Cholinergic neuronal lesions in the medial septum and vertical limb of the diagonal bands of Broca induce contextual fear memory generalization and impair acquisition of fear extinction

Previous research has shown that the ventral medial prefrontal cortex (vmPFC) and hippocampus (Hipp) are critical for extinction memory. Basal forebrain (BF) cholinergic input to the vmPFC and Hipp is critical for neural function in these substrates, which suggests BF cholinergic neurons may be critical for extinction memory. In order to test this hypothesis, we applied cholinergic lesions to different regions of the BF and observed the effects these lesions had on extinction memory. Complete BF cholinergic lesions induced contextual fear memory generalization, and this generalized fear was resistant to extinction. Animals with complete BF cholinergic lesions could not acquire cued fear extinction. Restricted cholinergic lesions in the medial septum and vertical diagonal bands of Broca (MS/vDBB) mimicked the effects that BF cholinergic lesions had on contextual fear memory generalization and acquisition of fear extinction. Cholinergic lesions in the horizontal diagonal band of Broca and nucleus basalis (hDBB/NBM) induced a small deficit in extinction of generalized contextual fear memory with no accompanying deficits in cued fear extinction. The results of this study reveal that MS/vDBB cholinergic neurons are critical for inhibition and extinction of generalized contextual fear memory, and via this process, may be critical for acquisition of cued fear extinction. Further studies delineating neural circuits and mechanisms through which MS/vDBB cholinergic neurons facilitate these emotional memory processes are needed. © 2015 Wiley Periodicals, Inc.     

Altered ATP-dependent mitochondrial Ca2+ uptake in cold ischemia is attenuated by ruthenium red

BACKGROUND: Graft dysfunction as a result of preservation injury remains a major clinical problem in liver transplantation. This is related in part to accumulation of mitochondrial calcium (Ca(2+)), which has been linked to activation of proapoptotic factors. We hypothesized that cold ischemia increases mitochondrial Ca(2+) uptake in a concentration dependent fashion and that ruthenium red (RR) will attenuate these changes by inhibiting the mitochondrial Ca(2+) uniporter. METHODS: Rat livers perfused with cold University of Wisconsin (UW) solution (4 degrees C) with or without RR (10 microM) via the portal vein (n = 3 per group) were processed immediately (no ischemia) or after 24 h cold-storage (24 h cold ischemia). Mitochondria were separated by differential centrifugation, and adenosine triphosphate (ATP)-dependent (45)Ca(2+) uptake was determined in the presence of ATP (5 mM), adenosine diphosphate (ADP), or adenosine 5'-beta,gamma-imidotriphosphate (AMP-PNP); variable concentrations of extramitochondrial (45)Ca(2+) were used. All measurements were performed in triplicate. Student's t test with P < 0.05 was taken as significant. RESULTS: Our data demonstrate the following: 1) ATP-dependent (45)Ca(2+) uptake in mitochondria separated from livers following 24 h of cold ischemia in UW alone was higher than in mitochondria isolated from non-ischemic livers; the increased uptake was dependent on the concentration of (45)Ca(2+) in the incubation buffer. 2) There was no difference in ATP-dependent (45)Ca(2+) uptake between nonischemic mitochondria and those separated from livers stored in UW-RR for 24 h. 3) (45)Ca(2+) uptake in mitochondria from livers subjected to 24 h of cold ischemia in UW-RR was significantly lower compared to those from livers stored in UW alone when (45)Ca(2+) concentrations were greater than 1 microM. CONCLUSION: 1) Cold ischemia affects mitochondrial Ca(2+) handling, especially when it is challenged by high extramitochondrial Ca(2+) concentrations. 2) The addition of RR in preservation solution attenuates the effects of cold ischemia on mitochondrial Ca(2+) handling. 3) Inhibition of mitochondrial Ca(2+) uniporter with RR protects mitochondria from Ca(2+) overload at high Ca(2+) concentrations. These findings may offer a potentially effective strategy for prevention of ischemia-reperfusion injury in liver transplantation.     

Distal revascularization-interval ligation: a durable and effective treatment for ischemic steal syndrome after hemodialysis access

PURPOSE: The treatment of hemodialysis access-induced ischemic steal syndrome is challenging. Despite promising early results with the distal revascularization-interval ligation (DRIL) procedure, the operation has not been widely adopted because of concerns about its complexity and long-term efficacy. The purpose of this report was to determine the efficacy and durability of the DRIL procedure in relieving hand ischemia and in maintaining access patency in the setting of hemodialysis access-induced ischemia. METHODS: A retrospective review was performed of all patients who underwent the DRIL procedure for access-induced ischemia. Demographic information was compiled, as were data regarding access and bypass patency, limb salvage, and patient survival. Arteriovenous access and brachial artery bypass patency rates were determined with life-table methods. RESULTS: Between 1995 and 2001, we performed 55 DRIL procedures in 52 patients (35 women and 17 men; mean age, 60.8 years; range, 30 to 86 years). The indications for surgery were ischemic pain in 27 patients, tissue loss in 20 patients, loss of neurologic function in four patients, and pain on hemodialysis in one patient. Most patients (92%) had diabetes. The mean interval from access placement to DRIL was 7.4 months (range, 1 to 84 months). The mean follow-up interval was 16 months (range, 1 to 67 months). The brachial artery bypass primary patency rate was 80% at 4 years, and the arteriovenous access primary patency rate was 83% at 1 year. Forty-seven of 52 patients (90%) had substantial or complete relief of ischemic hand symptoms, and 15 of 20 patients with digital ischemic lesions have healed completely. CONCLUSION: DRIL is a durable and effective procedure that reliably accomplishes the twin goals in the treatment of angioaccess-induced ischemia: persistent relief of hand ischemia and continued access patency.     

Human herpesvirus 6 and multiple sclerosis: systemic active infections in patients with early disease.

By means of immunohistochemical staining, cells actively infected with human herpesvirus 6 (HHV-6) were found in central nervous system tissues from 8 (73%) of 11 patients with definite multiple sclerosis (MS). Interestingly, 17 (90%) of 19 tissue sections showing active demyelination were positive for HHV-6-infected cells compared with only 3 (13%) of 23 tissue sections free of active disease (P<.0001). Central nervous system tissues from 2 of 28 normal persons and patients with other inflammatory demyelinative diseases were positive for HHV-6-infected cells (P<.0001), and the 2 positive cases were diagnosed as having HHV-6 leukoencephalitis. By use of a rapid culture assay, blood samples from 22 (54%) of 41 patients with definite MS were found to contain active HHV-6 infections, compared with 0 of 61 normal controls (P<.0001). No significant difference was found between HHV-6 viremia-positive and HHV-6 viremia-negative MS patients with respect to type of disease (relapsing/remitting or progressive). In contrast, patients with active HHV-6 viremia were significantly younger and had shorter durations of disease than did HHV-6 viremia-negative patients.     

Blood Pressure Variations During a Working Day at Age 28: Effects of Different Types of Work and Blood Pressure Level at Age 18

Abstract

During an ordinary work day blood pressure was self-monitored once every hour in two samples of asymptomatic nonmedicating 28-year-old men. They were selected on the basis of previous compulsory blood pressure recordings made at the age of 18 when they had been drafted for military service. Subjects in the ?original hypertensive sample” with ?strain” occupations (hectic and uncontrollable, such as waiter, driver and cook) had more marked elevations of systolic blood pressure during work hours than other subjects.     

Bcp1, a gene required for male fertility in Arabidopsis.

Male fertility in flowering plants is dependent on production of viable pollen grains within the anther. Genes expressed exclusively in the anther are likely to include those that control male fertility. On the basis of their tissue specificity, such genes have been isolated, yet in none of them has this function been demonstrated. Here we report that one such gene, Bcp1, is active in both diploid tapetum and haploid microspores and is required for pollen fertility. Perturbation of this gene in either tapetum or microspores prevents production of fertile pollen in transgenic Arabidopsis plants. When tapetum expression of this gene is perturbed, mature anthers contain dead shriveled pollen. On the other hand, when microspore expression is perturbed, anthers show 1:1 segregation of viable/aborted pollen. These findings identify a class of sporophytic/gametophytic genes controlling male fertility and, hence, reproduction in flowering plants.     

Clients' perspectives on therapy termination

Abstract

We used consensual qualitative research to analyze interviews with 12 clients about their termination from psychotherapy. Those who had positive termination experiences reported a strong therapeutic relationship and positive outcomes of therapy. They terminated primarily for logistical or financial reasons; their termination, post-termination plans, and feelings about termination were discussed in advance with their therapist, as was their growth in therapy, leading to mostly positive effects of the termination. In contrast, those who had problematic terminations reported a mixed therapeutic relationship and mixed outcomes of therapy. They usually terminated abruptly because of a therapeutic rupture, and thus termination was rarely planned and discussed in advance, rendering it a negative experience. Implications of these findings are addressed.