The Effects of Age,Adiposity, and Physical Activity on the Risk of Seven Site‐Specific Fractures in Postmenopausal Women

Risk factors for fracture of the neck of the femur are relatively well established, but those for fracture at other sites are little studied. In this large population study we explore the role of age, body mass index (BMI), and physical activity on the risk of fracture at seven sites in postmenopausal women. As part of the Million Women Study, 1,154,821 postmenopausal UK women with a mean age of 56.0 (SD 4.8) years provided health and lifestyle data at recruitment in 1996 to 2001. All participants were linked to National Health Service (NHS) hospital records for day‐case or overnight admissions with a mean follow‐up of 11 years per woman. Adjusted absolute and relative risks for seven site‐specific incident fractures were calculated using Cox regression models. During follow‐up, 4931 women had a fracture of the humerus; 2926 of the forearm; 15,883 of the wrist; 9887 of the neck of the femur; 1166 of the femur (not neck); 3199 a lower leg fracture; and 10,092 an ankle fracture. Age‐specific incidence rates increased gradually with age for fractures of forearm, lower leg, ankle, and femur (not neck), and steeply with age for fractures of neck of femur, wrist, and humerus. When compared to women with desirable BMI (20.0 to 24.9 kg/m²), higher BMI was associated with a reduced risk of fracture of the neck of femur, forearm, and wrist, but an increased risk of humerus, femur (not neck), lower leg, and ankle fractures (p < 0.001 for all). Strenuous activity was significantly associated with a decreased risk of fracture of the humerus and femur (both neck and remainder of femur) (p < 0.001), but was not significantly associated with lower leg, ankle, wrist, and forearm fractures. Postmenopausal women are at a high lifetime risk of fracture. BMI and physical activity are modifiable risk factors for fracture, but their associations with fracture risk differ substantially across fracture sites. © 2016 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR)     

Access and use of human tissues from the developing world: ethical challenges and a way forward using a tissue trust

Background  

Scientists engaged in global health research are increasingly faced with barriers to access and use of human tissues from the developing world communities where much of their research is targeted. In part, the problem can be traced to distrust of researchers from affluent countries, given the history of 'scientific-imperialism' and 'biocolonialism' reflected in past well publicized cases of exploitation of research participants from low to middle income countries.     

Body mass index and physical activity in relation to the incidence of hip fracture in postmenopausal women

Hip fracture risk is known to increase with physical inactivity and decrease with obesity, but there is little information on their combined effects. We report on the separate and combined effects of body mass index (BMI) and physical activity on hospital admissions for hip fracture among postmenopausal women in a large prospective UK study. Baseline information on body size, physical activity, and other relevant factors was collected in 1996–2001, and participants were followed for incident hip fractures by record linkage to National Health Service (NHS) hospital admission data. Cox regression was used to calculate adjusted relative risks of hip fracture. Among 925,345 postmenopausal women followed for an average of 6.2 years, 2582 were admitted to hospital with an incident hip fracture. Hip fracture risk increased with decreasing BMI: Compared with obese women (BMI of 30+ kg/m²), relative risks were 1.71 [95% confidence interval (CI) 1.47–1.97)] for BMI of 25.0 to 29.9 kg/m² and 2.55 (95% CI 2.22–2.94) for BMI of 20.0 to 24.9 kg/m². The increase in fracture risk per unit decrease in BMI was significantly greater among lean women than among overweight women (p < .001). For women in every category of BMI, physical inactivity was associated with an increased risk of hip fracture. There was no significant interaction between the relative effects of BMI and physical activity. For women who reported that they took any exercise versus no exercise, the adjusted relative risk of hip fracture was 0.68 (95% CI 0.62–0.75), with similar results for strenuous exercise. In this large cohort of postmenopausal women, BMI and physical activity had independent effects on hip fracture risk. © 2011 American Society for Bone and Mineral Research.     

Distribution and metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP) in female rats and their pups at dietary doses

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a mammary carcinogen in female rats and is present in a wide variety of cooked meats. We address here the excretion of PhIP and its metabolites into the breast-milk of lactating rats and the ability of chlorophyllin, a food product derivative with chemopreventive properties, to affect these levels at low PhIP doses. Lactating female F344 rats with suckling pups were orally administered 50, 500 and 1000 ng [14C]PhIP/kg body weight. The excretion of the [14C]PhIP into milk and its distribution among the mammary tissue, liver and blood of the dam, as well as among stomach contents and liver of their suckling pups was measured using accelerator mass spectrometry (AMS). PhIP, PhIP-4'- sulfate, 4'-hydroxy-PhIP, and N2-hydroxy-PhIP-N3-glucuronide were found in the milk at all doses. The chlorophyllin (500 microg/kg) co- administration with PhIP (500 ng/kg) caused increased levels of [14C]PhIP in the milk (32%) and stomach contents (35%) of the pups relative to the animals not receiving chlorophyllin at these low PhIP doses. In contrast, lower [14C]PhIP levels in the chlorophyllin treated animals were observed in the blood (47%) and mammary tissue (68%) of the dam, as well as the pup's liver tissue (37%) compared to the animals receiving only PhIP. Chlorophyllin co-administration resulted in an increased amount of N2-hydroxy-PhIP-N3-glucuronide (42%), increased PhIP (79%) and decreased levels of PhIP-4'-sulphate (77%) relative to the animals not receiving chlorophyllin. These results suggest that PhIP and PhIP metabolites are present in the breast-milk of lactating rats at human dietary PhIP exposures and that PhIP is absorbed by the newborn. Furthermore, these results suggest that other dietary components can affect the dosimetry of PhIP in breast-feeding offspring.      

In vivo photodynamic inactivation of Candida albicans using chloro‐aluminum phthalocyanine

This study evaluated the photoinactivation of Candida albicans in a murine model of oral candidiasis using chloro‐aluminum phthalocyanine (ClAlP) encapsulated in cationic nanoemulsions (NE) and chloro‐aluminum phthalocyanine (ClAlP) diluted in DMSO (DMSO) as photosensitizer (PS). Seventy‐five 6‐week‐old female Swiss mice were immunosuppressed and inoculated with C. albicans to induce oral candidiasis. PDT was performed on the tongue by the application of the photosensitizers and LED light (100 J cm^?2–660 nm). Twenty‐four hours and 7 days after treatments, microbiological evaluation was carried out by recovering C. albicans from the tongue of animals (CFU ml^?1). Then, mice were sacrificed and the tongues were surgically removed for histological and biomolecular analysis of pro‐ and anti‐inflammatory cytokines. Data were analyzed by ANOVA followed by Tukey's post hoc test. ClAlP‐NE‐mediated PDT reduced 2.26 log₁₀ of C. albicans recovered from the tongue when compared with the control group (P?L?) (P < 0.05). PDT did not promote adverse effects on the tongue tissue. Seven days after treatment, all animals were completely healthy. In summary, PDT mediated by chloro‐aluminum phthalocyanine entrapped in cationic nanoemulsions was effective in reducing C. albicans recovered from the oral lesions of immunocompromised mice.     

Purification and characterization of factor VII 304-Gln: a variant molecule with reduced activity isolated from a clinically unaffected male

Factor VII (FVII) is the plasma serine protease zymogen which, on binding to its cellular receptor tissue factor (TF), initiates blood coagulation. A 47-year-old man with no clinical bleeding tendency was found to have undetectable plasma FVII activity when tested in a one- stage assay using rabbit brain TF, but 0.3 U/mL using recombinant human TF and 1.04 U/mL FVII antigen. Variant FVII purified from his plasma showed an identical migration on sodium dodecyl sulfate-polyacrylamide gel electrophoresis to wild-type zymogen. By enzyme kinetic analysis the Km of the variant using FX as a substrate was 12-fold higher than that of normal FVII. Also, the variant FVII was unable to compete with wild-type FVII for limited rabbit TF binding sites. A ligand blot procedure was used to directly demonstrate reduced binding of recombinant human TF to the variant FVII compared with normal FVII. Genetic analysis of leukocyte DNA showed a G to A mutation in the propositus' gene at codon 304 that results in the substitution of a glutamine for an arginine residue in the catalytic domain of the protease. We conclude that this region of the FVII molecule is important for its function.     

Role of anticyclic citrullinated peptide 2 assay in long‐standing rheumatoid arthritis

Background: The anti‐cyclic citrullinated peptide (anti‐CCP) antibody test is a new serological marker with high specificity for rheumatoid arthritis (RA). Aims: This study evaluated the frequency of anti‐CCP antibodies in comparison to rheumatoid factor (RF) in a group of patients with inflammatory polyarthritis. Methods: Samples were obtained from 106 patients with established RA and non‐RA inflammatory polyarthritis. Anti‐CCP (second generation assay – INOVA) and RF antibodies were measured by enzyme‐linked immunosorbent assay. Patient demographics, disease duration and clinical diagnosis were obtained. Results: Fifty‐five patients had established RA and the remaining 51 had non‐RA inflammatory polyarthritis. The sensitivity of the anti‐CCP2 assay for a diagnosis of RA was 73% compared with 56% for RF. In the RA group, half the RF negative patients (12/24) tested positive for anti‐CCP. The specificity of anti‐CCP was extremely high at 98% compared with RF at 94%. In the non‐RA group, only one patient with lupus tested positive for anti‐CCP compared with three who were RF positive (all of whom also had lupus). Conclusion: The second generation anti‐CCP assay was more sensitive and specific than RF for a diagnosis of RA in this population. This test may improve accuracy of diagnosis in patients with long‐standing polyarthritis.