The effect of a multispecies probiotic on the composition of the faecal microbiota and bowel habits in chronic obstructive pulmonary disease patients treated with antibiotics

Short-term antibiotic treatment profoundly affects the intestinal microbiota, which may lead to sustained changes in microbiota composition. Probiotics may restore such a disturbance. The objective of the present study was to investigate the effect of a multispecies probiotic on the faecal microbiota during and after antibiotic intake in patients with a history of frequent antibiotic use. In this randomised, placebo-controlled, double-blind study, thirty chronic obstructive pulmonary disease (COPD) patients treated with antibiotics for a respiratory tract infection received 5 g of a multispecies probiotic or placebo twice daily for 2 weeks. Faecal samples were collected at 0, 7, 14 and 63 d. Changes in the composition of the dominant faecal microbiota were determined by PCR-denaturing gradient gel electrophoresis (DGGE). Changes in bacterial subgroups were determined by quantitative PCR and culture. Bowel movements were scored daily according to the Bristol stool form scale. During and after antibiotic treatment, DGGE-based similarity indices (SI) were high ( >/= 84 %) and band richness was relatively low, both remaining stable over time. No difference in SI was observed between patients with and without diarrhoea-like bowel movements. The multispecies probiotic had a modest effect on the bacterial subgroups. Nevertheless, it affected neither the composition of the dominant faecal microbiota nor the occurrence of diarrhoea-like bowel movements. The dominant faecal microbiota was not affected by antibiotics in this COPD population, suggesting an existing imbalance of the microbiota, which may also have contributed to the lack of effect by probiotic intak

A practical view of fine-mapping and gene prioritization in the post-genome-wide association era

Over the past 15 years, genome-wide association studies (GWASs) have enabled the systematic identification of genetic loci associated with traits and diseases. However, due to resolution issues and methodological limitations, the true causal variants and genes associated with traits remain difficult to identify. In this post-GWAS era, many biological and computational fine-mapping approaches now aim to solve these issues. Here, we review fine-mapping and gene prioritization approaches that, when combined, will improve the understanding of the underlying mechanisms of complex traits and diseases. Fine-mapping of genetic variants has become increasingly sophisticated: initially, variants were simply overlapped with functional elements, but now the impact of variants on regulatory activity and direct variant-gene 3D interactions can be identified. Moreover, gene manipulation by CRISPR/Cas9, the identification of expression quantitative trait loci and the use of co-expression networks have all increased our understanding of the genes and pathways affected by GWAS loci. However, despite this progress, limitations including the lack of cell-type- and disease-specific data and the ever-increasing complexity of polygenic models of traits pose serious challenges. Indeed, the combination of fine-mapping and gene prioritization by statistical, functional and population-based strategies will be necessary to truly understand how GWAS loci contribute to complex traits and diseases

Bacteria-based self-healing concrete

A typical durability-related phenomenon in many concrete constructions is crack formation. While larger cracks hamper structural integrity, also smaller sub-millimeter sized cracks may result in durability problems as particularly connected cracks increase matrix permeability. Ingress water and chemicals can cause premature matrix degradation and corrosion of embedded steel reinforcement. As regular manual maintenance and repair of concrete constructions is costly and in some cases not at all possible, inclusion of an autonomous self- healing repair mechanism would be highly beneficial as it could both reduce maintenance and increase material durability. Therefore, within the Delft Centre for Materials at the Delft University of Technology, the functionality of various self healing additives is investigated in order to develop a new generation of self-healing concretes. In the present study the crack healing capacity of a specific bio-chemical additive, consisting of a mixture of viable but dormant bacteria and organic compounds packed in porous expanded clay particles, was investigated. Microscopic techniques in combination with permeability tests revealed that complete healing of cracks occurred in bacterial concrete and only partly in control concrete. The mechanism of crack healing in bacterial concrete presumably occurs through metabolic conversion of calcium lactate to calcium carbonate what results in crack-sealing. This bio- chemically mediated process resulted in efficient sealing of sub-millimeter sized (0.15 mm width) cracks. It is expected that further development of this new type of self-healing concrete will result in a more durable and moreover sustainable concrete which will be particularly suited for applications in wet environments where reinforcement corrosion tends to impede durability of traditional concrete constructions.Academia de la Ingeniería de la provincia de Buenos Aire

On the flower formation, the dormancy and the early forcing of strawberries

It was investigated whether successful forcing of strawberries could start before 15 January. To study flower initiation the influences of daylength and temperature were traced for early, mid season and late cultivars, particularly the early Deutsch Evern. After leaf area bad reached a minimum 14-18 short-day cycles of 8h of light and 16h of darkness at 18°C initiated flowering of this cv. Probably a short cold period (e.g. 5°C) removed the light inhibition, and a longer period caused accumulation of a substance stimulating elongation and inhibiting flower initiation. After short-day treatment of parent plants the floral stimulus was not transported to daughter plants.No absolute dormancy was observed. The term relative dormancy was preferred. Fairly prolonged chilling promoted truss elongation, but in autumn fairly brief cold could do this if supplemented with long-day treatment and spraying with gibberellic acid (GA 3 ).The rate of plant development was mainly influenced by cv., later forcing and warmth. Prolongation of chilling and of day length, and spraying with GA 3 caused no acceleration. Yield was influenced by cv. and the time when forcing commenced. The prospects for early forcing were determined by all measures promoting the efficient use of assimilatory light

Photosynthesis-controlled calcification in a hypersaline microbial mat

We investigated the hypothesis that sulfate reduction rather than oxygenic photosynthesis promotes calcification in a hypersaline microbial mat by increasing the ion concentration product: ICP 5 [Ca2+] X [CO32-]. Pore‐water 3 calcium concentration profiles directly measured with microsensors show that calcium concentration in the photic zone decreased in illuminated mats and increased slightly in dark mats. High pH values in the photic zone of illuminated mats resulted in higher carbonate concentrations (2.25 mmol L-1) than in dark mats (0.75 mmol L-1), although the dissolved inorganic carbon (DIC) pore‐water concentration in the former was much lower (5.9 mmol L-1) than in the latter (9.9 mmol L-1). The pH‐induced rise in carbonate concentration in the light was the main factor influencing the ICP, while changes in Ca-1 concentration played a subsidiary role. Sulfate reduction did not result in a net pH increase in these mats, as rates in the photic zone were comparable between illuminated and dark mats (4 and 5 nmol cm-2 h-1, respectively), and pH increased in illuminated mats but not in dark mats. Calcium carbonate precipitation in the photic zone of these hypersaline mats is primarily controlled by photosynthesisinduced pH and carbonate concentration increases. However, heterotrophic bacteria, including sulfate reducers, play an important complementary role in calcification because they maintain high concentrations of DIC in the mat pore water

Self-healing concrete with bacteria encapsulated in expanded clay

Preparation process and the life service solicitations can cause damage on concrete’s internal structure, creating cracks that tend to propagate and increase with time. This poses a potential risk of failure as water penetrates, corroding the rebar what considerably reduces concrete’s life span. It is know that cement can exhibit up to a certain extent a natural ability to self-heal, a consequence of the long-term hydration phenomenon. Hence, some initial cracks can be spontaneously closed if the right conditions are met (humidity). This, however, will not be enough to repair most of the major cracks that are formed internally over a long period of use, so strategies need to be developed to achieve an efficient level of self-healing. Search for a more sustainable and durable concrete, less prone to cracking, lead to a new concept – self-healing. This concept, inspired by the natural ability of plants and human skin to spontaneously heal, inspired researchers to search for a method of conferring concrete with the ability to repair internal damage. The biological approach presents itself as a suitable alternative to achieve healing in concrete. In this work, bacteria were immobilized in expanded clay before being added to concrete. In order to incorporate the expanded clay, some of the aggregate was replaced within the concrete. This works presents the results obtained for the final mechanical strength and self-healing efficiency of concrete containing encapsulated bacteria

Effectiveness and cost-effectiveness of a minimal psychological intervention to reduce non-severe depression in chronically ill elderly patients: the design of a randomised controlled trial [ISRCTN92331982]

BACKGROUND: Depression is a prevalent disorder in chronically ill elderly persons. It may decrease quality of life, and increase functional disability, medical costs, and healthcare utilisation. Because patients may slip into a downward spiral, early recognition and treatment of depression is important. Depression can be treated with antidepressants or psychological interventions; the latter can also be applied by trained paraprofessionals. In this paper, we describe the design of the DELTA study (Depression in Elderly with Long-Term Afflictions). The first objective of the DELTA study is to evaluate the effectiveness and cost-effectiveness of a minimal psychological intervention (MPI) to reduce depression in chronically ill elderly patients. The second objective is to evaluate whether a potential effect of the MPI may differ between types of chronic illnesses. The tailor-made intervention is administered by nurses, who are trained in the principles of cognitive behavioural therapy and self-management. METHODS/DESIGN: DELTA is a two-armed randomised controlled trial, comparing MPI to usual care. A total number of 180 patients with diabetes mellitus type II (DM) and 180 patients with chronic obstructive pulmonary disease (COPD), who in addition suffer from non-severe depression, will be included in the study. In our study, non-severe depression is defined as having minor depression, mild major depression or moderate major depression. The primary outcome measure is depression using the Beck Depression Inventory. Secondary outcome measures include quality of life, daily functioning, self-efficacy, autonomy, and participation. In the economic evaluation, cost-effectiveness and cost-utility ratios will be calculated. Furthermore, a process evaluation will be carried out. Analyses will include both univariate and multivariate techniques and according to the intention to treat principle. The economic evaluation will be done from a societal perspective and data of the process evaluation will be analysed using descriptive techniques. DISCUSSION: A total number of 361 patients has been included in the study. All interventions have been administered and follow-up data will be complete in September 2006. Preliminary results from the process evaluation indicate that patients' satisfaction with the intervention is high. If this intervention proves to be effective, implementation of the DELTA intervention is considered and anticipated

Context-specific effects of genetic variants associated with autoimmune disease

Autoimmune diseases such as rheumatoid arthritis and coeliac disease are typical examples of complex genetic diseases caused by a combination of genetic and non-genetic risk factors. Insight into the genetic risk factors (single nucleotide polymorphisms (SNPs)) has increased since genome-wide association studies (GWAS) became possible in 2007 and, for individual diseases, SNPs can now explain some 15-50% of genetic risk. GWAS have also shown that some 50% of the genetic risk factors for individual autoimmune diseases overlap between different diseases. Thus, shared risk factors may converge to pathways that, when perturbed by genetic variation, predispose to autoimmunity in general. This raises the question of what determines disease specificity, and suggests that identical risk factors may have different effects in various autoimmune diseases. Addressing this question requires translation of genetic risk factors to causal genes and then to molecular and cellular pathways. Since > 90% of the genetic risk factors are found in the non-coding part of the genome (i.e. outside the exons of protein-coding genes) and can have an impact on gene regulation, there is an urgent need to better understand the non-coding part of the genome. Here, we will outline the methods being used to unravel the gene regulatory networks perturbed in autoimmune diseases and the importance of doing this in the relevant cell types. We will highlight findings in coeliac disease, which manifests in the small intestine, to demonstrate how cell type and disease context can impact on the consequences of genetic risk factors

Case Studies

To obtain input from practice and to validate the concepts and techniques explained in the previous chapters, several partner-specific case studies have been executed. These have also served as an important means for knowledge transfer from research to practice. This chapter will elaborate on three of these case studies