Use of anthropometric indicators in screening for undiagnosed vertebral fractures: A cross-sectional analysis of the Fukui Osteoporosis Cohort (FOC) study

<p>Abstract</p> <p>Background</p> <p>Vertebral fractures are the most common type of osteoporotic fracture. Although often asymptomatic, each vertebral fracture increases the risk of additional fractures. Development of a safe and simple screening method is necessary to identify individuals with asymptomatic vertebral fractures.</p> <p>Methods</p> <p>Lateral imaging of the spine by single energy X-ray absorptiometry and vertebral morphometry were conducted in 116 Japanese women (mean age: 69.9 ± 9.3 yr). Vertebral deformities were diagnosed by the McCloskey-Kanis criteria and were used as a proxy for vertebral fractures. We evaluated whether anthropometric parameters including arm span-height difference (AHD), wall-occiput distance (WOD), and rib-pelvis distance (RPD) were related to vertebral deformities. Positive findings were defined for AHD as ≥ 4.0 cm, for WOD as ≥ 5 mm, and for RPD as ≤ two fingerbreadths. Receiver operating characteristics curves analysis was performed, and cut-off values were determined to give maximum difference between sensitivity and false-positive rate. Expected probabilities for vertebral deformities were calculated using logistic regression analysis.</p> <p>Results</p> <p>The mean AHD for those participants with and without vertebral deformities were 7.0 ± 4.1 cm and 4.2 ± 4.2 cm (p < 0.01), respectively. Sensitivity and specificity for use of AHD-positive, WOD-positive and RPD-positive values in predicting vertebral deformities were 0.85 (95% CI: 0.69, 1.01) and 0.52 (95% CI: 0.42, 0.62); 0.70 (95% CI: 0.50, 0.90) and 0.67 (95% CI: 0.57, 0.76); and 0.67 (95% CI: 0.47, 0.87) and 0.59 (95% CI: 0.50, 0.69), respectively. The sensitivity, specificity, and likelihood ratio for a positive result (LR) for use of combined AHD-positive and WOD-positive values were 0.65 (95% CI: 0.44, 0.86), 0.81 (95% CI: 0.73, 0.89), and 3.47 (95% CI: 3.01, 3.99), respectively. The expected probability of vertebral deformities (P) was obtained by the equation; P = 1-(exp [-1.327-0.040 × body weight +1.332 × WOD-positive + 1.623 × AHD-positive])^-1. The sensitivity, specificity and LR for use of a 0.306 cut-off value for probability of vertebral fractures were 0.65 (95% CI: 0.44, 0.86), 0.87 (95% CI: 0.80, 0.93), and 4.82 (95% CI: 4.00, 5.77), respectively.</p> <p>Conclusion</p> <p>Both WOD and AHD effectively predicted vertebral deformities. This screening method could be used in a strategy to prevent additional vertebral fractures, even when X-ray technology is not available.</p

Pancreatic alpha cell mass in European subjects with type 2 diabetes

AIMS/HYPOTHESIS: Type 2 diabetes is a bi-hormonal disease characterised by relative hypoinsulinaemia and hyperglucagonaemia with elevated blood glucose levels. Besides pancreatic beta cell defects, a low number of beta cells (low beta cell mass) may contribute to the insufficient secretion of insulin. In this study our aim was to determine whether the alpha cell mass is also altered. METHODS: Using a point counting method, we measured the ratio of alpha to beta cell areas in pancreas samples obtained at autopsy from 50 type 2 diabetic subjects, whose beta cell mass had previously been found to be 36% lower than that of 52 non-diabetic subjects. RESULTS: The topography of alpha and beta cells was similar in both groups: many alpha cells were localised in the centre of the islets and the ratio of alpha/beta cell areas increased with islet size. The average ratio was significantly higher in type 2 diabetic subjects (0.72) than in non-diabetic subjects (0.42), with, however, a large overlap between the two groups. In contrast, the alpha cell mass was virtually identical in type 2 diabetic subjects (366 mg) and non-diabetic subjects (342 mg), and was not influenced by sex, BMI or type of diabetes treatment. CONCLUSIONS: The higher proportion of alpha to beta cells in the islets of some type 2 diabetic subjects is due to a decrease in beta cell number rather than an increase in alpha cell number. This imbalance may contribute to alterations in the normal inhibitory influence exerted by beta cells on alpha cells, and lead to the relative hyperglucagonaemia observed in type 2 diabete

Bone mineral density, body mass index and cigarette smoking among Iranian women: implications for prevention

BACKGROUND: While risk factors of osteoporosis in Western populations have been extensively documented, such a profile has not been well studied in Caucasians of non-European origin. This study was designed to estimate the modifiable distribution and determinants of bone mineral density (BMD) among Iranian women in Australia. METHODS: Ninety women aged 35 years and older completed a questionnaire on socio-demographic and lifestyle factors. BMD was measured at the lumbar spine (LS) and femoral neck (FN) using DXA (GE Lunar, WI, USA), and was expressed in g/cm(2 )as well as T-score. RESULTS: In multiple regression analysis, advancing age, lower body mass index (BMI), and smoking were independently associated with LS and FN BMD, with the 3 factors collectively accounting for 30% and 38% variance of LS and FN BMD, respectively. LS and FN BMD in smokers was 8% lower than that in non-smokers. Further analysis of interaction between BMI and smoking revealed that the effect of smoking was only observed in the obese group (p = 0.029 for LSBMD and p = 0.007 for FNBMD), but not in the overweight and normal groups. Using T-scores from two bone sites the prevalence of osteoporosis (T-scores ≤ -2.5) was 3.8% and 26.3% in pre-and post-menopausal women, respectively. Among current smokers, the prevalence was higher (31.3%) than that among ex-smokers (28.6%) and non-smokers (7.5%). CONCLUSION: These data, for the first time, indicate that apart from advancing age and lower body mass index, cigarette smoking is an important modifiable determinant of bone mineral density in these Caucasians of non-European origin

Irradiation-induced telomerase activity and gastric cancer risk: a case-control analysis in a Chinese Han population

<p>Abstract</p> <p>Background</p> <p>Telomerase expression is one of the characteristics of gastric cancer (GC) cells and telomerase activity is frequently up-regulated by a variety of mechanisms during GC development. Therefore, we hypothesized that elevated levels of activated telomerase might enhance GC risk due to increased propagation of cells with DNA damage, such as induced by γ-radiation.</p> <p>Methods</p> <p>To explore this hypothesis, 246 GC cases and 246 matched controls were recruited in our case-control study. TRAP-ELISA was used to assess the levels of telomerase activity at baseline and after γ-radiation and the γ-radiation-induced telomerase activity (defined as after γ-irradiation/baseline) in cultured peripheral blood lymphocytes (PBLs).</p> <p>Results</p> <p>Our data showed that there was no significant difference for the baseline telomerase activity between GC cases and controls (10.17 ± 7.21 <it>vs. </it>11.02 ± 8.03, <it>p </it>= 0.168). However, after γ-radiation treatment, γ-radiation-induced telomerase activity was significantly higher in the cases than in the controls (1.51 ± 0.93 <it>vs</it>. 1.22 ± 0.66, <it>p </it>< 0.001). Using the median value of γ-radiation-induced telomerase activity in the controls as a cutoff point, we observed that high γ-radiation-induced telomerase activity was associated with a significantly increased GC risk (adjusted odds ratio, 2.45; 95% confidence interval, 1.83-3.18). Moreover, a dose response association was noted between γ-radiation-induced telomerase activity and GC risk. Age, but not sex, smoking and drinking status seem to have a modulating effect on the γ-radiation-induced telomerase activities in both cases and controls.</p> <p>Conclusion</p> <p>Overall, our findings for the first time suggest that the increased γ-radiation-induced telomerase activity in PBLs might be associated with elevated GC risk. Further confirmation of this association using a prospective study design is warranted.</p

Prevalence of osteoporosis and incidence of hip fracture in women - secular trends over 30 years

<p>Abstract</p> <p>Background</p> <p>The number of hip fractures during recent decades has been reported to be increasing, partly because of an increasing proportion of elderly women in the society. However, whether changes in hip fracture annual incidence in women are attributable to secular changes in the prevalence of osteoporosis is unclear.</p> <p>Methods</p> <p>Bone mineral density was evaluated by single-photon absorptiometry at the distal radius in 456 women aged 50 years or above and living in the same city. The measurements were obtained by the same densitometer during three separate time periods: 1970-74 (n = 106), 1987-93 (n = 175) and 1998-1999 (n = 178), and the age-adjusted prevalence of osteoporosis in these three cohorts was calculated. Additionally, all hip fractures sustained in the target population of women aged 50 years or above between 1967 and 2001 were registered, whereupon the crude and the age-adjusted annual incidence of hip fractures were calculated.</p> <p>Results</p> <p>There was no significant difference in the age-adjusted prevalence of osteoporosis when the three cohorts were compared (P = 1.00). The crude annual incidence (per 10,000 women) of hip fracture in the target population increased by 110% from 40 in 1967 to 84 in 2001. The overall trend in the crude incidence between 1967 and 2001 was increasing (1.58 per 10,000 women per year; 95 percent confidence interval, 1.17 to 1.99), whereas the age-adjusted incidence was stable over the same period (0.22 per 10,000 women per year; 95 percent confidence interval, -0.16 to 0.60).</p> <p>Conclusions</p> <p>The increased number of hip fracture in elderly women is more likely to be attributable to demographic changes in the population than to secular increase in the prevalence of osteoporosis.</p

Screening for low bone mass with quantitative ultrasonography in a community without dual-energy X-ray absorptiometry: population-based survey

BACKGROUND: Dual-energy x-ray absorptiometry (DXA) is the criterion standard to identify low bone mineral density (BMD), but access to axial DXA may be limited or cost prohibitive. We screened for low bone mass with quantitative ultrasonography (QUS) in a community without DXA, analyzed its reliability and obtained reference values and estimated the prevalence of low QUS values. METHODS: We enrolled 6493 residents of Kinmen, Taiwan, and a reference group (96 men and 70 women aged 20–29 years) for this cross-sectional, community-based study. All participants completed a questionnaire and underwent ultrasonographic measurements. Reliability and validity of QUS measurements were evaluated. Broadband ultrasound attenuation (BUA) values were obtained and statistically analyzed by age, sex and weight. Annual loss of BUA was determined. Trends in the prevalence of QUS scores were evaluated. RESULTS: Two QUS were used and had a correlation coefficient of 0.90 (p < 0.001). Calcaneal BUA was significantly correlated with BMD in the femoral neck (r = 0.67, p < 0.001) and BMD of the total lumbar spine (r = 0.59, p < 0.001). BUAs in the reference group were 92.72 ± 13.36 and 87.90 ± 10.68 dB/MHz for men and women, respectively. Estimated annual losses of calcaneal BUA were 0.83% per year for women, 0.27% per year for men, and 0.51% per year for the total population. The prevalence of severely low QUS values (T-score = -2.5) tended to increase with aging in both sexes (p < 0.001). Across age strata, moderately low QUS values (-2.5 < T-score < -1.0) were 31.6–41.0% in men and 23.7–38.1% in women; a significant trend with age was observed in men (p < 0.001). CONCLUSION: Age-related decreases in calcaneal ultrasonometry, which reflected the prevalence of low bone mass, were more obvious in women than in men

Comparative Genomics Reveals Two Novel RNAi Factors in Trypanosoma brucei and Provides Insight into the Core Machinery

The introduction ten years ago of RNA interference (RNAi) as a tool for molecular exploration in Trypanosoma brucei has led to a surge in our understanding of the pathogenesis and biology of this human parasite. In particular, a genome-wide RNAi screen has recently been combined with next-generation Illumina sequencing to expose catalogues of genes associated with loss of fitness in distinct developmental stages. At present, this technology is restricted to RNAi-positive protozoan parasites, which excludes T. cruzi, Leishmania major, and Plasmodium falciparum. Therefore, elucidating the mechanism of RNAi and identifying the essential components of the pathway is fundamental for improving RNAi efficiency in T. brucei and for transferring the RNAi tool to RNAi-deficient pathogens. Here we used comparative genomics of RNAi-positive and -negative trypanosomatid protozoans to identify the repertoire of factors in T. brucei. In addition to the previously characterized Argonaute 1 (AGO1) protein and the cytoplasmic and nuclear Dicers, TbDCL1 and TbDCL2, respectively, we identified the RNA Interference Factors 4 and 5 (TbRIF4 and TbRIF5). TbRIF4 is a 3′-5′ exonuclease of the DnaQ superfamily and plays a critical role in the conversion of duplex siRNAs to the single-stranded form, thus generating a TbAGO1-siRNA complex required for target-specific cleavage. TbRIF5 is essential for cytoplasmic RNAi and appears to act as a TbDCL1 cofactor. The availability of the core RNAi machinery in T. brucei provides a platform to gain mechanistic insights in this ancient eukaryote and to identify the minimal set of components required to reconstitute RNAi in RNAi-deficient parasites

Genome-Wide Screen of Three Herpesviruses for Protein Subcellular Localization and Alteration of PML Nuclear Bodies

Herpesviruses are large, ubiquitous DNA viruses with complex host interactions, yet many of the proteins encoded by these viruses have not been functionally characterized. As a first step in functional characterization, we determined the subcellular localization of 234 epitope-tagged proteins from herpes simplex virus, cytomegalovirus, and Epstein–Barr virus. Twenty-four of the 93 proteins with nuclear localization formed subnuclear structures. Twelve of these localized to the nucleolus, and five at least partially localized with promyelocytic leukemia (PML) bodies, which are known to suppress viral lytic infection. In addition, two proteins disrupted Cajal bodies, and 19 of the nuclear proteins significantly decreased the number of PML bodies per cell, including six that were shown to be SUMO-modified. These results have provided the first functional insights into over 120 previously unstudied proteins and suggest that herpesviruses employ multiple strategies for manipulating nuclear bodies that control key cellular processes

The ERI-6/7 Helicase Acts at the First Stage of an siRNA Amplification Pathway That Targets Recent Gene Duplications

Endogenous small interfering RNAs (siRNAs) are a class of naturally occuring regulatory RNAs found in fungi, plants, and animals. Some endogenous siRNAs are required to silence transposons or function in chromosome segregation; however, the specific roles of most endogenous siRNAs are unclear. The helicase gene eri-6/7 was identified in the nematode Caenorhabditis elegans by the enhanced response to exogenous double-stranded RNAs (dsRNAs) of the null mutant. eri-6/7 encodes a helicase homologous to small RNA factors Armitage in Drosophila, SDE3 in Arabidopsis, and Mov10 in humans. Here we show that eri-6/7 mutations cause the loss of 26-nucleotide (nt) endogenous siRNAs derived from genes and pseudogenes in oocytes and embryos, as well as deficiencies in somatic 22-nucleotide secondary siRNAs corresponding to the same loci. About 80 genes are eri-6/7 targets that generate the embryonic endogenous siRNAs that silence the corresponding mRNAs. These 80 genes share extensive nucleotide sequence homology and are poorly conserved, suggesting a role for these endogenous siRNAs in silencing of and thereby directing the fate of recently acquired, duplicated genes. Unlike most endogenous siRNAs in C. elegans, eri-6/7–dependent siRNAs require Dicer. We identify that the eri-6/7–dependent siRNAs have a passenger strand that is ∼19 nt and is inset by ∼3–4 nts from both ends of the 26 nt guide siRNA, suggesting non-canonical Dicer processing. Mutations in the Argonaute ERGO-1, which associates with eri-6/7–dependent 26 nt siRNAs, cause passenger strand stabilization, indicating that ERGO-1 is required to separate the siRNA duplex, presumably through endonucleolytic cleavage of the passenger strand. Thus, like several other siRNA–associated Argonautes with a conserved RNaseH motif, ERGO-1 appears to be required for siRNA maturation