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

Lutzomyia Sand Fly Diversity and Rates of Infection by Wolbachia and an Exotic Leishmania Species on Barro Colorado Island, Panama

Certain sand fly species living inside or on the edge of tropical forests are well known to transmit a protozoan to humans, which in lowland Panama develops into a cutaneous form of leishmaniasis; open, itching sores on the face and extremities requiring aggressive treatment with antimonial compounds. Morphological characters and DNA sequence from mitochondrial and nuclear gene fragments permitted us to identify and then establish historical relationships among 20 common sand fly species occurring in the understory of Barro Colorado Island, a forested preserve in the middle of the Panama Canal. Individuals in three of these sand fly species were found to be 26–43% infected by Leishmania naiffi, a species hitherto known only from the Amazonian region and the Caribbean. We then screened the same 20 sand fly species for the cytoplasmically transmitted bacteria Wolbachia pipientis, finding three infected at high rates, each by a distinct strain. Lutzomyia trapidoi, the most likely transmitter of Leishmania to humans in Panama, was among the Wolbachia-infected species, thus marking it as a possible high-value target for future biocontrol studies using the bacteria either to induce mating incompatabilities or to drive selected genes into the population

A Conserved Role for Syndecan Family Members in the Regulation of Whole-Body Energy Metabolism

Syndecans are a family of type-I transmembrane proteins that are involved in cell-matrix adhesion, migration, neuronal development, and inflammation. Previous quantitative genetic studies pinpointed Drosophila Syndecan (dSdc) as a positional candidate gene affecting variation in fat storage between two Drosophila melanogaster strains. Here, we first used quantitative complementation tests with dSdc mutants to confirm that natural variation in this gene affects variability in Drosophila fat storage. Next, we examined the effects of a viable dSdc mutant on Drosophila whole-body energy metabolism and associated traits. We observed that young flies homozygous for the dSdc mutation had reduced fat storage and slept longer than homozygous wild-type flies. They also displayed significantly reduced metabolic rate, lower expression of spargel (the Drosophila homologue of PGC-1), and reduced mitochondrial respiration. Compared to control flies, dSdc mutants had lower expression of brain insulin-like peptides, were less fecund, more sensitive to starvation, and had reduced life span. Finally, we tested for association between single nucleotide polymorphisms (SNPs) in the human SDC4 gene and variation in body composition, metabolism, glucose homeostasis, and sleep traits in a cohort of healthy early pubertal children. We found that SNP rs4599 was significantly associated with resting energy expenditure (P = 0.001 after Bonferroni correction) and nominally associated with fasting glucose levels (P = 0.01) and sleep duration (P = 0.044). On average, children homozygous for the minor allele had lower levels of glucose, higher resting energy expenditure, and slept shorter than children homozygous for the common allele. We also observed that SNP rs1981429 was nominally associated with lean tissue mass (P = 0.035) and intra-abdominal fat (P = 0.049), and SNP rs2267871 with insulin sensitivity (P = 0.037). Collectively, our results in Drosophila and humans argue that syndecan family members play a key role in the regulation of body metabolism

Translational studies in the complex role of neurotransmitter systems in anxiety and anxiety disorders

Discovery of innovative anxiolytics is severely hampering. Existing anxiolytics are developed decades ago and are still the therapeutics of choice. Moreover, lack of new drug targets forecasts a severe jeopardy in the future treatment of the huge population of CNS-diseased patients. We simply lack the knowledge on what is wrong in brains of anxious people (normal and diseased). Translational research, based on interacting clinical and preclinical research, is extremely urgent. In this endeavor, genetic and genomic approaches are part of the spectrum of contributing factors. We focus on three druggable targets: serotonin transporter, 5-HT1A, and GABAA receptors. It is still uncertain whether and how these targets are involved in normal and diseased anxiety processes. For serotonergic anxiolytics, the slow onset of action points to indirect effects leading to plasticity changes in brain systems leading to reduced anxiety. For GABAA benzodiazepine drugs, acute anxiolytic effects are found indicating primary mechanisms directly influencing anxiety processes. Close translational collaboration between fundamental academic and discovery research will lead to badly needed breakthroughs in the search for new anxiolytics.</p

The 20 year evolution of dobutamine stress cardiovascular magnetic resonance

Over the past 20 years, investigators world-wide have developed and utilized dobutamine magnetic resonance stress testing procedures for the purpose of identifying ischemia, viability, and cardiac prognosis. This article traces these developments and reviews the data utilized to substantiate this relatively new noninvasive imaging procedure

Microbial Fuel Cells and Microbial Ecology: Applications in Ruminant Health and Production Research

Microbial fuel cell (MFC) systems employ the catalytic activity of microbes to produce electricity from the oxidation of organic, and in some cases inorganic, substrates. MFC systems have been primarily explored for their use in bioremediation and bioenergy applications; however, these systems also offer a unique strategy for the cultivation of synergistic microbial communities. It has been hypothesized that the mechanism(s) of microbial electron transfer that enable electricity production in MFCs may be a cooperative strategy within mixed microbial consortia that is associated with, or is an alternative to, interspecies hydrogen (H2) transfer. Microbial fermentation processes and methanogenesis in ruminant animals are highly dependent on the consumption and production of H2in the rumen. Given the crucial role that H2 plays in ruminant digestion, it is desirable to understand the microbial relationships that control H2 partial pressures within the rumen; MFCs may serve as unique tools for studying this complex ecological system. Further, MFC systems offer a novel approach to studying biofilms that form under different redox conditions and may be applied to achieve a greater understanding of how microbial biofilms impact animal health. Here, we present a brief summary of the efforts made towards understanding rumen microbial ecology, microbial biofilms related to animal health, and how MFCs may be further applied in ruminant research

Anxiety Levels in Children with Autism Spectrum Disorder:A Meta-Analysis

The aim of the current study was to meta-analytically examine whether anxiety levels in children with autism spectrum disorders (ASD) are elevated. A total of 83 articles were selected from a systematic literature search and were included in the meta-analyses. Results demonstrated that children with ASD had higher anxiety levels compared to typically developing children, and this difference increased with IQ. Youth with ASD also tended to have higher anxiety levels compared to clinically referred children, and this difference increased with age. Children with ASD had higher anxiety levels compared to youth with externalizing or developmental problems, but not when compared to youth with internalizing problems. The study findings highlight the importance of more research in order to fully understand the nature and development of anxiety in children with ASD. More specifically, the results suggest that especially high-functioning adolescents with ASD may be at risk for developing anxiety disorders. Therefore, it seems important to carefully follow and monitor children with ASD transcending to adolescenc

Basement membrane components are key players in specialized extracellular matrices

More than three decades ago, basement membranes (BMs) were described as membrane-like structures capable of isolating a cell from and connecting a cell to its environment. Since this time, it has been revealed that BMs are specialized extracellular matrices (sECMs) with unique components that support important functions including differentiation, proliferation, migration, and chemotaxis of cells during development. The composition of these sECM is as unique as the tissues to which they are localized, opening the possibility that such matrices can fulfill distinct functions. Changes in BM composition play significant roles in facilitating the development of various diseases. Furthermore, tissues have to provide sECM for their stem cells during development and for their adult life. Here, we briefly review the latest research on these unique sECM and their components with a special emphasis on embryonic and adult stem cells and their niches

Best practice for motor imagery: a systematic literature review on motor imagery training elements in five different disciplines

<p>Abstract</p> <p>Background</p> <p>The literature suggests a beneficial effect of motor imagery (MI) if combined with physical practice, but detailed descriptions of MI training session (MITS) elements and temporal parameters are lacking. The aim of this review was to identify the characteristics of a successful MITS and compare these for different disciplines, MI session types, task focus, age, gender and MI modification during intervention.</p> <p>Methods</p> <p>An extended systematic literature search using 24 databases was performed for five disciplines: Education, Medicine, Music, Psychology and Sports. References that described an MI intervention that focused on motor skills, performance or strength improvement were included. Information describing 17 MITS elements was extracted based on the PETTLEP (physical, environment, timing, task, learning, emotion, perspective) approach. Seven elements describing the MITS temporal parameters were calculated: study duration, intervention duration, MITS duration, total MITS count, MITS per week, MI trials per MITS and total MI training time.</p> <p>Results</p> <p>Both independent reviewers found 96% congruity, which was tested on a random sample of 20% of all references. After selection, 133 studies reporting 141 MI interventions were included. The locations of the MITS and position of the participants during MI were task-specific. Participants received acoustic detailed MI instructions, which were mostly standardised and live. During MI practice, participants kept their eyes closed. MI training was performed from an internal perspective with a kinaesthetic mode. Changes in MI content, duration and dosage were reported in 31 MI interventions. Familiarisation sessions before the start of the MI intervention were mentioned in 17 reports. MI interventions focused with decreasing relevance on motor-, cognitive- and strength-focused tasks. Average study intervention lasted 34 days, with participants practicing MI on average three times per week for 17 minutes, with 34 MI trials. Average total MI time was 178 minutes including 13 MITS. Reporting rate varied between 25.5% and 95.5%.</p> <p>Conclusions</p> <p>MITS elements of successful interventions were individual, supervised and non-directed sessions, added after physical practice. Successful design characteristics were dominant in the Psychology literature, in interventions focusing on motor and strength-related tasks, in interventions with participants aged 20 to 29 years old, and in MI interventions including participants of both genders. Systematic searching of the MI literature was constrained by the lack of a defined MeSH term.</p