Early Alterations in Hippocampal Circuitry and Theta Rhythm Generation in a Mouse Model of Prenatal Infection: Implications for Schizophrenia

Post-mortem studies suggest that GABAergic neurotransmission is impaired in schizophrenia. However, it remains unclear if these changes occur early during development and how they impact overall network activity. To investigate this, we used a mouse model of prenatal infection with the viral mimic, polyriboinosinic–polyribocytidilic acid (poly I∶C), a model based on epidemiological evidence that an immune challenge during pregnancy increases the prevalence of schizophrenia in the offspring. We found that prenatal infection reduced the density of parvalbumin- but not somatostatin-positive interneurons in the CA1 area of the hippocampus and strongly reduced the strength of inhibition early during postnatal development. Furthermore, using an intact hippocampal preparation in vitro, we found reduced theta oscillation generated in the CA1 area. Taken together, these results suggest that redistribution in excitatory and inhibitory transmission locally in the CA1 is associated with a significant alteration in network function. Furthermore, given the role of theta rhythm in memory, our results demonstrate how a risk factor for schizophrenia can affect network function early in development that could contribute to cognitive deficits observed later in the disease

Development of an ex vivo porcine lung model for studying growth, virulence, and signaling of Pseudomonas aeruginosa

Research into chronic infection by bacterial pathogens, such as Pseudomonas aeruginosa, uses various in vitro and live host models. While these have increased our understanding of pathogen growth, virulence, and evolution, each model has certain limitations. In vitro models cannot recapitulate the complex spatial structure of host organs, while experiments on live hosts are limited in terms of sample size and infection duration for ethical reasons; live mammal models also require specialized facilities which are costly to run. To address this, we have developed an ex vivo pig lung (EVPL) model for quantifying Pseudomonas aeruginosa growth, quorum sensing (QS), virulence factor production, and tissue damage in an environment that mimics a chronically infected cystic fibrosis (CF) lung. In a first test of our model, we show that lasR mutants, which do not respond to 3-oxo-C12-homoserine lactone (HSL)-mediated QS, exhibit reduced virulence factor production in EVPL. We also show that lasR mutants grow as well as or better than a corresponding wild-type strain in EVPL. lasR mutants frequently and repeatedly arise during chronic CF lung infection, but the evolutionary forces governing their appearance and spread are not clear. Our data are not consistent with the hypothesis that lasR mutants act as social “cheats” in the lung; rather, our results support the hypothesis that lasR mutants are more adapted to the lung environment. More generally, this model will facilitate improved studies of mi- crobial disease, especially studies of how cells of the same and different species interact in polymicrobial infections in a spatially structured environment

A Comparison of Patients’ and Physicians’ Knowledge and Expectations Regarding Precision Oncology Tests

(1) Background: As genomic testing is becoming a part of the mainstream oncology practice, it is vital to ensure that our patients fully understand the implications of these tests. This study aimed to compare the attitudes and expectations of cancer patients with those of their physicians regarding the role of biomarker testing in clinical decision making. (2) Methods: Two separate, complimentary, self-administered questionnaires for patients with cancer and their physicians, respectively, were collected in Calgary, Alberta, Canada. Out of 117, 113 completed patient surveys were included in the statistical analysis, constituting a 96.4% response rate. These surveys were subsequently matched with those of their corresponding oncologists to determine the concordance rates. (3) Results: Overall, patients demonstrated a good understanding of general cancer biology (80.0%) and diagnostic processes (90.0%) associated with precision oncology. Most patients wanted their tumours to be tested to guide treatment, and the oncologists broadly shared these views (concordance 65.1%). However, there were discrepancies between the knowledge and expectations regarding the applications of test results on actual diagnosis and prognosis between patients and their oncologists (concordance 26.1% and 36.0%, respectively). While only 28.0% of patients thought they had enough knowledge to make informed decisions, the majority (68.0%) said they needed more information. (4) Conclusion: Our study shows that patients and cancer physicians do not always agree with the roles and applications of genomic tests, which could lead to misplaced expectations and poor health outcomes. More research is needed to devise strategies to improve education and communication to align these expectations and improve the quality of clinical decision making

Factors affecting flux performance of forward osmosis systems

The performance of a forward osmosis (FO) system may be characterised by the assessment parameters: FO–RO flux ratio (Jw/Jw(RO)), apparent FO water permeability (Jw/(πds − πml)), and the newly developed flux efficiency factor (Jw,ob/Jw,re). The former two parameters offer information on extent of internal concentration polarisation and driving force utilisation, respectively. The Jw,ob/Jw,re factor has practical relevance, and reveals the inevitable trade-off between flux and recovery (φ) for a FO system. The derived Jw,ob/Jw,re factors corresponded well to experimental observations. High water permeability, low salt-to-water permeability ratio, and large mass transfer coefficient improve the performance of a FO system, but these may also be influenced by operational and fouling effects, such as draw solute transmission, fouling resistance and cake-enhanced concentration polarisation. It was shown that membrane properties also play a significant role in fouling behaviour. Fouling amelioration factors include aeration and osmotic backwash. A thin-film composite membrane showed potential for FO application with favourable intrinsic transport parameters. It was demonstrated that a FO system could achieve stable water production with both relatively high flux efficiency (Jw,ob/Jw,re = 0.8) and high recovery (φ = 95.8%), which attested to the technology potential

Analysis of salt accumulation in a forward osmosis system

An important issue concerning performance of forward osmosis (FO) systems is salt accumulation in the retentate. This occurs due to the highly retentive FO membrane and reverse diffusion of draw solutes. In this study, experimental data from an osmotic membrane bioreactor (OMBR), which epitomizes a challenging application for FO, was analyzed to investigate longer term effects of the above issue. It was found that salt accumulation is controlled by three factors: membrane, influent, and process. The role of the membrane is application-dependent and significant only when influent osmotic pressure is smaller or in the same order of magnitude as the salt to water permeability ratio (B/A). The study also shows that an experimental duration of 3 × solids retention time (SRT) is necessary for adequate study of salt accumulation in FO systems. Analysis of the B/A ratio provided fundamental information into system behavior. A reducing B/A could be associated with the formation of a mild secondary foulant layer, whereas an increasing B/A was observed for more severe fouling cases and indicated further flux reducing mechanisms. The study makes clear that knowledge of factors affecting salt accumulation is essential for optimization of FO systems

The Emerging Role of Innate Immunity in Chronic Kidney Diseases

Renal fibrosis is a common fate of chronic kidney diseases. Emerging studies suggest that unsolved inflammation will progressively transit into tissue fibrosis that finally results in an irreversible end-stage renal disease (ESRD). Renal inflammation recruits and activates immunocytes, which largely promotes tissue scarring of the diseased kidney. Importantly, studies have suggested a crucial role of innate immunity in the pathologic basis of kidney diseases. This review provides an update of both clinical and experimental information, focused on how innate immune signaling contributes to renal fibrogenesis. A better understanding of the underlying mechanisms may uncover a novel therapeutic strategy for ESRD