Establishment and Early Succession of a Multispecies Biofilm Composed of Soil Bacteria

Most soil bacteria are likely to be organized in biofilms on roots, litter, or soil particles. Studies of such biofilms are complicated by the many nonculturable species present in soil, as well as the interspecific bacterial interactions affecting biofilm biology. We in this study describe the development of a biofilm flow model and use this system to establish an early (days 1–7) flow biofilm of soil bacteria from agricultural soil. It was possible to follow the succession in the early flow biofilm by denaturing gradient gel electrophoresis (DGGE) analysis, and it was demonstrated that the majority of strains present in the biofilm were culturable. We isolated and identified nine strains, all associated with unique DGGE profiles, and related their intrinsic phenotypes regarding monospecies biofilm formation in microtiter plates and planktonic growth characteristics to the appearance of the strains in the flow biofilm. The ability of the strains to attach to and establish biofilm in microtiter plates was reflected in their flow biofilm appearance, whereas no such reflection of the planktonic growth characteristics in the flow biofilm appearance was observed. One strain-specific synergistic interaction, strongly promoting biofilm formation of two strains when cultured together in a dual-species biofilm, was observed, indicating that some strains promote biofilm formation of others. Thus, the biofilm flow model proved useful for investigations of how intrinsic phenotypic traits of individual species affect the succession in an early soil biofilm consortium.     

Point mutation of the xylose reductase (XR) gene reduces xylitol accumulation and increases citric acid production in Aspergillus carbonarius

Aspergillus carbonarius accumulates xylitol when it grows on d-xylose. In fungi, d-xylose is reduced to xylitol by the NAD(P)H-dependent xylose reductase (XR). Xylitol is then further oxidized by the NAD⁺-dependent xylitol dehydrogenase (XDH). The cofactor impairment between the XR and XDH can lead to the accumulation of xylitol under oxygen-limiting conditions. Most of the XRs are NADPH dependent and contain a conserved Ile-Pro-Lys-Ser motif. The only known naturally occurring NADH-dependent XR (from Candida parapsilosis) carries an arginine residue instead of the lysine in this motif. In order to overcome xylitol accumulation in A. carbonarius a Lys-274 to Arg point mutation was introduced into the XR with the aim of changing the specificity toward NADH. The effect of the genetic engineering was examined in fermentation for citric acid production and xylitol accumulation by using d-xylose as the sole carbon source. Fermentation with the mutant strain showed a 2.8-fold reduction in xylitol accumulation and 4.5-fold increase in citric acid production compared to the wild-type strain. The fact that the mutant strain shows decreased xylitol levels is assumed to be associated with the capability of the mutated XR to use the NADH generated by the XDH, thus preventing the inhibition of XDH by the high levels of NADH and ensuring the flux of xylose through the pathway. This work shows that enhanced production of citric acid can be achieved using xylose as the sole carbon source by reducing accumulation of other by-products, such as xylitol.     

Inhibition of AMPA Receptors by Polyamine Toxins is Regulated by Agonist Efficacy and Stargazin

The α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) are glutamate-gated cation channels mediating the majority of fast excitatory synaptic transmission in the central nervous system (CNS). Polyamine toxins derived from spiders and wasps are use- and voltage-dependent channel blockers of Ca²⁺-permeable AMPARs. Recent studies have suggested that AMPAR block by polyamine toxins is modulated by auxiliary subunits from the class of transmembrane AMPAR regulatory proteins (TARPs), which may have implications for their use as tool compounds in native systems. We have explored the effect of the TARP γ-2 (also known as stargazin) on the inhibitory potency of three structurally different polyamine toxins at Ca²⁺-permeable homomeric GluA1 AMPARs expressed in oocytes. We find that polyamine toxin IC₅₀ is differentially affected by presence of stargazin depending on the efficacy of the agonists used to activate GluA1. Co-assembly of GluA1 receptors with stargazin increases the potency of the polyamine toxins when activated by the weak partial agonist kainate, but has no effect in presence of full-agonist l-glutamate (Glu) and partial agonist (RS)-willardiine.     

Model Study of the Pressure Build-Up during Subcutaneous Injection

In this study we estimate the subcutaneous tissue counter pressure during drug infusion from a series of injections of insulin in type 2 diabetic patients using a non-invasive method. We construct a model for the pressure evolution in subcutaneous tissue based on mass continuity and the flow laws of a porous medium. For equivalent injection forces we measure the change in the infusion rate between injections in air at atmospheric pressure and in tissue. From a best fit with our model, we then determine the flow permeability as well as the bulk modulus of the tissue, estimated to be of the order 10⁻¹¹–10⁻¹⁰ m² and 10⁵ Pa, respectively. The permeability is in good agreement with reported values for adipose porcine tissue. We suggest our model as a general way to estimate the pressure build-up in tissue during subcutaneous injection.     

High Reinfection Rate after Preventive Chemotherapy for Fishborne Zoonotic Trematodes in Vietnam

Background

The World Health Organization aims for complete morbidity control of fishborne zoonotic trematodes (FZT) in endemic areas by 2020. The main intervention tool for achieving this goal is regular use of preventive chemotherapy by offering praziquantel to those at risk in endemic areas. The purpose of this study was to investigate the effectiveness of preventive chemotherapy to control FZT in an endemic area in Northern Vietnam.

Methodology and principle findings

We followed a cohort of 396 people who fulfilled the criteria for receiving preventive chemotherapy. Stool samples were examined by Kato-Katz technique for the presence of trematode eggs before, and two, 16, 29 and 60 weeks after preventive chemotherapy. The prevalence of trematode eggs in stool was 40.2% before, 2.3% two weeks after and increased to a cumulative prevalence of 29.8% sixty weeks after preventive chemotherapy.

Conclusions

The effectiveness of preventive chemotherapy as a main component in control of FZT is not well documented in most endemic areas. We found a high reinfection rate within the first year after preventive chemotherapy. Since these trematodes are zoonoses, preventive chemotherapy may not have sufficient impact alone on the transmission to have a lasting effect on the prevalence. Animal reservoirs and farm management practices must be targeted to achieve sustainable control of fishborne zoonotic trematode infections, hence control programs should consider a One Health approach.     

Time-Wise Change in Neck Pain in Response to Rehabilitation with Specific Resistance Training: Implications for Exercise Prescription

Purpose

To determine the time-wise effect of specific resistance training on neck pain among industrial technicians with frequent neck pain symptoms.

Methods

Secondary analysis of a parallel-group cluster randomized controlled trial of 20 weeks performed at two large industrial production units in Copenhagen, Denmark. Women with neck pain >30 mm VAS (N = 131) were included in the present analysis. The training group (N = 77) performed specific resistance training for the neck/shoulder muscles three times a week, and the control group (N = 54) received advice to stay active. Participants of both groups registered neck pain intensity (0–100 mm VAS) once a week.

Results

Neck pain intensity was 55 mm (SD 23) at baseline. There was a significant group by time interaction for neck pain (F-value 2.61, P<0.001, DF = 19). Between-group differences in neck pain reached significance after 4 weeks (11 mm, 95% CI 2 to 20). The time-wise change in pain showed three phases; a rapid decrease in the training group compared with the control group during the initial 7 weeks, a slower decrease in pain during the following weeks (week 8–15), and a plateau during the last weeks (week 16–20). Adherence to training followed a two-phase pattern, i.e. weekly participation rate was between 70–86% during the initial 7 weeks, dropping towards 55–63% during the latter half of the training period.

Conclusion

Four weeks of specific resistance training reduced neck pain significantly, but 15 weeks is required to achieve maximal pain reduction. The time-wise change in pain followed a three-phase pattern with a rapid effect during the initial 7 weeks followed by a slower but still positive effect, and finally a plateau from week 15 and onwards. Decreased participation rate may explain the decreased efficacy during the latter phase of the intervention.     

Maternal Pre-Pregnancy BMI and Intelligence Quotient (IQ) in 5-Year-Old Children: A Cohort Based Study

Background

An association between maternal pre-pregnancy BMI and childhood intelligence quotient (IQ) has repeatedly been found but it is unknown if this association is causal or due to confounding caused by genetic or social factors.

Methods

We used a cohort of 1,783 mothers and their 5-year-old children sampled from the Danish National Birth Cohort. The children participated between 2003 and 2008 in a neuropsychological assessment of cognitive ability including IQ tests taken by both the mother and the child. Linear regression analyses were used to estimate the associations between parental BMI and child IQ adjusted for a comprehensive set of potential confounders. Child IQ was assessed with the Wechsler Primary and Preschool Scales of Intelligence – Revised (WPPSI-R).

Results

The crude association between maternal BMI and child IQ showed that BMI was adversely associated with child IQ with a reduction in IQ of −0.40 point for each one unit increase in BMI. This association was attenuated after adjustment for social factors and maternal IQ to a value of −0.27 (−0.50 to −0.03). After mutual adjustment for the father''s BMI and all other factors except maternal IQ, the association between paternal BMI and child IQ yielded a regression coefficient of −0.26 (−0.59 to 0.07), which was comparable to that seen for maternal BMI (−0.20 (−0.44 to 0.04)).

Conclusion

Although maternal pre-pregnancy BMI was inversely associated with the IQ of her child, the similar association with paternal BMI suggests that it is not a specific pregnancy related adiposity effect.     

Model-Based Analysis of Costs and Outcomes of Non-Invasive Prenatal Testing for Down’s Syndrome Using Cell Free Fetal DNA in the UK National Health Service

Background

Non-invasive prenatal testing (NIPT) for Down’s syndrome (DS) using cell free fetal DNA in maternal blood has the potential to dramatically alter the way prenatal screening and diagnosis is delivered. Before NIPT can be implemented into routine practice, information is required on its costs and benefits. We investigated the costs and outcomes of NIPT for DS as contingent testing and as first-line testing compared with the current DS screening programme in the UK National Health Service.

Methods

We used a pre-existing model to evaluate the costs and outcomes associated with NIPT compared with the current DS screening programme. The analysis was based on a hypothetical screening population of 10,000 pregnant women. Model inputs were taken from published sources. The main outcome measures were number of DS cases detected, number of procedure-related miscarriages and total cost.

Results

At a screening risk cut-off of 1∶150 NIPT as contingent testing detects slightly fewer DS cases, has fewer procedure-related miscarriages, and costs the same as current DS screening (around UK£280,000) at a cost of £500 per NIPT. As first-line testing NIPT detects more DS cases, has fewer procedure-related miscarriages, and is more expensive than current screening at a cost of £50 per NIPT. When NIPT uptake increases, NIPT detects more DS cases with a small increase in procedure-related miscarriages and costs.

Conclusions

NIPT is currently available in the private sector in the UK at a price of £400-£900. If the NHS cost was at the lower end of this range then at a screening risk cut-off of 1∶150 NIPT as contingent testing would be cost neutral or cost saving compared with current DS screening. As first-line testing NIPT is likely to produce more favourable outcomes but at greater cost. Further research is needed to evaluate NIPT under real world conditions.