A novel approach to determining violence risk in schizophrenia: developing a stepped strategy in 13,806 discharged patients

Clinical guidelines recommend that violence risk be assessed in schizophrenia. Current approaches are resource-intensive as they employ detailed clinical assessments of dangerousness for most patients. An alternative approach would be to first screen out patients at very low risk of future violence prior to more costly and time-consuming assessments. In order to implement such a stepped strategy, we developed a simple tool to screen out individuals with schizophrenia at very low risk of violent offending. We merged high quality Swedish national registers containing information on psychiatric diagnoses, socio-demographic factors, and violent crime. A cohort of 13,806 individuals with hospital discharge diagnoses of schizophrenia was identified and followed for up to 33 years for violent crime. Cox regression was used to determine risk factors for violent crime and construct the screening tool, the predictive validity of which was measured using four outcome statistics. The instrument was calibrated on 6,903 participants and cross-validated using three independent replication samples of 2,301 participants each. Regression analyses resulted in a tool composed of five items: male sex, previous criminal conviction, young age at assessment, comorbid alcohol abuse, and comorbid drug abuse. At 5 years after discharge, the instrument had a negative predictive value of 0.99 (95% CI = 0.98–0.99), meaning that very few individuals who the tool screened out (n = 2,359 out of original sample of 6,903) were subsequently convicted of a violent offence. Screening out patients who are at very low risk of violence prior to more detailed clinical assessment may assist the risk assessment process in schizophrenia.     

Metabolic flux rearrangement in the amino acid metabolism reduces ammonia stress in the α1-antitrypsin producing human AGE1.HN cell line

This study focused on metabolic changes in the neuronal human cell line AGE1.HN upon increased ammonia stress. Batch cultivations of α(1)-antitrypsin (A1AT) producing AGE1.HN cells were carried out in media with initial ammonia concentrations ranging from 0mM to 5mM. Growth, A1AT production, metabolite dynamics and finally metabolic fluxes calculated by metabolite balancing were compared. Growth and A1AT production decreased with increasing ammonia concentration. The maximum A1AT concentration decreased from 0.63g/l to 0.51g/l. Central energy metabolism remained relatively unaffected exhibiting only slightly increased glycolytic flux at high initial ammonia concentration in the medium. However, the amino acid metabolism was significantly changed. Fluxes through transaminases involved in amino acid degradation were reduced concurrently with a reduced uptake of amino acids. On the other hand fluxes through transaminases working in the direction of amino acid synthesis, i.e., alanine and phosphoserine, were increased leading to increased storage of excess nitrogen in extracellular alanine and serine. Glutamate dehydrogenase flux was reversed increasingly fixing free ammonia with increasing ammonia concentration. Urea production additionally observed was associated with arginine uptake by the cells and did not increase at high ammonia stress. It was therefore not used as nitrogen sink to remove excess ammonia. The results indicate that the AGE1.HN cell line can adapt to ammonia concentrations usually present during the cultivation process to a large extent by changing metabolism but with slightly reduced A1AT production and growth.     

Peptidome Analysis of Cerebrospinal Fluid by LC-MALDI MS

We report on the analysis of endogenous peptides in cerebrospinal fluid (CSF) by mass spectrometry. A method was developed for preparation of peptide extracts from CSF. Analysis of the extracts by offline LC-MALDI MS resulted in the detection of 3,000-4,000 peptide-like features. Out of these, 730 peptides were identified by MS/MS. The majority of these peptides have not been previously reported in CSF. The identified peptides were found to originate from 104 proteins, of which several have been reported to be involved in different disorders of the central nervous system. These results support the notion that CSF peptidomics may be viable complement to proteomics in the search of biomarkers of CNS disorders.     

Sickness Absence following Coronary Revascularisation. A National Study of Women and Men of Working Age in Sweden 1994-2006

Background

Evidence based and gender specific knowledge about sickness absence following coronary revascularisation is lacking. The objective was to investigate sickness absence after a first coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) among women and men in a national Swedish study.

Materials and Methods

All patients 30–63 years of age, who underwent a first CABG (n = 22,985, 16% women) or PCI (40,891, 22% women) in Sweden between 1994 and 2006 were included. Information on sickness absence, co-morbidity, and other patient characteristics was obtained from national registers. Long-term sickness absence (LTSA) was defined as >180 and >90 sick-leave days in the first sick-leave spell following CABG and PCI, respectively. Prevalence ratio (PR) and 95% confidence interval (CI) of LTSA were calculated.

Findings

LTSA followed the interventions in 41% and 36% for CABG and PCI patients, respectively. Women had more often LTSA compared with men, (CABG PR = 1.23: 95% CI 1.19–1.28 and PCI PR = 1.19; 95% CI 1.16–1.23). A history of sickness absence the year before the intervention increased the risk for LTSA after the intervention in both genders. Among women, older age, or being self employed or unemployed was associated with a lower risk for LTSA. Among men previous cardiovascular disease, diabetes and low socio-economic position increased the risk. During the observation period, there was no change in sickness absence rates among PCI patients but an increase among CABG patients adjusting for patient characteristics.

Conclusion

This national study covering a 13-year period shows that long-term sickness absence following coronary revascularisation is common in Sweden, especially among women, and is associated with socio-economic position, co-morbidity, and sickness absence during the year before the intervention. Gender specific scientific knowledge about use and effects of sickness absence following coronary revascularisation is warranted for the patients, the treating physicians, the healthcare sector, and the society.     

Variants located upstream of CHRNB4 on chromosome 15q25.1 are associated with age at onset of daily smoking and habitual smoking

Several genome-wide association and candidate gene studies have linked chromosome 15q24-q25.1 (a region including the CHRNA5-CHRNA3-CHRNB4 gene cluster) with alcohol dependence, nicotine dependence and smoking-related illnesses such as lung cancer and chronic obstructive pulmonary disease. To further examine the impact of these genes on the development of substance use disorders, we tested whether variants within and flanking the CHRNA5-CHRNA3-CHRNB4 gene cluster affect the transition to daily smoking (individuals who smoked cigarettes 4 or more days per week) in a cross sectional sample of adolescents and young adults from the COGA (Collaborative Study of the Genetics of Alcoholism) families. Subjects were recruited from families affected with alcoholism (either as a first or second degree relative) and the comparison families. Participants completed the SSAGA interview, a comprehensive assessment of alcohol and other substance use and related behaviors. Using the Quantitative trait disequilibrium test (QTDT) significant association was detected between age at onset of daily smoking and variants located upstream of CHRNB4. Multivariate analysis using a Cox proportional hazards model further revealed that these variants significantly predict the age at onset of habitual smoking among daily smokers. These variants were not in high linkage disequilibrium (0.28相似文献   

Chemosensory proteins, major salivary factors in caterpillar mandibular glands

Research in the field of insect-host plant interactions has indicated that constituents of insect saliva play an important role in digestion and affect host chemical defense responses. However, most efforts have focused on studying the composition and function of regurgitant or saliva produced in the labial glands. Acknowledging the need for understanding the role of the mandibular glands in herbivory, we sought to make a qualitative and semi-quantitative comparison of soluble luminal protein fractions between mandibular and labial glands of Vanessa gonerilla butterfly larvae. Amylase and lysozyme were inspected as possible major enzymatic activities in the mandibular glands aiding in pre-digestion and antimicrobial defense. Although detected, neither of these enzymatic activities was prominent in the luminal protein preparation of a particular type of gland. Proteins isolated from the glands were identified by mass spectrometry and by searching an EST-library database generated for four other nymphalid butterfly species, in addition to the public NCBI database. The identified proteins were also quantified from the data using "Quanty", an in-house program. The proteomic analysis detected chemosensory proteins as the most abundant luminal proteins in the mandibular glands. In comparison to these proteins, the relative amounts of amylase and lysozyme were much lower in both gland types. Therefore, we speculate that the primary role of the mandibular glands in Lepidopteran larvae is chemoreception which may include the detection of microorganisms on plant surfaces, host plant recognition and communication with conspecifics.     

Glatiramer Acetate Increases Phagocytic Activity of Human Monocytes In Vitro and in Multiple Sclerosis Patients

Beside its effects on T cells, a direct influence on cells of the myelo-monocytic lineage by GA becomes evident. Recently, we demonstrated that GA drives microglia to adopt properties of type II antigen presenting cells (APC) and increases their phagocytic activity. In the present work, we focused on human blood monocytes in order to examine whether GA may increase phagocytic activity in vivo and to evaluate the molecular mechanisms explaining this new discovered mode of action. Peripheral blood mononuclear cells (PBMC) were obtained using a Biocoll-Isopaque gradient and monocytes were subsequently isolated by using CD14 MicroBeads. Phagocytic activity was determined by flow cytometric measurement of the ingestion of fluorescent beads. Flow cytometry was also used to assess monocytic differentiation and expression of phagocytic receptors. Monocytes of GA treated MS patients exhibited a significantly higher phagocytic activity than those of healthy controls or non-treated MS patients. In vitro, a significant phagocytic response was already detectable after 1 h of GA treatment at the concentrations of 62.5 and 125 µg/ml. A significant increase at all concentrations of GA was observed after 3 h and 24 h, respectively. Only monocytes co-expressing CD16, particularly CD14⁺⁺CD16⁺ cells, were observed to phagocytose. Treatment of monocytes with IL-10 and supernatants from GA-treated monocytes did not alter phagocytosis. We observed a decrease in CD11c expression by GA while no changes were found in the expression of CD11b, CD36, CD51/61, CD91, TIM-3, and CD206. In our blocking assays, treatment with anti-CD14, anti-CD16, anti-TIM3, anti-CD210, and particularly anti-CD36 antibodies led to a decrease in phagocytosis. Our results demonstrate a new mechanism of action of GA treatment that augments phagocytic activity of human monocytes in vivo and in vitro. This activity seems to arise from the CD14⁺⁺CD16⁺ monocyte subset.     

NK cell-mediated targeting of human cancer and possibilities for new means of immunotherapy

Insights into the molecular basis for natural killer (NK) cell recognition of human cancer have been obtained in recent years. Here, we review current knowledge on the molecular specificity and function of human NK cells. Evidence for NK cell targeting of human tumors is provided and new strategies for NK cell-based immunotherapy against human cancer are discussed. Based on current knowledge, we foresee a development where more cancers may be subject to treatment with drugs or other immunomodulatory agents affecting NK cells, either directly or indirectly. We also envisage a possibility that certain forms of cancers may be subject to treatment with adoptively transferred NK cells, either alone or in combination with other therapeutic interventions.     

木焦油污染土壤中微生物特性的空间变异性研究

运用地统计学方法研究了木焦油污染土壤中微生物量、微生物群落结构、微生物活性等的空间变异特征.分别采用26种主要磷脂类脂肪酸(PLFA)的总含量(totPLFA)、PLFA的第一主成分和第二主成分(PLFA PC1和PC2)以及土壤培养过程中CO₂-C的累积释放量(Cre)来表征土壤中的微生物量、微生物群落结构以及微生物活性.结果表明,多数微生物特性指标均存在不同程度的空间自相关性,其半变异函数曲线可用带块金效应的球状模型进行拟合.变量的空间相关距离在2.50～16.60 m之间.PLFA PC1、totPLFA和Cre均具有较强的空间依赖性,其相对结构变差（由结构性因素引起的空间变异）分别为82.3%、79.6%和64.7%,而PLFA PC2 不存在明显的空间依赖性.克立格空间插值图表明,样地中存在几处微生物相对密集分布且代谢活性较高的区域,其中优势微生物菌群是由PLFAs 16:1ω7t,cy17:0,18:1ω7 和cy19:0所表征的革兰氏阴性细菌.土壤中主要污染物多环芳烃含量和空间分布是影响微生物特性空间分布格局的重要因素之一.     

FTIR spectroscopy shows structural similarities between photosystems II from cyanobacteria and spinach.

Photosystem II (PSII), an essential component of oxygenic photosynthesis, is a membrane-bound pigment protein complex found in green plants and cyanobacteria. Whereas the molecular structure of cyanobacterial PSII has been resolved with at least medium resolution [Zouni, A., Witt, H.-T., Kern, J., Fromme, P., Krauss, N., Saenger, W. & Orth, P. (2001) Nature (London) 409, 739-743; Kamiya, N. & Shen, J.R. (2003) Proc. Natl Acad. Sci. USA 100, 98-103], the structure of higher plant PSII is only known at low resolution. Therefore Fourier transform infrared (FTIR) difference spectroscopy was used to compare PSII from both Thermosynechococcus elongatus and Synechocystis PCC6803 core complexes with PSII-enriched membranes from spinach (BBY). FTIR difference spectra of T. elongatus core complexes are presented for several different intermediates. As the FTIR difference spectra show close similarities among the three species, the structural arrangement of cofactors in PSII and their interactions with the protein microenvironment during photosynthetic charge separation must be very similar in higher plant PSII and cyanobacterial PSII. A structural model of higher plant PSII can therefore be predicted from the structure of cyanobacterial PSII.