International Society of Cardiovascular Infectious Diseases Guidelines for the Diagnosis, Treatment and Prevention of Disseminated Mycobacterium chimaera Infection Following Cardiac Surgery with Cardiopulmonary Bypass.

Mycobacterial infection-related morbidity and mortality in patients following cardiopulmonary bypass surgery is high and there is a growing need for a consensus-based expert opinion to provide international guidance for diagnosing, preventing and treating in these patients. In this document the International Society for Cardiovascular Infectious Diseases (ISCVID) covers aspects of prevention (field of hospital epidemiology), clinical management (infectious disease specialists, cardiac surgeons, ophthalmologists, others), laboratory diagnostics (microbiologists, molecular diagnostics), device management (perfusionists, cardiac surgeons) and public health aspects.

Preoperative Cerebral Oxygen Extraction Fraction Imaging Generated from 7T MR Quantitative Susceptibility Mapping Predicts Development of Cerebral Hyperperfusion following Carotid Endarterectomy.

BACKGROUND AND PURPOSE: Preoperative hemodynamic impairment in the affected cerebral hemisphere is associated with the development of cerebral hyperperfusion following carotid endarterectomy. Cerebral oxygen extraction fraction images generated from 7T MR quantitative susceptibility mapping correlate with oxygen extraction fraction images on positron-emission tomography. The present study aimed to determine whether preoperative oxygen extraction fraction imaging generated from 7T MR quantitative susceptibility mapping could identify patients at risk for cerebral hyperperfusion following carotid endarterectomy. MATERIALS AND METHODS: Seventy-seven patients with unilateral internal carotid artery stenosis (≥70%) underwent preoperative 3D T2*-weighted imaging using a multiple dipole-inversion algorithm with a 7T MR imager. Quantitative susceptibility mapping images were then obtained, and oxygen extraction fraction maps were generated. Quantitative brain perfusion single-photon emission CT was also performed before and immediately after carotid endarterectomy. ROIs were automatically placed in the bilateral middle cerebral artery territories in all images using a 3D stereotactic ROI template, and affected-to-contralateral ratios in the ROIs were calculated on quantitative susceptibility mapping-oxygen extraction fraction images. RESULTS: Ten patients (13%) showed post-carotid endarterectomy hyperperfusion (cerebral blood flow increases of ≥100% compared with preoperative values in the ROIs on brain perfusion SPECT). Multivariate analysis showed that a high quantitative susceptibility mapping-oxygen extraction fraction ratio was significantly associated with the development of post-carotid endarterectomy hyperperfusion (95% confidence interval, 33.5-249.7; P = .002). Sensitivity, specificity, and positive- and negative-predictive values of the quantitative susceptibility mapping-oxygen extraction fraction ratio for the prediction of the development of post-carotid endarterectomy hyperperfusion were 90%, 84%, 45%, and 98%, respectively. CONCLUSIONS: Preoperative oxygen extraction fraction imaging generated from 7T MR quantitative susceptibility mapping identifies patients at risk for cerebral hyperperfusion following carotid endarterectomy.

Role for neonatal D-serine signaling: prevention of physiological and behavioral deficits in adult Pick1 knockout mice.

NMDA glutamate receptors have key roles in brain development, function and dysfunction. Regulatory roles of D-serine in NMDA receptor-mediated synaptic plasticity have been reported. Nonetheless, it is unclear whether and how neonatal deficits in NMDA-receptor-mediated neurotransmission affect adult brain functions and behavior. Likewise, the role of D-serine during development remains elusive. Here we report behavioral and electrophysiological deficits associated with the frontal cortex in Pick1 knockout mice, which show D-serine deficits in a neonatal- and forebrain-specific manner. The pathological manifestations observed in adult Pick1 mice are rescued by transient neonatal supplementation of D-serine, but not by a similar treatment in adulthood. These results indicate a role for D-serine in neurodevelopment and provide novel insights on how we interpret data of psychiatric genetics, indicating the involvement of genes associated with D-serine synthesis and degradation, as well as how we consider animal models with neonatal application of NMDA receptor antagonists.

Pathogenic disruption of DISC1-serine racemase binding elicits schizophrenia-like behavior via D-serine depletion.

Perturbation of Disrupted-In-Schizophrenia-1 (DISC1) and D-serine/NMDA receptor hypofunction have both been implicated in the pathophysiology of schizophrenia and other psychiatric disorders. In the present study, we demonstrate that these two pathways intersect with behavioral consequences. DISC1 binds to and stabilizes serine racemase (SR), the enzyme that generates D-serine, an endogenous co-agonist of the NMDA receptor. Mutant DISC1 fails to bind to SR, facilitating ubiquitination and degradation of SR and a decrease in D-serine production. To elucidate DISC1-SR interactions in vivo, we generated a mouse model of selective and inducible expression of mutant DISC1 in astrocytes, the main source of D-serine in the brain. Expression of mutant DISC1 downregulates endogenous DISC1 and decreases protein but not mRNA levels of SR, resulting in diminished production of D-serine. In contrast, mutant DISC1 does not alter levels of ALDH1L1, connexins, GLT-1 or binding partners of DISC1 and SR, LIS1 or PICK1. Adult male and female mice with lifelong expression of mutant DISC1 exhibit behavioral abnormalities consistent with hypofunction of NMDA neurotransmission. Specifically, mutant mice display greater responses to an NMDA antagonist, MK-801, in open field and pre-pulse inhibition of the acoustic startle tests and are significantly more sensitive to the ameliorative effects of D-serine. These findings support a model wherein mutant DISC1 leads to SR degradation via dominant negative effects, resulting in D-serine deficiency that diminishes NMDA neurotransmission thus linking DISC1 and NMDA pathophysiological mechanisms in mental illness.

Synovial chondromatosis of the temporomandibular joint with calcium pyrophosphate dihydrate crystal deposition disease (pseudogout).

This report describes a very rare case of synovial chondromatosis with deposition of calcium pyrophosphate dihydrate (CPPD) crystals (pseudogout) in the temporomandibular joint (TMJ) of a 46-year-old male patient. Synovial chondromatosis is a non-neoplastic disease characterized by metaplasia of the connective tissue leading to chondrogenesis in the synovial membrane. Pseudogout is an inflammatory disease of the joints caused by the deposition of CPPD, producing similar symptoms to those observed in gout but not hyperuricaemia. Both diseases commonly affect the knee, hip and elbow joints, but rarely affect the TMJ.

Differential effects of prenatal and postnatal expressions of mutant human DISC1 on neurobehavioral phenotypes in transgenic mice: evidence for neurodevelopmental origin of major psychiatric disorders.

Strong genetic evidence implicates mutations and polymorphisms in the gene Disrupted-In-Schizophrenia-1 (DISC1) as risk factors for both schizophrenia and mood disorders. Recent studies have shown that DISC1 has important functions in both brain development and adult brain function. We have described earlier a transgenic mouse model of inducible expression of mutant human DISC1 (hDISC1) that acts in a dominant-negative manner to induce the marked neurobehavioral abnormalities. To gain insight into the roles of DISC1 at various stages of neurodevelopment, we examined the effects of mutant hDISC1 expressed during (1) only prenatal period, (2) only postnatal period, or (3) both periods. All periods of expression similarly led to decreased levels of cortical dopamine (DA) and fewer parvalbumin-positive neurons in the cortex. Combined prenatal and postnatal expression produced increased aggression and enhanced response to psychostimulants in male mice along with increased linear density of dendritic spines on neurons of the dentate gyrus of the hippocampus, and lower levels of endogenous DISC1 and LIS1. Prenatal expression only resulted in smaller brain volume, whereas selective postnatal expression gave rise to decreased social behavior in male mice and depression-like responses in female mice as well as enlarged lateral ventricles and decreased DA content in the hippocampus of female mice, and decreased level of endogenous DISC1. Our data show that mutant hDISC1 exerts differential effects on neurobehavioral phenotypes, depending on the stage of development at which the protein is expressed. The multiple and diverse abnormalities detected in mutant DISC1 mice are reminiscent of findings in major mental diseases.

A case of double cancer involving oral malignant melanoma and gastrointestinal stromal tumor (GIST).

We report a very rare case of double cancer involving palatal malignant melanoma and gastrointestinal stromal tumor (GIST), a rare tumor of the gastrointestinal tract originating from a primitive mesenchymal cell. After chemotherapy, radiation therapy, and treatment with interferon and OK-432, the GIST was resected and the melanoma disappeared. The patient has had no evidence of recurrent tumor, and the patient's clinical course has been uneventful for 1 year. This is probably the first report of synchronous double cancer involving oral malignant melanoma and GIST.

A case of thrombosis mimicking a buccal tumour: usefulness of MRI.

A rare case of thrombosis mimicking a tumour in the buccal region is reported. Since the entire round mass was located deeply, it was difficult to diagnose. Contrast computed tomography, magnetic resonance imaging (MRI) and ultrasound examinations may be useful, but MRI was most useful in this case because it allowed prediction of different kinds of histological structures in the soft tissue. The findings of T1 weighted imaging, T2 weighted imaging and examination with Gd-DTPA on T1 weighted imaging are useful for predicting the character of deeper soft tissue masses, and can differentiate thrombosis from lymphadenopathy, lipoma and other lesions.

Involvement of LEU13 in interferon-induced refractoriness of human RSa cells to cell killing by X rays.

Culture of human cells with human interferon alpha and beta (IFNA and IFNB) results in increased resistance of the cells to cell killing by X rays. To identify candidate genes responsible for the IFN-induced X-ray resistance, we searched for genes whose expression levels are increased in human RSa cells treated with IFNA, using an mRNA differential display method and Northern blotting analysis. RSa cells, which showed increased survival (assayed by colony formation) after X irradiation when they were treated with IFNA prior to irradiation, showed increased expression levels of LEU13 (IFITM1) mRNA after IFNA treatment alone. In contrast, IF(r) and F-IF(r) cells, both of which are derived from RSa cells, showed increased X-ray resistance and high constitutive LEU13 mRNA expression levels compared to the parental RSa cells. Furthermore, the IFNA-induced resistance of RSa cells to killing by X rays was suppressed by antisense oligonucleotides for LEU13 mRNA. LEU13, a leukocyte surface protein, was previously reported to mediate the actions of IFN such as inhibition of cell proliferation. The present results suggest a novel role of LEU13 different from that in the inhibition of cell proliferation, involved in IFNA-induced refractoriness of RSa cells to X rays.

Hypermutable change of human UV(r)-1 cells by p53 overexpression.

The p53 protein has been reported to regulate cellular responses to genetic stress such as far-ultraviolet light (UV), protecting human cells from mutation. Levels of p53 protein in hypermutable RSa cells were found here to increase soon after UV irradiation, while those in UV(r)-1 cells, a hypomutable variant of RSa cells, showed a delayed increase. Three cell lines overexpressing wild-type p53 in UV(r)-1 cells exhibited higher sensitivity to UV mutagenicity than did control U-V-7 cells transfected with vector alone, assessed using the ouabain-resistance phenotypic mutation test and identification of K-ras codon 12 base substitution mutation. On the other hand, U-V-7 cells showed UV-induced elevation of antipain-sensitive protease activity, but p53 transfectants did not. Moreover, antipain treatment to U-V-7 cells was increased susceptibility to UV mutagenicity. Thus, p53 protein overproduction may sensitize human cells, at least those tested, to UV mutagenicity, in association with inhibition of protease activity.

Study on real time control of non-point pollutants discharged from urban areas during a storm event.

In this research, we installed the storm water storage tank, which has three functions: pollutant control, flood control and water use, to the end pipe of a separate system. We examined the effect of real time control (RTC) introduction with the scenario selection in the study area in the catchment basin, which has measured data. As a result, a latter period centering-type case is satisfied with the pollutant reduction by the RTC and also at the water use tank, the best control settles COD concentration at about 0.45 mg/l. It was clarified how to use a RTC method as a measure of the discharge problem from an urban area during a storm event.

Increased and decreased expression of CD69 and CD23, respectively, in gravity-stressed lymphocytes.

BACKGROUND: Recent studies have shown that gravity-changing stress modulates expression levels of cell surface molecules on human lymphocytes. However, previous in vitro microgravity studies have been performed with lymphocytes treated with mitogenic agents. HYPOTHESIS: The aim of the study was to test if exposure of cells to gravity-changing stress alone alters the expression levels of cell surface molecules. Specifically, we examined whether the expression of activation markers is altered after exposure of lymphocytes to combinations of microgravity and hypergravity. METHODS: We used free-fall in parabolic flight for human subjects and a drop-shaft to expose peripheral blood mononuclear cells (PBMC) to gravity-changing stress. After such exposure, PBMC were isolated, and expression levels of CD69, CD23 and CD38 were estimated using three-color flow cytometry. RESULTS: Increased percentages of CD69-positive cells were observed with PBMC from 3 of 4 volunteers who undertook 10 parabolic flights. Exposure of blood to gravity-changing stress in the drop-shaft increased both ratios of CD69-positive cells and levels of CD69 expression on T and B cells. In contrast, the percentages of CD23-positive B cells was decreased. However, gravity-changing stress was not always followed by significant alteration in CD38 expression. CONCLUSIONS: Our findings suggest that CD69 and CD23 might be useful markers that are up- and down-regulated, respectively, after exposure of lymphocytes to gravity-changing stress.

Sotos syndrome with enamel hypoplasia: a case report.

A rare case of Sotos syndrome with enamel hypoplasia is described. Dental abnormalities include enamel hypoplasia, expansion of the pulp cavity, high arched palate, and absence of the bilateral pre-molar teeth of the mandible.

Enhancement of protease activity involved in modulation of cell mutability by microgravity stress in UVC-irradiated human cells.

It is an intriguing question whether gravity-changing stress modulates human cell mutability. To resolve this problem, it is necessary to determine the cellular events leading to modulation. We previously detected protease activation just after UV (UVC, principally 254 nm wavelength) irradiation followed by hypomutability in cultured human cells. We here investigated whether UV-activated protease activity is affected in human UVAP-1 cells exposed to gravity-changing stress prior to UV irradiation.

Modification of urinary secretion of 8-hydroxy-2'-deoxyguanosine and serum ACTH concentration following repetitive parabolic flights.

It is important to clarify the molecular mechanisms of physiological responses of the human body to changes in gravity. Previous reports demonstrated that gravity-changing stress increases the human urinary concentration of 8-hydroxy-2'-deoxyguanosine (8-OHdG). However, it has yet to be clarified whether repetitive parabolic flight modulates the urinary concentration of 8-OHdG after exposure to gravity-changing stress. In the present study, the effects of the number of previous experiences with parabolic flight on urinary excretion of 8-OHdG and concentration of serum ACTH were examined in 12 healthy volunteers.