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Objective To evaluate the effect of calcium (15 mmol/day) and vitamin D (625 µg/month) as single supplement or in combination versus no supplement on growth clinical signs of rickets and Kashin-Beck disease (KBD) and dental health. Methods Prospective controlled trial involving children aged 0-5 years living in 4 groups of villages in a KBD-endemic rural area of Central Tibet who received either calcium and/or vitamin D or no supplement. The cohort was followed over 3 years. Primary outcome was the impact of the different supplementation regimes on KBD rickets and growth; secondary outcomes were impact on urinary levels of calcium and phosphorus biomarkers of bone and cartilage turnover and dental health. Results No difference was observed between the 4 groups with regard to anthropometric data rickets KBD urinary levels of Croslaps® and Cartilaps®. Weight for height or age mid-upper arm circumference and skin fold thickness decreased in the 4 groups. Height for age increased and the prevalence of KBD fell in the four groups. Dental health was better in the group receiving calcium and vitamin D. Urinary calcium levels increased after 3 years of follow-up in all groups; the group receiving vitamin D had a higher increase (p-value: 0044). The same global increase was observed for urinary phosphorus levels; the group receiving calcium had a higher increase (p-value: 001). Conclusions Calcium and vitamin D failed to improve growth and bone metabolism of children living in a KBD-endemic rural area. Calcium and vitamin D supplementation improved dental health.

Background Aedes mosquitoes severely affect the health and wellbeing of human populations by transmitting infectious diseases. In French Polynesia, Aedes aegypti is the main vector of dengue, chikungunya and Zika, and Aedes polynesiensis the primary vector of Bancroftian filariasis and a secondary vector of arboviruses. Tools for assessing the risk of disease transmission or for measuring the efficacy of vector control programmes are scarce. A promising approach to quantify the human-vector contact relies on the detection and the quantification of antibodies directed against mosquito salivary proteins. Methodology/Principal findings An ELISA test was developed to detect and quantify the presence of immunoglobulin G (IgG) directed against proteins from salivary gland extracts (SGE) of Ae. aegypti and Ae. polynesiensis in human populations exposed to either species, through a cross-sectional study. In Tahiti and Moorea islands where Ae. aegypti and Ae. polynesiensis are present, the test revealed that 98% and 68% of individuals have developed IgG directed against Ae. aegypti and Ae. polynesiensis SGE, respectively. By comparison, ELISA tests conducted on a cohort of people from metropolitan France, not exposed to these Aedes mosquitoes, indicated that 97% of individuals had no IgG directed against SGE of either mosquito species. The analysis of additional cohorts representing different entomological Aedes contexts showed no ELISA IgG cross-reactivity between Ae. aegypti and Ae. polynesiensis SGE. Conclusions/Significance The IgG response to salivary gland extracts seems to be a valid and specific biomarker of human exposure to the bites of Ae. aegypti and Ae. polynesiensis. This new immuno-epidemiological tool will enhance our understanding of people exposure to mosquito bites, facilitate the identification of areas where disease transmission risk is high and permit to evaluate the efficacy of novel vector control strategies in Pacific islands and other tropical settings., Author summary In Pacific islands like in most tropical regions, Aedes mosquitoes affect the health of human populations by transmitting diseases like dengue, chikungunya, Zika and filariasis. The biting nuisance of Aedes mosquitoes also impacts local tourism, affecting the sustainability of island economies. Mosquito saliva is injected during the biting process, and the response triggered by the human immune system to proteins contained in mosquito saliva was shown to be a relevant biomarker of exposure to mosquito bites. Using this approach, we have developed an immuno-epidemiological tool to investigate the exposure of people to the bites of Aedes aegypti and Aedes polynesiensis, two significant mosquito vectors of infectious diseases in French Polynesia and other island countries and territories in the Pacific. This novel tool proved specific and reliable. It will improve the assessment of disease transmission risk and be useful for measuring the efficacy of both conventional and innovative vector control strategies.

To understand the primary care experiences of women who have a history of childhood trauma and chronic disease.Qualitative study using in-depth interviews with directed content analysis.Family health team in Kingston, Ont.Twenty-six women.Letters of invitation were sent to eligible participants followed by a telephone survey. Women with an adverse childhood experience (ACE) score of 4 or higher and with 2 or more chronic conditions were invited to participate in a one-on-one interview.Participants were frequent users of health care services. Most had not been asked about ACEs by their family physicians. Most participants believed that their history of ACEs was important to their health and that providers should ask about childhood experiences. When participants discussed their primary care experiences, the following 6 common themes evolved: the importance of continuity of care; challenges with family medicine residents; provider awareness of abuse history; distress due to triggering events; characteristics of clinic staff and space; and engagement in care plans and choice. These discussions revealed that participants' primary care experiences were not always informed by the principles of trauma-informed care.Understanding the effect of ACEs on women's health is important. Incorporating a trauma-informed approach can be beneficial and enhance the experience of patients. Physicians should learn to ask patients about their childhood experiences, as it is important to their health care.

Background and objectives: Several studies revealed clinical signs of stunting and rickets among rural populations of Tibet Autonomous Region (T.A.R.), and especially amid children. Further, these populations are affected by a bone disease named Kashin-Beck disease (KBD). However, little is known about the dietary status of this population. This survey aimed to assess the usual intakes of young Tibetan children living in rural areas around Lhasa for energy, water, and ten minerals and trace elements (Na, K, Ca, P, Mg, Fe, Zn, Cu, Mn, and Se) involved in bone metabolism. Design: A cross-sectional survey was designed. Totally, 250 pre-school children aged 3–5 years living in rural areas were enrolled. The 24-h food recall method was used to collect the intakes for two days, during two different seasons (September 2012 and April 2013). Because Tibetan foods are mainly derived from local agriculture and artisanal production, a combination of food composition tables was compiled, including specific and local food composition data. Results: The Chinese dietary recommended intakes are not met for most of the elements investigated. Intake of sodium is much too high, while usual intakes are too low for K, Ca, Zn, Cu, and Se. Bioavailability of Ca, Fe, and Zn may be of concern due to the high phytic acid content in the diet. Conclusion: These nutrient imbalances may impact growth and bone metabolism of young Tibetan children. The advantages of the implementation of food diversification programs are discussed as well as the relevance of supplements distribution., SCOPUS: ar.j, info:eu-repo/semantics/published

Traditional foods play a major role in the diet of rural people living in the Tibet Autonomous Region of the People's Republic of China. Because these foods are mainly derived from local agriculture as well as artisanal production, their mineral composition may show significant discrepancies when compared with food composition data. This study aims at providing relevant data on the mineral composition of the main Tibetan foods. Sixteen different foodstuffs were sampled, including water, concentrated brewed black tea, chang, tsampa, wheat flour, dried cheese, dried yak meat, dried mutton, blood sausage, dried wild peaches, dried Chinese radish, and dried nettles. They were analyzed by inductively coupled plasma mass spectrometry (ICP-MS) for 19 minerals: Na, K, P, Ca, Mg, Fe, Zn, Mn, Cu, Ni, Se, Mo, Al, As, Cr, Co, Cd, Pb, and V. The validity of the results was ensured by the use of standard reference materials. A statistical comparison of the mean mineral contents of the analyzed foods against food composition data from the China Food Composition (CFC) table was carried out. It revealed significant discrepancies, emphasizing the importance of food analysis for nutritional assessment in Tibet autonomous region. To the best of our knowledge, the mineral compositions of some traditional Tibetan foods are here reported for the first time.

Background The saliva of tsetse flies contains a cocktail of bioactive molecules inducing specific antibody responses in hosts exposed to bites. We have previously shown that an indirect-ELISA test using whole salivary extracts from Glossina morsitans submorsitans was able to discriminate between (i) cattle from tsetse infested and tsetse free areas and (ii) animals experimentally exposed to low or high numbers of tsetse flies. In the present study, our aim was to identify specific salivary synthetic peptides that could be used to develop simple immunoassays to measure cattle exposure to tsetse flies. Methods In a first step, 2D-electrophoresis immunoblotting, using sera from animals exposed to a variety of bloodsucking arthropods, was performed to identify specific salivary proteins recognised in cattle exposed to tsetse bites. Linear epitope prediction software and Blast analysis were then used to design synthetic peptides within the identified salivary proteins. Finally, candidate peptides were tested by indirect-ELISA on serum samples from tsetse infested and tsetse free areas, and from exposure experiments. Results The combined immunoblotting and bioinformatics analyses led to the identification of five peptides carrying putative linear epitopes within two salivary proteins: the tsetse salivary gland protein 1 (Tsal1) and the Salivary Secreted Adenosine (SSA). Of these, two were synthesised and tested further based on the absence of sequence homology with other arthropods or pathogen species. IgG responses to the Tsal152–75 synthetic peptide were shown to be specific of tsetse exposure in both naturally and experimentally exposed hosts. Nevertheless, anti-Tsal152–75 IgG responses were absent in animals exposed to high tsetse biting rates. Conclusions These results suggest that Tsal152–75 specific antibodies represent a biomarker of low cattle exposure to tsetse fly. These results are discussed in the light of the other available tsetse saliva based-immunoassays and in the perspective of developing a simple serological tool for tsetse eradication campaigns to assess the tsetse free status or to detect tsetse reemergence in previously cleared areas. Electronic supplementary material The online version of this article (doi:10.1186/s13071-016-1414-8) contains supplementary material, which is available to authorized users.

Background The Pacific region is an area unique in the world, composed of thousands of islands with differing climates and environments. The spreading and establishment of the mosquito Aedes aegypti in these islands might be linked to human migration. Ae. aegypti is the major vector of arboviruses (dengue, chikungunya and Zika viruses) in the region. The intense circulation of these viruses in the Pacific during the last decade led to an increase of vector control measures by local health authorities. The aim of this study is to analyze the genetic relationships among Ae. aegypti populations in this region. Methodology/Principal Finding We studied the genetic variability and population genetics of 270 Ae. aegypti, sampled from 9 locations in New Caledonia, Fiji, Tonga and French Polynesia by analyzing nine microsatellites and two mitochondrial DNA regions (CO1 and ND4). Microsatellite markers revealed heterogeneity in the genetic structure between the western, central and eastern Pacific island countries. The microsatellite markers indicate a statistically moderate differentiation (FST = 0.136; P < = 0.001) in relation to island isolation. A high degree of mixed ancestry can be observed in the most important towns (e.g. Noumea, Suva and Papeete) compared with the most isolated islands (e.g. Ouvea and Vaitahu). Phylogenetic analysis indicated that most of samples are related to Asian and American specimens. Conclusions/Significance Our results suggest a link between human migrations in the Pacific region and the origin of Ae. aegypti populations. The genetic pattern observed might be linked to the island isolation and to the different environmental conditions or ecosystems., Author Summary Aedes aegypti is the major arbovirus vector in the Pacific region. The spread of this mosquito in the different islands seems to be linked to human activities at the beginning of the twentieth century. Since 2010, occurrence of arbovirus outbreaks increased in this region, with the co-circulation of dengue, chikungunya and Zika viruses. The lack of vaccines and treatments for these pathogens led the health authorities to implement vector control measures. In this study, we present the genetic structure and the phylogenetic data obtained from the analysis of 270 Ae. aegypti collected in the Pacific region. The infestation of the islands seems to have American and Asian origins. The genetic structure of the vector populations indicates a differentiation of the mosquitoes between the western, central and eastern Pacific island countries and the specific island isolation context. This differentiation could be related to the different environmental conditions in each island country.

In order to describe the growth of 0–5-year-old Tibetan children living in a Kashin–Beck disease (KBD) endemic rural area and to examine the relationship between anthropometric indicators and clinical signs of rickets, we analyzed the baseline data of a cohort of 668 children enrolled in a prospective program of calcium and vitamin D supplementation. Tibetan children suffer from growth retardation. Z score of weight-for-age, height-for-age, weight-for-height was below −2 in 32.5%, 27.7%, and 12.1% of the children, respectively. Clinical signs of severe rickets are highly prevalent. Underweight, stunting, and clinical rickets increases with age. Prevalence of malnutrition was higher in the presence of signs of rickets. The proportion of children with a head circumference Z score

Background/Objectives Understanding the factors underlying the spatio-temporal distribution of infectious diseases provides useful information regarding their prevention and control. Dengue fever spatio-temporal patterns result from complex interactions between the virus, the host, and the vector. These interactions can be influenced by environmental conditions. Our objectives were to analyse dengue fever spatial distribution over New Caledonia during epidemic years, to identify some of the main underlying factors, and to predict the spatial evolution of dengue fever under changing climatic conditions, at the 2100 horizon. Methods We used principal component analysis and support vector machines to analyse and model the influence of climate and socio-economic variables on the mean spatial distribution of 24,272 dengue cases reported from 1995 to 2012 in thirty-three communes of New Caledonia. We then modelled and estimated the future evolution of dengue incidence rates using a regional downscaling of future climate projections. Results The spatial distribution of dengue fever cases is highly heterogeneous. The variables most associated with this observed heterogeneity are the mean temperature, the mean number of people per premise, and the mean percentage of unemployed people, a variable highly correlated with people's way of life. Rainfall does not seem to play an important role in the spatial distribution of dengue cases during epidemics. By the end of the 21st century, if temperature increases by approximately 3°C, mean incidence rates during epidemics could double. Conclusion In New Caledonia, a subtropical insular environment, both temperature and socio-economic conditions are influencing the spatial spread of dengue fever. Extension of this study to other countries worldwide should improve the knowledge about climate influence on dengue burden and about the complex interplay between different factors. This study presents a methodology that can be used as a step by step guide to model dengue spatial heterogeneity in other countries., Author Summary Dengue fever is the most important viral arthropod-borne disease worldwide and its geographical expansion during the past decades has been of growing concern for scientists and public health authorities because of its heavy sanitary burden and economic impacts. In the absence of an effective vaccine, control is currently limited to vector-control measures. In this context, understanding the sociologic, entomologic and environmental factors underlying dengue dynamics is essential and can provide public health authorities with sound information about control measures to be implemented. In this study, we analyse socio-economic, climatic and epidemiological data to understand the impact of the studied factors on the spatial distribution of dengue cases during epidemic years in New Caledonia, a French island located in the South Pacific. We identify at risk areas, and find that temperature and people’s way of life are key factors determining the level of viral circulation in New Caledonia. Hence, communication campaigns fostering individual protection measures against mosquito bites could help reduce dengue burden in New Caledonia. Using projections of temperature under different scenarios of climate change, we find that dengue incidence rates during epidemics could double by the end of the century, with areas at low risk of dengue fever being highly affected in the future.

Parasitic protozoa of the genus Leishmania are the causative agents of leishmaniasis. Survival and transmission of these parasites in their different hosts require membrane-bound or extracellular factors to interact with and modify their host environments. Over the last decade, several approaches have been applied to study all the extracellular proteins exported by an organism at a particular time or stage in its life cycle and under defined conditions, collectively termed the secretome or the exoproteome. In this review, we focus on emerging data shedding light on the secretion mechanisms involved in the production of the Leishmania exoproteome. We also describe other methodologies currently available that could be used to analyse the Leishmania exoproteome. Understanding the complexity of the Leishmania exoproteome is a key component to elucidating the mechanisms used by these parasites for exporting proteins to the extracellular space during its life cycle. Given the importance of extracellular factors, a detailed knowledge of the Leishmania exoproteome may provide novel targets for rational drug design and/or a source of antigens for vaccine development.

The human skeleton, made of 206 bones, plays vital roles including supporting the body, protecting organs, enabling movement, and storing minerals. Bones are made of organic structures, intimately connected with an inorganic matrix produced by bone cells. Many elements are ubiquitous in our environment, and many impact bone metabolism. Most elements have antagonistic actions depending on concentration. Indeed, some elements are essential, others are deleterious, and many can be both. Several pathways mediate effects of element deficiencies or excesses on bone metabolism. This paper aims to identify all elements that impact bone health and explore the mechanisms by which they act. To date, this is the first time that the effects of thirty minerals on bone metabolism have been summarized.

The cytoplasmic Leishmania silent information regulator 2 (SIR2)RP1 protein is essential for parasite growth and survival and constitutes an attractive therapeutic target. Little information is available on putative substrate(s) and/or partner(s) that could shed light on the pathways in which this enzyme plays a role. We carried out co-immunoprecipitation experiments on the soluble fractions of wild-type and parasites overexpressing LmSIR2RP1 and found that the essential chaperone heat shock protein (HSP) 83, the Leishmania ortholog of the mammalian HSP90, constantly co-immunoprecipitated with LmSIR2RP1. We found that Leishmania HSP83 is among the lysine acetylated protein, but the intracellular level of SIR2RP1 does not influence the acetylation status of HSP83. Finally, the modified Geldanamycin susceptibility (an inhibitor of HSP83) exhibited by SIR2RP1 mutant parasites support an in vivo relationship between the chaperone activity of HSP83 and LmSIR2RP1. An insight on the nature of the interaction in Leishmania is required to understand its role in the cell fate control during cytodifferentiation.

Clément Justinia, Mahieu Ronan, Mathieu Françoise. Les familles monoparentales et la précarité (1994-2003). In: Recherches et Prévisions, n°79, 2005. pp. 117-123.

Gram-negative bacteria were isolated from knots induced by Pseudomonas savastanoi in olive trees (Olea europaea L.). A total of nine endophytic bacterial strains were isolated, each from inside a different tree knot. Biochemical characterization indicated that all the strains belong to the family Enterobacteriaceae. Phylogenetic analyses of the 16S rRNA genes of these novel isolates revealed that they formed a homogeneous cluster within Erwinia species. DNA signatures of these isolates were identical to those described for the genus Erwinia. The strains formed a homogeneous group as shown by DNA–DNA hybridization analysis and numerical analysis of phenotypic data, clearly differentiated from all species of Erwinia with validly published names. The data provide strong evidence of the differentiation of these strains from the most closely related species. Therefore, these isolates represent a novel species, for which the name Erwinia toletana sp. nov. is proposed. The isolates are available at CFBP, CECT and ATCC. The G+C content is 52±0·5 mol%. The type strain is CFBP 6631T (=A37T=ATCC 700880T=CECT 5263T)., This work was supported in part by a grant from the Universidad San Pablo CEU (Facultad de Ciencias Experimentales y de la Salud), Spain and NIH grant AI34829.

Mahieu Ronan, Mathieu Françoise, Robert Marie-José, Salesses Chantal. Les bénéficiaires des prestations légales versées par les CAF. In: Recherches et Prévisions, n°77, 2004. pp. 91-96.

Mycotoxins are naturally occurring toxic chemical compounds produced by fungi infesting agricultural crops both during crop growth and storage. Such secondary metabolites, when ingested, can produce toxic syndromes in humans. This study is the first survey that documents the occurrence of mycotoxins in stored barley in Tibet Autonomous Region [P.R. China]. Twenty-five samples of barley collected from Tibet were analyzed for the presence of aflatoxins, fumonisins, ochratoxins, zearalenone, deoxynivalenol, and T-2 toxin using an easy, sensitive, competitive direct enzyme-linked immunosorbent assay. Ninety-six percent of the samples were contaminated with zearalenone at concentrations ranging from 25 to 270 µg/kg. Seventy-six percent of the samples were contaminated with T-2 toxin at concentrations ranging from 1 to 163 µg/kg. In contrast, deoxynivalenol was observed in only 12% of the samples, with toxin concentrations ranging from 25 to 270 µg/kg. Aflatoxin was observed in only 4% of the contamina...

Vector control is one of the most valuable strategies to fight the expanding distribution of arthropod-borne diseases (ABDs). However, its implementation and monitoring are time consuming and labor intensive that may impede regular entomological survey in the field. To increase the impact of vector control strategies in fighting ABDs, the current entomological methods should be improved by new complementary tools. The exploration of the close interactions between the human host and the vector through the antigenic salivary proteins of hematophagous arthropods has lead to the development of new salivary biomarkers (SBs). This chapter focuses on the methodologies used to develop the SB of vector bites. The relevancy of these immunological biomarkers in assessing the human exposure to vector bites and their capacity to evaluate the efficacy of vector control strategies as well as the risk of pathogen transmission are also discussed. List of Abbreviations Ab Antibody ABDs Arthropod-Borne Diseases ADP Adenosine Diphosphate Ae. Aedes An. Anopheles gSG6 Anopheles gambiae Salivary Protein Ig Immunoglobulin ITN Insecticide-Treated Net kDa Kilodalton Lu. Lutzomyia P. Phlebotomus SB Salivary Biomarker SGEs Salivary Gland Extracts Th T Helper VCP Vector Control Program 1178 S. Doucoure et al.

International audience; Insensitive acetylcholinesterase resistance due to a mutation in the acetylcholinesterase (ace) encoding ace-1 gene confers cross-resistance to organophosphate and carbamate insecticides in Anopheles gambiae populations from Central and West Africa. This mutation is associated with a strong genetic cost revealed through alterations of some life history traits but little is known about the physiological and behavioural changes in insects bearing the ace-1(R) allele. Comparative analysis of the salivary gland contents between An. gambiae susceptible and ace-1(R) resistant strains was carried out to charaterize factors that could be involved in modifications of blood meal process, trophic behaviour or pathogen interaction in the insecticide-resistant mosquitoes. Differential analysis of the salivary gland protein profiles revealed differences in abundance for several proteins, two of them showing major differences between the two strains. These two proteins identified as saglin and TRIO are salivary gland-1 related proteins, a family unique to anopheline mosquitoes, one of them playing a crucial role in salivary gland invasion by Plasmodium falciparum sporozoites. Differential expression of two other proteins previously identified in the Anopheles sialome was also observed. The differentially regulated proteins are involved in pathogen invasion, blood feeding process, and protection against oxidation, relevant steps in the outcome of malaria infection. Further functional studies and insect behaviour experiments would confirm the impact of the modification of the sialome composition on blood feeding and pathogen transmission abilities of the resistant mosquitoes. The data supports the hypothesis of alterations linked to insecticide resistance in the biology of the primary vector of human malaria in Africa.

A radiological study of osteoarticular changes in Kashin-Beck Disease (KBD) was undertaken on the appendicular skeleton in 105 patients with KBD, in 31 healthy subjects living in an endemic area and in 30 healthy subjects living in a non-endemic area. The bone age was delayed in all three populations with no significant difference between the three studied Tibetan populations. Radiological changes occur in 56% of patients with KBD, and are usually bilateral. An analysis of the distribution of lesions shows a proximo-distal gradient. The changes are more common in the distal aspect of the limb and the lower limb is involved more commonly than the upper limb. The foot and ankle are involved in 89.5% of cases. The radiological changes and their distribution might be explained by the hypothesis of inhibition of angiogenesis by mycotoxins, exacerbated by chemical and physical environmental factors.

We carried out a cross-sectional study in 12 rural villages in order to identify the risk factors for Kashin-Beck disease in Tibet. Children aged 5-15 years (n=575) were examined and their corresponding houses were visited. Samples were collected in order to study fungal contamination of stored grain and the organic matter content of drinking water. Multivariate analysis was performed using logistic regression and population attributable fractions were computed to estimate the impact of each factor. The following variables were independently associated with the disease: age, gender, low socio-economic status, indicators of a poorly diversified diet, iodine deficiency and small water container size (with higher organic matter levels in small containers). Selenium deficiency was severe in all study subjects. The degree of fungal contamination of barley grain was related to the highest percentage of cases (65%) in a sample of the study population. Higher urinary iodine levels were not associated with decreasing prevalence rates when Alternaria sp. was isolated. The data that we report supports the hypothesis that Kashin-Beck disease occurs as a consequence of oxidative damage to cartilage and bone cells when associated with decreased antioxidant defence. Another mechanism that may coexist is bone remodelling stimulated by thyroid hormones whose actions can be blocked by certain mycotoxins.

In order to clarify the association between mycotoxin-producing fungi in food and Kashin-Beck disease (KBD), we examined the occurrence and contamination levels of fungi in samples of barley grain, from KBD-affected families and from unaffected families in endemic areas. A control area without the occurrence of KBD served as reference. The first results obtained in 1995 showed that total mesophilic fungal contamination of barley grain was consistently higher in families with KBD. Trichothecium roseum (Pers) Link ex gray, Dreschlera Ito and Alternaria Nees ex Fr. were the three most common fungi significantly associated with KBD. In 1996 we again observed a significant difference between affected and non-affected families, especially with Trichothecium roseum and Ulocladium Preuss. On this basis, measures to prevent KBD were suggested and a preventive program has been set up since 1998 in 20 new villages.

Kashin-Beck disease is a degenerative osteoarticular disorder that is endemic to certain areas of Tibet, where selenium deficiency is also endemic. Because selenium is involved in thyroid hormone metabolism, we studied the relation among the serum selenium concentration, thyroid function, and Kashin-Beck disease in 575 subjects 5 to 15 years of age in 12 villages around Lhasa, Tibet, including 1 control village in which no subject had Kashin-Beck disease. Clinical, radiologic, and biochemical data were collected.Among the 575 subjects, 280 (49 percent) had Kashin-Beck disease, 267 (46 percent) had goiter, and 7 (1 percent) had cretinism. Of the 557 subjects in whom urinary iodine was measured, 66 percent had a urinary iodine concentration of less than 2 microg per deciliter (157 nmol per liter; normal, 5 to 25 microg per deciliter [394 to 1968 nmol per liter]). The mean urinary iodine concentration was lower in subjects with Kashin-Beck disease than in control subjects (1.2 vs. 1.8 microg per deciliter [94 vs. 142 nmol per liter], P0.001) and hypothyroidism was more frequent (23 percent vs. 4 percent, P=0.01). Severe selenium deficiency was documented in all villages; 38 percent of subjects had serum concentrations of less than 5 ng per milliliter (64 nmol per liter; normal, 60 to 105 ng per milliliter [762 to 1334 nmol per liter]). When age and sex were controlled for in a multivariate analysis, low urinary iodine, high serum thyrotropin, and low serum thyroxine-binding globulin values were associated with an increased risk of Kashin-Beck disease, but a low serum selenium concentration was not.In areas where severe selenium deficiency is endemic, iodine deficiency is a risk factor for Kashin-Beck disease.Selenium is involved in thyroid hormone metabolism. Kashin-Beck disease is a degenerative osteoarticular disorder endemic to certain areas of Tibet, where selenium deficiency is also endemic. Findings are reported from an investigation of the relationship among serum selenium concentration, thyroid function, and Kashin-Beck disease in 575 subjects aged 5-15 years in 12 villages around Lhasa, Tibet, including 1 control village in which no one had Kashin-Beck disease. Clinical, radiologic, and biochemical data were collected. 280 (49%) subjects had Kashin-Beck disease, 267 (46%) had goiter, and 7 (1%) had cretinism. Of the 557 subjects in whom urinary iodine was measured, 66% had a urinary iodine concentration of less than 2 mcg/dl. Mean urinary iodine concentration was lower in subjects with Kashin-Beck disease than in control subjects and hypothyroidism was more frequent. Severe selenium deficiency was documented in all villages, with 38% of subjects having serum concentrations of less than 5 ng/ml. When age and sex were controlled for in a multivariate analysis, low urinary iodine, high serum thyrotropin, and low serum thyroxine-binding globulin values were associated with an increased risk of Kashin-Beck disease, but a low serum selenium concentration was not.

A method is presented in which the reduced complexity and non-stoichiometric amplification intrinsic to RNA arbitrarily primed PCR fingerprinting (RAP-PCR) is used to advantage to generate probes for differential screening of cDNA arrays. RAP-PCR fingerprints were converted to probes for human cDNA clones arrayed as Escherichia coli colonies on nylon membranes. Each array contained 18 432 cDNA clones from the IMAGE consortium. Hybridization to approximately 1000 cDNA clones was detected using each RAP-PCR probe. Different RAP-PCR fingerprints gave hybridization patterns having very little overlap (

RNA fingerprinting by arbitrarily primed polymerase chain reaction (RAP-PCR) was used to identify genes that were differentially expressed during the life cycle of Trypanosoma brucei , as well as in response to heat shock. The standard RAP-PCR protocol was varied in two ways. First, the PCR reactions sometimes included a primer derived from the 5′ mini-exon sequence, to ensure that most of the products contained the 5′ end of mRNAs. Second, differentially amplified products were reamplified, isolated on single strand conformation polymorphism (SSCP) gels, cloned, and sequenced. Clones representing 32 different expressed sequence tags (ESTs) were obtained. Twenty-four ESTs were confirmed as differentially expressed by RT-PCR between different stages of the parasite cycle, or in response to temperature elevation. Nine clones had significant similarities to sequences already in the database. These transcripts included genes encoding cell surface proteins, metabolic enzymes, and heat shock proteins, either from trypanosomes or other organisms. Of particular interest, ESAG1 was shown to be heat-inducible in the procyclic stage. Most of the transcripts were unrelated to any other sequences in the database, and were deposited as new ESTs. The identification of stage-specific and heat shock-regulated transcripts will complement the growing T. brucei database. In addition, this experimental approach allows previous entries in the sequence database to be annotated with regulatory information.

Clinical manifestations of Kashin-Beck disease have been studied in Central Tibet. Statistical analysis of physical signs allowed a definition of the clinical diagnosis and a scale for the functional severity for the disease to be drawn up. This classification is used for the assessment of patients who received palliative physical treatment. A group of 136 patients have been examined and their disabled joints classified according to pain, bony enlargement and restriction of movement. 57% were between 20 and 35 years of age. The patients mainly complained about their distal weightbearing joints. The clinical evolution of the disease is described from childhood to adult life.

Dumon JC, Wantier H, Mathieu F, Mantia M, Body JJ, Technical and clinical validation of a new immunoradiometric assay for human osteocalcin. Eur J Endocrinol 1996;135:231–7. ISSN 0804–4643 The measurement of circulating osteocalcin or bone GLA protein (BGP) constitutes a well established and non-invasive means for evaluating preferentially the bone formation rate, but most available commercial assays suffer from several technical constraints, notably a rapid degradation of BGP at room temperature or after thawing and the inability to measure subnormal values. We evaluated, from a technical and a clinical viewpoint, a newly available two-site sandwich immunoradiometric assay (IRMA) using standards of human origin and two different monoclonal antibodies. The theoretical and functional assay detection limit was 0.3 ng/ml. Concentrations of BGP progressively decreased when the serum was left at 4°C or at room temperature (mean apparent loss of 15% after 24 h). Two cycles of freezing–thawing only slightly reduced the BGP concentrations. The mean (± sd) BGP concentration was 19.6 ± 7.9 ng/ml in healthy subjects (NI, N = 61); the normal range was 8.1–35.6 ng/ml. There was a marked difference between pre- and postmenopausal women: 15.1 ±4.4 vs 22.3 ± 8.4 ng/ml, respectively (p JJ Body, Institut Jules Bordet, Rue Héger-Bordet 1, 1000 Brussels, Belgium

Arbitrarily primed PCR fingerprinting of RNA and differential display resolved on an acrylamide gel has been extensively used to detect differentially expressed RNAs. However, after a differentially amplified product is detected the next steps are labor-intensive: a small portion of the fingerprinting gel that contains the differentially amplified product is cut out, reamplified and the correct product is determined, typically by cloning and sequencing what is often a mixture of products of similar size. Here we use a native acrylamide gel to separate DNAs in the reamplified mixture based on single-stranded conformation polymorphisms. Reamplifications are performed for the region carrying the differentially amplified product and a corresponding region from an adjacent lane where the product is less prominent or not visible. Denaturation of the reamplified DNA followed by side-by-side comparison on an SSCP gel allows the classification of reamplified material into (i) those that can be directly cloned because the differentially amplified product is relatively pure, (ii) those that need to be reamplified from the SSCP gel before cloning and (iii) those that are too complex for further study. This screen should save considerable effort now wasted on directly cloning unsuitable products from RNA fingerprinting experiments. An example is presented of cloning a gene differentially expressed in Trypanosoma brucei life cycle.

Deux mois apres le retour de Charles ii a Londres en 1660, Thomas Killigrew, un des favoris de Charles ii, et Sir William Davenant – qui, apres avoir compose les Masques les plus fastueux a la cour de Charles ier, avait presente, des 1656, en plein Commonwealth, son Siege de Rhodes, la premiere piece anglaise toute en musique avec recitatifs et arias –, obtinrent du roi le monopole absolu des representations theâtrales a Londres, en aout 1660. En octobre 1660, Killigrew constituait la « King...

Mycotoxins are naturally occurring toxic chemical compounds produced by fungi infesting agricultural crops both during their growth and storage. Such secondary metabolites, when ingested, can produce toxic syndromes in humans. As it has been suggested that mycotoxins might be involved in the development of Kashin-Beck disease (KBD), we undertook a survey of barley grains of KBD-affected families and non-affected families in that country. We found, by thin layer chromatography, a hitherto unknown metabolite of Alternaria sp. This was especially common on the barley grains of KBD-affected families.

A cross-sectional survey was carried out in order to study the relationship between Kashin-Beck disease and drinking water. The average volume of the water containers was larger in families unaffected by the disease. Organic material was measured by ultraviolet (UV) spectroscopy. The UV absorbency was significantly lower in drinking water of unaffected families. Thus, the organic material in drinking water may play a role in the pathogenesis of Kashin-Beck disease.

We evaluated iodine and selenium status in 575 children between 5 and 15 years with Kashin-Beck disease from endemic and non-endemic areas. Of these 267 (46%) children had goiter. The proportion of subjects with goiter was higher in the villages with Kashin-Beck disease than in the control village. In the villages with Kashin-Beck disease, 105 (23%) of the subjects had a serum thyrotropin greater than 10 mU/l as compared with 3 (4%) in the control village. The percentages of low serum thyroxine values and low serum tri-iodothyronine were greater in the villages where Kashin-Beck disease was endemic than in the control village. The percentages of low urinary iodine concentration were significantly greater in the subjects with Kashin-Beck disease. The results suggest that in areas where severe selenium deficiency is endemic, iodine deficiency is a risk factor for Kashin-Beck disease.

Extracellular factors produced byLeishmania spp., Trypanosoma cruzi,andTrypanosoma bruceiare important in the host-parasite relationship. Here, we describe a genome-based approach to identify putative extracellular proteins conserved among trypanosomatids that are likely involved in the classical secretory pathway. Potentially secreted proteins were identified by bioinformatic analysis of theT. cruzigenome. A subset of thirteen genes encoding unknown proteins with orthologs containing a signal peptide sequence inL. infantum, L. major,andT. bruceiwere transfected intoL. infantum. Tagged proteins detected in the extracellular medium confirmed computer predictions in about 25% of the hits. Secretion was confirmed for twoL. infantumorthologs proteins using the same experimental system. Infectivity studies of transgenicLeishmaniaparasites suggest that one of the secreted proteins increases parasite replication inside macrophages. This methodology can identify conserved secreted proteins involved in the classical secretory pathway, and they may represent potential virulence factors in trypanosomatids.

Plus de trois millions de personnes en France métropolitaine bénéficient d'un revenu minimum. La répartition géographique des bénéficiaires dessine une carte de la pauvreté. Le sud de la ligne Calvados-Alpes-Maritimes révèle une pauvreté surtout rurale et masculine de personnes âgées et de handicapés. Par contre, l'isolement se rencontre dans le pourtour méditerranéen et dans le nord de la France, et les faibles ressources dans les régions fortement marquées par le chômage., Mathieu Françoise. Une carte de France de la pauvreté : les bénéficiaires des minima sociaux. In: Recherches et Prévisions, n°29-30, Septembre – décembre 1992. Etudes locales : collaborations CAF / INSEE. pp. 57-62.

In previous studies we observed a proximo-distal gradient of lesion frequencies along the limb, with the distal joints being the most often affected. This suggests an associated effect of environmental factors on the most exposed joints. On a population of 820 children (mean age 13 years) of endemic areas distributed in groups of healthy and severity stages I to III of KBD (Kashin-Beck disease), the effects of different working activities were studied. Heavy work like that of a ploughman were compared to light physical work, e.g. school children, and exposure to cold and history of frostbite were also considered. The most severe stages, II and III, were present in 72% of the ploughman vs. 29% of the schoolchildren, 70% of the shepherds vs. 30% (p < 0.001) of the schoolchildren, and in 65% of the shepherds working in winter vs. 40% of those working in the other seasons (p < 0.001). In the group with history of frostbite, 58% present the severest stages vs. 40% without (p < 0.001). The results confirm a highly significant relation between microtrauma and cold and the severity of the KBD alterations.

Six Congolese and 3 Zairian Trypanosoma brucei stocks were studied by isozyme cellulose acetate electrophoresis. Twenty isozyme systems were used, of which only 5 showed variability. These 5 polymorphic systems made it possible to identify 5 different zymodemes. Zymodemes isolated from man were recorded both from pig and sheep too, which confirms the results of previous authors. This favors the existence of an animal reservoir of human African trypanosomiasis in the Congo, which could play a role in the transmission of the disease, at least by the maintenance of residual foci.

Circular extrachromosomal elements were observed in a variety of Leishmania species. We show here that two lines originating from the same isolate have been found to contain a circular DNA molecule of 26.6 kb and a linear chromosome of about 250 kb, respectively, which share a homology of more than 20 kb. The circular DNA molecule and its related region on the linear chromosome were cloned and their restriction maps compared. This investigation reveals information about chromosome rearrangement in L. mexicana M379. Further examination will enable us to understand the nature of chromosome rearrangement such as circularization or linearization.