The study was to explored potential mechanisms underlying the association between sleep disordered breathing (SDB) and clinical outcomes in a convenience sample heart failure (HF) patients (n=66) and controls (n=53). Subjects participated in a sleep study, and physical assessments and blood draws were performed. Longitudinal outcomes were extracted from the HF patient medical records, and deaths were confirmed using the Social Security Death Index. Depressive symptoms were assessed using the Beck Depression Inventory (BDI). Mediation models were performed, and a test of product coefficients (PRODCLIN) was used to assess statistical significance of compound paths. Regression analyses showed disease status, but not SDB severity, predicted BDI scores and inflammation levels (p<.01). There was a significant second-order effect for two measures of hypoxia (average % oxygen saturation and lowest % oxygen saturation) by disease status for somatic BDI scores (p<.05), and a significant second-order effect for indices of obstructive and mixed apnea-hypopnea by disease status for C-Reactive Protein (CRP; p<.05). Simple slopes analyses revealed that these interaction effects were only significant for controls. Controls evidenced an expected association where worse SDB related to higher somatic scores and higher resting mean levels of CRP, respectively. In HF patients somatic symptom scores remained relatively constant, and CRP levels decreased in the presence of higher SDB severity. During the 3 year follow-up, HF patients experienced an average of 3 (SD=3.9) hospital admissions and 18% (n=12) died. There was a moderated-mediated effect of cognitive-affective depressive symptomatology and resting levels of circulating CRP on the association between total minutes oxygen saturation fell below 90% and mortality (p<.05). Among patients with lower cognitive-affective BDI scores, higher resting levels of CRP corresponded with more minutes that oxygen saturation was below 90%. Among those with higher cognitive-affective scores, lower resting levels of CRP corresponded with more minutes oxygen saturation was lower than 90% (p<.05). In those with lower cognitive-affective scores, higher resting CRP levels corresponded with greater percentage of mortality. Among those with higher cognitive-affective scores, higher resting mean levels of CRP corresponded to fewer deaths. Simple slopes analyses were not significant. The patterns seen in HF patients may be evidence of dysregulation of inflammatory responses resulting from HF syndrome and/or cognitive-affective aspects of depression. Inflammatory mechanisms may mediate associations between SDB and morbidity and mortality, although this association appears to vary by levels of cognitive-affective depressive symptoms

While the hippocampus has been classically studied for its role in learning and memory, there is significant support for a role of the HPC in regulating emotional behavior. Emerging research suggests these functions may be segregated along the dorsoventral axis of the HPC. In addition to this regional heterogeneity, within the HPC, the dentate gyrus is one of two areas in the adult brain where stem cells continuously give rise to new neurons. This process can influence and be modulated by the emotional state of the animal, suggesting that adult neurogenesis within the DG may contribute to psychiatric disorders and cognitive abilities. Yet, the exact mechanism by which these newborn neurons influence behavior remains unknown. Here, we will examine the contribution of hippocampal neurogenesis to the output of the HPC, and suggest that the role of neurogenesis may vary along the DV axis. Next, we will review literature indicating that anatomical connectivity varies along the DV axis of the HPC, and that this underlies the functional segregation along this axis. This analysis will allow us to synthesize novel hypotheses for the differential contribution of the HPC to cognition and mood.

Giant cell myositis (GCM) is a rare inflammatory myopathy associated with myasthenia gravis and thymoma. Here, we report on a woman in her late 50s with a history of myasthenia gravis, systemic lupus erythematosus and stage IV thymoma with pleural metastases, who presented with proximal weakness, neuromuscular respiratory failure and hypercalcaemia. She was diagnosed with GCM via muscle biopsy and screened for myocarditis but showed no evidence of myocardial involvement. Her hypercalcaemia was consistent with a granulomatous process, likely driven by her GCM. Her strength gradually improved, and her hypercalcaemia did not recur after treatment with high dose steroids, intravenous immune globulin and plasma exchange. Her course was complicated by several opportunistic infections in the setting of her immunosuppression. Despite the high morbidity associated with GCM, she demonstrated clinical improvement after initiating immunosuppressive therapy and continues to be managed in the outpatient setting.

Ventral hippocampal CA1 (vCA1) projections to the amygdala are necessary for contextual fear memory. Here we used in vivo Ca²⁺ imaging in mice to assess the temporal dynamics by which ensembles of vCA1 neurons mediate encoding and retrieval of contextual fear memories. We found that a subset of vCA1 neurons were responsive to the aversive shock during context conditioning, their activity was necessary for memory encoding, and these shock-responsive neurons were enriched in the vCA1 projection to the amygdala. During memory retrieval, a population of vCA1 neurons became correlated with shock-encoding neurons, and the magnitude of synchronized activity within this population was proportional to memory strength. The emergence of these correlated networks was disrupted by inhibiting vCA1 shock responses during memory encoding. Thus, our findings suggest that networks of cells that become correlated with shock-responsive neurons in vCA1 are essential components of contextual fear memory ensembles.

Anal human papillomavirus (HPV) disproportionately affects men who have sex with men (MSM), particularly those who are older and those living with HIV. After experiencing difficulty recruiting older MSM into a study on aging and anal HPV, we conducted a sub-study to gain feedback on our recruitment methods and explore barriers and facilitators to participating in anal HPV research. We conducted focus groups with 30 men who have sex with men (MSM), both HIV-negative and MSM living with HIV, ages 50-75. We identified multiple themes that were barriers to participation including: (1) lack of knowledge about human papillomavirus and anal cancer; (2) research focused on anal cancer or discomfort with topics or procedures concerning the anus; (3) stigma including stigma associated with being men who have sex with men, being out, being a receptive partner, and being considered "older" in the gay community; and (4) confidentiality concerns including a fear of breach of confidentiality. Facilitators to participation were also identified; these motivational factors include altruism, wanting recommendations from a doctor, and desire to receive the best available care. Researchers seeking to enroll older men who have sex with men should be aware of these barriers and facilitators to participation in order to maximize recruitment.

Cajal-Retzius (CR) neurons play a critical role in cortical neuronal migration, but their exact fate after the completion of neocortical lamination remains a mystery. Histological evidence has been unable to unequivocally determine whether these cells die or undergo a phenotypic transformation to become resident interneurons of Layer 1 in the adult neocortex. To determine their ultimate fate, we performed chronic in vivo two-photon imaging of identified CR neurons during postnatal development in mice that express the green fluorescent protein (GFP) under the control of the early B-cell factor 2 (Ebf2) promoter. We find that, after birth, virtually all CR neurons in mouse neocortex express Ebf2. Although postnatal CR neurons undergo dramatic morphological transformations, they do not migrate to deeper layers. Instead, their gradual disappearance from the cortex is due to apoptotic death during the second postnatal week. A small fraction of CR neurons present at birth survive into adulthood. We conclude that, in addition to orchestrating cortical layering, a subset of CR neurons must play other roles beyond the third postnatal week.

Defects in DNA repair have been extensively linked to neurodegenerative diseases, but the exact mechanisms remain poorly understood. We found that FUS, an RNA/DNA-binding protein that has been linked to amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration, is important for the DNA damage response (DDR). The function of FUS in DDR involved a direct interaction with histone deacetylase 1 (HDAC1), and the recruitment of FUS to double-stranded break sites was important for proper DDR signaling. Notably, FUS proteins carrying familial ALS mutations were defective in DDR and DNA repair and showed a diminished interaction with HDAC1. Moreover, we observed increased DNA damage in human ALS patients harboring FUS mutations. Our findings suggest that an impaired DDR and DNA repair may contribute to the pathogenesis of neurodegenerative diseases linked to FUS mutations.

Neurons are often considered specialized functional units that encode a single variable. However, many neurons are observed to respond to a mix of disparate sensory, cognitive, and behavioral variables. For such representations, information is distributed across multiple neurons. Here we find this distributed code in the dentate gyrus and CA1 subregions of the hippocampus. Using calcium imaging in freely moving mice, we decoded an animal's position, direction of motion, and speed from the activity of hundreds of cells. The response properties of individual neurons were only partially predictive of their importance for encoding position. Non-place cells encoded position and contributed to position encoding when combined with other cells. Indeed, disrupting the correlations between neural activities decreased decoding performance, mostly in CA1. Our analysis indicates that population methods rather than classical analyses based on single-cell response properties may more accurately characterize the neural code in the hippocampus.

Pair-bond formation depends vitally on neuromodulatory signaling within the nucleus accumbens, but the neuronal dynamics underlying this behavior remain unclear. Using 1-photon in vivo Ca2+ imaging in monogamous prairie voles, we found that pair bonding does not elicit differences in overall nucleus accumbens Ca2+ activity. Instead, we identified distinct ensembles of neurons in this region that are recruited during approach to either a partner or a novel vole. The partner-approach neuronal ensemble increased in size following bond formation, and differences in the size of approach ensembles for partner and novel voles predict bond strength. In contrast, neurons comprising departure ensembles do not change over time and are not correlated with bond strength, indicating that ensemble plasticity is specific to partner approach. Furthermore, the neurons comprising partner and novel-approach ensembles are nonoverlapping while departure ensembles are more overlapping than chance, which may reflect another key feature of approach ensembles. We posit that the features of the partner-approach ensemble and its expansion upon bond formation potentially make it a key neuronal substrate associated with bond formation and maturation.