The impact of caspase-12 on susceptibility to candidemia

Candida is one of the leading causes of sepsis, and an effective host immune response to Candida critically depends on the cytokines IL-1β and IL-18, which need caspase-1 cleavage to become bioactive. Caspase-12 has been suggested to inhibit caspase-1 activation and has been implicated as a susceptibility factor for bacterial sepsis. In populations of African descent, CASPASE-12 is either functional or non-functional. Here, we have assessed the frequencies of both CASPASE-12 alleles in an African-American Candida sepsis patients cohort compared to uninfected patients with similar predisposing factors. African-American Candida sepsis patients (n = 93) and non-infected African-American patients (n = 88) were genotyped for the CASPASE-12 genotype. Serum cytokine concentrations of IL-6, IL-8, and IFNγ were measured in the serum of infected patients. Statistical comparisons were performed in order to assess the effect of the CASPASE-12 genotype on susceptibility to candidemia and on serum cytokine concentrations. Our findings demonstrate that CASPASE-12 does not influence the susceptibility to Candida sepsis, nor has any effect on the serum cytokine concentrations in Candida sepsis patients during the course of infection. Although the functional CASPASE-12 allele has been suggested to increase susceptibility to bacterial sepsis, this could not be confirmed in our larger cohort of fungal sepsis patients

A multi-element psychosocial intervention for early psychosis (GET UP PIANO TRIAL) conducted in a catchment area of 10 million inhabitants: study protocol for a pragmatic cluster randomized controlled trial

Multi-element interventions for first-episode psychosis (FEP) are promising, but have mostly been conducted in non-epidemiologically representative samples, thereby raising the risk of underestimating the complexities involved in treating FEP in 'real-world' services

Bridging the gap between education and appropriate use of benzodiazepines in psychiatric clinical practice.

More than half a century after their discovery, benzodiazepines (BDZs) still represent one of the largest and most widely prescribed groups of psychotropic compounds, not only in clinical psychiatry but also in the entire medical field. Over the last two decades, however, there has been an increased focus on the development of antidepressants and antipsychotics on the part of the pharmaceutical industry, clinicians, and researchers, with a reduced interest in BDZs, in spite of their widespread clinical use. As a consequence, many psychiatric residents, medical students, nurses, and other mental health professionals might receive poor academic teaching and training regarding these agents, and have the false impression that BDZs represent an outdated chapter in clinical psychopharmacology. However, recent advances in the field, including findings concerning epidemiology, addiction risk, and drug interactions, as well as the introduction of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition with related diagnostic changes, strongly encourage an updated appraisal of the use of BDZs in clinical practice. During a recent thematic event convened with the aim of approaching this topic in a critical manner, a group of young Italian psychiatrists attempted to highlight possible flaws in current teaching pathways, identify the main clinical pros and cons regarding current use of BDZs in clinical practice, and provide an updated overview of their use across specific clinical areas and patient populations. The main results are presented and discussed in this review

Vδ2+ T cell response to malaria correlates with protection from infection but is attenuated with repeated exposure

Abstract Vδ2+ γδ T cells are semi-innate T cells that expand markedly following P. falciparum (Pf) infection in naïve adults, but are lost and become dysfunctional among children repeatedly exposed to malaria. The role of these cells in mediating clinical immunity (i.e. protection against symptoms) to malaria remains unclear. We measured Vδ2+ T cell absolute counts at acute and convalescent malaria timepoints (n = 43), and Vδ2+ counts, cellular phenotype, and cytokine production following in vitro stimulation at asymptomatic visits (n = 377), among children aged 6 months to 10 years living in Uganda. Increasing age was associated with diminished in vivo expansion following malaria, and lower Vδ2 absolute counts overall, among children living in a high transmission setting. Microscopic parasitemia and expression of the immunoregulatory markers Tim-3 and CD57 were associated with diminished Vδ2+ T cell pro-inflammatory cytokine production. Higher Vδ2 pro-inflammatory cytokine production was associated with protection from subsequent Pf infection, but also with an increased odds of symptoms once infected. Vδ2+ T cells may play a role in preventing malaria infection in children living in endemic settings; progressive loss and dysfunction of these cells may represent a disease tolerance mechanism that contributes to the development of clinical immunity to malaria