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041) in the healthy hippocampus. Using a cut-off point for a survival analysis, we found that patients with lower values of MD of the molecular layer and the CA1 remained SF during long-term post-operative follow-up (p less then 0.0001). CONCLUSIONS The contralateral hippocampal internal microstructure may have be implicated in post-surgery seizure freedom in patients with TLE-HS. BACKGROUND Continuous ambulatory peritoneal dialysis (CAPD) is the first option for patients with end-stage renal disease under the benefit package of Thailand. Nevertheless, automated peritoneal dialysis (APD) may benefit these patients in terms of both medical and quality-of-life aspects, but it is more expensive. The economic evidence for the comparison between CAPD and APD is not inconclusive. Thus, this study aims to evaluate the cost-effectiveness of CAPD compared with APD in PD patients. OBJECTIVES To assess the health-related quality of life and costs between patients treated with CAPD and APD. METHODS A Markov model was developed to evaluate the cost-effectiveness of CAPD and APD from the societal perspective. Costs and outcomes were calculated over a lifetime horizon and discounted at an annual rate of 3%. The outcomes were presented as quality-adjusted life-years (QALYs) of CAPD and APD. Utility scores were calculated from the utility values of the 5-level EuroQol questionnaire. A probabilistic sensitivity analysis using 5000 Monte Carlo simulations was performed to evaluate the stability of the results. RESULTS The costs of APD and CAPD were 12 868 080 and 11 144 786 Thai baht, respectively, whereas the QALYs were 24.28 and 24.72 QALYs, respectively. APD was more costly but less effective than CAPD. The most sensitive parameter was direct medical cost of outpatient visits. When the willingness-to-pay threshold was 160 000 Thai baht per QALY, the probability of APD providing a cost-effective alternative to CAPD was 19%. CONCLUSION APD was not a cost-effective strategy as compared with CAPD at the current Thai threshold. These findings should encourage clinicians and policy makers to encompass the use of CAPD as a good value for money for PD treatment. OBJECTIVES Countries have constrained healthcare budgets and must prioritize new interventions depending on health goals and time frame. This situation is relevant in the sphere of national immunization programs, for which many different vaccines are proposed, budgets are limited, and efficient choices must be made in the order of vaccine introduction. METHODS A constrained optimization (CO) model for infectious diseases was developed in which different intervention types (prophylaxis and treatment) were combined for consideration in Malaysia. Local experts defined their priority public health issues pneumococcal disease, dengue, hepatitis B and C, rotavirus, neonatal pertussis, and cholera. Epidemiological, cost, and effectiveness data were informed from local or regionally published literature. The model aimed to maximize quality-adjusted life-year (QALY) gain through the reduction of events in each of the different diseases, under budget and intervention coverage constraints. The QALY impact of the interventions was assessed over 2 periods lifetime and 20 years. The period of investment was limited to 15 years. RESULTS The assessment time horizon influenced the prioritization of interventions maximizing QALY gain. The incremental health gains compared with a uninformed prioritization were large for the first 8 years and declined thereafter. Rotaviral and pneumococcal vaccines were identified as key priorities irrespective of time horizon, hepatitis B immune prophylaxis and hepatitis C treatment were priorities with the lifetime horizon, and dengue vaccination replaced these with the 20-year horizon. CONCLUSIONS CO modeling is a useful tool for making economically efficient decisions within public health programs for the control of infectious diseases by helping prioritize the selection of interventions to maximize health gain under annual budget constraints. When Stanley Falkow introduced Molecular Koch's Postulates (Falkow, 1988) as a conceptual framework to identify microbial factors that contributed to disease, he reaffirmed the prominent role that the basic principles of genetic analysis should play in defining genotype-phenotype associations in microbial pathogens. In classical bacterial genetics the nature of mutations is inferred through cis-trans complementation and by indirectly mapping their relative position and physical distance through recombination frequencies - all of which were made possible by the genetic tools of the day natural transformations, conjugation and transduction. Unfortunately, many of these genetic tools are not always available to study pathogenic bacteria. The recombinant DNA revolution in the 1980s launched the field of molecular pathogenesis as genes could be treated as physical units that could be cut, spliced and transplanted from one microbe to another and thus not only 'prove' that an individual gene complemented a virulence defect in a mutant strain but also could impart pathogenic properties to otherwise benign microbes. The recombinant DNA revolution also enabled the generation of newer versions of genetic tools to generate mutations and engineer microbial genomes. The last decade has ushered in next generation sequencing technologies as a new powerful tool for bacterial genetics. The routine and inexpensive sequencing of microbial genomes has increased the number and phylogenetic scope of microbes that are amenable to functional characterization and experimentation. BMS-927711 ic50 In this review, we highlight some salient advances in this rapidly evolving area. Intravacuolar bacterial pathogens establish intracellular niches by constructing membrane-encompassed compartments. The vacuoles surrounding the bacteria are remarkably stable, facilitating microbial replication and preventing exposure to host cytoplasmically localized innate immune sensing mechanisms. To maintain integrity of the membrane compartment, the pathogen is armed with defensive weapons that prevent loss of vacuole integrity and potential exposure to host innate signaling. In some cases, the microbial components that maintain vacuolar integrity have been identified, but the basis for why the compartment degrades in their absence is unclear. In this review, we point out that lessons from the microbial-programmed degradation of the vacuole by the cytoplasmically localized Shigella flexneri provide crucial insights into how degradation of pathogen vacuoles occurs. We propose that in the absence of bacterial-encoded guard proteins, aberrant trafficking of host membrane-associated components results in a dysfunctional pathogen compartment.