Non-coding RNAs in the nervous system

Increasing evidence suggests that the development and function of the nervous system is heavily dependent on RNA editing and the intricate spatiotemporal expression of a wide repertoire of non-coding RNAs, including micro RNAs, small nucleolar RNAs and longer non-coding RNAs. Non-coding RNAs may provide the key to understanding the multi-tiered links between neural development, nervous system function, and neurological diseases.

Synthesis and immunological evaluation of M protein targeted tetra-valent and tri-valent group A streptococcal vaccine candidates based on the lipid-core peptide system

Group A streptococcus (GAS) is responsible for causing many clinical complications including the relatively benign streptococcal pharyngitis and impetigo. However. if left untreated. these conditions may lead to more severe diseases such as rheumatic fever (RF) and rheumatic heart disease (RHD). These diseases exhibit high morbidity and mortality, Particularly in developing countries and in indigenous populations of affluent countries. Only ever occur following GAS infection, a vaccine offers Promise for their Prevention. As stich, we have investigated the Use of the lipid-core peptide (LCP) system for the development of multi-valent Prophylactic GAS vaccines. The current study has investigated the capacity of this system to adjuvant LIP to four different GAS peptide epitopes. Presented are the synthesis and immunological assessment of tetra-valent and tri-valent GAS LCP systems. We demonstrated their capacity to elicit systemic IgG antibody responses in B10.BR mice to all GAS peptide epitopes. The data also showed that the LCP systems Were self-adjuvanting. These findings are particularly encouraging for the development of multi-valent LCP-based GAS vaccines.

A Bronchoscopic scoring system for airway secretions - Airway cellularity and microbiological validation

There is currently no validated scoring system for quantification of airway secretions in children. A user friendly, valid scoring system of airway secretions during flexible bronchoscopy (FB) would be useful for comparative purposes in clinical medicine and research. The objective of this study was to validate our bronchoscopic secretion (BS) scoring system by examining the relationship between the amount of secretions seen at bronchoscopy with airway cellularity and microbiology. In 106 children undergoing FIB, the relationship of BS grades with bronchocalveolar lavage (BAL) cellularity and infective state (bacterial and viral infections) were examined using receptor operator curves (ROC). BAL was obtained according to European Respiratory Society guidelines; first lavage for microbiology and second lavage for cellularity Area under the ROC was significant for total cell count (TCC) and neutrophil % but not for lymphocyte %. BS grade significantly related to infection positive state (chi(2)(trend) = 5.85, P = 0,016). The area under the ROC for infection positive state versus BS grade was 0.645, 95% Cl 0.527-0.763. The BS scoring system is a valid method for quantifying airway secretions in children undergoing bronchoscopy The system related well to airway cellularity and neutrophilia, as well as to an airway infective state. However, the system is only complementary to cell counts and cultures and cannot replace these laboratory quantification techniques.

Method for the synthesis of highly pure vaccines using the lipid core peptide system

Traditional vaccines consisting of whole attenuated microorganisms, killed microorganisms, or microbial components, administered with an adjuvant (e.g. alum), have been proved to be extremely successful. However, to develop new vaccines, or to improve upon current vaccines, new vaccine development techniques are required. Peptide vaccines offer the capacity to administer only the minimal microbial components necessary to elicit appropriate immune responses, minimizing the risk of vaccination associated adverse effects, and focusing the immune response toward important antigens. Peptide vaccines, however, are generally poorly immunogenic, necessitating administration with powerful, and potentially toxic adjuvants. The attachment of lipids to peptide antigens has been demonstrated as a potentially safe method for adjuvanting peptide epitopes. The lipid core peptide (LCP) system, which incorporates a lipidic adjuvant, carrier, and peptide epitopes into a single molecular entity, has been demonstrated to boost immunogenicity of attached peptide epitopes without the need for additional adjuvants. The synthesis of LCP systems normally yields a product that cannot be purified to homogeneity. The current study describes the development of methods for the synthesis of highly pure LCP analogs using native chemical ligation. Because of the highly lipophilic nature of the LCP lipid adjuvant, difficulties (e.g. poor solubility) were experienced with the ligation reactions. The addition of organic solvents to the ligation buffer solubilized lipidic species, but did not result in successful ligation reactions. In comparison, the addition of approximately 1% (w/v) sodium dodecyl sulfate (SDS) proved successful, enabling the synthesis of two highly pure, tri-epitopic Streptococcus pyogenes LCP analogs. Subcutaneous immunization of B10.BR (H-2(k)) mice with one of these vaccines, without the addition of any adjuvant, elicited high levels of systemic IgG antibodies against each of the incorporated peptides. Copyright (c) 2006 European Peptide Society and John Wiley & Sons, Ltd.

Design and implementation of an automatic message-routing system for low-cost telemedicine

Email has been used for some years as a low-cost telemedicine medium to provide support for developing countries. However, all operations have been relatively small scale and fairly labour intensive to administer. A scalable, automatic message-routing system was constructed which automates many of the tasks. During a four-month study period in 2002, 485 messages were processed automatically. There were 31 referrals from eight hospitals in three countries. These referrals were handled by 25 volunteer specialists from a panel of 42. Two system operators, located 10 time zones apart, managed the system. The median time from receipt of a new referral to its allocation to a specialist was 1.0 days (interquartile range 0.7-2.4). The median interval between allocation and first reply was 0.7 days (interquartile range 0.3-2.3). Automatic message handling solves many of the problems of manual email telemedicine systems and represents a potentially scalable way of doing low-cost telemedicine in the developing world.