Common firing patterns of hippocampal cells in a differential reinforcement of low rates of response schedule.

Lesion studies show that the hippocampus is critically involved in timing behavior, but so far there has been little analysis of how it might encode time. We recorded the activity of 266 CA1 neurons, 51 CA3 neurons, and 219 entorhinal neurons from rats performing on a differential reinforcement of low rates (DRL) 15 sec schedule in which reinforcement was contingent on responses that occurred at least 15 sec after the preceding response. The unit data were analyzed using two different methods. First, each unit was subjected to an ANOVA that examined the effects of the following: (1) the outcome of the previous response (reward or nonreward); (2) the outcome of the response on which the firing of the cell was synchronized; and (3) time. This showed that, for CA1, CA3, and entorhinal cortex, changes in unit activity were related to all aspects of the task, with the firing of >90% of units recorded in each region being related to at least one of the three factors. Second, intercorrelations between the firing profiles of individual units revealed several functional categories of hippocampal neurons but no clear categories of entorhinal neurons. Of the hippocampal categories, the most common profile was an initial increase in unit activity at the beginning of the DRL interval, followed by a gradual decrease throughout the interval. We suggest that this profile reflects temporal decay in circuits that may code details of the previous trial and that could be used to "time" the DRL interval.     

Randomized placebo-controlled study of low-dose warfarin for the prevention of central venous catheter-associated thrombosis in patients with cancer.

PURPOSE: In this multicenter, randomized, placebo-controlled clinical trial, we studied whether warfarin 1 mg daily reduces the incidence of symptomatic central venous catheter (CVC) -associated thrombosis in patients with cancer. PATIENTS AND METHODS: Two hundred fifty-five patients with cancer who required a CVC for at least 7 days were randomly assigned to receive warfarin 1 mg or placebo. RESULTS: There were 11 (4.3%) symptomatic CVC-associated thromboses among 255 patients, with no difference in the incidence of symptomatic CVC-associated thrombosis between patients taking warfarin 1 mg daily (six of 130 patients; 4.6%) and patients taking placebo (five of 125 patients; 4.0%; hazard ratio, 1.20; 95% CI, 0.37 to 3.94). Warfarin had no effect on CVC life span (84 days v 63 days in control and warfarin groups, respectively; 95% confidence limit, -16 to 55 days; P = .09), and it did not affect the number of premature CVC removals (23.2% v 25.4% in control and warfarin groups, respectively; 95% confidence limit of difference -8.34 to 12.71; P = .68) or the frequency of major bleeding episodes (2% v 0% in control and warfarin groups, respectively; P = .5, Fisher's exact test). CONCLUSION: Symptomatic CVC-associated thrombosis in patients with cancer, although significant, is less common than previously reported. In this study, the administration of warfarin 1 mg daily did not reduce the incidence of symptomatic CVC-associated thrombosis in patients with cancer. However, the low rate of symptomatic CVC-associated thrombosis means that a much larger trial is required to address this issue definitively.     

Anxiolytic-like action of melatonin on acquisition but not performance of DRL

The behavioural effects of melatonin have been attributed to a general reduction in motor activity; interference with memory fixation; a decrease in emotionality; or an anxiolytic action. The present experiments compared the effects of melatonin with an anxiolytic benzodiazepine, chlordiazepoxide (Librium), on a schedule of differential reinforcement of low rates of response (DRL) increasing 'burst' responding and premature responding. No doses of melatonin tested (0.03-8.1 mg/kg, IP) affected performance of well-learned DRL. Both low (0.03 mg/kg) and high (1.0 mg/kg) doses of melatonin impaired acquisition of DRL in a similar manner to chlordiazepoxide (5.0 mg/kg) and to much the same extent. Chlordiazepoxide had its usual effects on both acquisition and performance of DRL. These results show that melatonin shares a subset of the effects of chlordiazepoxide. The nature of the effects favours an 'anxiolytic' hypothesis of melatonin action rather than the other hypotheses so far proposed.     

Alpha7 Nicotinic Acetylcholine Receptors Modulate Motivation to Self-Administer Nicotine: Implications for Smoking and Schizophrenia

Individuals diagnosed with schizophrenia have an exceptionally high risk for tobacco dependence. Postmortem studies show that these individuals have significant reductions in α7 nicotinic acetylcholine receptors (nAChRs) in several brain areas. Decreased α7-mediated function might not only be linked to schizophrenia but also to increased tobacco consumption. The purpose of this study was to determine whether pharmacological blockade of α7 nAChRs would increase motivation of rats to intravenously self-administer nicotine (NIC) during a progressive ratio schedule of reinforcement (PR). Before PR, rats received local infusions of 0, 10, or 20 pmol of a selective α7 nAChR antagonist, α-conotoxin ArIB [V11L,V16D] (ArIB) into the nucleus accumbens (NAc) shell or the anterior cingulate cortex, brain areas that contribute to motivation for drug reward. We additionally sought to determine whether local infusion of 0, 10, or 40 nmol of a selective α7 nAChR agonist, PNU 282987, into these brain areas would decrease motivation for NIC use. Infusion of ArIB into the NAc shell and anterior cingulate cortex resulted in a significant increase in active lever pressing, breakpoints, and NIC intake, suggesting that a decrease in α7 nAChR function increases motivation to work for NIC. In contrast, PNU 282987 infusion resulted in reductions in these measures when administered into the NAc shell, but had no effect after administration into the anterior cingulate cortex. These data identify reduction of α7 nAChR function as a potential mechanism for elevated tobacco use in schizophrenia and also identify activation of α7 nAChRs as a potential strategy for tobacco cessation therapy.     

Analytical validation of anti-toxoplasma IgG immunoassays

There are often discrepancies when using different methods to measure anti-Toxoplasma gondii IgG levels in patient samples. The diagnostic performance of a chemiluminescent immunoassay (CLIA) and an enzyme-linked fluorescent assay (ELFA) used as confirmatory tests for samples identified as positive or equivocal by an electrochemiluminescent immunoassay (ECLIA) were examined. Cut-off values were those stated by the manufacturer, and Western blot was used to confirm the results of all methods. All samples identified as positive by ECLIA (n = 93) were confirmed as positive by Western blot, as were 14 of the 28 samples identified as equivocal. When these 121 samples were retested, the sensitivities of CLIA and ELFA were 64.4% and 73.8%, respectively. Both methods exhibited a specificity of 100%. This study confirms that the results obtained from the different immunoassays are not comparable, and neither CLIA nor ELFA should be used to confirm ECLIA results, which should instead be confirmed by methods such as Western blot or Sabin-Feldman dye test.     

High versus low glycemic index 3-h recovery diets following glycogen-depleting exercise has no effect on subsequent 5-km cycling time trial performance

ObjectivesSome athletes train/compete multiple times in a single day and rapid restoration of muscle and hepatic glycogen stores is therefore important for athletic performance.DesignRandomised, counterbalanced, crossover, single blinded study investigated the effects of low/high glycaemic index (GI) meals on the physiological responses to a 3-h recovery period and subsequent 5-km cycling time trial (TT).MethodsSeven male cyclists completed glycogen-depleting exercise followed by a 3-h recovery period, when participants consumed either a high or low GI meal providing 2 g kg^?1 BM of carbohydrate. Participants then performed a 5-km cycling TT. Blood samples were analysed for glucose insulin, free fatty acid (FFA) and triglyceride.ResultsThere was no significant difference between the median (IQR) cycling TT time of 8.5 (3.0) min in the LGI condition and 8.4 (1.8) min in the HGI condition (p = 0.45). Serum insulin was significantly higher in the HGI condition throughout the 3-h recovery period (p = 0.025), FFA concentrations were higher in the HGI condition only at 30 min into recovery (p = 0.008). The respiratory exchange ratio (p = 0.028) and carbohydrate oxidation rate (p = 0.015) increased over time in the HGI condition, whereas the rate of fat oxidation demonstrated the opposite response (p = 0.001). No significant differences between conditions were observed for any physiological variables at the end of the 5-km TT.ConclusionsAlthough the GI of the two meals indicated important metabolic differences during the recovery period, there was no evidence suggesting these differences influenced subsequent 5-km TT performance.     

Measurement of Quality of Life in Head and Neck Cancer Patients Utilizing the Quality of Life Radiation Therapy Questionnaire

BACKGROUND: Quality of life (QOL) measures give patients the possibility to express subjective changes in wellbeing. We aimed to translate the radiation specific quality of life questionnaire (QOL-RTI) and the companion head and neck module (H&N) questionnaire into German and to test its reliability, validity and sensitivity. PATIENTS AND METHODS: After translation and final revisions based on qualitative interviews with ten patients, 97 head and neck cancer patients were screened for eligibility. Patients answered the 38 items questionnaire at baseline and twice in week 4 of radiotherapy for test-retest reliability. Internal consistency was calculated using Chronbach's alpha. Patients also completed the functional assessment of cancer tool plus head and neck (FACT-G plus H&N) for concurrent validity. Item analyses were performed to test the sensitivity. RESULTS: Chronbach's alpha yielded alpha = 0.85 for the QOL-RTI and alpha = 0.80 for the H&N module, test-retest reliability scores were r = 0.87 and r = 0.83, respectively. The correlation of the QOL-RTI plus H&N and the FACT plus H&N was r = 0.79. Questionnaire sensitivity was supported by significant changes in the mean score of 45.8% of the QOL-RTI items and 78.6% of the H&N items between baseline and week 4 of radiotherapy. CONCLUSIONS: The German version of the QOL-RTI was shown to be a reliable, valid and sensitive tool to assess the quality of life of patients undergoing radiotherapy. The H&N module is useful for patients undergoing treatment for head and neck cancer.     

Neuroimaging in posttraumatic hypopituitarism

Posttraumatic hypopituitarism is the failure of the hypothalamic-pituitary axis secondary to traumatic brain injury. It can clinically present as decreased muscle mass, concentration, libido, and fertility. It can also present as increased fatigue, depression, and cognitive deficits. In addition, electrolyte abnormalities such as hyponatremia can occur in hypopituitarism. As a result of heightened awareness of posttraumatic hypopituitarism, it is a phenomenon that is becoming more commonly diagnosed. Posttraumatic hypopituitarism is a diagnosis based on clinical evaluation, laboratory testing, and neuroimaging. Of the radiological techniques, magnetic resonance imaging is the preferred technique to image the pituitary gland. This article contains coronal and sagittal magnetic resonance imaging of the posterior fossa, illustrating the normal hypothalamus and pituitary gland as well as adjacent structures. The sequential enhancement pattern of the normal pituitary gland is consistent with its vascular supply. A colored illustration was created to display the vascular supply to the hypothalamus, pituitary stalk, and pituitary gland.     

Pre-exercise alkalosis and acid-base recovery

The aim of this study was to observe the influence of pre-exercise sodium bicarbonate (NaHCO3) ingestion and varying recovery modes on acid-base recovery from a single bout of supramaximal exercise. Nine male subjects completed four separate, randomized cycle ergometer exercise trials to volitional fatigue at 120% maximum power output, under the following conditions: 0.3 g.kg(-1) BW NaHCO3 ingestion with passive recovery (BICARB P), 0.3 g.kg (-1) BW NaHCO3 ingestion with active recovery (BICARB A), placebo ingestion with passive recovery (PLAC P) and placebo ingestion with active recovery (PLAC A). Capillary blood samples were obtained every minute for 15 min during recovery. Significant main effects for pH were observed for time (F = 42.1, p < 0.001), intervention (BICARB and PLAC) (F = 1117.3, p < 0.001) and recovery condition (F = 150.0, p < 0.001), as the BICARB condition reduced acid-base perturbation. Significant interaction effects were observed between conditions (BICARB and PLAC) for active and passive recovery modes (F = 29.1, p < 0.001) as the active recovery facilitated H+ removal better than the passive condition. Pre-exercise alkalosis attenuates blood acid-base perturbations from supramaximal exercise to exhaustion, regardless of whether the recovery mode is active or passive. These findings suggest that individuals may benefit from introducing a pre-exercise alkalotic condition while including passive recovery during high-intensity training protocols.