Associations Between Prenatal Selective Serotonin Reuptake Inhibitor Exposure, Depression and Brain Morphology in Middle Childhood

Objective: Selective Serotonin Reuptake Inhibitors (SSRIs) are one of the most widely used prescribed medicine by pregnant women. A mixed literature suggests that prenatal SSRI exposure may increase depression risk among offspring. Method: Using data from children (n=11,076) who completed the baseline session of the Adolescent Brain and Cognitive Development (ABCD) study, we examined whether prenatal exposure to SSRIs is associated with child depression and variability in depression-related brain structures (i.e., hippocampus, amygdala, nucleus accumbens, caudate, putamen; rostral anterior cingulate; rostral and caudal middle frontal, superior frontal, and lateral and medical orbitofrontal cortices). Analyses were cross-sectional and included the following covariates: sex, race, ethnicity, age, birthweight, household income, maternal education, whether pregnancy was planned, gestational age when mother aware of pregnancy, prenatal exposure to prenatal vitamins, tobacco, marijuana, and alcohol. Lifetime maternal depression was included when not the independent variable of interest, and intracranial volume was included for brain structure analyses. Results: Prenatal SSRI exposure and maternal depression were each independently associated with depressive symptoms among children. No gray matter-based imaging metrics were associated with SSRI exposure following correction for multiple testing. SSRI exposure was nominally associated with reduced caudate, amygdala, and hippocampal volumes (all ps \u3c0.045). Conclusion: We find evidence that prenatal SSRI exposure is associated with elevated depressive symptoms among children, even after accounting for lifetime maternal depression. Imaging derived metrics of gray matter (i.e., subcortical volume, cortical thickness of brain regions associated with depression) may not play a mechanistic role in prenatal SSRI exposure-related offspring depression risk

Toward integrated conservation of North America's crop wild relatives

North America harbors a rich native flora of crop wild relatives—the progenitors and closely related species of domesticated plants—as well as a range of culturally significant wild utilized plants. Despite their current and potential future value, they are rarely prioritized for conservation efforts; thus many species are threatened in their natural habitats, and most are underrepresented in plant genebanks and botanical gardens. Further coordination of efforts among land management, botanical, and agricultural science organizations will improve conservation and general public awareness with regard to these species. We present examples of productive collaborations focused on wild cranberries (Vaccinium macrocarpon and Vaccinium oxycoccos) and chile peppers (Capsicum annuum var. glabriusculum). We then discuss five shared priorities for further action: (1) understand and document North America's crop wild relatives and wild utilized plants, (2) protect threatened species in their natural habitats, (3) collect and conserve ex situ the diversity of prioritized species, (4) make this diversity accessible and attractive for plant breeding, research, and education, and (5) raise public awareness of their value and the threats to their persistence

Frontiers of Brachial Plexus Injury: Future Revolutions in the Field

The field of brachial plexus surgery has undergone dramatic changes in the past 40 years. Most of these have been incremental in nature. We have seen increased use of nerve grafts and nerve transfers. We have seen the introduction of robotic limb replacements for the most severe flail limbs where surgical intervention has failed. In some cases, we have seen an increase in the use of computer simulation and virtual reality to train surgeons to plan and execute surgeries. More recently, we have seen the introduction of technologies derived from regenerative medicine research

Multimodal magnetic resonance neuroimaging measures characteristic of early cART-treated pediatric HIV: A feature selection approach

Children with perinatally acquired HIV (CPHIV) have poor cognitive outcomes despite early combination antiretroviral therapy (cART). While CPHIV-related brain alterations can be investigated separately using proton magnetic resonance spectroscopy

People pollinating partnerships: harnessing collaborations between botanic gardens and agricultural research organizations on crop diversity

The world's botanic gardens are repositories of plant diversity but are seldom considered to be major contributors to conservation and research of crops. Thus, botanic gardens and agricultural research organizations have had somewhat limited interactions historically. An unprecedented three-year collaboration between the American Society of Agronomy, Crop Science Society of America, Soil Science Society of America, the American Public Gardens Association, and the World Food Prize Foundation brought together experts from botanic gardens and the agricultural research community, culminating in a Symposium in April 2019 in Des Moines, Iowa. Funded by a grant from the United States Department of Agriculture – National Institute of Food and Agriculture (USDA – NIFA), one of the major outcomes of this collaboration was the development of a shared Road Map for conservation, use, and public engagement around North America’s crop wild relatives and wild utilized plants – species of interest to both communities. Key takeaways from this collaboration are discussed

Multimodal characterization of the late effects of traumatic brain injury: a methodological overview of the Late Effects of Traumatic Brain Injury Project

Epidemiological studies suggest that a single moderate-to-severe traumatic brain injury (TBI) is associated with an increased risk of neurodegenerative disease, including Alzheimer’s and Parkinson’s disease (AD and PD). Histopathological studies describe complex neurodegenerative pathologies in individuals exposed to single moderate-to-severe TBI or repetitive mild TBI, including chronic traumatic encephalopathy (CTE). However, the clinicopathological links between TBI and post-traumatic neurodegenerative diseases such as AD, PD, and CTE remain poorly understood. Here we describe the methodology of the Late Effects of TBI (LETBI) study, whose goals are to characterize chronic post-traumatic neuropathology and to identify in vivo biomarkers of post-traumatic neurodegeneration. LETBI participants undergo extensive clinical evaluation using National Institutes of Health TBI Common Data Elements, proteomic and genomic analysis, structural and functional MRI, and prospective consent for brain donation. Selected brain specimens undergo ultra-high resolution ex vivo MRI and histopathological evaluation including whole mount analysis. Co-registration of ex vivo and in vivo MRI data enables identification of ex vivo lesions that were present during life. In vivo signatures of postmortem pathology are then correlated with cognitive and behavioral data to characterize the clinical phenotype(s) associated with pathological brain lesions. We illustrate the study methods and demonstrate proof of concept for this approach by reporting results from the first LETBI participant, who despite the presence of multiple in vivo and ex vivo pathoanatomic lesions had normal cognition and was functionally independent until her mid-80s. The LETBI project represents a multidisciplinary effort to characterize post-traumatic neuropathology and identify in vivo signatures of postmortem pathology in a prospective study

Targeting the Monocyte–Macrophage Lineage in Solid Organ Transplantation

textabstractThere is an unmet clinical need for immunotherapeutic strategies that specifically target the active immune cells participating in the process of rejection after solid organ transplantation. The monocyte-macrophage cell lineage is increasingly recognized as a major player in acute and chronic allograft immunopathology. The dominant presence of cells of this lineage in rejecting allograft tissue is associated with worse graft function and survival. Monocytes and macrophages contribute to alloimmunity via diverse pathways: antigen processing and presentation, costimulation, pro-inflammatory cytokine production, and tissue repair. Cross talk with other recipient immune competent cells and donor endothelial cells leads to amplification of inflammation and a cytolytic response in the graft. Surprisingly, little is known about therapeutic manipulation of the function of cells of the monocyte-macrophage lineage in transplantation by immunosuppressive agents. Although not primarily designed to target monocyte-macrophage lineage cells, multiple categories of currently prescribed immunosuppressive drugs, such as mycophenolate mofetil, mammalian target of rapamycin inhibitors, and calcineurin inhibitors, do have limited inhibitory effects. These effects include diminishing the degree of cytokine production, thereby blocking costimulation and inhibiting the migration of monocytes to the site of rejection. Outside the field of transplantation, some clinical studies have shown that the monoclonal antibodies canakinumab, tocilizumab, and infliximab are effective in inhibiting monocyte functions. Indirect effects have also been shown for simvastatin, a lipid lowering drug, and bromodomain and extra-terminal motif inhibitors that reduce the cytokine production by monocytes-macrophages in patients with diabetes mellitus and rheumatoid arthritis. To date, detailed knowledge concerning the origin, the developmental requirements, and functions of diverse specialized monocyte-macrophage subsets justifies research for therapeutic manipulation. Here, we will discuss the effects of currently prescribed immunosuppressive drugs on monocyte/macrophage features and the future challenges

WalkMore: a randomized controlled trial of pedometer-based interventions differing on intensity messages

Pedometer-based programs have elicited increased walking behaviors associated with improvements in blood pressure in sedentary/low active postmenopausal women, a population at increased risk of cardiovascular disease. Such programs typically encourage increasing the volume of physical activity with little regard for its intensity. Recent advances in commercially available pedometer technology now permit tracking of both steps/day and time in moderate (or greater) intensity physical activity on a daily basis. It is not known whether the dual message to increase steps/day while also increasing time spent at higher intensity walking will elicit additional improvements in blood pressure relative to a message to only focus on increasing steps/day. The purpose of this paper is to present the rationale, study design, and protocols employed in WalkMore, a 3-arm 3-month blinded and randomized controlled trial (RCT) designed to compare the effects of two community pedometer-based walking interventions (reflecting these separate and combined messages) relative to a control group on blood pressure in sedentary/low active post-menopausal women, a population at increased risk of cardiovascular disease. 120 sedentary/low active post-menopausal women (45-74 years of age) will be randomly assigned (computer-generated) to 1 of 3 groups: A) 10,000 steps/day (with no guidance on walking intensity/speed/cadence; BASIC intervention, n = 50); B) 10,000 steps/day and at least 30 minutes in moderate intensity (i.e., a cadence of at least 100 steps/min; ENHANCED intervention, n = 50); or a Control group (n = 20). An important strength of the study is the strict control and quantification of the pedometer-based physical activity interventions. The primary outcome is systolic blood pressure. Secondary outcomes include diastolic blood pressure, anthropometric measurements, fasting blood glucose and insulin, flow mediated dilation, gait speed, and accelerometer-determined physical activity and sedentary behavior. This study can make important contributions to our understanding of the relative benefits that walking volume and/or intensity may have on blood pressure in a population at risk of cardiovascular disease. ClinicalTrials.gov Record NCT01519583, January 18, 2012

Comparative genomics explains the evolutionary success of reef-forming corals

Transcriptome and genome data from twenty stony coral species and a selection of reference bilaterians were studied to elucidate coral evolutionary history. We identified genes that encode the proteins responsible for the precipitation and aggregation of the aragonite skeleton on which the organisms live, and revealed a network of environmental sensors that coordinate responses of the host animals to temperature, light, and pH. Furthermore, we describe a variety of stress-related pathways, including apoptotic pathways that allow the host animals to detoxify reactive oxygen and nitrogen species that are generated by their intracellular photosynthetic symbionts, and determine the fate of corals under environmental stress. Some of these genes arose through horizontal gene transfer and comprise at least 0.2% of the animal gene inventory. Our analysis elucidates the evolutionary strategies that have allowed symbiotic corals to adapt and thrive for hundreds of millions of years.This work was made possible by grants from the National Science Foundation, EF-1041143/RU 432635 and EF-1416785 awarded to PGF, DB, and TM, respectively. RDG, HMP, and AJS were supported by grants from the National Institutes of Health, NIMHD P20MD006084, the Hawaii Community Foundation, Leahi Fund 13ADVC-60228 and NSF OCE PRF 1323822 and National Science Foundation Experimental Program to Stimulate Competitive Research Hawaii: EPS- 0903833. CRV and MA acknowledge funding by the King Abdullah University of Science and Technology (KAUST)

T cell cytolytic capacity is independent of initial stimulation strength.

How cells respond to myriad stimuli with finite signaling machinery is central to immunology. In naive T cells, the inherent effect of ligand strength on activation pathways and endpoints has remained controversial, confounded by environmental fluctuations and intercellular variability within populations. Here we studied how ligand potency affected the activation of CD8+ T cells in vitro, through the use of genome-wide RNA, multi-dimensional protein and functional measurements in single cells. Our data revealed that strong ligands drove more efficient and uniform activation than did weak ligands, but all activated cells were fully cytolytic. Notably, activation followed the same transcriptional pathways regardless of ligand potency. Thus, stimulation strength did not intrinsically dictate the T cell-activation route or phenotype; instead, it controlled how rapidly and simultaneously the cells initiated activation, allowing limited machinery to elicit wide-ranging responses