT and AVP immunoreactivity, varied by early treatment. In brain areas including the nucleus accumbens, bed nucleus of stria terminalis and lateral septum, MAN0 females showed increased OT receptor binding. MAN1 animals also displayed higher numbers of immunoreactive OT cell bodies in the supraoptic nucleus. Taken together these findings support the broader hypothesis that experiences in the first few days of life, mediated in part by sexually dimorphic changes in neuropeptides, especially in the receptor for OT, may have adaptive consequences for sociality and emotion regulation

Temporal changes and determinants of childhood nutritional status in Kenya and Zambia

Background: The prevalence of undernutrition is decreasing in many parts of the developing world, but challenges remain in many countries. The objective of this study was to determine factors influencing childhood nutrition status in Kenya and Zambia. The objective of this study is to determine factors associated with temporal changes in childhood nutritional status in two countries in sub-Saharan Africa. Methods: Data from national demographic and health surveys from the World Bank for Kenya (1998\u20132009) and Zambia (1996\u20132014) were used to select the youngest child of each household with complete data for all variables studied. Multiple linear regression analyses were used for data from 2902 and 11,335 children from Kenya and Zambia, respectively, in each year to determine the relationship between social and economic factors and measures of nutritional status, including wasting, stunting, and overweight. Results: There was a decreased prevalence of stunting (35% in Kenya and 40% in Zambia), while the prevalence of wasting was unchanged (6\u20138% in both countries). From 1998 to 2009, there was a protective effect against stunting for wealthier families and households with electricity, for both countries. Finally, better educated mothers were less likely to have stunted children and girls were less likely to be stunted than boys. Conclusions: Based on the data analyzed, there was a higher risk of stunting in both Kenya and Zambia, for those with lower literacy, less education, no electricity, living in rural areas, no formal toilet, no car ownership, and those with an overall lower wealth index. Improving the education of mothers was also a significant determinant in improving the nutritional status of children in Kenya and Zambia. More broad-based efforts to reduce the prevalence of undernutrition need to focus on reducing the prevalence of undernutrition without promoting excess weight gain. Future economic advances need to consider integrated approaches to improving economic standings of households without increasing the risk for overnutrition

Target of rapamycin signaling orchestrates growth-defense trade-offs in plants

Plant defense to microbial pathogens is often accompanied by significant growth inhibition. How plants merge immune system function with normal growth and development is still poorly understood. Here, we investigated the role of target of rapamycin (TOR), an evolutionary conserved serine/threonine kinase, in the plant defense response. We used rice as a model system and applied a combination of chemical, genetic, genomic and cell-based analyses. We demonstrate that ectopic expression of TOR and Raptor (regulatory-associated protein of mTOR), a protein previously demonstrated to interact with TOR in Arabidopsis, positively regulates growth and development in rice. Transcriptome analysis of rice cells treated with the TOR-specific inhibitor rapamycin revealed that TOR not only dictates transcriptional reprogramming of extensive gene sets involved in central and secondary metabolism, cell cycle and transcription, but also suppresses many defense-related genes. TOR overexpression lines displayed increased susceptibility to both bacterial and fungal pathogens, whereas plants with reduced TOR signaling displayed enhanced resistance. Finally, we found that TOR antagonizes the action of the classic defense hormones salicylic acid and jasmonic acid. Together, these results indicate that TOR acts as a molecular switch for the activation of cell proliferation and plant growth at the expense of cellular immunity

Identification of transcripts with enriched expression in the developing and adult pancreas

The expression profile of different developmental stages of the murine pancreas and predictions of transcription factor interactions, provides a framework for pancreas regulatory networks and development

Targeted DNA Methylation by a DNA Methyltransferase Coupled to a Triple Helix Forming Oligonucleotide To Down-Regulate the Epithelial Cell Adhesion Molecule

The epithelial cell adhesion molecule (EpCAM) is a membrane glycoprotein that has been identified as a marker of cancer-initiating cells. EpCAM is highly expressed on most carcinomas, and transient silencing of EpCAM expression leads to reduced oncogenic potential. To silence the EpCAM gene in a persistent manner via targeted DNA methylation, a low activity mutant (C141S) of the CpG-specific DNA methyltransferase M.SssI was coupled to a triple-helix-forming oligonucleotide (TFO−C141S) specifically designed for the EpCAM gene. Reporter plasmids encoding the green fluorescent protein under control of different EpCAM promoter fragments were treated with the TFO−C141S conjugate to determine the specificity of targeted DNA methylation in the context of a functional EpCAM promoter. Treatment of the plasmids with TFO−C141S resulted in efficient and specific methylation of the targeted CpG located directly downstream of the triple helix forming site (TFS). No background DNA methylation was observed neither in a 700 bp region of the EpCAM promoter nor in a 400 bp region of the reporter gene downstream of the TFS. Methylation of the target CpG did not have a detectable effect on promoter activity. This study shows that the combination of a specific TFO and a reduced activity methyltransferase variant can be used to target DNA methylation to predetermined sites with high specificity, allowing determination of crucial CpGs for promoter activity

Mosaic nanoparticles elicit cross-reactive immune responses to zoonotic coronaviruses in mice

Protection against SARS-CoV-2 and SARS-related emergent zoonotic coronaviruses is urgently needed. We made homotypic nanoparticles displaying the receptor-binding domain (RBD) of SARS-CoV-2 or co-displaying SARS-CoV-2 RBD along with RBDs from animal betacoronaviruses that represent threats to humans (mosaic nanoparticles; 4-8 distinct RBDs). Mice immunized with RBD-nanoparticles, but not soluble antigen, elicited cross-reactive binding and neutralization responses. Mosaic-RBD-nanoparticles elicited antibodies with superior cross-reactive recognition of heterologous RBDs compared to sera from immunizations with homotypic SARS-CoV-2–RBD-nanoparticles or COVID-19 convalescent human plasmas. Moreover, sera from mosaic-RBD–immunized mice neutralized heterologous pseudotyped coronaviruses equivalently or better after priming than sera from homotypic SARS-CoV-2–RBD-nanoparticle immunizations, demonstrating no immunogenicity loss against particular RBDs resulting from co-display. A single immunization with mosaic-RBD-nanoparticles provides a potential strategy to simultaneously protect against SARS-CoV-2 and emerging zoonotic coronaviruses