Characteristics of the 101 studies included in the systematic review.

<p>Characteristics of the 101 studies included in the systematic review.</p

Forest plot lifetime prevalence of psychotic disorders.

<p>Forest plot lifetime prevalence of psychotic disorders.</p

Quantiles and moments of 12-month prevalence per 1,000 persons.

<p>Quantiles and moments of 12-month prevalence per 1,000 persons.</p

Prevalence of psychotic disorders and its association with methodological issues. A systematic review and meta-analyses

<div><p>Objectives</p><p>The purpose of this study is to provide an updated systematic review to identify studies describing the prevalence of psychosis in order to explore methodological factors that could account for the variation in prevalence estimates.</p><p>Methods</p><p>Studies with original data related to the prevalence of psychosis (published between 1990 and 2015) were identified via searching electronic databases and reviewing manual citations. Prevalence estimates were sorted according to prevalence type (point, 12-months and lifetime). The independent association between key methodological variables and the mean effect of prevalence was examined (prevalence type, case-finding setting, method of confirming diagnosis, international classification of diseases, diagnosis category, and study quality) by meta-analytical techniques and random-effects meta-regression.</p><p>Results</p><p>Seventy-three primary studies were included, providing a total of 101 estimates of prevalence rates of psychosis. Across these studies, the pooled median point and 12-month prevalence for persons was 3.89 and 4.03 per 1000 respectively; and the median lifetime prevalence was 7.49 per 1000. The result of the random-effects meta-regression analysis revealed a significant effect for the prevalence type, with higher rates of lifetime prevalence than 12-month prevalence (p<0.001). Studies conducted in the general population presented higher prevalence rates than those carried out in populations attended in health/social services (p = 0.006). Compared to the diagnosis of schizophrenia only, prevalence rates were higher in the probable psychotic disorder (p = 0.022) and non-affective psychosis (p = 0.009). Finally, a higher study quality is associated with a lower estimated prevalence of psychotic disorders (p<0.001).</p><p>Conclusions</p><p>This systematic review provides a comprehensive comparison of methodologies used in studies of the prevalence of psychosis, which can provide insightful information for future epidemiological studies in adopting the most relevant methodological approach.</p></div

Flow diagram (selection strategy) of included studies from 1990 to 2015.

<p>Flow diagram (selection strategy) of included studies from 1990 to 2015.</p

Quantiles and moments of point prevalence per 1,000 persons.

<p>Quantiles and moments of point prevalence per 1,000 persons.</p

Forest plot point prevalence of psychotic disorders.

<p>Forest plot point prevalence of psychotic disorders.</p

New insights into the transposition mechanisms of IS<i>6110</i> and its dynamic distribution between <i>Mycobacterium tuberculosis</i> Complex lineages

<div><p>The insertion Sequence IS<i>6110</i>, only present in the pathogens of the <i>Mycobacterium tuberculosis</i> Complex (MTBC), has been the gold-standard epidemiological marker for TB for more than 25 years, but biological implications of IS<i>6110</i> transposition during MTBC adaptation to humans remain elusive. By studying 2,236 clinical isolates typed by IS<i>6110</i>-RFLP and covering the MTBC, we remarked a lineage-specific content of IS<i>6110</i> being higher in modern globally distributed strains. Once observed the IS<i>6110</i> distribution in the MTBC, we selected representative isolates and found a correlation between the normalized expression of IS<i>6110</i> and its abundance in MTBC chromosomes. We also studied the molecular regulation of IS<i>6110</i> transposition and we found a synergistic action of two post-transcriptional mechanisms: a -1 ribosomal frameshift and a RNA pseudoknot which interferes translation. The construction of a transcriptionally active transposase resulted in 20-fold increase of the transposition frequency. Finally, we examined transposition in <i>M</i>. <i>bovis</i> and <i>M</i>. <i>tuberculosis</i> during laboratory starvation and in a mouse infection model of TB. Our results shown a higher transposition in <i>M</i>. <i>tuberculosis</i>, that preferably happens during TB infection in mice and after one year of laboratory culture, suggesting that IS<i>6110</i> transposition is dynamically adapted to the host and to adverse growth conditions.</p></div

IS<i>6110</i> in the MTBC.

<p>(<b>a</b>) Schematic phylogenetic relationships of MTBC members arisen from a most recent common ancestor (MRCA) after an evolutionary bottleneck. For <i>M</i>. <i>tuberculosis</i> different lineages and families are indicated. The position of IS<i>6110</i> sequences in fully assembled genomes in indicated by black dots. The arrow indicates the position of IS<i>6110</i> in the Direct Repeat region of the CRISPR-Cas locus, which is common to most MTBC strains. For the remaining 17 <i>M</i>. <i>tuberculosis</i> strains different from H37Rv, the number of IS<i>6110</i> sequences is indicated by a box plot (median = 17). (<b>b</b>) Box plots showing the IS<i>6110</i> copies in MTBC families. For each family, the lineage according to panel (a) is provided in parenthesis in the X-axis. For clarity, L4 have been subdivided into 5 different families according to spoligotyping.</p

IS<i>6110</i> gene expression and determination of transposition dynamics in the MTBC.

<p>(<b>a</b>) Total IS<i>6110</i> expression in representative strains from the MTBC. Data are relative to BCG Pasteur. Columns and error bars are the average and standard deviation from three independent cultures. (<b>b</b>) IS<i>6110</i> RFLP from MTBC strains analysed in panel (a). (<b>c</b>) IS<i>6110</i> expression values normalised to the copy number content of this element. Columns represent normalised expression of IS<i>6110</i> according to the left Y-axis. Red squares show the IS<i>6110</i> copy number in each strain indicated in the right Y-axis. Normalised expression of BCG Pasteur is used as reference. (<b>d</b>) Expression per <i>IS6110</i> copy relative to the copy number content in MTBC strains. Data fit with an exponential curve (r² = 0.80) indicated by a grey shadowed line.</p