Expression of the NUP153 and YWHAB genes from their canonical promoters and alternative promoters of the LINE-1 retrotransposon in the placenta of the first trimester of pregnancy.

The placenta has a unique hypomethylated genome. Due to this feature of the placenta, there is a potential possibility of using regulatory elements derived from retroviruses and retrotransposons, which are suppressed by DNA methylation in the adult body. In addition, there is an abnormal increase in the level of methylation of the LINE-1 retrotransposon in the chorionic trophoblast in spontaneous abortions with both normal karyotype and aneuploidy on different chromosomes, which may be associated with impaired gene transcription using LINE-1 regulatory elements. To date, 988 genes that can be expressed from alternative LINE-1 promoters have been identified. Using the STRING tool, genes (NUP153 and YWHAB) were selected, the products of which have significant functional relationships with proteins highly expressed in the placenta and involved in trophoblast differentiation. This study aimed to analyze the expression of the NUP153 and YWHAB genes, highly active in the placenta, from canonical and alternative LINE-1 promoters in the germinal part of the placenta of spontaneous and induced abortions. Gene expression analysis was performed using real-time PCR in chorionic villi and extraembryonic mesoderm of induced abortions (n = 10), adult lymphocytes (n = 10), spontaneous abortions with normal karyotype (n = 10), and with the most frequent aneuploidies in the first trimester of pregnancy (trisomy 16 (n = 8) and monosomy X (n = 6)). The LINE-1 methylation index was assessed in the chorionic villi of spontaneous abortions using targeted bisulfite massive parallel sequencing. The level of expression of both genes from canonical promoters was higher in blood lymphocytes than in placental tissues (p < 0.05). However, the expression level of the NUP153 gene from the alternative LINE-1 promoter was 17 times higher in chorionic villi and 23 times higher in extraembryonic mesoderm than in lymphocytes (p < 0.05). The expression level of NUP153 and YWHAB from canonical promoters was higher in the group of spontaneous abortions with monosomy X compared to all other groups (p <0.05). The LINE-1 methylation index negatively correlated with the level of gene expression from both canonical (NUP153 - R = -0.59, YWHAB - R = -0.52, p < 0.05) and alternative LINE-1 promoters (NUP153 - R = -0.46, YWHAB - R = -0.66, p < 0.05). Thus, the observed increase in the LINE-1 methylation index in the placenta of spontaneous abortions is associated with the level of expression of the NUP153 and YWHAB genes not only from alternative but also from canonical promoters, which can subsequently lead to negative consequences for normal embryogenesis.

Trajectories of antidepressant use and characteristics associated with trajectory groups among young refugees and their Swedish-born peers with diagnosed common mental disorders-findings from the REMAIN study.

PURPOSE: This study aimed to (1) identify the trajectories of prescribed antidepressants in refugee youth and matched Swedish-born peers diagnosed with common mental disorder (CMD) and (2) characterize the trajectories according to sociodemographic and medical factors. METHODS: The study population comprised 2,198 refugees and 12,199 Swedish-born individuals with both Swedish-born parents, aged 16-25 years in 2011, residing in Sweden and treated in specialised healthcare for CMD 2009-11. Group-based trajectory modelling was used to identify different trajectory groups of antidepressant use-based on annual defined daily dosages (DDDs). Multinomial logistic regression was applied to investigate the association of sociodemographic and medical characteristics with the identified trajectories. Nagelkerke pseudo-R2 values were estimated to evaluate the strength of these associations. RESULTS: Four trajectory groups of antidepressant use among young refugees were identified with following proportions and DDD levels in 2011: 'low constant' (88%, < 100), 'low increasing' (2%, ≈710), 'medium decreasing' (8%, ≈170) and 'high increasing' (2%, ≈860). Similar trajectories, however, with different proportions were identified in Swedish-born: 67%, 7%, 21% and 5%, respectively. The most influential factors discriminating the trajectory groups among refugees were 'duration of stay in Sweden' (R2 = 0.013), comorbid 'other mental disorders' (R2 = 0.009) and 'disability pension' (R2 = 0.007), while 'disability pension' (R2 = 0.017), comorbid 'other mental disorders' (R2 = 0.008) and 'educational level' (R2 = 0.008) were the most important determinants discriminating trajectory groups among Swedish-born youth. CONCLUSION: The lower use of antidepressants in refugees with CMDs compared to their Swedish-born counterparts warrants health literacy programs for refugees and training in transcultural psychiatry for healthcare professionals.

The Finnish psychiatric birth cohort consortium (PSYCOHORTS) - content, plans and perspectives.

Background: Psychiatric disorders tend to be developmental, and longitudinal settings are required to examine predictors of psychiatric phenomena. Replicating and combining data and results from different birth cohorts, which are a source of reliable data, can make research even more valuable. The Finnish Psychiatric Birth Cohort Consortium (PSYCOHORTS) project combines birth cohorts in Finland. Aim: The aim of this paper is to introduce content, plans and perspectives of the PSYCOHORTS project that brings together researchers from Finland. In addition, we illustrate an example of data harmonization using available data on causes of death. Content: PSYCOHORTS includes eight Finnish birth cohorts. The project has several plans: to harmonize different data from birth cohorts, to incorporate biobanks into psychiatric birth cohort research, to apply multigenerational perspectives, to integrate longitudinal patterns of marginalization and inequality in mental health, and to utilize data in health economics research. Data on causes of death, originally obtained from Finnish Cause of Death register, were harmonized across the six birth cohorts using SAS macro facility. Results: Harmonization of the cause of death data resulted in a total of 21,993 observations from 1965 to 2015. For example, the percentage of deaths due to suicide and the sequelae of intentional self-harm was 14% and alcohol-related diseases, including accidental poisoning by alcohol, was 13%. Conclusions: PSYCOHORTS lays the foundation for complex examinations of psychiatric disorders that is based on compatible datasets, use of biobanks and multigenerational approach to risk factors, and extensive data on marginalization and inequality.

Early motor developmental milestones and schizophrenia: A systematic review and meta-analysis.

The neurodevelopmental hypothesis of schizophrenia proposes that impaired brain development is a cause of the illness. Early motor developmental milestones, such as learning to walk, are predictors of later schizophrenia but studies have not been systematically reviewed. The aim of the present systematic review and meta-analysis was to explore the association between early motor developmental milestones and the risk of adult schizophrenia. In addition, we updated a systematic review on motor function and risk of schizophrenia. The PubMed, PsycINFO and Scopus databases were searched for original research articles published up to July 2015. Motor milestones were measured between ages 0 and 13years. Random effect meta-analysis calculated effect estimates (Hedges' g) for the association between individual motor milestones and schizophrenia risk. An electronic database and selected articles reference list search identified 5990 articles after removing duplicates. Sixty-nine full text articles were assessed for eligibility of which six were included in the review. Five studies provided sufficient data for meta-analyses. The following motor milestones were significantly associated with adult schizophrenia risk: walking unsupported (g=0.46; 95% CI 0.27-0.64; p<0.001), standing unsupported (g=0.28; 0.16-0.40; p<0.001) and sitting unsupported (g=0.18; 0.05-0.31; p=0.007). Results for the milestones 'holding head up' and 'grabbing object' were not statistically significant. Delayed walking, sitting and standing unsupported were associated with adult onset schizophrenia. The findings emphasise the importance of timely achievement of these motor milestones in childhood and can contribute to the identification of individuals at risk of psychosis.

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.

[Immune status of patients with chronic tonsillitis before and after tonsillectomy]. / Immunnyi status bol'nykh khronicheskim tonzillitom do i posle tonzilléktomii.

Immune status was examined before and after tonsillectomy in 35 patients with various forms of chronic tonsillitis (CT). Measurements were made of main lymphocyte populations, IgA, IgG, IgM levels, functional activity of neutrophils, titers of antibodies to opportunistic microorganisms of the upper airways. It is shown that tonsillectomy produces positive changes in some immunological indices: serum IgG normalized, titers of antibodies to Haemophillus influenzae, Streptococcus pneumoniae and streptolysin-0 lowered, initially low count of B-lymphocytes, natural killers, T-helpers rose, neutrophil chemiluminescence normalized.

[Clinico-immunological effectiveness of likopid in conservative treatment of patients with chronic tonsillitis and chronic sinusitis]. / Kliniko-immunologicheskaia éffektivnost' likopida pri konservativnom lechenii bol'nykh khronicheskim tonszillitom i khronicheskim sinusitom.

30 patients with chronic tonsillitis (CT) and 20 patients with chronic sinusitis (CS) received likopid (4 mg/day for 10 days). CT patients were additionally treated with tonsil lacunar lavage with dioxidine solution. Likopid was found effective in CT patients (good response--31%, partial response--59%). 9% did not respond to likopid. CS patients benefited less (good response--10%, partial response--50%). 40% were non-responders. In CT patients likopid demonstrated also an immunomodulating effect. Positive changes were observed in the counts of B-lymphocytes, T-lymphocytes, T-helpers, natural killers, level of serum IgG, titers of specific antibodies, functional activity of neutrophils. In CS this effect was less pronounced.

[The effect of various protein kinase inhibitors on the response of snail neurons to the intracellular injection of cAMP]. / Vliianie razlichnykh ingibitorov proteinkinazy na éffekt vnutrikletochnoi in''ektsii tsAMF v neirony vinogradnoi ulitki.

Drugs preventing cAMP interaction with regulatory subunit of cAMP-dependent protein kinase, tolbutamide and db-cAMP injected into neurons of Helix lucorum decreased the cell response to cAMP, but H-8-a potent inhibitor of this enzyme catalytic subunit did not produce such effect. It is suggested that the neuron electric response to cAMP injection is not caused by protein phosphorylation.

[An intracellular inhibitory activity of RNase secreted by Bacillus intermedius]. / Vnutrikletochnaia ingibitornaia aktivnost' RNKazy, sekretiruemoi Bacillus intermedius.

Bacillus intermedius cells producing extracellular RNAse were found to contain its inhibitor and an RNAse-inhibitor complex. Bacillus subtilis and Escherichia coli cell lysates did not inhibit the activity of homogeneous extracellular RNAse produced by B. intermedius. The inhibitor was shown to be specific for this RNAse and did not interact with other RNAses. As was demonstrated by biochemical tests and electrophoretic analysis, the inhibitor is released when the protoplasts are disintegrated, i.e. it is located in the cytoplasm. A correlation has been established between the biosynthesis of extracellular RNAse and its intracellular inhibitor.

[Intracellular and extracellular ribonucleases of Bacillus intermedius]. / Izuchenie vnutrikletochnykh i vnekletochnykh ribonukleaz Bacillus intermedius.

Endocellular and exocellular ribonucleases were studied in Bacillus intermedius. Two fractions of ribonucleases (Rf 0.72 and 0.96) were found to be associated with the cellular surface and seven fractions (Rf 0.1, 0.17, 0.33, 0.45, 0.72, 0.82 and 0.96) were detected in the cytoplasm. RNAase with Rf 0,096 had the highest activity and was repressed by inorganic orthophosphate. This RNase accumulated in the cell during the stationary growth phase just as the free enzyme form did in the culture medium. The immunological characteristics of these enzymes were identical as was shown by immunochemical analysis.