Comparative genomic analysis of toxin-negative strains of Clostridium difficile from humans and animals with symptoms of gastrointestinal disease

Background: Clostridium difficile infections (CDI) are a significant health problem to humans and food animals. Clostridial toxins ToxA and ToxB encoded by genes tcdA and tcdB are located on a pathogenicity locus known as the PaLoc and are the major virulence factors of C. difficile. While toxin-negative strains of C. difficile are often isolated from faeces of animals and patients suffering from CDI, they are not considered to play a role in disease. Toxin-negative strains of C. difficile have been used successfully to treat recurring CDI but their propensity to acquire the PaLoc via lateral gene transfer and express clinically relevant levels of toxins has reinforced the need to characterise them genetically. In addition, further studies that examine the pathogenic potential of toxin-negative strains of C. difficile and the frequency by which toxin-negative strains may acquire the PaLoc are needed. Results: We undertook a comparative genomic analysis of five Australian toxin-negative isolates of C. difficile that lack tcdA, tcdB and both binary toxin genes cdtA and cdtB that were recovered from humans and farm animals with symptoms of gastrointestinal disease. Our analyses show that the five C. difficile isolates cluster closely with virulent toxigenic strains of C. difficile belonging to the same sequence type (ST) and have virulence gene profiles akin to those in toxigenic strains. Furthermore, phage acquisition appears to have played a key role in the evolution of C. difficile. Conclusions: Our results are consistent with the C. difficile global population structure comprising six clades each containing both toxin-positive and toxin-negative strains. Our data also suggests that toxin-negative strains of C. difficile encode a repertoire of putative virulence factors that are similar to those found in toxigenic strains of C. difficile, raising the possibility that acquisition of PaLoc by toxin-negative strains poses a threat to human health. Studies in appropriate animal models are needed to examine the pathogenic potential of toxin-negative strains of C. difficile and to determine the frequency by which toxin-negative strains may acquire the PaLoc

In Search of the Optimal Surgical Treatment for Velopharyngeal Dysfunction in 22q11.2 Deletion Syndrome: A Systematic Review

<div><h3>Background</h3><p>Patients with the 22q11.2 deletion syndrome (22qDS) and velopharyngeal dysfunction (VPD) tend to have residual VPD following surgery. This systematic review seeks to determine whether a particular surgical procedure results in superior speech outcome or less morbidity.</p> <h3>Methodology/ Principal Findings</h3><p>A combined computerized and hand-search yielded 70 studies, of which 27 were deemed relevant for this review, reporting on a total of 525 patients with 22qDS and VPD undergoing surgery for VPD. All studies were levels 2c or 4 evidence. The methodological quality of these studies was assessed using criteria based on the Cochrane Collaboration's tool for assessing risk of bias. Heterogeneous groups of patients were reported on in the studies. The surgical procedure was often tailored to findings on preoperative imaging. Overall, 50% of patients attained normal resonance, 48% attained normal nasal emissions scores, and 83% had understandable speech postoperatively. However, 5% became hyponasal, 1% had obstructive sleep apnea (OSA), and 17% required further surgery. There were no significant differences in speech outcome between patients who underwent a fat injection, Furlow or intravelar veloplasty, pharyngeal flap pharyngoplasty, Honig pharyngoplasty, or sphincter pharyngoplasty or Hynes procedures. There was a trend that a lower percentage of patients attained normal resonance after a fat injection or palatoplasty than after the more obstructive pharyngoplasties (11–18% versus 44–62%, p = 0.08). Only patients who underwent pharyngeal flaps or sphincter pharyngoplasties incurred OSA, yet this was not statistically significantly more often than after other procedures (p = 0.25). More patients who underwent a palatoplasty needed further surgery than those who underwent a pharyngoplasty (50% versus 7–13%, p = 0.03).</p> <h3>Conclusions/ Significance</h3><p>In the heterogeneous group of patients with 22qDS and VPD, a grade C recommendation can be made to minimize the morbidity of further surgery by choosing to perform a pharyngoplasty directly instead of only a palatoplasty.</p> </div

Clostridium difficile infection.

Infection of the colon with the Gram-positive bacterium Clostridium difficile is potentially life threatening, especially in elderly people and in patients who have dysbiosis of the gut microbiota following antimicrobial drug exposure. C. difficile is the leading cause of health-care-associated infective diarrhoea. The life cycle of C. difficile is influenced by antimicrobial agents, the host immune system, and the host microbiota and its associated metabolites. The primary mediators of inflammation in C. difficile infection (CDI) are large clostridial toxins, toxin A (TcdA) and toxin B (TcdB), and, in some bacterial strains, the binary toxin CDT. The toxins trigger a complex cascade of host cellular responses to cause diarrhoea, inflammation and tissue necrosis - the major symptoms of CDI. The factors responsible for the epidemic of some C. difficile strains are poorly understood. Recurrent infections are common and can be debilitating. Toxin detection for diagnosis is important for accurate epidemiological study, and for optimal management and prevention strategies. Infections are commonly treated with specific antimicrobial agents, but faecal microbiota transplants have shown promise for recurrent infections. Future biotherapies for C. difficile infections are likely to involve defined combinations of key gut microbiota

Language disorders in young children: when is speech therapy recommended?

Objective: Analysis of treatment recommendation given by speech therapists. Evaluation of the language abilities in the examined children and re-examination of those abilities after 12 months. Materials and methods: Thirty-four children, aged between 2.0 and 5.3 years, referred to speech therapists by their General Practitioners because of possible language problems were included in a prospective study. The number of children receiving speech therapy and the number of speech therapy sessions received during 1 year, and the therapy effect on three quantitative language measures were compiled. Results: In 97% of the children referred to a speech therapist, speech therapy was recommended. Most of these children showed average to above-average language scores on standardised tests for sentence development (61%) and Language comprehension (79%). In addition, for most children spontaneous speech, as screened by the Groningen Diagnostic Speech Norms, was age-adequate (76%). The children's problems consisted of pronunciation difficulties or periods of stammering. After 12 months for 50% of these children speech therapy was still continued which means that the articulation problems still were present. The mean number of speech therapy sessions was 26.7. The language scores on the three language tests remained relatively stable over the 12-month interval. Conclusions: In young children pronunciation difficulties often lead to the recommendation for speech therapy. For a Large number of children therapy takes more than a year, indicating that speech therapy cannot influence these problems to a great extent. In addition language scores remained relatively stable. Therefore, Language problems and especially articulation problems in young children should! be reconsidered regarding maturation and normal variations in speech motor development. A 'watchful waiting' approach should be taken more often. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved

Efficacy of speech therapy in children with language disorders:specific language impairment compared with language impairment in comorbidity with cognitive delay

Objective: this article discusses the effect of speech therapy on language comprehension, language production and non-verbal functioning in two groups of children with developmental language disorders. Design: retrospective study-a follow-up after a mean of 2 years, Materials and methods: verbal and non-verbal functioning before and after therapy were examined in 31 language-impaired children with normal hearing and good health. In 16 children the language functioning was substantial behind their non-verbal functioning. They were categorised as children with specific language impairment (SLI). In 15 children the language problem was in comorbidity with cognitive delay, and these were categorised as children with non-SLI. At the first examination the children were at the age of 1;5-5;4 years and at the second examination they were at the age of 3;4-6;11 years. The children were examined for language comprehension (Standardised Dutch version of the Reynell Developmental Comprehension Scale), spontaneous language production (Groningen Diagnostic Speech norms) and non-verbal functioning (Snijders-Oomen non-verbal intelligence scale for children between 21/2 and 7 years). Results: in both groups, a significant improvement was found in language functioning as well as in non-verbal functioning. Language comprehension and non-verbal IQ-scores in both groups improved by about the same amount. Language production made significantly more progress in the SLI group than in the non-SLI group. The improvements in the SLI group were mainly reached by speech therapy, whereas in the non-SLI group this was less the case. Conclusions: verbal and non-verbal development can improve in young children with developmental language delay. This underlines the idea that language and cognitive development are interacting and influencing each other in a positive way. Children with SLI seem to benefit more from speech therapy, whereas children with cognitive delay seem to benefit more from special education. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved

Specific language impairment in children with velocardiofacial syndrome: Four case studies

Objective: To describe specific language impairment in four children with velocardiofacial syndrome (VCFS). Design: A descriptive, retrospective study of four cases. Setting: University Hospital Groningen, tertiary clinical care. Patients: Of 350 patients with cleft plate, 18 children were diagnosed with VCFS. Four children are described. Interventions: In all children, cardiac and plastic surgery was carried out in the first year of life. Afterward, interventions consisted of hearing improvement, pharyngoplasty, and speech therapy. Main Outcome: Inadequate and uncharacteristic development of articulation and expressive language in four children with VCFS were observed. They differed from the majority in two ways: their nonverbal 10 was in the normal range, and their language skills were below expectations for their IQ. Results: Four of 18 patients with VCFS (22%) showed poor response to therapy and did not develop language in accordance with their normal learning abilities (nonverbal learning capacities and language comprehension). Persistent hypernasal resonance and severe articulation problems remained in all four children. In two children the expressive language profile was also not in agreement with the nonverbal profile: they produced only two- and three-word utterances at the age of 6.0 and 5.3 years. The other two children at the age of 6.8 and 6.4 years produced very long sentences, but they were unintelligible. Conclusions: The speech and language impairment of the four children may be characterized as a phonological or verbal programming deficit syndrome and as such can be described as a specific language impairment in conjunction with VCFS

A 10-year review of perioperative complications in pharyngeal flap surgery

A 10-year retrospective study was undertaken to investigate perioperative complications in pharyngeal flap surgery in one institution using inferiorly and superiorly based flaps. In this fashion the current practice of surgical technique based on local findings and perioperative care, through regular monitoring by experienced nurses on the ward, was evaluated for adequacy. The charts of 275 patients who had 287 pharyngeal flap procedures were studied. Demographics, type and duration of operation, associated procedures, surgeon, anesthetist, duration of hospital stay, associated medical conditions, and perioperative complications such as bleeding, respiratory insufficiency, or flap dehiscence were evaluated. In this series a total complication rate of 6 percent was found, with 2.4 percent early (6 weeks) complications. Only two patients (0.7 percent) had postoperative bleeding requiring reoperation, and one patient (0.3 percent) needed reintubation. The most frequent complication was flap dehiscence in nine patients (3.1 percent), which occurred early in three and late in six. Pharyngeal flap surgery can be performed safely with very few complications provided the correct experience and infrastructure are present. Careful surgery, in conjunction with adequate anesthesia and postoperative monitoring, makes these procedures safe and rewarding