Skinfold thickness versus isotope dilution for body fat assessment during simulated microgravity: results from three bed-rest campaigns in men and women with and without countermeasures

Because body composition is altered during head-down bed rest (HDBR), body mass can not be used as an index of energy balance. Consequently diet allowances should not be based on body mass evolution but on fat mass changes. Though criticized, skinfold thickness (ST) is the costless, easiest and fastest method to use for such an objective. The aim of this study was to compare the percentage of body fat (%BF) estimated by ST with the isotope dilution of H₂¹⁸O. We compiled data from three HDBR campaigns, one on women (n=8) in November 1998 and two on the same men (n=8) in December 1997 (without countermeasure) and January 1998 (with thigh-cuffs countermeasure), according to a crossover design. Body composition was assessed before and after 6 days of HDBR. %BF was derived from the biceps, triceps, sub-scapular and sup-iliac ST according to Durnin and Wormersly (1974). Fat-free mass was measured on the same day by H₂¹⁸O dilution and fat mass was calculated by the difference with body mass and expressed as a percentage. Based on precision tests, the minimum measurable change by ST was 1.1%BF for single measurement point. Both intercepts (F _4,30=0.89, P=0.45) and slopes (F _4,30=0.74; P=0.57) of the ST versus dilution relationships were not affected by the periods (December vs January), experimental conditions (control vs HDBR vs HDBR + thigh cuffs) or sex allowing the derivation of a common relationship %BF_st=0.94 × %BF_dil (F _1,47=97.9, P<0.0001; non-significant intercept excluded) with a bias between methods of −1.7±2.0 %BF (95% CI: −5.8, 2.4 %BF). ST can be used to measure %BF during HDBR provided great care is placed on training and changes are higher than 1.1 %BF. If the method can be applied for in-flight energy balance monitoring given the high observed energy deficit, a tight monitoring of the individual nutritional status as needed during simulation appears, however, dubious based on this solely method.     

Specificity and regioselectivity of the conjugation of estradiol, estrone, and their catecholestrogen and methoxyestrogen metabolites by human uridine diphospho-glucuronosyltransferases expressed in endometrium

Uridine diphospho-glucuronosyltransferases (UGTs) inactivate and facilitate the excretion of estrogens to glucuronides (-G), the most abundant circulating estrogen conjugates. The identity of the conjugated estrogens formed by all known overexpressed UGTs (n = 16) was analyzed by comparison with retention time and mass fragmentation of authentic standards by HPLC tandem mass spectrometry methods. Six UGTs, namely 1A1, 1A3, 1A8, 1A9, 1A10, and 2B7, were found to glucuronidate estradiol (E(2)) and estrone (E(1)), their hydroxyls (OH), and their methoxy derivatives (MeO). Addition of glucuronic acid was catalyzed by specific UGTs at positions 2, 3, and 4 of the estrogens, whereas only E(2) was conjugated at position 17 by UGT2B7. Kinetic parameters indicate that the conjugation of E(2) at position 3 was predominantly catalyzed by 1A1, 1A3, and 1A8 and by 1A8 for E(1). Conjugation of 2-OHE(1)/E(2) and 2- and 4-MeOE(1)/E(2) was selective at position 3, mostly catalyzed by 1A1 and 1A8. Of all UGTs, UGT2B7 demonstrated the highest catalytic activities for estrogens and at least 10- to 50-fold higher activity for the conjugation of genotoxic 4-hydroxycatecholestrogens at position 4, compared with the conjugation of E(2), E(1), and 2-hydroxycatecholestrogens. Its presence was further shown in the endometrium by RT-PCR and immunohistochemistry, localizing in the same cells expressing CYP1B1, involved locally in the formation of 4-hydroxycatecholestrogens. Data show that several UGT enzymes detected in the endometrium are involved in the glucuronidation of E(2) and its 2-OH, 4-OH, and 2-MeO metabolites that exert various biological effects in the tissue.     

Seasonal variations of systemic lupus erythematosus flares in southern France

ObjectiveExposure to sunlight is one of the environmental factors involved in the pathogenesis of systemic lupus erythematosus. We investigated whether there is seasonal variation in the incidence of cutaneous and noncutaneous severe lupus flares in southern France.MethodsWe retrospectively reviewed clinical and biological data from all SLE patients hospitalized for a flare of the disease during a two year period in our centre and collected corresponding meteorological data from the official website of MeteoFrance.ResultsForty one patients, mean age 36.7 ± 13.8 years, were included. Twenty-six patients (63.4%) had kidney biopsy performed, showing in all cases proliferative nephritis, associated with membranous nephritis in 9 (22%). We found a clear seasonal pattern for overall lupus flares with 39% of flares occurred in Spring. Among patients without any cutaneous involvement, this seasonal pattern was still observed (p = 0.024). Patients under antimalarials presented flares significantly later in the sunny season than those without (respectively median in July versus May, p = 0.044). There were strong positive correlations between occurrence of lupus flares and maximum temperature increase (ρ = 0.87, p < 0.001), minimum temperature increase (ρ = 0.87, p < 0.001), and duration of sunshine increase (ρ = 0.78, p = 0.003). These correlations were also observed in patients with renal flares.ConclusionWe confirmed a seasonal pattern for lupus flares among patients living in Southern France, with most flares in spring, in correlation with an increase in temperature and duration of sunshine. A similar seasonal pattern was observed in patients with no cutaneous involvement and with visceral involvement.     

The impact of patient characteristics on enzalutamide pharmacokinetics and how this relates to treatment toxicity and efficacy in metastatic prostate cancer patients

The aim of the study is to investigate the influence of patient characteristics, age and body mass index (BMI), on pharmacokinetics of enzalutamide, and to study the relationships between drug exposure and enzalutamide efficacy and toxicity, in mCRPC patients. Data were collected in a longitudinal cohort study (ANDROPS) and a prospective observational study (ILUMINATE), both in mCRPC patients treated with enzalutamide. To investigate the influence of age and BMI on exposure, enzalutamide and N-desmethylenzalutamide levels were compared by ANOVA. To investigate the relation of exposure versus time to progression (TTP), the sum plasma levels were divided into quartiles and compared by Kaplan–Meier analysis. To assess the relation of exposure with fatigue, plasma levels in patients experiencing fatigue vs. no fatigue were compared by and independent t test. Data of 68 mCRPC patients were included for analysis. Plasma levels were not different for age or BMI. No difference in TTP between both studies was observed (383 days (95% CI 287–859), and 567 days (95% CI 351–NR), p = 0.36). Kaplan–Meier analysis of quartiles of sum levels showed no difference for TTP. Fatigue was reported by 22 patients, no difference in sum plasma levels was observed between patients with and without fatigue. We observed that age and BMI did not influence systemic exposure in patients treated with enzalutamide. No relation of exposure with efficacy or fatigue was observed. Further research using enzalutamide at a lower dose is needed to understand the relation of enzalutamide exposure and fatigue.     

Mineral Preservatives in the Wood of Stradivari and Guarneri

Following the futile efforts of generations to reach the high standard of excellence achieved by the luthiers in Cremona, Italy, by variations of design and plate tuning, current interest is being focused on differences in material properties. The long-standing question whether the wood of Stradivari and Guarneri were treated with wood preservative materials could be answered only by the examination of wood specimens from the precious antique instruments. In a recent communication (Nature, 2006), we reported about the degradation of the wood polymers in instruments of Stradivari and Guarneri, which could be explained only by chemical manipulations, possibly by preservatives. The aim of the current work was to identify the minerals from the small samples of the maple wood which were available to us from the antique instruments. The ashes of wood from one violin and one cello by Stradivari, two violins by Guarneri, one viola by H. Jay, one violin by Gand-Bernardel were analyzed and compared with a variety of commercial tone woods. The methods of analysis were the following: back-scattered electron imaging, X-ray fluorescence maps for individual elements, wave-length dispersive spectroscopy, energy dispersive X-ray spectroscopy and quantitative microprobe analysis. All four Cremonese instruments showed the unmistakable signs of chemical treatments in the form of chemicals which are not present in natural woods, such as BaSO₄, CaF₂, borate, and ZrSiO₄. In addition to these, there were also changes in the common wood minerals. Statistical evaluation of 12 minerals by discriminant analysis revealed: a. a difference among all four Cremona instruments, b. the difference of the Cremonese instruments from the French and English antiques, and c. only the Cremonese instruments differed from all commercial woods. These findings may provide the answer why all attempts to recreate the Stradivarius from natural wood have failed. There are many obvious implications with regard to how the green tone wood should be treated, which chould lead to changes in the practice of violin-making. This research should inspire others to analyze more antique violins for their chemical contents.     

Differences between obstetricians in caesarean section rates and the management of labour.

OBJECTIVE: To determine if interobstetrician variation in caesarean section rates was associated with different approaches to the management of labour. DESIGN: A retrospective cohort study. SETTING: A tertiary care teaching hospital in Quebec, Canada. SUBJECTS: 546 nulliparae in spontaneous labour at term were grouped according to the rate of caesarean sections for dystocia of their obstetrician (high: women of two obstetricians with rates of 13.2% and 15.0%; and low: women of three obstetricians with rates of 6.0%, 6.2% and 6.5%). MAIN OUTCOME MEASURES: Frequency and timing of oxytocin, epidural, amniotomy, forceps. SECONDARY OUTCOME MEASURES: Indicators of neonatal asphyxia and trauma. RESULTS: No difference between groups was observed in the frequency or timing of use of oxytocin or epidural analgesia. Amniotomy was practised earlier by the obstetricians in the high group. Differences in section rates for dystocia were greatest in the second stage (low-2.4%, high-7.9%). Obstetricians in the low group intervened earlier with forceps or vacuum extractor. Nine babies (all in the low group), 8 of whom had had an instrumental vaginal delivery, suffered trauma (5 clavicular fractures, 4 facial palsies) (Fisher's exact test, P = 0.0139). CONCLUSION: The practice patterns of the two groups are distinguished by differences in management of the second stage. Although lower section rates were associated with an increase in mild neonatal trauma, this appears to have been mediated by the earlier use of forceps in this group.