The actions of dopamine receptors in the guinea pig cochlea.

Dopamine, a major lateral olivocochlear efferent neurotransmitter, exerts both excitatory and inhibitory effects on the central nervous system depending on the receptor involved. We investigated the effects of different dopamine receptors on the cochlea by perilymphatic perfusion with D(1/5), D(2) and D(3) receptor agonists and antagonists and recording neural and hair cell responses (compound action potential - CAP; summating potential - SP) before, during and after perfusions. The D(1/5) agonist resulted in marked suppression of CAP amplitudes whilst leaving SP amplitudes unchanged, suggesting an inhibitory action of these receptors on afferent dendrites. The D(1/5) antagonist had little or no effect, suggesting that there is no influence of tonic dopamine release on these receptors. In contrast, perfusing a D(2) receptor antagonist resulted in marked suppression of CAP suggesting an excitatory action of the receptors and a strong influence of tonic dopamine release on the D(2) receptors. The D(2) agonist had little effect, implying that tonic dopamine release is maximally activating this class of dopamine receptors. D(2) antagonists resulted in reduction of SP, cochlear microphonic and distortion product otoacoustic emission amplitudes, suggesting that D(2) receptor action is not confined to afferent dendrites. Perfusion with D(3) agonists and antagonists had no effect.

Epidemiology of functional neurological disorder, active component, U.S. Armed Forces, 2000-2018.

Functional neurological disorder (FND) is a complex neuropsychiatric disorder characterized by abnormal or atypical sensorimotor, gait, dissociative, or special sensory symptoms in the absence of structural nervous system lesions to explain the symptoms. Several factors are thought to be associated with FND, including comorbid mental health conditions; exposure to physical, emotional, or sexual trauma; young age, and low socioeconomic status. U.S. military service members may be at increased risk for FND because of the prevalence of some of these factors. The current study evaluated the incidence of FND in the U.S. Armed Forces between 2000 and 2018. The overall incidence rate was 29.5 per 100,000 person-years, with the highest rates among women and individuals less than 20 years old. The overall median annual prevalence rate was 37.2 per 100,000 persons. In addition, there were 162 medical evacuations out of the Central Command (CENTCOM) area of responsibility for FND during the study period. Most medical evacuations occurred among men and those with no history of depression or post-traumatic stress disorder (PTSD).

Epidemiology of impulse control disorders and association with dopamine agonist exposure, active component, U.S. Armed Forces, 2014-2018.

Impulse control disorders (ICDs) are a group of behavioral disorders characterized by failure to resist impulsive thoughts and behaviors that can lead to significant adverse social, legal, and financial consequences. ICDs have been associated with previous diagnoses of depression, anxiety, and post-traumatic stress disorder and have been widely recognized as an adverse effect of dopamine agonist (DA) therapy. The epidemiology of these disorders in the U.S. Armed Forces is unknown. The current study evaluated the incidence of ICD diagnoses in the U.S. Armed Forces during 2014-2018. The overall incidence was 13.7 per 10,000 person-years (p-yrs), with the highest rates among females and younger personnel. The current case-control study evaluated the association between DA exposure in the year preceding an incident ICD diagnosis. Although few individuals had received DA therapy in the past year, DA therapy was independently associated with incident ICD diagnosis (adjusted odds ratio [AOR]=2.34; 95% confidence interval [CI]: 1.29-4.24, p<.0001). Previous mental health disorder diagnosis (AOR=12.0; 95% CI: 11.09-12.98, p<.0001) and fibromyalgia (AOR=1.30; 95% CI: 1.14-1.48, p<.0001) were also associated with incident ICD diagnosis. The impact of ICDs on mission readiness, medical evacuation, and deployability should be further evaluated.

SSRI-associated bruxism: A systematic review of published case reports.

PURPOSE OF REVIEW: Antidepressant-associated movement disorders are a well-described phenomenon. However, antidepressant-associated bruxism, jaw pain, or jaw spasm, while reported in dental literature, is less commonly recognized among neurologists. We summarize the clinical features and treatment of antidepressant-associated bruxism and associated jaw pain through a systematic review of case reports. RECENT FINDINGS: Antidepressant-associated bruxism may occur in pediatric and adult patients, most commonly among female patients. Patients may develop symptoms with short-term and long-term antidepressant use. Fluoxetine, sertraline, and venlafaxine were the most commonly reported offending agents. Symptoms may begin within 3-4 weeks of medication initiation and may resolve within 3-4 weeks of drug discontinuation, addition of buspirone, or substitution with another pharmacologic agent. The incidence of this phenomenon is unknown. SUMMARY: Bruxism associated with antidepressant use is an underrecognized phenomenon among neurologists, and may be treated with the addition of buspirone, dose modification, or medication discontinuation.

Assessing the Feasibility of a Social Media to Promote Weight Management Engagement in Adolescents with Severe Obesity: Pilot Study.

BACKGROUND: Severe obesity in adolescents has deleterious physical and psychological complications necessitating frequent multi-disciplinary clinic visits. Greater treatment engagement has been equated with weight-loss. However, traditional medical weight-loss programs for adolescents have high attrition rates. Social media is widely used by adolescents and may enhance medical weight management engagement and success. OBJECTIVE: The first objective was to examine the acceptability and feasibility of using a private social media group as an adjunct to medical weight management in youth ages 14 to 20 years with severe obesity [body mass index (BMI) ≥ 35 kg/m2]. The second objective was to pilot test the use of social media to improve treatment engagement and decrease attrition rates. METHODS: In this single arm, 12 week pre-post study, participants attended individual clinic visits and participated in a moderated private social media group that received nutrition, exercise, and behavior change social media communications or "posts" 3 to 4 times/week. Youth commented and/or liked posts from the moderator and each other. Social media engagement was measured with the number of likes and comments on social media. Clinic attrition was compared, measuring clinic visit attendance 12 weeks prior, during, and after the intervention with mixed linear regression models. Correlations of social media engagement with changes from baseline for BMI, BMI-z score, and psychosocial measures were fit. RESULTS: All 13 enrolled youth completed the study and reported that the group was enjoyable, helpful, reinforced their weight management program, and would recommend using social media to support other youth. The pilot trial was acceptable and feasible. Youth mean weekly engagement (likes + comments) in social media was greater than once a day (8.6 ±3.6). Compared to 12 weeks prior to the intervention, there was no significant decrease in clinic visit attendance at the end of the intervention (M=.231, P=.69) or 12 weeks at the conclusion of the intervention (M=.589, P=.28). Increased social media comments correlated with weight change (r=-.633, P=.04). CONCLUSIONS: This pilot trial demonstrated that the use of social media as an adjunct to medical weight management was feasible and acceptable to adolescents with severe obesity. Based upon these preliminary findings, social media may be an effective way to mitigate attrition from obesity treatment programs, and improve health outcomes in this high-risk population.

Low-intensity repetitive magnetic stimulation lowers action potential threshold and increases spike firing in layer 5 pyramidal neurons in vitro.

Repetitive transcranial magnetic stimulation (rTMS) has become a popular method of modulating neural plasticity in humans. Clinically, rTMS is delivered at high intensities to modulate neuronal excitability. While the high-intensity magnetic field can be targeted to stimulate specific cortical regions, areas adjacent to the targeted area receive stimulation at a lower intensity and may contribute to the overall plasticity induced by rTMS. We have previously shown that low-intensity rTMS induces molecular and structural plasticity in vivo, but the effects on membrane properties and neural excitability have not been investigated. Here we investigated the acute effect of low-intensity repetitive magnetic stimulation (LI-rMS) on neuronal excitability and potential changes on the passive and active electrophysiological properties of layer 5 pyramidal neurons in vitro. Whole-cell current clamp recordings were made at baseline prior to subthreshold LI-rMS (600 pulses of iTBS, n=9 cells from 7 animals) or sham (n=10 cells from 9 animals), immediately after stimulation, as well as 10 and 20min post-stimulation. Our results show that LI-rMS does not alter passive membrane properties (resting membrane potential and input resistance) but hyperpolarises action potential threshold and increases evoked spike-firing frequency. Increases in spike firing frequency were present throughout the 20min post-stimulation whereas action potential (AP) threshold hyperpolarization was present immediately after stimulation and at 20min post-stimulation. These results provide evidence that LI-rMS alters neuronal excitability of excitatory neurons. We suggest that regions outside the targeted region of high-intensity rTMS are susceptible to neuromodulation and may contribute to rTMS-induced plasticity.

Construction and Evaluation of Rodent-Specific rTMS Coils.

Rodent models of transcranial magnetic stimulation (TMS) play a crucial role in aiding the understanding of the cellular and molecular mechanisms underlying TMS induced plasticity. Rodent-specific TMS have previously been used to deliver focal stimulation at the cost of stimulus intensity (12 mT). Here we describe two novel TMS coils designed to deliver repetitive TMS (rTMS) at greater stimulation intensities whilst maintaining spatial resolution. Two circular coils (8 mm outer diameter) were constructed with either an air or pure iron-core. Peak magnetic field strength for the air and iron-cores were 90 and 120 mT, respectively, with the iron-core coil exhibiting less focality. Coil temperature and magnetic field stability for the two coils undergoing rTMS, were similar at 1 Hz but varied at 10 Hz. Finite element modeling of 10 Hz rTMS with the iron-core in a simplified rat brain model suggests a peak electric field of 85 and 12.7 V/m, within the skull and the brain, respectively. Delivering 10 Hz rTMS to the motor cortex of anaesthetized rats with the iron-core coil significantly increased motor evoked potential amplitudes immediately after stimulation (n = 4). Our results suggest these novel coils generate modest magnetic and electric fields, capable of altering cortical excitability and provide an alternative method to investigate the mechanisms underlying rTMS-induced plasticity in an experimental setting.

A novel method for predicting antioxidant activity based on amino acid structure.

Epidemiological studies show a positive correlation between oxidative stress and chronic disease development such as heart disease and cancer. While several antioxidant compounds with varying physical and chemical characteristics are able to reduce oxidative stress in biological systems, relatively few studies have been performed to examine the structural characteristics that produce potent antioxidants. We examined 20 essential and non-essential amino acids using the ORAC assay and used a simplest-case amino acid model to gather data to make predictions regarding the antioxidant activity of non-amino acid compounds; we also tested our findings on chalcone and nitrone data from the current literature. We observed that the sp(2)-hybridized carbons were the most consistent predictors of antioxidant activity in all groups. Valence electron to carbon ratio and length of conjugated double bond groups also emerged as important structural characteristics. Further testing may help to elucidate more accurate trends, as well as nonlinear relationships.

The role of oxidative stress in prostate cancer.

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are not only byproducts of normal cellular metabolism, but also play important roles in cell signaling. However, when the levels of ROS and RNS increase, cells are exposed to oxidative stresses, which activate a variety of mechanisms to allow them to cope with these changes. Studies have shown that oxidative stress conditions play an important role in both the initiation and the progression of prostate cancer by regulating molecules such as DNA, enhancers, transcription factors, and cell cycle regulators. Other studies have shown that antioxidants, molecules that protect cells against oxidative stress, play a role in prevention of prostate cancer. This review summarizes the effects of oxidative stress on the development of prostate cancer and explores the potential of ROS regulators as preventatives for prostate cancer.

Measuring antioxidant capacity using the ORAC and TOSC assays.

Recent epidemiological studies have shown that there may be a link between oxidative stress and the development of several types of chronic diseases. Studies have also shown that diets rich in fruits and vegetables may decrease the incidence of cancer and other chronic diseases. The antioxidant activity of the phytochemicals these foods contain may be partially responsible for the decreased incidence of these diseases in people who regularly consume them. While there are several assays currently used to assess the antioxidant activity of phytochemicals and other antioxidant compounds, two are reviewed here in detail. The first is the oxygen radical absorbance capacity (ORAC) assay, which measures the decrease in fluorescence decay caused by antioxidants, and the second is the total oxyradical scavenging capacity (TOSC) assay, which measures the decrease in ethylene gas production caused by the inhibition of the thermal hydrolysis of ABAP (2,2'-Azobis(2-methyl-(propionamidine) dihydrochloride) by KMBA (alpha-keto-gamma-(methylthio)butyric acid sodium salt) in the presence of antioxidant compounds. These two assays are discussed here, with an in depth review of their methodology and correlation.