Implementation of Vitamin D Screening and Planned Intervention of Supplementation for Deficient Collegiate Athletes of the Rio Grande Valley

In the past decade, studies on vitamin D levels and relationships to orthopaedic patients have increased exponentially worldwide. Journals have established risk factors, proper assessment of vitamin D levels, supplementation standards, and dependent variables that effect prevalence.1 More specifically, many vitamin D studies in the field of orthopaedics and sports medicine have been conducted by analyzing NFL teams and NCAA Division I athletes and dividing the cohorts into player parameters such as age, BMI, race, team position, and supplement type. The results of these studies concluded that there is a large prevalence of vitamin D deficiency amongst athletes and an even higher abnormality of serum vitamin D levels in races with darker skin tones.3 Studies also have been conducted on the benefits of vitamin D and calcium supplementation to prevent over-use injuries like stress fractures.4 An example would be a study showing a 20% lower incidence of stress fractures in navy recruits in a 24-month period.5 But despite such a high level of interest in analyses of vitamin D in athletes, the prevalence of hypovitaminosis D and its influence in overuse injuries like stress fractures within the population of collegiate athletes in the Rio Grande Valley has not yet been investigated

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

Aversive Stimuli Drive Drug Seeking in a State of Low Dopamine Tone

Background Stressors negatively impact emotional state and drive drug seeking, in part, by modulating the activity of the mesolimbic dopamine system. Unfortunately, the rapid regulation of dopamine signaling by the aversive stimuli that cause drug seeking is not well characterized. In a series of experiments, we scrutinized the subsecond regulation of dopamine signaling by the aversive stimulus, quinine, and tested its ability to cause cocaine seeking. Additionally, we examined the midbrain regulation of both dopamine signaling and cocaine seeking by the stress-sensitive peptide, corticotropin releasing factor (CRF). Methods Combining fast-scan cyclic voltammetry with behavioral pharmacology, we examined the effect of intraoral quinine administration on nucleus accumbens dopamine signaling and hedonic expression in 21 male Sprague-Dawley rats. We tested the role of CRF in modulating aversion-induced changes in dopamine concentration and cocaine seeking by bilaterally infusing the CRF antagonist, CP-376395, into the ventral tegmental area (VTA). Results We found that quinine rapidly reduced dopamine signaling on two distinct time scales. We determined that CRF acted in the VTA to mediate this reduction on only one of these time scales. Further, we found that the reduction of dopamine tone and quinine-induced cocaine seeking were eliminated by blocking the actions of CRF in the VTA during the experience of the aversive stimulus. Conclusions These data demonstrate that stress-induced drug seeking can occur in a terminal environment of low dopamine tone that is dependent on a CRF-induced decrease in midbrain dopamine activity

Corticosterone Regulates Both Naturally Occurring and Cocaine‐Induced Dopamine Signaling by Selectively Decreasing Dopamine Uptake

Stressful and aversive events promote maladaptive reward‐seeking behaviors such as drug addiction by acting, in part, on the mesolimbic dopamine system. Using animal models, data from our laboratory and others show that stress and cocaine can interact to produce a synergistic effect on reward circuitry. This effect is also observed when the stress hormone corticosterone is administered directly into the nucleus accumbens (NAc), indicating that glucocorticoids act locally in dopamine terminal regions to enhance cocaine\u27s effects on dopamine signaling. However, prior studies in behaving animals have not provided mechanistic insight. Using fast‐scan cyclic voltammetry, we examined the effect of systemic corticosterone on spontaneous dopamine release events (transients) in the NAc core and shell in behaving rats. A physiologically relevant systemic injection of corticosterone (2 mg/kg i.p.) induced an increase in dopamine transient amplitude and duration (both voltammetric measures sensitive to decreases in dopamine clearance), but had no effect on the frequency of transient release events. This effect was compounded by cocaine (2.5 mg/kg i.p.). However, a second experiment indicated that the same injection of corticosterone had no detectable effect on the dopaminergic encoding of a palatable natural reward (saccharin). Taken together, these results suggest that corticosterone interferes with naturally occurring dopamine uptake locally, and this effect is a critical determinant of dopamine concentration specifically in situations in which the dopamine transporter is pharmacologically blocked by cocaine

Postprandial And Fasting Lipopolysaccharide Levels In Healthy Hispanic Residents Of Southeast Texas With Positive Family History Of Type 2 Diabetes

PURPOSE: Healthy people with a family history (FH+) of type 2 diabetes (T2D) display impaired metabolic and microvascular function prior to glucose intolerance, and are at greater risk for developing T2D. While mechanisms to explain this disparity are lacking, it is possible that intestinal permeability plays a role, as it is also linked with insulin resistance, glucose intolerance, and chronic inflammation. Lipopolysaccharides (LPS) act as an outer membrane component of gram-negative bacteria in intestines and play a role in inflammation and chronic disease when in circulation, thus serving as a surrogate measure of intestinal permeability. However, the link between FH+ health disparities and intestinal permeability has not been studied. Thus, the purpose of this study was to quantify circulating plasma LPS in healthy FH+ and FH-. METHODS: In this cross-sectional study, FH- (n=14) and FH+ (n=18) participants matched for age (24.4 ± 1.6 and 25.0 ± 2.3 respectively) and BMI (25.0 ± 1.1 and 25.0 ± 1.1 years respectively) had blood drawn while fasting, and 60-min after consuming a mixed composition meal to quantify changes in plasma LPS, and had body composition determined via iDXA. Other anthropogenic data were collected. RESULTS: Fasting LPS was lower in FH- than FH+ (p \u3c 0.5, 42.3ng/ml ± 5.3 and 48.1ng/ml ± 6.8 respectively) with postprandial LPS increasing more in FH- than FH+ (p\u3c0.05, +10.3ng/ml ± 3.1 and + 1.4ng/ml ± 3.1 respectively). No group differences (p\u3e0.5) were noted in blood pressure (115/69 and 116/69mmHG) LDL-c (4.3mmol/L and 4.4mmol/L), HDL-c (2.2mmol/L and 2.3mmol/L), body fat (29% and 28%), or android fat (30.4% and 30.7%) between FH- and FH+ groups respectively. CONCLUSION: Disparities noted for increase T2D risk in FH+ have been linked to microvascular and metabolic function, with mechanisms for these remaining elusive. However, differences in circulating LPS suggest varying intestinal permeability in these groups, which may help explain the varying risk for T2D. Further work to characterize intestinal microbiota may advance our understanding of health disparities in this and other high-risk populations

Cardiovascular Responses Differ Between Different Orders of Upper- and Lower-Body Resistance Exercise

Upper-body resistance exercise (RE) induces different cardiovascular responses compared to lower-body RE. However, combination of upper- and lower-body RE with different orders on cardiovascular responses are unclear. PURPOSE: To evaluate the effects of different orders of upper-and lower-body RE on cardiovascular responses in active men. METHODS: Thirteen active men (22±2 years old) participated in the study. Heart rate (HR), systolic and diastolic blood pressure (BP), cardiac output (CO), stroke volume (SV), and total peripheral resistance (TPR) were assessed at rest, 15-20 (R1), and 25-30 (R2) minutes after performing upper- and lower-body RE (UL) or lower- and upper-body RE (LU) for 3 sets of 10 repetitions at 75% 1-repetition maximum with 90-second and 2-minute rests between sets and exercises, respectively. The upper-body RE consisted of pulldown and chest press while lower-body RE consisted of knee extension and knee flexion. A repeated measures ANOVA was used to evaluate the conditions (UL, LU) across time (rest, R1, R2) on cardiovascular responses. RESULTS: There were time-by-condition interactions (p\u3c0.05) for CO and SV such that CO was significantly elevated at R1 and R2 after UL and LU compared to rest while UL had higher CO compared to LU at R1 (UL: rest: 5.68±0.99 L/min; R1: 9.09±1.44 L/min; R2: 7.65±1.87 L/min; and LU: rest: 5.55±0.78 L/min; R1: 8.14±1.65 L/min; R2: 7.23±1.76 L/min). SV was significantly increased after UL at R1 compared to rest and LU (UL: rest: 85.2±16.5 ml/beat; R1: 90.9±14.3 ml/beat; R2: 81.8±18.8 ml/beat; and LU: rest: 84.7±12.7 ml/beat; R1: 83.0±13.9 ml/beat; R2: 78.6±16.2 ml/beat). TPR was significantly (p\u3c0.001) reduced at R1 and R2 compared to rest after UL and LU with greater reduction after UL compared to LU (UL: rest: 0.96±0.27 mmHg•min/L; R1: 0.53±0.16 mmHg•min/L; R2: 0.68±0.22 mmHg•min/L; and LU: rest: 1.03±0.33 mmHg•min/L; R1: 00.67±0.26 mmHg•min/L; R2: 0.77±0.26 mmHg•min/L). HR was significantly (p\u3c0.001) increased at R1 and R2 after UL and LU compared to rest. Systolic BP was significantly (p=0.026) decreased after LU at R1 compared to rest and R2. However, there was no change for diastolic BP. CONCLUSION: These data suggest that UL significantly increases cardiac output and stroke volume than LU which means different orders of RE change cardiovascular responses

Pharmacotherapy for treatment-resistant schizophrenia

Schizophrenia is a disabling mental illness with a lifetime prevalence of 0.7% worldwide and significant, often devastating, consequences on social and occupational functioning. A range of antipsychotic medications are available; however, suboptimal therapeutic response in terms of psychotic symptoms is common and affects up to one-third of people with schizophrenia. Negative symptoms are generally less amenable to treatment. Because of the consequences of inadequate symptom control, effective treatment strategies are required for people with treatment-resistant schizophrenia. Clozapine has been shown to be more effective than other antipsychotics in treatment-resistant populations in several studies; however, the occurrence of adverse effects, some of which are potentially life-threatening, are important limitations. In addition to those who are intolerant to clozapine, only 30% to 50% experience clinically significant symptom improvement. This review describes the recent evidence for treatment strategies for people not responding to nonclozapine antipsychotic agents and people not responding or only partially responding to clozapine

Corticosterone Acts in the Nucleus Accumbens to Enhance Dopamine Signaling and Potentiate Reinstatement of Cocaine Seeking

Stressful life events are important contributors to relapse in recovering cocaine addicts, but the mechanisms by which they influence motivational systems are poorly understood. Studies suggest that stress may “set the stage” for relapse by increasing the sensitivity of brain reward circuits to drug-associated stimuli. We examined the effects of stress and corticosterone on behavioral and neurochemical responses of rats to a cocaine prime after cocaine self-administration and extinction. Exposure of rats to acute electric footshock stress did not by itself reinstate drug-seeking behavior but potentiated reinstatement in response to a subthreshold dose of cocaine. This effect of stress was not observed in adrenalectomized animals, and was reproduced in nonstressed animals by administration of corticosterone at a dose that reproduced stress-induced plasma levels. Pretreatment with the glucocorticoid receptor antagonist RU38486 did not block the corticosterone effect. Corticosterone potentiated cocaine-induced increases in extracellular dopamine in the nucleus accumbens (NAc), and pharmacological blockade of NAc dopamine receptors blocked corticosterone-induced potentiation of reinstatement. Intra-accumbens administration of corticosterone reproduced the behavioral effects of stress and systemic corticosterone. Corticosterone treatment acutely decreased NAc dopamine clearance measured by fast-scan cyclic voltammetry, suggesting that inhibition of uptake2-mediated dopamine clearance may underlie corticosterone effects. Consistent with this hypothesis, intra-accumbens administration of the uptake2 inhibitor normetanephrine potentiated cocaine-induced reinstatement. Expression of organic cation transporter 3, a corticosterone-sensitive uptake2 transporter, was detected on NAc neurons. These findings reveal a novel mechanism by which stress hormones can rapidly regulate dopamine signaling and contribute to the impact of stress on drug intake

Using Global Positioning Systems (GPS) and temperature data to generate time-activity classifications for estimating personal exposure in air monitoring studies: an automated method

Background: Personal exposure studies of air pollution generally use self-reported diaries to capture individuals’ time-activity data. Enhancements in the accuracy, size, memory and battery life of personal Global Positioning Systems (GPS) units have allowed for higher resolution tracking of study participants’ locations. Improved time activity classifications combined with personal continuous air pollution sampling can improve assessments of location-related air pollution exposures for health studies. Methods: Data was collected using a GPS and personal temperature from 54 children with asthma living in Montreal, Canada, who participated in a 10-day personal air pollution exposure study. A method was developed that incorporated personal temperature data and then matched a participant’s position against available spatial data (i.e., road networks) to generate time-activity categories. The diary-based and GPS-generated time-activity categories were compared and combined with continuous personal PM2.5 data to assess the impact of exposure misclassification when using diary based methods. Results: There was good agreement between the automated method and the diary method; however, the automated method (means: outdoors = 5.1%, indoors other =9.8%) estimated less time spent in some locations compared to the diary method (outdoors = 6.7%, indoors other = 14.4%). Agreement statistics (AC1 = 0.778) suggest ‘good’ agreement between methods over all location categories. However, location categories (Outdoors and Transit) where less time is spent show greater disagreement: e.g., mean time “Indoors Other” using the time-activity diary was 14.4% compared to 9.8% using the automated method. While mean daily time “In Transit” was relatively consistent between the methods, the mean daily exposure to PM2.5 while “In Transit” was 15.9 μg/m3 using the automated method compared to 6.8 μg/m3 using the daily diary. Conclusions: Mean times spent in different locations as categorized by a GPS-based method were comparable to those from a time-activity diary, but there were differences in estimates of exposure to PM2.5 from the two methods. An automated GPS-based time-activity method will reduce participant burden, potentially providing more accurate and unbiased assessments of location. Combined with continuous air measurements, the higher resolution GPS data could present a different and more accurate picture of personal exposures to air pollution