In elderly men and women treated for osteoporosis a low creatinine clearance of <65ml/min is a risk factor for falls and fractures

Recently, a low creatinine clearance (CrCl) of <65ml/min was described as a new significant and independent risk factor for the number of fallers and falls in a community-dwelling elderly population. In this study we investigated if a low creatinine clearance of <65ml/min is also a risk factor for falls and fractures in elderly men and women treated for osteoporosis. In a cross-sectional study with the help of questionnaires we assessed the prevalence of having experienced falls within the last 12months according to renal function in 5,313 German men and women receiving treatment for osteoporosis. The CrCl was calculated using the established Cockcroft-Gault formula. The prevalence of falls and fractures was assessed in multivariate-controlled logistic regression models according to a CrCl cut off of 65ml/min. The P -values were two-sided. In this study of elderly men and women treated for osteoporosis ( n =5,313), 60.9% ( n =3,238) had a CrCl of <65ml/min, which was associated in multivariate controlled analyses, compared to a CrCl of ≥65ml/min ( n =2,075), with a significant increased risk of experiencing falls (1,775/3,238 vs. 773/2,075, OR 1.69, 95% CI 1.50-1.91, P <0.0001) and an increased risk for multiple falls (37.1 vs. 22.6%, OR 1.63, 95% CI 1.42-1.87, P <0.0001). Furthermore, compared to a creatinine clearance of ≥65ml/min, a creatinine clearance of <65ml/min was also associated with a significant increased multivariate controlled risk for hip fractures (OR 1.57, 95%CI 1.18-2.09, P =0.002), for radial fractures (OR 1.79, 95%CI 1.39-2.31, P =<0.0001), for total vertebral fractures (OR 1.31, 95%CI 1.19-1.55, P =0.003) and for fall-associated vertebral fractures (OR 1.24, 95% CI 1.03-1.54, P =0.031). Similar to community-dwelling elderly, in elderly men and women treated for osteoporosis a CrCl of less than 65ml/min is a significant and independent risk factor for falls. Furthermore, we could show for the first time that a low creatinine clearance in elderly men and women treated for osteoporosis is also associated with a significantly increased risk of vertebral, hip and radial fracture

A new significant and independent risk factor for falls in elderly men and women: a low creatinine clearance of less than 65ml/min

Objectives: Because impaired renal function is detrimental for the conversion of calcidiol to calcitriol (D-hormone) and since D-hormone analogues have been shown to decrease the risk of falls, we investigated whether creatinine clearance (CrCl) is associated with the number of fallers and falls in elderly men and women. Methods: Within a randomized controlled study, we observed for 36weeks 186 placebo-treated community-dwelling elderly men and women over 70, in an attempt to determine the influence of baseline CrCl on calcitropic hormone serum levels, as well as the influence of baseline CrCl on the number of fallers and falls over time. With the help of questionnaires, we regularly assessed fall incidence and frequency. The risk of falls and the risk of becoming a faller were assessed in multivariate-controlled logistic regression models according to a cutoff value of the CrCl set at 65ml/min. Results: At baseline, serum levels of 1.25(OH)2D3 and iPTH were, in multivariate-controlled analyses, significantly associated with CrCl (p<0.0001, p=0.001, respectively), whereas serum levels of 25(OH)D3 were not associated with CrCl. Below a CrCl of 65ml/min, 1.25(OH)2D3 serum levels steadily declined. We therefore chose a CrCl of 65ml/min as cutoff for further analyses. During the 36weeks of observation, elderly people with a CrCl of <65ml/min had, in multivariate controlled analyses, compared with elderly with a CrCl of ≥65ml/min, a significantly higher incidence of number of fallers (25/70 vs 21/116; OR=4.01; 95% CI, 1.48-10.98; p=0.006), and a significantly higher incidence of falls (28/70 vs 23/116; OR=3.68; 95% CI, 1.38-9.82; p=0.009). Conclusions: For the first time we showed that in a community-dwelling population of elderly men and women, a CrCl of less than 65ml/min is a significant and independent risk factor for fallers and fall

Treatment with alfacalcidol in elderly people significantly decreases the high risk of falls associated with a low creatinine clearance of <65ml/min

We previously observed that a creatinine clearance (CrCl) of <65ml/min is a significant and independent risk factor for the number of fallers and falls in a community-dwelling elderly population and postulated that this increased risk is due to the associated significant lower D-hormone serum levels. To test our hypothesis, we investigated in a post hoc analysis of a double-blind randomized study whether treatment with alfacalcidol, a synthetic prodrug of the D-hormone, can reduce the high incidence of fallers and the high risk of falls associated with low CrCl. Of 378 Swiss community-dwelling women (n=191) and men (n=187), aged 70 years and older, 191 received randomly 1μg capsules of alfacalcidol (AlphaD3: Teva), and 187 received one capsule of placebo daily. With the help of questionnaires we regularly assessed the incidence and frequency of falls. The risk of becoming a faller and the risk of falling were assessed in multivariate-controlled logistic regression models according to treatment groups and according to a CrCl cut-off of 65ml/min. The presented results are from ITT analyses. In participants with a CrCl of <65ml/min, the 36 weeks of treatment with alfacalcidol was, compared with placebo, associated with a significant reduction in the number of fallers (14/72 versus 25/70; OR 0.26, 95% CI 0.08-0.80, P=0.019), and a significant reduction of the number of falls (16/72 versus 28/70; OR 0.29, 95% CI 0.09-0.88, P=0.028). No such association was observed in participants with a CrCl of ≥65ml/min (for fallers 26/120 versus 21/116; OR 0.92 95% CI 0.34-2.52, P=0.875; for falls 32/120 versus 23/116; OR 0.93 95% CI 0.34-2.54, P=0.885). In the placebo group frequency of falls was dependent on CrCl (P=0.006), whereas in the alfacalcidol treatment group frequency of falls was independent of CrCl (P=0.494). No cases of clinically relevant hypercalcemia were observed. In a community-dwelling population of elderly men and women with a CrCl of <65ml/min, treatment with alfacalcidol can significantly and safely reduce the low CrCl associated increased number of fallers and the high risk of fall

Prospective Study of Bowel Movement, Laxative Use, and Risk of Colorectal Cancer among Women

The authors prospectively examined the association between bowel movement frequency, laxative use, and the risk of colorectal cancer in 84, 577 women of the Nurses' Health Study living in the United States, 36-61 years of age and free of cancer in 1982. Between 1984 and 1996, 611 incident cases of colorectal cancer were documented. After controlling for age, body mass index, fiber intake, postmenopausal status and hormone use, physical activity, and use of laxatives, the relative risks associated with having bowel movements every third day or less, compared with those with bowel movements once daily, were 0.94 (95% confidence interval (Cl): 0.69, 1.28) for colorectal cancer, 0.88 (95% Cl: 0.62, 1.26) for colon cancer, and 1.18 (95% Cl: 0.63, 2.20) for rectal cancer. Compared with women who never used laxatives, the multivariate relative risks associated with weekly to daily laxative use were 1.00 (95% Cl: 0.72, 1.40) for colorectal cancer, 1.09 (95% Cl: 0.76, 1.57) for colon cancer, and 0.68 (95% Cl: 0.29, 1.57) for rectal cancer. These findings do not support an association between infrequent bowel movement, laxative use, and risk of colorectal cancer and indicate that simple questions directed at bowel movement frequency are unlikely to enhance our ability to predict colorectal cancer risk. Am J Epidemiol2000; 151: 958-6

Salmonella antibacterial Rhs polymorphic toxin inhibits translation through ADP-ribosylation of EF-Tu P-loop

International audienceAbstract Rearrangement hot spot (Rhs) proteins are members of the broad family of polymorphic toxins. Polymorphic toxins are modular proteins composed of an N-terminal region that specifies their mode of secretion into the medium or into the target cell, a central delivery module, and a C-terminal domain that has toxic activity. Here, we structurally and functionally characterize the C-terminal toxic domain of the antibacterial Rhsmain protein, TreTu, which is delivered by the type VI secretion system of Salmonella enterica Typhimurium. We show that this domain adopts an ADP-ribosyltransferase fold and inhibits protein synthesis by transferring an ADP-ribose group from NAD+ to the elongation factor Tu (EF-Tu). This modification is specifically placed on the side chain of the conserved D21 residue located on the P-loop of the EF-Tu G-domain. Finally, we demonstrate that the TriTu immunity protein neutralizes TreTu activity by acting like a lid that closes the catalytic site and traps the NAD+

Salmonella antibacterial Rhs polymorphic toxin inhibits translation through ADP-ribosylation of EF-Tu P-loop

International audienceAbstract Rearrangement hot spot (Rhs) proteins are members of the broad family of polymorphic toxins. Polymorphic toxins are modular proteins composed of an N-terminal region that specifies their mode of secretion into the medium or into the target cell, a central delivery module, and a C-terminal domain that has toxic activity. Here, we structurally and functionally characterize the C-terminal toxic domain of the antibacterial Rhsmain protein, TreTu, which is delivered by the type VI secretion system of Salmonella enterica Typhimurium. We show that this domain adopts an ADP-ribosyltransferase fold and inhibits protein synthesis by transferring an ADP-ribose group from NAD+ to the elongation factor Tu (EF-Tu). This modification is specifically placed on the side chain of the conserved D21 residue located on the P-loop of the EF-Tu G-domain. Finally, we demonstrate that the TriTu immunity protein neutralizes TreTu activity by acting like a lid that closes the catalytic site and traps the NAD+

A systematic survey of floral nectaries

The construction of classifications, as well as the understanding of biological diversity, depends upon a careful comparison of attributes of the organisms studied (Stuessy, 1990). It is widely known that data from diverse sources showing differences from taxon to taxon are of systematic significance. Dur-ing the 20th century, systematists have emphasized that their discipline involves a synthesis of all knowledge (Stevens, 1994) or, in other words, the variation of as many relevant characters as possible should be incorporated into the natural system to be constructed. The extent to which particular characters are constant or labile will determine their usefulness to syste-matics. In general, more conservative characters will be valuable in defining families and orders, whereas more labile characters may be useful at the ge-neric and specific levels (Webb, 1984). There is no doubt that floral characters are among the most used in the classification of flowering plants. At the same time, they constitute essential features in diagnostic keys to taxa in both taxonomic treatments and Floras (Cronquist, 1981, 1988).Fil: Bernardello, Gabriel Luis Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentin