Findings from three methods to identify falls in hospitals: Results from the Ambient Intelligent Geriatric Management system fall prevention trial.

OBJECTIVE: To (a) compare characteristics of patients who fall with those of patients who did not fall; and (b) characterise falls (time, injury severity and location) through three fall reporting methods (incident system reports, medical notes and clinician reports). METHODS: A substudy design within a stepped-wedge clinical trial was used: 3239 trial participants were recruited from two inpatient Geriatric Evaluation and Management Units and one general medicine ward in two Australian states. To compare the characteristics of patients who had fallen with those who had not, descriptive tests were used. To characterise falls through three reporting methods, bivariate logistic regressions were used. RESULTS: Patients who had fallen were more likely than patients who had not fallen to be cognitively impaired (51% vs. 29%, p < 0.01), admitted with falls (38% vs. 28%, p = 0.01) and have poor health outcomes such as prolonged length of stay (24 [16-34] vs. 12 [8-19] days [IQR], p < 0.01) and less likely to be discharged directly to the community (62% vs. 47%, p < 0.01). Most falls were captured from medical notes (93%), with clinician (71%) and incident reports (68%) missing 21%-25% of falls. The proportion of injurious falls identified through incident reports was higher than medical records or clinician reports (40% vs. 34% vs. 37%). CONCLUSIONS: This study reaffirms the need to improve reporting falls in incident systems and at clinical handover to the team leader. Research should continue to use more than one method of identifying falls, but include data from medical records. Many falls cause injury, resulting in poor health outcomes.

Toward synthesis of carbasugars (+)-gabosine C, (+)-COTC, (+)-pericosine B, and (+)-pericosine C.

Asymmetric total synthesis of (+)-gabosine C, (+)-pericosine B, and (+)-pericosine C has been reported from readily available d-(-)-isoascorbic acid and d-ribose involving Grubbs ring closing metathesis, Morita-Baylis-Hillman (MBH) reaction, and Luche reduction.

Discovery and optimization of a new class of pyruvate kinase inhibitors as potential therapeutics for the treatment of methicillin-resistant Staphylococcus aureus infections.

A novel series of bis-indoles derived from naturally occurring marine alkaloid 4 were synthesized and evaluated as inhibitors of methicillin-resistant Staphylococcus aureus (MRSA) pyruvate kinase (PK). PK is not only critical for bacterial survival which would make it a target for development of novel antibiotics, but it is reported to be one of the most highly connected 'hub proteins' in MRSA, and thus should be very sensitive to mutations and making it difficult for the bacteria to develop resistance. From the co-crystal structure of cis-3-4-dihydrohamacanthin B (4) bound to S. aureus PK we were able to identify the pharmacophore needed for activity. Consequently, we prepared simple direct linked bis-indoles such as 10b that have similar anti-MRSA activity as compound 4. Structure-activity relationship (SAR) studies were carried out on 10b and led us to discover more potent compounds such as 10c, 10d, 10k and 10 m with enzyme inhibiting activities in the low nanomolar range that effectively inhibited the bacteria growth in culture with minimum inhibitory concentrations (MIC) for MRSA as low as 0.5 µg/ml. Some potent PK inhibitors, such as 10b, exhibited attenuated antibacterial activity and were found to be substrates for an efflux mechanism in S. aureus. Studies comparing a wild type S. aureus with a construct (S. aureus LAC Δpyk::Erm(R)) that lacks PK activity confirmed that bactericidal activity of 10d was PK-dependant.

Modulatory efficacy of hesperetin (citrus flavanone) on xenobiotic-metabolizing enzymes during 1,2-dimethylhydrazine-induced colon carcinogenesis.

Colorectal cancer is the second leading cause of cancer death worldwide with diet playing a prominent role in disease initiation and progression. Diet and nutrition play an important role during this multistep colon carcinogenic process. We have investigated the modulatory efficacy of hesperetin on aberrant crypt foci (ACF) and xenobiotic-metabolizing enzymes on 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis. Male albino Wistar rats were randomly divided into six groups. Group 1 served as control, received modified pellet diet and group 2 rats received 20mg/kg body weight of hesperetin p.o. every day. Groups 3-6 rats were given subcutaneous injections of 1,2-dimethylhydrazine (20mg/kg body weight) once a week for 15 weeks to induce ACF in the colon. In addition, rats in group 4 received hesperetin as in group 2 orally for the first 15 weeks (initiation), group 5 rats received hesperetin as in group 2 after the last injection of DMH and continued till the end of the experimental period (post-initiation). Group 6 received hesperetin as in group 2 throughout the entire period of 32 weeks. DMH exposure showed high incidence (90%) of ACF (280+/-24.5 aberrant crypt/colon) and dysplastic ACF, elevated activities of phase I enzymes and reduced the activities of phase II enzymes in the liver and colonic mucosa of colon cancer bearing rats. Hesperetin supplementation significantly reversed these effects, the effect being more pronounced in group 6 rats (hesperetin supplemented throughout the study period). These findings suggest that hesperetin can significantly reduce the formation of preneoplastic lesions and effectively modulate the xenobiotic-metabolizing enzymes in rats.