Mortality,Rehospitalisation and Violent Crime in Forensic Psychiatric Patients Discharged from Hospital: Rates and Risk Factors

ObjectivesTo determine rates and risk factors for adverse outcomes in patients discharged from forensic psychiatric services.MethodWe conducted a historical cohort study of all 6,520 psychiatric patients discharged from forensic psychiatric hospitals between 1973 and 2009 in Sweden. We calculated hazard ratios for mortality, rehospitalisation, and violent crime using Cox regression to investigate the effect of different psychiatric diagnoses and two comorbidities (personality or substance use disorder) on outcomes.ResultsOver mean follow-up of 15.6 years, 30% of patients died (n = 1,949) after discharge with an average age at death of 52 years. Over two-thirds were rehospitalised (n = 4,472, 69%), and 40% violently offended after discharge (n = 2,613) with a mean time to violent crime of 4.2 years. The association between psychiatric diagnosis and outcome varied—substance use disorder as a primary diagnosis was associated with highest risk of mortality and rehospitalisation, and personality disorder was linked with the highest risk of violent offending. Furthermore comorbid substance use disorder typically increased risk of adverse outcomes.ConclusionViolent offending, premature mortality and rehospitalisation are prevalent in patients discharged from forensic psychiatric hospitals. Individualised treatment plans for such patients should take into account primary and comorbid psychiatric diagnoses.     

Identification of Amino Acid Residues of ERH Required for Its Recruitment to Nuclear Speckles and Replication Foci in HeLa Cells

ERH is a small, highly evolutionarily conserved nuclear protein of unknown function. Its three-dimensional structure is absolutely unique and it can form a homodimer through a β sheet surface. ERH has been shown to interact, among others, with PDIP46/SKAR and Ciz1. When coexpressed with the latter protein, ERH accumulates in replication foci in the nucleus of HeLa cells. Here, we report that when ERH is coexpressed with PDIP46/SKAR in HeLa cells, it is recruited to nuclear speckles, and identify amino acid residues critical for targeting ERH to both these subnuclear structures. ERH H3A Q9A shows a diminished recruitment to nuclear speckles but it is recruited to replication foci. ERH E37A T51A is very poorly recruited to replication foci while still accumulating in nuclear speckles. Consequently, ERH H3A Q9A E37A T51A is recruited neither to nuclear speckles nor to replication foci. The lack of interactions of these three ERH forms with PDIP46/SKAR and/or Ciz1 was further confirmed in vitro by GST pull-down assay. The residues whose substitutions interfere with the accumulation in nuclear speckles are situated on the β sheet surface of ERH, indicating that only the monomer of ERH can interact with PDIP46/SKAR. Substitutions affecting the recruitment to replication foci map to the other side of ERH, near a long loop between the α1 and α2 helices, thus both the monomer and the dimer of ERH could interact with Ciz1. The construction of the ERH mutants not recruited to nuclear speckles or replication foci will facilitate further studies on ERH actions in these subnuclear structures.     

Mutations in radial spoke head genes and ultrastructural cilia defects in East-European cohort of primary ciliary dyskinesia patients

Primary ciliary dyskinesia (PCD) is a rare (1/20,000), multisystem disease with a complex phenotype caused by the impaired motility of cilia/flagella, usually related to ultrastructural defects of these organelles. Mutations in genes encoding radial spoke head (RSPH) proteins, elements of the ciliary ultrastructure, have been recently described. However, the relative involvement of RSPH genes in PCD pathogenesis remained unknown, due to a small number of PCD families examined for mutations in these genes. The purpose of this study was to estimate the involvement of RSPH4A and RSPH9 in PCD pathogenesis among East Europeans (West Slavs), and to shed more light on ultrastructural ciliary defects caused by mutations in these genes. The coding sequences of RSPH4A and RSPH9 were screened in PCD patients from 184 families, using single strand conformational polymorphism analysis and sequencing. Two previously described (Q109X; R490X) and two new RSPH4A mutations (W356X; IVS3_2-5del), in/around exons 1 and 3, were identified; no mutations were found in RSPH9. We estimate that mutations in RSPH4A, but not in RSPH9, are responsible for 2-3% of cases in the East European PCD population (4% in PCD families without situs inversus; 11% in families preselected for microtubular defects). Analysis of the SNP-haplotype background provided insight into the ancestry of repetitively found mutations (Q109X; R490X; IVS3_2-5del), but further studies involving other PCD cohorts are required to elucidate whether these mutations are specific for Slavic people or spread among other European populations. Ultrastructural defects associated with the mutations were analyzed in the transmission electron microscope images; almost half of the ciliary cross-sections examined in patients with RSPH4A mutations had the microtubule transposition phenotype (9+0 and 8+1 pattern). While microtubule transposition was a prevalent ultrastructural defect in cilia from patients with RSPH4A mutations, similar defects were also observed in PCD patients with mutations in other genes.     

Interferon signaling in the liver during hepatitis C virus infection

Hepatitis C virus is a global health concern, estimated to infect 2-3% of the world's population. Inter-individual differences in the course of infection and response to therapy, highlighted by recent genomewide association studies, point to the crucial role of the host immune system in the efficient control of infection. Ongoing progress in the studies of the role of innate immunity during hepatitis C virus infection has improved our understanding of the intricacies of the host-virus interactions. In this review, we summarize and discuss the current knowledge concerning interferon signaling in the liver during acute and chronic hepatitis C virus infection and its implications for the outcome of interferon-α-based antiviral therapies.     

Contribution of transgenic Casuarinaceae to our knowledge of the actinorhizal symbioses

The Casuarinaceae family is a group of 96 species of trees and shrubs that are tolerant to adverse soil and climatic conditions. In the field, Casuarinaceae bears nitrogen-fixing root nodules (so called actinorhizal nodules) resulting from infection by the soil actinomycete Frankia. The association between Casuarina and Frankia is of tremendous ecological importance in tropical and subtropical areas where these trees contribute to land stabilization and soil reclamation. During differentiation of the actinorhizal nodule, a set of genes called actinorhizal nodulins is activated in the developing nodule. Understanding the molecular basis of actinorhizal nodule ontogenesis requires molecular tools such as genomics together with gene transfer technologies for functional analysis of symbiotic genes. Using the biological vectors Agrobacterium rhizogenes and A. tumefaciens, gene transfer into the two species Allocasuarina verticillata and Casuarina glauca has been successful. Transgenic Casuarinaceae plants proved to be valuable tools for exploring the molecular mechanisms resulting from the infection process of actinorhizal plants by Frankia.     

Isolation and characterisation of KP34--a novel φKMV-like bacteriophage for Klebsiella pneumoniae

Bacteriophage KP34 is a novel virus belonging to the subfamily Autographivirinae lytic for extended-spectrum ??-lactamase-producing Klebsiella pneumoniae strains. Its biological features, morphology, susceptibility to chemical and physical agents, burst size, host specificity and activity spectrum were determined. As a potential antibacterial agent used in therapy, KP34 molecular features including genome sequence and protein composition were examined. Phylogenetic analyses and clustering of KP34 phage genome sequences revealed its clear relationships with ??phiKMV-like viruses??. Simultaneously, whole-genome analyses permitted clustering and classification of all phages, with completely sequenced genomes, belonging to the Podoviridae.     

Structural basis for antiviral inhibition of the main protease, 3C, from human enterovirus 93

Members of the Enterovirus genus of the Picornaviridae family are abundant, with common human pathogens that belong to the rhinovirus (HRV) and enterovirus (EV) species, including diverse echo-, coxsackie- and polioviruses. They cause a wide spectrum of clinical manifestations ranging from asymptomatic to severe diseases with neurological and/or cardiac manifestations. Pandemic outbreaks of EVs may be accompanied by meningitis and/or paralysis and can be fatal. However, no effective prophylaxis or antiviral treatment against most EVs is available. The EV RNA genome directs the synthesis of a single polyprotein that is autocatalytically processed into mature proteins at Gln↓Gly cleavage sites by the 3C protease (3C^pro), which has narrow, conserved substrate specificity. These cleavages are essential for virus replication, making 3C^pro an excellent target for antivirus drug development. In this study, we report the first determination of the crystal structure of 3C^pro from an enterovirus B, EV-93, a recently identified pathogen, alone and in complex with the anti-HRV molecules compound 1 (AG7404) and rupintrivir (AG7088) at resolutions of 1.9, 1.3, and 1.5 Å, respectively. The EV-93 3C^pro adopts a chymotrypsin-like fold with a canonically configured oxyanion hole and a substrate binding pocket similar to that of rhino-, coxsackie- and poliovirus 3C proteases. We show that compound 1 and rupintrivir are both active against EV-93 in infected cells and inhibit the proteolytic activity of EV-93 3C^pro in vitro. These results provide a framework for further structure-guided optimization of the tested compounds to produce antiviral drugs against a broad range of EV species.     

Serum RBP4 positively correlates with triglyceride level but not with BMI,fat mass and insulin resistance in healthy obese and non-obese individuals

Abstract

Purpose: Retinol binding protein 4 (RBP4) has recently been identified as an adipokine possibly involved in the development of impaired glucose metabolism. We aimed to test serum RBP4 in healthy non-obese individuals and in patients with well-characterized phenotype: obesity without confounding effects of diabetes, metabolic syndrome or dyslipidaemia. Additionally, we examined whether serum RBP4 is associated with anthropometric parameters, insulin resistance and blood lipid parameters.

Patients and methods: Twenty-eight patients with obesity and no co-morbidities and twenty-five age-matched lean controls were recruited. Anthropometric parameters, body composition, fasting blood lipid profile, RBP4, glucose and insulin were assessed and HOMA-IR was calculated.

Results: Mean concentration of RBP4 did not differ between studied groups (in obese patients was 33.93?±?4.46?µg/ml and 32.53?±?2.53?µg/ml in non-obese controls). RBP4 positively correlated with serum triglycerides in obese and non-obese individuals (r?=?0.74, p?=?0.03 and r?=?0.62, p?=?0.02, respectively) and did not show any significant associations with HOMA-IR, anthropometric and body composition parameters.

Conclusions: Excessive adiposity without co-morbidities is not associated with higher levels of circulating RBP4. Serum RBP4 cannot be considered as a direct predictive marker for impaired glucose metabolism. RBP4 possibly contributes to lipid metabolism.     

Urbanization Level and Woodland Size Are Major Drivers of Woodpecker Species Richness and Abundance

Urbanization is a process globally responsible for loss of biodiversity and for biological homogenization. Urbanization may have a direct negative impact on species behaviour and indirect effects on species populations through alterations of their habitats, for example patch size and habitat quality. Woodpeckers are species potentially susceptible to urbanization. These birds are mostly forest specialists and the development of urban areas in former forests may be an important factor influencing their richness and abundance, but documented examples are rare. In this study we investigated how woodpeckers responded to changes in forest habitats as a consequence of urbanization, namely size and isolation of habitat patches, and other within-patch characteristics. We selected 42 woodland patches in a gradient from a semi-natural rural landscape to the city centre of Poznań (Western Poland) in spring 2010. Both species richness and abundance of woodpeckers correlated positively to woodland patch area and negatively to increasing urbanization. Abundance of woodpeckers was also positively correlated with shrub cover and percentage of deciduous tree species. Furthermore, species richness and abundance of woodpeckers were highest at moderate values of canopy openness. Ordination analyses confirmed that urbanization level and woodland patch area were variables contributing most to species abundance in the woodpecker community. Similar results were obtained in presence-absence models for particular species. Thus, to sustain woodpecker species within cities it is important to keep woodland patches large, multi-layered and rich in deciduous tree species.