Are we studying the right populations to understand suicide?

International audienc

Personality Disorders and Health Problems Distinguish Suicide Attempters from Completers in a Direct Comparison

Background Whether suicide attempters and completers represent the same population evaluated at different points along a progression towards suicide death, overlapping populations, or completely different populations is a problem still unresolved. Methods 446 Adult suicide attempters and knowledgeable collateral informants for 190 adult suicide probands were interviewed. Sociodemographic and clinical data was collected for both groups using semi-structured interviews and structured assessments. Univariate analyses and logistic regression models were conducted to explore the similarities and differences between suicide attempters and completers. Results Univariate analyses yielded significant differences in sociodemographics, recent life events, impulsivity, suicide intent, and distribution of Axis I and II disorders. A logistic regression model aimed at distinguishing suicide completers from attempters properly classified 90% of subjects. The most significant variables that distinguished suicide from attempted suicide were the presence of narcissistic personality disorder (OR=21.4; 95% CI=6.8–67.7), health problems (OR=20.6; 95% CI=5.6–75.9), male sex (OR=9.6; 95% CI=4.42–20.9), and alcohol abuse (OR=5.5; 95% CI=2.3–14.2). Limitations Our study shares the limitations of studies comparing suicide attempters and completers, namely that information from attempters can be obtained from the subject himself, whereas the assessment of completers depends on information from close family or friends. Furthermore, different semi-structured instruments assessed Axis I and Axis II disorders in suicide attempters and completers. Finally, we have no data on inter-rater reliability data. Conclusions Suicide completers are more likely to be male and suffer from alcohol abuse, health problems (e.g. somatic illness), and narcissistic personality disorder. The findings emphasize the importance of implementing suicide prevention programs tailored to suicide attempters and completers

Factors Contributing to the Utilization of Adult Mental Health Services in Children and Adolescents Diagnosed with Hyperkinetic Disorder

Objectives. To examine whether age of First diagnosis, gender, psychiatric comorbidity, and treatment modalities (pharmacotherapy or psychotherapy) at Child and Adolescent Mental Health Services (CAMHS) moderate the risk of Adult Mental Health Services (AMHS) utilization in patients diagnosed with hyperkinetic disorder at CAMHS. Methods. Data were derived from the Madrid Psychiatric Cumulative Register Study. The target population comprised 32,183 patients who had 3 or more visits at CAMHS. Kaplan-Meier curves were used to assess survival data. A series of logistic regression analyses were performed to study the role of age of diagnosis, gender, psychiatric comorbidity, and treatment modalities. Results. 7.1% of patients presented with hyperkinetic disorder at CAMHS. Compared to preschool children, children and adolescents first diagnosed with hyperkinetic disorder at CAMHS were more likely to use AMHS. Female gender and comorbidity with affective disorders, schizophrenia, schizotypal and delusional disorders increased the risk of use of AMHS. Pharmacological or combined treatment of hyperkinetic disorder diagnosed at CAMHS was associated with increased risk of use at AMHS. Conclusions. Older age of first diagnosis, female gender, psychiatric comorbidity, and pharmacological treatment at CAMHS are markers of risk for the transition from CAMHS to AMHS in patients with hyperkinetic disorder diagnosed at CAMHS

How the oxygen tolerance of a [NiFe]-hydrogenase depends on quaternary structure

‘Oxygen-tolerant’ [NiFe]-hydrogenases can catalyze H(2) oxidation under aerobic conditions, avoiding oxygenation and destruction of the active site. In one mechanism accounting for this special property, membrane-bound [NiFe]-hydrogenases accommodate a pool of electrons that allows an O(2) molecule attacking the active site to be converted rapidly to harmless water. An important advantage may stem from having a dimeric or higher-order quaternary structure in which the electron-transfer relay chain of one partner is electronically coupled to that in the other. Hydrogenase-1 from E. coli has a dimeric structure in which the distal [4Fe-4S] clusters in each monomer are located approximately 12 Å apart, a distance conducive to fast electron tunneling. Such an arrangement can ensure that electrons from H(2) oxidation released at the active site of one partner are immediately transferred to its counterpart when an O(2) molecule attacks. This paper addresses the role of long-range, inter-domain electron transfer in the mechanism of O(2)-tolerance by comparing the properties of monomeric and dimeric forms of Hydrogenase-1. The results reveal a further interesting advantage that quaternary structure affords to proteins

Desafíos y tendencias del México actual

Conjunto de once ensayos cuyo propósito es suscitar la reflexión sobre las tendencias más importantes que marcan el inicio del siglo XXI en México y Jalisco, sin obviar las direcciones que a escala mundial toman la vida social, política y económica.ITESO, A.C

Hydrogen activation by [NiFe]-hydrogenases

Hydrogenase-1 (Hyd-1) from Escherichia coli is a membrane-bound enzyme that catalyses the reversible oxidation of molecular H2 The active site contains one Fe and one Ni atom and several conserved amino acids including an arginine (Arg(509)), which interacts with two conserved aspartate residues (Asp(118) and Asp(574)) forming an outer shell canopy over the metals. There is also a highly conserved glutamate (Glu(28)) positioned on the opposite side of the active site to the canopy. The mechanism of hydrogen activation has been dissected by site-directed mutagenesis to identify the catalytic base responsible for splitting molecular hydrogen and possible proton transfer pathways to/from the active site. Previous reported attempts to mutate residues in the canopy were unsuccessful, leading to an assumption of a purely structural role. Recent discoveries, however, suggest a catalytic requirement, for example replacing the arginine with lysine (R509K) leaves the structure virtually unchanged, but catalytic activity falls by more than 100-fold. Variants containing amino acid substitutions at either or both, aspartates retain significant activity. We now propose a new mechanism: heterolytic H2 cleavage is via a mechanism akin to that of a frustrated Lewis pair (FLP), where H2 is polarized by simultaneous binding to the metal(s) (the acid) and a nitrogen from Arg(509) (the base)

Wiring of Photosystem II to Hydrogenase for Photoelectrochemical Water Splitting.

In natural photosynthesis, light is used for the production of chemical energy carriers to fuel biological activity. The re-engineering of natural photosynthetic pathways can provide inspiration for sustainable fuel production and insights for understanding the process itself. Here, we employ a semiartificial approach to study photobiological water splitting via a pathway unavailable to nature: the direct coupling of the water oxidation enzyme, photosystem II, to the H2 evolving enzyme, hydrogenase. Essential to this approach is the integration of the isolated enzymes into the artificial circuit of a photoelectrochemical cell. We therefore developed a tailor-made hierarchically structured indium-tin oxide electrode that gives rise to the excellent integration of both photosystem II and hydrogenase for performing the anodic and cathodic half-reactions, respectively. When connected together with the aid of an applied bias, the semiartificial cell demonstrated quantitative electron flow from photosystem II to the hydrogenase with the production of H2 and O2 being in the expected two-to-one ratio and a light-to-hydrogen conversion efficiency of 5.4% under low-intensity red-light irradiation. We thereby demonstrate efficient light-driven water splitting using a pathway inaccessible to biology and report on a widely applicable in vitro platform for the controlled coupling of enzymatic redox processes to meaningfully study photocatalytic reactions.This work was supported by the U.K. Engineering and Physical Sciences Research Council (EP/H00338X/2 to E.R. and EP/G037221/1, nanoDTC, to D.M.), the UK Biology and Biotechnological Sciences Research Council (BB/K002627/1 to A.W.R. and BB/K010220/1 to E.R.), a Marie Curie Intra-European Fellowship (PIEF-GA-2013-625034 to C.Y.L), a Marie Curie International Incoming Fellowship (PIIF-GA-2012-328085 RPSII to J.J.Z) and the CEA and the CNRS (to J.C.F.C.). A.W.R. holds a Wolfson Merit Award from the Royal Society.This is the final version of the article. It first appeared from ACS Publications via http://dx.doi.org/10.1021/jacs.5b0373

Characteristics of Suicide Attempts in Anorexia and Bulimia Nervosa: A Case–Control Study

Objective: Compared to other eating disorders, anorexia nervosa (AN) has the highest rates of completed suicide whereas suicide attempt rates are similar or lower than in bulimia nervosa (BN). Attempted suicide is a key predictor of suicide, thus this mismatch is intriguing. We sought to explore whether the clinical characteristics of suicidal acts differ between suicide attempters with AN, BN or without an eating disorders (ED). Method: Case-control study in a cohort of suicide attempters (n = 1563). Forty-four patients with AN and 71 with BN were compared with 235 non-ED attempters matched for sex, age and education, using interview measures of suicidal intent and severity. Results: AN patients were more likely to have made a serious attempt (OR = 3.4, 95 % CI 1.4–7.9), with a higher expectation of dying (OR = 3.7,95 % CI 1.1–13.5), and an increased risk of severity (OR = 3.4,95 % CI 1.2–9.6). BN patients did not differ from the control group. Clinical markers of the severity of ED were associated with the seriousness of the attempt. Conclusion: There are distinct features of suicide attempts in AN. This may explain the higher suicide rates in AN. Higher completed suicide rates in AN may be partially explained by AN patients ’ higher desire to die and their more severe and lethal attempts

Functional Role of Glutamine 28 and Arginine 39 in Double Stranded RNA Cleavage by Human Pancreatic Ribonuclease

Human pancreatic ribonuclease (HPR), a member of RNase A superfamily, has a high activity on double stranded (ds) RNA. By virtue of this activity HPR appears to be involved in the host-defense against pathogenic viruses. To delineate the mechanism of dsRNA cleavage by HPR, we have investigated the role of glutamine 28 and arginine 39 of HPR in its activity on dsRNA. A non-basic residue glycine 38, earlier shown to be important for dsRNA cleavage by HPR was also included in the study in the context of glutamine 28 and arginine 39. Nine variants of HPR respectively containing Q28A, Q28L, R39A, G38D, Q28A/R39A, Q28L/R39A, Q28A/G38D, R39A/G38D and Q28A/G38D/R39A mutations were generated and functionally characterized. The far-UV CD-spectral analysis revealed all variants, except R39A, to have structures similar to that of HPR. The catalytic activity of all HPR variants on single stranded RNA substrate was similar to that of HPR, whereas on dsRNA, the catalytic efficiency of all single residue variants, except for the Q28L, was significantly reduced. The dsRNA cleavage activity of R39A/G38D and Q28A/G38D/R39A variants was most drastically reduced to 4% of that of HPR. The variants having reduced dsRNA cleavage activity also had reduction in their dsDNA melting activity and thermal stability. Our results indicate that in HPR both glutamine 28 and arginine 39 are important for the cleavage of dsRNA. Although these residues are not directly involved in catalysis, both arginine 39 and glutamine 28 appear to be facilitating a productive substrate-enzyme interaction during the dsRNA cleavage by HPR