Drug Predictive Cues Activate Aversion-Sensitive Striatal Neurons That Encode Drug Seeking

Drug-associated cues have profound effects on an addict’s emotional state and drug-seeking behavior. Although this influence must involve the motivational neural system that initiates and encodes the drug-seeking act, surprisingly little is known about the nature of such physiological events and their motivational consequences. Three experiments investigated the effect of a cocaine-predictive stimulus on dopamine signaling, neuronal activity, and reinstatement of cocaine seeking. In all experiments, rats were divided into two groups (paired and unpaired), and trained to self-administer cocaine in the presence of a tone that signaled the immediate availability of the drug. For rats in the paired group, self-administration sessions were preceded by a taste cue that signaled delayed drug availability. Assessments of hedonic responses indicated that this delay cue became aversive during training. Both the self-administration behavior and the immediate cue were subsequently extinguished in the absence of cocaine. After extinction of self-administration behavior, the presentation of the aversive delay cue reinstated drug seeking. In vivo electrophysiology and voltammetry recordings in the nucleus accumbens measured the neural responses to both the delay and immediate drug cues after extinction. Interestingly, the presentation of the delay cue simultaneously decreased dopamine signaling and increased excitatory encoding of the immediate cue. Most importantly, the delay cue selectively enhanced the baseline activity of neurons that would later encode drug seeking. Together these observations reveal how cocaine cues can modulate not only affective state, but also the neurochemical and downstream neurophysiological environment of striatal circuits in a manner that promotes drug seeking

Navigating the noise-depth tradeoff in adiabatic quantum circuits

Adiabatic quantum algorithms solve computational problems by slowly evolving a trivial state to the desired solution. On an ideal quantum computer, the solution quality improves monotonically with increasing circuit depth. By contrast, increasing the depth in current noisy computers introduces more noise and eventually deteriorates any computational advantage. What is the optimal circuit depth that provides the best solution? Here, we address this question by investigating an adiabatic circuit that interpolates between the paramagnetic and ferromagnetic ground states of the one-dimensional quantum Ising model. We characterize the quality of the final output by the density of defects $d$, as a function of the circuit depth $N$ and noise strength $\sigma$. We find that $d$ is well-described by the simple form $d_\mathrm{ideal}+d_\mathrm{noise}$, where the ideal case $d_\mathrm{ideal}\sim N^{-1/2}$ is controlled by the Kibble-Zurek mechanism, and the noise contribution scales as $d_\mathrm{noise}\sim N\sigma^2$. It follows that the optimal number of steps minimizing the number of defects goes as $\sim\sigma^{-4/3}$. We implement this algorithm on a noisy superconducting quantum processor and find that the dependence of the density of defects on the circuit depth follows the predicted non-monotonous behavior and agrees well with noisy simulations. Our work allows one to efficiently benchmark quantum devices and extract their effective noise strength $\sigma$

Can off-field ‘brains’ provide a competitive advantage in professional football?

‘Working-fast and working-slow’ in sport describes the concept that practice and research can be integrated to improve high-performance outcomes and enhance professional practice.1 ‘Working-fast’ is the task of the fast-thinking, intuitive practitioner operating on ‘the ground’ at a frenetic pace, interacting with coaches and athletes, and delivering the daily preparation programme. ‘Working-slow’ is key for the team's deliberate, focused researcher acting as the resident sceptic, operating behind the scenes on tasks that the ‘fast-practitioner’ may not have time and/or skills to undertake. Such hidden, but important, tasks include determining measurement noise/error in performance tests, establishing proof of concept for new ideas and ensuring validity of methods. Embedding research into the fast environment of high-performance football may provide a competitive advantage using ethical and evidence-based methods.

The Effects of a Korean Ginseng, GINST15, on Hypo-Pituitary-Adrenal and Oxidative Activity Induced by Intense Work Stress

The effect of GINST15, an enzyme fermented ginseng supplement, on hormonal and inflammatory responses to physical stress in humans is unknown. The purpose of this investigation was to examine the constitutive and stress-induced effects of GINST15 supplement on hypo-pituitary-adrenal (HPA) and antioxidant activity in addition to muscle damage. Ten women (age: 38.7 ± 7.8 years; height: 163.81 ± 4.4 cm; body mass 76.0 ± 11.6 kg) and nine men (age: 41.2. ± 9.7 years; height: 177.4 ± 5.3 cm; body mass: 88.5 ± 5.0 kg) participated in a double-blinded, placebo-controlled, counterbalanced within-group study. Participants completed three 14-day treatment cycles with different doses (high: 960 mg; low: 160 mg; placebo: 0 mg) separated by a 1-week washout period. At the end of treatment, physical stress was imposed with intense resistance exercise work stress. Participants provided blood at rest and various time points after exercise (immediately [IP], 30 min [30], 60 min [60], 24 h [+24HR]). Cortisol (CORT), superoxide dismutase (SOD), total glutathione, nonspecific antioxidant activity, total antioxidant power (TAP), and creatine kinase were measured. GINST15 supplementation produced stress-inducible dose-dependent reductions in circulating cortisol and increased enzymatic and nonspecific antioxidant activity. Twenty-four hours after intense exercise, a high dose GINST15, a bioactive ginsenoside metabolite, significantly reduces muscle damage and HPA responses to physical stress in humans; these effects may result from increased antioxidant expression

The Effects Combining Cryocompression Therapy following an Acute Bout of Resistance Exercise on Performance and Recovery

Compression and cold therapy used separately have shown to reduce negative effects of tissue damage. The combining compression and cold therapy (cryocompression) as a single recovery modality has yet to be fully examined. To examine the effects of cryocompression on recovery following a bout of heavy resistance exercise, recreationally resistance trained men (n =16) were recruited, matched, and randomly assigned to either a cryocompression group (CRC) or control group (CON). Testing was performed before and then immediately after exercise, 60 minutes, 24 hours, and 48 hours after a heavy resistance exercise workout (barbell back squats for 4 sets of 6 reps at 80% 1RM, 90 sec rest between sets, stiff legged deadlifts for 4 sets of 8 reps at 1.0 X body mass with 60 sec rest between sets, 4 sets of 10 eccentric Nordic hamstring curls, 45 sec rest between sets). The CRC group used the CRC system for 20-mins of cryocompression treatment immediately after exercise, 24 hours, and 48 hours after exercise. CON sat quietly for 20-mins at the same time points. Muscle damage [creatine kinase], soreness (visual analog scale, 0-100), pain (McGill Pain Q, 0-5), fatigue, sleep quality, and jump power were significantly (p \u3c 0.05) improved for CRC compared to CON at 24 and 48 hours after exercise. Pain was also significantly lower for CRC compared to CON at 60-mins post exercise. These findings show that cryocompression can enhance recovery and performance following a heavy resistance exercise workout

The Effects of a Korean Ginseng, GINST15, on Perceptual Effort, Psychomotor Performance, and Physical Performance in Men and Women

The purpose of this double-blind, placebo-controlled investigation was to examine the effects of a Korean Ginseng (GINST15) on measures of perception and physical performance following an acute bout of resistance exercise. Ten women (age: 38.7 ± 7.8 years; height: 1.64 ± 0.05 m; body mass: 76.0 ± 11.6 kg) and nine men (age: 41.2. ± 9.7 years; height: 1.77 ± 0.05 m; body mass: 88.5 ± 5.0 kg) completed the investigation. Participants were randomized to a three-cycle testing scheme consisting of high dose ginseng (HIGH: 960 mg/day), low dose ginseng (LOW: 160 mg/day) and placebo (PBO: 0 mg/day). After 14 days of supplementation participants returned to the laboratory for an acute resistance exercise trial (5 sets of 12 repetitions of the leg press at 70% of one-repetition-maximum [1RM]). Ratings of perceived exertion (RPE) were assessed after each set. Muscle pain/soreness was assessed before exercise and 24 hours post exercise. Psychomotor performance and peak power were measured before exercise, immediately post exercise and 24 hours after exercise. Each treatment cycle was separated by a minimum one-week washout period. HIGH significantly reduced perceived exertion during exercise. HIGH and LOW significantly reduced change in muscle soreness at 24 hours post exercise. Analysis of peak power demonstrated the presence of responders (n = 13) and non-responders (n = 6). Responders showed a significant effect of HIGH GINST15 on maintenance of neuromuscular function. The appearance of responders and non-responders, could explain the mixed literature base on the ergogenic properties of ginseng

Changes of Hydration Measures in Elite National Collegiate Athletic Association Division I Wrestlers

Purpose: To evaluate the changes in the state of hydration in elite National Collegiate Athletic Association (NCAA) Division I college wrestlers during and after a season. Methods: Ohio State University wrestling team members (N = 6; mean [SD] age = 19.6 [1.1] y; height = 171.6 [2.9] cm; body mass = 69.5 [8.1] kg) gave informed consent to participate in the investigation with measurements (ie, body mass, urine-specific gravity [USG; 2 methods], Visual Analog Scale thirst scale, plasma osmolality) obtained during and after the season. Results: Measurements for USG, regardless of methods, were not significantly different between visits, but plasma osmolality was significantly (P = .001) higher at the beginning of the season—295.5 (4.9) mOsm·kg−1 compared with 279.6 (6.1) mOsm·kg−1 after the season. No changes in thirst ratings were observed, and the 2 measures of USG were highly correlated (r \u3e .9, P = .000) at each time point, but USG and plasma osmolality were not related. Conclusions: A paradox in the clinical interpretation of euhydration in the beginning of the season was observed with the USG, indicating that the wrestlers were properly hydrated, while the plasma osmolality showed they were not. Thus, the tracking of hydration status during the season is a concern when using only NCAA policies and procedures. The wrestlers did return to normal euhydration levels after the season on both biomarkers, which is remarkable, as previous studies have indicated that this may not happen because of the reregulation of the osmol-regulatory center in the brain

Epidemiology of Coxiella burnetii infection in Africa: a OneHealth systematic review

Background: Q fever is a common cause of febrile illness and community-acquired pneumonia in resource-limited settings. Coxiella burnetii, the causative pathogen, is transmitted among varied host species, but the epidemiology of the organism in Africa is poorly understood. We conducted a systematic review of C. burnetii epidemiology in Africa from a “One Health” perspective to synthesize the published data and identify knowledge gaps.<p></p> Methods/Principal Findings: We searched nine databases to identify articles relevant to four key aspects of C. burnetii epidemiology in human and animal populations in Africa: infection prevalence; disease incidence; transmission risk factors; and infection control efforts. We identified 929 unique articles, 100 of which remained after full-text review. Of these, 41 articles describing 51 studies qualified for data extraction. Animal seroprevalence studies revealed infection by C. burnetii (≤13%) among cattle except for studies in Western and Middle Africa (18–55%). Small ruminant seroprevalence ranged from 11–33%. Human seroprevalence was <8% with the exception of studies among children and in Egypt (10–32%). Close contact with camels and rural residence were associated with increased seropositivity among humans. C. burnetii infection has been associated with livestock abortion. In human cohort studies, Q fever accounted for 2–9% of febrile illness hospitalizations and 1–3% of infective endocarditis cases. We found no studies of disease incidence estimates or disease control efforts.<p></p> Conclusions/Significance: C. burnetii infection is detected in humans and in a wide range of animal species across Africa, but seroprevalence varies widely by species and location. Risk factors underlying this variability are poorly understood as is the role of C. burnetii in livestock abortion. Q fever consistently accounts for a notable proportion of undifferentiated human febrile illness and infective endocarditis in cohort studies, but incidence estimates are lacking. C. burnetii presents a real yet underappreciated threat to human and animal health throughout Africa.<p></p&gt

Clinical practice guidelines on the evidenceâ based use of integrative therapies during and after breast cancer treatment

Answer questions and earn CME/CNEPatients with breast cancer commonly use complementary and integrative therapies as supportive care during cancer treatment and to manage treatmentâ related side effects. However, evidence supporting the use of such therapies in the oncology setting is limited. This report provides updated clinical practice guidelines from the Society for Integrative Oncology on the use of integrative therapies for specific clinical indications during and after breast cancer treatment, including anxiety/stress, depression/mood disorders, fatigue, quality of life/physical functioning, chemotherapyâ induced nausea and vomiting, lymphedema, chemotherapyâ induced peripheral neuropathy, pain, and sleep disturbance. Clinical practice guidelines are based on a systematic literature review from 1990 through 2015. Music therapy, meditation, stress management, and yoga are recommended for anxiety/stress reduction. Meditation, relaxation, yoga, massage, and music therapy are recommended for depression/mood disorders. Meditation and yoga are recommended to improve quality of life. Acupressure and acupuncture are recommended for reducing chemotherapyâ induced nausea and vomiting. Acetylâ Lâ carnitine is not recommended to prevent chemotherapyâ induced peripheral neuropathy due to a possibility of harm. No strong evidence supports the use of ingested dietary supplements to manage breast cancer treatmentâ related side effects. In summary, there is a growing body of evidence supporting the use of integrative therapies, especially mindâ body therapies, as effective supportive care strategies during breast cancer treatment. Many integrative practices, however, remain understudied, with insufficient evidence to be definitively recommended or avoided. CA Cancer J Clin 2017;67:194â 232. © 2017 American Cancer Society.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136746/1/caac21397_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136746/2/caac21397.pd

Estrogen promotes cutaneous wound healing via estrogen receptor β independent of its antiinflammatory activities

Post-menopausal women have an increased risk of developing a number of degenerative pathological conditions, linked by the common theme of excessive inflammation. Systemic estrogen replacement (in the form of hormone replacement therapy) is able to accelerate healing of acute cutaneous wounds in elderly females, linked to its potent antiinflammatory activity. However, in contrast to many other age-associated pathologies, the detailed mechanisms through which estrogen modulates skin repair, particularly the cell type–specific role of the two estrogen receptors, ERα and ERβ, has yet to be determined. Here, we use pharmacological activation and genetic deletion to investigate the role of both ERα and ERβ in cutaneous tissue repair. Unexpectedly, we report that exogenous estrogen replacement to ovariectomised mice in the absence of ERβ actually delayed wound healing. Moreover, healing in epidermal-specific ERβ null mice (K14-cre/ERβL2/L2) largely resembled that in global ERβ null mice. Thus, the beneficial effects of estrogen on skin wound healing are mediated by epidermal ERβ, in marked contrast to most other tissues in the body where ERα is predominant. Surprisingly, agonists to both ERα and ERβ are potently antiinflammatory during skin repair, indicating clear uncoupling of inflammation and overall efficiency of repair. Thus, estrogen-mediated antiinflammatory activity is not the principal factor in accelerated wound healing