White crystalline powder
Epoxylathyrol/euphorbiasteroid/Benzeneacetic acid, (1aR,4aR,6S,7S,7aR,8S,9R,11aS)-4a,8-bis(acetyloxy)-1,1a,4,4a,5,6,7,7a,8,10,11,11a-dodecahydro-1,1,3,6-tetramethyl-4-oxospiro[9H-cyclopenta[a]cyclopropa[f]cycloundecene-9,2'-oxiran]-7-yl ester/Benzeneacetic acid, (1aR,2E,4aR,6S,7S,7aR,8S,9R,11aS)-4a,8-bis(acetyloxy)-1,1a,4,4a,5,6,7,7a,8,10,11,11a-dodecahydro-1,1,3,6-tetramethyl-4-oxospiro[9H-cyclopenta[a]cyclopropa[f]cycloundecene-9,2'-oxiran]-7-yl ester/6,20-Epoxylathyrol-5,10-diacetat-3-phenylacetat/(1aR,4aR,6S,7S,7aR,8S,9R,11aS)-4a,8-Diacetoxy-1,1,3,6-tetramethyl-4-oxo-1,1a,4,4a,5,6,7,7a,8,10,11,11a-dodecahydrospiro[cyclopenta[a]cyclopropa[f]annulene-9,2'-oxiran]-7-yl phenylacetate/(1aR,2E,4aR,6S,7S,7aR,8S,9R,11aS)-4a,8-Diacetoxy-1,1,3,6-tetramethyl-4-oxo-1,1a,4,4a,5,6,7,7a,8,10,11,11a-dodecahydrospiro[cyclopenta[a]cyclopropa[f]annulene-9,2'-oxiran]-7-yl phenylacetate/1,10-epoxyaristolane
Methanol; Ethyl Acetate
633.1±55.0 °C at 760 mmHg
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Falls in care facilities and hospitals are common events that cause considerable morbidity and mortality for older people. This is an update of a review first published in 2010 and updated in 2012.
To assess the effects of interventions designed to reduce the incidence of falls in older people in care facilities and hospitals.
We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (August 2017); Cochrane Central Register of Controlled Trials (2017, Issue 8); and MEDLINE, Embase, CINAHL and trial registers to August 2017.
Randomised controlled trials of interventions for preventing falls in older people in residential or nursing care facilities, or hospitals.
Data collection and analysis
One review author screened abstracts; two review authors screened full‐text articles for inclusion. Two review authors independently performed study selection, ‘Risk of bias’ assessment and data extraction. We calculated rate ratios (RaR) with 95% confidence intervals (CIs) for rate of falls and risk ratios (RRs) and 95% CIs for outcomes such as risk of falling (number of people falling). We pooled results where appropriate. We used GRADE to assess the quality of evidence.
Thirty‐five new trials (77,869 participants) were included in this update. Overall, we included 95 trials (138,164 participants), 71 (40,374 participants; mean age 84 years; 75% women) in care facilities and 24 (97,790 participants; mean age 78 years; 52% women) in hospitals. The majority of trials were at high risk of bias in one or more domains, mostly relating to lack of blinding. With few exceptions, the quality of evidence for individual interventions in either setting was generally rated as low or very low. Risk of fracture and adverse events were generally poorly reported and, where reported, the evidence was very low‐quality, which means that we are uncertain of the estimates. Only the falls outcomes for the main comparisons are reported here.
Seventeen trials compared exercise with control (typically usual care alone). We are uncertain of the effect of exercise on rate of falls (RaR 0.93, 95% CI 0.72 to 1.20; 2002 participants, 10 studies; I² = 76%; very low‐quality evidence). Exercise may make little or no difference to the risk of falling (RR 1.02, 95% CI 0.88 to 1.18; 2090 participants, 10 studies; I² = 23%; low‐quality evidence).
There is low‐quality evidence that general medication review (tested in 12 trials) may make little or no difference to the rate of falls (RaR 0.93, 95% CI 0.64 to 1.35; 2409 participants, 6 studies; I² = 93%) or the risk of falling (RR 0.93, 95% CI 0.80 to 1.09; 5139 participants, 6 studies; I² = 48%).
There is moderate‐quality evidence that vitamin D supplementation (4512 participants, 4 studies) probably reduces the rate of falls (RaR 0.72, 95% CI 0.55 to 0.95; I² = 62%), but probably makes little or no difference to the risk of falling (RR 0.92, 95% CI 0.76 to 1.12; I² = 42%). The population included in these studies had low vitamin D levels.
Multifactorial interventions were tested in 13 trials. We are uncertain of the effect of multifactorial interventions on the rate of falls (RaR 0.88, 95% CI 0.66 to 1.18; 3439 participants, 10 studies; I² = 84%; very low‐quality evidence). They may make little or no difference to the risk of falling (RR 0.92, 95% CI 0.81 to 1.05; 3153 participants, 9 studies; I² = 42%; low‐quality evidence).
Three trials tested the effect of additional physiotherapy (supervised exercises) in rehabilitation wards (subacute setting). The very low‐quality evidence means we are uncertain of the effect of additional physiotherapy on the rate of falls (RaR 0.59, 95% CI 0.26 to 1.34; 215 participants, 2 studies; I² = 0%), or whether it reduces the risk of falling (RR 0.36, 95% CI 0.14 to 0.93; 83 participants, 2 studies; I² = 0%).
We are uncertain of the effects of bed and chair sensor alarms in hospitals, tested in two trials (28,649 participants) on rate of falls (RaR 0.60, 95% CI 0.27 to 1.34; I² = 0%; very low‐quality evidence) or risk of falling (RR 0.93, 95% CI 0.38 to 2.24; I² = 0%; very low‐quality evidence).
Multifactorial interventions in hospitals may reduce rate of falls in hospitals (RaR 0.80, 95% CI 0.64 to 1.01; 44,664 participants, 5 studies; I² = 52%). A subgroup analysis by setting suggests the reduction may be more likely in a subacute setting (RaR 0.67, 95% CI 0.54 to 0.83; 3747 participants, 2 studies; I² = 0%; low‐quality evidence). We are uncertain of the effect of multifactorial interventions on the risk of falling (RR 0.82, 95% CI 0.62 to 1.09; 39,889 participants; 3 studies; I² = 0%; very low‐quality evidence).
In care facilities: we are uncertain of the effect of exercise on rate of falls and it may make little or no difference to the risk of falling. General medication review may make little or no difference to the rate of falls or risk of falling. Vitamin D supplementation probably reduces the rate of falls but not risk of falling. We are uncertain of the effect of multifactorial interventions on the rate of falls; they may make little or no difference to the risk of falling.
In hospitals: we are uncertain of the effect of additional physiotherapy on the rate of falls or whether it reduces the risk of falling. We are uncertain of the effect of providing bed sensor alarms on the rate of falls or risk of falling. Multifactorial interventions may reduce rate of falls, although subgroup analysis suggests this may apply mostly to a subacute setting; we are uncertain of the effect of these interventions on risk of falling.
Interventions for preventing falls in older people in care facilities and hospitals
Ian D Cameron,corresponding author Suzanne M Dyer, Claire E Panagoda, Geoffrey R Murray, Keith D Hill, Robert G Cumming, Ngaire Kerse, and Cochrane Bone, Joint and Muscle Trauma Group
2018 Sep 7
Spatial patterning is a ubiquitous feature of biological systems. Meiotic crossovers provide an interesting example, defined by the classical phenomenon of crossover interference. Here, analysis of crossover patterns in budding yeast identifies a molecular pathway for interference. Topoisomerase II (Topo II) plays a central role, thus identifying a new function for this critical molecule. SUMOylation [of TopoII and axis component Red1] and ubiquitin-mediated removal of SUMOylated proteins are also required. These and other findings support the hypothesis that crossover interference involves accumulation, relief and redistribution of mechanical stress along the protein/DNA meshwork of meiotic chromosome axes, with TopoII required to adjust spatial relationships among DNA segments.
During meiosis, crossovers (COs) promote genetic diversity and create physical connections between homologs that ensure their accurate segregation (review in refs 1-3). COs arise stochastically from a larger set of undifferentiated precursor recombination complexes, at different chromosomal positions in different meiotic nuclei. Nonetheless, along any given chromosome in any given nucleus, COs tend to be evenly spaced (review in refs 3, 4). This feature was originally recognized early in the 20th century as the genetic phenomenon of CO interference5,6.
CO interference is particularly interesting because it implies the occurrence of communication along chromosomes. Remarkably, communication can extend over distances ranging from 300 nanometers to >30 microns 4,7,8. Some models for CO interference invoke spreading of a molecular-based change along the chromosomes9. Even spacing can also be achieved by a reaction-diffusion process10. We have proposed, alternatively, that interference involves the accumulation, relief and redistribution of mechanical stress, with spreading molecular changes following as a consequence of spreading stress relief 4. Aberrant CO patterns are observed in mutants defective for recombination enzymology, chromosome structure, chromatin state and DNA-based signal transduction. However, no specific molecular process has been defined. To address this deficit, we examined CO patterns in wild-type (WT) and mutant strains of budding yeast as defined by cytological localization of CO-correlated molecular foci.
Topoisomerase II Mediates Meiotic Crossover Interference
Liangran Zhang,1 Shunxin Wang,1 Shen Yin,1 Soogil Hong,2 Keun P. Kim,2 and Nancy Kleckner1,
2014 Jul 13
Background & Aims
Late diagnosis of colorectal carcinomas results in a significant reduction of average survival times. Yet, despite screening programs about 70% of tumors are detected at advanced stages (UICC III/IV). We explored whether detection of malignant disease would be possible through identification of tumor specific protein biomarkers in serum samples.
A discovery set of sera from patients with colorectal malignancy (n=58) and healthy control individuals (n=32) were screened for potential differences using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). Candidate proteins were identified, and their expression levels validated in independent sample sets using a specific immunoassay (ELISA).
Utilizing class comparison and custom developed algorithms we identified several m/z values that were differentially expressed between the malignant samples and the healthy controls of the discovery set. Characterization of the most prominent m/z values revealed a member of the complement system, the stable form of C3a anaphylatoxin, i.e., C3a-desArg. Based on a specific ELISA, serum levels of complement C3a-desArg predicted the presence of colorectal malignancy in a blinded validation set (n=59) with a sensitivity of 96.8% and a specificity of 96.2%. Increased serum levels were also detected in 86.1% of independently collected sera from patients with colorectal adenomas (n=36), while only 5.6% were classified as normal.
Complement C3a-desArg is present at significantly higher levels in serum from patients with colorectal adenomas (p<0.0001) and carcinomas (p<0.0001) than in healthy individuals. This suggests that quantification of C3a-desArg levels could ameliorate existing screening tests for colorectal cancer.
Colorectal Cancer, Polyps, Screening, Serum, SELDI-TOF MS, C3a-desArg
Increased serum levels of complement C3a anaphylatoxin indicate the presence of colorectal tumors
Jens K. Habermann,1,2,8,* Uwe J. Roblick,2,8,* Brian T. Luke,4 DaRue A. Prieto,5 William J. J. Finlay,6 Vladimir N. Podust,7 John M. Roman,5 Elisabeth Oevermann,2 Thomas Schiedeck,2 Nils Homann,3 Michael Duchrow,2 Thomas P. Conrads,5 Timothy D. Veenstra,5 Stanley K. Burt,4 Hans-Peter Bruch,2 Gert Auer,8 and Thomas Ried1
2008 Sep 8.
Euphorbiasteroid is a tricyclic diperpene of Euphorbia lathyris L., inhibits tyrosinase, and increases the phosphorylation of AMPK, with anti-cancer, anti-virus, anti-obesity and multidrug resistance-modulating effect.