Effect of postural alignment alteration with age on vertebral strength.

EOS biplane radiographs of 117 subjects between 20 and 83 years were analyzed to compute the upper body lever arm over the L1 vertebra and its impact on vertebral strength. Postural sagittal alignment alteration was observed with age and resulted in a greater lever arm causing vertebral strength to decrease. PURPOSE: The purpose of this study was to analyze the impact of postural alignment changes with age on vertebral strength using finite element analysis and barycentremetry. METHODS: A total of 117 subjects from 20 to 83 years were divided in three age groups: young (20 to 40 years, 62 subjects), intermediate (40 to 60 years, 26 subjects), and elderly (60 years and over, 29 subjects). EOS biplane radiographs were acquired, allowing 3D reconstruction of the spine and body envelope as well as spinal, pelvic, and sagittal alignment parameter measurements. A barycentremetry method allowed the estimation of the mass and center of mass (CoM) position of the upper body above L1, relatively to the center of the L1 vertebra (lever arm). To investigate the effect of this lever arm, vertebral strength of a generic finite element model (with constant geometry and mechanical properties for all subjects) was successively computed applying the personalized lever arm of each subject. RESULTS: A combination of an increase in thoracic kyphosis, cervical lordosis, and pelvic tilt with a loss of lumbar lordosis was observed between the young and the older groups. Sagittal alignment parameters indicated a more forward position as age increased. The lever arm of the CoM above L1 varied from an average of 1 mm backward for the young group, to averages of 10 and 24 mm forward, respectively, for the intermediate and elderly group. As a result, vertebral strength decreased from 2527 N for the young group to 1820 N for the elderly group. CONCLUSION: The global sagittal alignment modifications observed with age were consistent with the literature. Posture alteration with age reduced vertebral strength significantly in this simplified loading model. Postural alignment seems essential to be considered in the evaluation of osteoporotic patients.

[Immunotherapy adaptation in lung cancer during the COVID-19 pandemic]. / COVID-19 et cancer bronchique : adaptation des schémas d'immunothérapie et qualité de vie.

INTRODUCTION: COVID-19 pandemics required changes in medical practices. In thoracic oncology, pembrolizumab was doubled to 400mg every 6weeks, nivolumab to 480mg every 4weeks. The objective of our study was to assess the impact on quality of life, and on psychological state, as well as the tolerance, of this new schedule. METHODS: Thoracic oncologic patients who underwent these therapeutic changes in our center during the first COVID-19 epidemic wave were included. Their quality of life was assessed using the Quality of Life Questionnaire-30, their psychological state by the Hospital Anxiety Depression (HAD) scale. We also reported the preferred administration schedule, as well as adverse events. RESULTS: Thirty patients were included. The overall quality of life was preserved. Rates on HAD scale were low. Tolerance was acceptable. In majority, patients preferred the new procedure. They had a significantly better quality of life compared to those who preferred the old one. CONCLUSIONS: This new immunotherapy schedule in thoracic oncology is well tolerated and allows a preservation of quality of life. This therapeutic option may be favored in the context of COVID-19 pandemics.

Effect of methanol extract of Basella alba L. (Basellaceae) on the fecundity and testosterone level in male rats exposed to flutamide in utero.

We evaluated the effect of the methanol extract of Basella alba (MEBa) on testosterone level and fecundity/fertility in male rats exposed in utero to flutamide - an androgen receptor antagonist. For this purpose, 1.5- and 2.5 -month-old male rats exposed in utero to flutamide were treated with the MEBa (1 mg kg(-1) ) for 2 and 1 month respectively. Five days before the end of treatment, rats were housed with females to assess their fecundity/fertility. Thereafter, rats were sacrificed and blood collected for the quantification of testosterone. Flutamide-exposed male rats showed a decrease in their ano-genital distance (AGD, P < 0.05) and were infertile. In normal (methylcellulose-exposed) animals, MEBa provoked an increase in testosterone level in 1.5- (P < 0.008) and 2.5 -month-old rats (P < 0.01) concomitantly with the improvement in their fecundity by 25%. In flutamide-exposed male rats, MEBa increased testosterone level in 1.5 -month-old rats (P < 0.001) without any effect on their fecundity; while in 2.5- month-old rats, MEBa did not affect the testosterone level but improved fecundity (by 25%) and fertility (P < 0.001). This study demonstrated the positive effect of MEBa to enhance fecundity/fertility in normal male rats and in rats exposed to the antiandrogen flutamide during their foetal life.

Variations in vertebral body dimensions in women measured by 3D-XA: a longitudinal in vivo study.

Bone size and shape play an important role in bone strength, as shown by biomechanical testing and clinical studies. Vertebral body dimensions determine vertebral body strength even after adjustment for bone mineral density. We have recently proposed an in vivo method for 3D reconstruction of vertebral bodies using the whole spine imaging on a standard DXA device (3D-XA). The aim of our study was to measure in vivo vertebral body dimension changes by 3D-XA in women over a 6 year period. A total of 174 women were included in this study. They were divided into 3 groups: premenopausal (20-40 years; N=53), postmenopausal women (55-60 years; N=65) and elderly women (70-80 years; N=56). Thoracic and lumbar spine (T4-L4) were reconstructed using the 3D-XA method at baseline and 6 years later. Biochemical markers of bone remodeling were measured at baseline. In premenopausal women, there was an increase in minimal cross-sectional area (minCSA), vertebral body volume as well as end plate width of the lumbar vertebrae, without statistically significant change of these parameters at the thoracic spine; there was no change in anterior heights. In postmenopausal women, there was a decrease in vertebral body anterior height and depth, driven by results in the elderly group at both the thoracic and lumbar spine. Vertebral body width decreased at the thoracic spine but increased at the lumbar spine. MinCSA and volume decreased at the thoracic spine, in contrast with an increase of these 2 parameters at the lumbar spine in early postmenopausal women (55-60 years). In elderly women (70-80 years), the change in minCSA and volume of the lumbar spine was not statistically significant over 6 years. In postmenopausal women, there was no correlation between changes in vertebral dimensions and baseline biochemical markers of bone remodeling except for NTX/Cr and anterior height decrease. Our study confirms that an increase in geometric dimensions of lumbar vertebrae occurs through adult life. This could be related to a compensation for bone loss, aiming to maintain bone strength through increase in size. However, this phenomenon is not observed at all levels in the spine; since we do not confirm this increase at the thoracic spine. This might be one of the determinants of the higher risk of fractures in this part of the spine.

[In vitro capacitation]. / La capacitation in vitro.

Capacitation is a prerequisite for mammalian spermatozoa to fertilize oocytes. Lipids play a crucial role in the structural and functional organization of sperm plasma membrane. Lipid and membrane protein ordering changes dramatically during sperm capacitation but the resulting effects differ according to the regions of the sperm head. Lipids modifications are mainly characterized by a cholesterol efflux, dynamic cholesterol redistribution in particular in the apical zone of the head and also a phospholipids reorganization resulting to the scramblase activation. The existence of lipids ordered microdomains (lipid rafts) has been recently observed in sperm membranes. These lipid and membrane protein movements are believed to play a role in modulating signaling pathways mainly, the AMPc/PKA and ERK pathways. One of the early key events is the activation of adenylate cyclase by high levels of bicarbonate. All these pathways lead finally to the phosphorylation of Tyr-proteins. But capacitation seems to be more complex with the contribution of other kinases (from the PI3K/Akt pathway and phosphotyrosine kinases) towards the phosphorylation of other Ser/Thr and Tyr proteins. The reactive oxygen species (ROS) seem to be important in the control of mechanisms involved in capacitation.

New insights about the evaluation of human sperm quality: the aromatase example.

Male contribution to the couple's infertility is at first evaluated by the routine examination of semen parameters upon optical microscopy providing valuable information for a rational initial diagnosis and for a clinical management of infertility. But the different forms of infertility defined according to the WHO criteria especially teratozoospermia are not always related to the chromatin structure or to the fertilization capacity. New investigations at the molecular level (transcript and protein) could be developed in order to understand the nature of sperm malformation responsible of human infertility and thus to evaluate the sperm quality. The profile analysis of spermatozoal transcripts could be considered as a fingerprint of the past spermatogenic events. The selection of representative transcripts of normal spermatozoa remains complex because a differential expression (increased, decreased or not modified levels) of specific transcripts has been revealed between immotile and motile sperm fractions issued from normozoospermic donors. Microarrays tests or real-time quantitative PCR could be helpful for the identification of factors involved in the male infertility. Differences in the expression of specific transcripts have been reported between normal and abnormal semen samples. With the aromatase example, we have noted a negative strong correlation between the amount of transcript and the percentage of abnormal forms especially in presence of head defects. Immunocytochemical procedures using fluorescent probes associated with either confocal microscopy or flow cytometry can be also helpful to proceed with further investigations about the localization of proteins in the compartmentalized spermatozoa or the acrosome reaction. The dual location of aromatase both in the equatorial segment, the mid-piece and the tail could explain the double role of this enzyme in acrosome reaction and motility.

Time- and dose-dependent effects of roundup on human embryonic and placental cells.

Roundup is the major herbicide used worldwide, in particular on genetically modified plants that have been designed to tolerate it. We have tested the toxicity and endocrine disruption potential of Roundup (Bioforce on human embryonic 293 and placental-derived JEG3 cells, but also on normal human placenta and equine testis. The cell lines have proven to be suitable to estimate hormonal activity and toxicity of pollutants. The median lethal dose (LD(50)) of Roundup with embryonic cells is 0.3% within 1 h in serum-free medium, and it decreases to reach 0.06% (containing among other compounds 1.27 mM glyphosate) after 72 h in the presence of serum. In these conditions, the embryonic cells appear to be 2-4 times more sensitive than the placental ones. In all instances, Roundup (generally used in agriculture at 1-2%, i.e., with 21-42 mM glyphosate) is more efficient than its active ingredient, glyphosate, suggesting a synergistic effect provoked by the adjuvants present in Roundup. We demonstrated that serum-free cultures, even on a short-term basis (1 h), reveal the xenobiotic impacts that are visible 1-2 days later in serum. We also document at lower non-overtly toxic doses, from 0.01% (with 210 microM glyphosate) in 24 h, that Roundup is an aromatase disruptor. The direct inhibition is temperature-dependent and is confirmed in different tissues and species (cell lines from placenta or embryonic kidney, equine testicular, or human fresh placental extracts). Furthermore, glyphosate acts directly as a partial inactivator on microsomal aromatase, independently of its acidity, and in a dose-dependent manner. The cytotoxic, and potentially endocrine-disrupting effects of Roundup are thus amplified with time. Taken together, these data suggest that Roundup exposure may affect human reproduction and fetal development in case of contamination. Chemical mixtures in formulations appear to be underestimated regarding their toxic or hormonal impact.

Rat Leydig cells use apolipoprotein E depleted high density lipoprotein to regulate testosterone production.

Rat HDL are known to increase testosterone production by cultured Leydig cells either following gonadotropin stimulation or cholesteryl ester depletion. However, rat HDL contain apolipoprotein E and have a high affinity for the members of the low density receptor family such as LDL receptor, LDL receptor related protein and VLDL receptor. In contrast with the adrenal cells, the contribution of apo A-I and apo E pathways in HDL cholesterol uptake has not been yet evidenced in rat Leydig cells. Recent data provided evidence that hCG stimulates scavenger receptor BI expression in testes. In order to investigate if testosterone production can be stimulated by apo E depleted HDL, we compared the level of testosterone stimulation by HDL with or without apo E first, in presence of saturating dose of hCG (1 IU/ml) and second, after depletion of cholesterol synthesis by pravastatin, an inhibitor of HMG-CoA reductase. In presence of hCG, HDL with or without apo E increased testosterone production respectively by 37 and 25%. Pravastatin at 100 microg/ml inhibited the cholesterol synthesis and the testosterone production by 25% and decreased the cholesteryl content by 25%. The addition of HDL with or without apo E (50 microg protein HDL/ ml) completely overcame the depletion of cellular cholesteryl esters and the inhibition of testosterone production induced by pravastatin. In the presence of heparin, apo E depleted HDL overcame the testosterone production induced by pravastatin, indicating that uptake of HDL without apo E via a secretion of apo E by the cells themselves was not involved. Therefore, in absence of apo E, it is suggested that rat Leydig cells used HDL to regulate steroidogenesis via an apolipoprotein A-I pathway.

Evaluation of cholesteryl ester transfer in the seminiferous tubule cells of immature rats in vivo and in vitro.

Sertoli cells and germ cells are separated from the interstitial blood capillaries by an extracellular matrix and the peritubular cells, which constitute a barrier to the movement of plasma lipoproteins. The present study was undertaken to evaluate in vivo and in vitro the high density lipoprotein (HDL) cholesteryl ester transfer from plasma to seminiferous tubule cells in the testis of 30-day-old rats. Firstly, the transfer of HDL cholesteryl oleate from plasma to testicular compartments was evaluated and, secondly, the role of apolipoproteins A-I and E in the uptake of cholesteryl ester by Sertoli cells was investigated. At 2 h after the administration of HDL reconstituted with [3H]cholesteryl ester, dimyristoyl phosphatidylcholine and apolipoproteins, the tissue space in the interstitial cells (740 +/- 60 microliters g-1 cell protein) was fourfold higher than that in the seminiferous tubule cells (170 +/- 10 microliters g-1). Sertoli cells were isolated and incubated with [3H]cholesteryl ester HDL reconstituted with apolipoprotein A-I or E to evaluate the mechanisms of cholesteryl ester influx. At the same apolipoprotein concentration (50 micrograms apolipoprotein ml-1 medium), the uptake of [3H]cholesteryl oleate from phospholipid-apolipoprotein E vesicles was twofold higher than that with phospholipid-apolipoprotein A-I vesicles. The presence of heparin reduced the uptake of cholesteryl ester from apolipoprotein E vesicles but not with apolipoprotein A-I vesicles, indicating that uptake of apolipoprotein A-I vesicles via a secretion of apolipoprotein E by the cells themselves was not involved. These results demonstrate that plasma lipoprotein cholesterol is able to cross the testis lamina propria and that Sertoli cells take up cholesteryl ester for seminiferous tubule cell metabolism mainly via an apolipoprotein E pathway.