Decision support in psychiatry – a comparison between the diagnostic outcomes using a computerized decision support system versus manual diagnosis

Background  

Correct diagnosis in psychiatry may be improved by novel diagnostic procedures. Computerized Decision Support Systems (CDSS) are suggested to be able to improve diagnostic procedures, but some studies indicate possible problems. Therefore, it could be important to investigate CDSS systems with regard to their feasibility to improve diagnostic procedures as well as to save time.     

Regulation of experimental autoimmune encephalomyelitis by CD4+, CD25+ and CD8+ T cells: analysis using depleting antibodies

Experimental Autoimmune Encephalomyelitis (EAE) can be induced in mice of the C57BL/6 strain by subcutaneous immunization with myelin/oligodendrocyte glycoprotein (MOG) peptide p35-55 in CFA, administered twice at an interval of one week and supplemented with Bordetella pertussis toxin given IV. Here, we studied the effect on the induction of EAE of depleting antibodies to CD4, CD8, or CD25 administered before either the first or the second dose of MOG p35-55. We found that anti-CD4 abolished EAE when given before the first immunization; anti-CD4 did not affect the disease when it was given before the second immunization. Anti-CD8 enhanced EAE induction when given before either of the two immunizations. Anti-CD25 enhanced EAE to the same degree as anti-CD8 when given before the first immunization, but anti-CD25 was even more effective in enhancing EAE when given before the second immunization. The anti-CD25 treatment led to significantly enhanced IFNgamma production by T cells responding to MOG p35-55 and persisting anti-MOG antibodies detectable 56 days after the first immunization. Administration of anti-CD8 or anti-CD25 abolished the need for pertussis toxin to induce EAE. These findings are compatible with the idea that CD4 T cells are required for the initial induction of EAE and that the disease is down-regulated by T cells expressing CD8 or CD25. These regulatory T cells exist prior to MOG immunization, but the CD25+ regulators appear to be further amplified by immunization.     

Effects of lumbar extensor fatigue and fatigue rate on postural sway

Falls from heights resulting from a loss of balance are a major concern in the occupational setting. Previous studies have documented a deleterious effect of lower extremity fatigue on balance. The purpose of this study was to investigate the effect of lumbar extensor fatigue on balance during quiet standing. Additionally, the effects of fatigue rate on balance and balance recovery rate were assessed. Eight center-of-pressure-based measures of postural sway were collected from 13 participants, both before and after a protocol that fatigued the lumbar extensors to 60% of their unfatigued maximum voluntary exertion force. In addition, postural sway was measured for 30 min after the fatiguing protocol, at 5-min intervals, to quantify balance recovery rate during recovery from fatigue. Two different fatigue rates were achieved by fatiguing participants over either 10 min or 90 min. Results show an increase up to 58% in time-domain postural sway measures with lumbar extensor fatigue, but no change in frequency-domain measures. Fatigue rate did not affect the magnitude of these postural sway increases, nor did it affect the rate of balance recovery following fatigue. Statistical power for the latter result, however, was low. These results show that lumbar extensor fatigue increases postural sway and may contribute to fall-from-height accidents.     

Human and mouse alpha-synuclein genes: comparative genomic sequence analysis and identification of a novel gene regulatory element

The human alpha-synuclein gene (SNCA) encodes a presynaptic nerve terminal protein that was originally identified as a precursor of the non-beta-amyloid component of Alzheimer's disease plaques. More recently, mutations in SNCA have been identified in some cases of familial Parkinson's disease, presenting numerous new areas of investigation for this important disease. Molecular studies would benefit from detailed information about the long-range sequence context of SNCA. To that end, we have established the complete genomic sequence of the chromosomal regions containing the human and mouse alpha-synuclein genes, with the objective of using the resulting sequence information to identify conserved regions of biological importance through comparative sequence analysis. These efforts have yielded approximately 146 and approximately 119 kb of high-accuracy human and mouse genomic sequence, respectively, revealing the precise genetic architecture of the alpha-synuclein gene in both species. A simple repeat element upstream of SNCA/Snca has been identified and shown to be necessary for normal expression in transient transfection assays using a luciferase reporter construct. Together, these studies provide valuable data that should facilitate more detailed analysis of this medically important gene.     

Immunoelectron microscopic localization of the M6a antigen in rat brain

The monoclonal antibody M6-7, which recognizes both native and denatured immunopurified M6a antigen, was used in the present immunocytochemical study to localize its corresponding antigen in young rat brain. Strong labelling was observed in the cerebellar molecular layer, which corresponds to heavily stained axon terminals originating from granule cells. The immunodeposit, as observed by electron microscopy, is present only on the cytoplasmic side of the presynaptic membrane and on the membrane of synaptic vesicles. In contrast, the Purkinje cells and their processes are unstained. Stained synapses are also found, although less frequently, in several other cerebral areas. The pattern of staining at these synapses is similar to that observed in the cerebellar molecular layer. It is hypothesized, on the basis of its restricted distribution in certain neuronal endings and its high homology with myelin proteolipids, that the M6a antigen revealed by the M6-7 antibody is probably involved in a specific biological function in these structures.     

Two anonymous X-specific human sequences detecting restriction fragment length polymorphisms in region Xq26→qter

Two anonymous X-specific sequences isolated from a genomic library of flow-sorted X chromosomal DNA were selected for study because they revealed restriction fragment length polymorphisms in the region Xq26 qter. One sequence, DXS10, detected a two-allele TaqI polymorphic system with allele frequencies of 0.33 and 0.67. The other, 4D-8, defined an Mspl polymorphism with allele frequencies of 0.18 and 0.82. DXS10 is tightly linked to the hypoxanthine phosphoribosyltransferase (HPRT)locus with recombination distance =0 cM at LOD=5.55 (95 % probability limit <15 cM). DXS10 maps to Xq26 but is not contained within the HPRTlocus itself. 4D-8 shows no detectable linkage to the HPRTlocus, with maximum likelihood estimate for =50 cM and a LOD score of –2.61 at = 5 cM. These two polymorphisms provide additional chromosomal loci for gene mapping by linkage at the distal end of the long arm of the human X chromosome.     

Immunohistochemical and ultrastructural analysis of a mammary cystic hypersecretory carcinoma

Cystic hypersecretory carcinoma (CHC) is a rare variant of intraductal carcinoma. A CHC in a 50-year-old woman was excised and processed for light and electron microscopy and immunohistochemistry. The tumor had a marked cystic appearance. The walls of the cysts consisted of epithelial and myoepithelial cells and a well-developed basement membrane. The epithelial cells contained well-developed rough-surfaced endoplasmatic reticulum and Golgi apparatus. Secretory granules were not detected, with the exception of a few mucus-producing cells. The secretion was predominantly homogenous, reminiscent of thyroid colloid, and demonstrated distinct PAS positivity. The cells displayed a strong labeling with epithelial membrane antigen (EMA) and EMA-positive structures were observed within the intraluminal secretion, too. Some of these were stained by alcian blue. In addition, the colloid-like material was admixed with mucus showing a filamentous internal structure and lipid droplets resulting in some heterogenity of the secretion. Intraductal micropapillary proliferation in some of the cysts and adjacent nondistended ducts was a further defining feature of the tumor. Steroid hormone receptor and Ki-67 proliferation marker immuno his Tochemistry showed scattered positivity among the tumor cells. These results are in agreement with previous observations and further clarify the nature of this low-grade in situ cancer.     

Periodontal pathogens Porphyromonas gingivalis and Fusobacterium nucleatum promote tumor progression in an oral-specific chemical carcinogenesis model

Oral squamous cell carcinoma (OSCC) is a lethal disease whose incidence is increasing. Epidemiologic studies demonstrate an association between periodontitis and oral cancer, and periodontal pathogens are implicated in the pathogenesis of numerous disorders, including rheumatoid arthritis, cardiovascular diseases, diabetes and gastrointestinal malignancies. Nevertheless, a causal role for periodontal pathogens in OSCC has not been shown, partly due to the lack of an appropriate animal model. Here, utilizing a newly-established murine model of periodontitis-associated oral tumorigenesis, we report that chronic bacterial infection promotes OSCC, and that augmented signaling along the IL-6-STAT3 axis underlies this effect. Our results indicate that periodontal pathogens P. gingivalis and F. nucleatum stimulate tumorigenesis via direct interaction with oral epithelial cells through Toll-like receptors. Furthermore, oral pathogens stimulate human OSCC proliferation and induce expression of key molecules implicated in tumorigenesis. To the best of our knowledge, these findings represent the first demonstration of a mechanistic role for oral bacteria in chemically induced OSCC tumorigenesis. These results are highly relevant for the design of effective prevention and treatment strategies for OSCC.