Lactate, a product of aerobic glycolysis in astrocytes, is required for memory formation and consolidation, and has recently emerged as a signaling molecule for neurons and various cell types in peripheral tissues. In particular lactate stimulates mRNA expression of a few plasticity-related genes. Here, we describe a RNA-seq study that unravels genome-wide transcriptomic responses to this energy metabolite in cortical neurons. Our results show that mRNA expression of 20 immediate-early genes involved in the MAPK signaling pathway and in synaptic plasticity were increased by more than twofold following 1 h of lactate stimulation. This effect was dependent on NMDA receptor (NMDAR) activity since it was prevented by pre-treatment with MK-801. Comparison with published datasets showed that a significant proportion of genes modulated by lactate were similarly regulated by a stimulation protocol activating specifically synaptic NMDARs known to result in upregulation of pro-survival and downregulation of pro-death genes. Remarkably, transcriptional responses to lactate were reproduced by NADH (for 74 of the 113 genes, FDR < 0.05), suggesting a redox-dependent mechanism of action. Longer-term gene expression changes observed after 6 h of lactate treatment affected genes involved in regulating neuronal excitability and genes coding for proteins localized at synapses. Gene set enrichment analyses performed with ranked lists of expressed genes revealed effects on molecular functions involved in epigenetic modulation, and on processes relevant to sleep physiology and behavioral phenotypes such as anxiety and hyperactivity. Overall, these results strengthen the notion that lactate effectively regulates activity-dependent and synaptic genes, and highlight new signaling effects of lactate in plasticity and neuroprotection.

Our objective in this study was to evaluate whether measurement of quantitative uptake of 99m Tc-methylene diphosphate (MDP) and 99m Tc-hexamethylpropyleneamine oxime (HMPAO) white blood cells (WBCs) is useful in detecting osteomyelitis in peripheral bony lesions. Methods: Twenty-four patients (12 men and 12 women; age range, 25-72 y) were referred for imaging because of clinically suspected osteomyelitis. They had a traumatic fracture (n 5 10), knee prosthesis (n 5 5), hip prosthesis (n 5 2), diabetic foot (n 5 4), or chronic osteomyelitis (n 5 3). Threephase bone scanning and 99m Tc-HMPAO WBC studies were performed on all patients within the same week. Regions of interest were drawn over the abnormal bony sites and the contralateral normal sites, and the abnormal-to-normal uptake ratios (A/N ratios) were obtained for both studies. Results: All patients had abnormal findings on 3-phase bone scanning, whereas 17 (71%) had abnormal findings on 99m Tc-HMPAO WBC studies, of which 15 were confirmed to be true-positive. In those 15 patients, the mean A/N ratios for 99m Tc-MDP and 99m Tc-HMPAO WBC were 3.0 6 1.6 (range, 1.3-6.2) and 1.8 6 0.3 (range, 1.4-2.2), respectively. In the other 9 patients, whose scan results were clinically confirmed to be true-negative, the mean A/N ratios for 99m Tc-MDP and 99m Tc-HMPAO WBC were 2.1 6 1.2 and 1.2 6 0.2, respectively. In the group with a 99m Tc-MDP A/N ratio greater than 2 (n 5 15), 87% (13/15) had a high 99m Tc-HMPAO WBC A/N ratio (.1.5), including 2 that were falsepositive. In the remaining 2 patients, one with chronic osteomyelitis and the other with a recent hip prosthesis, 99m Tc-HMPAO WBC ratios were normal. In the group with a bone A/N ratio of less than 2 (n 5 9), only 4 patients (44%) were true-positive for acute osteomyelitis. Conclusion: 99m Tc-MDP bone scanning alone, with an A/N ratio of more than 2, is useful in detecting osteomyelitis in violated bone except in the case of a recent hip prosthesis or chronic osteomyelitis.

c Mycobacterium fortuitum is a member of the rapidly growing nontuberculous mycobacteria (NTM). It is ubiquitous in water and soil habitats, including hospital environments. M. fortuitum is increasingly recognized as an opportunistic nosocomial pathogen causing disseminated infection. Here we report the genome sequence of M. fortuitum subsp. fortuitum type strain DSM46621. Mycobacterium fortuitum is a nonpigmented rapidly growing Mycobacterium classified in Runyon group IV (5), first isolated from an amphibian source in 1905 and subsequently identified as the cause of a human cutaneous infection in a patient in 1938 (3). Like many other nontuberculous mycobacteria (NTM), M. fortuitum is found worldwide in natural and processed water sources, including chlorine-treated water, as well as in sewage, dirt, and hospital environments (4,8). Major types of disease caused by M. fortuitum include, in decreasing order of frequency, infections of postsurgical wounds, soft tissue, skin, and lung (3, 5, 11). Occasionally reported miscellaneous infections include keratitis, endocarditis, lymphadenitis, meningitis, hepatitis, peritonitis, catheter-related sepsis, and disseminated infections (3, 6, 11). The M. fortuitum group is attracting attention due to its increasing number of cases, its virulence, and its emerging resistance to antibiotics. However, in the genome database, there is no whole genome of this species present until now. To facilitate a more reliable genetic identification in the M. fortuitum complex, we have characterized the complete genome sequence of M. fortuitum subsp. fortuitum type strain DSM46621.To sequence the genome of M. fortuitum subsp. fortuitum type strain DSM46621, we used a shotgun sequencing method and Illumina HiSeq 2000 technology using a paired-end library, with a read length of 100 bp and an insert size of 500 bp. A total of 2.95 million Illumina sequencing reads were generated. These short sequence reads were first quality trimmed before de novo assembled using Velvet (12). The draft genome was further improved with iCORN (7) and IMAGE (10), as described in PAGIT (9), before it was scaffolded with SSPACE (2). The final assembly has 82 supercontigs and an N 50 of 159,889 bp. The genome annotation was performed using the NCBI Prokaryotic Genomes Automatic Annotation Pipeline (PGAAP).The M. fortuitum subsp. fortuitum type strain DSM46621 genome sequence is 6,349,738 bp in length, with 6,241 predicted coding sequences. The overall GC content of the chromosome was 66%. There are 54 tRNA genes and four sets of rRNA operons as predicted by the PGAAP pipeline. It was possible to assign a biological function to 67.7% (4,225) of the coding sequences on the M. fortuitum subsp. fortuitum chromosome.The RAST server annotation pipeline (1) revealed that M. fortuitum subsp. fortuitum has the highest similarity with Mycobacterium smegmatis strain MC2 155, among all mycobacteria with complete genome sequences determined. The M. fortuitum subsp. fortuitum genome was found to be smaller (6.38 Mb) than the ge...

Aims : The aim of the current study was to evaluate dentists and patients choices of type of restorative materials applied in fillings and their knowledge about the mercury content in amalgam restorations. Matrials and Methods: a cross sectional descriptive study based on two types of questionnaire, one for the dentists(119) and the other specific for the patients (500) were distributed to determine the knowledge and awareness, preference of amalgam and composite restorations. Results: showed that the awareness of the dentists about the amalgam controversy came from different sources, half of the dentists sample stated amalgam restorations were safe, were as 21% of the sample stated it unsafe. Placement of the selected restoration(either type) was influenced by different factors, recall appointments of patients complaining from several complaint was mostly from composite, 67.6 % of patients didn't have any knowledge about harmful effect of mercury release from amalgam with the majority of the patients stating that they preferred composite or a tooth colored restoration. Conclusion: within the limitations of this study awareness of safety of dental amalgam among the dentists was low, with a large agreement that postoperative complications were mainly due to composite restorations. For the patients, the majority of them did not know anything about issues related to the mercury content of the amalgam and the majority of them favored the placement of composite restoration similar to the color of their teeth.

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