BackgroundPatients with major depressive disorder (MDD) have a high risk of suicide. Many pathophysiological factors involved in MDD and suicide such us a low cholesterol levels have been associated with MDD and increased vulnerability to suicide. In this study, we investigate the relation between lipid parameters and suicide risk in patients with MDD.MethodsPlasma levels of total cholesterol, triglycerides, and high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c) were determined in 160 patients meeting the DSM-IV-TR criteria for MDD (110 patients without suicidal behavior and 52 suicidal attempters) and 151 healthy controls.ResultsA significant decrease in plasma cholesterol levels was observed in the group of suicidal depressive patients compared to those without suicidal behavior (p < 0.001). For the other lipid levels (triglycerides, HDL cholesterol, and LDL cholesterol), there were no significant differences between suicidal and non-suicidal patients.ConclusionsOur study showed a significant decrease in plasma cholesterol levels in suicidal patients. This result support the hypothesis of the association of low plasma cholesterol level and suicidal behavior in patients with major depressive disorder.

Hereditary combined vitamin K-dependent (VKD) coagulation factor deficiency is an autosomal recessive bleeding disorder associated with defects in either the ␥-carboxylase, which carboxylates VKD proteins to render them active, or the vitamin K epoxide reductase (VKORC1), which supplies the reduced vitamin K cofactor required for carboxylation. Such deficiencies are rare, and we report the fourth case resulting from mutations in the carboxylase gene, identified in a Tunisian girl who exhibited impaired function in hemostatic VKD factors that was not restored by vitamin K administration. Sequence analysis of the proposita did not identify any mutations in the VKORC1 gene but, remarkably, revealed 3 heterozygous mutations in the carboxylase gene that caused the substitutions Asp31Asn, Trp157Arg, and Thr591Lys. None of these mutations have previously been reported. Family analysis showed that Asp31Asn and Thr591Lys were coallelic and maternally transmitted while Trp157Arg was transmitted by the father, and a genomic screen of 100 healthy individuals ruled out frequent polymorphisms. Mutational analysis indicated wild-type activity for the Asp31Asn carboxylase. In contrast, the respective Trp157Arg and Thr591Lys activities were 8% and 0% that of wildtype carboxylase, and their compound heterozygosity can therefore account for functional VKD factor deficiency. The implications for carboxylase mechanism are discussed. IntroductionHereditary combined vitamin K-dependent (VKD) factor deficiency is a bleeding disorder characterized by the reduced activities of the procoagulant factors II, VII, IX, and X and anticoagulant proteins C, S, and Z. [1][2][3][4][5][6][7][8] The inheritance of the disease is autosomal recessive and is due to mutations in the genes for either the ␥-carboxylase 9-12 or the vitamin K epoxide reductase (VKORC1). 13 The carboxylase converts clusters of Glus to ␥-carboxylated Glus (Glas) in the Gla domains of VKD proteins, which renders them active by generating a calcium-binding module that binds either to anionic phospholipids that become exposed on cell surfaces or to hydroxyapatite in the extracellular matrix. 14,15 The carboxylase uses reduced vitamin K (KH 2 ) as a cofactor to drive Glu carboxylation, and the KH 2 becomes oxygenated to a vitamin K epoxide (KO) product that must be recycled for continuous carboxylation. Recycling is accomplished by VKORC1, which is the target of anticoagulant therapy with coumarin derivatives like warfarin that block KH 2 regeneration and consequently inhibit VKD protein carboxylation. Both VKORC1 and the carboxylase are integral membrane enzymes that reside in the endoplasmic reticulum (ER), where the VKD hemostatic factors are modified during their secretion from the cell. The concerted action of these 2 enzymes can therefore explain why congenital defects in either the carboxylase or VKORC1 lead to combined functional deficiency of the VKD factors.The interactions between VKD proteins and the carboxylase are complex and not well understood. 16,17 All VKD prot...

This paper proposes a systematized presentation and a terminology for observations in a Bayesian network. It focuses on the three main concepts of uncertain evidence, namely likelihood evidence and fixed and not-fixed probabilistic evidence, using a review of previous literature. A probabilistic finding on a variable is specified by a local probability distribution and replaces any former belief in that variable. It is said to be fixed or not fixed regarding whether it has to be kept unchanged or not after the arrival of observation on other variables. Fixed probabilistic evidence Véronique Delcroix Science and Enterprise Parks, LE11 3TU Leicestershire, UK is defined by Valtorta et al. (J Approx Reason 29(1):71-106 2002) under the name soft evidence, whereas the concept of not-fixed probabilistic evidence has been discussed by Chan and Darwiche (Artif Intell 163(1):67-90 2005). Both concepts have to be clearly distinguished from likelihood evidence defined by Pearl (1988), also called virtual evidence, for which evidence is specified as a likelihood ratio, that often represents the unreliability of the evidence. Since these three concepts of uncertain evidence are not widely understood, and the terms used to describe these concepts are not well established, most Bayesian networks engines do not offer well defined propagation functions to handle them. Firstly, we present a review of uncertain evidence and the proposed terminology, definitions and concepts related to the use of uncertain evidence in Bayesian networks. Then we describe updating algorithms for the propagation of uncertain evidence. Finally, we propose several results where the use of fixed or not-fixed probabilistic evidence is required.

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Fast atom bombardment mass spectrometry has already been used for the identification of mutations in abnormal human hemoglobin chains. This paper presents new results obtained with this technique. The methodology used here is compared with more conventional biochemical techniques and automated microsequencing. In every case, a well-chosen combination of peptide-high performance liquid chromatography, mass spectrometry, amino acid analysis, and sequence analysis led rapidly to the identification of the mutant. The high sensitivity of these techniques holds great promise for the analysis of molecular abnormalities in various genetic disorders presently detectable only by the application of a molecular biological approach.

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During a routine hematological investigation of a child from Tunis, a silent hemoglobin variant was discovered by isoelectric-focusing. This variant was not detectable by conventional electrophoretic methods, had normal stability, expression, and oxygen affinity, and did not produce any clinical symptoms. This new variant beta 124(H2)Pro----Ser was named Hb Tunis.