Toward the development of a synthetic group A streptococcal vaccine of high purity and broad protective coverage

Using native chemical ligation, we synthesized a group A streptococcal. (GAS) vaccine that contained three different GAS M protein peptide epitopes in a chemically well-characterized construct in high purity. Two of the peptide epitopes represented variable amino terminal serotype determinants, and the third represented a carboxyl terminal conserved region determinant of the GAS M protein. We also synthesized a lipid core peptide (LCP) construct containing the same three peptides. Upon immunization of mice, the non-LCP construct only elicited antibody responses to all three epitopes with the use of adjuvant. The LCP construct, however, elicited excellent antibody responses to all three epitopes without the need for any additional adjuvant or carrier. We have synthesized the LCP synthetic vaccine system with good reproducibility.

Correlation of non-uniform protein expression with variation in transmitter release probability

The strength of synaptic transmission is highly variable between different synapses. The present study examined some factors that may contribute to this variation in the strength of neurotransmission in sympathetic varicosities of the mouse vas deferens. Transmitter release was measured using a focal macropatch electrode placed over pairs of visualised varicosities. By regulating the calcium concentration of the solutions inside the recording electrode and in the bath independently of each other, transmitter release was restricted to one or two surface varicosities at each recording site. Using this technique, transmitter release probability was shown to be highly variable, even between adjacent varicosities on single axon branches. Very little variation was observed in the calcium influx following single impulse nerve stimulation between adjacent Oregon Green BAPTA-1 loaded varicosities. However, the staining intensities of three vesicular proteins, SV2, synaptophysin, and synaptotagmin 1, showed considerable variation between adjacent varicosities on single axon branches. This variation in staining intensity may be partly explained by variation in the density of synaptic vesicles. However, double staining experiments using two vesicular antigens showed some varicosities staining for one vesicular antigen, but not for the second, suggesting that the expression of these release machinery proteins is regulated locally within the varicosities. The results of the present study strengthen suggestions that synaptic strength is at least in part, regulated by variation in the expression of vesicular proteins. (C) 2004 Wiley-Liss, Inc.

Benchmarking of performance of Mexican states with effective coverage

Benchmarking of the performance of states, provinces, or districts in a decentralised health system is important for fostering of accountability, monitoring of progress, identification of determinants of success and failure, and creation of a culture of evidence. The Mexican Ministry of Health has, since 2001, used a benchmarking approach based on the World Health Organization (WHO) concept of effective coverage of an intervention, which is defined as the proportion of potential health gain that could be delivered by the health system to that which is actually delivered. Using data collection systems, including state representative examination surveys, vital registration, and hospital discharge registries, we have monitored the delivery of 14 interventions for 2005-06. Overall effective coverage ranges from 54.0% in Chiapas, a poor state, to 65.1% in the Federal District. Effective coverage for maternal and child health interventions is substantially higher than that for interventions that target other health problems. Effective coverage for the lowest wealth quintile is 52% compared with 61% for the highest quintile. Effective coverage is closely related to public-health spending per head across states; this relation is stronger for interventions that are not related to maternal and child health than those for maternal and child health. Considerable variation also exists in effective coverage at similar amounts of spending. We discuss the implications of these issues for the further development of the Mexican health-information system. Benchmarking of performance by measuring effective coverage encourages decision-makers to focus on quality service provision, not only service availability. The effective coverage calculation is an important device for health-system stewardship. In adopting this approach, other countries should select interventions to be measured on the basis of the criteria of affordability, effect on population health, effect on health inequalities, and capacity to measure the effects of the intervention. The national institutions undertaking this benchmarking must have the mandate, skills, resources, and independence to succeed.