Network analysis of nitrate-sensitive oral microbiome reveals interactions with cognitive function and cardiovascular health across dietary interventions

Many oral bacteria reduce inorganic nitrate, a natural part of a vegetable-rich diet, into nitrite that acts as a precursor to nitric oxide, a regulator of vascular tone and neurotransmission. Aging is hallmarked by reduced nitric oxide production with associated detriments to cardiovascular and cognitive function. This study applied a systems-level bacterial co-occurrence network analysis across 10-day dietary nitrate and placebo interventions to test the stability of relationships between physiological and cognitive traits and clusters of co-occurring oral bacteria in older people. Relative abundances of Proteobacteria increased, while Bacteroidetes, Firmicutes and Fusobacteria decreased after nitrate supplementation. Two distinct microbiome modules of co-occurring bacteria, that were sensitive to nitrate supplementation, showed stable relationships with cardiovascular (Rothia-Streptococcus) and cognitive (Neisseria-Haemophilus) indices of health across both dietary conditions. A microbiome module (Prevotella-Veillonella) that has been associated with pro-inflammatory metabolism was diminished after nitrate supplementation, including a decrease in relative abundance of pathogenic Clostridium difficile. These nitrate-sensitive oral microbiome modules are proposed as potential pre- and probiotic targets to ameliorate age-induced impairments in cardiovascular and cognitive health.publishedVersio

Direct Analysis of Aerosolized Chemical Warfare Simulants Captured on a Modified Glass-Based Substrate by “Paper-Spray” Ionization

Paper spray ionization mass spectrometry offers a rapid alternative platform requiring no sample preparation. Aerosolized chemical warfare agent (CWA) simulants trimethyl phosphate, dimethyl methylphosphonate, and diisopropyl methylphosphonate were captured by passing air through a glass fiber filter disk within a disposable paper spray cartridge. CWA simulants were aerosolized at varying concentrations using an in-house built aerosol chamber. A custom 3D-printed holder was designed and built to facilitate the aerosol capture onto the paper spray cartridges. The air flow through each of the collection devices was maintained equally to ensure the same volume of air sampled across methods. Each approach yielded linear calibration curves with R2 values between 0.98–0.99 for each compound and similar limits of detection in terms of disbursed aerosol concentration. While the glass fiber filter disk has a higher capture efficiency (≈40%), the paper spray method produces analogous results even with a lower capture efficiency (≈1%). Improvements were made to include glass fiber filters as the substrate within the paper spray cartridge consumable. Glass fiber filters were then treated with ammonium sulfate to decrease chemical interaction with the simulants. This allowed for improved direct aerosol capture efficiency (>40%). Ultimately, the limits of detection were reduced to levels comparable to current worker population limits of 1 × 10–6 mg/m3

Human urocortin II, a selective agonist for the type 2 corticotropinreleasing factor receptor, decreases feeding and drinking in the rat

ABSTRACT Corticotropin-releasing factor (CRF) has been hypothesized to modulate consummatory behavior through the Type 2 CRF (CRF 2 ) receptor. However, behavioral functions subserved by the CRF 2 receptor remain poorly understood. Recently, human urocortin II (hUcn II), a selective CRF 2 receptor agonist, was identified. To study the effects of this neuropeptide on ingestive behavior, we examined the effects of centrally infused hUcn II (i.c.v. 0, 0.01, 0.1, 1.0, 10.0 g) on the microstructure of nosepoke responding for food and water in nondeprived, male rats. Malaise-inducing properties of the peptide were monitored using conditioned taste aversion (CTA) testing. To identify potential sites of action, central induction of Fos protein expression was examined. hUcn II dose dependently reduced the quantity and duration of responding for food and water at doses lower (0.01-1.0 g) than that forming a CTA (10 g). Effects were most evident during hours 4 to 6 of the dark cycle. Meal pattern analysis showed that hUcn II potently (0.1 g) increased the satiating value of food. Rats ate and drank smaller and shorter meals without changing meal frequency. Rats also ate more slowly. hUcn II induced Fos in regions involved in visceral sensory processing and autonomic/neuroendocrine regulation and resembling those activated by appetite suppressants. hUcn II is a promising neuropeptide for investigating the role of the CRF 2 receptor in ingestive behavior. Corticotropin-releasing factor (CRF) is hypothesized to mediate behavioral, autonomic, endocrine, and immunological responses to stres

Casimir force on amplifying bodies

Based on a unified approach to macroscopic QED that allows for the inclusion of amplification in a limited space and frequency range, we study the Casimir force as a Lorentz force on an arbitrary partially amplifying system of linearly locally responding (isotropic) magnetoelectric bodies. We demonstrate that the force on a weakly polarisable/magnetisable amplifying object in the presence of a purely absorbing environment can be expressed as a sum over the Casimir--Polder forces on the excited atoms inside the body. As an example, the resonant force between a plate consisting of a dilute gas of excited atoms and a perfect mirror is calculated

General Practitioners involvement in enteral tube feeding at home: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Complex medical treatment is moving from hospital to primary care and General Practitioners (GPs) are increasingly asked to undertake new roles. There are now an estimated 19,500 patients being fed in the UK in the community on enteral tube feeding using a variety of different feeding tubes (Percutaneous endoscopic gastrostomy (PEG), Jejunostomy, or nasogastric (NG). The majority of patients are over the age of 65 years when they had artificial feeding initiated and mainly because of dysphagia. The aim of this study was to explore GPs knowledge, attitudes and skills relating to enteral feeding in the community.</p> <p>Methods</p> <p>Semi-structured one-to-one interviews with a convenience sample of GPs in Northern Ireland.</p> <p>Results</p> <p>Twenty-three GPs in three health boards in Northern Ireland participated in the study. Most found dealing with enteral feeding to be a predominantly negative experience. They had little involvement in patient selection for the procedure and poor or no discharge information. GPs felt inadequately trained, there was poor communication between primary and secondary care and little support. There was anger and frustration among GPs about lack of resources (funding and training), and the perception that primary care was used as a dumping ground.</p> <p>Conclusion</p> <p>Moving complex medical treatment from secondary to primary care has major implications for GPs who should be included in the patient selection process, have adequate discharge information about their patients, be adequately resourced and have appropriate support and training.</p

Horizontal DNA transfer mechanisms of bacteria as weapons of intragenomic conflict

Horizontal DNA transfer (HDT) is a pervasive mechanism of diversification in many microbial species, but its primary evolutionary role remains controversial. Much recent research has emphasised the adaptive benefit of acquiring novel DNA, but here we argue instead that intragenomic conflict provides a coherent framework for understanding the evolutionary origins of HDT. To test this hypothesis, we developed a mathematical model of a clonally descended bacterial population undergoing HDT through transmission of mobile genetic elements (MGEs) and genetic transformation. Including the known bias of transformation toward the acquisition of shorter alleles into the model suggested it could be an effective means of counteracting the spread of MGEs. Both constitutive and transient competence for transformation were found to provide an effective defence against parasitic MGEs; transient competence could also be effective at permitting the selective spread of MGEs conferring a benefit on their host bacterium. The coordination of transient competence with cell-cell killing, observed in multiple species, was found to result in synergistic blocking of MGE transmission through releasing genomic DNA for homologous recombination while simultaneously reducing horizontal MGE spread by lowering the local cell density. To evaluate the feasibility of the functions suggested by the modelling analysis, we analysed genomic data from longitudinal sampling of individuals carrying Streptococcus pneumoniae. This revealed the frequent within-host coexistence of clonally descended cells that differed in their MGE infection status, a necessary condition for the proposed mechanism to operate. Additionally, we found multiple examples of MGEs inhibiting transformation through integrative disruption of genes encoding the competence machinery across many species, providing evidence of an ongoing "arms race." Reduced rates of transformation have also been observed in cells infected by MGEs that reduce the concentration of extracellular DNA through secretion of DNases. Simulations predicted that either mechanism of limiting transformation would benefit individual MGEs, but also that this tactic's effectiveness was limited by competition with other MGEs coinfecting the same cell. A further observed behaviour we hypothesised to reduce elimination by transformation was MGE activation when cells become competent. Our model predicted that this response was effective at counteracting transformation independently of competing MGEs. Therefore, this framework is able to explain both common properties of MGEs, and the seemingly paradoxical bacterial behaviours of transformation and cell-cell killing within clonally related populations, as the consequences of intragenomic conflict between self-replicating chromosomes and parasitic MGEs. The antagonistic nature of the different mechanisms of HDT over short timescales means their contribution to bacterial evolution is likely to be substantially greater than previously appreciated

Livestock-associated Methicillin-Resistant Staphylococcus aureus Sequence Type 398 in Humans, Canada

Recent emergence of infections resulting from this strain is of public health concern