A secure home, public and hospital environment, without access to suicidal means is a necessary strategy in suicide prevention. Each treatment option, prescription of medication and discharge of the patient from hospital should be carefully evaluated against the involved risks. TRAINING OF PERSONNEL: Training of general practitioners (GPs) is effective in the prevention of suicide. It improves treatment of depression and anxiety, quality of the provided care and attitudes towards suicide. Continuous training including discussions about ethical and legal issues is necessary for psychiatrists and other mental health professionals.

Human papillomavirus (HPV) type 16 belongs to the group of "high risk" HPV types that are frequently detected in anogenital cancers. The expression of HPV-16 late genes encoding the virus capsid proteins L1 and L2 is restricted to terminally differentiated epithelial cells in the superficial layers of the squamous epithelium. We have previously identified negative elements in the 3 end of L2 RNA that act in cis to reduce mRNA utilization without substantially affecting mRNA levels. The experiments reported here demonstrate the interaction of cellular proteins with an inhibitory sequence present in the coding region of the L2 mRNA. Using RNA gel shift assays and UV cross-linking, we have detected three cellular proteins interacting specifically with the sense strand of the L2 mRNA, two of which were identified as heterogeneous ribonucleoprotein K (hnRNP K) and the poly(rC) binding-protein (PCBP). Recombinant hnRNP K, PCBP-1, and PCBP-2 that were over expressed in bacteria and partially purified bound to the HPV-16 L2 mRNA in a sequence-specific manner. Interestingly, PCBP-1, PCBP-2, and hnRNP K specifically and efficiently inhibited translation of the HPV-16 L2 mRNA in vitro. Therefore, these proteins may play an important role in the regulation of HPV-16 late gene expression and virus production in vivo.Human papillomaviruses (HPVs) 1 are nonenveloped, epitheliotropic DNA tumor viruses with a circular double-stranded genome of approximately 8 kilobases (1). At present more than 70 different types of HPVs have been identified that can be divided into mucosal or cutaneous types on the basis of the epithelium they infect (2). The major stimulus for current interest in the HPV group originates from the discovery of the casual relationship to carcinoma of the cervix of certain HPV types, primarily types 16 and 18 (3, 4). The genomic organization of the various HPV types is very similar. All of the open reading frames are located on one strand of viral genomic DNA that consists of an early, a late, and a noncoding region (1). Early genes are expressed throughout the infected epithelium and are responsible for initiation of viral DNA replication, regulation of transcription, and transformation of cells (1, 5-9). The late genes code for the major and minor capsid proteins, L1 and L2, respectively, and their expression is thought to be regulated at both the transcriptional and the post-transcriptional level. Production of L1 and L2 protein is seen to be inhibited in dividing cells, and the L1 and L2 proteins are detected primarily in the superficial layers of terminally differentiated squamous epithelial cells (1, 5-9). Sequences with inhibitory function have been identified on HPV-1 (10), HPV-16 (11), and BPV-1 (12) late mRNAs. Inhibitory RNA elements present in the HPV-16 L1 and L2 coding regions (13-15) reduce the levels of late mRNAs and proteins, and a negative element in the late 3Ј-untranslated region (11,13,16,19) was seen to reduce RNA stability in vitro (11). The inhibitory RNA sequences on the late papilloma...

The risk for suicidal behavior (SB) is elevated in schizophrenia (SCZ), bipolar disorder (BPD) and major depressive disorder (MDD), but also occurs in subjects without psychiatric diagnoses. Genome-wide association studies (GWAS) on SB may help to understand this risk, but have been hampered by low power due to limited sample sizes, weakly ascertained SB or a reliance on single-nucleotide protein (SNP)-by-SNP analyses. Here, we tried to mitigate such issues with polygenic risk score (PRS) association tests combined with hypothesis-driven strategies using a family-based sample of 660 trios with a well-ascertained suicide attempt (SA) outcome in the offspring (Genetic Investigation of Suicide and SA, GISS). Two complementary sources of PRS information were used. First, a PRS that was discovered and validated in the GISS SA revealed the polygenic association of SNPs in 750 neurodevelopmental genes, which was driven by the SA phenotype, rather than the major psychiatric diagnoses. Second, a PRS based on three different genome-wide association studies (on SCZ, BPD or MDD) from the Psychiatric Genomics Consortium (PGC) showed an association of the PGC-SCZ PRS in the SA subjects with and without major psychiatric diagnoses. We characterized the PGC-SCZ overlap in the SA subjects without diagnoses. The extended major histocompatibility complex region did not contribute to the overlap, but we delineated the genic overlap to neurodevelopmental genes that partially overlapped with those identified by the GISS PRS. Among the 590 SA polygenes implicated here, there were several developmentally important functions (cell adhesion/migration, small GTPase and receptor tyrosine kinase signaling), and 16 of the SA polygenes have previously been studied in SB (BDNF, CDH10, CDH12, CDH13, CDH9, CREB1, DLK1, DLK2, EFEMP1, FOXN3, IL2, LSAMP, NCAM1, nerve growth factor (NGF), NTRK2 and TBC1D1). These novel genome-wide insights, supported by two lines of evidence, suggested the importance of a polygenic neurodevelopmental etiology in SB, even in the absence of major psychiatric diagnoses.

The risk of suicide, which causes about 1 million deaths each year, is considered to augment as the levels of stress increases. Dysregulation in the stress response of the hypothalamic-pituitary-adrenocortical (HPA) axis, involving the corticotrophin-releasing hormone (CRH) and its main receptor (CRHR1), is associated with depression, frequent among suicidal males. Here we have analyzed single nucleotide polymorphisms (SNPs) in these genes, in family trios with suicide attempter offspring (n 5 542), by using the transmission disequilibrium test both in a two-staged screening/replication sample design and in detailed reanalysis in the entire sample. Stratification based on the levels of lifetime stress showed reproducible association and linkage of an SNP in the CRHR1 gene (rs4792887) to suicide attempters exposed to low levels of stress (P 5 0.002), among whom most males were depressed (P 5 0.001). The identified allele may represent a part of the genetic susceptibility for suicidality by increasing HPA axis activity upon exposure to low levels of stress.