Ecological and evolutionary mechanisms driving within-patient emergence of antimicrobial resistance.

The ecological and evolutionary mechanisms of antimicrobial resistance (AMR) emergence within patients and how these vary across bacterial infections are poorly understood. Increasingly widespread use of pathogen genome sequencing in the clinic enables a deeper understanding of these processes. In this Review, we explore the clinical evidence to support four major mechanisms of within-patient AMR emergence in bacteria: spontaneous resistance mutations; in situ horizontal gene transfer of resistance genes; selection of pre-existing resistance; and immigration of resistant lineages.

Pseudomonas aeruginosa's adaptive trajectory: diverse origins, convergent paths.

Does genetic background contribute to populations following the same or divergent adaptive trajectories? A recent study by Filipow et al. evolved multiple genetically distinct Pseudomonas aeruginosa strains to an artificial cystic fibrosis lung sputum media. The strains adapted at different rates but converged on similar phenotypes despite their initial diversity.

Evolutionary innovation through transcription factor rewiring in microbes is shaped by levels of transcription factor activity, expression, and existing connectivity.

The survival of a population during environmental shifts depends on whether the rate of phenotypic adaptation keeps up with the rate of changing conditions. A common way to achieve this is via change to gene regulatory network (GRN) connections-known as rewiring-that facilitate novel interactions and innovation of transcription factors. To understand the success of rapidly adapting organisms, we therefore need to determine the rules that create and constrain opportunities for GRN rewiring.

Transcription factor expression levels and environmental signals constrain transcription factor innovation.

Evolutionary innovation of transcription factors frequently drives phenotypic diversification and adaptation to environmental change. Transcription factors can gain or lose connections to target genes, resulting in novel regulatory responses and phenotypes. However the frequency of functional adaptation varies between different regulators, even when they are closely related.

Natural selection on crosstalk between gene regulatory networks facilitates bacterial adaptation to novel environments.

At the level of the gene, mutation is the raw material for natural selection. However, at the level of the gene regulatory network (GRN), variation is revealed to selection via promiscuous regulator activity ('crosstalk'), which creates opportunities for genetic innovation that can facilitate adaptation. Many genetic and environmental features can contribute to increasing potential for crosstalk by facilitating non-cognate interactions between regulatory elements.

Pseudomonas aeruginosa adapts to octenidine via a combination of efflux and membrane remodelling.

Pseudomonas aeruginosa is an opportunistic pathogen capable of stably adapting to the antiseptic octenidine by an unknown mechanism. Here we characterise this adaptation, both in the laboratory and a simulated clinical setting, and identify a novel antiseptic resistance mechanism. In both settings, 2 to 4-fold increase in octenidine tolerance was associated with stable mutations and a specific 12 base pair deletion in a putative Tet-repressor family gene (smvR), associated with a constitutive increase in expression of the Major Facilitator Superfamily (MFS) efflux pump SmvA.

YouthCHAT as a Primary Care E-Screening Tool for Mental Health Issues Among Te Tai Tokerau Youth: Protocol for a Co-Design Study.

Background: In New Zealand (NZ), 1 in 4 adolescents is affected by mental health issues (eg, depression and anxiety) and engages in risk behaviors (eg, harmful drinking and substance abuse), with rates among Māori youth being significantly higher. The majority of NZ secondary school students visit their local primary health care providers (PHPs) at least annually, yet most do not seek help for mental health and risk behavior (MHB) concerns. While youth think it acceptable to discuss sensitive issues during a consultation with their PHPs, unless problems are severe, such conversations are not initiated by PHPs.

Computer-Based and Online Therapy for Depression and Anxiety in Children and Adolescents.

Objective: The purpose of this study was to provide an overview of computer-based and online therapies (e-therapy) to treat children and adolescents with depression and/or anxiety, and to outline programs that are evidence based or currently being researched.

Methods: We began by defining the topic and highlighting the issues at the forefront of the field. We identified computer and Internet-based interventions designed to prevent or treat depression or anxiety that were tested with children and young people <18 years of age (or inclusive of this age range together with emerging adults).