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Background: The human parainfluenza virus 3 (HPIV-3) outbreak at the haemato-oncology ward of the Maastricht University Medical Centre in the summer of 2016. Aim: To describe an effective strategy to control the largest reported HPIV-3 outbreak at an adult haematology–oncology ward in the Netherlands by implementing infection control measures and molecular epidemiology investigation. Methods: Clinical, patient and diagnostic data were both pro- and retrospectively collected. HPIV-3 real-time polymerase chain reaction (HPIV-3 RT-PCR) was validated using oropharyngeal rinse samples. Screening of all new and admitted patients was implemented to identify asymptomatic infection or prolonged shedding of HPIV-3 allowing cohort isolation. Findings: The HPIV-3 outbreak occurred between 9 July and 28 September 2016 and affected 53 patients. HPIV-3 RT-PCR on oropharyngeal rinse samples demonstrated an up to 10-fold higher sensitivity compared with pharyngeal swabs. Monitoring showed that at first positive PCR, 20 patients (38%) were asymptomatic (of which 11 remained asymptomatic) and the average duration of shedding was 14 days (range 1–58). Asymptomatic patients had lower viral load, shorter period of viral shedding (≤14 days) and were mostly immune-competent oncology patients. The outbreak was under control five weeks after implementation of screening of asymptomatic patients. Conclusion: Implementation of a sensitive screening method identified both symptomatic and asymptomatic patients which had lower viral loads and allowed early cohort isolation. This is especially important in a ward that combines patients with varying immune status, because both immunocompromised and immune-competent patients are likely to spread the HPIV-3 virus, either through prolonged shedding or through asymptomatic course of disease.

Cell surface mucins configure the cell surface by presenting extended protein backbones that are heavily O-glycosylated. The glycopeptide structures establish physicochemical properties at the cell surface that enable and block the formation of biologically important molecular complexes. Some mucins, such as MUC1, associate with receptor tyrosine kinases and other cell surface receptors, and engage in signal transduction in order to communicate information regarding conditions at the cell surface to the nucleus. In that context, the MUC1 cytoplasmic tail (MUC1CT) receives phosphorylation signals from receptor tyrosine kinases and serine/threonine kinases, which enables its association with different signaling complexes that conduct these signals to the nucleus and perhaps other subcellular organelles. We have detected the MUC1CT at promoters of over 500 genes, in association with several different transcription factors, and have shown that promoter occupancy can vary under different growth factor conditions. However, the full biochemical nature of the nuclear forms of MUC1 and its function at these promoter regions remain undefined. I will present evidence that nuclear forms of the MUC1CT include extracellular and cytoplasmic tail domains. In addition, I will discuss evidence for a hypothesis that the MUC1CT possesses a novel catalytic function that enables remodeling of the transcription factor occupancy of promoters, and thereby engages in regulation of gene expression.

Organisaties maken in toenemende mate gebruik van Facebook. Ze zetten berichten op hun Facebookpagina en stellen bezoekers in de gelegenheid om dat ook te doen. Voor elke bezoeker is te zien wat andere bezoekers over de organisatie zeggen en hoe de organisatie daarop reageert. Met deze vorm van transparantie staan organisaties voor de uitdaging ervoor te zorgen dat hun imago versterkt wordt en, in ieder geval, geen schade oploopt. De vraagstelling van dit experiment is welke invloed uitgaat van het lezen van positieve, negatieve of neutrale berichten van anderen op Facebook en of het daarbij verschil maakt wanneer de organisatie op deze berichten reageert. 102 deelnemers lazen berichten op een Facebookpagina van een fictieve goede doelenorganisatie die hetzij allemaal negatief waren, hetzij allemaal positief, hetzij zowel positief als negatief. De organisatie reageerde in de helft van de gevallen op de berichten. Lezers beoordelen het imago van de organisatie niet lager en zijn niet minder overtuigd van de goede besteding van de donaties wanneer de organisatie op de berichten reageert, maar wel wanneer de organisatie dat nalaat.

Aangenomen wordt dat zorgboerderijen een zinvolle vorm van dagbesteding kunnen bieden aan mensen met een lichte verstandelijke beperking. Gezien de ruime vertegenwoordiging van mensen met een lichte verstandelijke beperking binnen zorgboerderijen, is het opvallend dat er relatief weinig onderzoek is gedaan naar de effecten en de betekenis van het werken op de boerderij voor deze doelgroep. Dit onderzoek verschaft verder inzicht in de betekenis die zorgboerderijen hebben in het leven van mensen met een lichte verstandelijke beperking / zwakbegaafdheid. Het betreft 60 mensen, die minstens twee dagen per week werkzaam op de boerderij, en die ouder zijn dan 18 jaar.

In this study, we describe the first response regulator of Streptococcus suis serotype 2, designated RevS. RevS was cloned and the sequence was determined. No histidine kinase was found in the vicinity ofrevS , therefore RevS was considered to be an orphan response regulator. An isogenic knock-out mutant of RevS was shown to be attenuated in colonising the S. suis specific organs in a competitive assay in four piglets, indicating thatrevS plays a role in the pathogenesis of S. suis infections. We analysed the protein expression profiles of various fractions of the wild-type strain 10 and the mutant strain 10¿RevS. The expression of known virulence factors ofS. suis by wild-type and the mutant strain, was not different. However, one protein in the protoplast fraction, with unknown identity was shown to be repressed by revS in the exponential growth phase of the mutant

The genome sequences of Neisseria meningitidis serogroup B strain MC58 and serogroup A strain Z2491 were systematically searched for open reading frames (ORFs) encoding autotransporters. Eight ORFs were identified, six of which were present in both genomes, whereas two were specific for MC58. Among the identified ORFs was the gene encoding the known autotransporter IgA1 protease. The deduced amino acid sequences of the other identified ORFs were homologous to known autotransporters and found to contain an N-terminal signal sequence and a C-terminal domain that could constitute a beta-barrel in the outer membrane. The ORFs NMB1985 and NMB0992, encoding homologs of the Hap (for Haemophilus adhesion and penetration protein) and Hia (for Haemophilus influenzae adherence protein) autotransporters of H. influenzae, were cloned from serogroup B strain H44/76 and expressed in Escherichia coli. Western blots revealed that all sera of patients (n=14) and healthy carriers (n=3) tested contained antibodies against at least one of the recombinant proteins. These results indicate that both genes are widely distributed among N. meningitidis isolates and expressed during colonization and infection

Ter voorkoming van sterfte, morbiditeit en blijvende schade als gevolg van invasieve Hib-infecties heeft de Gezondheidsraad geadviseerd vaccinatie tegen Hib in het Rijksvaccinatieprogramma op te nemen, hetgeen in 1993 is gerealiseerd. Vaccinatie wordt aangeboden aan alle kinderen geboren sinds 1 april 1993. Om de effectiviteit van deze immunisatie te beoordelen is surveillance geindiceerd. In dit rapport over de surveillance van invasieve infecties door Haemophilus influenzae (Hi) door het Nederlands Surveillance-Centrum Kindergeneeskunde (NSCK) en het Nederlands Referentie Laboratorium voor Bacteriele Meningitis (RBM) in de periode 1994-1996 wordt het voortschrijdende effect van Hib vaccinatie duidelijk. Het aantal gevallen van invasieve Hi-infectie was 179 in 1994, 68 in 1995 en 40 in 1996. Dit betekent een belangrijke vermindering vergeleken met de geschatte aantallen van voor de start van vaccinatie. De daling vond plaats bij alle klinische ziektebeelden. Een verschuiving in de leeftijdsverdeling vond plaats, wat verklaard kan worden door de geleidelijke invoering van immunisatie vanaf april 1993. In 1994 manifesteerde nog drie kwart van de invasieve Hi-infecties zich als meningitis, in 1996 was dit nog de helft van het totale aantal aan het RBM gerapporteerde gevallen. Vanaf 1 januari 1995 werd de casus-definitie voor de NSCK surveillance veranderd naar invasieve Hi-infecties ongeacht het serotype. Als gevolg hiervan werd het ook mogelijk om invasieve Hi-ziektebeelden veroorzaakt door niet serotype b stammen te bestuderen. Serotypering werd door het RBM verricht bij alle ingestuurde stammen. Het deel van de gevallen in het NSCK systeem waarbij serotypering plaatsvond steeg van 84% in 1994 tot ruim 90% in 1996. De gegevens van het RBM tonen een duidelijke daling in het deel van de invasieve Hi-infecties veroorzaakt door serotype b. Zeven gevallen van echt vaccin-falen, 4 van schijnbaar- en 2 van mogelijk vaccin-falen werden geregistreerd. In de toekomst zal het RBM verdere immunologische gegevens verzamelen voor de evaluatie van gevallen van vaccin-falen.

BACKGROUND: Natural compounds with anti-microbial properties are attractive reagents to reduce the use of conventional antibiotics. Carvacrol, the main constituent of oregano oil, inhibits the growth of a variety of bacterial foodborne pathogens. As concentrations of carvacrol may vary in vivo or when used in animal feed, we here investigated the effect of subinhibitory concentrations of the compound on major virulence traits of the principal bacterial foodborne pathogen Campylobacter jejuni. METHODS/PRINCIPAL FINDINGS: Motility assays revealed that subinhibitory concentrations of carvacrol inhibited the motility of C. jejuni without affecting bacterial growth. Immunoblotting and electron microscopy showed that carvacrol-treated C. jejuni still expressed flagella. The loss of motility was not caused by reduced intracellular ATP levels. In vitro infection assays demonstrated that subinhibitory concentrations of carvacrol also abolished C. jejuni invasion of human epithelial cells. Bacterial uptake of invasive Escherichia coli was not blocked by carvacrol. Exposure of C. jejuni to carvacrol prior to infection also inhibited cellular infection, indicating that the inhibition of invasion was likely caused by an effect on the bacteria rather than inhibition of epithelial cell function. CONCLUSIONS/SIGNIFICANCE: Bacterial motility and invasion of eukaryotic cells are considered key steps in C. jejuni infection. Our results indicate that subinhibitory concentrations of carvacrol effectively block these virulence traits by interfering with flagella function without disturbing intracellular ATP levels. These results broaden the spectrum of anti-microbial activity of carvacrol and support the potential of the compound for use in novel infection prevention strategies.

Background Social integration of people with intellectual disability (ID) moving into regular neighbourhoods tends to be studied and evaluated without detailed knowledge about the social psychological aspects of everyday interaction between neighbours with and without ID. The goal of the present paper is to show how the authors' social psychological research programme may contribute to this field of inquiry. Methods The different ways in which societies respond to features and behaviours that may be perceived as deviant are theoretically analysed. Results of empirical studies are reported to clarify how social responses to people with ID are special in terms of perceptions, emotions and interaction desires of people with and without ID during a pre-contact and contact phase. Results On the basis of the theoretical analysis, it is concluded that regular neighbouring in modern Western society often takes the form of benevolent tolerance, rather than stigmatisation and prejudice. However, empirical studies reveal that, prior to getting people with ID as new neighbours, prospective neighbours without ID experience a specific pattern of emotions that are associated with specific desires (e. g. with respect to information supply or a caring relationship). These anticipatory reactions are dependent on the expected size of the group moving in and on the severity of ID. Furthermore, while actually engaging in neighbouring, neighbours with and without ID appear to have experiences related to behaviour of residents, staff and features of housing facilities that are perceived as (in) congruent with regular neighbouring. Conclusions It is concluded that interpersonal relationships between neighbours with and without ID should not be simplified in terms of attitudes that would be primarily prejudiced/stigmatising versus entirely accepting. Rather, our studies paint a more complex picture of sometimes ambivalent thoughts, feelings and interaction needs that all should be taken into account to make social integration a success.

We present an in silico, structure-based approach for design and evaluation of conformationally restricted peptide-vaccines. In particular, we designed four cyclic peptides of ten or 11 residues mimicking the crystallographically observed beta-turn conformation of a predicted immunodominant loop of PorA from Neisseria meningitidis. Conformational correctness and stability of the peptide designs, as evaluated by molecular dynamics simulations, correctly predicted the immunogenicity of the peptides. We observed a peptide-induced functional antibody response that, remarkably, exceeded the response induced by the native protein in outer membrane vesicles, without losing specificity for related strains. The presented approach offers tools for a priori design and selection of peptide-vaccine candidates with full biological activity. This approach could be widely applicable: to outer membrane proteins of Gram-negative bacteria, and to other epitopes in a large range of pathogens.

The adherence of clinical isolates of nonencapsulated Haemophilus influenzae strains from patients with chronic bronchitis to distinct immobilized extracellular matrix components was determined. With selected strains the induction of plasmin formation by these isolates was studied. The strains could be divided into two groups: strains that showed a very high level of adherence to laminin and type I collagen, as well as adhesion to fibronectin and strains that showed only a moderate level of adhesion to laminin and a low level of adhesion to fibronectin. Plasmin formation was demonstrated for three out of eight isolates. Persisting and nonpersisting strains did not differ quantitatively or qualitatively with respect to the level of adhesiveness to the distinct matrix proteins and in their ability to induce plasmin formation

We investigated the relationship between susceptibility to p-lactam antibiotics and variation in the major outer membrane protein P2 (OmpP2; also called porin) of persistent nonencapsulated Haemophilus influenzae isolated from cystic fibrosis patients. Nine OmpP2 variants were selected from two distinct H. influenzae strains from two patients extensively treated with beta-lactam antibiotics. The variants differed in their susceptibilities to at least two beta-lactam antibiotics. By detergent extraction and column chromatography, OmpP2 was purified from two variants that were derived from strain 70 and that differed notably in their susceptibilities to beta-lactam antibiotics. The proteins were reconstituted into black lipid membranes for measurement of porin function. OmpP2 from the more resistant isolate (isolate 70b) had a smaller channel conductance than OmpP2 of the more susceptible isolate (isolate 70f). DNA sequencing of ompP2 of these isolates revealed single nonsynonymous base differences; there were changes in the amino acid sequence corresponding to surface-exposed loops 4, 5, 6, and 8. Changes in loops 4, 5, and 6 were previously shown to result in antigenic differences. Beside these mutations, variants of strain 70 showed additional mutations in loop 1 and nonexposed loop 3. Taken together, our results suggest that in variants of strain 70, nonsynonymous point mutations accumulated both in the sequences of ompP2 coding for antigen-variable loops and in other loops, notably, loops I and 3, The latter changes are suggested to affect the permeability of the porin channel.

We analyzed the antimicrobial susceptibilities of Haemophilus influenzae isolates from 157 sputum specimens prospectively collected from 39 cystic fibrosis (CF) patients during a 2-year study, These isolates were characterized by random amplified polymorphic DNA analysis and major outer membrane protein (MOMP) analysis to identify H. influenzae strains and MOMP variants and to assess their persistence in the respiratory tract. Among the 247 H. influenzae isolates, 16 (6.5%) produced beta-lactamase. The 231 beta-lactamase-negative isolates represented 85 H. influenzae strains, 61 MOMP variants derived from 27 of these strains, and 85 persistent isolates identical to strains or MOMP variants. All beta-lactamase-negative isolates were tested for susceptibility to ampicillin, amoxicillin-clavulanic acid, cefuroxime, cefotaxime, cefaclor, imipenem, tetracycline, and trimethoprim-sulfamethoxazole by disk diffusion testing. Eleven (13%) H. influenzae strains, 18 (30%) MOMP variants, acid 30 (35%) persistent isolates were resistant to one or more of the antibiotics tested, Antimicrobial susceptibility was decreased among MOMP variants and persistent isolates compared to nonpersistent H. influenzae strains, and changes in susceptibility occurred irrespective of MOMP variation, We conclude that the decreased antimicrobial susceptibility of H. influenzae during persistence contributes to the poor eradication of H. influenzae from the respiratory tracts of CF patients.

The occurrence of fimbria gene clusters in nonencapsulated Haemophilus influenzae strains from chronic bronchitis patients (n = 58), patients with acute otitis media (n = 13), and healthy carriers (n = 12) was determined by DNA hybridization and PCR, based on sequences of fimbriate H. influenzae type b. Although an average of 18% of all nonencapsulated strains had a fimbria gene cluster consisting of hifA to hifE inserted in the chromosome between purE and pepN, differences in the frequency of fimbria cluster-positive strains were observed, depending on the source of isolates. The compositions of the fimbria gene clusters of seven strains from chronic bronchitis patients and one strain from an otitis media patient were analyzed in more detail. After enrichment for fimbria expression, the promoter of the gene cluster contained 10 TA repeats (n = 2), leading to optimal positioning between the -10 and -35 promoter regions. The promoter regions of five fimbria-negative strains were sequenced; four were found to have nine TA repeats, and one had only four TA repeats. The protein sequence of three ganglioside GM1-specific HifA adhesins consisted of conserved regions intermingled with regions of sequence diversity. hifA appeared to be flanked by intergenic regions that varied between strains and contained both direct and inverted DNA repeats. Since noncoding DNA between hifA and purE has not been found in H. influenzae type b, these DNA sequences are probably not essential for fimbria expression. An analysis of strains lacking the gene cluster revealed the presence of similar sequences in 13 of 15 strains from chronic bronchitis patients, 5 of 5 strains from otitis media patients, and 3 of 5 strains from healthy carriers. The lengths of these intergenic regions were the same for multiple isolates of strains obtained during persistent infections. The presence or absence and the composition of the fimbria gene cluster and other sequences between the flanking genes purE and pepN suggest that the fimbria gene cluster was originally contained on a mobile element

OBJECTIVE: To determine the two-year results of nationwide vaccination with Haemophilus influenzae type b (Hib) vaccine on the occurrence of Hib meningitis in the Netherlands. DESIGN: Retrospective controlled study. SETTING: The Netherlands. METHOD: Children born since April 1, 1993 are vaccinated at the age of 3, 4, 5 and 11 months to protect them from infections with Hib. The number of Hib meningitis patients in the period 1 April, 1993 to 1 April, 1995, among infants born in this period who were offered the Hib vaccine (study group), was compared with the number of Hib meningitis patients in the period 1 April, 1991 to 1 April, 1993 among children born in last-mentioned period (control group). RESULTS: Twenty-one cases of meningitis by Hib were observed in the study group. Twelve children who, as a consequence of their age, had only been vaccinated once or not at all; 7 children were not vaccinated for several reasons. In addition one patient was infected by H. influenzae type f strain and one by a non-typable strain. In the control group 185 cases of Hib meningitis occurred. CONCLUSION: Hib meningitis was not observed among infants who had been vaccinated at least twice

Haemophilus influenzae infections are preceded by airway colonization, a process facilitated by fimbriae. Here, we identified the complete fimbrial gene cluster of H. influenzae type b. HifA forms the major subunit. HifB, a periplasmic chaperone, and HifC, an outer membrane usher, are typical assembly genes; their inactivation abolished fimbriae formation. HifD and HifE are putative minor subunits, both participating in fimbriae biogenesis. Inactivation of either one drastically reduced fimbriae expression. HifD represents a novel type of fimbrial subunit with lipoprotein characteristics, pointing to a membrane-associated function of HifD. Transcription of all fimbrial genes is coregulated through two clustered promoters. The flanking of the fimbrial gene cluster by repetitive extragenic palindromic sequences together with a partial duplication of an adjacent unrelated operon indicated that the cluster was once inserted in the H. influenzae genome as a mobile virulence unit