Enabling usable science takes a community: Using our roles as funders to catalyze change.

Calls to support co-designed and usable science to inform management of natural resources are growing. Making the shift will require diverse collaborations between those who hold, share, and use knowledge.

Targeting Molecular Mechanisms of Obesity- and Type 2 Diabetes Mellitus-Induced Skeletal Muscle Atrophy with Nerve Growth Factor.

Skeletal muscle plays a critical role in metabolic diseases, such as obesity and type 2 diabetes mellitus (T2DM). Muscle atrophy, characterized by a decrease in muscle mass and function, occurs due to an imbalance between the rates of muscle protein synthesis and degradation. This study aimed to investigate the molecular mechanisms that lead to muscle atrophy in obese and T2DM mouse models. Additionally, the effect of nerve growth factor (NGF) on the protein synthesis and degradation pathways was examined. Male mice were divided into three groups: a control group that was fed a standard chow diet, and two experimental groups that were fed a Western diet. After 8 weeks, the diabetic group was injected with streptozotocin to induce T2DM. Each group was then further divided into NGF-treated or non-treated control group. In the gastrocnemius muscles of the Western diet group, increased expressions of myostatin, autophagy markers, and ubiquitin ligases were observed. Skeletal muscle tissue morphology indicated signs of muscle atrophy in both obese and diabetic mice. The NGF-treated group showed a prominent decrease in the protein levels of myostatin and autophagy markers. Furthermore, the NGF-treated group showed an increased Cyclin D1 level. Western diet-induced obesity and T2DM may be linked to muscle atrophy through upregulation of myostatin and subsequent increase in the ubiquitin and autophagy systems. Moreover, NGF treatment may improve muscle protein synthesis and cell cycling.

Measuring Dynamic Glycosomal pH Changes in Living Trypanosoma brucei.

Glucose metabolism is critical for the African trypanosome, Trypanosoma brucei, as an essential metabolic process and regulator of parasite development. Little is known about the cellular responses generated when environmental glucose levels change. In both bloodstream and procyclic form (insect stage) parasites, glycosomes house most of glycolysis. These organelles are rapidly acidified in response to glucose deprivation, which likely results in the allosteric regulation of glycolytic enzymes such as hexokinase. In previous work, localizing the chemical probe used to make pH measurements was challenging, limiting its utility in other applications. This paper describes the development and use of parasites that express glycosomally localized pHluorin2, a heritable protein pH biosensor. pHluorin2 is a ratiometric pHluorin variant that displays a pH (acid)-dependent decrease in excitation at 395 nm while simultaneously yielding an increase in excitation at 475 nm. Transgenic parasites were generated by cloning the pHluorin2 open reading frame into the trypanosome expression vector pLEW100v5, enabling inducible protein expression in either lifecycle stage. Immunofluorescence was used to confirm the glycosomal localization of the pHluorin2 biosensor, comparing the localization of the biosensor to the glycosomal resident protein aldolase. The sensor responsiveness was calibrated at differing pH levels by incubating cells in a series of buffers that ranged in pH from 4 to 8, an approach we have previously used to calibrate a fluorescein-based pH sensor. We then measured pHluorin2 fluorescence at 405 nm and 488 nm using flow cytometry to determine glycosomal pH. We validated the performance of the live transgenic pHluorin2-expressing parasites, monitoring pH over time in response to glucose deprivation, a known trigger of glycosomal acidification in PF parasites. This tool has a range of potential applications, including potentially being used in high-throughput drug screening. Beyond glycosomal pH, the sensor could be adapted to other organelles or used in other trypanosomatids to understand pH dynamics in the live cell setting.

It's all in the timing: Delayed feedback in autism may weaken predictive mechanisms during contour integration.

Humans rely on predictive mechanisms during visual processing to efficiently resolve incomplete or ambiguous sensory signals. While initial low-level sensory data are conveyed by feedforward connections, feedback connections are believed to shape sensory processing through conveyance of statistical predictions based on prior exposure to stimulus configurations. Individuals with autism spectrum disorder (ASD) show biases in stimulus processing toward parts rather than wholes, suggesting their sensory processing may be less shaped by statistical predictions acquired through prior exposure to global stimulus properties. Investigations of illusory contour (IC) processing in neurotypical (NT) adults have established a well-tested marker of contour integration characterized by a robust modulation of the visually evoked potential (VEP) - the IC-effect - that occurs over lateral occipital scalp during the timeframe of the N1 component. Converging evidence strongly supports the notion that this IC-effect indexes a signal with significant feedback contributions. Using high-density VEPs, we compared the IC-effect in 6-17-year-old children with ASD (n=32) or NT development (n=53). Both groups of children generated an IC-effect that was equivalent in amplitude. However, the IC-effect notably onset 21ms later in ASD, even though timing of initial VEP afference was identical across groups. This suggests that feedforward information predominated during perceptual processing for 15% longer in ASD compared to NT children. This delay in the feedback dependent IC-effect, in the context of known developmental differences between feedforward and feedback fibers, suggests a potential pathophysiological mechanism of visual processing in ASD, whereby ongoing stimulus processing is less shaped by statistical prediction mechanisms.

Enolase Inhibitors as Early Lead Therapeutics against Trypanosoma brucei.

Glucose metabolism is critical for the African trypanosome, Trypanosoma brucei, serving as the lone source of ATP production for the bloodstream form (BSF) parasite in the glucose-rich environment of the host blood. Recently, phosphonate inhibitors of human enolase (ENO), the enzyme responsible for the interconversion of 2-phosphoglycerate (2-PG) to phosphoenolpyruvate (PEP) in glycolysis or PEP to 2-PG in gluconeogenesis, have been developed for the treatment of glioblastoma multiforme (GBM). Here, we have tested these agents against T. brucei ENO (TbENO) and found the compounds to be potent enzyme inhibitors and trypanocides. For example, (1-hydroxy-2-oxopyrrolidin-3-yl) phosphonic acid (deoxy-SF2312) was a potent enzyme inhibitor (IC50 value of 0.60 ± 0.23 µM), while a six-membered ring-bearing phosphonate, (1-hydroxy-2-oxopiperidin-3-yl) phosphonic acid (HEX), was less potent (IC50 value of 2.1 ± 1.1 µM). An analog with a larger seven-membered ring, (1-hydroxy-2-oxoazepan-3-yl) phosphonic acid (HEPTA), was not active. Molecular docking simulations revealed that deoxy-SF2312 and HEX had binding affinities of -6.8 and -7.5 kcal/mol, respectively, while the larger HEPTA did not bind as well, with a binding of affinity of -4.8 kcal/mol. None of these compounds were toxic to BSF parasites; however, modification of enzyme-active phosphonates through the addition of pivaloyloxymethyl (POM) groups improved activity against T. brucei, with POM-modified (1,5-dihydroxy-2-oxopyrrolidin-3-yl) phosphonic acid (POMSF) and POMHEX having EC50 values of 0.45 ± 0.10 and 0.61 ± 0.08 µM, respectively. These findings suggest that HEX is a promising lead against T. brucei and that further development of prodrug HEX analogs is warranted.

Severely Attenuated Visual Feedback Processing in Children on the Autism Spectrum.

Individuals on the autism spectrum often exhibit atypicality in their sensory perception, but the neural underpinnings of these perceptual differences remain incompletely understood. One proposed mechanism is an imbalance in higher-order feedback re-entrant inputs to early sensory cortices during sensory perception, leading to increased propensity to focus on local object features over global context. We explored this theory by measuring visual evoked potentials during contour integration as considerable work has revealed that these processes are largely driven by feedback inputs from higher-order ventral visual stream regions. We tested the hypothesis that autistic individuals would have attenuated evoked responses to illusory contours compared with neurotypical controls. Electrophysiology was acquired while 29 autistic and 31 neurotypical children (7-17 years old, inclusive of both males and females) passively viewed a random series of Kanizsa figure stimuli, each consisting of four inducers that were aligned either at random rotational angles or such that contour integration would form an illusory square. Autistic children demonstrated attenuated automatic contour integration over lateral occipital regions relative to neurotypical controls. The data are discussed in terms of the role of predictive feedback processes on perception of global stimulus features and the notion that weakened "priors" may play a role in the visual processing anomalies seen in autism.SIGNIFICANCE STATEMENT Children on the autism spectrum differ from typically developing children in many aspects of their processing of sensory stimuli. One proposed mechanism for these differences is an imbalance in higher-order feedback to primary sensory regions, leading to an increased focus on local object features rather than global context. However, systematic investigation of these feedback mechanisms remains limited. Using EEG and a visual illusion paradigm that is highly dependent on intact feedback processing, we demonstrated significant disruptions to visual feedback processing in children with autism. This provides much needed experimental evidence that advances our understanding of the contribution of feedback processing to visual perception in autism spectrum disorder.

The Role of Dietary Antioxidants and Their Potential Mechanisms in Alzheimer's Disease Treatment.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with cognitive decline and characterized by amyloid-ß plaques and neurofibrillary tau tangles. Although AD's exact pathophysiology remains unclear, oxidative stress is known to play a role in the neurodegenerative process. Since no curative treatment exists, antioxidants represent a potential treatment for AD due to their ability to modulate oxidative stress. Therefore, this review aims to examine the impact of antioxidant supplementation and its potential mechanisms on cognitive function. The review primarily discusses research articles published between 2012 and 2022 reporting the results of clinical trials involving antioxidant supplementation on cognitive function in individuals with AD. Antioxidant supplementation included probiotics, selenium, melatonin, resveratrol, rosmarinic acid, carotenoids, curcumin, vitamin E, and coenzyme Q. While the studies included in this review did not provide much evidence for the beneficial role of antioxidant supplements on cognitive function in AD, the results varied from antioxidant to antioxidant and among trials examining the same antioxidant. Furthermore, many of the studies' findings face several limitations, including short trial durations, small sample sizes, and a lack of diversity among study participants. As a result, more research is required to examine the impact of antioxidant supplementation on cognitive function in AD.

The Role of Diet and Dietary Patterns in Parkinson's Disease.

Parkinson's Disease (PD) is a neurodegenerative disorder associated with diminished nutrition status and decreased quality of life. While the prevalence of PD is expected to increase, no preventative or curative therapy for PD exists at this time. Although nutrition and diet represent modifiable risk factors for reducing chronic disease risk, research on the impact of single nutrients on PD has yielded mixed results. As a result, this single-nutrient approach may be the driving force behind the inconsistency, and a holistic dietary approach may overcome this inconsistency by accounting for the interactions between nutrients. The following review aims to examine the impact of a generally healthy dietary pattern, the protein-restricted diet (PRD), the ketogenic diet (KD), the Mediterranean diet (MD), and the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet on PD risk, progression, and severity. While most of the included studies support the role of diet and dietary patterns in reducing the risk of PD or alleviating PD severity, the inconsistent results and need for further evidence necessitate more research being conducted before making dietary recommendations. Research on the potential beneficial effects of dietary patterns on PD should also investigate potential risks.

Hypothetical proteins play a role in stage conversion, virulence, and the stress response in the Entamoeba species.

Entamoeba histolytica is a protozoan parasite that causes amoebic dysentery and amoebic liver abscess in humans, affecting millions of people worldwide. This pathogen possesses a two-stage life cycle consisting of an environmentally stable cyst and a pathogenic amoeboid trophozoite. As cysts can be ingested from contaminated food and water, this parasite is prevalent in underdeveloped countries and poses a significant health burden. Until recently there was no reliable method for inducing stage conversion in E. histolytica in vitro. As such, the reptilian pathogen, Entamoeba invadens, has long-served as a surrogate. Much remains unclear about stage conversion in these parasites and current treatments for amoebiasis are lacking, as they cause severe side effects. Therefore, new therapeutic strategies are needed. The genomes of these parasites remain enigmatic as approximately 54% of E. histolytica genes and 66% of E. invadens genes are annotated as hypothetical proteins. In this study, we characterized two hypothetical proteins in the Entamoeba species, EIN_059080, in E. invadens, and its homolog, EHI_056700, in the human pathogen, E. histolytica. EHI_056700 has no homolog in the human host. We used an RNAi-based silencing system to reduce expression of these genes in E. invadens and E. histolytica trophozoites. Loss of EIN_059080 resulted in a decreased rate of encystation and an increased rate of erythrophagocytosis, an important virulence function. Additionally, mutant parasites were more susceptible to oxidative stress. Similarly, loss of EHI_056700 in E. histolytica trophozoites resulted in increased susceptibility to oxidative stress and glucose deprivation, but not to nitrosative stress. Unlike the E. invadens mutants, E. histolytica parasites with decreased reduced expression of EHI_056700 exhibited a decreased rate of erythrophagocytosis of and adhesion to host cells. Taken together, these data suggest that these hypothetical proteins play a role in stage conversion, virulence, and the response to stress in the Entamoebae. Since parasites with reduced expression of EHI_056700 show decreased virulence functions and increased susceptibility to physiologically relevant stressors, EHI_056700 may represent a possible therapeutic target for the treatment of amoebiasis.

Attentional influences on neural processing of biological motion in typically developing children and those on the autism spectrum.

BACKGROUND: Biological motion imparts rich information related to the movement, actions, intentions and affective state of others, which can provide foundational support for various aspects of social cognition and behavior. Given that atypical social communication and cognition are hallmark symptoms of autism spectrum disorder (ASD), many have theorized that a potential source of this deficit may lie in dysfunctional neural mechanisms of biological motion processing. Synthesis of existing literature provides some support for biological motion processing deficits in autism spectrum disorder, although high study heterogeneity and inconsistent findings complicate interpretation. Here, we attempted to reconcile some of this residual controversy by investigating a possible modulating role for attention in biological motion processing in ASD. METHODS: We employed high-density electroencephalographic recordings while participants observed point-light displays of upright, inverted and scrambled biological motion under two task conditions to explore spatiotemporal dynamics of intentional and unintentional biological motion processing in children and adolescents with ASD (n = 27), comparing them to a control cohort of neurotypical (NT) participants (n = 35). RESULTS: Behaviorally, ASD participants were able to discriminate biological motion with similar accuracy to NT controls. However, electrophysiologic investigation revealed reduced automatic selective processing of upright biologic versus scrambled motion stimuli in ASD relative to NT individuals, which was ameliorated when task demands required explicit attention to biological motion. Additionally, we observed distinctive patterns of covariance between visual potentials evoked by biological motion and functional social ability, such that Vineland Adaptive Behavior Scale-Socialization domain scores were differentially associated with biological motion processing in the N1 period in the ASD but not the NT group. LIMITATIONS: The cross-sectional design of this study does not allow us to definitively answer the question of whether developmental differences in attention to biological motion cause disruption in social communication, and the sample was limited to children with average or above cognitive ability. CONCLUSIONS: Together, these data suggest that individuals with ASD are able to discriminate, with explicit attention, biological from non-biological motion but demonstrate diminished automatic neural specificity for biological motion processing, which may have cascading implications for the development of higher-order social cognition.

The strength of feedback processing is associated with resistance to visual backward masking during Illusory Contour processing in adult humans.

Re-entrant feedback processing is a key mechanism of visual object-recognition, especially under compromised viewing conditions where only sparse information is available and object features must be interpolated. Illusory Contour stimuli are commonly used in conjunction with Visual Evoked Potentials (VEP) to study these filling-in processes, with characteristic modulation of the VEP in the ∼100-150 ms timeframe associated with this re-entrant processing. Substantial inter-individual variability in timing and amplitude of feedback-related VEP modulation is observed, raising the question whether this variability might underlie inter-individual differences in the ability to form strong perceptual gestalts. Backward masking paradig ms have been used to study inter-individual variance in the ability to form robust object perceptions before processing of the mask interferes with object-recognition. Some individuals recognize objects when the time between target object and mask is extremely short, whereas others struggle to do so even at longer target-to-mask intervals. We asked whether timing and amplitude of feedback-related VEP modulations were associated with individual differences in resistance to backward masking. Participants (N=40) showed substantial performance variability in detecting Illusory Contours at intermediate target-to-mask intervals (67 ms and 117 ms), allowing us to use kmeans clustering to divide the population into four performance groups (poor, low-average, high-average, superior). There was a clear relationship between the amplitude (but not the timing) of feedback-related VEP modulation and Illusory Contour detection during backward masking. We conclude that individual differences in the strength of feedback processing in neurotypical humans lead to differences in the ability to quickly establish perceptual awareness of incomplete visual objects.

Individuals With Autism Have No Detectable Deficit in Neural Markers of Prediction Error When Presented With Auditory Rhythms of Varied Temporal Complexity.

The brain's ability to encode temporal patterns and predict upcoming events is critical for speech perception and other aspects of social communication. Deficits in predictive coding may contribute to difficulties with social communication and overreliance on repetitive predictable environments in individuals with autism spectrum disorder (ASD). Using a mismatch negativity (MMN) task involving rhythmic tone sequences of varying complexity, we tested the hypotheses that (1) individuals with ASD have reduced MMN response to auditory stimuli that deviate in presentation timing from expected patterns, particularly as pattern complexity increases and (2) amplitude of MMN signal is inversely correlated with level of impairment in social communication and repetitive behaviors. Electroencephalography was acquired as individuals (age 6-21 years) listened to repeated five-rhythm tones that varied in the Shannon entropy of the rhythm across three conditions (zero, medium-1 bit, and high-2 bit entropy). The majority of the tones conformed to the established rhythm (standard tones); occasionally the fourth tone was temporally shifted relative to its expected time of occurrence (deviant tones). Social communication and repetitive behaviors were measured using the Social Responsiveness Scale and Repetitive Behavior Scale-Revised. Both neurotypical controls (n = 19) and individuals with ASD (n = 21) show stepwise decreases in MMN as a function of increasing entropy. Contrary to the result forecasted by a predictive coding hypothesis, individuals with ASD do not differ from controls in these neural mechanisms of prediction error to auditory rhythms of varied temporal complexity, and there is no relationship between these signals and social communication or repetitive behavior measures. LAY SUMMARY: We tested the idea that the brain's ability to use previous experience to influence processing of sounds is weaker in individuals with autism spectrum disorder (ASD) than in neurotypical individuals. We found no difference between individuals with ASD and neurotypical controls in brain wave responses to sounds that occurred earlier than expected in either simple or complex rhythms. There was also no relationship between these brain waves and social communication or repetitive behavior scores.

Kinome scale profiling of venom effects on cancer cells reveals potential new venom activities.

The search for novel and relevant cancer therapeutics is continuous and ongoing. Cancer adaptations, resulting in therapeutic treatment failures, fuel this continuous necessity for new drugs to novel targets. Recently, researchers have started to investigate the effect of venoms and venom components on different types of cancer, investigating their mechanisms of action. Receptor tyrosine kinases (RTKs) comprise a family of highly conserved and functionally important druggable targets for cancer therapy. This research exploits the novelty of complex venom mixtures to affect phosphorylation of the epidermal growth factor receptor (EGFR) and related RTK family members, dually identifying new activities and unexplored avenues for future cancer and venom research. Six whole venoms from diverse species taxa, were evaluated for their ability to illicit changes in the phosphorylated expression of a panel of 49 commonly expressed RTKs. The triple negative breast cancer cell line MDA-MB-468 was treated with optimised venom doses, pre-determined by SDS PAGE and Western blot analysis. The phosphorylated expression levels of 49 RTKs in response to the venoms were assessed with the use of Human Phospho-RTK Arrays and analysed using ImageLab 5.2.1 analysis software (BioRad). Inhibition of EGFR phosphorylation occurred with treatment of venom from Acanthoscurria geniculata (Theraphosidae), Heterometrus swammerdami (Scorpionidae), Crotalus durissus vegrandis (Crotalidae) and Naja naja (Elapidae). Western green mamba Dendroaspis viridis venom increased EGFR phosphorylation. Eph, HGFR and HER were the most affected receptor families by venoms. Whilst the importance of these changes in terms of effect on MDA-MB-468 cells' long-term viability and functionality are still unclear, the findings present exciting opportunities for further investigation as potential drug targets in cancer and as tools to understand better how these pathways interact.

Mapping BOLD Activation by Pharmacologically Evoked Tremor in Swine.

Harmaline-induced tremor is one of the most commonly utilized disease models for essential tremor (ET). However, the underlying neural networks involved in harmaline-induced tremor and the degree to which these are a representative model of the pathophysiologic mechanism of ET are incompletely understood. In this study, we evaluated the functional brain network effects induced by systemic injection of harmaline using pharmacological functional magnetic resonance imaging (ph-fMRI) in the swine model. With harmaline administration, we observed significant activation changes in cerebellum, thalamus, and inferior olivary nucleus (ION). In addition, inter-regional correlations in activity between cerebellum and deep cerebellar nuclei and between cerebellum and thalamus were significantly enhanced. These harmaline-induced effects gradually decreased with repeated administration of drug, replicating the previously demonstrated 'tolerance' effect. This study demonstrates that harmaline-induced tremor is associated with activity changes in brain regions previously implicated in humans with ET. Thus, harmaline-induction of tremor in the swine may be a useful model to explore the neurological effects of novel therapeutic agents and/or neuromodulation techniques for ET.

pH: the silent variable significantly impacting meiotic spindle assembly in mouse oocytes.

RESEARCH QUESTION: Temperature fluctuation negatively impacts the assembly and function of the meiotic spindle, but does pH have a similar effect? DESIGN: Polarized light microscopy was used to study the spindle in living mouse oocytes under different pH conditions. Female mice (n = 53) were superovulated, and oocytes collected, denuded and allocated to treatment groups. All experiments were performed at 37°C, and standard bicarbonate-buffered medium was used either pre-equilibrated in 6% CO2 or unequilibrated (in ambient CO2). Mean oocyte spindle retardance was measured over time in response to changing pH. Spindles were also assessed to understand whether this effect was reversible, by using a fixed pH in a zwitterionic buffer. RESULTS: The data show the spindle is impacted by pH fluctuation, with mean retardance significantly higher at pH 7.4-7.5 than at the point of media equilibration (P < 0.001). This effect was found to be reversible; retardance significantly decreased after transition of the oocytes from pH 7.43 or pH 7.53 back to the original pre-equilibration pH of 7.32 (P < 0.05). CONCLUSIONS: This study has shown that the meiotic spindle in mouse oocytes is highly sensitive to changes in oocyte culture media pH. If comparable in humans, this has significance as to the pH level of culture media currently used in assisted reproductive technology clinics worldwide, and reinforces the requirement for stringent control over extrinsic variables in the IVF laboratory.

Scoping Review of Dance for Adults With Fibromyalgia: What Do We Know About It?

BACKGROUND: Fibromyalgia is a chronic disorder characterized by widespread muscular tenderness, pain, fatigue, and cognitive difficulties. Nonpharmacological treatment options, such as physical activity, are important for people with fibromyalgia. There are strong recommendations to support engagement in physical activity for symptom management among adults with fibromyalgia. Dance is a mode of physical activity that may allow individuals with fibromyalgia to improve their physical function, health, and well-being. Dance has the potential to promote improved pain processing while simultaneously providing the health and social benefits of engaging in physical activity that contributes to symptom management and overall function rehabilitation. However, we are unaware of current evidence on dance as a nonpharmacological/physical activity intervention for adults with fibromyalgia. OBJECTIVE: The aims of this study were to understand how dance is used therapeutically by individuals with fibromyalgia; to examine the extent, range and nature of research activity in the area; and to determine the value of undertaking a systematic review of interventions. METHODS: We used and adapted the Arksey and O'Malley scoping framework. The search strategy involved a comprehensive search of main health and electronic social databases, trial registries and grey literature without language limits. Pairs of reviewers independently screened and extracted data and evaluated the methodological quality of randomized control trials. RESULTS: Twenty-one unique records for 13 studies met inclusion criteria; the studies included mostly middle-aged women. Types of dance included were aerobic dance, belly dance, dance movement therapy, biodanza and Zumba. Intervention parameters were different among studies. Frequency varied between one to three times a week; all were done in small group settings. Studies evaluated a variety of outcomes in the symptoms, wellness, psychosocial, physical functioning, balance and fitness categories; no studies evaluated the safety or adverse events systematically which is a major weakness of the literature. CONCLUSIONS: There are few studies in the field of dance and fibromyalgia, suggesting research is in its infancy but slowly growing. They are of European and South American origin, focusing on female participants and a limited number of dance modes. Because the body of literature is small, of low quality and highly heterogeneous, we concluded that a systematic review of interventions on dance is not warranted at this time.

Development of Harmaline-induced Tremor in a Swine Model.

Background: In the field of translational neuroscience research, it is critical to utilize a large animal model to test the feasibility, safety, and functionality of novel therapies. Here, we describe a protocol for the development of a large animal model of tremor. Methods: In a pig model, tremor was induced with harmaline and measured with wireless accelerometers attached to the limbs. Three different doses of harmaline were tested and three repetitive injections were made at 72-hour intervals. To fully characterize the drug-induced tremor, onset time, tremor amplitude, maintained duration, and peak tremor frequency were analyzed. Results: Harmaline-induced tremor appeared immediately following intravenous injection of harmaline. Tremor was maintained over 2 hours. Its frequency was 10-16 Hz, which was independent of doses. Dose-dependent responses were observed in tremor amplitude, triggering time, and tremor-maintained duration. Repetitive injection of harmaline desensitized the harmaline effect. Discussion: We provide a detailed protocol for training, drug injection, device selection, and tremor recording optimized to create a swine model of tremor with harmaline. Our protocol provides reliable tremor in pigs and suggests pig as a valid translational large animal model of tremor.

The role of smartphones in encouraging physical activity in adults.

Lack of physical activity is a global public health issue. Behavioral change interventions utilizing smartphone applications (apps) are considered a potential solution. The purpose of this literature review was to: 1) determine whether smartphone-based interventions encourage the initiation of, and participation in, physical activity; 2) explore the success of interventions in different populations; and 3) examine the key factors of the interventions that successfully encouraged physical activity. Eight databases (Medline, Scopus, EBM Reviews-Cochrane Central Register of Controlled Trials, EBM Reviews-Cochrane Database of Systematic Reviews, PsycInfo, SportDISCUS, CINAHL, and EMBASE) were searched and studies reporting physical activity outcomes following interventions using smartphone apps in adults were included in the narrative review. Results were mixed with eight studies reporting increased physical activity and ten reporting no change. Interventions did not appear to be successful in specific populations defined by age, sex, country, or clinical diagnosis. There was no conclusive evidence that a specific behavioral theory or behavioral change technique was superior in eliciting behavioral change. The literature remains limited primarily to short-term studies, many of which are underpowered feasibility or pilot studies; therefore, many knowledge gaps regarding the effectiveness of smartphone apps in encouraging physical activity remain. Robust studies that can accommodate the fast pace of the technology industry are needed to examine outcomes in large populations.

Dance for Adults With Fibromyalgia-What Do We Know About It? Protocol for a Scoping Review.

BACKGROUND: Fibromyalgia is a chronic disorder characterized by widespread muscular tenderness, pain, fatigue, and cognitive difficulties. Nonpharmacological treatment options, such as physical activity, are important for people with fibromyalgia. There are strong recommendations to support engagement in physical activity for symptom management among adults with fibromyalgia. Dance is a mode of physical activity that may allow individuals with fibromyalgia to improve their physical function, health, and well-being. Dance has the potential to promote improved pain processing while simultaneously providing the health and social benefits of engaging in physical activity that contributes to symptom management. However, we are unaware of current evidence on dance as a nonpharmacological/physical activity intervention for adults with fibromyalgia. OBJECTIVE: The aims of the study are to provide an overview of the extant evidence to understand how dance is used for individuals with fibromyalgia; to examine the extent, range, and nature of research activity in the area; and to determine the value of undertaking a full systematic review. METHODS: Scoping reviews are useful to comprehensively and systematically map the literature and identify key evidence, or research gaps. The search strategy will involve electronic databases including Medline, Embase, Cochrane Library, PsycInfo, Cumulative Index of Nursing and Allied Health Literature (CINAHL), Literature in the Health Sciences in Latin America and the Caribbean (LILACS), Allied and Complementary Medicine (AMED), International Bibliography of Theatre and Dance, Physiotherapy Evidence Database (PEDro), Trip, Proquest Theses/Dissertations, Web of Science, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. The study will be mapped in seven stages: (1) identifying the research questions, (2) identifying relevant studies, (3) selecting the studies, (4) charting the data, (5) collating, summarizing and reporting the results, (6) consulting, and (7) disseminating the knowledge. RESULTS: The search, title, and abstract are now completed; full text screening was carried out and authors are awaiting interlibrary loans and translations. Data extraction will start shortly after full text 'screening' is completed. Completion is expected in Fall 2017. CONCLUSIONS: To our knowledge this will be the first attempt to systematically identify knowledge of dance as a potential intervention for adults with fibromyalgia. This scoping review offers a feasible means for describing the evidence specific to dance and fibromyalgia; results will provide unique insights concerning the breadth and depth of literature in the area. An analysis of this body of literature as a whole may reveal new research directions or unknown ways this intervention could strengthen current management approaches of the disease.

A Qualitative Study of the Context of Child and Adolescent Substance Use Initiation and Patterns of Use in the First Year for Early and Later Initiators.

Individuals who initiate substance use before high school are at higher risk of negative outcomes. Eighty-six young adults between the ages of 18 and 28 participated in semi-structured qualitative interviews focused on the circumstances surrounding participants' first use of substances and their pattern of use in the year following initiation in order to investigate similarities and differences between early versus later initiators. Initiation and use among early initiators were more likely to be encouraged by poor parental monitoring or active facilitation of use by parents. Early initiators were more likely to report risky patterns of use such as daily use and using alone. The data suggest that interventions targeting this population should focus on improving parental monitoring and decreasing positive parental attitudes toward adolescent substance use and efforts to increase identification and intervention by middle school staff to reach youth from high-risk families.