Sustained remission of rheumatoid arthritis with a specific serotonin reuptake inhibitor antidepressant: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>The mainstay of pharmacologic therapy for rheumatoid arthritis includes the use of disease-modifying agents like sulfasalazine and methothrexate, and more recently, anti-tumor necrosis factor-α agents. Depression remains a major co-morbidity in patients with rheumatoid arthritis and is thought to contribute to disability and mortality in these patients. Evidence now suggests that a biologic link exists between substrates responsible for inflammatory conditions and mood disorders. Most of this evidence comes from preclinical studies. Nevertheless, more research into this area is helping us to understand the possible mechanisms through which these conditions interact with each other.</p> <p>Case presentation</p> <p>We describe a 60-year-old Indian man with rheumatoid arthritis diagnosed 15 years ago who had minimal response to multiple therapies with disease-modifying agents and whose arthritis symptoms surprisingly remitted when he was started on a specific serotonin reuptake inhibitor antidepressant, three years ago, for co-morbid major depression. This remission has been maintained with this medication, and the patient is currently not taking any antirheumatoid medications.</p> <p>Conclusion</p> <p>Possible mechanisms linking substrates of mood disorders and inflammation are reviewed in this case report, particularly the serotonergic system. Evidence seems to suggest a significant interaction between the serotonergic systems and inflammation. This interaction seems to be bidirectional. An understanding of this relation is most important to gain insight not only into pathophysiological mechanisms underlying this condition, but also into how treatments for these conditions may complement each other and possibly provide greater therapeutic options in both of these disabling conditions.</p

Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis.

Molecular, genetic and pathological evidence suggests that deficits in GABAergic parvalbumin-positive interneurons contribute to schizophrenia pathophysiology through alterations in the brain's excitation-inhibition balance that result in impaired behaviour and cognition. Although the factors that trigger these deficits are diverse, there is increasing evidence that they converge on a common pathological hub that involves NMDA receptor hypofunction and oxidative stress. These factors have been separately linked to schizophrenia pathogenesis, but evidence now suggests that they are mechanistically interdependent and contribute to a common schizophrenia-associated pathology

School-level variation in health outcomes in adolescence: analysis of three longitudinal studies in England

School factors are associated with many health outcomes in adolescence. However, previous studies report inconsistent findings regarding the degree of school-level variation for health outcomes, particularly for risk behaviours. This study uses data from three large longitudinal studies in England to investigate school-level variation in a range of health indicators. Participants were drawn from the Longitudinal Study of Young People in England, the Me and My School Study and the Research with East London Adolescent Community Health Survey. Outcome variables included risk behaviours (smoking, alcohol/cannabis use, sexual behaviour), behavioural difficulties and victimisation, obesity and physical activity, mental and emotional health, and educational attainment. Multi-level models were used to calculate the proportion of variance in outcomes explained at school level, expressed as intraclass correlations (ICCs) adjusted for gender, ethnicity and socio-economic status of the participants. ICCs for health outcomes ranged from nearly nil to .28 and were almost uniformly lower than for attainment (.17-.23). Most adjusted ICCs were smaller than unadjusted values, suggesting that school-level variation partly reflects differences in pupil demographics. School-level variation was highest for risk behaviours. ICCs were largely comparable across datasets, as well as across years within datasets, suggesting that school-level variation in health remains fairly constant across adolescence. School-level variation in health outcomes remains significant after adjustment for individual demographic differences between schools, confirming likely effects for school environment. Variance is highest for risk behaviours, supporting the utility of school environment interventions for these outcomes

Clonal diversification and histogenesis of malignant germ cell tumours.

Funder: Max Williamson FundGerm cell tumours (GCTs) are a collection of benign and malignant neoplasms derived from primordial germ cells. They are uniquely able to recapitulate embryonic and extraembryonic tissues, which carries prognostic and therapeutic significance. The developmental pathways underpinning GCT initiation and histogenesis are incompletely understood. Here, we study the relationship of histogenesis and clonal diversification in GCTs by analysing the genomes and transcriptomes of 547 microdissected histological units. We find no correlation between genomic and histological heterogeneity. However, we identify unifying features including the retention of fetal developmental transcripts across tissues, expression changes on chromosome 12p, and a conserved somatic evolutionary sequence of whole genome duplication followed by clonal diversification. While this pattern is preserved across all GCTs, the developmental timing of the duplication varies between prepubertal and postpubertal cases. In addition, tumours of younger children exhibit distinct substitution signatures which may lend themselves as potential biomarkers for risk stratification. Our findings portray the extensive diversification of GCT tissues and genetic subclones as randomly distributed, while identifying overarching transcriptional and genomic features