RESUMEN
Chlorosphaerolactylate B, a newly discovered antimicrobial halometabolite from the cyanobacterium Sphaerospermopsis sp. LEGE 00249 has been synthesized in three steps by using 12-bromododecanoic acid as starting material. A total of 0.5 g was produced for in vitro and in vivo antimicrobial efficacy testing. In vitro, the minimal inhibitory concentration (MIC) was estimated to be 256 mg/L for Staphylococcus aureus, while the minimal biofilm inhibitory concentration (MBIC) was estimated to be 74 mg/L. The in vivo study utilized a porcine model of implant-associated osteomyelitis. In total, 12 female pigs were allocated into 3 groups based on inoculum (n = 4 in each group). An implant cavity (IC) was drilled in the right tibia and followed by inoculation and insertion of a steel implant. All pigs were inoculated with 10 µL containing either: 11.79 mg synthetic Chlorosphaerolactylate B + 104 CFU of S. aureus (Group A), 104 CFU of S. aureus (Group B), or pure saline (Group C), respectively. Pigs were euthanized five days after inoculation. All Group B animals showed macroscopic and microscopic signs of bone infection and both tissue and implant harbored S. aureus bacteria (mean CFU on implants = 1.9 × 105). In contrast, S. aureus could not be isolated from animals inoculated with saline. In Group A, two animals had a low number of S. aureus (CFU = 6.7 × 101 and 3.8 × 101, respectively) on the implants, otherwise all Group A animals were similar to Group C animals. In conclusion, synthetic Chlorosphaerolactylate B holds potential to be a novel antimicrobial and antibiofilm compound.
RESUMEN
OBJECTIVE: Multimorbidity (MM) is more prevalent among people of lower socioeconomic status (SES), and both MM and SES are associated with higher mortality rates. However, little is known about the relationship between SES, MM, and mortality. This study investigates the association between educational level and mortality, and to what extent MM modifies this association. METHODS: We followed 239,547 individuals invited to participate in the Danish National Health Survey 2010 (mean follow-up time: 3.8 years). MM was assessed by using information on drug prescriptions and diagnoses for 39 long-term conditions. Data on educational level were provided by Statistics Denmark. Date of death was obtained from the Civil Registration System. Information on lifestyle factors and quality of life was collected from the survey. The main outcomes were overall and premature mortality (death before the age of 75). RESULTS: Of a total of 12,480 deaths, 6,607 (9.5%) were of people with low educational level (LEL) and 1,272 (2.3%) were of people with high educational level (HEL). The mortality rate was higher among people with LEL compared with HEL in groups of people with 0-1 disease (hazard ratio: 2.26, 95% confidence interval: 2.00-2.55) and ≥4 diseases (hazard ratio: 1.14, 95% confidence interval: 1.04-1.24), respectively (adjusted model). The absolute number of deaths was six times higher among people with LEL than those with HEL in those with ≥4 diseases. The 1-year cumulative mortality proportions for overall death in those with ≥4 diseases was 5.59% for people with HEL versus 7.27% for people with LEL, and 1-year cumulative mortality proportions for premature death was 2.93% for people with HEL versus 4.04% for people with LEL. Adjusting for potential mediating factors such as lifestyle and quality of life eliminated the statistical association between educational level and mortality in people with MM. CONCLUSION: Our study suggests that LEL is associated with higher overall and premature mortality and that the association is affected by MM, lifestyle factors, and quality of life.