Coaggregation properties of trimeric autotransporter adhesins

Trimeric autotransporter adhesins (TAAs) comprise a group of virulence‐related proteins in Gram‐negative bacteria. Members of this family bind to extracellular matrix components such as collagen and fibronectin, but also they exhibit several other functions, such as conferring serum resistance and autoaggregation. Autoaggregation promoted by TAAs is homotypic and mediated by the sticky, globular head domains of these lollipop‐like molecules. However, whether TAAs mediate heterotypic interactions (i.e., coaggregation) has not been studied. To address this question, we investigated the coaggregation of two model TAA groups: YadA from the enteropathogenic Yersiniae and the immunoglobulin‐binding Eib proteins from Escherichia coli. To study TAA coaggregation, we coexpressed a fluorescent label together with a particular TAA and followed the aggregative interactions using fluorescence microscopy and quantified the interactions using a novel script implemented in Fiji. Our results show that there is coaggregation between some populations expressing different TAAs, which can be explained by relatively high sequence similarity between the interacting TAAs. Generally, the level of coaggregation correlated with the sequence similarity. However, some TAAs did not interact despite high sequence similarity, showing exclusion of bacteria producing a noncompatible TAA. These data demonstrate that TAAs can mediate bacterial coaggregation, but in some cases prevent coaggregation of bacteria with disparate TAAs. Our results have implications for the ecology of TAA‐producing bacteria, where coaggregation may promote co‐operation whereas exclusion might be an indication of competition

A comparison of teaching three common ear, nose, and throat conditions to medical students through video podcasts and written handouts: a pilot study

BACKGROUND: This pilot study conducted at the Peninsula Medical School is one of very few studies to compare the use of video podcasts to traditional learning resources for medical students. METHODS: We developed written handouts and video podcasts for three common ear, nose, and throat conditions; epistaxis, otitis media, and tonsillitis. Forty-one second-year students were recruited via email. Students completed a 60-item true or false statement test written by the senior author (20 questions per subject). Students were subsequently randomized to podcast or handouts. Students were able to access their resource via their unique university login on the university homepage and were given 3 weeks to use their resource. They then completed the same 60-item test. RESULTS: Both podcasts and handouts demonstrated a statistically significant increase in student scores (podcasts mean increase in scores 4.7, P=0.004, 95% confidence interval =0.07). Handout mean increase in scores 5.3, P=0.015, 95% confidence interval =0.11). However, there was no significant difference (P=0.07) between the two, with the handout group scoring fractionally higher (podcasts average post-exposure score =37.3 vs handout 37.8) with a larger average improvement. A 5-point Likert scale questionnaire demonstrated that medical students enjoy using reusable learning objects such as podcasts and feel that they should be used more in their curriculum. CONCLUSION: Podcasts are as good as traditional handouts in teaching second-year medical students three core ear, nose, and throat conditions and enhance their learning experience

Bacterial autoaggregation

Many bacteria, both environmental and pathogenic, exhibit the property of autoaggregation. In autoaggregation (sometimes also called autoagglutination or flocculation), bacteria of the same type form multicellular clumps that eventually settle at the bottom of culture tubes. Autoaggregation is generally mediated by self-recognising surface structures, such as proteins and exopolysaccharides, which we term collectively as autoagglutinins. Although a widespread phenomenon, in most cases the function of autoaggregation is poorly understood, though there is evidence to show that aggregating bacteria are protected from environmental stresses or host responses. Autoaggregation is also often among the first steps in forming biofilms. Here, we review the current knowledge on autoaggregation, the role of autoaggregation in biofilm formation and pathogenesis, and molecular mechanisms leading to aggregation using specific examples

Clival Mucocele: A Rare Yet not Forgotten Pathology

Primary clival mucoceles are a rare clinical entity that usually represents an incidental finding on computed tomography or magnetic resonance imaging scanning. There are only a few reports in the literature of patients who presented with vague symptoms such as headaches, facial paresthesia, and numbness. Clival mucoceles can also be secondary, by extension of a sphenoid mucocele to the clivus. We present a case of primary clival mucocele, aiming to highlight the importance of a multidisciplinary approach. </jats:p

Histopathological changes in the human larynx following expanded polytetrafluroethylene (Gore-Tex(®)) implantation

BACKGROUND: Expanded polytetrafluroethelyne (e PTFE, Gore-Tex(®)) has been advocated as an implant material for medialization of the vocal fold. Animal studies involving rabbits and a porcine model have demonstrated host tolerance of the implant. There have been no reports describing the histological changes in a human laryngectomy specimen with a Gore-Tex implant. CASE PRESENTATION: The histological findings in a laryngectomy specimen of a patient previously implanted with e PTFE for medialization of a paralyzed vocal fold following excision of a vagal neurofibroma were studied. Histopathology revealed a mild foreign-body giant cell granulomatous reaction with some associated fibrosis. The granulomatous response was limited to the periphery of the Gore-Tex and although it closely followed the profile of the material it did not encroach into or significantly break up the material. There was no significant neutrophilic or lymphocytic inflammation. CONCLUSIONS: Our findings are consistent with the animal models confirming that Gore-Tex implantation does not result in a significant granulomatous reaction in the human larynx over a 13-month period. Moreover, there is no evidence of resorption or infection. Further, the lack of lymphocytes in association with the granulomas indicates that there is no significant immunological hypersensitivity. Histologically, the slight permeation by connective tissue is similar to that seen in Gore-Tex vascular and cardiac implants. The degree of the slight giant cell response appears to be dependent on the profile of the material; a sharp edge incited more of a response than a flat surface

Prime movers : mechanochemistry of mitotic kinesins

Mitotic spindles are self-organizing protein machines that harness teams of multiple force generators to drive chromosome segregation. Kinesins are key members of these force-generating teams. Different kinesins walk directionally along dynamic microtubules, anchor, crosslink, align and sort microtubules into polarized bundles, and influence microtubule dynamics by interacting with microtubule tips. The mechanochemical mechanisms of these kinesins are specialized to enable each type to make a specific contribution to spindle self-organization and chromosome segregation

Peri-conceptual and mid-pregnancy drinking:a cross-sectional assessment in two Scottish health board areas using a 7-day Retrospective Diary

Aims: The aim of this study was to evaluate the use of a 7-day Retrospective Diary to assess peri-conceptual and mid-pregnancy alcohol consumption. Background: Alcohol consumption among women has increased significantly and is of international concern. Heavy episodic (‘binge’) drinking is commonplace and is associated with unintended pregnancy. Pre-pregnancy drinking is strongly associated with continued drinking in pregnancy. Routine antenatal assessment of alcohol history and current drinking is variable; potentially harmful peri-conceptual drinking may be missed if a woman reports low or no drinking during pregnancy. Design: Cross-sectional study (n=510) in two Scottish health board areas. Methods: Face-to-face Retrospective Diary administration from February to June 2015 assessing alcohol consumption in peri-conceptual and mid-pregnancy periods. Women were recruited at the mid-pregnancy ultrasound clinic. Results: Of 510 women, 470 (92·0%) drank alcohol before their pregnancy; 187 (39·9%) drank every week. Retrospective assessment of peri-conceptual consumption identified heavy episodic drinking (more than six units on one occasion) in 52·2% (n=266); 19·6% (n=100) reported drinking more than 14 units per week, mostly at the weekend; ‘mixing’ of drinks was associated with significantly higher consumption. While consumption tailed off following pregnancy recognition, 5·5% (n=28) still exceeded the recommended daily two-unit limit in pregnancy. Multivariable logistic regression identified that women who ‘binged’ peri-conceptually were 3·2 times more likely to do this. Conclusion: Statistically significant peri-conceptual consumption levels suggest a substantial proportion of alcohol-exposed pregnancies before pregnancy recognition. Not taking a detailed alcohol history, including patterns of consumption, will result in under-detection of alcohol-exposed pregnancies. The Retrospective Diary offers practitioners a detailed way of enquiring about alcohol history for this population

A systematic review and meta-analysis of evidence for correlation between molecular markers of parasite resistance and treatment outcome in falciparum malaria

<p>Abstract</p> <p>Background</p> <p>An assessment of the correlation between anti-malarial treatment outcome and molecular markers would improve the early detection and monitoring of drug resistance by <it>Plasmodium falciparum</it>. The purpose of this systematic review was to determine the risk of treatment failure associated with specific polymorphisms in the parasite genome or gene copy number.</p> <p>Methods</p> <p>Clinical studies of non-severe malaria reporting on target genetic markers (SNPs for <it>pfmdr1</it>, <it>pfcrt</it>, <it>dhfr</it>, <it>dhps</it>, gene copy number for <it>pfmdr1</it>) providing complete information on inclusion criteria, outcome, follow up and genotyping, were included. Three investigators independently extracted data from articles. Results were stratified by gene, codon, drug and duration of follow-up. For each study and aggregate data the random effect odds ratio (OR) with 95%CIs was estimated and presented as Forest plots. An OR with a lower 95^thconfidence interval > 1 was considered consistent with a failure being associated to a given gene mutation.</p> <p>Results</p> <p>92 studies were eligible among the selection from computerized search, with information on <it>pfcrt </it>(25/159 studies), <it>pfmdr1 </it>(29/236 studies), <it>dhfr </it>(18/373 studies), <it>dhps </it>(20/195 studies). The risk of therapeutic failure after chloroquine was increased by the presence of <it>pfcrt </it>K76T (Day 28, OR = 7.2 [95%CI: 4.5–11.5]), <it>pfmdr1 </it>N86Y was associated with both chloroquine (Day 28, OR = 1.8 [95%CI: 1.3–2.4]) and amodiaquine failures (OR = 5.4 [95%CI: 2.6–11.3, p < 0.001]). For sulphadoxine-pyrimethamine the <it>dhfr </it>single (S108N) (Day 28, OR = 3.5 [95%CI: 1.9–6.3]) and triple mutants (S108N, N51I, C59R) (Day 28, OR = 3.1 [95%CI: 2.0–4.9]) and <it>dhfr</it>-<it>dhps </it>quintuple mutants (Day 28, OR = 5.2 [95%CI: 3.2–8.8]) also increased the risk of treatment failure. Increased <it>pfmdr1 </it>copy number was correlated with treatment failure following mefloquine (OR = 8.6 [95%CI: 3.3–22.9]).</p> <p>Conclusion</p> <p>When applying the selection procedure for comparative analysis, few studies fulfilled all inclusion criteria compared to the large number of papers identified, but heterogeneity was limited. Genetic molecular markers were related to an increased risk of therapeutic failure. Guidelines are discussed and a checklist for further studies is proposed.</p

The lancet weight determines wheal diameter in response to skin prick testing with histamine

BACKGROUND:Skin prick test (SPT) is a common test for diagnosing immunoglobulin E-mediated allergies. In clinical routine, technicalities, human errors or patient-related biases, occasionally results in suboptimal diagnosis of sensitization. OBJECTIVE:Although not previously assessed qualitatively, lancet weight is hypothesized to be important when performing SPT to minimize the frequency of false positives, false negatives, and unwanted discomfort. METHODS:Accurate weight-controlled SPT was performed on the volar forearms and backs of 20 healthy subjects. Four predetermined lancet weights were applied (25 g, 85 g, 135 g and 265 g) using two positive control histamine solutions (1 mg/mL and 10 mg/mL) and one negative control (saline). A total of 400 SPTs were conducted. The outcome parameters were: wheal size, neurogenic inflammation (measured by superficial blood perfusion), frequency of bleeding, and the lancet provoked pain response. RESULTS:The mean wheal diameter increased significantly as higher weights were applied to the SPT lancet, e.g. from 3.2 ± 0.28 mm at 25 g to 5.4 ± 1.7 mm at 265 g (p<0.01). Similarly, the frequency of bleeding, the provoked pain, and the neurogenic inflammatory response increased significantly. At 265 g saline evoked two wheal responses (/160 pricks) below 3 mm. CONCLUSION AND CLINICAL RELEVANCE:The applied weight of the lancet during the SPT-procedure is an important factor. Higher lancet weights precipitate significantly larger wheal reactions with potential diagnostic implications. This warrants additional research of the optimal lancet weight in relation to SPT-guidelines to improve the specificity and sensitivity of the procedure