Parasites alter food-web topology of a subarctic lake food web and its pelagic and benthic compartments.

We compared three sets of highly resolved food webs with and without parasites for a subarctic lake system corresponding to its pelagic and benthic compartments and the whole-lake food web. Key topological food-web metrics were calculated for each set of compartments to explore the role parasites play in food-web topology in these highly contrasting webs. After controlling for effects from differences in web size, we observed similar responses to the addition of parasites in both the pelagic and benthic compartments demonstrated by increases in trophic levels, linkage density, connectance, generality, and vulnerability despite the contrasting composition of free-living and parasitic species between the two compartments. Similar effects on food-web topology can be expected with the inclusion of parasites, regardless of the physical characteristics and taxonomic community compositions of contrasting environments. Additionally, similar increases in key topological metrics were found in the whole-lake food web that combines the pelagic and benthic webs, effects that are comparable to parasite food-web analyses from other systems. These changes in topological metrics are a result of the unique properties of parasites as infectious agents and the links they participate in. Trematodes were key contributors to these results, as these parasites have distinct characteristics in aquatic systems that introduce new link types and increase the food web's generality and vulnerability disproportionate to other parasites. Our analysis highlights the importance of incorporating parasites, especially trophically transmitted parasites, into food webs as they significantly alter key topological metrics and are thus essential for understanding an ecosystem's structure and functioning.

Rational affinity maturation of anti-amyloid antibodies with high conformational and sequence specificity.

The aggregation of amyloidogenic polypeptides is strongly linked to several neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. Conformational antibodies that selectively recognize protein aggregates are leading therapeutic agents for selectively neutralizing toxic aggregates, diagnostic and imaging agents for detecting disease, and biomedical reagents for elucidating disease mechanisms. Despite their importance, it is challenging to generate high-quality conformational antibodies in a systematic and site-specific manner due to the properties of protein aggregates (hydrophobic, multivalent, and heterogeneous) and limitations of immunization (uncontrolled antigen presentation and immunodominant epitopes). Toward addressing these challenges, we have developed a systematic directed evolution procedure for affinity maturing antibodies against Alzheimer's Aß fibrils and selecting variants with strict conformational and sequence specificity. We first designed a library based on a lead conformational antibody by sampling combinations of amino acids in the antigen-binding site predicted to mediate high antibody specificity. Next, we displayed this library on the surface of yeast, sorted it against Aß42 aggregates, and identified promising clones using deep sequencing. The resulting antibodies displayed similar or higher affinities than clinical-stage Aß antibodies (aducanumab and crenezumab). Moreover, the affinity-matured antibodies retained high conformational specificity for Aß aggregates, as observed for aducanumab and unlike crenezumab. Notably, the affinity-maturated antibodies displayed extremely low levels of nonspecific interactions, as observed for crenezumab and unlike aducanumab. We expect that our systematic methods for generating antibodies with unique combinations of desirable properties will improve the generation of high-quality conformational antibodies specific for diverse types of aggregated conformers.

Tissue Plasminogen Activator in Central Nervous System Physiology and Pathology: From Synaptic Plasticity to Alzheimer's Disease.

Tissue plasminogen activator's (tPA) fibrinolytic function in the vasculature is well-established. This specific role for tPA in the vasculature, however, contrasts with its pleiotropic activities in the central nervous system. Numerous physiological and pathological functions have been attributed to tPA in the central nervous system, including neurite outgrowth and regeneration; synaptic and spine plasticity; neurovascular coupling; neurodegeneration; microglial activation; and blood-brain barrier permeability. In addition, multiple substrates, both plasminogen-dependent and -independent, have been proposed to be responsible for tPA's action(s) in the central nervous system. This review aims to dissect a subset of these different functions and the different molecular mechanisms attributed to tPA in the context of learning and memory. We start from the original research that identified tPA as an immediate-early gene with a putative role in synaptic plasticity to what is currently known about tPA's role in a learning and memory disorder, Alzheimer's disease. We specifically focus on studies demonstrating tPA's involvement in the clearance of amyloid-ß and neurovascular coupling. In addition, given that tPA has been shown to regulate blood-brain barrier permeability, which is perturbed in Alzheimer's disease, this review also discusses tPA-mediated vascular dysfunction and possible alternative mechanisms of action for tPA in Alzheimer's disease pathology.

Turning strains into strengths for understanding psychiatric disorders.

There is a paucity in the development of new mechanistic insights and therapeutic approaches for treating psychiatric disease. One of the major challenges is reflected in the growing consensus that risk for these diseases is not determined by a single gene, but rather is polygenic, arising from the action and interaction of multiple genes. Canonically, experimental models in mice have been designed to ascertain the relative contribution of a single gene to a disease by systematic manipulation (e.g., mutation or deletion) of a known candidate gene. Because these studies have been largely carried out using inbred isogenic mouse strains, in which there is no (or very little) genetic diversity among subjects, it is difficult to identify unique allelic variants, gene modifiers, and epigenetic factors that strongly affect the nature and severity of these diseases. Here, we review various methods that take advantage of existing genetic diversity or that increase genetic variance in mouse models to (1) strengthen conclusions of single-gene function; (2) model diversity among human populations; and (3) dissect complex phenotypes that arise from the actions of multiple genes.

Uneven balance of power between hypothalamic peptidergic neurons in the control of feeding.

Two classes of peptide-producing neurons in the arcuate nucleus (Arc) of the hypothalamus are known to exert opposing actions on feeding: the anorexigenic neurons that express proopiomelanocortin (POMC) and the orexigenic neurons that express agouti-related protein (AgRP) and neuropeptide Y (NPY). These neurons are thought to arise from a common embryonic progenitor, but our anatomical and functional understanding of the interplay of these two peptidergic systems that contribute to the control of feeding remains incomplete. The present study uses a combination of optogenetic stimulation with viral and transgenic approaches, coupled with neural activity mapping and brain transparency visualization to demonstrate the following: (i) selective activation of Arc POMC neurons inhibits food consumption rapidly in unsated animals; (ii) activation of Arc neurons arising from POMC-expressing progenitors, including POMC and a subset of AgRP neurons, triggers robust feeding behavior, even in the face of satiety signals from POMC neurons; (iii) the opposing effects on food intake are associated with distinct neuronal projection and activation patterns of adult hypothalamic POMC neurons versus Arc neurons derived from POMC-expressing lineages; and (iv) the increased food intake following the activation of orexigenic neurons derived from POMC-expressing progenitors engages an extensive neural network that involves the endogenous opioid system. Together, these findings shed further light on the dynamic balance between two peptidergic systems in the moment-to-moment regulation of feeding behavior.

Altered Synaptic Drive onto Birthdated Dentate Granule Cells in Experimental Temporal Lobe Epilepsy.

Dysregulated adult hippocampal neurogenesis occurs in many temporal lobe epilepsy (TLE) models. Most dentate granule cells (DGCs) generated in response to an epileptic insult develop features that promote increased excitability, including ectopic location, persistent hilar basal dendrites (HBDs), and mossy fiber sprouting. However, some appear to integrate normally and even exhibit reduced excitability compared to other DGCs. To examine the relationship between DGC birthdate, morphology, and network integration in a model of TLE, we retrovirally birthdated either early-born [EB; postnatal day (P)7] or adult-born (AB; P60) DGCs. Male rats underwent pilocarpine-induced status epilepticus (SE) or sham treatment at P56. Three to six months after SE or sham treatment, we used whole-cell patch-clamp and fluorescence microscopy to record spontaneous excitatory and inhibitory currents from birthdated DGCs. We found that both AB and EB populations of DGCs recorded from epileptic rats received increased excitatory input compared with age-matched controls. Interestingly, when AB populations were separated into normally integrated (normotopic) and aberrant (ectopic or HBD-containing) subpopulations, only the aberrant populations exhibited a relative increase in excitatory input (amplitude, frequency, and charge transfer). The ratio of excitatory-to-inhibitory input was most dramatically upregulated for ectopically localized DGCs. These data provide definitive physiological evidence that aberrant integration of post-SE, AB DGCs contributes to increased synaptic drive and support the idea that ectopic DGCs serve as putative hub cells to promote seizures.SIGNIFICANCE STATEMENT Adult dentate granule cell (DGC) neurogenesis is altered in rodent models of temporal lobe epilepsy (TLE). Some of the new neurons show abnormal morphology and integration, but whether adult-generated DGCs contribute to the development of epilepsy is controversial. We examined the synaptic inputs of age-defined populations of DGCs using electrophysiological recordings and fluorescent retroviral reporter birthdating. DGCs generated neonatally were compared with those generated in adulthood, and adult-born (AB) neurons with normal versus aberrant morphology or integration were examined. We found that AB, ectopically located DGCs exhibit the most pro-excitatory physiological changes, implicating this population in seizure generation or progression.

Modeling UBQLN2-mediated neurodegenerative disease in mice: Shared and divergent properties of wild type and mutant UBQLN2 in phase separation, subcellular localization, altered proteostasis pathways, and selective cytotoxicity.

The ubiquitin-binding proteasomal shuttle protein UBQLN2 is implicated in common neurodegenerative disorders due to its accumulation in disease-specific aggregates and, when mutated, directly causes familial frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS). Like other proteins linked to FTD/ALS, UBQLN2 undergoes phase separation to form condensates. The relationship of UBQLN2 phase separation and accumulation to neurodegeneration, however, remains uncertain. Employing biochemical, neuropathological and behavioral assays, we studied the impact of overexpressing WT or mutant UBQLN2 in the CNS of transgenic mice. Expression of UBQLN2 harboring a pathogenic mutation (P506T) elicited profound and widespread intraneuronal inclusion formation and aggregation without prominent neurodegenerative or behavioral changes. Both WT and mutant UBQLN2 formed ubiquitin- and P62-positive inclusions in neurons, supporting the view that UBQLN2 is intrinsically prone to phase separate, with the size, shape and frequency of inclusions depending on expression level and the presence or absence of a pathogenic mutation. Overexpression of WT or mutant UBQLN2 resulted in a dose-dependent decrease in levels of a key interacting chaperone, HSP70, as well as dose-dependent profound degeneration of the retina. We conclude that, at least in mice, robust aggregation of a pathogenic form of UBQLN2 is insufficient to cause neuronal loss recapitulating that of human FTD/ALS. Our results nevertheless support the view that altering the normal cellular balance of UBQLN2, whether wild type or mutant protein, has deleterious effects on cells of the CNS and retina that likely reflect perturbations in ubiquitin-dependent protein homeostasis.

The role of L-type calcium channels in neuronal excitability and aging.

Over the last two decades there has been significant progress towards understanding the neural substrates that underlie age-related cognitive decline. Although many of the exact molecular and cellular mechanisms have yet to be fully understood, there is consensus that alterations in neuronal calcium homeostasis contribute to age-related deficits in learning and memory. Furthermore, it is thought that the age-related changes in calcium homeostasis are driven, at least in part, by changes in calcium channel expression. In this review, we focus on the role of a specific class of calcium channels: L-type voltage-gated calcium channels (LVGCCs). We provide the reader with a general introduction to voltage-gated calcium channels, followed by a more detailed description of LVGCCs and how they serve to regulate neuronal excitability via the post burst afterhyperpolarization (AHP). We conclude by reviewing studies that link the slow component of the AHP to learning and memory, and discuss how age-related increases in LVGCC expression may underlie cognitive decline by mediating a decrease in neuronal excitability.

Prevalence of monarch (Danaus plexippus) and queen (Danaus gilippus) butterflies in West Texas during the fall of 2018.

BACKGROUND: The monarch butterfly (Danaus plexippus) is a conspicuous insect that has experienced a drastic population decline over the past two decades. While there are several factors contributing to dwindling monarch populations, habitat loss is considered the most significant threat to monarchs. In the United States, loss of milkweed, particularly in the Midwest, has greatly reduced the available breeding habitat of monarchs. This has led to extensive efforts to conserve and restore milkweed resources throughout the Midwest. Recently, these research and conservation efforts have been expanded to include other important areas along the monarch's migratory path. RESULTS: During the fall of 2018, we conducted surveys of monarch eggs and larvae through West Texas. We documented monarch and queen butterfly (Danaus gilippus) reproduction throughout the region and used the proportion of monarch and queen larva to estimate the number of monarch eggs. Peak egg densities for monarchs were as high as 0.78 per milkweed ramet after correction for the presence of queens. Despite our observations encompassing only a limited sample across one season, the peak monarch egg densities we observed exceeded published reports from when monarch populations were higher. CONCLUSIONS: To our knowledge, this is the first study to correct for the presence of queens when calculating the density of monarch eggs. This research also provides insight into monarch utilization of less well-known regions, such as West Texas, and highlights the need to expand the scope of monarch monitoring and conservation initiatives. While the importance of monarch research and conservation in the Midwest is unquestionable, more comprehensive efforts may identify new priorities in monarch conservation and lead to a more robust and effective overall strategy, particularly given the dynamic and rapidly changing global environment.

Children's physical pain: relations with maternal and paternal pain and prediction from maternal depressive symptoms and hope during infancy.

Chronic pain is common in children and increases their risk for developing a chronic pain condition in adulthood, yet relatively little is known about early parental psychosocial factors that predict the development of chronic pain in childhood. We examined the extent to which chronic pain frequency in a community sample of 6-year-old children was related to frequency of chronic pain in their parents, and was prospectively predicted by early maternal risk (i.e., depressive symptoms) and promotive (i.e., hope) factors. Fifty primary caregivers (94% mothers) of 6-year-old twin children who were enrolled in a larger study during children's infancy were randomly selected to complete a telephone interview regarding their own, their partner's, and their children's pain symptoms and functioning. Pain symptom scores were derived by summing the number of seven possible body areas that were painful at least monthly during the prior 6 months. Pain symptoms at three or more sites were coded as multisite pain. Prior maternal depressive symptoms and hope were assessed when children were aged 12-months. Pain symptom scores were positively correlated within families, and risk of child pain increased in a dose-response fashion according to whether neither, one, or both parents experienced multisite pain. Maternal hope but not depressive symptoms prospectively predicted fewer painful body regions in children five years later. Findings suggest that pain runs in families and pain in childhood may be influenced by early maternal psychosocial factors. Future research should focus on how parents' own health and psychological attributes influence risk for children's chronic pain.

A Quality Improvement Initiative: Using Lean Methodology to Improve Efficiency of the Morning Cycle Monitoring at an Ambulatory Academic Fertility Clinic.

OBJECTIVE: Patients receiving fertility treatments require near-daily blood work and ultrasound for cycle monitoring. Patient volumes at an academic hospital-based ambulatory clinic were expected to increase with expanded provincial funding. The aim of this quality improvement project was for 85% of cycle monitoring patients to have a turnaround time (TAT) of 20 minutes or less from arrival until checkout. METHODS: This is a time series study analyzed with statistical process control methodology. A baseline survey was conducted to understand patient priorities. Multiple site-specific change ideas were developed by front-line staff using lean methodology including standard processes, standard work, supportive tools, visual management, and staffing and scheduling to meet Takt time. Patient and staff satisfaction surveys were conducted after implementation (Canadian Task Force Classification II-2). RESULTS: With the start of funding in December 2015 the clinic accommodated a 17% increase in daily patient volumes and increased the proportion of patients receiving education at each visit from 50% to 100%. Despite increased patient volumes and added education time, the control chart showed special cause variation with decreased TATs from 38.2 to 34.7 minutes. Patient surveys showed that their priorities were being met or exceeded, and all staff reported increased satisfaction with the new process. CONCLUSION: By using lean methodology in an ambulatory fertility setting, the clinic was able to improve efficiency in the morning monitoring process to decrease patient TATs while accommodating increased patient volumes and improving the quality of patient care.

Use of Placental/Umbilical Blood Sampling for Neonatal Admission Blood Cultures: Benefits, Challenges, and Strategies for Implementation.

Placental blood remains an underused resource for early neonatal care despite ample evidence that placental blood provides the same clinical decision making information without the need for painful, invasive blood sampling procedures. Potential benefits of placental/umbilical blood sampling (PUBS) for neonatal admission labs include decreases in pain reactivity, rates of anemia, need for blood transfusions, use of vasopressors, and rates of intraventricular hemorrhage. Here, we present a unique case study of a critically ill infant with contradictory blood culture results from PUBS and direct infant sampling. A negative admission direct sample blood culture result compared with a positive admission PUBS blood culture result suggests that infection may have been missed in the direct infant sample. Relevant placental embryology and circulation is also described, as well as the benefits of PUBS for neonatal admission labs (with focus on the blood culture), challenges associated with PUBS practice, and strategies for implementation of PUBS.

Loss of F-box only protein 2 (Fbxo2) disrupts levels and localization of select NMDA receptor subunits, and promotes aberrant synaptic connectivity.

NMDA receptors (NMDARs) play an essential role in some forms of synaptic plasticity, learning, and memory. Therefore, these receptors are highly regulated with respect to their localization, activation, and abundance both within and on the surface of mammalian neurons. Fundamental questions remain, however, regarding how this complex regulation is achieved. Using cell-based models and F-box Only Protein 2 (Fbxo2) knock-out mice, we found that the ubiquitin ligase substrate adaptor protein Fbxo2, previously reported to facilitate the degradation of the NMDAR subunit GluN1 in vitro, also functions to regulate GluN1 and GluN2A subunit levels in the adult mouse brain. In contrast, GluN2B subunit levels are not affected by the loss of Fbxo2. The loss of Fbxo2 results in greater surface localization of GluN1 and GluN2A, together with increases in the synaptic markers PSD-95 and Vglut1. These synaptic changes do not manifest as neurophysiological differences or alterations in dendritic spine density in Fbxo2 knock-out mice, but result instead in increased axo-dendritic shaft synapses. Together, these findings suggest that Fbxo2 controls the abundance and localization of specific NMDAR subunits in the brain and may influence synapse formation and maintenance.

Understanding motivations to participate in an observational research study: Why do patients enroll?

By understanding common motivations for participating in observational research studies, clinicians may better understand the perceived benefits of research participation from their clients' perspective. We enrolled 164 cardiac patients in a study about the effects of gratitude and optimism. Two weeks post-enrollment, participants completed a four-item questionnaire regarding motivations for study enrollment. Altruistic motivation ranked highest, while intellectual, health-related, and financial motivations rated lower. Four subgroups of participants emerged, each with distinct characteristics and different priorities for participating. These findings may help front-line clinicians to understand which motivations for participation apply to their clients who enroll in non-treatment-based research projects.

A Positive Psychology Intervention for Patients with an Acute Coronary Syndrome: Treatment Development and Proof-of-Concept Trial.

Positive psychological constructs are associated with superior outcomes in cardiac patients, but there has been minimal study of positive psychology (PP) interventions in this population. Our objective was to describe the intervention development and pilot testing of an 8-week phone-based PP intervention for patients following an acute coronary syndrome (ACS). Initial intervention development and single-arm proof-of-concept trial, plus comparison of the PP intervention to a subsequently-recruited treatment as usual (TAU) cohort. PP development utilized existing literature, expert input, and qualitative interview data in ACS patients. In the proof-of-concept trial, the primary outcomes were feasibility and acceptability, measured by rates of exercise completion and participant ratings of exercise ease/utility. Secondary outcomes were pre-post changes in psychological outcomes and TAU comparisons, measured using effect sizes (Cohen's d). The PP intervention and treatment manual were successfully created. In the proof-of-concept trial, 17/23 PP participants (74 %) completed at least 5 of 8 exercises. Participants rated the ease (M = 7.4/10; SD = 2.1) and utility (M = 8.1/10, SD = 1.6) of PP exercises highly. There were moderate pre-post improvements (ds = .46-.69) in positive affect, anxiety, and depression, but minimal effects on dispositional optimism (d = .08). Compared to TAU participants (n = 22), PP participants demonstrated greater improvements in positive affect, anxiety, and depression (ds = . 47-.71), but not optimism. A PP intervention was feasible, well-accepted, and associated with improvements in most psychological measures among cardiac patients. These results provide support for a larger trial focusing on behavioral outcomes.

Mechanistic, mathematical model to predict the dynamics of tissue genesis in bone defects via mechanical feedback and mediation of biochemical factors.

The link between mechanics and biology in the generation and the adaptation of bone has been well studied in context of skeletal development and fracture healing. Yet, the prediction of tissue genesis within - and the spatiotemporal healing of - postnatal defects, necessitates a quantitative evaluation of mechano-biological interactions using experimental and clinical parameters. To address this current gap in knowledge, this study aims to develop a mechanistic mathematical model of tissue genesis using bone morphogenetic protein (BMP) to represent of a class of factors that may coordinate bone healing. Specifically, we developed a mechanistic, mathematical model to predict the dynamics of tissue genesis by periosteal progenitor cells within a long bone defect surrounded by periosteum and stabilized via an intramedullary nail. The emergent material properties and mechanical environment associated with nascent tissue genesis influence the strain stimulus sensed by progenitor cells within the periosteum. Using a mechanical finite element model, periosteal surface strains are predicted as a function of emergent, nascent tissue properties. Strains are then input to a mechanistic mathematical model, where mechanical regulation of BMP-2 production mediates rates of cellular proliferation, differentiation and tissue production, to predict healing outcomes. A parametric approach enables the spatial and temporal prediction of endochondral tissue regeneration, assessed as areas of cartilage and mineralized bone, as functions of radial distance from the periosteum and time. Comparing model results to histological outcomes from two previous studies of periosteum-mediated bone regeneration in a common ovine model, it was shown that mechanistic models incorporating mechanical feedback successfully predict patterns (spatial) and trends (temporal) of bone tissue regeneration. The novel model framework presented here integrates a mechanistic feedback system based on the mechanosensitivity of periosteal progenitor cells, which allows for modeling and prediction of tissue regeneration on multiple length and time scales. Through combination of computational, physical and engineering science approaches, the model platform provides a means to test new hypotheses in silico and to elucidate conditions conducive to endogenous tissue genesis. Next generation models will serve to unravel intrinsic differences in bone genesis by endochondral and intramembranous mechanisms.

Use of the Patient Health Questionnaire-9 and a detailed suicide evaluation in determining imminent suicidality in distressed patients with cardiac disease.

BACKGROUND: The risk of suicide is elevated in patients with cardiac disease in comparison with the general population. OBJECTIVE: In distressed cardiac inpatients, we explored the use of Item 9 of the Patient Health Questionnaire-9, which inquires about thoughts of death or suicide, and a detailed suicide evaluation (DSE) triggered by positive responses to Item 9 as means of assessing suicide. METHODS: Among cardiac inpatients endorsing current emotional distress, we recorded the prevalence of positive responses to Item 9, gathered information about outcomes and time spent completing the DSE, and examined the frequency of imminent suicidality identified by the DSE among Item 9-positive patients. RESULTS: Among 366 patients, 77 (21%) answered affirmatively to Item 9. All DSEs were successfully completed but consumed 17 clinician hours. Among the 71 patients receiving the DSE, 2 (0.5% of total sample; 2.8% of Item 9-positive patients) were imminently suicidal (i.e., had intent or plan). CONCLUSION: Nearly 1 in 4 patients had a positive response to Item 9, but very few had imminent suicidality; the DSE was easy to use and acceptable to patients but time consuming. A more narrowly focused alternative to Item 9 may more accurately predict imminent suicidality and reduce the burden of further detailed suicide screening.

An exploratory mixed methods analysis of adherence predictors following acute coronary syndrome.

Adherence to cardiac health behaviors is a critical predictor of prognosis in the months following an acute coronary syndrome (ACS). However, there has been minimal concomitant study of multiple nonadherence risk factors, as assessed via record review, structured assessments, and qualitative interviews, among hospitalized ACS patients. Accordingly, we completed an exploratory mixed methods study with 22 individuals who were admitted for ACS and had suboptimal pre-ACS adherence to physical activity, heart-healthy diet, and/or medications, defined by a Medical Outcomes Study Specific Adherence Scale (MOS SAS) score <15/18. During hospitalization, participants underwent quantitative assessments of sociodemographic, medical, and psychological variables, followed by in-depth semi-structured interviews to explore intentions, plans, and perceived barriers related to post-discharge health behavior changes. The MOS SAS was readministered at 3 months and participants were designated as persistently nonadherent (MOS SAS <15; n = 9) or newly adherent (n = 13). Interviews were transcribed and coded by trained raters via content analysis, and quantitative variables were compared between groups using chi-square analysis and independent-samples t-tests. On our primary qualitative analysis, we found that participants with vaguely described intentions/plans regarding health behavior change, and those who focused on barriers to change that were perceived as static, were more likely to be persistently nonadherent. On exploratory quantitative analyses, greater medical burden, diabetes, depressive symptoms, and low optimism/positive affect at baseline were associated with subsequent post-ACS nonadherence (all p < .05). In conclusion, this appears to be the first study to prospectively examine all of these constructs in hospitalized ACS patients, and we found that specific factors were associated with nonadherence to key health behaviors 3 months later. Therefore it may be possible to predict future nonadherence in ACS patients, even during hospitalization, and specific interventions during admission may be indicated to prevent adverse outcomes among patients at highest risk for post-ACS nonadherence.

Periosteal thickness and cellularity in mid-diaphyseal cross-sections from human femora and tibiae of aged donors.

Due to lack of access in healthy patients, the structural properties underlying the inherent regenerative power and advanced material properties of the human periosteum are not well understood. Periosteum comprises a cellular cambium layer directly apposing the outer surface of bone and an outer fibrous layer encompassed by the surrounding soft tissues. As a first step to elucidating the structural and cellular characteristics of periosteum in human bone, the current study aims to measure cambium and fibrous layer thickness as well as cambium cellularity in human femora and tibiae of aged donors. The major and minor centroidal axes (CA) serve as automated reference points in cross-sections of cadaveric mid-diaphyseal femora and tibiae. Based on the results of this study, within a given individual, the cambium layer of the major CA of the tibia is significantly thicker and more cellular than the respective layer of the femur. These significant intraindividual differences do not translate to significant interindividual differences. Further, mid-diaphyseal periosteal measures including cambium and fibrous layer thickness and cellularity do not correlate significantly with age or body mass. Finally, qualitative observations of periosteum in amputated and contralateral or proximal long bones of the lower extremity show stark changes in layer organization, thickness, and cellularity. In a translational context, these novel data, though inherently limited by availability and accessibility of human mid-diaphyseal periosteum tissue, provide important reference values for the use of periosteum in the context of facilitated healing and regeneration of tissue.

Conversion of short-term to long-term memory in the novel object recognition paradigm.

It is well-known that stress can significantly impact learning; however, whether this effect facilitates or impairs the resultant memory depends on the characteristics of the stressor. Investigation of these dynamics can be confounded by the role of the stressor in motivating performance in a task. Positing a cohesive model of the effect of stress on learning and memory necessitates elucidating the consequences of stressful stimuli independently from task-specific functions. Therefore, the goal of this study was to examine the effect of manipulating a task-independent stressor (elevated light level) on short-term and long-term memory in the novel object recognition paradigm. Short-term memory was elicited in both low light and high light conditions, but long-term memory specifically required high light conditions during the acquisition phase (familiarization trial) and was independent of the light level during retrieval (test trial). Additionally, long-term memory appeared to be independent of stress-mediated glucocorticoid release, as both low and high light produced similar levels of plasma corticosterone, which further did not correlate with subsequent memory performance. Finally, both short-term and long-term memory showed no savings between repeated experiments suggesting that this novel object recognition paradigm may be useful for longitudinal studies, particularly when investigating treatments to stabilize or enhance weak memories in neurodegenerative diseases or during age-related cognitive decline.