Early life feeding accelerates gut microbiome maturation and suppresses acute post-weaning stress in piglets.

Early life microbiome perturbations can have important effects on host development, physiology and behaviour. In this longitudinal study, we evaluated the impact of early feeding on gut microbiome colonization in neonatal piglets. Early-fed (EF) piglets had access to a customized fibrous diet from 2 days after birth until weaning in addition to mother's milk, whereas control piglets suckled mother's milk only. Rectal swabs were collected at multiple time points until 6 weeks of age to investigate microbiota development using 16S rRNA gene profiling. The dynamic pre-weaning microbiota colonization was followed by a relatively stable post-weaning microbiota, represented by Prevotella, Roseburia, Faecalibacterium, Ruminococcus, Megasphaera, Catenibacterium and Subdoligranulum. EF piglets showed an accelerated microbiota maturation, characterized by increased microbial diversity, pre-weaning emergence of post-weaning-associated microbes and a more rapid decline of typical pre-weaning microbes. Furthermore, the individual eating behaviour scores of piglets quantitatively correlated with their accelerated microbiome. Importantly, EF piglets displayed a smoother relative weight gain and tended to reach a higher relative weight gain, in addition to reduced diarrhoea scores in the first week post-weaning. Overall, these findings demonstrate the beneficial impact of early feeding on microbiota development as well as pig health and performance during the weaning transition.

Long-term functional and psychosocial outcome in adolescents and young adults treated for lower urinary tract dysfunction in childhood.

BACKGROUND: Lower urinary tract dysfunction (LUTD) in childhood might affect lower urinary tract function and psychological wellbeing later in life. This study presents long-term functional outcome, psychological outcome and quality of life (QOL) of adolescents and young adults treated for childhood LUTD compared to healthy age-matched controls. In addition, association with past treatment outcomes is evaluated. STUDY DESIGN: A single-centre cross-sectional study of former patients treated in childhood (currently 16-26 years old) was conducted. Participants completed a survey composed from validated questionnaires: the Overactive Bladder Questionnaire, the Hospital Anxiety and Depression Scale, the Pediatric Quality of Life Inventory and the Short Form 36 Health Survey. RESULTS: Fifty-two former patients (out of 133) agreed to participate and returned the survey (mean age 21 ± 4.1 years). Sixty-nine control subjects were included (mean age 21 ± 2.9 years). Urinary tract symptoms were more common in former patients than controls. Storage symptoms more frequently reported were (urge) urinary incontinence, stress urinary incontinence (SUI) and nocturia. Voiding symptoms more frequently reported were intermittency and feeling of incomplete emptying, Fig. 1. There were no differences in urinary tract symptoms or urinary incontinence subdivided by childhood treatment outcome (complete response, partial response or no response), respectively p = 0.17 and p = 0.58. Results of the overactive bladder questionnaire revealed higher urinary symptom bother scores (score 14 versus 5 p < 0.01) and lower disease-specific QOL (score 95 versus 98 p = 0.02) in former patients compared to controls. General QOL and psychosocial wellbeing were not significantly different between the two groups. A childhood treatment duration extending 2,5 years was an independent prognostic factor for subsequent urinary tract symptoms later in life (OR = 1.5, 95% CI 1.1-2.0). Psychological comorbidity was more often present in former patients (35%) versus controls (10%), p < 0.01. CONCLUSION: Adolescents and young adults treated for childhood LUTD are more prone to report urinary tract symptoms later in life, especially if treatment duration was extensive. However general QOL and psychosocial wellbeing later in life are not or only mildly affected.

Biodiversity of mannose-specific adhesion in Lactobacillus plantarum revisited: strain-specific domain composition of the mannose-adhesin.

Recently, we have identified the mannose-specific adhesin encoding gene (msa) of Lactobacillus plantarum. In the current study, structure and function of this potentially probiotic effector gene were further investigated, exploring genetic diversity of msa in L. plantarum in relation to mannose adhesion capacity. The results demonstrate that there is considerable variation in quantitative in vitro mannose adhesion capacity, which is paralleled by msa gene sequence variation. The msa genes of different L. plantarum strains encode proteins with variable domain composition. Construction of L. plantarum 299v mutant strains revealed that the msa gene product is the key-protein for mannose adhesion, also in a strain with high mannose adhering capacity. However, no straightforward correlation between adhesion capacity and domain composition of Msa in L. plantarum could be identified. Nevertheless, differences in Msa sequences in combination with variable genetic background of specific bacterial strains appears to determine mannose adhesion capacity and potentially affects probiotic properties. These findings exemplify the strain-specificity of probiotic characteristics and illustrate the need for careful and molecular selection of new candidate probiotics.

Factor VIII genotype and inhibitor development in patients with haemophilia A: highest risk in patients with splice site mutations.

The appearance of inhibitory antibodies against factor VIII (FVIII) is the most severe and costly complication of replacement therapy in patients with haemophilia A (HA). To determine the relationship between FVIII genotype and inhibitor development, baseline FVIII activity, genotype and inhibitor development were reviewed in 1104 patients with HA. In patients with severe HA, splicing errors present the highest frequency of inhibitors, ahead of inversion of intron 1 and of intron 22, nonsense mutations and large deletions. The lowest inhibitor frequency in severe HA is found in patients with missense mutations and small deletions/insertions. Subanalyses indicate that nonsense mutations and small deletions/insertions leading to a frameshift in the light chain are associated with a significant higher risk of inhibitor formation than similar mutations occurring in the heavy chain (27% vs. 14%). These mutation types also have a higher frequency of inhibitors when occurring in exons 23-26, where a second FVIII transcript originates, compared with similar mutations in exons 1-22 (28% vs. 17%). These results suggest that complete absence of FVIII because of null mutations, including splice site mutations, or the absence of a second transcript result in an increased risk of inhibitor development.

An international multi-clinic study comparing the therapeutic efficacy of colloidal bismuth subcitrate coated tablets with chewing tablets in the treatment of duodenal ulceration.

The results of a randomized, single-blind, multi-clinic study comparing the therapeutic efficacy and degree of oral staining of new colloidal bismuth subcitrate (CBS) coated tablets over 4 weeks of treatment in patients suffering from duodenal ulceration are reported. The data were collected from 9 clinics in the Netherlands, Belgium, Ireland, the United Kingdom, and Italy. The results from 94 patients treated with CBS coated tablets and 95 patients treated with CBS chewing tablets were statistically evaluated. Healing rates after 4 weeks of therapy appeared to be 76% for CBS coated tablets and 72% for CBS chewing tablets, so no statistically significant difference in therapeutic efficacy was seen. A highly significant degree of discolouration of all parts of the oral cavity was observed in patients treated with CBS chewing tablets, whereas only a few patients treated with CBS coated tablets experienced a slight staining of the tongue. Blood bismuth concentrations during the study had a range of less than or equal to 3 to 33 micrograms/l. The new CBS coated tablet form has an excellent patient compliance as compared to the chewing tablets.

Effect of cyproterone acetate orally on hair density and diameter and endocrine factors in women with idiopathic hirsutism.

The effect of oral cyproterone acetate on hair density and diameter was studied in a clinically homogeneous group of 11 women with idiopathic hirsutism. Therapy was continued for 12 cycles of treatment. Hair density and mean hair diameter on the chin and left upper leg were measured before, immediately after and 3 months after therapy. Generally, the effect of treatment consisted of a quantitative reduction of both parameters, but the effect was not permanent after termination of therapy. Concurrently, the possible influence on plasma androgen was studied. No significant differences were found between the concentrations of plasma testosterone, dehydroepiandrosterone and androstenedione before and after treatment.