Presynaptic D1 dopamine receptors facilitate glutamatergic neurotransmission in the rat globus pallidus

The effects of D1/5 dopamine agonists on spontaneous excitatory postsynaptic currents (sEPSCs) were studied in neurons of the rat globus pallidus using whole-cell recordings in the presence of TTX and bicuculline. In this condition, CNQX abolished the sEPSCs, indicating that they were solely mediated by AMPA receptors. SKF 38393, a D1-like agonist, increased the frequency but not the amplitude of the sEPSCs, suggesting a presynaptic site of action. The increase in frequency was blocked by SCH 23390, a D1/5 antagonist. Quinpirole, a D2-like agonist, decreased the frequency but did not affect the amplitude of the synaptic currents. SKF 38393 increased the frequency of sEPSCs currents, even in presence of quinpirole, indicating that D1/5- and D2-like receptors independently modulate glutamate release upon a single neuron. The results suggest that the dopaminergic control of the glutamate transmission in the globus pallidus may play a role in processing cortical information in the indirect pathway of the basal ganglia.     

Aversive Learning in Adolescents: Modulation by Amygdala–Prefrontal and Amygdala–Hippocampal Connectivity and Neuroticism

Neuroticism involves a tendency for enhanced emotional and cognitive processing of negative affective stimuli and a propensity to worry and be anxious. It is known that this trait modulates fear learning and the activation of brain regions involved in it such as the amygdala, hippocampus, and prefrontal cortex and their connectivity. Thirty-nine (21 female) 14-year-old healthy adolescents participated in functional magnetic resonance imaging (fMRI) of aversive pavlovian differential delay conditioning. An unpleasant sound served as unconditioned stimulus (US) and pictures of neutral male faces as conditioned stimuli (CS+ followed by the US in 50% of the cases; CS− never followed by the US). During acquisition (CS+/− differentiation), higher levels of neuroticism were associated with a stronger interaction between the right amygdala and the right hippocampus as well as the right amygdala and prefrontal cortical regions, specifically ventromedial prefrontal cortex, dorsolateral prefrontal cortex, and anterior cingulate cortex. The association of stronger conditionability of fear and connectivity of brain regions related to consolidation of fear associations and neuroticism points to underlying mechanisms of the enhanced propensity for anxiety disorders in highly neurotic participants. This is especially important in adolescence, a vulnerable time for the onset of mental disorders such as anxiety disorders.     

Evaluation of magnesium status in Crohn's disease as assessed by intracellular analysis and intravenous magnesium infusion

The magnesium status was evaluated in 30 subjects with Crohn's disease and in 30 controls. Subjects with Crohn's disease had lower concentrations of magnesium in muscle biopsy specimens (p less than 0.001), mononuclear cells (p less than 0.05), and in urine collected during 24 h (p less than 0.001) as compared with controls. After intravenous infusion of 60 mmol magnesium and 80 mmol potassium to 17 subjects with Crohn's disease a significant increase in concentrations of magnesium in muscle specimens (p less than 0.05), mononuclear cells (p less than 0.01), and plasma (p less than 0.01) was noted. The retention of intravenously infused magnesium was significantly higher in subjects with Crohn's disease than in 11 healthy controls (p less than 0.001) and was inversely correlated with the content of magnesium in muscle specimens (r = -0.52; p less than 0.05). The implication of these findings is that analysis of magnesium in muscle specimens and estimation of magnesium retention during an intravenous magnesium infusion are useful to confirm a suspected magnesium deficiency.     

Associations of delay discounting and drinking trajectories from ages 14 to 22

Background

While drinking alcohol, one must choose between the immediate rewarding effects and the delayed reward of a healthier lifestyle. Individuals differ in their devaluation of a delayed reward based on the time required to receive it, i.e., delay discounting (DD). Previous studies have shown that adolescents discount more steeply than adults and that steeper DD is associated with heavier alcohol use in both groups.

Methods

In a large-scale longitudinal study, we investigated whether higher rates of DD are an antecedent or a consequence of alcohol use during adolescent development. As part of the IMAGEN project, 2220 adolescents completed the Monetary Choice Questionnaire as a DD measure, the Alcohol Use Disorders Identification Test, and the Timeline Follow Back interview at ages 14, 16, 18, and 22. Bivariate latent growth curve models were applied to investigate the relationship between DD and drinking. To explore the consequences of drinking, we computed the cumulative alcohol consumption and correlated it with the development of discounting. A subsample of 221 participants completed an intertemporal choice task (iTeCh) during functional magnetic resonance imaging at ages 14, 16, and 18. Repeated-measures ANOVA was used to differentiate between high-risk and low-risk drinkers on the development of neural processing during intertemporal choices.

Results

Overall, high rates of DD at age 14 predicted a greater increase in drinking over 8 years. In contrast, on average, moderate alcohol use did not affect DD from ages 14 to 22. Of note, we found indicators for less brain activity in top-down control areas during intertemporal choices in the participants who drank more.

Conclusions

Steep DD was shown to be a predictor rather than a consequence of alcohol use in low-level drinking adolescents. Important considerations for future longitudinal studies are the sampling strategies to be used and the reliability of the assessments.

     

Syndemic and syndemogenesis of low back pain in Latin-American population: a network and cluster analysis

Clinical Rheumatology - Although low back pain (LBP) is a high-impact health condition, its burden has not been examined from the syndemic perspective. To compare and assess clinical,...     

Clinical outcome and quality of life of patients surviving 20 years or longer after heart transplantation

To evaluate outcome and quality of life (QoL) in ≥20 years survivors after heart transplantation. Patients surviving ≥20 years with a single graft were retrospectively reviewed. Heterotopic, multiorgan and retransplantations were excluded. QoL was evaluated using the SF‐36 survey. Eight hundred and twenty‐seven heart transplants were performed from 1981 to 1993, and among these, 131 (16%) patients survived ≥20 years; 98 (75%) were male and mean age at transplant was 43 ± 13 years. Conditional survival in these 20 years survivors was 74.1 ± 4.3% at 23 years and 60.9 ± 5.3% at 25 years (45 deaths, 34%). Forty‐four (34%) patients suffered rejection ≥2R. Conditional survival free from rejection ≥2R was 68 ± 4.1% at 5 years and 66.4 ± 4.2% at 10 years. Thirty‐five (27%) patients had cardiac allograft vasculopathy (CAV) grade 2–3. Conditional CAV‐free survival was 76 ± 3.8% at 20 years and 72.1 ± 4% at 25. Sixty‐nine (53%) patients developed malignancy, mostly skin cancers. Conditional malignancy‐free survival was 53.5 ± 4.4% at 20 years and 45.2 ± 4.6% at 25 years. At latest follow‐up, 24.0 ± 3.0 years after transplantation, mean left ventricular ejection fraction was 62 ± 11% and mean physical and mental scores were 57 ± 23 and 58 ± 21, respectively. Sixteen per cent of heart recipients survived ≥20 years with good ventricular performance and QoL. CAV and malignancies account for late morbidity and mortality.     

Bigger is better! Hippocampal volume and declarative memory performance in healthy young men

The importance of the hippocampus for declarative memory processes is firmly established. Nevertheless, the issue of a correlation between declarative memory performance and hippocampal volume in healthy subjects still remains controversial. The aim of the present study was to investigate this relationship in more detail. For this purpose, 50 healthy young male participants performed the California Verbal Learning Test. Hippocampal volume was assessed by manual segmentation of high-resolution 3D magnetic resonance images. We found a significant positive correlation between putatively hippocampus-dependent memory measures like short-delay retention, long-delay retention and discriminability and percent hippocampal volume. No significant correlation with measures related to executive processes was found. In addition, percent amygdala volume was not related to any of these measures. Our data advance previous findings reported in studies of brain-damaged individuals in a large and homogeneous young healthy sample and are important for theories on the neural basis of episodic memory.     

Impact of chronic pain on the spouse: marital, emotional and physical consequences

The effects of chronic illness on marital relationships and the spouses' emotional and physical health were examined in chronic pain patients, their spouses, and a control sample of spouses of diabetic patients. Results indicated that pain patients and their spouses experienced considerable change in marital and sexual satisfaction. Patients with better marital adjustment also reported higher overall pain levels and had more solicitous and maritally satisfied spouses. Spouses' marital adjustment was positively associated with patients' marital satisfaction and spouses' own mood. Spouses' dysphoric mood was related to patients' negative appraisal of the pain experience, spouses' perceived lack of life control, and spouses' marital dissatisfaction. Although spouses of chronic pain patients showed no more physical symptoms than spouses of diabetics, they reported significantly more pain symptoms that were related to elevated levels of depressed mood. The results indicate that not only is chronic pain associated with problems in the marital relationship but heightened distress and physical symptoms in spouses as well. These effects are related less to the existence of a chronic pain problem per se but rather to patients' and spouses' manner of coping with the situation.     

Angiogenesis and lymphangiogenesis in mucoepidermoid carcinoma of minor salivary glands

J Oral Pathol Med (2012) 41: 603-609 Background: Mucoepidermoid carcinoma is the most common malignant tumor of salivary glands. This tumor is characterized by a great variability in clinical behavior, and little is known about the pathological mechanisms involved in its variance. Angiogenesis is an important step in tumor progression and is believed to be an essential event for metastatic dissemination. Methods: We aimed to investigate angiogenesis and lymphangiogenesis in mucoepidermoid carcinoma measuring the density of neoformed and lymphatic vessels using CD105 and D2-40 antibodies, respectively, and by immunohistochemical evaluation of VEGF-A and VEGF-C proteins. It was also investigated the expression of D2-40 in neoplastic cells. Results: We studied 26 cases of mucoepidermoid carcinoma, which showed great angiogenic activity measured by neoformed vessel density. However, a low density of lymphatics was observed. VEGF-A, VEGF-C, and D2-40 were commonly detected in mucoepidermoid carcinoma, but only VEGF-A expression correlated with neoformed vessel density. Recurrence and nodal metastasis were associated with low VEGF-A expression and low neoformed vessel density, indicating that impaired angiogenesis could lead to an aggressive phenotype. Conclusions: Angiogenesis seems important in the modulation of mucoepidermoid carcinoma pathogenesis; however, none of the parameters analyzed could predict tumor behavior.