Introduction. We present a case of serpiginous choroidopathy (SC) with novel OCTA and en face OCT reflectance findings which help identify subclinical disease progression. Case Presentation. En face OCT reflectance images demonstrated outer retinal tubules (ORT) at the serpiginous lesion margins of affected and unaffected retina on multimodal imaging. OCTA findings demonstrate variable dropout of choriocapillaris in “normal” retina beyond lesion borders which was not visible on standard imaging and which demonstrated a clear transition zone beyond the ORT. Discussion. This is the first report of choriocapillaris atrophy identified on OCTA not identified on traditional multimodal imaging in serpiginous choroidopathy. Damage to vasculature only visible with OCTA may help characterize the distribution of inflammation, aiding in monitoring of suppression not illustrated by traditional imaging and which may threaten the central macula. ORT in SC suggest death and reorganization of outer segments from dysfunction of the choriocapillaris and RPE, as well as serve to demarcate the area of chronic or old inflammation, supporting the hypothesis that the choriocapillaris is the primary site of inflammation in SC. Based on these findings, we recommend OCTA on all patients with serpiginous choroidopathy to monitor underlying state of inflammation and help determine immunosuppressive threshold. The pathogenesis of SC is poorly understood, with clinical and histologic studies suggesting autoimmune, infectious, vasculopathic, and retinal degenerative etiologies , 2. ReceA 37-year-old female with no past medical or ocular history presented with 2 weeks of redness, pain, and photophobia of her right eye (OD). She was diagnosed with acute anterior uveitis by an outside provider and started on topical difluprednate four times daily (QID) and cyclopentolate once daily (QD) OD. Upon presentation to our facility, she reported slight improvement in her symptoms 2 weeks into treatment.On initial examination, visual acuity was 20/20 in her right and 20/20 in her left eye (OS) with unremarkable pupillary exam and normal intraocular pressure. Anterior segment examination of the right eye (OD) revealed 2 areas of anterior corneal stromal scarring and 0.5+ anterior chamber cell without flare. One area of anterior stromal scarring and trace cell without flare was seen OS. Fundoscopy revealed 0.5+ vitreous cell without haze in both eyes (OU); healthy appearing optic nerves OU; and extensive, serpentine peripapillary chorioretinal scarring OU with extension into the macula Figures . There wThe patient rapidly improved, and immunomodulatory therapy was initiated with a standard steroid taper. At one-month follow-up, en face OCT reflectance and OCTA imaging were obtained, which demonstrated severe atrophy with outer retinal tubules and patchy dropout of choriocapillaris in areas of otherwise normal-appearing retina, respectively . Over thWe present a case of serpiginous choroidopathy (SC) imaged with OCTA and en face OCT reflectance imaging. Images were obtained and processed based upon previously described methodologies in the literature , 4.OCTA imaging showed dropout of the choriocapillaris at lesion margins and discontinuously in adjacent areas centrally which appeared normal on traditional imaging such as FA . Prior tOCT angiography allows a noninvasive assessment of choroidal and deep vasculature sometimes not evident on fluorescein angiography (FA). Recently, several small case series of OCTA in SC have suggested extensive inflammation in deep retinal vessels, RPE, and choriocapillaris. Desai et al. reported a series of 6 eyes of 3 patients with active and inactive SC. In this series, active patients demonstrated absence of choriocapillaris with thickening of overlying RPE and outer retinal layers on OCTA in areas of atrophic serpiginous lesions . InactivWe analyzed en face OCT reflectance image slabs, as well as cross-sectional OCT images. En face OCT reflectance imaging demonstrated outer retinal tubules at the quiescent serpiginous margins just adjacent to those areas of atrophic choriocapillaris on OCT which were normal-appearing on funduscopy and FA . Cross-sOn SD-OCT imaging, outer retinal tubules appear as circular areas of hyporeflectivity with a ring of hyperreflectivity contained within the outer nuclear layer. Prior investigations of outer retinal tubules have centered around age-related macular degeneration (AMD) and spectral domain OCT (SD-OCT) but never reported in SC. Of the 69 eyes with outer retinal tubules identified in one study, 81% were attributable to AMD , 11. GivSevere choriocapillaris inflammation may be the cause of outer retinal atrophy in serpiginous choroidopathy, with the presence of ORT signifying reorganization of photoreceptors localizing inflammation to this area. Current multimodal imaging without use of OCTA is widely accepted for the diagnosis and monitoring of SC. In this report, we describe a patient with OCTA findings of choriocapillaris atrophy demonstrating subclinical disease beyond serpiginous lesion borders visible on standard imaging. Loss of choriocapillaris integrity in areas outside of the serpiginous borders suggests subclinical activity which, if followed with OCTA, may aid in earlier identification of progression or more targeted timing for tapering of immunomodulatory therapy if stable. This suggests that OCTA may be more sensitive than SD-OCT and FA in identifying activity in SC and should be more widely adopted in the long-term management of these patients.


Understanding age-related change in cognition and identification of pathological changes requires sensitive and valid measurement of cognitive performance across time. Technological advances, such as ambulatory assessment of cognition using smartphones, have enabled intensive longitudinal methods where data is collected with many measurements over time. Our research group has developed novel ambulatory assessments that provide reliable, sensitive, and ecologically valid measurement of cognition across multiple timescales; from momentary changes to change across years. This symposium will present a spectrum of approaches to analysis of intensive longitudinal data that can inform models of cognitive aging. All three presentations will draw on data from measurement burst studies that apply our ambulatory cognitive assessment methods in community-based samples . For each measurement burst, participants undergo assessment consisting of brief surveys and cognitive tests via smartphone, up to 7 times per day across 14 days. Oravecz et al. will discuss the application of a Bayesian multilevel implementation of the double exponential model to account for retest effects while quantifying change in peak cognitive performance across time. Kang et al., will demonstrate a growth curve modeling approach for assessing the effects of between-person variables  on change in cognition across measurement bursts. Harrington et al., will demonstrate a model-based cluster analysis approach, leveraging ambulatory assessments of subjective and objective cognitive function to unpack latent groups as a function of age and loneliness. Measurement, Statistics, and Research Design Interest Group Sponsored Symposium.


Evidence suggests a growing retirement crisis in the United States among older adults placing many of them at risk of falling into poverty. While Social Security provides income assistance to retirees, the average monthly benefit is $1,300. Among older adults nearing or in retirement, the use of public assistance programs is increasing. Using data collected by the Associated Press-NORC Center for Public Affairs Research we examine retirement preparedness, borrowing from retirement plans, and use of social welfare programs. Findings indicate increased borrowing from retirement plans due to debt, significant differences in racial and gender groups accessing and receiving services among those 75 and older. Increasing rates of unpreparedness for retirement exist among older Americans, particularly among adults of color. An increase in the use of safety net services among older adults is occurring concurrently with severe funding reductions in social welfare programming.


Migraine is a multifaceted brain disorder where multisensory disturbances are associated with headache. Yet sensory symptoms are conventionally justified by dysfunctions confined to the cerebral cortex, a perspective through the complex interplay of thalamocortical network would provide the entire picture, more pertinent to the central sensory processing. It is important to consider thalamus as a hub that integrates multiple domains via extensive connections among anatomically and functionally separate cortical areas. Accordingly, cortical spreading depression (CSD), implicated in migraine pathophysiology can be seen as a tool to disconnect thalamocortical network by functionally eliminating cerebral cortex. Hence, including thalamic reticular nucleus and higher order thalamic nuclei, which conveys the information transthalamically among visual, somatosensory, language and motor cortical areas, would greatly improve our current understanding of migraine. Migraine is the most prevalent brain disorder under age of 50 all around the globe and the first cause of disability due to severe headache and associated sensory disorders [1]. The characteristic features of pain are one sided, severe, pulsating headache attacks, worsening by daily movements and lasting 4–72 h. Accompanying sensorial symptoms suggesting hyperresponsivity in the somatosensory, visual, auditory, and olfactory systems are distinguishing features of migraine attacks and multisensory stimuli may worsen the headache severity [2]. Additionally, prior to the headache phase more pronounced sensorial disruptions can occur in the visual and somatosensory system such as scintillations, scotoma or paresthesia, numbness in the extremities. These slowly propagating sensory deficits are recognized as aura symptoms and implicated by underlying cortical spreading depression (CSD) waves [3]. CSD is a neuronal and glial depolarization wave that slowly propagates within the cerebral cortex, causing transient electrical and functional silence of the involved area. Propagation of massive depolarizations and accompanying electrical DC shift and regional blood flow increase along the cortex, left long-lasting decreased neuronal excitability and reduced regional blood flow behind . The sensory aura symptoms are considered solely due to cerebral cortical dysfunction by CSD. However, this conventional approach disregards several facts that i) propagation of CSD in gyrencephalic brains such as humans, primates and even felines is very restricted [4], ii) cerebral cortex functions in a synchrony with thalamus and brain network systems. In that sense CSD was essentially used to generate functional ablation of cerebral cortex in thalamic studies [4]. Understanding the function of cerebral cortex requires knowledge of complex interaction between the cortex and the thalamus, known as thalamocortical network. The cerebral cortex and the thalamus operate in continuous interaction during the process of any information particularly related to somatosensory, visual and auditory sensory systems, movement, language, cognition and consciousness . The thalamus sends projections to majority of the cerebral cortex, and receives cortical outputs in return. Thalamic nuclei transmitting peripheral sensory inputs to the primary cerebral cortical areas are considered as the first-order relay nuclei such as the ventral posteromedial (VPM) and lateral geniculate nucleus (LGN) that relay cephalic somatosensory inputs and visual stimuli respectively. Likewise, the higher-order thalamic nuclei receive inputs from the deep cerebral cortical layers and relay information from one cortical area to another . By this means, higher-order thalamic nuclei function as hubs that synchronize distant cerebral cortical areas via transthalamic cortico-cortical connections [7]. The deep cortical cells particularly from the 6th layer, also project to inhibitory neurons in the thalamic reticular nucleus (TRN) and modulate the frequency-dependent thalamic function [6–8]. The TRN consists of GABAergic inhibitory neurons and surrounds the dorsal thalamus. While the TRN exclusively projects to the thalamus and inhibits thalamic drive to the cortex, its neurons are driven by the first- and higher-order thalamic nuclei as well as the cerebral cortex . TRN involvement during CSD was demonstrated in awake, consciously behaving experimental animals . CSD induced SD waves were recorded in TRN and neuronal activation was demonstrated. It is likely that either SD in the cerebral cortex could provoke SD in TRN or SD waves propagate from cerebral cortex to the TRN, as subcortical structures are more susceptible compared to highly convoluted cerebral cortex in humans [4]. Involvement of the TRN may play a role in reduced sensory discrimination, lateral inhibition and increased response to sensory stimuli in different modalities such as light, sound and touch during migraine attacks. A subset of cortical deep projection neurons was shown to project selectively to higher order thalamic nuclei in mice and recently the higher order thalamic dysfunction was proposed to be involved in the development of migraine symptoms . Instead of attributing sensory dysfunctions merely to the cerebral cortex, alternative view proposes a complex interaction of first- and higher-order thalamocortical areas along with TRN . A minimum critical volume of 1 mm3 rodent cortical brain tissue was estimated to be depolarized to ignite CSD [11]. Even if the propagation of CSD is blocked, such a depolarized cortical focus is sufficient to create a change in ongoing cortico-thalamic drive on thalamic relay nuclei and thalamic reticular nucleus. During CSD, abrupt cessation of cortical neuronal firing, would result in decreased excitatory glutamatergic drive from cortexto the thalamus, leading to a reduced GABAergic output from TRN on to thalamic relay nuclei and increased sensory impulses through thalamic relay to the cortex . That would account for the increased sensory excitation, sensory hyperresponsivity, reduced discrimination and reduced lateral inhibition and bidirectional role of sleep in migraine. Therefore, the processing of somatosensory stimulus and sensory discrimination was investigated in migraine patients [12–16]. For that purpose, somatosensory temporal discrimination (STD) test was employed. STD detects the temporal threshold to perceive two consecutive somesthetic stimuli as undoubtedly distinct [12–14]. STD was remarkably prolonged during the migraine attack while STD threshold values outside the migraine attacks were comparable to healthy volunteers [12]. STD studies also revealed that such a prolongation was specific to migraine attacks and was not detected during tension type headache, which is another common headache disorder [14]. It is an intriguing finding that discrimination of somatosensory stimuli applied to the hand that is transmitted through a pathway via thalamic ventral posterolateral nucleus (VPL), is disturbed during migraine attacks. Indeed, migraine headache is transmitted through a different pathway via trigeminal nerve to the thalamic ventral posteromedial nucleus (VPM). Hence, it is unlikely that prolonged temporal discrimination of somatosensory stimulus applied to hand is merely mediated as a direct result of trigeminal nerve or thalamic VPM activation. Transient impairment in the ability of discriminating the exact entry of somatosensory stimuli suggested a central processing dysfunction. Further study was conducted by short afferent inhibition (SAI) paradigm using transcranial magnetic stimulation [16]. SAI evaluates integration of somatosensory input through the thalamic relay neurons in the sensorimotor cortex. The SAI results revealed that impaired sensorimotor integrity and reduced cortico-cortical inhibition between somatosensory and motor cortices were associated with migraine attacks [16]. SAI impairment during migraine attacks, indicated a disinhibition in the sensorimotor integration. Remarkably, the facilitation of motor responses to a conditioned sensory stimulus was detected even several hours prior to the onset of migraine headache [16]. Therefore, the possible involvement of higher order centers seems undisputable. In the higher order thalamic nuclei such as pulvinar, that would be manifested by the disrupted visual information processing and may be related to positive visual hallucinations superimposed on to a first-order incoming information, similar to the patients’ visual auras [4]. Also, higher order visual areas and somatosensory areas are associated with medial and anterior part of the pulvinar that is a multimodal sensory integration area [17]. Therefore, loss of any incoming information by CSD from one of the interconnected cortical areas such sensorimotor cortex or visual cortex to the pulvinar would change impulse trafficking and may yield multisensory sensory symptoms synchronously and/or sequentially.Thus, the view of thalamocortical network dysfunction would clarify positive aura symptoms and simultaneous manifestation of different symptoms related to distant cortical areas such as visual, sensorimotor and language cortices interconnected through a thalamic hub. Additionally, sensorial disruptions in more than one domain accompanying migraine headache can be attributed to multisensory integration dysfunction of the higher order thalamocortical network. Involvement of TRN would contribute sensory hypersensitivity in multiple sensory modalities, lateral inhibition and sensory discrimination problems associated with migraine headache. Additionally, activation of trigeminal pain nucleus through central pathways as a result of thalamocortical dysfunction could also contribute to the development of lateralized migraine headache.


The proportion of women of reproductive age who are overweight or obese is increasing globally. Gestational obesity is strongly associated in both human studies and animal models with early-onset development of adult-associated metabolic diseases including metabolic syndrome in the exposed offspring. However, animal model studies have suggested that gestational diet in obese pregnancies is an independent but underappreciated mediator of offspring risk for later life metabolic disease, and human diet consumption data have highlighted that many women do not follow nutritional guidelines prior to and during pregnancy. Thus, this review will highlight how maternal diet independent from maternal body composition impacts the risk for later-life metabolic disease in obesity-exposed offspring. A poor maternal diet, in combination with the obese metabolic state, are understood to facilitate pathological in utero programming, specifically through changes in lipid handling processes in the villous trophoblast layer of the placenta that promote an environment associated with the development of metabolic disease in the offspring. This review will additionally highlight how maternal obesity modulates villous trophoblast lipid processing functions including fatty acid transport, esterification and beta-oxidation. Further, this review will discuss how altering maternal gestational diet may ameliorate these functional changes in lipid metabolic processes in the obese placenta.  Throughout the gestational period, maternal nutrient handling must adapt to the increasing needs of the growing fetal-placental unit to ensure developmental processes continue in a healthy and physiological manner. For example, maternal insulin sensitivity diminishes, and fasting serum lipid levels rise late in gestation to preserve necessary macronutrients for trans-placental transport into fetal circulation ,2,3. HowFurthermore, alterations in lipid processing functions of the placenta—including fatty acid (FA) transport, lipid esterification and FA beta-oxidation—have been thought to modulate materno-fetal lipid transport and the resulting changes to fetal lipid exposures may underlie metabolic disease programming. This review will additionally highlight how maternal obesity modulates these lipid handling processes in the placenta and discuss how maternal diet may program these placental processes independently from increased maternal adiposity.The study of the impacts of maternal gestational environment on fetal growth and development is encompassed within the field of research known as The Developmental Origins of Health and Disease (DOHaD) ,5. This 2), whereby a BMI > 25 is overweight and a BMI > 30 is obese palmitate oxidation rates in cultured villous trophoblast cells from otherwise healthy obese Ohioan women [Maternal diet has been identified to impact placental lipid oxidative function in some obese women. Specifically, obese Hawaiian women, who consume the Pacific diet, have been found to have similar mRNA expression levels of mitochondrial and peroxisomal beta-oxidation enzymes as lean Hawaiian women  Figure . This maan women . While POne potential method to quantify placental beta-oxidative function is to examine the acylcarnitine profiles of maternal blood products. Under normal physiological conditions, complete beta-oxidation occurs whereby all carbon atoms in the FA backbone are converted into acetyl-CoA molecules that are oxidized for ATP production ,96. HoweAcylcarnitine profiles have previously been examined as potential biomarkers for the early detection of other placental diseases such as pre-eclampsia ,111. SpeAccumulation of shortened acylcarnitine species has also previously been linked to an increased expression of pro-inflammatory molecules . For exaOverall, acylcarnitine analysis may represent a relatively unexplored field in placenta physiology. Analysis of differences within these profiles of obese and lean women may allow clinicians to diagnose placental mitochondrial dysfunctions in conjunction with inflammatory responses early during the gestation period. In turn, acylcarnitine biomarkers may allow clinicians to monitor the impact of dietary interventions on placental lipid handling during gestational period and modulate the course of treatment to limit the risks of offspring development of later life disease.A maternal consumption of a diet high in saturated FA species and low in PUFA species during the gestational period may promote adverse placental function that underlies the development of placental and fetal metabolic dysfunction, independent to maternal body composition. Understanding the mechanisms that underlie placental metabolic dysfunctions associated with dietary fat in obese pregnancies and the accompanying offspring metabolic disorders will require a robust understanding of placental lipid transport, esterification and oxidation . A great


Human brain organoids cultured from human pluripotent stem cells provide a promising platform to recapitulate histological features of the human brain and model neural disorders. However, unlike animal models, brain organoids lack a reproducible topographic organization, which limits their application in modeling intricate biology, such as the interaction between different brain regions. To overcome these drawbacks, brain organoids have been pre-patterned into specific brain regions and fused to form an assembloid that represents reproducible models recapitulating more complex biological processes of human brain development and neurological diseases. This approach has been applied to model interneuron migration, neuronal projections, tumor invasion, oligodendrogenesis, forebrain axis establishment, and brain vascularization. In this review article, we will summarize the usage of this technology to understand the fundamental biology underpinning human brain development and disorders. The human central nervous system (CNS) develops from several distinct vesicles into multiple intertwined regions. During this process, a range of migratory streams arise where progenitors generated in one place migrate and integrate into other areas : the medial ganglionic eminence (MGE) and the caudal ganglionic eminence /CGE cells were observed to migrate into dorsal regions. Slice culture of dorso-ventral fusion organoids and time-lapse imaging analysis revealed characteristic interneuron migratory dynamics. Administration of the CXCR4 antagonist AMD3100 onto organoid slice cultures perturbed the migration, supporting a potential application of the fusion platform for drug screening.Bagley et al.  also estNKX2-1::GFP reporter human embryonic stem cell (hESC) line. RNA-seq, scRNA-seq, and chromatin accessibility analysis revealed that hMGEOs exhibited a strong correlation with the transcriptional signature of the MGE tissues from of human fetal brain. By fusing human cortical organoids (hCOs) and hMGEOs, they established hMGEOs-hCOs fusion organoids, named hfMCOs. GFP+ but RFP− interneuron progenitors migrated into the neuronal layer of hCOs. Their migration can be inhibited by the application of blebbistatin, a myosin II inhibitor. Besides, functional synapses in hfMCOs were also observed by calcium imaging analysis.Further, Xiang et al.  generateFurthermore, using a dorsoventral organoid fusion model, Yuan et al.  showed tLong distance-projections play essential roles in brain functions. According to recent reports, corticothalamic interactions are relevant for sensorimotor interplay, selective attention, and arousal behaviors  is the deadliest and most widespread primary brain tumor in adults. Their property to spread through infiltration in the host brain tissue is associated with high resistance and recurrence rate. To understand the mechanism underpinning this invasive phenotype, organoid-GBM fusion models are particularly appropriate. Ogawa et al.  fused tuvβ5 axis as a potential mechanism for ZIKV tropism. Thus, organoid-GSC fusion models could be used as in vitro platforms to characterize GBM invasiveness and screen for potential therapeutics.Tumor-organoid fusion models have been used for preclinical therapeutic studies. Previously, the Zika virus (ZIKV) has been proven to be a potential oncolytic virus for brain tumor therapy because of its tropism towards tumor cells  are the myelinating glial cells of the brain and the last type of neural cells to be generated after neurons and astroglial cells during mammalian brain development  spheroids, endothelial cell (iEC) spheroids, and mesenchymal stem cells (MSCs; Song et al., in vivo vascularization during brain development, and significant improvements still need to be done before obtaining functional vascular networks in organoid cultures.During brain development, the vasculature is one of the important niche components for neural stem cells and plays critical roles in neurogenesis (Bjornsson et al., in vitro. The fusion strategy should not be limited to the fusion of brain tissues as it can be applied to assemble brain organoids with other types of organoids to study the interaction between different organs. For instance, hepato-biliary-pancreatic organogenesis has been modeled using a multi-organoid fusion approach (Koike et al., Brain organoid fusion technology allows us to study more complicated biology during human brain development and neural disorders using hESCs or patient-derived iPSCs, including interneuron migration, and neuronal projections. Using the same technique, researchers can also study other pathological processes and potential mechanisms, such as corpus callosum deformity. Assembling multiple different brain regions would be the next step towards a more complete human “mini-brain,” which could then be used to study biological mechanisms requiring the interaction of several brain regions AC, ZG, and LF wrote the manuscript. AC and ZG prepared the figures. SB directed the manuscript preparation and wrote the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


We discuss synergies between sequencing and imaging techniques for the discovery and validation of local molecular signaling mechanisms regulating synaptic development, plasticity, and maintenance in circuits.A key challenge in developmental neuroscience is identifying the local regulatory mechanisms that control neurite and synaptic refinement over large brain volumes. Innovative molecular techniques and high-resolution imaging tools are beginning to reshape our view of how local protein translation in subcellular compartments drives axonal, dendritic, and synaptic development and plasticity. Here we review recent progress in three areas of neurite and synaptic study  In neuroscience, physical maps of synaptic connections between neurons (“connectomes”) help to refine hypotheses about neural computation and provide a shared anatomical resource to guide investigations of circuit function and pathologies associated with human brain disease. Physical maps of developing circuits can also help to identify progressive structural changes across stages of neuronal and synaptic maturation. Connectomic maps are produced using volumetric electron microscopy (EM) techniques that provide dense reconstructions of all cellular processes and synaptic connections in brain tissue. Continued progress in automated sample collection, high-throughput imaging, and computational analysis  molecular-genetic approaches for quantifying mRNA diversity, abundance, and regulation of the local transcriptome/translatome in targeted subcellular compartments; (2) proteomic techniques for labeling, isolating, and quantifying nascent proteins and protein-protein interaction networks in specific synaptic connections; and (3) super-resolution fluorescence microscopy for multi-scale imaging and quantitative analysis of subsynaptic molecular organization within developing microcircuits. When applied together, advanced techniques in these areas have important synergies that facilitate discovery, validation, and throughput in new experiments designed to study the local molecular regulation of neural circuit development.In this review article, we discuss a bottom-up “developmental molecular connectomics” approach for investigating the regulation of local molecular remodeling during circuit refinement . We highNeural circuit development requires the precise formation and selective plasticity of synaptic connections distributed across each neuron’s polarized geometry (axons/dendrites) at significant distances from the soma. Because each synapse is an intricate molecular machine assembled from thousands of proteins, the development of circuit connections creates a significant metabolic demand for individual neurons  and perform RNA sequencing analysis of compartment-specific isolates for comparison . Such exTo address questions about directed trafficking and mRNA enrichment in specific spatiotemporal contexts, an immunopurification approach called Translating Ribosome Affinity Purification (TRAP) was developed for isolating genetically-tagged ribosomes and their associated mRNAs in targeted circuits  uses the transgenic expression of synapse-specific fluorescent fusion proteins to purify specific synapse types from total synaptosomal fractions based on fluorescence-activated cell sorting  granules over long distances to dendrites and axons to establish local transcriptome pools  axons is developmentally-regulated and shifts during different stages of circuit refinement  where mRNAs encoding essential respiratory chain complex proteins are locally translated and assembled into mitochondria in response to stimulation . The induction of hippocampal LTP/LTD Direct evidence for local (synaptic) protein production in response to synaptic stimulation comes from glutamate photouncaging experiments which drive spine growth and local protein synthesis in single activated spines  to isolate proteins for quantitative analysis , genetically-encoded proximity-labeling tools have been developed to selectively tag and purify interacting protein complexes from synapses Proximity-labeling experiments with APEX2 fused to presynaptic terminal protein alpha-synuclein identified hundreds of interactors including synaptic proteins, vesicle trafficking proteins, RBPs, and translation initiation factors important for local protein synthesis  has been mapped both with BioID  or inhibitory (gephyrin) scaffolding molecules conjugated to BirA, the promiscuous biotin ligase  was used to study the developmental maturation of olfactory projection neurons  provides unparalleled image resolution for synapse analysis but is difficult to combine with conventional molecular labeling tools due to challenges imposed by the use of strong chemical fixatives and epoxy resins in the sample preparation. Further development of EM-compatible transgenic labeling tools will be useful for identifying specific molecular targets and cell/synapse types in EM images  patterned excitation approaches [e.g., STimulated Emission Depletion (STED) microscopy , a structural protein at the Drosophila neuromuscular junction (NMJ) essential for the developmental positioning of Ca2+ channels and synaptic vesicles  to reconstruct the relative spatial positions of pre/postsynaptic proteins in thin cryosections of brain tissue to map synaptic structure with molecular specificity and nanoscale resolution  organization  and antibody elution on ultrathin sectioned brain material to achieve multiplexed proteomic imaging with improved axial image resolution while further enabling correlative electron microscopy (Micheva and Smith, in situ (Lein et al., in situ RNA sequencing (FISSEQ; Lee et al., in situ hybridization methods such as multiplexed error-robust fluorescence in situ hybridization (MERFISH; Chen K. H. et al., in situ hybridization (seqFISH; Lubeck et al., in situ and has been further used to identify cell populations that are specifically active during social behaviors (Moffitt et al., in situ hybridization has been performed with expansion microscopy (Chen et al., Multi-round labeling has also been used to develop spatial transcriptomic approaches for mapping RNA identity and position in vitro using PAINT (Guo et al., in situ hybridization strategies for spatial transcriptomic imaging (Chen K. H. et al., In a step toward this goal, multiplexed super-resolution synaptic proteome imaging has been achieved using DNA-oligo-linked primary antibodies which are imaged across multiple rounds of hybridization using complementary detection oligos (Wang et al., The developmental connectomics strategy presented here enables new experiments to determine the molecular blueprint for synaptic development and plasticity in neural circuits. The application of complementary techniques in transcriptomics, translatomics, proteomics, and super-resolution structural imaging establishes an integrative framework for investigating mechanistic links between mRNA trafficking, local protein synthesis regulation, and changes in subsynaptic molecular organization underlying circuit development.Molecular sequencing experiments, both at the RNA and protein levels, generate foundational databases identifying regulators of connectome development and plasticity. Also, proteomic (Sharma et al., Several analytical approaches for integrating multiomic data have been applied to better define cell types in the mature and developing brain (Stuart et al., Though deep learning methods have thus far been developed for analyzing cell types and spatial organization, related approaches should facilitate integrative analysis of subcompartment-specific multiomic and super-resolution imaging data to characterize molecular networks driving synaptic/neurite maturation and plasticity (Poulopoulos et al., JM and CS wrote the manuscript and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Continuous, long-term monitoring with remote capabilities using wearable technology is ideal for capturing information about patient/participant symptoms synced to sensor-based information. The Real-time Online Assessment and Mobility Monitor (ROAMM) is a smartwatch framework configured to collect data in free-living settings from both sensor-based (location and movement) and responses to symptom notifications through a visual display. The symposium presents the overall framework and preliminary findings from a demonstration study in older adults with knee osteoarthritis. Karnati will present the general framework of ROAMM explaining the data flow from the smartwatch to end users (clinicians and research). He will highlight components in the design that makes the framework unique and highly flexible to serve different studies with different research questions. Rouzaud evaluated satisfaction, usability and compliance wearing a smartwatch and using the ROAMM app. Participants were compliant to ecological prompts about pain, fatigue and mood three times a day (82.5% compliance rate). Additionally, > 70% reported being satisfied with the function/usability and comfort with using ROAMM and wearing the smartwatch. Mardini examined the temporal relationship between ecological pain and derived life-space mobility features from Global Positioning System coordinates. Results suggested that higher level of knee pain in older adults was associated with lower life-space mobility. Manini examined physician perception towards an electronic health record (EHR) graphical interface of top ranked patient attributes of pain, falls, hydration and mobility patterns. Results indicated a relatively high level of usability of the EHR interface depicting smartwatch data.


We propose that trauma history is important context for understanding the adaptive capacity of aging adults to achieve a suitable person-environment fit. We conducted a scoping review using bibliographic databases to identify studies focused on aging in place, vulnerability and traumatic personal experiences, and aging adults’ maladaptive behaviors. Our review showed little research directly exploring the connection between trauma-related needs and aging in place and limited research about the community’s role in supporting those needs. Literature about the impacts of trauma revealed that trauma could stem from adverse childhood experiences  and adult adverse experiences . Adults who have experienced trauma may have increased physiological  and psychological  conditions. Sensory sensitivities in the home environment—including sounds , air quality , and lighting —can substantially decrease quality-of-life. Strong emotional reactions can make interpersonal relationships, such as those with a landlord or neighbors, difficult and increase the likelihood of eviction. Aging adults with trauma histories also experience greater poverty rates, increasing the likelihood of substandard housing . Because the housing environment is a significant aspect of overall well-being, challenges to aging in place for adults with trauma histories warrants further research, as does the role of community supports in mitigating housing-related stressors. Examples may include trauma-informed approaches in universal design, the availability of safe affordable housing, community education, and funding for intermediaries who can support aging adults.


Suillus brevipes, a mycorrhizal fungus adapted to coastal and montane habitats in California. In order to assess whether gene copy number variation mirrored population structure and selection in this species, we investigated two previously studied locally adapted populations showing a highly differentiated genomic region encompassing a gene predicted to confer salt tolerance. In addition, we examined whether copy number in the genes related to salt homeostasis was differentiated between the two populations. Although we found many instances of CNV regions across the genomes of S. brevipes individuals, we also found CNVs did not recover population structure and known salt-tolerance-related genes were not under selection across the coastal population. Our results contrast with predictions of CNVs matching single-nucleotide polymorphism divergence and showed CNVs of genes for salt homeostasis are not under selection in S. brevipes.Gene copy number variation across individuals has been shown to track population structure and be a source of adaptive genetic variation with significant fitness impacts. In this study, we report opposite results for both predictions based on the analysis of gene copy number variants (CNVs) of  Brachipodium distachyon (Zymoseptoria tritici and Aspergillus fumigatus (Copy-number variants (CNVs) are genes or genomic regions of varying size with different numbers of copies across individuals. Copy-number differences can arise through genomic rearrangements  or produce functional divergence across gene copies resulting in differentially adaptive phenotypes . Furthermore, no SNP variation was found in this gene across coastal individuals strongly suggesting a selective sweep for adaptive alleles allowing colonization of saline environments in coastal California. Nha-1 homologs have been reported as important for salt tolerance in other organisms, including increased Nha-1 expression levels in Arabidopsis thaliana allowing survival in high sodium concentrations  and montane  California populations previously analyzed in Suillus brevipes is a dikaryotic fungus which means two haploid genomes inhabit the same cell, we therefore assumed diploidy of our samples and followed ST following ST formula is available from https://github.com/abazzical/sbrevCNV). Given the reference genome is rather fragmented .We estimated gene copy number variation from the processed Illumina reads of 27 ape package  enrichment analysis on the top 1% diverged CNVs between the two Suillus brevipes reference genome , there were no significant differences in CNV number or CNV size between montane and coastal populations (Wilcoxon rank sum test P > 0.05). The vast majority of CNVs were losses across the whole genome , suggesting salt homeostasis genes are not under selection for different copy numbers in the two populations. However, as shown in the heatmap in We found 83 genes involved in salt homeostasis across the Nha-1-like gene; ProteinID 1095265) showed a range of copy numbers across individuals  and its annotation incomplete and based on sequence similarity-based gene predictions  and there might be adaptive CNVs related to salt tolerance in the remainder of the genome that remained undetected.Both biological and technical factors likely contributed for the absence of concordance between CNVs and SNPs in lifornia , the preS. brevipes (In conclusion, our results complement findings from previous studies on environmental adaptation in the mycorrhizal fungus


Biliary and pancreatic cancers occur silently in the initial stage and become unresectable within a short time. When these diseases become symptomatic, biliary obstruction, either with or without infection, occurs frequently due to the anatomy associated with these cancers. The endoscopic management of these patients has changed, both with time and with improvements in medical devices. In this review, we present updated and integrated concepts for the endoscopic management of malignant biliary stricture. Endoscopic biliary drainage had been indicated in malignant biliary obstruction, but the concept of endoscopic management has changed with time. Although routine endoscopic stenting should not be performed in resectable malignant distal biliary obstruction (MDBO) patients, endoscopic biliary drainage is the treatment of choice for palliation in unresectable MDBO patients. Self-expanding metal stents (SEMS) have better stent patency and lower costs compared with plastic stents (PS). For malignant hilum obstruction, PS and uncovered SEMS yield similar short-term outcomes, while a covered stent is not usually used due to a potential unintentional obstruction of contralateral ducts. Percutaneous transhepatic biliary drainage was introduced ~40 years ago  for the Differences in the level of obstruction of the biliary system allow for a further division of these kinds of problems into resectable or unresectable hilum or distal biliary obstructions. Computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance cholangiopancreatography (MRCP), and even endoscopic ultrasound sonography (EUS) should be used to evaluate the stage and primary source of a malignancy ,10.Treatment plans for malignancies with different primary origins differ from one another when resectable biliary obstructive malignancy diseases are discussed. In general, routine endoscopic stenting has no obvious clinical benefits for patients with malignant distal biliary obstruction (MDBO) ,12,13,14For cholangiocarcinoma, the Bismuth classifications  have beeFor hilum cholangiocarcinoma without distant metastasis, resectable tumors present the possibility of resection of the involved intra- and extrahepatic bile ducts as well as the associated hepatic lobes and caudate lobe. Some recent reports have shown excellent results after surgical resection in patients with Bismuth III and IV disease ,23, but Endoscopic stenting is the mainstream endoscopic management approach for malignant distal biliary obstruction of cholangiocarcinoma or pancreatic cancers, but most clinical studies ,24 and mIn ampullary neoplasms, EUS and intraductal ultrasound sonography (IDUS) can assess the depth of invasion as well as the intraductal extension. Importantly, surgical ampullectomy can reduce medical expenses yet have similar clinical outcomes for those that are achieved via pancreaticoduodenectomy  for ampuEndoscopic biliary drainage with biliary stent placement is the treatment of choice for palliation in patients with distal malignant biliary obstruction that is caused by unresectable neoplasms, with a success rate of up to 95% ,29,30 anIn some situations, PTCD has been used as part of a rendezvous endoscopic approach. A comparison in 2016 between EUS-guided and PTCD rendezvous drainage after the failure of primary ERCP in MDBO showed that EUS rendezvous had a significantly lower success rate than the PTCD rendezvous . HoweverDifferent stent types are available for the treatment of MDBO. SEMS  have a lEUS is a valuable diagnostic modality for the staging of hilum cholangiocarcinomas, particularly for the evaluation of unresectable perihilar cholangiocarcinoma for liver transplantation . PercutaSome evidence indicates that in cases of bilateral biliary opacification, bilateral drainage offers a better survival benefit when compared to unilateral drainage ,70. AfteThe evidence is still insufficient and no clear consensus has been reached regarding the benefits of unilateral versus bilateral drainage for hilar malignant obstruction, although the bilateral approach can be used by most experts using the SEMS stent-within-stent placement ,76 with Plastic stents and uncovered SEMS yield similar short-term outcomes in patients with malignant hilar strictures due to stent migration in SEMS . SEMS prEUS-guided biliary drainage via EUS-guided hepaticogastrostomy (EUS-HGS) is a good alternative for draining malignant hilar biliary obstruction following the failure of an initial ERCP. An EUS-guided rendezvous procedure with the conventional ERCP access ,86 is tyIn cases of malignant biliary obstruction, CT, MRI, MRCP, and EUS should be used for tumor staging and further drainage planning. For resectable malignant biliary obstruction lesions, routine endoscopic drainage or ERCP are not advised, except in cases of concurrent infection. Endoscopic drainage is the treatment of choice for unresectable biliary obstructions. PTCD and EUS-guided biliary drainage can serve as alternative approach methods. EUS-guided biliary drainage can provide equal clinical benefits without increasing complications in a high-tech endoscopy center. In addition, PTCD plays an important role in community hospitals, where the ERCP and/or EUS approaches are not available.For MDBO, single-stent insertion is adequate, and SEMS have better patency than plastic stents; however, the superiority of FCSEMS, PCSEMS, and UCSEMS remains under debate. For malignant hilar biliary obstructions, drainage of >50% of the liver volume should be achieved by either bilateral stenting or multi-segmental stenting, and SEMS’ longer biliary patency when compared with plastic stents should be considered. The general approaches to malignant biliary obstruction are summarized in the flow chart presented in


The effects of retirement on cognition are still unclear and empirical evidence is conflicting. Especially for retirement from cognitively demanding jobs, positive as well as negative effects have been reported. Leisure activity engagement has been hypothesized to play an important role in explaining the mixed evidence. In this study, we examine the interplay between job demands before retirement and changes in leisure activities before and after retirement and their relation to post-retirement cognitive functioning. Using data from the HEalth, Aging and Retirement in Sweden (HEARTS) study, cognitive trajectories before and after retirement were modeled in a multi-level piecewise model (N = 2688 observations). Post-retirement memory and reasoning ability were predicted by self-reported work demands and changes in leisure activity engagement. Results imply a stable increase in memory over the retirement transition and less steep increase in abstract reasoning after retirement. Work demands and leisure activity participation were not related to post-retirement cognitive change. Job demands and leisure activity engagement may not play an important role for short-term post-retirement cognitive functioning. These findings support the conclusion that retirement, independent of prior work demands, does not affect cognitive functioning negatively.


The purpose of our Geriatric Workforce Enhancement Program is to provide geriatric and primary care education and training to long-term care (LTC) providers and staff, health professions students and community members. Our LTC partners and the communities we serve are often very rural and travel to urban areas for training can be difficult. Therefore, we have developed four online training that are offered free to our partners and rural communities statewide. These programs are designed to integrate the aims of the Age-Friendly 4M’s model . The LTC nurse residency program provides gerontological nursing and inter-professional leadership training , in a synchronous online environment. The asynchronous Alzheimer’s Disease and Related Dementias training modules educate LTC staff and family caregivers about types, diagnosis and care of older adults with dementia (Mentation and Medication). The asynchronous Opioid Use in LTC modules were developed with partners to deliver live at LTC staff trainings about opioid stewardship (Medication). The LTC Learning Communities are monthly tele-health sessions for inter-professional LTC teams to discuss current issues and propose solutions . We have successfully leveraged different synchronous and asynchronous online modalities to increase educational opportunities for formal and informal caregivers, including those in rural areas whose educational opportunities are geographically limited. To date our programs have reached over 500 individuals across our state, increasing knowledge about geriatric concepts, communication and team leadership. Moving forward, we will continue to develop and refine educational programs that promote the Age-Friendly geriatric-focused health care.


The widespread consumption of ‘western’-style diets along with sedentary lifestyles has led to a global epidemic of obesity. Epidemiological, clinical and preclinical evidence suggests that maternal obesity, overnutrition and unhealthy dietary patterns programs have lasting adverse effects on the physical and mental health of offspring. We review currently available preclinical and clinical evidence and summarise possible underlying neurobiological mechanisms by which maternal overnutrition may perturb offspring cognitive function, affective state and psychosocial behaviour, with a focus on (1) neuroinflammation; (2) disrupted neuronal circuities and connectivity; and (3) dysregulated brain hormones. We briefly summarise research implicating the gut microbiota in maternal obesity-induced changes to offspring behaviour. In animal models, maternal obesogenic diet consumption disrupts CNS homeostasis in offspring, which is critical for healthy neurodevelopment, by altering hypothalamic and hippocampal development and recruitment of glial cells, which subsequently dysregulates dopaminergic and serotonergic systems. The adverse effects of maternal obesogenic diets are also conferred through changes to hormones including leptin, insulin and oxytocin which interact with these brain regions and neuronal circuits. Furthermore, accumulating evidence suggests that the gut microbiome may directly and indirectly contribute to these maternal diet effects in both human and animal studies. As the specific pathways shaping abnormal behaviour in offspring in the context of maternal obesogenic diet exposure remain unknown, further investigations are needed to address this knowledge gap. Use of animal models permits investigation of changes in neuroinflammation, neurotransmitter activity and hormones across global brain network and sex differences, which could be directly and indirectly modulated by the gut microbiome. The worldwide prevalence of obesity has tripled since 1975, accompanied by a sharp increase in obesity among women of reproductive age . MaternaObservations regarding neurodevelopmental impacts of maternal obesity have emerged more recently, building on extensive evidence linking higher maternal body mass index (BMI) to adverse offspring metabolic and cardiovascular outcomes. This literature has been reviewed elsewhere and is not examined here ,8,9. RatHuman and preclinical studies of the impacts of maternal obesity and overnutrition on offspring behaviour can be categorised into three areas: cognition, affective states and psychosocial behaviour. Although human studies have shown associations between these domains and maternal body weight and diet  on offspring cognition. One of the challenges in interpreting behavioural data regarding cognition is the heterogeneity in tests and test parameters employed across studies, as noted in a recent meta-analysis and systematic review  which coIncreased proinflammatory signals including IL1β and TNFα were found in the whole brain of male and female mouse offspring of obese mothers at P0, with mixed effects seen at P7 and P21 . ElevateResults from several studies in humans indicate that maternal obesity alters affective states in children. For example, extreme maternal obesity (pre-pregnancy BMI ≥ 40) was associated with hyper-reactivity and affective changes in children, independent of demographic variables, prenatal factors or maternal anxiety and depression . A populBy contrast, preclinical studies using affective measures in rodents show mixed results, with maternal obesity found to increase ,39,41,53Although behavioural measurements differ between studies, preclinical studies have often sought to link affective changes to dysfunctional HPA axis activity, altered neuronal plasticity and increased neuroinflammation. The HPA axis regulates physiological stress responses and modulates behaviour in response to stressful stimuli, and its function is programmed by maternal obesity. An association between hyper- and hypo-active HPA axes and anxiety- and depressive-like behaviour, respectively, has been well documented . Two stuApart from differences in experimental research protocols  one possible reason for the discrepancy between the results seen in human research and the mixed results from animal models might relate to methodological differences in reporting negative emotional states in humans and rodents. Human studies tend to use parental reports regarding child emotional states, whereas studies using rodents monitor anxiety- and depressive-like behaviour using ethologically relevant tests in the offspring themselves, such as forced swim, open field, elevated plus maze, dark-light box and sucrose preference tests, which cannot fully capture the breadth of negative affective states in human children. We argue that despite these challenges, the ability to associate behavioural outcomes with neurohumoral and molecular readouts in preclinical research has merit.The potential link between maternal obesity and Autism Spectrum Disorder (ASD) has been extensively investigated over the past decade or so. Several recent meta-analyses and reviews indicate an increased risk of ASD in children of mothers who were overweight or obese at the time of conception ,50. In aDespite growing interest in the link between maternal obesity and aspects of psychosocial behaviour in children in human studies, few studies have explored this relationship in animal models. Research to date has examined social interaction, anxiety and locomotor activity. Several studies have found evidence that neuroinflammation might contribute to impaired social behaviour in offspring of overfed dams: Kang et al.  reportedObesity during pregnancy alters neuroendocrine, metabolic and inflammatory status and these exposures might affect foetal development, in turn influencing behaviour, emotion and cognition. In addition to neuroinflammation, altered neuronal plasticity and dysregulated brain metabolism  likely contribute. Another mechanism attracting recent attention is changes in the composition of the gut microbiome, which contains trillions of bacteria, and plays a crucial role in health and disease of the host . In the Rodent models of maternal obesity have shown evidence of hypothalamic inflammation in offspring, characterised by elevated levels of TNFα, IL1b, and IL6 in adulthood, both in rats  and miceAnother possibility is the involvement of glial cells. Glial cells such as microglia and astrocytes are essential for regulating immune responses and act as metabolic sensors . SeveralIn the context of maternal obesity and effects on offspring behaviour, an experimental study showed changes in glial cell proliferation and reactivity in mouse offspring of obese mothers, characterised by astrocyte proliferation and elevated levels of IL6 in the hypothalamic arcuate nucleus (ARC) and the supraoptic nucleus (SON) compared with offspring from normal weight dams . This evLactobacillus reuteri suppressed neuroinflammation by binding to a receptor expressed on astrocytes [L.reuteri produces gamma-aminobutyric acid (GABA) which has inhibitory effects on neuronal circuity [L.reuteri regulates social behaviour in mice via the vagus nerve pathway interacting with oxytocin in the VTA [Lastly, increasing evidence suggests an intriguing relationship between glial cells and the gut microbiome. Preclinical studies using conventional and germ-free mice showed that the gut microbiota indirectly regulate homeostasis and immune reactivity of microglia . Gut mictrocytes . Neurointrocytes . Notablycircuity . A recen the VTA . In summStudies in rodents and humans link maternal obesity to neurological changes in offspring. A recent human study reported a negative association between maternal BMI and hippocampal volume in male children at 7–11 years of age . FurtherRecent studies using functional magnetic resonance imaging technology indicate an association between higher pre-pregnancy BMI and altered white matter microstructure , neuronaDopamine is a neurotransmitter regulating motivational and reward-related functions. A recent preclinical study showed that consumption of cafeteria diets during pregnancy induced epigenetic changes in the dopamine receptor (DAT), dopamine transporter 1 (DRD1) and dopamine transporter 2 (DRD2) genes in the nucleus accumbens (NAc) and VTA, two key regions of the dopaminergic pathway . In the Perinatal exposure to maternal obesity and poor diet induces lasting effects on the central serotonergic system in female offspring . High faEvidence from animal models shows maternal obesity programs the rat offspring’s health trajectory towards obesity by impaired lipid and glucose metabolism and appetite regulators ,94. InteMaternal overnutrition also alters the endocannabinoid system through impaired leptin signalling in the hypothalamus. Interestingly, only male rat offspring of HFD-fed dams exhibited impaired leptin signalling, with epigenetic changes in promoter regions of sex hormone signalling at birth . The sexThe adverse changes in brain metabolism in offspring from obese dams include altered mammalian target of rapamycin (mTOR) signalling in the rat hypothalamus  and in tOxytocin is another brain hormone for which there is evidence of a relationship between maternal obesity and aberrant offspring behaviour. Oxytocinergic neurons in the PVN project to the amygdala, hippocampus, NAc and VTA, and peripherally project to the pituitary into the blood stream ,115. OxyThe ‘gut-brain axis’ describes the complex communication network between the gut and brain, comprising the enteric nervous system, sympathetic and parasympathetic branches of the autonomic nervous system, in addition to neuroendocrine signalling pathways, and neuroimmune systems . Emerginlactobacillus spp. abundance in the infant gut [Only limited evidence is currently available for an association between maternal diet and offspring gut microbiome composition in humans. Savage et al. showed a weak but positive association between maternal diet, characterised by high vegetable intake and low processed/fried food intake, and fant gut . A recenfant gut . Exposinfant gut . A caveafant gut . We havefant gut . Therefofant gut .Staphylococcus and Lactobacillus and lower numbers of Bifidobacterium bacteria relative to normal weight mothers [Lactation is another key period that shapes the offspring’s gut microbiome, immune system and behaviour. Breast milk is comprised of non-nutrient components such as immunoglobulins, oligosaccharides, growth factors, and epithelial and immune cells, which could reflect maternal health, and DNA—essential bioactive compounds that foster the development of the gastrointestinal, immune and neurological systems in offspring . Indeed, mothers . A recen mothers . What isThere is now broad evidence from human and animal studies indicating that maternal obesity, overnutrition and unhealthy dietary patterns induce adverse effects on behaviour and neurodevelopment in offspring. This review has identified possible underlying neurobiological mechanisms for these effects, which include neuroinflammation, disrupted neural circuitries and connectivity and dysregulated brain hormones. Dynamic interactions between these factors shape behaviour during gestation and lactation through the offspring’s exposure to maternal obesity via the placenta, gut microbiome and breast milk. Future research should continue to examine behaviour and brain changes in maternal obesity models beyond the hippocampus and hypothalamus, given recent evidence from imaging studies suggesting that aberrant behaviour might be a result of dysregulated global network in the brain, in addition to region-specific dysfunctions. In addition, future research should be targeted at characterising the intriguing sex differences evident in many maternal obesity studies, given that current preclinical studies are still skewed towards males. Human studies using advanced imaging techniques could provide a useful resource to guide animal studies to further elaborate underlying mechanisms. Further, animal models need to incorporate experimental protocols that maximise translational relevance to align with human studies in terms of dietary components, feeding duration and behavioural tests, to allow behavioural and molecular outcomes to be systematically assessed longitudinally and compared across species where possible. Studies currently underway should yield more valuable data on the longer-term effects in humans.


Diffuse gliomas, such as glioblastoma (GBM), represent the most common and aggressive form of brain cancer with an unfortunate dearth of treatment advances despite decades of ongoing research . PerhapsDespite this prospect, the aggressive biology and low incidence of gliomas make them poor candidates for conventional screening strategies. Case reports of serial neuro-imaging studies of GBM, with scans taken as few as 68 days apart, show that even small cortical lesions can rapidly evolve into established disease within a very short clinical time frame (< 3 months) . This shConsequently, when conceptualizing an effective screening tool for gliomas, brain health changes would need to be monitored over short intervals (days to weeks) using tools that could be practically applied to the general population. Herein lies the immense potential of using emerging non-invasive electroencephalography (EEG)-based biotracking devices to serve as agents that gather continuous health data from our nervous system Fig. a. These With these exciting prospects in mind, several potential limitations at present are worth highlighting. Current EEG wearables, designed for niche application , only require a handful of sensors for their intended uses. The optimal quantity and spatial distribution of sensors for effective screening of central nervous system pathologies therefore still need to be defined. Additionally, the amount and timing of daily wear needed to detect subtle baseline changes would also need optimization and balance with enthusiasm to wear such devices. Despite these current unknowns, rapid and widespread acceptance of other smart wearables offers encouraging insights. For example, despite only debuting in 2015, Apple shipped > 40 million smartwatches in 2018 with the global wearable market expected to grow to > 279 million users by 2023. This estimate of the wearable market alone could allow the detection of tens of thousands of brain tumors annually! With increasing possibilities and interest at the intersection between artificial intelligence and brain-machine interfaces , such devices may soon even become essential tools to intellectually compete in society. It is therefore possible that consumer demand for brain wearables may quickly mirror the rapid growth of their hardware manufacturers and extend far beyond current niche applications and existing smartwatch demands . Lastly,The ability of these devices to provide continuous longitudinal and personalized data, along with the advent of modern deep learning computational tools, could provide new solutions for the early detection and differentiation of various nervous system pathologies. Large-scale detection of incipient tumor formation could also provide new epidemiological insights of unappreciated risk factors and mechanisms of gliomagenesis. Deployment of these devices to existing brain tumor patients could also help monitor disease recurrence and understand treatment-related neurocognitive sequalae.Brain tumors such as GBM carry a dismal prognosis which has challenged conventional treatment paradigms for decades. Conceptualizing novel early detection-based approaches for these tumors may provide success in a patient population where conventional late-stage diagnosis and treatment have failed. While the role of early detection in the management of brain tumors is still unclear, recent innovations in personal brain wearables, artificial intelligence, and evidence for the benefits of aggressive surgery offer new opportunities to refine our clinical approach to these challenging clinical entities.


Under physiological conditions, a balance between oxidants and antioxidants exists. Reactive oxygen species (ROS) are continuously generated by aerobic cells and eliminated through scavenging systems to maintain redox homeostasis. Disruption of redox homeostasis results in oxidative stress and altered ROS signaling. Higher ROS levels can lead to DNA mutation and genomic instability which can play causal role in cancer development and progression. These mutations coupled with distorted redox signaling pathways orchestrate pathologic events inside cancer cells, resulting in resistance to stress and death signals, aberrant proliferation, and inefficient repair mechanisms.Cancer cells are energy intensive, owing to their high rate of proliferation. However, due to impaired TCA cycle and poor blood perfusion, cancer cells switch towards glycolytic pathway for energy generation termed as “Warburg effect.” Such pathways lead to a higher oxidative environment. The oxidative environment is also enhanced by tumor-infiltrating macrophages and neutrophils. Thus, cancer cells are used to a high ROS environment. This redox imbalance allows for protumorigenic cell signaling. In this issue, we explore the relation between ROS and cancer. The issue comprises of twenty original articles and comprehensive reviews.Reactive oxygen species (ROS) mediates cisplatin-induced cytotoxicity in tumor cells. However, when cisplatin-induced ROS do not reach cytotoxic levels, cancer cells may develop chemoresistance. Di Vito et al. reported the association of ferritin heavy subunit (FHC)-ROS axis with cisplatin resistance in ovarian cancer cells. Thus, implying that inhibition of FHC might be a potential approach for restoring cisplatin sensitivity of resistant ovarian cancer cells. The authors investigated whether the modulation of H-Ferritin might affect cisplatin-induced cytotoxicity in ovarian cancer cells. H-Ferritin knockdown strengthened cisplatin-mediated ROS increase and significantly restored sensitivity resistant ovarian cancer cells.via a ROS-dependent mitochondria-mediated pathway. Hämäläinen et al. investigated the expression of redox regulator nuclear factor erythroid-2-related factor (NRF)1 and NRF2 in skin lesions like naevi and melanoma from 172 patients. NRF1 and NRF2 are transcription factors essential for maintaining redox homeostasis and coordinating cellular stress responses. The study found the association of redox microRNAs (miRs)  with aggressive melanoma feature. This study opens up avenues to test these redox miRs as possible prognostic value in larger cohorts. The research article by Pires et al. described label-free mass spectrometry- (MS) based proteomics of breast cancer (BC) plasma to investigate the differences between circulating proteins between chemoresponsive and chemoresistant luminal A breast cancer. Protein-protein interaction networks were created utilizing using in silico tools. The study reports interesting findings on differences in inflammatory, complement system, and oxidative stress pathways in both BC phenotypes which holds potential clinical implications. Moreira et al. presented their findings about the antitumor effect of celastrol, a natural pentacyclic triterpenoid, in colon cancer cells with acquired resistant to cytotoxic drugs. Yang et al. have evaluated the anticancer and anti-invasive properties of alpha-lipoic acid (ALA) in gastric cancer cells. ALA is a naturally occurring thiol antioxidant which is known to exhibit antiproliferative and cytotoxic effects on several cancers. The study found that the Mucin 4 (MUC4) gene was strongly expressed in human gastric cancer tissues. ALA administration reduced the proliferation and invasion of human gastric cancer cells by suppressing MUC4 expression. Helfinger et al. reported expression of Nox4 in macrophages and the role played by them in determining the polarization and the phenotype of macrophages. In the report by Acheva et al., authors showed epithelial to mesenchymal transition (EMT) in lung cancer cells postexposure to oxidative stress of gamma radiation. The authors conclude that induction of EMT in bronchial epithelial cells by radiation requires more than single acute exposure to gamma radiation and that the presence of stromal component might enhance the effect through free radical production and accumulation.Studies by Zhao et al. in osteosarcoma cells found that metformin (drug for type 2 diabetes) suppressed the self-renewal ability of osteosarcoma stem cells (OSCs) and induced G0/G1 phase arrest by blocking the activity of cyclin-dependent kinases. Metformin triggered apoptosis in these cells, which promoted cell death Gao et al. investigated the association of nitric oxide metabolites and lung cancer incidence through a matched case-control study based on the German ESTHER cohort. The study deduced that subjects with high urinary nitrite/nitrate concentrations had an increased risk of lung cancer. Butturini et al. highlighted plant-derived Sesquiterpene as a potential for cancer therapeutics. The authors exhibited that the compound downregulated STAT3 signaling leading to an antitumor effect and correlated the anti-STAT3 activity with their ability to decrease GSH levels in cancer cells. These properties make them lead compounds for the development of a new therapeutic strategy for cancer treatment.In addition to these original works, Kim et al. listed a comprehensive report on the ROS-inducing strategy in anticancer therapy. The review by Xian et al. summarized the role of ROS in cutaneous carcinogenesis and skin cancer progression. Akanji et al. provides a comprehensive account of hypoxia-inducible factors (HIFs). In the review by Lv et al., the authors discussed recent understanding in the involvement of Glutathione (GSH) in cell death pathways such as apoptosis, necroptosis, ferroptosis, and autophagy. Goh et al. performed online literature search to identify studies reporting metabolic biomarkers of aerodigestive squamous cell carcinomas (ASCC). Akbari et al. have focused on the role of hydrogen sulfide in bladder, kidney, and prostate malignancies.In the review by Tataranni et al., the authors have addressed the therapeutic potential of dichloroacetate (DCA) in cancer therapy. DCA is a 150 Dalton, water-soluble acid molecule, analog of acetic acid in which two of the three hydrogen atoms of the methyl group have been replaced by chlorine atoms. The authors have summarized recent reports suggesting the employment of DCA in cancer therapy, in combination with chemotherapy agents, radiotherapy, and other chemical or natural compounds showing anticancer properties. Paz et al. in their review have discussed the pharmacological effects and toxicogenetic impacts of omeprazole in context of cancer. This extensive report highlights that omeprazole therapy may induce genomic instability and increase the risk of certain types of cancer and hence advocates for taking adequate precautions, especially in long-term therapeutic strategies. The review by Fiocchetti et al. focused studies conducted on Neuroglobin (NGB), a globin primarily described in neurons as an oxidative stress sensor and cytoprotective factor against redox imbalance.Although ROS sustain tumorigenesis and cancer progression, these can also be efficient therapeutic tools to fight cancer. Oxidative stress-based therapies like radiotherapy, chemotherapeutic agents, and photodynamic theory increase ROS levels in the tumor niche and take advantage of the cytotoxic face of ROS for killing tumor cells by a nonphysiologically sudden, localized, and intense oxidative burst. Clinical efficacy of anticancer therapies is often subdued by multidrug resistance (MDR). Redox therapy by using redox-active drugs or inhibitors of inducible antioxidant defense in tumor microenvironment has reported to be effective against MDR tumors. Further insight into such redox biology will enable precisely targeted manipulation of ROS for effective medical therapies against carcinomas.


Caenorhabditis elegans. We discuss how cell surface receptor complexes link to and modulate actin dynamics to regulate dendritic and axonal branch formation. The mechanisms of neurite branching are often coupled with other neural circuit developmental processes, such as synapse formation and axon guidance, via the same cell-cell surface molecular interactions. We also cover ectopic and sex-specific neurite branching in C. elegans in an attempt to illustrate the importance of these studies in contributing to our understanding of conserved cell surface molecule regulation of neurite branch formation.The high synaptic density in the nervous system results from the ability of neurites to branch. Neuronal cell surface molecules play central roles during neurite branch formation. The underlying mechanisms of surface molecule activity have often been elucidated using invertebrates with simple nervous systems. Here, we review recent advances in understanding the molecular mechanisms of neurite branching in the nematode  An extensive neurite branching morphology is a fundamental aspect of neuronal structure. Each axon and dendrite contain numerous neurite branches that enhance neural circuit complexity by allowing for interaction with a large number of target neurons and non-neuronal cells. For example, a single neuron can synapse onto multiple target neurons due to the extensive branching of the axonal shaft. Dendrites have an extremely complex branching thereby producing a large dendritic field to receive synaptic or sensory inputs. These neurite branch networks allow for the formation of highly complex neural circuits that integrate and process information, thereby coordinating specific nervous system functions. Growing evidence suggests that dysregulation of neurite branching could underlie various neurological and neurodevelopmental disorders such as autism, schizophrenia, and Down syndrome  or synaptic output functions  of the posterior section of the body. These neurons extend elaborate dendritic branches throughout the body excluding the head , leading to defects in harsh touch response , an IgSF cell surface protein  and their modifying enzymes , it also possesses 294 sex-shared neurons, some of which show notable sex differences in neuronal structure, branching pattern, and synaptic connectivity  and regulated by conserved cell surface molecules , DD06 neurons , and PHC neurons (male-specific axon extension; Cook et al., Drosophila brain revealed several conserved, but previously unidentified, cell surface molecules that act as regulators of neural circuit formation (Li et al., Over the past decades, studies have identified numerous cell surface molecule interactions implicated in neural circuit formation processes including neurite branching. Most of these molecules possess conserved structural domains, such as LRR, Ig domains, and cadherin repeats, which mediate protein-protein interactions necessary during neuronal morphogenesis (De Wit and Ghosh, HJ and BK developed the concept. Both have written and edited the text.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Benevolence directed towards older adults can cross the line between respect and overaccommodation that undermines their physical and cognitive capabilities ; however, little research has examined the subtleties of the influence of benevolent ageism on older adults’ ratings of their own functioning. Because stereotypes about older adults include the decline of mental abilities, this study examined whether their (N= 155) experiences with benevolent ageism, or overaccommodative offers of assistance and protection, influenced their own appraisals of memory abilities through their feelings of self-compassion. Older adults with fewer benevolent ageist experiences had higher rates of self-compassion, which in turn translated into better evaluations of their memory abilities. Future research should consider the potential pernicious influences that benevolent ageism has on older adults’ self-evaluations and performance, consider self-compassion as a buffer in these relationships, and test whether these relationships have downstream consequences on well-being outcomes.


This symposium will examine positive and negative aspects of older adults’ relationships and their impacts on health and well-being. We will begin by reviewing the past decade of research on family gerontology. Seidel’s meta-analysis of 995 articles will identify prominent theories and methods, as well as remaining research gaps. The subsequent presentations provide current, cutting-edge research. Marini examines how associations between rumination and sleep unfold within a social context. The findings highlight how spousal support protects older adults’ sleep quality from rumination, whereas support from family and friends is vulnerable to rumination. Using an actor-partner approach, Novak investigates the dynamics of support and control on health among older gay couples. Results reveal the benefits of support and risks of control for partners’ diet quality and depression. Ermer adopts a dyadic perspective to examine links between self-perceptions of aging and inflammation. Results highlight how wives’ inflammation is sensitive to husbands’ aging perceptions, particularly if marital strain is low. Finally, Wilson characterizes age-graded patterns of relationship narratives and their protective effects on emotional well-being. The findings demonstrate how older-adult couples’ narratives are less self- and present-focused, which helps explain protective linkages between age and negative mood. The symposium will conclude with remarks from discussant Katherine Fiori, a GSA Fellow and internationally recognized scholar on older adults’ social networks. She will synthesize the research and put forth her new theory about the importance of peripheral ties in later life to help direct the future of research on older adults within a social context.


Stroke is a life-threatening disease that leads to mortality, with survivors subjected to long-term disability. Microvascular damage is implicated as a key pathological feature, as well as a therapeutic target for stroke. In this review, we present evidence detailing subacute diaschisis in a focal ischemic stroke rat model with a focus on blood–brain barrier (BBB) integrity and related pathogenic processes in contralateral brain areas. Additionally, we discuss BBB competence in chronic diaschisis in a similar rat stroke model, highlighting the pathological changes in contralateral brain areas that indicate progressive morphological brain disturbances overtime after stroke onset. With diaschisis closely approximating stroke onset and progression, it stands as a treatment of interest for stroke. Indeed, the use of stem cell transplantation for the repair of microvascular damage has been investigated, demonstrating that bone marrow stem cells intravenously transplanted into rats 48 h post-stroke survive and integrate into the microvasculature. Ultrastructural analysis of transplanted stroke brains reveals that microvessels display a near-normal morphology of endothelial cells and their mitochondria. Cell-based therapeutics represent a new mechanism in BBB and microvascular repair for stroke. Stroke is currently the fifth leading cause of death in the US, and someone dies of one approximately every 4 min. Stroke occurs due to the interruption of blood flow to the brain, and is typed as ischemic or hemorrhagic. Ischemic stroke makes up approximately 87% of total strokes. Ischemic stroke survivors may not fully recover and develop long-term disabilities ,2,3, sucCerebral functional insufficiency in chronic stroke might be due to pathological changes in brain areas remote from the initial ischemic lesion, for example, diaschisis. In this review, the BBB is implicated in subacute diaschisis. Additionally, BBB competence in chronic diaschisis using a transient middle cerebral artery occlusion (tMCAO) rat model is discussed as well. BBB alterations can be demonstrated in not only the ipsilateral hemisphere, but also the contralateral hemisphere, an area with remote brain structures not directly affected by ischemia. The microvascular damage in the subacute phase likely reveals ischemic diaschisis, and should be considered in the development of treatment strategies for stroke. The direct targeting of cell delivery into the injured vasculature might be a feasible approach for stroke treatment, and endothelial progenitor cells (EPCs) serve as a promising cell source for BBB restoration in stroke. The ability to preserve the mitochondria and increase these organelles’ pinocytosis via cell-based therapeutics represents a new neurorestorative mechanism in BBB repair.Microvascular damage in ischemic stroke demonstrates ischemic diaschisis. In this review, the investigation of subacute diaschisis in ischemic stroke rat models exhibits stroke-induced pathological disturbances in ipsilateral and contralateral brain areas, and causes microvascular damage with BBB breakdown in remote brain microvessels. Additionally, widespread microvascular alterations in ipsilateral and contralateral brain hemispheres suggests continued BBB damage in chronic ischemic stroke. Because of the rampant pathological microvascular changes in remote brain areas in both subacute and chronic ischemic diaschisis, such vascular damage presents as a therapeutic target for stroke. The use of bone marrow-derived mesenchymal stem cells has been initiated to treat patients with acute ischemic stroke. Here, we discuss the potential use of EPCs as an effective cell source for BBB restoration in stroke by promoting neurovascular repair and preserving the mitochondrial morphology of the microvasculature.Following an ischemic stroke, substantial alterations in both cellular and molecular activity take place due to stroke-induced cerebral pathology ,6. StrokStroke pathology due to vascular injury is time-dependent and can be classified into three types: acute (minutes to hours), subacute (hours to days) and chronic (days to months). The acute and subacute stages of ischemic stroke can be grouped into one period, as secondary cell death following both phases drastically overlap ,6,8. NotIn-depth investigations into stroke pathology have brought about the phenomenon of diaschisis, an abrupt change in activity in regions of the brain far-off from the ischemic lesion generated by stroke-induced impairments. Transhemisphere diaschisis was first recognized through blood flow and metabolism alterations in unilateral and contralateral ischemic hemispheres in the brain . After iNevertheless, in the context of the subacute phase, BBB functionality and the associated pathology in distal brain regions have received less focus . A comprThe effects of subacute diaschisis on BBB stability and associated pathological mechanisms in contralateral regions of the brain were evaluated in focal ischemic stroke rat models . Using tMoreover, BBB impairment in distal cerebral microvessels and endothelial autophagosome build-up could be correlated with the injuries observed in the ipsilateral and contralateral brain regions spurred by focal ischemic stroke . ImportaBy utilizing a focal ischemic stroke rat model, subacute diaschisis could be explored ,29,36,37A major pathologic characteristic of subacute tMCAO involves BBB impairment in the ipsilateral and contralateral striatum and motor cortex ,29,36,37Parenchymal extravasation plays a role in secondary cell death following an ischemic stroke, and can be linked to diaschisis and BBB impairment. An in vivo study illustrated that EB extravasation was amplified in the MCAO group when compared to the control group, and could be associated with exacerbated BBB integrity . A high Autophagy in capillary ECs following ischemic stroke may heavily contribute to cell impairment and BBB alteration. It is still unknown whether enhanced autophagy is part of cell survival or death in an ischemic environment. Autophagosome accumulated in ipsilateral and contralateral capillary ECs following tMCAO. Autophagy plays a pivotal role in managing cell homeostasis by the degradation of cytosolic components via an autophagosomal–lysosomal pathway . ExcessiAdditionally, reactive astrocytes and activated microglia populated in remote striatum, motor and somatosensory cortices 7 days post-tMCAO, potentially indicating an inflammatory response. Inflammation is a major event in ischemic stroke ,53,54. INeuronal pyknosis was also found in subacute ischemia in remote striatum, motor and somatosensory cortices. This post-ischemia damage potentially contributes to stroke pathology and inhibits recovery processes. Secondary neuronal damage and glial cell reactions were explored via two ischemic rat models . The resIn the ipsilateral hemisphere, diminished myelin was found in brain structures with neuronal damage. Decreased myelin was found in the contralateral hemisphere with reduced striatosome size. Communication between different regions of the brain is vital to normal brain function, making white matter damage harmful ,60. In oThe magnitude of the primary stroke lesion is important in predicting patient outcomes. However, the location of the lesion is also essential, especially during chronic stages. Motor recovery and functional outcome in hemiplegic stroke patients during the chronic stage had a stronger correlation with brain lesion size and location compared to that of only lesion size . Post-stAs noted in the preceding section, BBB pathological changes occur in both the ipsilateral hemisphere and contralateral brain regions, indicating the presence of subacute ischemic diaschisis . An assoChronic parenchymal extravasation was also revealed via electron microscopy imaging in ipsilateral and contralateral hemispheres ,74. The Excessive autophagosome production in both ipsilateral and contralateral striatum and motor cortex areas was observed in previous studies, primarily in subacute post-tMCAO settings, which was also exhibited in ECs in chronic stages due to the upregulation of Belcin-1 expression ,74. IncrThe analysis of vascular damage, such as BBB impairment, in cerebral brain structures represents a key pathological feature of chronic tMCAO at the ultrastructural levels ,74. AbnoAstrocyte reactivity in both ipsilateral and contralateral hemispheres displayed significant increases in glial fibrillary acid protein (GFAP) immunoreactivity in striatal areas of the ipsilateral hemisphere, while significant increases in GFAP expression were observed in the dorsal area of the contralateral striatum despite enhanced astrocyte reactivity in the striatum regions. The overexpression of bilateral astrocyte was only present in the dorsal striatum, but the causation of this phenomenon is unknown. Astrogliosis in the striatum may indicate spatial differences in astrocyte reactivity due to the structural location of the striatal area relative to the corpus callosum. Studies have demonstrated the degeneration of transcallosal fibers in subacute and chronic stroke settings using MRI . To explInvestigation of damaged BBB integrity in the cerebral hemisphere capillaries  in chronic post-ischemic rats may reveal chronic diaschisis. Large autophagosome accumulation and astrocyte degeneration led to EC impairment, ultimately inducing extensive microvascular damage and neuronal degeneration in chronic ischemia. Chronic diaschisis should be included in stroke therapeutic strategies, primarily reviving endothelial and astrocytic integrity for BBB repair. Cell therapy is a possible stroke treatment option for BBB repair by replacing dysfunctional ECs through EPC transplantation. Combining cell therapy with pro-inflammatory inhibitors may prove to be a worthy stroke treatment.Currently, the only FDA-approved treatment for ischemic stroke is tissue plasminogen activator (tPA) for dissolving the blood clot and improving blood flow in the brain. When tPA is administered intravenously up to 4.5 h after stroke onset in patients with acute ischemic stroke, it reduces mortality and increases the rates of independent ambulation when thrombolytic treatment is given early . HoweverIn MCAO-induced rat models, various cell types including bone marrow stromal cells , umbilicA feasible approach for stroke treatment may involve directly targeting cell delivery into the injured vasculature. Since pervasive BBB impairment is an important factor in ischemic stroke pathogenesis, BBB repair might serve as a primary target for cell therapy development. An early study has shown that the intrastriatal transplantation of bone marrow stromal cells in MCAO rats restored local cerebral blood flow and decreased BBB permeability . AdditioThe ability of transplanted human bone marrow EPCs (hBMEPCs) to repair the BBB in adult Sprague-Dawley rats subjected to tMCAO can be evaluated via electron microscopy . When β-With intravenously transplanted β-gal pre-labeled hBMEPCs into rats 48 h after tMCAO, the rats experienced vascular repair in the brain structures of both hemispheres via transplanted cell engraftment into the vascular wall, which helped to re-establish BBB integrity post-stroke . BBB repAt 7 days post-tMCAO, BBB damage in the ipsilateral and contralateral striatum and motor cortex was observed , consistIntravenously transplanted hBMEPCs in tMCAO rats provide beneficial effects that are visualized by quantitative mitochondrial morphology analysis within ECs and perivascular astrocytes. Mitochondrial alterations can lead to cellular energy deficits and oxidative stresses that result in cell death, and mitochondrial dysfunction can occur after stroke which results in the reduced number and size of the mitochondria in astrocytes , neuronaIn cell-treated post-tMCAO animals, numerous pinocytic vesicles found solely in engrafted hBMEPCs were present . TypicalThe pinocytic vesicles were found only in engrafted hBMEPCs within the cerebral capillaries of cell-treated post-tMCAO rats, and represent a new line of investigation for cell therapy . AdminisAlthough intravenously transplanted hBMEPCs replaced post-stroke damaged ECs, it is possible that the administered cells were involved in capillary sprouting, or might have extravasated to the brain parenchyma via paracellular migration across cell–cell junctions similarly to leukocyte diapedesis in various pathological conditions, given the new vessel formation ,127. TraAdditionally, transplanted hBMEPCs might not only exogenously but also endogenously enhance post-stroke vasculogenesis, via the secretion of angiogenic or growth factors. Local transplantation of the human EC cell line improved endogenous vasculogenesis and neurogenesis by the VEGF signaling pathway . SignifiIn conclusion, β-gal pre-labeled hBMEPCs intravenously transplanted into rats 48 h after tMCAO engrafted within the capillary wall at 5 days after its administration and closely participated in the vasculature repair of the BBB in subacute stroke . The anaStroke is a devastating disease, and further investigation regarding the underlying pathophysiological changes is warranted so as to unveil an effective neurodegenerative treatment. Acute and chronic microvascular damage, as a result of ischemia, may act as a potential mechanism to target when contemplating stem cell therapy . Similar


Sex and gender are important sources of variation in Alzheimer’s disease and related dementias (ADRD) and associated caregiving. Women comprise 2/3 of ADRD cases and the majority of ADRD caregivers. Sex encompasses biological differences due to sex chromosomes, reproductive tract, and hormones, while gender constitutes socioculturally constructed psychosocial aspects of sex. Several lines of research have begun to interrogate sex differences, but less is known about the relation of gender and lesbian, gay, bisexual, transgender, and/or queer (LGBTQ) status with ADRD. In this symposium featuring both trainees and faculty we highlight novel research addressing these factors from multiple perspectives. Two presentations address how psychosocial characteristics and their strengths of association with brain health may vary by gender. C. Elizabeth Shaaban presents analyses testing whether gendered psychosocial factors explain sex differences in white matter hyperintensities, a neuroimaging marker of cerebral small vessel disease and risk factor for ADRD. Justina Avila-Rieger presents results testing region of birth-based spatial patterning of dementia risk among Black men and women. Next, Jason Flatt presents prevalence estimates of subjective memory problems and dementia and describe factors associated with dementia among LGBTQ older adults. Finally, gender may also impact perceptions of individuals with dementia. Shana Stites explores gender differences in AD stigma and discuss implications for who is willing to be an AD caregiver. Michelle Mielke, an expert in sex and gender differences in neurodegenerative and age-associated diseases will facilitate conversation about these results and place them in the context of current sex and gender-based ADRD research.


Recent conceptualizations of depression and supporting empirical work suggests that elevations and allievations of depressive symptoms can be understood from a dynamic systems perspective. Specifically, depression is proposed to result from strong-feedback loops in a system comprised of highly interdependent component parts . Supporting this perspective, individual differences in emotional interia and strong connections across emotions at micro-level timescales have been consistently associated with individual differences in depressive symptomatology such that individuals with greater emotional inertia and cross-emotion relations show higher levels of depressive symptoms. Importantly, however, individual differences do not necessarily translate to intraindividual change. The present study explores whether emotional connectivity at the daily timescale differs within individuals across a ten-year span and how these associations relate to intraindividual changes in depressive symptomatology. The results of these individual-level analyses will help further a dynamic systems perspective of depression and help inform clinical interventions for depression.