Prolonged exposure to cocaine self-administration results in a continued progression of alterations in functional activity in a nonhuman primate model.

Background: Studies of nonhuman primates with exposures of up to 100 days of cocaine self-administration (SA) have provided evidence that the central effects of cocaine progress over time. These durations of cocaine exposure, however, may be insufficient to capture the extent of the neurobiological alterations observed in cocaine users, many of whom use the drug for years. The goal of the present study was to determine whether 1.5 years of cocaine SA would result in further progression of alterations in functional brain activity. Methods: Adult male rhesus monkeys were exposed to 300 sessions of high-dose cocaine SA over 1.5 years. Following the final session rates of local cerebral glucose utilization (LCGU) were assessed with the 2-[14C]-deoxyglucose method and compared to rates of LCGU in control monkeys who responded for food reinforcement. In addition, LCGU in these animals was compared to a previously published group of monkeys that had self-administered cocaine or food for 100 sessions over a 4-5 month period. Results: Compared to 100 days of exposure, 300 days of cocaine SA further reduced LCGU in the post-commissural striatum and produced reductions in areas unaffected by the shorter duration of exposure, such as the hypothalamus, all of the amygdala, and large expanses of cortex. Conclusions: These findings demonstrate a clear progression of the impact of cocaine on functional activity with increasing durations of drug experience and have important implications for the development of potential strategies for the treatment of cocaine use disorder.

Residual deficits in functional brain activity after chronic cocaine self-administration in rhesus monkeys.

Previous studies in humans and in animals have shown dramatic effects of cocaine on measures of brain function that persist into abstinence. The purpose of this study was to examine the neurobiological consequences of abstinence from cocaine, using a model that removes the potential confound of cocaine cues. Adult male rhesus monkeys self-administered cocaine (0.3 mg/kg/injection; N = 8) during daily sessions or served as food-reinforcement controls (N = 4). Two times per week, monkeys were placed in a neutral environment and presented with a cartoon video for ~30 min, sometimes pre- and sometimes post-operant session, but no reinforcement was presented during the video. After ~100 sessions and when the cocaine groups had self-administered 900 mg/kg cocaine, the final experimental condition was a terminal 2-[14C]-deoxyglucose procedure, which occurred in the neutral (cartoon video) environment; for half of the monkeys in each group, this occurred after 1 day of abstinence and for the others after 30 days of abstinence. Rates of local cerebral glucose metabolism were measured in 57 brain regions. Global rates of cerebral metabolism were significantly lower in animals 1 day and 30 days post-cocaine self-administration when compared to those of food-reinforced controls. Effects were larger in 30- vs. 1-day cocaine abstinence, especially in prefrontal, parietal and cingulate cortex, as well as dorsal striatum and thalamus. Because these measures were obtained from monkeys while in a neutral environment, the deficits in glucose utilization can be attributed to the consequences of cocaine exposure and not to effects of conditioned stimuli associated with cocaine.

Role of the caudal peduncle in a fish-inspired robotic model: how changing stiffness and angle of attack affects swimming performance.

In fish, the tail is a key element of propulsive anatomy that contributes to thrust during swimming. Fish possess the ability to alter tail stiffness, surface area and conformation. Specifically, the region at the base of the tail, the caudal peduncle, is proposed to be a key location of fish stiffness modulation during locomotion. Most previous analyses have focused on the overall body or tail stiffness, and not on the effects of changing stiffness specifically at the base of the tail in fish and robotic models. We used both computational fluid dynamics analysis and experimental measurements of propulsive forces in physical models with different peduncle stiffnesses to analyze the effect of altering stiffness on the tail angle of attack and propulsive force and efficiency. By changing the motion program input to the tail, we were able to alter the phase relationship between the front and back tail sections between 0° and 330°. Computational simulations showed that power consumption was nearly minimized and thrust production was nearly maximized at the kinematic pattern whereφ= 270°, the approximate phase lag observed in the experimental foils and in free swimming tuna. We observed reduced thrust and efficiency at high angles of attack, suggesting that the tail driven during these motion programs experiences stalling and loss of lift. However, there is no single peduncle stiffness that consistently maximizes performance, particularly in physical models. This result highlights the fact that the optimal caudal peduncle stiffness is highly context dependent. Therefore, incorporating the ability to control peduncle stiffness in future robotic models of fish propulsion promises to increase the ability of robots to approach the performance of fish.

Chronic phenmetrazine treatment promotes D2 dopaminergic and α2-adrenergic receptor desensitization and alters phosphorylation of signaling proteins and local cerebral glucose metabolism in the rat brain.

Phenmetrazine (PHEN) is a putative treatment for cocaine and psychostimulant recidivism; however, neurochemical changes underlying its activity have not been fully elucidated. We sought to characterize brain homeostatic adaptations to chronic PHEN, specifically on functional brain activity (local cerebral glucose utilization), G-Protein Coupled Receptor-stimulated G-protein activation, and phosphorylation of ERK1/2Thr202/Tyr204, GSK3ßTyr216, and DARPP-32Thr34. Male Sprague-Dawley rats were implanted with sub-cutaneous minipumps delivering either saline (vehicle), acute (2-day) or chronic (14-day) low dose (25 mg/kg/day) or high dose (50 mg/kg/day) PHEN. Acute administration of high dose PHEN increased local cerebral glucose utilization measured by 2-[14C]-deoxyglucose uptake in basal ganglia and motor-related regions of the rat brain. However, chronically treated animals developed tolerance to these effects. To identify the neurochemical changes associated with PHEN's activity, we performed [35S]GTPγS binding assays on unfixed and immunohistochemistry on fixed coronal brain sections. Chronic PHEN treatment dose-dependently attenuated D2 dopamine and α2-adrenergic, but not 5-HT1A, receptor-mediated G-protein activation. Two distinct patterns of effects on pERK1/2 and pDARPP-32 were observed: 1) chronic low dose PHEN decreased pERK1/2, and also significantly increased pDARPP-32 levels in some regions; 2) acute and chronic PHEN increased pERK1/2, but chronic high dose PHEN treatment tended to decrease pDARPP-32. Chronic low dose, but not high dose, PHEN significantly reduced pGSK3ß levels in several regions. Our study provides definitive evidence that extended length PHEN dosage schedules elicit distinct modes of neuronal acclimatization in cellular signaling. These pharmacodynamic modifications should be considered in drug development for chronic use.

Tuna robotics: hydrodynamics of rapid linear accelerations.

Fish routinely accelerate during locomotor manoeuvres, yet little is known about the dynamics of acceleration performance. Thunniform fish use their lunate caudal fin to generate lift-based thrust during steady swimming, but the lift is limited during acceleration from rest because required oncoming flows are slow. To investigate what other thrust-generating mechanisms occur during this behaviour, we used the robotic system termed Tunabot Flex, which is a research platform featuring yellowfin tuna-inspired body and tail profiles. We generated linear accelerations from rest of various magnitudes (maximum acceleration of [Formula: see text] at [Formula: see text] tail beat frequency) and recorded instantaneous electrical power consumption. Using particle image velocimetry data, we quantified body kinematics and flow patterns to then compute surface pressures, thrust forces and mechanical power output along the body through time. We found that the head generates net drag and that the posterior body generates significant thrust, which reveals an additional propulsion mechanism to the lift-based caudal fin in this thunniform swimmer during linear accelerations from rest. Studying fish acceleration performance with an experimental platform capable of simultaneously measuring electrical power consumption, kinematics, fluid flow and mechanical power output provides a new opportunity to understand unsteady locomotor behaviours in both fishes and bioinspired aquatic robotic systems.

Tunabot Flex: a tuna-inspired robot with body flexibility improves high-performance swimming.

Tunas are flexible, high-performance open ocean swimmers that operate at high frequencies to achieve high swimming speeds. Most fish-like robotic systems operate at low frequencies (≤3 Hz) resulting in low swim speeds (≤1.5 body lengths per second), and the cost of transport (COT) is often one to four orders of magnitude higher than that of tunas. Furthermore, the impact of body flexibility on high-performance fish swimming remains unknown. Here we design and test a research platform based on yellowfin tuna (Thunnus albacares) to investigate the role of body flexibility and to close the performance gap between robotic and biological systems. This single-motor platform, termed Tunabot Flex, measures 25.5 cm in length. Flexibility is varied through joints in the tail to produce three tested configurations. We find that increasing body flexibility improves self-propelled swimming speeds on average by 0.5 body lengths per second while reducing the minimum COT by 53%. The most flexible configuration swims 4.60 body lengths per second with a tail beat frequency of 8.0 Hz and a COT measuring 18.4 J kg-1m-1. We then compare these results in addition to the midline kinematics, stride length, and Strouhal number with yellowfin tuna data. The COT of Tunabot Flex's most flexible configuration is less than a half-order of magnitude greater than that of yellowfin tuna across all tested speeds. Tunabot Flex provides a new baseline for the development of future bio-inspired underwater vehicles that aim to explore a fish-like, high-performance space and close the gap between engineered robotic systems and fish swimming ability.

Credentialing for eating disorder clinicians: a pathway for implementation of clinical practice standards.

Advances are needed to ensure safe and effective treatment is available for people with eating disorders. Recently developed clinical practice and training standards for mental health professionals and dietitians represent a significant step in this direction by providing a consensus statement on eating disorder treatment as a foundation on which to build competent practice. This commentary argues that a credentialing system could promote implementation of these practice standards through formal recognition of qualifications, knowledge, training and professional activities to meet minimum standards for delivery of safe and effective eating disorder treatment. Drivers for credentialing include the imperative to provide safe and effective care, promotion of workforce development in eating disorder practice and, importantly, readily available and transparent information for referrers, consumers, and carers to identify health professionals credentialed to provide eating disorder treatment. However, a number of factors must be considered to ensure that credentialing does not restrict access to care, such as prohibitively narrow criteria to become credentialed, absence of pathways for education, training, or professional development opportunities, and lack of consultation with or endorsement by stakeholders of the credentialing criteria, application and approval processes, and ways of identifying credentialed practitioners. Further work, including development of credentialing criteria and aligned training opportunities, currently being undertaken by the Australia & New Zealand Academy for Eating Disorders and the National Eating Disorders Collaboration in consultation with stakeholders in the eating disorders sector and health professions will advance understanding of the feasibility of a system of credentialing for eating disorders within Australia and New Zealand. The availability of clinical practice and training standards, supported by implementation pathways, including credentialing of eating disorders practitioners, aim to improve quality of life, reduce financial burden, and close the treatment gap.

Intracranial injuries on computed tomography head scans in infants investigated for suspected physical abuse: a retrospective review.

BACKGROUND: UK national guidelines recommend that investigation of infants (aged <12 months) with suspected physical abuse should always include CT head scans. Such imaging carries small but recognised risks from radiation exposure. Studies report a range of yields for occult intracranial injuries in suspected physical abuse. AIMS: To report the yield of intracranial injuries on CT head scans carried out for suspected physical abuse in infants, compare yields for those presenting with or without signs of head injury and to describe selected clinical and radiological features. METHODS: A retrospective cross-sectional review of case records of infants undergoing skeletal survey for suspected physical abuse in Wessex, England. The main outcome measure was yield of intracranial injuries on CT head scan. RESULTS: In total, n=363 CT head scans were included (n=275 aged <6 months). The overall yield of intracranial injury was 37 (10%). Among 68 infants presenting with neurological signs or skull fractures, yield was 36 (53%) compared with just 1 (0.34%) of 295 without neurological signs or skull fractures. This one intracranial injury was found to be consistent with an accidental fall. Scalp injury was the only additional clinical feature associated with intracranial injury. CONCLUSION: In suspected physical abuse, CT head scans should be carried out in infants who present with neurological signs, skull fractures or scalp injuries. However, in balancing potential risks and benefits, we question the value of performing a CT head scan in every infant investigated for suspected physical abuse.

Short-term Adverse Events With BIC/FTC/TAF: Postmarketing Study.

Bictegravir (BIC)/emtricitabine (FTC)/tenofovir alafenamide (TAF) was Food and Drug Administration approved in February 2018. The paucity of real-world data prompted this retrospective, observational evaluation of discontinuation rates, adverse effects, and virologic control. In a Southern US, predominantly African American overweight population, we found optimal virologic control and low discontinuation rates, with 4% discontinuing BIC/FTC/TAF due to rash, low platelets, loss of appetite, and insomnia.

The Australian Institute of Sport (AIS) and National Eating Disorders Collaboration (NEDC) position statement on disordered eating in high performance sport.

Identification, evaluation and management of disordered eating (DE) is complex. DE exists along the spectrum from optimised nutrition through to clinical eating disorders (EDs). Individual athletes can move back and forth along the spectrum of eating behaviour at any point in time over their career and within different stages of a training cycle. Athletes are more likely to present with DE than a clinical ED. Overall, there is a higher prevalence of DE and EDs in athletes compared with non-athletes. Additionally, athletes participating in aesthetic, gravitational and weight-class sports are at higher risk of DE and EDs than those in sports without these characteristics. The evaluation and management of DE requires a cohesive team of professional practitioners consisting of, at minimum, a doctor, a sports dietitian and a psychologist, termed within this statement as the core multidisciplinary team. The Australian Institute of Sport and the National Eating Disorders Collaboration have collaborated to provide this position statement, containing guidelines for athletes, coaches, support staff, clinicians and sporting organisations. The guidelines support the prevention and early identification of DE, and promote timely intervention to optimise nutrition for performance in a safe, supported, purposeful and individualised manner. This position statement is a call to action to all involved in sport to be aware of poor self-image and poor body image among athletes. The practical recommendations should guide the clinical management of DE in high performance sport.

Functional brain activity is globally elevated by dopamine D2 receptor knockdown in the ventral tegmental area.

The mesocorticolimbic system is comprised of dopaminergic neurons in the ventral tegmental area (VTA) and their projection targets in the ventral striatum, amygdala, prefrontal cortex, and hippocampus, among others. Regulation of dopamine transmission within this system is achieved in part through a negative feedback mechanism via dopamine D2 autoreceptors located on somatodendrites and terminals of VTA dopaminergic neurons. Dysregulation of this mechanism has been implicated in addiction and other psychiatric disorders, although the biological bases for these associations are unclear. In order to elucidate the functional consequences of VTA D2 receptor dysregulation, this study investigated alterations in local cerebral glucose utilization throughout the brain following Drd2 knockdown in the VTA. Male Sprague-Dawley rats received bilateral injections of lentivirus encoding shRNAs against the rat dopamine D2 receptor, scrambled shRNA or phosphate buffered saline. The autoradiographic 2-[14C]deoxyglucose metabolic mapping procedure was conducted 22 days post-infection. Brains were sectioned for autoradiography and glucose utilization was measured across distinct regions throughout the brain. Local cerebral glucose utilization was found to be elevated in the Drd2 knockdown group as compared to control groups. These greater levels of metabolic activity following Drd2 knockdown in the VTA were observed not only in the mesocorticolimbic system and associated dopamine pathways, but also in a global pattern that included many areas with far less concentrated VTA dopamine inputs. This suggests that even a partial Drd2 deletion in the VTA can have widespread consequences and impact information flow in diverse networks that process sensory, cognitive, motor and emotional information.

Regional elevations in microglial activation and cerebral glucose utilization in frontal white matter tracts of rhesus monkeys following prolonged cocaine self-administration.

It has been shown that exposure to cocaine can result in neuroinflammatory responses. Microglia, the resident CNS immune cells, undergo a transition to an activated state when challenged. In rodents, and possibly humans, cocaine exposure activates microglia. The goal of this study was to assess the extent and magnitude of microglial activation in rhesus monkeys with an extensive history of cocaine self-administration. Male rhesus monkeys (N = 4/group) were trained to respond on a fixed-interval 3-min schedule of food or 0.3 mg/kg/injection cocaine presentation (30 reinforcers/session) for 300 sessions. At the end of the final session, monkeys were administered 2-[14C]deoxyglucose intravenously and 45 min later euthanized. Brain sections were used for autoradiographic assessments of glucose utilization and for microglia activation with [3H]PK11195, a marker for the microglial 18-kDa translocator protein. There were no group differences in gray matter [3H]PK11195 binding, while binding was significantly greater in cocaine self-administration animals as compared to food controls in 8 of the 11 white matter tracts measured at the striatal level. Binding did not differ from control at other levels. There were also significant increases in white matter local cerebral glucose utilization at the striatal level, which were positively correlated with [3H]PK11195 binding. The present findings demonstrate an elevation in [3H]PK11195 binding in forebrain white matter tracts of nonhuman primates with a prolonged history of cocaine self-administration. These elevations were also associated with greater cerebral metabolic rates. These data suggest that white matter deficits may contribute to behavioral, motivational, and cognitive impairments observed in cocaine abusers.

Kinematics of swimming of the manta ray: three-dimensional analysis of open-water maneuverability.

For aquatic animals, turning maneuvers represent a locomotor activity that may not be confined to a single coordinate plane, making analysis difficult, particularly in the field. To measure turning performance in a three-dimensional space for the manta ray (Mobula birostris), a large open-water swimmer, scaled stereo video recordings were collected. Movements of the cephalic lobes, eye and tail base were tracked to obtain three-dimensional coordinates. A mathematical analysis was performed on the coordinate data to calculate the turning rate and curvature (1/turning radius) as a function of time by numerically estimating the derivative of manta trajectories through three-dimensional space. Principal component analysis was used to project the three-dimensional trajectory onto the two-dimensional turn. Smoothing splines were applied to these turns. These are flexible models that minimize a cost function with a parameter controlling the balance between data fidelity and regularity of the derivative. Data for 30 sequences of rays performing slow, steady turns showed the highest 20% of values for the turning rate and smallest 20% of turn radii were 42.65±16.66 deg s-1 and 2.05±1.26 m, respectively. Such turning maneuvers fall within the range of performance exhibited by swimmers with rigid bodies.

Morphology of the core fibrous layer of the cetacean tail fluke.

The cetacean tail fluke blades are not supported by any vertebral elements. Instead, the majority of the blades are composed of a densely packed collagenous fiber matrix known as the core layer. Fluke blades from six species of odontocete cetaceans were examined to compare the morphology and orientation of fibers at different locations along the spanwise and chordwise fluke blade axes. The general fiber morphology was consistent with a three-dimensional structure comprised of two-dimensional sheets of fibers aligned tightly in a laminated configuration along the spanwise axis. The laminated configuration of the fluke blades helps to maintain spanwise rigidity while allowing partial flexibility during swimming. When viewing the chordwise sectional face at the leading edge and mid-chord regions, fibers displayed a crossing pattern. This configuration relates to bending and structural support of the fluke blade. The trailing edge core was found to have parallel fibers arranged more dorso-ventrally. The fiber morphology of the fluke blades was dorso-ventrally symmetrical and similar in all species except the pygmy sperm whale (Kogia breviceps), which was found to have additional core layer fiber bundles running along the span of the fluke blade. These additional fibers may increase stiffness of the structure by resisting tension along their long spanwise axis.

Understanding Depressive Symptoms and Psychosocial Stressors on Twitter: A Corpus-Based Study.

BACKGROUND: With a lifetime prevalence of 16.2%, major depressive disorder is the fifth biggest contributor to the disease burden in the United States. OBJECTIVE: The aim of this study, building on previous work qualitatively analyzing depression-related Twitter data, was to describe the development of a comprehensive annotation scheme (ie, coding scheme) for manually annotating Twitter data with Diagnostic and Statistical Manual of Mental Disorders, Edition 5 (DSM 5) major depressive symptoms (eg, depressed mood, weight change, psychomotor agitation, or retardation) and Diagnostic and Statistical Manual of Mental Disorders, Edition IV (DSM-IV) psychosocial stressors (eg, educational problems, problems with primary support group, housing problems). METHODS: Using this annotation scheme, we developed an annotated corpus, Depressive Symptom and Psychosocial Stressors Acquired Depression, the SAD corpus, consisting of 9300 tweets randomly sampled from the Twitter application programming interface (API) using depression-related keywords (eg, depressed, gloomy, grief). An analysis of our annotated corpus yielded several key results. RESULTS: First, 72.09% (6829/9473) of tweets containing relevant keywords were nonindicative of depressive symptoms (eg, "we're in for a new economic depression"). Second, the most prevalent symptoms in our dataset were depressed mood and fatigue or loss of energy. Third, less than 2% of tweets contained more than one depression related category (eg, diminished ability to think or concentrate, depressed mood). Finally, we found very high positive correlations between some depression-related symptoms in our annotated dataset (eg, fatigue or loss of energy and educational problems; educational problems and diminished ability to think). CONCLUSIONS: We successfully developed an annotation scheme and an annotated corpus, the SAD corpus, consisting of 9300 tweets randomly-selected from the Twitter application programming interface using depression-related keywords. Our analyses suggest that keyword queries alone might not be suitable for public health monitoring because context can change the meaning of keyword in a statement. However, postprocessing approaches could be useful for reducing the noise and improving the signal needed to detect depression symptoms using social media.

Body Image in Primary Schools: A pilot evaluation of a primary school intervention program designed by teachers to improve children's body satisfaction.

Body Image in the Primary School (Hutchinson & Calland, 2011) is a body image curriculum that is widely available but has not yet been evaluated. This study evaluates a set of 6 of the 49 available lessons from this curriculum. Seventy-four girls and 70 boys aged 9-10 were recruited from four primary schools in the UK. Schools were randomly allocated into the intervention condition, where students received 6hours of body image lessons, or to lessons as normal. Body esteem was significantly higher among girls in the intervention group, compared to the control group, immediately post intervention, and at 3-month follow-up. Moreover, girls with lowest levels of body esteem at baseline reported the largest gains. Internalization was significantly lower among boys in the control group compared to the intervention group at 3-month follow-up. The pattern of results among the control group raises interesting issues for intervention evaluation.