School success in childhood and subsequent prodromal symptoms and psychoses in the Northern Finland Birth Cohort 1986.

BACKGROUND: Low IQ is a risk factor for psychosis, but the effect of high IQ is more controversial. The aim was to explore the association of childhood school success with prodromal symptoms in adolescence and psychoses in adulthood. METHODS: In the general population-based Northern Finland Birth Cohort 1986 (n = 8 229), we studied the relationship between teacher-assessed learning deficits, special talents and general school success at age 8 years and both prodromal symptoms (PROD-screen) at age 15-16 years and the occurrence of psychoses by age 30 years. RESULTS: More prodromal symptoms were experienced by those talented in oral presentation [boys: adjusted odds ratio (OR) 1.49; 95% confidence interval 1.14-1.96; girls: 1.23; 1.00-1.52] or drawing (boys: 1.44; 1.10-1.87). Conversely, being talented in athletics decreased the probability of psychotic-like symptoms (boys: OR 0.72; 0.58-0.90). School success below average predicted less prodromal symptoms with boys (OR 0.68; 0.48-0.97), whereas above-average success predicted more prodromal symptoms with girls (OR 1.22; 1.03-1.44). The occurrence of psychoses was not affected. Learning deficits did not associate with prodromal symptoms or psychoses. CONCLUSIONS: Learning deficits in childhood did not increase the risk of prodromal symptoms in adolescence or later psychosis in this large birth cohort. Learning deficits are not always associated with increased risk of psychosis, which might be due to, e.g. special support given in schools. The higher prevalence of prodromal symptoms in talented children may reflect a different kind of relationship of school success with prodromal symptoms compared to full psychoses.

Smokin' hot: adolescent smoking and the risk of psychosis.

OBJECTIVE: Daily smoking has been associated with a greater risk of psychosis. However, we are still lacking studies to adjust for baseline psychotic experiences and other substance use. We examined associations between daily smoking and psychosis risk in a 15-year follow-up while accounting for these covariates in a prospective sample (N = 6081) from the Northern Finland Birth Cohort 1986. METHODS: Self-report questionnaires on psychotic experiences (PROD-screen), tobacco smoking and other substance use were completed when the cohort members were 15-16 years old. Tobacco smoking was categorized into three groups (non-smokers, 1-9 cigarettes and ≥10 cigarettes/day). Psychosis diagnoses were obtained from national registers until the age of 30 years. RESULTS: Subjects in heaviest smoking category were at increased risk of subsequent psychosis (unadjusted HR = 3.15; 95% CI 1.94-5.13). When adjusted for baseline psychotic experiences the association persisted (HR = 2.87; 1.76-4.68) and remained significant even after adjustments for multiple known risk factors such as cannabis use, frequent alcohol use, other illicit substance use, parental substance abuse, and psychosis. Furthermore, number of smoked cigarettes increased psychosis risk in a dose-response manner (adjusted OR = 1.05; 1.01-1.08). CONCLUSION: Heavy tobacco smoking in adolescence was associated with a greater risk for psychosis even after adjustment for confounders.

Structural properties of the human corpus callosum: Multimodal assessment and sex differences.

A number of structural properties of white matter can be assessed in vivo using multimodal magnetic resonance imaging (MRI). We measured profiles of R1 and R2 relaxation rates, myelin water fraction (MWF) and diffusion tensor measures (fractional anisotropy [FA], mean diffusivity [MD]) across the mid-sagittal section of the corpus callosum in two samples of young individuals. In Part 1, we compared histology-derived axon diameter (Aboitiz et al., 1992) to MRI measures obtained in 402 young men (19.55 ± 0.84 years) recruited from the Avon Longitudinal Study on Parents and Children. In Part 2, we examined sex differences in FA, MD and magnetization transfer ratio (MTR) across the corpus callosum in 433 young (26.50 ± 0.51 years) men and women recruited from the Northern Finland Birth Cohort 1986. We found that R1, R2, and MWF follow the anterior-to-posterior profile of small-axon density. Sex differences in mean MTR were similar across the corpus callosum (males > females) while these in FA differed by the callosal segment (Body: M>F; Splenium: F>M). We suggest that the values of R1, R2 and MWF are driven by high surface area of myelin in regions with high density of "small axons".

Latent variable mixture modeling in psychiatric research--a review and application.

Latent variable mixture modeling represents a flexible approach to investigating population heterogeneity by sorting cases into latent but non-arbitrary subgroups that are more homogeneous. The purpose of this selective review is to provide a non-technical introduction to mixture modeling in a cross-sectional context. Latent class analysis is used to classify individuals into homogeneous subgroups (latent classes). Factor mixture modeling represents a newer approach that represents a fusion of latent class analysis and factor analysis. Factor mixture models are adaptable to representing categorical and dimensional states of affairs. This article provides an overview of latent variable mixture models and illustrates the application of these methods by applying them to the study of the latent structure of psychotic experiences. The flexibility of latent variable mixture models makes them adaptable to the study of heterogeneity in complex psychiatric and psychological phenomena. They also allow researchers to address research questions that directly compare the viability of dimensional, categorical and hybrid conceptions of constructs.

Response initiation in young adults at risk for psychosis in the Northern Finland 1986 Birth Cohort.

INTRODUCTION: This is one of the very few studies to investigate the specific executive function/processing speed component of response initiation in subjects at familial risk (FR) for psychosis, and the first such study in subjects at clinical risk (CR) for psychosis. METHODS: Participants (N = 177) were members of the general population-based Northern Finland 1986 Birth Cohort in the following four groups: FR for psychosis (n = 62), CR for psychosis (n = 21), psychosis (n = 25) and control subjects (n = 69). The response initiation of these groups was compared in three different tests: Semantic fluency, Stockings of Cambridge and Spatial working memory. RESULTS: The two risk groups did not differ significantly from control group, but differed from, and outperformed the psychosis group in semantic fluency response initiation. CONCLUSIONS: Response initiation deficits were not evident in a non-help seeking psychosis high-risk sample.

Disruptive behaviour disorder with and without attention deficit hyperactivity disorder is a risk of psychiatric hospitalization.

AIM: To evaluate the psychiatric hospitalization among adolescents diagnosed with disruptive behaviour disorders (DBD) and/or attention deficit hyperactivity disorder (ADHD). METHODS: The sample (N = 457) was drawn from the Northern Finland Birth Cohort 1986. Four groups were formed, based on the K-SADS-PL diagnostic interview procedure: adolescents with DBD (n = 44), ADHD (n = 91), comorbid DBD and ADHD (n = 72) and without either DBD or ADHD (n = 250). Information from the Finnish Hospital Discharge Register (FHDR) was used to evaluate the psychiatric hospitalization among the study subjects. RESULTS: When compared with no diagnosis group, the adolescents with behavioural disorders had an increased risk (adjusted odds ratios: DBD = 4.4, ADHD = 2.2, comorbid DBD & ADHD = 5.6) of having also psychiatric disorder in the FHDR. The onset age of the psychiatric disorders in the FHDR (medians: DBD = 14.9, ADHD = 7.5 and DBD & ADHD = 15.3 years) and the combined length of hospitalization (medians: 25, 50 and 26 days, respectively) differed among adolescents with behavioural disorders compared with those with no diagnosis (median age 12.1 years and length of hospitalization 4 days). CONCLUSION: Adolescents diagnosed with DBD (with and without ADHD) are at high risk of undergoing psychiatric hospitalization during their life.

Vitamin D status and correlates of low vitamin D in schizophrenia, other psychoses and non-psychotic depression - The Northern Finland Birth Cohort 1966 study.

There is limited knowledge available on the association of vitamin D with psychiatric disorders in young adults. We aimed to investigate vitamin D levels and associating factors in schizophrenia, other psychoses and non-psychotic depression. We studied 4,987 participants from the Northern Finland Birth Cohort 1966 (31 years) with available serum 25-hydroxyvitamin D [25(OH)D] measurements. The final sample was divided into four groups: schizophrenia (n = 40), other psychoses (n = 24), non-psychotic depression (n = 264) and control (n = 4659). To account for the influence of environmental and technical covariates, we generated a vitamin D score variable with correction for season, sex, batch effect and latitude. We further examined how vitamin D levels correlate with anthropometric, lifestyle, socioeconomic and psychiatric measures. Neither serum 25(OH)D concentration nor vitamin D score differed between schizophrenia, other psychoses, non-psychotic depression and control group. The prevalence of vitamin D deficiency was 3.2%, insufficiency 25.5%, and sufficiency 71.3%. Low vitamin D score correlated with regular smoking in the group with schizophrenia. No difference was observed in other psychiatric conditions. We did not find any difference in vitamin D status between schizophrenia, psychoses, non-psychotic depression and control groups, but future studies are warranted to elucidate the role of vitamin D in psychiatric conditions.

Association between family history of mental disorders and outcome in psychotic disorders.

We investigated the association of family history of mental disorders, especially psychosis, with occupational and clinical outcome in psychotic disorders in a longitudinal population-based cohort. The Northern Finland Birth Cohort 1986 (n = 9432) was used to gather the data. In total 189 individuals with psychosis were identified by age of 28. The outcome was assessed by using register information regarding occupational activity, disability pension and hospital treatments due to psychiatric cause. Parental psychosis and any psychiatric disorder were used as predictors of outcome. The results showed that presence of any parental psychiatric disorder was associated with higher number of days spent at hospital and higher number of hospitalizations in psychotic disorders, but was not associated with occupational outcome or disability pension. The presence of parental psychosis was not associated with outcome. These findings suggest that the presence of any psychiatric disorder among parents may increase the risk of poorer outcome in psychoses in terms of need of hospitalisations. Based on this study the presence of parental psychosis is not associated with outcome, but the result should be interpreted with caution due to the small sample size and conflict with the results of earlier studies.

Prostate cancer screening in men aged 50 to 69 years (STHLM3): A prospective population-based diagnostic study. Grönberg H, Adolfsson J, Aly M, Nordström T, Wiklund P, Brandberg Y, Thompson J, Wiklund F, Lindberg J, Clements M, Egevad L, Eklund M.Lancet Oncol. 2015 Dec;16(16):1667-76. [Epub 2015 Nov 10]. doi: 10.1016/S1470-2045(15)00361-7.

BACKGROUND: The prostate-specific antigen (PSA) test is used to screen for prostate cancer but has a high false-positive rate that translates into unnecessary prostate biopsies and overdiagnosis of low-risk prostate cancers. We aimed to develop and validate a model to identify high-risk prostate cancer (with a Gleason score of at least 7) with better test characteristics than that provided by PSA screening alone. METHODS: The Stockholm 3 (STHLM3) study is a prospective, population-based, paired, screen-positive, diagnostic study of men without prostate cancer aged 50 to 69 years randomly invited by date of birth from the Swedish Population Register kept by the Swedish Tax Agency. Men with prostate cancer at enrolment were excluded from the study. The predefined STHLM3 model (a combination of plasma protein biomarkers [PSA, free PSA, intact PSA, hK2, MSMB, MIC1], genetic polymorphisms [232 SNPs], and clinical variables [age, family, history, previous prostate biopsy, prostate exam]), and PSA concentration were both tested in all participants enrolled. The primary aim was to increase the specificity compared with PSA without decreasing the sensitivity to diagnose high-risk prostate cancer. The primary outcomes were number of detected high-risk cancers (sensitivity) and the number of performed prostate biopsies (specificity). The STHLM3 training cohort was used to train the STHLM3 model, which was prospectively tested in the STHLM3 validation cohort. Logistic regression was used to test for associations between biomarkers and clinical variables and prostate cancer with a Gleason score of at least 7. This study is registered with ISCRTN.com, number ISRCTN84445406. FINDINGS: The STHLM3 model performed significantly better than PSA alone for detection of cancers with a Gleason score of at least 7 (P<0.0001), the area under the curve was 0·56 (95% CI: 0·55-0·60) with PSA alone and 0·74 (95% CI: 0·72-0·75) with the STHLM3 model. All variables used in the STHLM3 model were significantly associated with prostate cancers with a Gleason score of at least 7 (P<0·05) in a multiple logistic regression model. At the same level of sensitivity as the PSA test using a cutoff of≥3ng/ml to diagnose high-risk prostate cancer, use of the STHLM3 model could reduce the number of biopsies by 32% (95% CI: 24-39) and could avoid 44% (35-54) of benign biopsies. INTERPRETATION: The STHLM3 model could reduce unnecessary biopsies without compromising the ability to diagnose prostate cancer with a Gleason score of at least 7, and could be a step towards personalised risk-based prostate cancer diagnostic programmes. FUNDING: Stockholm County Council (Stockholms Läns Landsting).

A comparison of the cumulative incidence and early risk factors for psychotic disorder in young adults in the Northern Finland Birth Cohorts 1966 and 1986.

AIMS: Few studies have compared time trends for the incidence of psychosis. To date, the results have been inconsistent, showing a decline, an increase or no significant change. As far as we know, no studies explored changes in prevalence of early risk factors. The aim of this study was to investigate differences in early risk factors and cumulative incidences of psychosis by type of psychosis in two comparable birth cohorts. METHODS: The Northern Finland Birth cohorts (NFBCs) 1966 (N = 12 058) and 1986 (N = 9432) are prospective general population-based cohorts with the children followed since mother's mid-pregnancy. The data for psychoses, i.e. schizophrenia (narrow, spectrum), bipolar disorder with psychotic features, major depressive episode with psychotic features, brief psychosis and other psychoses (ICD 8-10) were collected from nationwide registers including both inpatients and outpatients. The data on early risk factors including sex and place of birth of the offspring, parental age and psychosis, maternal education at birth were prospectively collected from the population registers. The follow-up reached until the age of 27 years. RESULTS: An increase in the cumulative incidence of all psychoses was seen (1.01% in NFBC 1966 v. 1.90% in NFBC 1986; p < 0.001), which was due to an increase in diagnosed affective and other psychoses. Earlier onset of cases and relatively more psychoses in women were observed in the NFBC 1986. Changes in prevalence of potential early risk factors were identified, but only parental psychosis was a significant predictor in both cohorts (hazard ratios ≥3.0; 95% CI 1.86-4.88). The difference in psychosis incidence was not dependent on changes in prevalence of studied early risk factors. CONCLUSIONS: Surprisingly, increase in the cumulative incidence of psychosis and also changes in the types of psychoses were found between two birth cohorts 20 years apart. The observed differences could be due to real changes in incidence or they can be attributable to changes in diagnostic practices, or to early psychosis detection and treatment.

Inhibition of CD3-induced Ca2+ signals in Jurkat T-cells by myristic acid.

Stimulation of T lymphocytes with antibodies against the T cell receptor/CD3 complex induces within seconds a rise in the concentration of intracellular free Ca2+. Here we show that treatment with 20 microM free myristic acid completely inhibits this Ca2+ signal and the cellular proliferation in Jurkat T cells. Also lauric acid inhibited cell growth while its blocking effect on the Ca2+ signal was weaker than that of myristic acid. Other saturated free fatty acids were inactive. The inhibitory effect of myristic acid could be reversed by the addition of fatty acid free albumin, which will bind the fatty acid. Myristic acid, but not its methyl ester, inhibited both the anti-CD3-induced Ca2+ influx across the cell membrane and Ca2+ release from intracellular stores, but not the formation of inositol phosphates. In contrast, thapsigargin-induced release of Ca2+ from the same intracellular stores was unaffected by myristic acid. Thus, myristic acid specifically blocks T cell antigen receptor-CD3 induced Ca2+ mobilization in T cells.

Protein kinase C activation accelerates proton extrusion by vacuolar-type H(+)-ATPases in murine peritoneal macrophages.

The role of protein kinase C in the regulation of vacuolar-type H(+)-ATPase (V-ATPase) activity was studied in thioglycolate-elicited mouse peritoneal macrophages. Acid-loaded macrophages suspended in a Na(+)- and HCO(3-)-free K(+)-medium containing Zn2+, a H(+)-conductance blocker, exhibited an initial intracellular pH recovery rate of 0.33 +/- 0.04 pH/min (n = 9). Pretreatment with 12-O-tetradecanoyl phorbol 13-acetate (TPA) or mezerein for as little as 3 min induced a marked (82%) increase in the initial pH recovery rate. Stimulation was prevented by the V-ATPase inhibitor, bafilomycin A1 (200 nM) indicating that the effect of the protein kinase C agonist was via augmentation of proton pump activity. The protein kinase C inhibitor, staurosporine (100 nM) completely blocked the stimulatory effects of TPA and mezerein, suggesting involvement of protein kinase C. In keeping with this notion, the inactive analogue of TPA, 4-phorbol didecanoate did not stimulate recovery from an acid load. Extracellular pH determinations revealed that the observed increase in cytosolic pH recovery rate by the protein kinase C agonists was due to increased extrusion of protons from the cells, likely through V-ATPases located in the plasma membrane. Considered together, these data demonstrate regulation of plasmalemmal V-ATPase-mediated proton extrusion by protein kinase C.

Real-time bioluminometric method for detection of nucleoside diphosphate kinase activity.

A real-time, simple and sensitive method for detection of nucleoside diphosphate (NDP) kinase activity has been developed. The assay is based on detection of ATP, generated in the NDP kinase reaction between a nucleoside triphosphate and adenosine diphosphate (ADP), by the firefly luciferase system. In the presence of 0.3 mM dGTP, the Km for ADP was found to be approximately 30 microM for the NDP kinase from Baker's yeast. In the presence of 250 microM ADP, the Km for dATP alpha S, dTTP alpha S, dGTP, dTTP, dCTP and GTP was found to be approximately 0.01, 0.03, 0.05, 0.25, 0.75 and 0.2 mM, respectively. The assay is sensitive and yields linear responses between 0.05-50 mU. The detection limit was found to be 0.05 mU of NDP kinase. The method was used to detect NDP kinase contamination in commercial enzyme preparations.

Fetal and adult human CNS stem cells have similar molecular characteristics and developmental potential.

The mammalian central nervous system (CNS) contains multipotent stem cells that develop into neurons, astrocytes and oligodendrocytes. Our current data show that fetal and adult human CNS stem cell isolates display similar proliferation kinetics, differentiate into three major cell types of the nervous system and express similar sets of regulatory genes. However, each individual CNS stem cell isolate could be distinguished by its specific gene expression and developmental potential.

Production and partial characterization of mouse monoclonal antibodies recognizing common cytokine receptor gamma chain (gammac) of human, mouse and primate origin.

Monoclonal antibodies specific for the common cytokine receptor gamma chain, gammac, were produced using traditional hybridoma technology. Fusion of P3X63-Ag8.653 myeloma cells with splenocytes from Balb/c mice immunized with Spodoptera frugiperda insect cells infected with the recombinant baculovirus VL1392-hIL-2Rgamma resulted in several hybridoma cell clones producing monoclonal gammac-specific antibodies. Four of these antibody-producing clones, IIIC3, IIIE8, IG3 and IF10C5, were further characterized by immunoblotting, flow cytometry and ELISA. Data are presented demonstrating that the generated monoclonal antibodies can identify the extracellular domain of the common cytokine receptor gamma chain of human and mouse origin, and two of the antibodies recognize gammac of primate origin as well.

Development of a physical performance and mobility examination.

OBJECTIVE: To develop and validate the Physical Performance and Mobility Examination (PPME), an observer-administered, performance-based instrument assessing 6 domains of physical functioning and mobility for hospitalized elderly. DESIGN: Development of a pass-fail and 3-level scoring system and training manuals for the PPME instrument for use in both clinical and research settings. Two patient samples were used to assess construct validity and interrater reliability of the PPME. A third sample was selected to assess the test-retest reliability of the instrument. SETTING/PATIENTS: (1) 146 subjects > or = 65 years of age with impaired mobility admitted to Medical Units of Stanford University Hospital. (2) 352 subjects > or = 65 admitted to acute Medical and Surgical Services of the Palo Alto VA Medical Center. Patient samples were obtained during hospitalization and followed until 3 months post-discharge. To study test-retest reliability, 50 additional patients, whose clinical condition was stable, were selected from both settings. METHODS: An expert panel selected 6 mobility tasks integral to daily life: bed mobility, transfer skills, multiple stands from chair, standing balance, step-up, and ambulation. Tasks were piloted with frail hospitalized subjects for appropriateness and safety. Test-retest and interrater reliability and construct validity were evaluated. Construct validity was tested using the Folstein Mini-Mental State Examination, Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), Geriatric Depression Scale, and modified Medical Outcomes Study Measure of Physical Functioning (MOS-PFR). Two scoring schema were developed for each task: (1) dichotomous pass-fail and (2) 3-level high pass, low pass, and fail. A summary scale was developed for each method of scoring. MAIN RESULTS: High interrater reliability and intrarater reliability were demonstrated for individual tasks. The mean percent agreement (interrater) for each pass/fail task ranged from 96 to 100% and from 90 to 100% for the 3 pairs of raters for each task using the 3-level scoring. Kappas for individual pairs of raters ranged from .80 to 1.0 for pass-fail scoring and from .75 to 1.0 for 3-level scoring (all P < 0.01). Intraclass correlation coefficients for 3-level scoring by pairs of raters ranged from .66 to 1.0. For summary scales, the mean intraclass correlation was .99 for both scoring schema. Test-retest reliability for summary scales using kappa coefficients was .99 for both pass-fail and 3-level scoring, and .99 and .98, respectively, using Pearson Product Moment Correlation. Correlations of PPME with other instruments (construct validity) suggest that the PPME adds a unique dimension of mobility beyond that measured by self-reported ADLS and physical functioning, and it is not greatly influenced by mood or mental status (r = 0.70 (ADL), r = 0.43 (IADL), r = 0.36 (MMSE), r = 0.71 (MOS-PFR), r = 0.23 (GDS)). The 3-level summary scale was sensitive to the variability in the patient population and exhibited neither ceiling nor floor effects. CONCLUSIONS: The PPME is a reliable and valid performance-based instrument measuring physical functioning and mobility in hospitalized and frail elderly.

Oxidant stress inhibits pH regulatory mechanisms in murine peritoneal macrophages.

BACKGROUND: Maintenance of cytoplasmic pH (pHi) close to the physiologic range is vital to normal cellular homeostasis. We have previously reported that a vacuolar-type H(+)-adenosine triphosphatase (V-ATPase) situated in the plasma membrane of macrophages and poised to extrude protons from the cytoplasmic to the extracellular space is an important pHi regulatory mechanism. Since the inflammatory microenvironment is frequently characterized by the influx of cells known to release reactive oxygen metabolites, we performed studies to examine the effect of oxidant stress on pHi regulation in peritoneal macrophages. Specifically, the effect of hydrogen peroxide on V-ATPase-mediated proton extrusion from acid-loaded macrophages was investigated. METHODS: Thioglycollate-elicited murine peritoneal macrophages were exposed to varying concentrations of hydrogen peroxide and examined for their ability to recover from an acid-load. pHi was studied by preloading cells with the pH-sensitive fluorescent dye, bis-carboxyethyl-carboxyfluorescein, and monitoring changes in fluorescence under various conditions using a fluorescence spectrometer. RESULTS: Hydrogen peroxide caused a time- and dose-dependent decrease in proton pump-mediated pHi recovery in peritoneal macrophages. This effect occurred without cytotoxicity and was a specific effect as evidenced by the ability of catalase to reverse the inhibition. Since hydrogen peroxide is known to deplete intracellular ATP, a substrate for V-ATPase activity, we hypothesized that ATP depletion may underlie the effect. These studies showed that hydrogen peroxide-mediated ATP depletion was both necessary and sufficient for the effect. Finally, depletion of intracellular glutathione in vivo by using diethyl maleate increased the sensitivity of V-ATPase activity to oxidant stress. CONCLUSIONS: Oxidant stress within the inflammatory milieu impairs macrophage pHi regulation. This effect is magnified by depletion of intracellular antioxidants, as occurs during sepsis. This represents another mechanism whereby oxidants may contribute to cellular dysfunction associated with inflammatory states.

Generation of a new protein purification matrix by loading ceramic hydroxyapatite with metal ions--demonstration with poly-histidine tagged green fluorescent protein.

The gene encoding the green fluorescent protein (GFP) from the jellyfish Aequorea victoria, was inserted under transcriptional control of the polyhedrin promoter of the Autographa californica nuclear polyhedrosis virus and expressed in the Spodoptera frugiperda insect cell line Sf9 during viral infection. The baculovirus transfervector pBlueBacHisB was used for constructing the recombinant baculovirus, so that the green fluorescent protein could be tagged with a poly-histidine tail. This fusion protein was utilized as a marker for evaluating the properties of metal ion loaded ceramic hydroxyapatite as a matrix in protein purification. Ceramic hydroxyapatite loaded with Zn(II) was the best choice for purifying this poly-histidine tagged GFP, followed by Fe(III) of the metal ions tested. Ni(II) that is superior especially in many poly-histidine purification systems did not, when loaded to hydroxyapatite, have binding properties comparable to Zn(II) or Fe(III). Elution of poly-histidine tagged GFP was best performed with phosphate buffers or EDTA that could compete with the phosphate molecules in hydroxyapatite or complexly bind the metal ions, respectively.

Successive bilateral total knee replacement.

We studied the results of 304 posterior stabilized condylar knee arthroplasties, performed over a two and a half-year period, to compare unilateral, bilateral one-stage, and bilateral staged arthroplasty. The minimum length of clinical follow-up was two years. Using The Hospital for Special Surgery rating system, we found the clinical results to be identical for all three groups. The medical complications were similar in each group except that there was a higher incidence of thromboembolism and pulmonary embolism, as seen venographically, in the patients with staged procedures. We concluded that one-stage bilateral knee arthroplasty is preferable in a patient who requires replacement for severely arthritic knees.

Difficulty in making contact with others and social withdrawal as early signs of psychosis in adolescents--the Northern Finland Birth Cohort 1986.

AIM: Social withdrawal is among the first signs of the prodromal state of psychosis seen in clinical samples. The aim of this prospective study was to find out whether difficulty in making contact with others and social withdrawal precede first episode psychosis in the young general population. METHODS: The members of the Northern Finland Birth Cohort 1986 (n=6274) completed the PROD-screen questionnaire in 2001-2002. The Finnish Hospital Discharge Register was used to detect both new psychotic and non-psychotic disorders requiring hospitalisation during 2003-2008. RESULTS: Twenty-three subjects developed psychosis and 89 developed a non-psychotic mental disorder requiring hospitalisation during the follow-up. Of those who developed psychosis, 35% had reported difficulty or uncertainty in making contact with others and 30% social withdrawal in adolescence. In hospitalised non-psychotic disorder, the corresponding precentages were 10 and 13% and in the control group without hospital-treated mental disorder 9 and 11%. The differences between psychotic and non-psychotic hospitalised subjects (P<0.01) as well as controls (P<0.001) were statistically significant regarding difficulty or uncertainty in making contact with others. CONCLUSIONS: In this general population-based sample self-reported difficulty or uncertainty in making contact with others in adolescence preceded psychosis specifically compared to hospitalised non-psychotic mental disorders and controls.