Ancient Human Parasites in Ethnic Chinese Populations

Whilst archaeological evidence for many aspects of life in ancient China is well studied, there has been much less interest in ancient infectious diseases, such as intestinal parasites in past Chinese populations. Here, we bring together evidence from mummies, ancient latrines, and pelvic soil from burials, dating from the Neolithic Period to the Qing Dynasty, in order to better understand the health of the past inhabitants of China and the diseases endemic in the region. Seven species of intestinal parasite have been identified, namely roundworm, whipworm, Chinese liver fluke, oriental schistosome, pinworm, Taenia sp. tapeworm, and the intestinal fluke Fasciolopsis buski. It was found that in the past, roundworm, whipworm, and Chinese liver fluke appear to have been much more common than the other species. While roundworm and whipworm remained common into the late 20th century, Chinese liver fluke seems to have undergone a marked decline in its prevalence over time. The iconic transport route known as the Silk Road has been shown to have acted as a vector for the transmission of ancient diseases, highlighted by the discovery of Chinese liver fluke in a 2,000 year-old relay station in northwest China, 1,500 km outside its endemic range

Variation in the psychosocial determinants of the intention to prescribe hormone therapy prior to the release of the Women's Health Initiative trial: a survey of general practitioners and gynaecologists in France and Quebec

BACKGROUND: Theory-based approaches are advocated to improve our understanding of prescription behaviour. This study is an application of the theory of planned behaviour (TPB) with additional variables. It was designed to assess which variables were associated with the intention to prescribe hormone therapy (HT). In addition, variations in the measures across medical specialities (GPs and gynaecologists) and across countries (France and Quebec) were investigated. METHODS: A survey among 2,000 doctors from France and 1,044 doctors from Quebec was conducted. Data were collected by means of a self-administered questionnaire. A clinical vignette was used to elicit doctors' opinions. The following TPB variables were assessed: attitude, subjective norm, perceived behavioural control, attitudinal beliefs, normative beliefs and power of control beliefs. Additional variables (role belief, moral norm and practice pattern-related factors) were also assessed. A stepwise logistic regression was used to assess which variables were associated with the intention to prescribe HT. GPs and gynaecologists were compared to each other within countries and the two countries were compared within the specialties. RESULTS: Overall, 1,085 doctors from France returned their questionnaire and 516 doctors from Quebec (response rate = 54% and 49%, respectively). In the overall regression model, power of control beliefs, moral norm and role belief were significantly associated with intention (all at p < 0.0001). The models by specialty and country were: for GPs in Quebec, power of control beliefs (p < 0.0001), moral norm (p < 0.01) and cytology and hormonal dosage (both at p < 0.05); for GPs in France, power of control beliefs and role belief (both at p < 0.0001) and perception of behavioural control (p < 0.05) and cessation of menses (p < 0.01); for gynaecologists in Quebec, moral norm and power of control beliefs (both at p = 0.01); and for gynaecologists in France, power of control beliefs (p < 0.0001), and moral norm, role belief and lipid profile (all at p < 0.05). CONCLUSION: In both countries, compared with GPs, intention to prescribe HT was higher for gynaecologists. Psychosocial determinants of doctors' intention to prescribe HT varied according to the specialty and the country thus, suggesting an influence of contextual factors on these determinants

Organizational and managerial factors associated with clinical practice guideline adherence: a simulation-based study in 36 French hospital wards

International audienceObjectives: To identify managerial and organizational characteristics of multi-specialty medicine wards and individual characteristics of health professionals that are most strongly associated with clinical practice guidelines (CPG) adherence.Design: Cross-sectional stratified cluster sample design.Setting: Data were gathered from 36 randomly selected multi-specialty medicine wards.Participants: The study population included all health professionals involved in patient care working in the participating wards.Main outcome measures: The degree of CPG adherence was measured using clinical vignettes on three topics: pain management, managing heart failure and managing diabetes. Responses from each professional to each clinical case were quantified using a 10-point scale. Managerial and organizational characteristics of medical department and individual characteristics of health professionals were obtained using three questionnaires.Results: The study sample consisted of 859 professionals (362 orderlies, 361 nurses and 136 physicians). Factors independently and positively associated with CPG adherence were (i) individual factors: low age of professionals, expertise in diabetology and activity in cardiology; (ii) organizational and managerial factors: good understanding between physicians and other personnel; and (iii) structural factors: computer-based test results and prescriptions, presence of medical specialists, inter-department mobility of orderlies, medium-length stay (between 7 and 10 days) and large bed capacity.Conclusions: Good CPG adherence in general medicine needs institutional dynamism, availability of clinical competence and team culture based on cooperation

Adult Cerebellar Ataxia, Axonal Neuropathy, and Sensory Impairments Caused by Biallelic SCO2 Variants

International audienceSCO2 encodes a 266-amino-acid metallochaperone involved in copper supply for the assembly of cytochrome c oxidase or complex IV (CIV). CIV is the terminal enzyme of the energy-transducing respiratory chain that transfers electrons from reduced cytochrome c to oxygen via 3 copper ions.1 SCO2 pathogenic variants were first identified in children with hypertrophic cardiomyopathy, often associated with developmental delay and lactic acidosis2 (Figure, A). SCO2 variants were then reported in children with Leigh syndrome3 and early-onset axonal neuropathy,4 possibly associated with cerebellar ataxia5 (Figure, A). Here, we report heterozygous missense SCO2 variants in a 48-year-old patient presenting with a complex neurologic and sensory phenotype comprising cerebellar ataxia, sensory neuronopathy, deafness, pigmentary retinopathy, and cataract

Custom oligonucleotide array-based CGH: a reliable diagnostic tool for detection of exonic copy-number changes in multiple targeted genes

International audiencehe frequency of disease-related large rearrangements (referred to as copy-number mutations, CNMs) varies among genes, and search for these mutations has an important place in diagnostic strategies. In recent years, CGH method using custom-designed high-density oligonucleotide-based arrays allowed the development of a powerful tool for detection of alterations at the level of exons and made it possible to provide flexibility through the possibility of modeling chips. The aim of our study was to test custom-designed oligonucleotide CGH array in a diagnostic laboratory setting that analyses several genes involved in various genetic diseases, and to compare it with conventional strategies. To this end, we designed a 12-plex CGH array (135k; 135 000 probes/subarray) (Roche Nimblegen) with exonic and intronic oligonucleotide probes covering 26 genes routinely analyzed in the laboratory. We tested control samples with known CNMs and patients for whom genetic causes underlying their disorders were unknown. The contribution of this technique is undeniable. Indeed, it appeared reproducible, reliable and sensitive enough to detect heterozygous single-exon deletions or duplications, complex rearrangements and somatic mosaicism. In addition, it improves reliability of CNM detection and allows determination of boundaries precisely enough to direct targeted sequencing of breakpoints. All of these points, associated with the possibility of a simultaneous analysis of several genes and scalability 'homemade' make it a valuable tool as a new diagnostic approach of CNMs

Additional file 1: Table S1. of A novel somatic mutation in ACD induces telomere lengthening and apoptosis resistance in leukemia cells

Description of data: Non-synonymous and frame-shift mutations in ACD referenced in the public cancer database COSMIC version 71. (PDF 120 kb

Whole-exome sequencing reveals a rapid change in the frequency of rare functional variants in a founding population of humans

Whole-exome or gene targeted resequencing in hundreds to thousands of individuals has shown that the majority of genetic variants are at low frequency in human populations. Rare variants are enriched for functional mutations and are expected to explain an important fraction of the genetic etiology of human disease, therefore having a potential medical interest. In this work, we analyze the whole-exome sequences of French-Canadian individuals, a founder population with a unique demographic history that includes an original population bottleneck less than 20 generations ago, followed by a demographic explosion, and the whole exomes of French individuals sampled from France. We show that in less than 20 generations of genetic isolation from the French population, the genetic pool of French-Canadians shows reduced levels of diversity, higher homozygosity, and an excess of rare variants with low variant sharing with Europeans. Furthermore, the French-Canadian population contains a larger proportion of putatively damaging functional variants, which could partially explain the increased incidence of genetic disease in the province. Our results highlight the impact of population demography on genetic fitness and the contribution of rare variants to the human genetic variation landscape, emphasizing the need for deep cataloguing of genetic variants by resequencing worldwide human populations in order to truly assess disease risk

Rare allelic forms of PRDM9 associated with childhood leukemogenesis

One of the most rapidly evolving genes in humans, PRDM9, is a key determinant of the distribution of meiotic recombination events. Mutations in this meiotic-specific gene have previously been associated with male infertility in humans and recent studies suggest that PRDM9 may be involved in pathological genomic rearrangements. In studying genomes from families with children affected by B-cell precursor acute lymphoblastic leukemia (B-ALL), we characterized meiotic recombination patterns within a family with two siblings having hyperdiploid childhood B-ALL and observed unusual localization of maternal recombination events. The mother of the family carries a rare PRDM9 allele, potentially explaining the unusual patterns found. From exomes sequenced in 44 additional parents of children affected with B-ALL, we discovered a substantial and significant excess of rare allelic forms of PRDM9. The rare PRDM9 alleles are transmitted to the affected children in half the cases; nonetheless there remains a significant excess of rare alleles among patients relative to controls. We successfully replicated this latter observation in an independent cohort of 50 children with B-ALL, where we found an excess of rare PRDM9 alleles in aneuploid and infant B-ALL patients. PRDM9 variability in humans is thought to influence genomic instability, and these data support a potential role for PRDM9 variation in risk of acquiring aneuploidies or genomic rearrangements associated with childhood leukemogenesis.Julie Hussin, Daniel Sinnett, Ferran Casals, Youssef Idaghdour, Vanessa Bruat, Virginie Saillour, Jasmine Healy, Jean-Christophe Grenier, Thibault de Malliard, Stephan Busche, Jean-François Spinella, Mathieu Larivière, Greg Gibson, Anna Andersson, Linda Holmfeldt, Jing Ma, Lei Wei, Jinghui Zhang, Gregor Andelfinger, James R. Downing, Charles G. Mullighan, and Philip Awadall

ATP2B2 de novo variants as a cause of variable neurodevelopmental disorders that feature dystonia, ataxia, intellectual disability, behavioral symptoms, and seizures

Purpose: ATP2B2 encodes the variant-constrained plasma-membrane calcium-transporting ATPase-2, expressed in sensory ear cells and specialized neurons. ATP2B2/Atp2b2 variants were previously linked to isolated hearing loss in patients and neurodevelopmental deficits with ataxia in mice. We aimed to establish the association between ATP2B2 and human neurological disorders. Methods: Multinational case recruitment, scrutiny of trio-based genomics data, in-silico analyses, and functional variant characterization were performed. Results: We assembled seven individuals harboring rare, predicted deleterious heterozygous ATP2B2 variants. The alleles comprised five missense substitutions affecting evolutionarily conserved sites and two frameshift variants in the penultimate exon. For six variants, a de-novo status was confirmed. Unlike described patients with hearing loss, the individuals displayed a spectrum of neurological abnormalities, ranging from ataxia with dystonic features to complex neurodevelopmental manifestations with intellectual disability, autism, and seizures. Two cases with recurrent amino-acid variation showed distinctive overlap with cerebellar atrophy-associated ataxia and epilepsy. In cell-based studies, all variants caused significant alterations in cytosolic calcium handling with both loss- and gain-of-function effects. Conclusion: Presentations in our series recapitulate key phenotypic aspects of Atp2b2-mouse models and underline the importance of precise calcium regulation for neurodevelopment and cerebellar function. Our study documents a role for ATP2B2 variants in causing heterogeneous neurodevelopmental and movement-disorder syndromes