Fibrous dysplasia of bone (FD) is a rare congenital bone disease, due to a somatic mutation of GNAS. This mutation results in a defect of osteoblast differentiation and mineralization and also an ...increase in bone resorption by large active osteoclasts. Bone pain is present in half of patients and is the main determinant of quality of life of patients with FD. Bisphosphonates are known to reduce bone pain and reduce the risk of fracture in patients with bone metastases or Paget's disease. Bisphosphonates may have similar effects in FD.
In this article, we have reviewed the therapeutic potential of bisphosphonates to reduce bone pain due to FD, improve bone strength and reduce the occurrence of fracture.
We have reviewed 234 articles examining the effect of bisphosphonates on FD/McCune Albright Syndrome with no date limit, in PubMed and selected the articles with highest quality of methodology.
Pamidronate therapy significantly decreased bone pain and bone resorption (urinary NTX, urinary and serum CTX). Pamidronate may improve radiological lesions of FD patients (filling of osteolytic lesion and/or cortical thickening). This data with intravenous pamidronate, however, has been obtained from observational studies and no randomized controlled trial is available. Randomized placebo-controlled trials of oral bisphosphonates (alendronate or risedronate) have failed to demonstrate a significant decrease in bone pain over placebo. Several studies including one randomized controlled trial have shown an increase in bone mineral density (BMD) at FD sites with oral and intravenous bisphosphonate treatment. No effect on occurrence of fracture has been reported.
In conclusion, intravenous bisphosphonates may be proposed to treat persistent, moderate to severe bone pain of FD, e.g., according to the guidelines from the FD/MAS International Consortium. Oral bisphosphonates should not be used in this indication.
•Intravenous bisphosphonates have been used in the treatment of fibrous dysplasia for more than 2 decades•Treatment efficacy has been obtained from observational studies•Oral bisphosphonates are not recommended because their absence of efficacy has been demonstrated
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Bacteria have evolved a wide range of mechanisms to harm and kill their competitors, including chemical, mechanical and biological weapons. Here we review the incredible diversity of bacterial weapon ...systems, which comprise antibiotics, toxic proteins, mechanical weapons that stab and pierce, viruses, and more. The evolution of bacterial weapons is shaped by many factors, including cell density and nutrient abundance, and how strains are arranged in space. Bacteria also employ a diverse range of combat behaviours, including pre-emptive attacks, suicidal attacks, and reciprocation (tit-for-tat). However, why bacteria carry so many weapons, and why they are so often used, remains poorly understood. By comparison with animals, we argue that the way that bacteria live — often in dense and genetically diverse communities — is likely to be key to their aggression as it encourages them to dig in and fight alongside their clonemates. The intensity of bacterial aggression is such that it can strongly affect communities, via complex coevolutionary and eco-evolutionary dynamics, which influence species over space and time. Bacterial warfare is a fascinating topic for ecology and evolution, as well as one of increasing relevance. Understanding how bacteria win wars is important for the goal of manipulating the human microbiome and other important microbial systems.
Bacteria have evolved a wide range of mechanisms to harm and kill their competitors, but why they do so remains poorly understood. Granato et al. explore the diversity and evolution of bacterial weapons and argue that the way bacteria live is key to their aggression, which drives complex coevolutionary dynamics over space and time.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Information-driven control can be used to develop intelligent sensors that can optimize their measurement value based on environmental feedback. In object tracking applications, sensor actions are ...chosen based on the expected reduction in uncertainty also known as information gain. Random finite set (RFS) theory provides a formalism for quantifying and estimating information gain in multi-object tracking problems. However, estimating information gain in these applications remains computationally challenging. This paper presents a new tractable approximation of the RFS expected information gain applicable to sensor control for multi-object search and tracking. Unlike existing RFS approaches, the information gain approximation presented in this paper considers the contributions of non-ideal noisy measurements, missed detections, false alarms, and object appearance/disappearance. The effectiveness of the information-driven sensor control is demonstrated through two multi-vehicle search-while-tracking experiments using real video data from remote terrestrial and satellite sensors.
Evolution is often an obstacle to the engineering of stable biological systems due to the selection of mutations inactivating costly gene circuits. Gene overlaps induce important constraints on ...sequences and their evolution. We show that these constraints can be harnessed to increase the stability of costly genes by purging loss-of-function mutations. We combine computational and synthetic biology approaches to rationally design an overlapping reading frame expressing an essential gene within an existing gene to protect. Our algorithm succeeded in creating overlapping reading frames in 80% of E. coli genes. Experimentally, scoring mutations in both genes of such overlapping construct, we found that a significant fraction of mutations impacting the gene to protect have a deleterious effect on the essential gene. Such an overlap thus protects a costly gene from removal by natural selection by associating the benefit of this removal with a larger or even lethal cost. In our synthetic constructs, the overlap converts many of the possible mutants into evolutionary dead-ends, reducing the evolutionary potential of the system and thus increasing its stability over time.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The aim of the current study was to assess if cows preferred pasture or indoor housing, and how diurnal and environmental factors affected this preference. Lactating dairy cows (n=5 groups, each ...containing 5 cows) were sequentially housed either in a free-stall barn on pasture, or given the choice between the 2 environments. Each group was tested 3 times under each condition, for a total of 21 d, to assess the effects of varying climatic conditions (outdoor temperature ranged from 9.9 to 28.2°C and daily rainfall from 0 to 65mm/d over the course of the experiment). When provided the choice, cows spent on average (± SD) 13.0±0.6h/d on pasture, mainly at night. The time cows spent on pasture during the day decreased with the temperature-humidity index (R2=0.55); time on pasture at night decreased with rainfall (R2=0.12). When provided a choice, cows spent more of their lying time on pasture (69.4±0.02% of the total lying time/d) than indoors in the free-stalls. Cows also spent more time in total lying down when provided a choice than when confined to pasture 0.6h/d more lying time; standard error of the difference (SED) = 0.21h/d and spent even more time lying down when confined indoors (1.1h/d more time; SED=0.21h/d). Cows used the indoor housing especially for feeding; feeder use peaked when cows returned from morning and afternoon milkings. However, cows with free access to pasture spent 1.0h/d (SED=0.09h/d) less time eating the TMR available indoors, resulting in a decline in intake of 2.9kg of dry matter/d (SED=0.36kg of dry matter/d). How cows used the indoor housing differed when cows were provided a choice; for example, cows spent a greater percentage of their time indoors at the feed alley both during the day (47% of the total time spent indoors, versus 41% for cows confined indoors, SED=0.02%) and at night (22 vs. 5%, SED=0.04%). In conclusion, under the housing and environmental conditions tested, cows showed a strong preference for access to pasture at night and for access to indoor housing during the day when temperature and humidity increased.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
The Stroop task and subtraction rely on the different cognitive processes and cerebral regions, but both these cognitive functions interact with posture. The study of cognitive-motor interactions ...falls under the concept of sharing resources, implying that resources for processing are limited. Researchers try to understand this interaction by constructing dual task (DT) paradigms. None have investigated the Stroop and subtraction tasks in three inherently simple postures in two groups of young adults. This study aimed to test whether a given posture benefits a given cognitive function when cognitive and postural tasks are not overly demanding and are underpinned by common cerebral structures. This study presents the results of 60 healthy young adults performing a subtraction task in three postures (sitting, standing, and walking) and 57 healthy young adults performing the Stroop task in the same three postures. Our results showed that performance at the Stroop task, in terms of number of correct answers and interference, are better while standing or even walking compared to sitting while subtraction is better sitting compared to standing and walking. Moreover, static postural parameters did not vary when in DT compared to single task. This means that there was no additional cost on posture when achieving the cognitive activity simultaneously. The absence of impact of the DT on postural parameters in static postures and the changes in the gait pace when walking suggest that cognitive tasks can be achieved in various postures, without being too costly on posture.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Bacteria often live in diverse communities where the spatial arrangement of strains and species is considered critical for their ecology. However, a test of this hypothesis requires manipulation at ...the fine scales at which spatial structure naturally occurs. Here we develop a droplet-based printing method to arrange bacterial genotypes across a sub-millimetre array. We print strains of the gut bacterium Escherichia coli that naturally compete with one another using protein toxins. Our experiments reveal that toxin-producing strains largely eliminate susceptible non-producers when genotypes are well-mixed. However, printing strains side-by-side creates an ecological refuge where susceptible strains can persist in large numbers. Moving to competitions between toxin producers reveals that spatial structure can make the difference between one strain winning and mutual destruction. Finally, we print different potential barriers between competing strains to understand how ecological refuges form, which shows that cells closest to a toxin producer mop up the toxin and protect their clonemates. Our work provides a method to generate customised bacterial communities with defined spatial distributions, and reveals that micron-scale changes in these distributions can drive major shifts in ecology.
•This is the first set of dietary recommendations in the prevention and treatment of Osteoporosis.•These recommendations were established by a multidisciplinary working group and resulted in 15 ...questions and recommendations pertaining to “daily practices”.•A Mediterranean-type diet and the daily consumption of 2 to 3 dairy products are recommended.•Conversely, unbalanced Western diets, vegan diets, weight-loss diets in non-overweight individuals, alcohol consumption and daily consumption of sodas are advised against.
This article presents the initial recommendations of the French Rheumatology Society (Société Française de Rhumatologie – SFR) and the Osteoporosis Research and Information Group (Groupe de Recherche et d’Informations sur les Ostéoporoses – GRIO) on the role of diet in the prevention and treatment of osteoporosis.
The recommendations were produced by a working group composed of rheumatologists, physician nutrition specialists and a geriatrician. Fifteen (15) questions pertaining to “daily practices” were preselected by the working group. For the literature review, the working group focussed mainly on the effects of diet on bone mineral density (BMD) and fractures, and primarily on meta-analyses of longitudinal studies and dietary intervention studies.
A Mediterranean-type diet and the daily consumption of 2 to 3 dairy products are recommended. Together, these provide the calcium and “high quality” protein required to maintain a normal calcium-phosphorus balance and bone metabolism, and are associated with lower fracture risk. Conversely, unbalanced Western diets, vegan diets, weight-loss diets in non-overweight individuals, alcohol consumption and daily consumption of sodas are advised against. In terms of the beneficial effects on bone mineral density and fracture risk, current scientific data are either insufficient or too divergent to recommend increasing or restricting the consumption of tea or coffee, vitamins other than vitamin D, vitamin D-enriched or phytoestrogen-rich foods, calcium-enriched plant-based beverages, oral nutritional supplements, or dietary sources of prebiotics and probiotics.
These are the first set of recommendations addressing the role of diet in the prevention and treatment of osteoporosis. More research is necessary to direct and support guidelines.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Abstract
STUDY QUESTION
Is prenatal exposure to persistent organic pollutants (POPs) associated with variations of sex hormone levels in cord blood?
SUMMARY ANSWER
Prenatal exposure to a number of ...POPs is associated with a disruption of hormone levels in cord blood, with sex specificities.
WHAT IS KNOWN ALREADY
Epidemiological studies have reported disorders of reproductive health, in relation with POPs exposure during early life and the endocrine disruption properties of these chemicals have been suggested as possible mechanisms.
STUDY DESIGN, SIZE, DURATION
A subset of 282 mother-child pairs was selected from the prospective population-based PELAGIE birth cohort (n = 3421, 2002–2006, Brittany, France). Pregnant women were recruited before 19 weeks of gestation and followed until delivery.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Sex hormone levels including sex hormone-binding globulin (SHBG), estradiol (E2), total testosterone (T), free testosterone (fT = T/SHBG) and the aromatase index (AI = T/E2) were measured in 282 cord blood samples. Anti-Müllerian hormone (AMH) was measured in male newborns only. Pesticide concentrations of α-endosulfan, β-hexachlorocyclohexane (β-HCH), γ-HCH, dieldrin, pp′-dichlorodiphenyldichloroethylene (p,p′-DDE), hexachlorobenzene (HCB), heptachlor epoxide (HCE), as well as PCBs (congeners 153, 187 and the sum of anti-estrogenic PCBs 118, 138, and 170) and decabrominated diphenyl ether (BDE209) were also measured in cord blood. Associations between sex hormones and POPs exposure were explored using multiple linear regressions adjusted for potential confounders.
MAIN RESULTS AND THE ROLE OF CHANCE
High PCB levels were associated with an increase of SHBG (P-trend < 0.01) and AMH (P-trend < 0.05) and a decrease of fT (P-trend < 0.05) and AI (P-trend < 0.01). High pesticide levels, particularly α-endosulfan and HCE, were associated with an increase of SHBG (P < 0.05) and E2 (P < 0.01) and a decrease of fT (P < 0.05) and AI (P < 0.01). Several of these associations were stronger, or specific, among male or female newborns. The associations were not altered in the sensitivity analyses.
LIMITATIONS, REASONS FOR CAUTION
The study population was of relatively small sample size, and some compounds rarely detected in cord blood. The high level of correlation between POPs makes it difficult to identify the most contributing POPs. Hormone measurements were performed at birth (in cord blood) and may not adequately represent the infant endocrine system. Multiple statistical testing may have led to false-positive associations.
WIDER IMPLICATIONS OF THE FINDINGS
Our results are in discordance with those reported in the only published study of the kind but in accordance with studies about prenatal exposure to other endocrine disruptors such as phthalates. These findings may help understanding the pathways involved in adverse reproductive outcomes associated with POPs exposure.
STUDY FUNDING/COMPETING INTEREST(S)
The PELAGIE cohort is funded by Inserm, French Ministry of Health, French Ministry of Labor, InVS, ANR, ANSES, and French Ministry of Ecology. None of the authors has any competing interest to declare.
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