Sex differences in oxycodone-taking behaviors are linked to disruptions in reward-guided, decision-making functions.

Problematic opioid use that emerges in a subset of individuals may be due to pre-existing disruptions in the biobehavioral mechanisms that regulate drug use. The identity of these mechanisms is not known, but emerging evidence suggests that suboptimal decision-making that is observable prior to drug use may contribute to the pathology of addiction and, notably, serve as a powerful phenotype for interrogating biologically based differences in opiate-taking behaviors. The current study investigated the relationship between decision-making phenotypes and opioid-taking behaviors in male and female Long Evans rats. Adaptive decision-making processes were assessed using a probabilistic reversal-learning task and oxycodone- (or vehicle, as a control) taking behaviors assessed for 32 days using a saccharin fading procedure that promoted dynamic intake of oxycodone. Tests of motivation, extinction, and reinstatement were also performed. Computational analyses of decision-making and opioid-taking behaviors revealed that attenuated reward-guided decision-making was associated with greater self-administration of oxycodone and addiction-relevant behaviors. Moreover, pre-existing impairments in reward-guided decision-making observed in female rats was associated with greater oxycodone use and addiction-relevant behaviors when compared to males. These results provide new insights into the biobehavioral mechanisms that regulate opiate-taking behaviors and offer a novel phenotypic approach for interrogating sex differences in addiction susceptibility and opioid use disorders.

COVID-19 pandemic ramifications on residential Smart homes energy use load profiles.

The COVID-19 pandemic has significantly affected people's behavioral patterns and schedules because of stay-at-home orders and a reduction of social interactions. Therefore, the shape of electrical loads associated with residential buildings has also changed. In this paper, we quantify the changes and perform a detailed analysis on how the load shapes have changed, and we make potential recommendations for utilities to handle peak load and demand response. Our analysis incorporates data from before and after the onset of the COVID-19 pandemic, from an Alabama Power Smart Neighborhood with energy-efficient/smart devices, using around 40 advanced metering infrastructure data points. This paper highlights the energy usage pattern changes between weekdays and weekends pre- and post-COVID-19 pandemic times. The weekend usage patterns look similar pre- and post-COVID-19 pandemic, but weekday patterns show significant changes. We also compare energy use of the Smart Neighborhood with a traditional neighborhood to better understand how energy-efficient/smart devices can provide energy savings, especially because of increased work-from-home situations. HVAC and water heating remain the largest consumers of electricity in residential homes, and our findings indicate an even further increase in energy use by these systems.

A meal enriched in saturated fat acutely impairs cognitive performance in obese men.

BACKGROUND: Diets chronically high in saturated fat (SFA) associate with obesity and insulin resistance (IR), which in turn associate with cognitive decline and dementia. However, understanding how acute SFA consumption influences cognition is less clear despite short-term SFA-enriched diets inducing whole-body IR. We examined how consuming meals enriched with SFA or monounsaturated fat (MUFA) acutely influence cognitive function in lean and obese men. We hypothesized that greater diet-induced IR following a SFA-enriched meal would associate with decreased cognitive performance. METHODS: Twelve lean and 12 obese males ingested meals containing no fat (CTL), enriched with SFA, or enriched with MUFA in a single-blind, randomized fashion. Cognitive testing and blood sampling were performed pre- and 2 h post-meal. Oral glucose tolerance (OGTT) and body composition were also assessed. RESULTS: At baseline, fasting glucose, insulin, HOMA-IR, triglyceride, IL-6, and 2-hr glucose during an OGTT were higher in obese men (p < 0.001), while executive function (Stroop Test and Trail Making Test B-A) and working memory (Digit Span Test) were lower in obese men (p < 0.05). In response to the CTL and MUFA-enriched, no differences in cognitive measures were observed in lean or obese subjects. Following a SFA-enriched meal, obese subjects scored worse during cognitive testing (Stroop Test, Trail Making Test B-A, and Digit Span Test) compared to pre-meal scores (p < 0.05). These impairments in cognitive testing scores following the SFA-enriched meal associated with increased HOMA-IR (p < 0.01) and decreased plasma IL-6 (p < 0.05). No changes in cognitive function were observed in lean subjects following a SFA-enriched meal. CONCLUSIONS: These data demonstrate that cognitive performance of obese men acutely worsens following a high-SFA meal. Reductions in cognitive performance associated with increased IR, suggesting that diet-induced IR may acutely decrease cognitive function.

Results from the Field: Development and Evaluation of a Psychiatry Residency Training Rotation in Cognitive-Behavioral Therapies.

OBJECTIVE: The goal of this project was to develop and evaluate a new residency training rotation focused on cognitive-behavioral therapies (CBT) and to assess outcomes across multiple domains. METHODS: Data are presented from 30 psychiatry residents. Primary learning-related outcomes included content knowledge, self-efficacy, and attitudes and behavioral intentions towards evidence-based psychotherapies (e.g., CBT). RESULTS: Residents reported significant increases in CBT knowledge, CBT-specific self-efficacy, overall psychotherapy self-efficacy, belief in patient benefit from CBT, and behavioral intention to use CBT. However, there were almost no changes in attitudes towards evidence-based practice more broadly, with one significant finding showing an increase in skepticism towards such practices. CONCLUSIONS: This empirically based example of training program development, implementation, and evaluation appears largely successful and represents one approach for addressing the CBT competency goals outlined by the Accreditation Council for Graduate Medical Education (ACGME) and Milestone Project Guidelines. Despite these initial, positive findings, conclusions should be tempered by limitations of the project design (e.g., the lack of comparison group, absence of objective measures of resident behavioral change, or assessment of the effect of such changes on patient outcomes). Findings highlight the need for continued development and evaluation of training methods in CBT for residency programs.

Thermoelectric property enhancement via pore confinement in template grown bismuth telluride nanowire arrays.

Nanostructuring of thermoelectric materials can lead to thermal-to-electrical conversion efficiencies comparable with mechanical energy conversion. Theory predicts that characteristic length scales of <10 nm are necessary to achieve high thermoelectric figures of merit (zT > 3). While sub-10 nm diameter nanowire arrays have been difficult to fabricate, we present here a novel template for sub-10 nm thermoelectric nanowire array fabrication using anodized aluminum oxide followed by silica wall coating for pore confinement. Electrodeposited bismuth telluride nanowires displayed increasing electrical-to-thermal conductivity ratio as the pore diameter decreased, in agreement with theoretical predictions. Achieving the desired stoichiometric ratio of Bi2Te3 through electrodeposition was non-trivial, which limited the Seebeck coefficient of the nanowires. However, hydrolysis of the nanopore walls led to improved electrodeposition, achieving near stoichiometric bismuth-to-tellurium ratios and ultimately p-type thermoelectric nanowire arrays with a Seebeck coefficient of up to 79 µV K-1.

Optimal pacing and carbohydrate intake strategies for ultramarathons.

PURPOSE: The purpose of this research is to determine the pacing and nutrition strategies which minimize completion time and carbohydrate intake for athletes competing in ultramarathon races. METHODS: We present the formulation of a two-phase optimization model. The first-phase mixed-integer nonlinear program (MINLP) determines the minimum completion time subject to the altitude, terrain, and distance of the race, as well as the mass and cardiovascular fitness of the athlete. The second-phase MINLP determines the minimum carbohydrate intake required for the athlete to achieve the completion time prescribed by the first-phase subject to the flow of carbohydrates through the stomach, liver, and muscles. Consequently, the second-phase model provides the optimal pacing and nutrition strategies for a particular athlete for each kilometer of a particular race. RESULTS: We validate model results for a wide range of athlete parameters by comparing completion times to those reported for two case-study events. We also compare the kilometer-by-kilometer pacing and nutrition strategies prescribed by the model to those of a particular athlete. In all cases, the model results closely match those witnessed in the actual events. CONCLUSION: We have developed a baseline metabolic model that provides athletes prescriptive guidance regarding optimal pacing and carbohydrate intake strategies prior to competing in ultramarathon races. Given the highly variable topographical characteristics common to many ultramarathon courses and the potential inexperience of many athletes with such courses, our model provides valuable insight to competitors who might otherwise fail to complete the event due to exhaustion or carbohydrate depletion.

Identification of High-Potency Human TLR8 and Dual TLR7/TLR8 Agonists in Pyrimidine-2,4-diamines.

The induction of toll-like receptor 7 (TLR7)-dependent type I interferons (IFN-α/ß) from plasmacytoid dendritic cells as well as the production of TLR8-dependent type II interferon (IFN-γ), TNF-α, and IL-12 in myeloid dendritic cells are of importance in generating T helper-1 biased adaptive immune responses. In an effort to identify novel dual TLR7/TLR8-active compounds, we undertook structure-activity relationship studies in pyrimidine 2,4-diamines, focusing on substituents at C5. Several analogues substituted with aminopropyl appendages at C5 displayed dominant TLR8-agonistic activity. N4-Butyl-6-methyl-5-(3-morpholinopropyl)pyrimidine-2,4-diamine was found to be a very potent dual TLR7/TLR8 agonist. Employing novel cytokine reporter cell assays, we verified that potency at TLR7 correlates with IFN-α/ß production in human blood, whereas IFN-γ and TNF-α induction is largely TLR8-dependent. Dual TLR7/TLR8 agonists markedly upregulate CD80 expression in multiple dendritic cell subsets, providing insight into the immunological basis for the superior adjuvantic properties of such innate immune stimuli.

Human Toll-like Receptor (TLR) 8-Specific Agonistic Activity in Substituted Pyrimidine-2,4-diamines.

Activation of human toll-like receptor-8 (TLR8) evokes a distinct cytokine profile favoring the generation of Type 1 helper T cells. A multiplexed high-throughput screen had led to the identification of N(4)-butyl-5-iodo-6-methylpyrimidine-2,4-diamine as a pure TLR8 agonist, and a detailed structure-activity relationship study of this chemotype was undertaken. A butyl substituent at N(4) was optimal, and replacement of the 5-iodo group with chloro, bromo, or fluoro groups led to losses in potency, as did the introduction of aromatic bulk. Drawing from our previous structure-based design, several 5-alkylamino derivatives were evaluated. Significant enhancement of potency was achieved in 5-(4-aminobutyl)-N(4)-butyl-6-methylpyrimidine-2,4-diamine. This compound potently induced Th1-biasing IFN-γ and IL-12 in human blood, but lower levels of the proinflammatory cytokines IL-1ß, IL-6, and IL-8. These results suggest that the inflammatory and reactogenic propensities of this compound could be considerably more favorable than other TLR8 agonists under evaluation.

Targeting the vasculature to improve neural progenitor transplant survival.

Neural progenitor transplantation is a promising therapeutic option for several neurological diseases and injuries. In nearly all human clinical trials and animal models that have tested this strategy, the low survival rate of progenitors after engraftment remains a significant challenge to overcome. Developing methods to improve the survival rate will reduce the number of cells required for transplant and will likely enhance functional improvements produced by the procedure. Here we briefly review the close relationship between the blood vasculature and neural progenitors in both the embryo and adult nervous system. We also discuss previous studies that have explored the role of the vasculature and hypoxic pre-conditioning in neural transplants. From these studies, we suggest that hypoxic pre-conditioning of a progenitor pool containing both neural and endothelial cells will improve engrafted transplanted neuronal survival rates.

The epigenetics of stroke recovery and rehabilitation: from polycomb to histone deacetylases.

Classical de-afferentation studies, as well as experience-dependent visual plasticity paradigms, have confirmed that both the developing and adult nervous system are capable of unexpected levels of plasticity. This capacity is underscored by the significant spontaneous recovery that can occur in patients with mild-to-moderate impairment following stroke. An evolving model is that an interaction of biological and environmental factors during all epochs post-stroke influences the extent and quality of this plasticity. Here, we discuss data that have implicated specific epigenetic proteins as integrators of environmental influences in 3 aspects of stroke recovery: spontaneous impairment reduction in humans; peri-infarct rewiring in animals as a paradigm for developing therapeutically-driven impairment reduction beyond natural spontaneous recovery; and, finally, classical hippocampal learning and memory paradigms that are theoretically important in skill acquisition for both impairment reduction and compensatory strategies in the rehabilitation setting. Our discussion focuses primarily on B lymphoma Mo-MLV1 insertion region proteins of the polycomb repressive complex, alpha thalassemia/mental retardation syndrome X-linked chromatin remodeling factors, and the best known and most dynamic gene repressors, histone deacetylases. We will highlight exciting current data associated with these proteins and provide promising speculation about how they can be manipulated by drugs, biologics, or noninvasive stimulation for stroke recovery.

Effect of a contralateral lesion on neurological recovery from stroke in rats.

PURPOSE: Clinical studies suggest a correlation between changes in activity of the contralesional cerebral cortex and spontaneous recovery from stroke, but whether this is a causal relationship is uncertain. METHODS: Young adult Sprague-Dawley male rats underwent unilateral or bilateral permanent distal middle cerebral artery occlusion (dMCAO). Infarct volume was determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining 24 hr after dMCAO, and functional outcome was assessed 1-28 days after dMCAO using the ladder rung walking and limb placing tests. RESULTS: Infarct volume was unchanged, but functional neurological deficits were reduced 1 day after bilateral compared to unilateral dMCAO. CONCLUSIONS: Activity in the contralesional cerebral cortex may inhibit functional motor recovery after experimental stroke.

Intracerebral chondroitinase ABC and heparan sulfate proteoglycan glypican improve outcome from chronic stroke in rats.

Physical and chemical constraints imposed by the periinfarct glial scar may contribute to the limited clinical improvement often observed after ischemic brain injury. To investigate the role of some of these mediators in outcome from cerebral ischemia, we treated rats with the growth-inhibitory chondroitin sulfate proteoglycan neurocan, the growth-stimulating heparan sulfate proteoglycan glypican, or the chondroitin sulfate proteoglycan-degrading enzyme chondroitinase ABC. Neurocan, glypican, or chondroitinase ABC was infused directly into the infarct cavity for 7 d, beginning 7 d after middle cerebral artery occlusion. Glypican and chondroitinase ABC reduced glial fibrillary acidic protein immunoreactivity and increased microtubule-associated protein-2 immunoreactivity in the periinfarct region, and glypican- and chondroitinase ABC-treated rats showed behavioral improvement compared with neurocan- or saline-treated rats. Glypican and chondroitinase ABC also increased neurite extension in cortical neuron cultures. Glypican increased fibroblast growth factor-2 expression and chondroitinase ABC increased brain-derived neurotrophic factor expression in these cultures, whereas no such effects were seen following neurocan treatment. Thus, treatment with glypican or enzymatic disruption of neurocan with chondroitinase ABC improves gross anatomical, histological, and functional outcome in the chronic phase of experimental stroke in rats. Changes in growth factor expression and neuritogenesis may help to mediate these effects.

An interfacial and bulk charge transport model for dye-sensitized solar cells based on photoanodes consisting of core-shell nanowire arrays.

Dye-sensitized solar cells (DSSCs) based on ordered photoanode morphologies, such as nanotubes and nanowires, are widely gaining attention because these geometries are believed to enhance interfacial charge transfer and bulk charge transport. Unfortunately, experimental results have yet to show substantial improvement to conversion efficiency over nanoparticle-based DSSCs. A model is developed to characterize the performance of an idealized photoanode based on an ordered array of transparent conductive nanowires coated with an anatase titania shell. The role of the interfacial electric field in nanowire-based DSSCs is explored computationally by turning electron migration ON or OFF. The results show that back-reaction rates are most strongly influenced by the electric field. These electron loss mechanisms can be reduced by several orders of magnitude, leading to improvements in short-circuit current, open-circuit voltage, and fill factor.

The development of a brief acceptance and mindfulness-based program aimed at reducing sexual revictimization among college women with a history of childhood sexual abuse.

Women with a history of childhood sexual assault (CSA) are more likely to be revictimized; however, most existing programs aimed at reducing sexual victimization do not expressly address the issue of revictimization. The present study examined the efficacy of a brief mindfulness-based program in reducing rates of sexual assault and revictimization in college women over the course of an academic semester. Although the results were not statistically significant, a large-magnitude effect was noted, whereby women with a history of CSA who participated in the program were less likely to be sexually assaulted and raped at 2-month follow-up.

Eliminating capillary coalescence of nanowire arrays with applied electric fields.

Surface tension induces significant forces on wetted nanostructures, such as vertically oriented nanowire arrays, that can force them to aggregate when dried. This aggregation decreases the homogeneity and surface area of the array, often inhibiting their intended application. These aggregation forces are eliminated by introducing small electric fields ( approximately 100 V/m) during drying, providing a simple approach that is applicable to a broad range of nanowire materials, diameters, lengths, and spacing. A model based on the forces acting on two nanowires shows that electrostatic repulsion, rather than field-induced changes to the surface tension, provides the necessary forces to prevent aggregation. These calculations also highlight the substantial surface tension forces acting on nanostructures and the difficulties associated with preventing their aggregation.

Psychosocial predictors of employment status among men living with spinal cord injury.

OBJECTIVE: To explore the relationship between employment status and community access, perceived community discrimination, social support from significant others, depressive symptoms, and gender-related variables for 83 men living with spinal cord injury. STUDY DESIGN: Correlational research. SETTING: Internet-based investigation employing spinal cord injury listservs. MAIN OUTCOME MEASURE: Participant employment status. RESULTS: A forced-entry hierarchical logistic regression indicated that means of injury, community access and perceived community discrimination, social support from significant others, depressive symptoms, and men's adherence to masculine norms for primacy of work, self-reliance, and emotional control significantly predicted employment status. CONCLUSIONS: Psychosocial variables such as community access, perceived discrimination, social support from significant others, depressive symptoms, and gender identity represent important and understudied predictors of employment status among men living with spinal cord injury.

Men's adjustment to spinal cord injury: the unique contributions of conformity to masculine gender norms.

Men constitute 82% of the approximately 250,000 people in the United States living with a spinal cord injury. Unfortunately, however, little is known about the impact of men's adherence to gender norms on their adjustment to such injuries. The present investigation examined the utility of masculine norms in explaining variance in depression beyond that accounted for by commonly identified predictors of men's adjustment following spinal cord injury. As hypothesized, results suggested that men's adherence to masculine norms accounted for unique variance in their depression scores beyond that contributed by social support, environmental barriers/access, and erectile functioning. Respondents who adhered to norms stressing the primacy of men's work demonstrated lower rates of depression, whereas those who conformed to norms for self-reliance demonstrated higher depression scores. The authors discuss future research directions and potential psychotherapeutic strategies for working with men with spinal cord injuries.

Monitoring stress levels in postgraduate medical training.

OBJECTIVES: The Accreditation Council for Graduate Medical Education (ACGME) mandates that residency Program Directors (PD) monitor resident well-being, including stress. Burnout, as a measure of work-related stress, is defined by a high degree of emotional exhaustion and depersonalization, and a low degree of personal accomplishment using the Maslach Burnout Inventory-Human Services Survey (MBI-HSS). The purpose of this study is to describe the use of the MBI-HSS as a method of monitoring stress levels in an academic otolaryngology residency training program and introduce this survey as a tool for wider use in meeting ACGME requirements. METHODS: The MBI-HSS was administered to residents in an academic otolaryngology residency training program on three separate occasions: at the beginning, middle, and end of different academic years. In addition, at the time of the third administration, the MBI-HSS was completed by faculty and staff in the same department. Surveys were completed and collected anonymously. Responses were scored against normative data from the MBI-HSS overall sample and the medicine subscale. Low, average, and high levels of burnout were identified for the individual categories of emotional exhaustion (EE), depersonalization (DP), and personal accomplishment (PA); average levels for each category were calculated. RESULTS: Twenty-two residents completed the first survey, taken near the end of an academic year; 19 completed the second administration in the middle of the following academic year; and 24 completed the third survey at the beginning of the subsequent academic year. Thirteen faculty and 23 staff also completed the third survey. We found that three, one, and one residents reported high levels of burnout on the first, second, and third surveys, respectively. These figures compare to one faculty member and no staff members in the same department reporting high levels of burnout. CONCLUSIONS: The MBI-HSS is an established and validated tool for identifying burnout in resident physicians. Residency PDs may find the MBI-HSS useful as an aid in monitoring resident well-being and stress. In our own department, we found levels of burnout comparable to those previously reported for residents and faculty in this specialty.

An intimate collaboration between peroxisomes and lipid bodies.

Although peroxisomes oxidize lipids, the metabolism of lipid bodies and peroxisomes is thought to be largely uncoupled from one another. In this study, using oleic acid-cultured Saccharomyces cerevisiae as a model system, we provide evidence that lipid bodies and peroxisomes have a close physiological relationship. Peroxisomes adhere stably to lipid bodies, and they can even extend processes into lipid body cores. Biochemical experiments and proteomic analysis of the purified lipid bodies suggest that these processes are limited to enzymes of fatty acid beta oxidation. Peroxisomes that are unable to oxidize fatty acids promote novel structures within lipid bodies ("gnarls"), which may be organized arrays of accumulated free fatty acids. However, gnarls are suppressed, and fatty acids are not accumulated in the absence of peroxisomal membranes. Our results suggest that the extensive physical contact between peroxisomes and lipid bodies promotes the coupling of lipolysis within lipid bodies with peroxisomal fatty acid oxidation.