Panel 4 : Report of the Microbiology Panel

Objective. To perform a comprehensive review of the literature from July 2011 until June 2015 on the virology and bacteriology of otitis media in children. Data Sources. PubMed database of the National Library of Medicine. Review Methods. Two subpanels comprising experts in the virology and bacteriology of otitis media were created. Each panel reviewed the relevant literature in the fields of virology and bacteriology and generated draft reviews. These initial reviews were distributed to all panel members prior to meeting together at the Post-symposium Research Conference of the 18th International Symposium on Recent Advances in Otitis Media, National Harbor, Maryland, in June 2015. A final draft was created, circulated, and approved by all panel members. Conclusions. Excellent progress has been made in the past 4 years in advancing our understanding of the microbiology of otitis media. Numerous advances were made in basic laboratory studies, in animal models of otitis media, in better understanding the epidemiology of disease, and in clinical practice. Implications for Practice. (1) Many viruses cause acute otitis media without bacterial coinfection, and such cases do not require antibiotic treatment. (2) When respiratory syncytial virus, metapneumovirus, and influenza virus peak in the community, practitioners can expect to see an increase in clinical otitis media cases. (3) Biomarkers that predict which children with upper respiratory tract infections will develop otitis media may be available in the future. (4) Compounds that target newly identified bacterial virulence determinants may be available as future treatment options for children with otitis media.Peer reviewe

Panel 6 : Vaccines

Objective. To review the literature on progress regarding (1) effectiveness of vaccines for prevention of otitis media (OM) and (2) development of vaccine antigens for OM bacterial and viral pathogens. Data Sources. PubMed database of the National Library of Science. Review Methods. We performed literature searches in PubMed for OM pathogens and candidate vaccine antigens, and we restricted the searches to articles in English that were published between July 2011 and June 2015. Panel members reviewed literature in their area of expertise. Conclusions. Pneumococcal conjugate vaccines (PCVs) are somewhat effective for the prevention of pneumococcal OM, recurrent OM, OM visits, and tympanostomy tube insertions. Widespread use of PCVs has been associated with shifts in pneumococcal serotypes and bacterial pathogens associated with OM, diminishing PCV effectiveness against AOM. The 10-valent pneumococcal vaccine containing Haemophilus influenzae protein D (PHiD-CV) is effective for pneumococcal OM, but results from studies describing the potential impact on OM due to H influenzae have been inconsistent. Progress in vaccine development for H influenzae, Moraxella catarrhalis, and OM-associated respiratory viruses has been limited. Additional research is needed to extend vaccine protection to additional pneumococcal serotypes and other otopathogens. There are likely to be licensure challenges for protein-based vaccines, and data on correlates of protection for OM vaccine antigens are urgently needed. Implications for Practice. OM continues to be a significant health care burden globally. Prevention is preferable to treatment, and vaccine development remains an important goal. As a polymicrobial disease, OM poses significant but not insurmountable challenges for vaccine development.Peer reviewe

A multi-disciplinary education process related to the discharging of children from hospital when the child has been diagnosed with type 1 diabetes - a qualitative study

<p>Abstract</p> <p>Background</p> <p>Worldwide, insulin-dependent type 1 diabetes is one of the most frequently diagnosed long-term endocrine disorders found in children and the incidences of this diseased is still increasing. In Sweden the routines are, according to national guidelines, when the child is diagnosed with type 1 diabetes, the child and its family remains at the hospital for about two weeks. There is limited knowledge about how a diabetes team handles a child and its family from admission to discharge, therefore the purpose of this study was to seek a deeper understanding of how the diabetes team's parent/child education process works, from admission to discharge, among families with a child newly diagnosed with type 1 diabetes.</p> <p>Methods</p> <p>Qualitative data collection was used. Four focus-group interviews, with a sample of three diabetes teams from different paediatric hospitals in the south western part of Sweden, were conducted and the data recorded on tape and then analysed using qualitative content analysis.</p> <p>Results</p> <p>The results indicate that achieving a status of self-care on the part of the patient is the goal of the diabetes education programme. Part of the programme is aimed at guiding the child and its parents towards self-help through the means of providing them with knowledge of the disease and its treatment to enable the whole family to understand the need for cooperation in the process. To do this requires an understanding, by the diabetes team, of the individualities of the family in order to gain an overall picture.</p> <p>Conclusion</p> <p>The results of this study show that the diabetes education programme is specifically designed for each family using the internationally recommended clinical practice guidelines with its specific aims and objectives. Achieving the families' willingness to assist in the self-care of the child care is the goal of the parent education process. To achieve this, the paediatric diabetes specialist nurse and the diabetes specialist paediatrician immediately and deliberately start the process of educating the family using a programme designed to give them the necessary knowledge and skills they will need to manage their child's type 1 diabetes at home.</p

E2F1 Regulates Cellular Growth by mTORC1 Signaling

During cell proliferation, growth must occur to maintain homeostatic cell size. Here we show that E2F1 is capable of inducing growth by regulating mTORC1 activity. The activation of cell growth and mTORC1 by E2F1 is dependent on both E2F1's ability to bind DNA and to regulate gene transcription, demonstrating that a gene induction expression program is required in this process. Unlike E2F1, E2F3 is unable to activate mTORC1, suggesting that growth activity could be restricted to individual E2F members. The effect of E2F1 on the activation of mTORC1 does not depend on Akt. Furthermore, over-expression of TSC2 does not interfere with the effect of E2F1, indicating that the E2F1-induced signal pathway can compensate for the inhibitory effect of TSC2 on Rheb. Immunolocalization studies demonstrate that E2F1 induces the translocation of mTORC1 to the late endosome vesicles, in a mechanism dependent of leucine. E2F1 and leucine, or insulin, together affect the activation of S6K stronger than alone suggesting that they are complementary in activating the signal pathway. From these studies, E2F1 emerges as a key protein that integrates cell division and growth, both of which are essential for cell proliferation

Comparative Lipidomics in Clinical Isolates of Candida albicans Reveal Crosstalk between Mitochondria, Cell Wall Integrity and Azole Resistance

Prolonged usage of antifungal azoles which target enzymes involved in lipid biosynthesis invariably leads to the development of multi-drug resistance (MDR) in Candida albicans. We had earlier shown that membrane lipids and their fluidity are closely linked to the MDR phenomenon. In one of our recent studies involving comparative lipidomics between azole susceptible (AS) and azole resistant (AR) matched pair clinical isolates of C. albicans, we could not see consistent differences in the lipid profiles of AS and AR strains because they came from different patients and so in this study, we have used genetically related variant recovered from the same patient collected over a period of 2-years. During this time, the levels of fluconazole (FLC) resistance of the strain increased by over 200-fold. By comparing the lipid profiles of select isolates, we were able to observe gradual and statistically significant changes in several lipid classes, particularly in plasma membrane microdomain specific lipids such as mannosylinositolphosphorylceramides and ergosterol, and in a mitochondrial specific phosphoglyceride, phosphatidyl glycerol. Superimposed with these quantitative and qualitative changes in the lipid profiles, were simultaneous changes at the molecular lipid species levels which again coincided with the development of resistance to FLC. Reverse transcriptase-PCR of the key genes of the lipid metabolism validated lipidomic picture. Taken together, this study illustrates how the gradual corrective changes in Candida lipidome correspond to the development of FLC tolerance. Our study also shows a first instance of the mitochondrial membrane dysfunction and defective cell wall (CW) in clinical AR isolates of C. albicans, and provides evidence of a cross-talk between mitochondrial lipid homeostasis, CW integrity and azole tolerance

A genome-wide SNP-association study confirms a sequence variant (g.66493737C>T) in the equine myostatin (MSTN) gene as the most powerful predictor of optimum racing distance for Thoroughbred racehorses

<p>Abstract</p> <p>Background</p> <p>Thoroughbred horses have been selected for traits contributing to speed and stamina for centuries. It is widely recognized that inherited variation in physical and physiological characteristics is responsible for variation in individual aptitude for race distance, and that muscle phenotypes in particular are important.</p> <p>Results</p> <p>A genome-wide SNP-association study for optimum racing distance was performed using the EquineSNP50 Bead Chip genotyping array in a cohort of <it>n </it>= 118 elite Thoroughbred racehorses divergent for race distance aptitude. In a cohort-based association test we evaluated genotypic variation at 40,977 SNPs between horses suited to short distance (≤ 8 f) and middle-long distance (> 8 f) races. The most significant SNP was located on chromosome 18: BIEC2-417495 ~690 kb from the gene encoding myostatin (<it>MSTN</it>) [<it>P</it>_unadj.= 6.96 × 10^-6]. Considering best race distance as a quantitative phenotype, a peak of association on chromosome 18 (chr18:65809482-67545806) comprising eight SNPs encompassing a 1.7 Mb region was observed. Again, similar to the cohort-based analysis, the most significant SNP was BIEC2-417495 (<it>P</it>_unadj.= 1.61 × 10^-9; <it>P</it>_Bonf.= 6.58 × 10^-5). In a candidate gene study we have previously reported a SNP (g.66493737C>T) in <it>MSTN </it>associated with best race distance in Thoroughbreds; however, its functional and genome-wide relevance were uncertain. Additional re-sequencing in the flanking regions of the <it>MSTN </it>gene revealed four novel 3' UTR SNPs and a 227 bp SINE insertion polymorphism in the 5' UTR promoter sequence. Linkage disequilibrium was highest between g.66493737C>T and BIEC2-417495 (<it>r</it>²= 0.86).</p> <p>Conclusions</p> <p>Comparative association tests consistently demonstrated the g.66493737C>T SNP as the superior variant in the prediction of distance aptitude in racehorses (g.66493737C>T, <it>P </it>= 1.02 × 10^-10; BIEC2-417495, <it>P</it>_unadj.= 1.61 × 10^-9). Functional investigations will be required to determine whether this polymorphism affects putative transcription-factor binding and gives rise to variation in gene and protein expression. Nonetheless, this study demonstrates that the g.66493737C>T SNP provides the most powerful genetic marker for prediction of race distance aptitude in Thoroughbreds.</p

EBP1 Is a Novel E2F Target Gene Regulated by Transforming Growth Factor-β

Regulation of gene expression requires transcription factor binding to specific DNA elements, and a large body of work has focused on the identification of such sequences. However, it is becoming increasingly clear that eukaryotic transcription factors can exhibit widespread, nonfunctional binding to genomic DNA sites. Conversely, some of these proteins, such as E2F, can also modulate gene expression by binding to non-consensus elements. E2F comprises a family of transcription factors that play key roles in a wide variety of cellular functions, including survival, differentiation, activation during tissue regeneration, metabolism, and proliferation. E2F factors bind to the Erb3-binding protein 1 (EBP1) promoter in live cells. We now show that E2F binding to the EBP1 promoter occurs through two tandem DNA elements that do not conform to typical consensus E2F motifs. Exogenously expressed E2F1 activates EBP1 reporters lacking one, but not both sites, suggesting a degree of redundancy under certain conditions. E2F1 increases the levels of endogenous EBP1 mRNA in breast carcinoma and other transformed cell lines. In contrast, in non-transformed primary epidermal keratinocytes, E2F, together with the retinoblastoma family of proteins, appears to be involved in decreasing EBP1 mRNA abundance in response to growth inhibition by transforming growth factor-β1. Thus, E2F is likely a central coordinator of multiple responses that culminate in regulation of EBP1 gene expression, and which may vary depending on cell type and context

The willingness of final year medical and dental students to perform bystander cardiopulmonary resuscitation in an Asian community

Background Despite the importance of early effective chest compressions to improve the chance of survival of an out-of-hospital cardiac arrest victim, it is still largely unknown how willing our Malaysian population is to perform bystander cardiopulmonary resuscitation (CPR). Aims We conducted a voluntary, anonymous self-administered questionnaire survey of a group of 164 final year medical students and 60 final year dental students to unravel their attitudes towards performing bystander CPR. Methods Using a 4-point Likert scale of “definitely yes,” “probably yes,” “probably no,” and “definitely no,” the students were asked to rate their willingness to perform bystander CPR under three categories: chest compressions with mouth-to-mouth ventilation (CC + MMV), chest compressions with mask-to-mouth ventilation (CC + PMV), and chest compressions only (CC). Under each category, the students were given ten hypothetical victim scenarios. Categorical data analysis was done using the McNemar test, chi-square test, and Fisher exact test where appropriate. For selected analysis, “definitely yes” and “probably yes” were recoded as a “positive response.” Results Generally, we found that only 51.4% of the medical and 45.5% of the dental students are willing to perform bystander CPR. When analyzed under different hypothetical scenarios, we found that, except for the scenario where the victim is their own family member, all other scenarios showed a dismally low rate of positive responses in the category of CC + MMV, but their willingness was significantly improved under the CC + PMV and CC categories. Conclusion This study shows that there are unique sociocultural factors that contribute to the reluctance of our students to perform CC + MMV. Keywords Cardiopulmonary resuscitation Mouth-to-mouth resuscitation Basic cardiac life support Asian communit