The epidemiology of suicide and attempted suicide in Dutch general practice 1983–2003

BACKGROUND: Many patients attempting or committing suicide consult their general practitioner (GP) in the preceding period, indicating that GPs might play an important role in prevention. The aim of the present study was to analyse the epidemiology of suicidal behaviour in Dutch General Practice in order to find possible clues for prevention. METHOD: Description of trends in suicide and suicide attempts occurring from 1983–2003 in the Dutch General Practice Sentinel Network, representing 1% of the Dutch population. The data were analysed with regard to: 1) suicidal behaviour trends and their association with household situation; 2) presence of depression, treatment of depression and referral rate by GPs; 3) contact with GP before suicide or suicide attempt and discussion of suicidal ideation. RESULTS: Between 1983 and 2003 the annual number of suicide and suicide attempts decreased by 50%. Sixty percent of the patients who committed or attempted suicide were diagnosed as depressed, of whom 91% were treated by their GP with an antidepressant. Living alone was a risk factor for suicide (odds ratio 1.99; 95% CI 1.50 to 2.64), whereas living in a household of 3 or more persons was a relative risk for a suicide attempt (odds ratio 1.81; 95% CI 1.34 to 2.46). Referral to a psychiatrist or other mental health professionals occurred in 65% of the cases. GPs recalled having discussed suicidal ideation in only 7% of the cases, and in retrospect estimated that they had foreseen suicide or suicide attempts in 31% and 22% of the cases, respectively, if there had been contact in the preceding month. CONCLUSION: With regard to the prescription of antidepressants and referral of suicidal patients to a psychiatrist, Dutch GPs fulfil their role as gatekeeper satisfactorily. However, since few patients discuss their suicidal ideation with their GP, there is room for improvement. GPs should take the lead to make this subject debatable. It may improve early recognition of depressed patients at risk and accelerate their referral to mental health professionals

A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer's disease

Late-onset Alzheimer’s disease is a prevalent age-related polygenic disease that accounts for 50–70% of dementia cases. Currently, only a fraction of the genetic variants underlying Alzheimer’s disease have been identified. Here we show that increased sample sizes allowed identification of seven previously unidentified genetic loci contributing to Alzheimer’s disease. This study highlights microglia, immune cells and protein catabolism as relevant to late-onset Alzheimer’s disease, while identifying and prioritizing previously unidentified genes of potential interest. We anticipate that these results can be included in larger meta-analyses of Alzheimer’s disease to identify further genetic variants that contribute to Alzheimer’s pathology

Mental health literacy and attitudes in a Swedish community sample – Investigating the role of personal experience of mental health care

<p>Abstract</p> <p>Background</p> <p>Mental ill health is a common condition in the general population, yet only about half of those with a mental disorder have treatment contact. Personal experience may affect attitudes, which in turn influence the help-seeking process. This study investigated differences in mental health literacy and attitudes among mentally healthy persons and in persons with symptoms of mental illness with and without treatment contact.</p> <p>Method</p> <p>A postal screening questionnaire was sent to a random sample of the general population aged 20–64 in the county of Skaraborg, Sweden in order to ascertain mental health status and history of treatment contact; 3538 responded (49%). Face-to-face interviews were carried out in random sub samples of mentally healthy persons (n = 128) and in mentally ill persons with (n = 125) and without (n = 105) mental health care contact. Mental health literacy and attitudes to treatment were assessed using questions based on a vignette depicting a person with depression. Past month mental disorder was diagnosed according to the Schedule for Clinical Assessment in Neuropsychiatry (SCAN).</p> <p>Results</p> <p>Two thirds failed to recognize depression in a vignette; recognition was equally poor in mentally healthy persons and in persons with symptoms of mental illness with and without treatment contact. In response to an open-ended question concerning appropriate interventions, one third suggested counselling and only one percent proposed antidepressant treatment. Again, proportions were similar in all groups. Persons with a history of mental health contact more often suggested that a GP would provide the best form of help. When presented with a list of possible interventions, those with a history of mental health contact were more positive to medical interventions such as antidepressants, hypnotics, and inpatient psychiatric treatment. When asked about the prognosis for the condition described in the vignette, persons with treatment contact were less likely to believe in full recovery without intervention; mentally ill without treatment contact were more optimistic.</p> <p>Conclusion</p> <p>Mental health literacy, specially concerning attitudes towards interventions is associated with personal history of mental health care.</p

A new family of mono- and dicarboxylic ruthenium complexes [Ru(DIP)(2)(L-2)](2+) (DIP=4,7-diphenyl-1,10-phenanthroline): Synthesis, solution behavior, and X-ray molecular structure of trans-[Ru(DIP)(2)(MeOH)(2)][OTf](2)

9 pagesA new family of ruthenium complexes of general formula [Ru(DIP)(2)(L-2)](2+), where DIP) 4,7-diphenyl-1,10-phenanthroline,a bidentate ligand with an extended aromatic system, was prepared and fully characterized. When L is a monodentate ligand, the following complexes were obtained: L = CF3SO3-1 (2), CH3CN (3), and MeOH (4). When L-2 is a bidentate ligand, the compounds [Ru(DIP)(2)(Hcmbpy)][Cl](2) (5) and [Ru(DIP)(2)(H(2)dcbpy)][Cl](2) ( 6) were prepared (Hcmbpy = 4-carboxy-4'-methyl-2,2-bipyridine, H(2)dcbpy = 4,4'-dicarboxy-2,2'-bipyridine). Complex [Ru(DIP)(2)(MeOH)(2)][OTf](2) (4) displayed a trans configuration of the DIP ligands, which is rare for octahedral complexes featuring DIP bidentate ligands. DFT calculations carried out on 4 showed that the cis isomer is more stable by 12.2 kcal/ mol relative to the trans species. The solution behaviors of monocarboxylic complex [ Ru( DIP) 2( Hcmbpy)][Cl](2) ( 5) and dicarboxylic complex [Ru(DIP)(2)(H(2)dcbpy)][Cl](2) (6) were investigated by H-1 NMR spectroscopy. VT-NMR, concentration dependence, and reaction with NaOD allowed us to suggest that aggregation of the cationic species in solution, especially for 6, originates mainly from hydrogen bonding interactions

Mapping 3' transcript ends in the bank vole (Clethrionomys glareolus) mitochondrial genome with RNA-Seq

Background: Although posttranscriptional modification of mitochondrial (mt) transcripts plays key roles in completion of the coding information and in the expression of mtDNA-encoded genes, there is little experimental evidence on the polyadenylation status and the location of mt gene poly(A) sites for non-human mammals. Results: Poly(A)-enriched RNA-Seq reads collected for two wild-caught bank voles (Clethrionomys glareolus) were mapped to the complete mitochondrial genome of that species. Transcript polyadenylation was detected as unmapped adenine residues at the ends of the mapped reads. Where the tRNA punctuation model applied, there was the expected polyadenylation, except for the nad5 transcript, whose polyadenylated 3' end is at an intergenic sequence/cytochrome b boundary. As in human, two pairs of bank vole genes, nad4l/nad4 and atp8/atp6, are expressed from bicistronic transcripts. TAA stop codons of four bank vole protein-coding genes (nad1, atp6, cox3 and nad4) are incompletely encoded in the DNA and are completed by polyadenylation. This is three genes (nad2, nad3 and cob) less than in human. The bank vole nad2 gene encodes a full stop codon (TAA in one vole and TAG in the other), which is followed by a 2bp UTR and the gene conforms to the tRNA punctuation model. In contrast, the annotations of the reference mouse and some other rodent mt genomes in GenBank include complete TAG stop codons in both nad1 and nad2, which overlap downstream trnI and trnW, respectively. Thus the RNA-Seq data of bank voles provides a model for stop codons of mt-encoded genes in mammals comparable to humans, but at odds with some of the interpretation based purely on genomic data in mouse and other rodents. Conclusions: This work demonstrates how RNA-Seq data were useful to recover mtDNA transcriptome data in a non-model rodent and to shed more light on mammalian mtDNA transcriptome and post-transcriptional modification. Even though gene content and organisation of mtDNA are strongly conserved among mammals, annotations that neglect the transcriptome may be prone to errors in relation to the stop codons.The work was carried out with the support from the Czech Science Foundation (grant number P506-11-1872) and the institutional support (RVO 67985904)

X-ray fluorescence imaging of single human cancer cells reveals that the N-heterocyclic ligands of iodinated analogues of ruthenium anticancer drugs remain coordinated after cellular uptake

Analogues of KP1019 containing iodinated indazole ligands were prepared to investigate the biological fate of the Ru-N-heterocycle bond in this class of anticancer agents. The new complexes, 5-iodoindazolium trans-tetrachloridobis(5-iodoindazole)ruthen(III)ate (1) and 5-iodoindazolium trans-tetrachlorido(dimethyl sulfoxide)(5-iodoindazole)ruthen(III)ate (3), were characterized by elemental analysis, mass spectrometry and UV-vis spectrophotometry. Tetramethylammonium salts of these complexes (2 and 4) were synthesized and characterized in a similar manner. Half-maximum inhibitory concentrations of 2 and 4 with regard to A549 cells at 24 h were determined on the basis of the dose-response curves derived from real-time cell adhesion impedance measurements and were shown to be in the same range as those determined for KP1019 and NAMI-A using the same method. X-ray fluorescence imaging of single cultured A549 cells treated with 2 or 4 showed that, in both cases, the distribution of ruthenium and iodine was identical, indicating that the Ru-N bonds in the anionic complexes remained intact after incubation in culture medium and subsequent cellular uptake and processing.Sumy Antony, Jade B. Aitken, Stefan Vogt, Barry Lai, Tracey Brown, Leone Spiccia, Hugh H. Harri