Rapid clinical screening using specific geriatric criteria is effective in identifying frail older subjects at risk for mortality and nursing home utilization. Our findings suggest that geriatric syndromes are more predictive of adverse outcomes than diagnosis per se. This well operationalized screening process is inexpensive as well as effective and could easily be introduced into other hospital settings.
The nucleotide sequence of 1.5 Mb of genomic DNA from Mycobacterium leprae was determined using computer-assisted multiplex sequencing technology. This brings the 2.8-Mb M. leprae genome sequence to ∼66% completion. The sequences, derived from 43 recombinant cosmids, contain 1046 putative protein-coding genes, 44 repetitive regions, 3 rRNAs, and 15 tRNAs. The gene density of one per 1.4 kb is slightly lower than that of Mycoplasma (1.2 kb). Of the protein coding genes, 44% have significant matches to genes with well-defined functions. Comparison of 1157 M. leprae and 1564 Mycobacterium tuberculosis proteins shows a complex mosaic of homologous genomic blocks with up to 22 adjacent proteins in conserved map order. Matches to known enzymatic, antigenic, membrane, cell wall, cell division, multidrug resistance, and virulence proteins suggest therapeutic and vaccine targets. Unusual features of the M. leprae genome include large polyketide synthase (pks) operons, inteins, and highly fragmented pseudogenes.[The sequence data described in this paper have been submitted to GenBank under accession nos. L78811-L78829, U00010-U00023, U15180-U15184, U15186, U15187, L01095, L01536, L04666, and L01263. On-line supplementary information for Table 1 is available at http://www.cshl.org/gr.]Despite improved medical care and large vaccination programs, infectious organisms are still the leading cause of death, worldwide, and the pathogenic mycobacteria are among the worst offenders. There are estimated to be ∼5 million cases of leprosy, globally, while tuberculosis kills ∼3 million persons per year. The frequent occurrence of multidrug resistant Mycobacterium tuberculosis and the documented appearance of dapsone resistant Mycobacterium leprae are reminders that current therapies may not always be effective and that we should continue to search for and develop new antiinfective agents.M. leprae is one of the few bacterial pathogens that infects humans and cannot be cultivated outside of animals. The organism is an intracellular parasite that grows extremely slowly (generation
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