Buchananholmgaard4810

Interestingly, reduction of GLUT3 on plasma membrane led to lower glucose transport and intracellular Ca2+ accumulation. It was observed that the reduction of glucose transport directed the neuron to decrease the removal and increase of intracellular Ca2+ at rest. Therefore, we concluded that reduced glucose transport impairs neuronal viability and compromise the activity of Ca2+ removal from the neuron. Thus, it is expected that changes in glucose transport may lead to a more susceptible condition or trigger a neurodegenerative condition resulting in accumulation of intracellular Ca2+. Rodents' behavioural analysis can be influenced by several factors, including housing. The PhenoWorld (PhW) is an enriched housing and testing paradigm, which proved to be relevant for screening depressive-like behaviours in rats, being remarkably sensitive for hedonic behaviour. Herein, we assessed neuronal plasticity as a consequence of living in the PhW, by comparing the structure of the medial prefrontal cortex (mPFC) and the nucleus accumbens (NAc), two brain areas involved in the circuitry regulating motivation and reward. Our findings indicate that male rats living in the PhW display increased mPFC layer II volumes, as well as increased immature spine densities and total numbers in the mPFC pyramidal neurons. The NAc volumes and NAc medium spiny neurons branching tend also to be higher in animals experiencing the physical enrichment provided in the PhW, but significant differences were not found between animals living in PhW compared to animals living in standard cages (STD6). These results demonstrate that living in a more naturalistic complex environment, closer to real life experience, impacts on the structure of brain regions implicated in complex multidimensional disorders. Alzheimer's disease (AD) is a neurodegenerative disease characterised by progressive cognitive decline and the accumulation of two hallmark proteins, amyloid-beta (Aβ) and tau. Traditionally, transgenic mouse models for AD have generally focused on Aβ pathology, however, in recent years a number of tauopathy transgenic mouse models have been developed, including the TAU58/2 mouse model. These mice develop tau pathology and neurofibrillary tangles from 2 months of age and show motor impairments and alterations in the behavioural response to elevated plus maze (EPM) testing. The cognitive and social phenotype of this model has not yet been assessed comprehensively. Furthermore, the behavioural changes seen in the EPM have previously been linked to both anxiety and disinhibitory phenotypes. Thus, this study assessed 4-month-old TAU58/2 males comprehensively for disinhibitory and social behaviours, social recognition memory, and sensorimotor gating. TAU58/2 males demonstrated reduced exploration and anxiety-like behaviours but no changes to disinhibitory behaviours, reduced sociability in the social preference test and impaired acoustic startle and prepulse inhibition. Aggressive and socio-positive behaviours were not affected except a reduction in the occurrence of nosing and anogenital sniffing. Our study identified new phenotypic characteristics of young adult male TAU58/2 transgenic mice and clarified the nature of changes detected in the behavioural response of these mice to EPM testing. Social withdrawal and inappropriate social behaviours are common symptoms in both AD and FTD patients and impaired sensorimotor gating is seen in moderate-late stage AD, emphasising the relevance of the TAU58/2 model to these diseases. Visual aesthetics influence consumers' perception, acquisition, and usage of products, but the level of significance that a commercial product's visual aesthetics hold for each consumer varies from one person to another. Such individual difference is referred to as the centrality of visual product aesthetics (CVPA). Previous research has revealed that female adults scored higher than male adults in the self-reported CVPA scale. In order to identify the neuroanatomical correlates of this gender difference, we conducted a voxel-based morphometry (VBM) study to examine the association between the CVPA and gray matter volume (GMV) in a large sample of healthy adults from mainland China. The results revealed positive correlations between the female participants' CVPA scores and the GMV in two brain areas liked to reward processing, namely the left medial orbitofrontal cortex (mOFC) and the left dorsal striatum. By contrast, the results revealed a negative correlation between the male participants' CVPA scores and their GMV in the left mOFC. Collectively, these findings suggest that the level of significance that a commercial product's visual aesthetics hold for consumers may be associated with the rewards that they are able to receive from them. These findings also provide empirical evidence about the neuroanatomical correlates of self-reported values. Intracranial hemorrhage (ICH) is a devastating disease that induces hematoma formation with poor neuronal outcome. Levetiracetam (LEV) has been approval for epilepsy seizures. In a previous study, LEV exerted protective effects on cerebral ischemia models; however, the detail effects and the influence of LEV on ICH are still unknown. The aim of this study was to investigate whether oral administration of LEV (50 or 150 mg/kg) has protective effects on ICH injury using both in vivo and in vitro experiments. In in vivo experiments, we utilized ICH models induced by autologous blood (bICH) or collagenase (cICH) injection. Moreover, we established a neuronal injury model using SYSH5Y human neuroblastoma cell lines. In the bICH model, frequently oral administration of LEV attenuated both cerebral edema and neurological deficits. In addition, the expression levels of phosphorylation-extracellular signal‑related kinase (ERK) 1/2 and cleaved caspase-7 were increased after ICH, and LEV suppressed such alterations. In in vitro experiments, hematoma releasing factors, such as hemoglobin (Hb) and hemin, induced neuronal cell death, and LEV treatment attenuated neuronal injury in a dose-dependent manner. Wnt inhibitor In the cICH model, neurological deficits induced by extensive hematoma formation were attenuated by LEV without affecting hematoma volume. link2 Taken together, these findings suggested that LEV has protective effect on neurons after ICH injury. Therefore, LEV may not only be an efficacious therapeutic agent for seizures, but also for post-hemorrhagic stroke brain injury. INTRODUCTION The ATP6AP1 gene encodes for ATPase H+ transporting protein. ATP6AP1 gene mutations are associated with congenital disorders of glycosylation (CDG) and can affect multiple organ system. Descriptions of postnatal phenotype include immunodeficiency, hepatopathy and cognitive impairment. No prenatal phenotype of these gene mutations has been described to date. CASE This is a description of the prenatal workup of an infant diagnosed with a X-linked ATP6AP1 gene mutation. First trimester ultrasound demonstrated a thickened nuchal translucency measured at 3.27 mm and dysmorphic spinal canal, corresponding to kyphoscoliosis finding postnatally. Findings from amniocentesis at 15 weeks included elevated amniotic fluid alpha-fetoprotein (AF-AFP) and positive acetylcholinesterase (AchE). Dilation of the aortic arch was seen on fetal echocardiogram at 20 weeks. Throughout the second trimester, a rim of fluid collection was seen under the skin covering the thoracic and lumbar fetal spine, consistent with a large Aplasia Cutis below the right scapula present at birth. CONCLUSION To our knowledge, this is the first description of prenatal phenotype of an X-linked ATP6AP1 gene mutation, and the association of this gene mutation with increased NT, elevated AF-AFP and AchE and Aplasia Cutis Congenita. This variant was submitted to ClinVar public database, submission ID SUB6537411. The application of next-generation sequencing to fetal pathology has proved to increase the diagnostic yield in fetuses with abnormal ultrasounds. We retrospectively reviewed genetic data of 30 selected cases studied through targeted resequencing of OMIM genes. In our experience, clinical data proved to be essential to support diagnostic reasoning and enhance variants' assessment. The molecular diagnosis was reached in 19/30 (63%) cases. Only in 7/19 cases the molecular diagnosis confirmed the initial diagnostic hypothesis, showing the relevance of the genotype-first approach. According to the genotype-phenotype correlation, we were able to divide the solved cases into three groups i) the correlation is well established but it was missed due to lack of specificity, unusual presentation or recent description; ii) the clinical presentation is much more severe than currently known for the underlying condition; iii) the correlation does not recapitulate the entire phenotype, possibly due to the fetal presentation or multiple coexisting conditions. Moreover, we found a higher proportion of recessive diagnosis in abnormal fetuses compared to cohorts of individuals with developmental delay. Our findings suggest that fetal pathology may be enriched in rare alleles and/or in unusual combinations, counter-selected in postnatal genomes and thus contributing to both phenotypic extremeness and atypical presentation. INTRODUCTION Male Breast Cancer (MBC) is a rare disease, about 1% of all breast cancers worldwide and less than 1% of cancers occurring in men. The bilateral male breast cancer (bMBC) is extremely rare. Germline mutations of BRCA1/BRCA2 genes are associated with a significantly increased risk of cancer in MBC; the role of PALB2 remains to be clarified. Our main goal was to provide contribution on characterization of BRCA1/BRCA2 and PALB2 mutations in MBC patients. METHODS We observed 28 MBC cases; one of them was a bMBC. Screening for BRCA1, BRCA2 and PALB2 genes was performed on all 28 MBC patients. Mutational analysis was extended to family members of mutated patients. RESULTS In our study, the MBC incidence was 5.2% and for bMBC was 3.6%. Mutation analysis showed pathogenic mutations in 11/28 (39.3%) patients; 2/28 (7.1%) displayed a mutation in BRCA1, 8/28 (28.6%) in BRCA2 and 1/28 (3.6%) in PALB2. Out of 11 mutated patients, one (9.1%) reported a double mutation in BRCA2. Personal history of other cancers was reported in 2/28 (7.1%) patients affected by bladder cancer. A first/second degree family history of breast/ovarian and other cancers occurred in 23/28 (82.1%) patients. CONCLUSION Our findings indicate BRCA2 as the main MBC susceptibility gene and describe an increased risk of bMBC and bladder cancer in mutated patients. The identification of mutations in MBC susceptibility genes supports the usage of oncology prevention programs in affected patients and their relatives carrying the mutation. INTRODUCTION Cowden syndrome is a cancer predisposition syndrome caused by pathogenic variants in PTEN. The affected patients possess an increased risk of breast, thyroid, renal, colorectal, endometrial cancers as well as malignant melanoma. Thus prophylactic surveillance and follow up is crucial for these patients. METHODS A review of the literature including existing guidelines from the years 1996 until 2017 was carried out. In total, 2078 scientific papers were identified through database searches on Cowden syndrome. link3 Among these, 11 manuscripts were included based on scientific relevance and quality. Expert consensus was reached to define management guidelines. RESULTS The literature revealed a high risk of cancer in specific organs for patients diagnosed with Cowden Syndrome. Alternative management guidelines were proposed and discussed. CONCLUSIONS Here we propose a revised set of management guidelines for patients with Cowden syndrome in Denmark to address the increased risk of various cancer types.