Deletion of calcineurin from GFAP-expressing astrocytes impairs excitability of cerebellar and hippocampal neurons through astroglial Na+/K+ ATPase

Astrocytes perform important housekeeping functions in the nervous system including maintenance of adequate neuronal excitability, although the regulatory mechanisms are currently poorly understood. The astrocytic Ca²⁺/calmodulin-activated phosphatase calcineurin (CaN) is implicated in the development of reactive gliosis and neuroinflammation, but its roles, including the control of neuronal excitability, in healthy brain is unknown. We have generated a mouse line with conditional knockout (KO) of CaN B1 (CaNB1) in glial fibrillary acidic protein-expressing astrocytes (a stroglial c alcin eurin KO [ACN-KO]). Here, we report that postnatal and astrocyte-specific ablation of CaNB1 did not alter normal growth and development as well as adult neurogenesis. Yet, we found that specific deletion of astrocytic CaN selectively impairs intrinsic neuronal excitability in hippocampal CA1 pyramidal neurons and cerebellar granule cells (CGCs). This impairment was associated with a decrease in after hyperpolarization in CGC, while passive properties were unchanged, suggesting impairment of K⁺ homeostasis. Indeed, blockade of Na⁺/K⁺-ATPase (NKA) with ouabain phenocopied the electrophysiological alterations observed in ACN-KO CGCs. In addition, NKA activity was significantly lower in cerebellar and hippocampal lysates and in pure astrocytic cultures from ACN-KO mice. While no changes were found in protein levels, NKA activity was inhibited by the specific CaN inhibitor FK506 in both cerebellar lysates and primary astroglia from control mice, suggesting that CaN directly modulates NKA activity and in this manner controls neuronal excitability. In summary, our data provide formal evidence for the notion that astroglia is fundamental for controlling basic neuronal functions and place CaN center-stage as an astrocytic Ca²⁺-sensitive switch.     

A clinical trial of Empress II porcelain inlays luted to vital teeth with a dual-curing adhesive system and a self-curing resin cement

PURPOSE: The aim of the study was to clinically evaluate Empress II inlays cemented with a dual-curing bonding agent and a self-curing luting system. MATERIALS AND METHODS: Forty patients were selected to receive one Empress II inlay. Empress II is a heat-pressed glass ceramic containing lithium disilicate and lithium orthophosphate crystals, purported to provide higher stress resistance and improved strength. The restorations were placed between March and May 2000. Recalls were performed after 6, 12, 24, and 36 months. At the 3-year recall, 7 patients were lost to follow-up. Inlays were evaluated for postoperative sensitivity, marginal integrity, marginal leakage, color stability, surface staining, retention, and surface crazing (microcracks). RESULTS: At the 3-year recall, all the restorations were in place and only one showed postoperative sensitivity (at the first recall, 1 week after placement). Only 3 inlays showed slight marginal staining, and 4 inlays showed gaps, with little surface staining or microcracks. CONCLUSIONS: No inlay debonded or fractured during theobservation period. All the evaluated inlays were in place and acceptable.     

Density of dentinal tubules affects the tensile strength of root dentin.

OBJECTIVES: The aim of this study is to count the dentinal tubules in the coronal and middle-apical third of root dentin of teeth extracted due to the progression of periodontal disease, and to compare the Ultimate Tensile Strength (UTS) of the same areas. The research hypothesis was that root dentin areas with different densities of dentinal tubules would also show different UTS values. METHODS: From 10 caries free maxillary central, lateral incisors and canines, extracted for periodontal reasons from three patients, cylindrical specimens approximately 10 mm long were prepared parallel to the long axis of the root and then divided into two parts using a low speed diamond saw one from the coronal third of the root, (Group 1) and one from the middle-apical third of the root (Group 2). The density of the dentinal tubules of the specimens of the two groups was measured by means of a scanning electron microscope and the UTS of the specimens was measured by a microtensile test. One way ANOVA was used to assess the effect of specimen location (coronal specimens vs. middle-apical specimens) on UTS. The differences in the density of dentinal tubules between coronal and middle-apical specimens were also subjected to statistical analysis using one-way ANOVA. RESULTS: UTS values of middle-apical specimens were found to be significantly (p < 0.05) higher than those of coronal specimens. The results of the one-way analysis of variance showed that the number of dentinal tubules of the samples from the coronal part of the root groups was significantly higher than that of samples from the middle-apical part (p < 0.05). SIGNIFICANCE: These results suggest that high values of tensile strength of the dentin are associated with low densities of dentinal tubules and that apical areas of root dentin are more resistant to tension than coronal ones.     

Suicidal Ideation in Bipolar Disorder: The Relation with Clinical and Sociodemographic Variables

Psychiatric Quarterly - Bipolar disorder (BD) has the highest risk of suicide among all mental disorders. Thus, identifying factors related to suicidal ideation is essential for a better assessment...     

Pathological findings of Angiostrongylus vasorum infection in red foxes (Vulpes vulpes) from Central Italy,with the first report of a disseminated infection in this host species

In Europe, the red fox (Vulpes vulpes) is considered the reservoir of Angiostrongylus vasorum, nematode residing in the pulmonary arteries and right heart of dogs and many species of wild carnivores. Italy is considered one of the European countries where this nematode is actually spreading. Between May 2007 and November 2013, 62 foxes found dead in Central Italy were necropsied. Right heart and pulmonary arteries were opened and checked for the presence of adult parasites. Impression smears from sectioned lungs were examined for the presence of first-stage larvae, and samples of lungs were processed for histological examination. In order to detect eventual disseminated infections, samples of heart, pulmonary lymph nodes, liver, kidneys, and brain of foxes positive for A. vasorum at necropsy or lungs histological examination were processed for histological examination. An overall prevalence of 43.5 % was recorded. Light, mild, and severe lung lesions were detected in 33.3, 22.2, and 25.9 % of infected animals, respectively. Severe lesions were more frequent in animals younger than 12 months. In five infected foxes (18.5 %), no gross lesions were observed, while for three animals, angiostrongylosis was considered the cause of death. A case of disseminated angiostrongylosis was detected and another one was suspected. This is the firs report of disseminated angiostrongylosis in the fox.     

Facing somatic symptom disorder in the emergency department

Somatic symptom disorder is a condition in which a patient's subjective report of physical symptoms is associated with distress; disruption of day‐to‐day functioning; or disproportionate thoughts, feelings and behaviours regarding the symptoms, whether or not they are associated with an identified medical condition. While somatic symptom disorder affects a considerable proportion of children and adolescents presenting to the emergency department (ED), it has not been well investigated in the ED literature, nor is there much formal training in, or guidelines for, how to care for affected patients in the ED. The aim of this paper is to highlight the historical clues commonly reported by these patients in order to try to help the emergency physicians recognise patients affected by a somatic symptom disorder. Adolescent age, the presence of daily subjective symptoms presenting daily for weeks or months, a long medical history record, an extensive diagnostic workup and, most of all, disproportionate functional impairment related to the symptoms are all features strongly suggestive of this disorder. Emergency physicians should become used to taking advantage of these clues to formulate a positive diagnosis of somatic symptom disorder according to the most recent diagnostic criteria. Emergency physicians have the unique opportunity to contribute to the correct diagnosis and treatment of these patients and to have a positive impact on their prognosis.