Psychometric properties of the HSE Indicator Tool: evidence from Argentina.

BACKGROUND: The Health and Safety Executive's Management Standards Indicator Tool (MSIT) is a 35-item self-report questionnaire that assesses seven psychosocial risk factors associated with work-related stress. Although the instrument has been validated in the UK, Italy, Iran and Malta, no validation studies have been carried out in Latin America. AIMS: To examine the factor structure, validity and reliability of the MSIT among Argentine employees. METHODS: A sample of employees of different organizations from Rafaela and Rosario, Argentina, completed an anonymous questionnaire that included the Argentine MSIT and specific scales to measure job satisfaction, workplace resilience and perceived mental and physical health (12-item Short Form Health Survey). Confirmatory factor analysis was used to determine the factor structure of the Argentine MSIT. RESULTS: A total of 532 employees participated in the study (74% response rate). After testing three measurement models, the final respecified model was composed of 24 items distributed in six factors (demands, control, manager support, peer support, relationships and role clarity), showing satisfactory fit indices. The original MSIT change factor was discarded. Composite reliability ranged from 0.70 to 0.82. Although all dimensions showed adequate discriminant validity, convergent validity for control, role clarity and relationships is a matter of concern (average variance extracted values ≤ 0.50). Criterion-related validity was demonstrated by significant correlations between the MSIT subscales and job satisfaction, workplace resilience and mental and physical health. CONCLUSIONS: The Argentine version of the MSIT presents good psychometric properties for use among employees of the region. Further research is needed to provide more evidence on the convergent validity of the questionnaire.

Experience of a multidisciplinary task force with exome sequencing for Mendelian disorders.

BACKGROUND: In order to optimally integrate the use of high-throughput sequencing (HTS) as a tool in clinical diagnostics of likely monogenic disorders, we have created a multidisciplinary "Genome Clinic Task Force" at the University Hospitals of Geneva, which is composed of clinical and molecular geneticists, bioinformaticians, technicians, bioethicists, and a coordinator. METHODS AND RESULTS: We have implemented whole exome sequencing (WES) with subsequent targeted bioinformatics analysis of gene lists for specific disorders. Clinical cases of heterogeneous Mendelian disorders that could potentially benefit from HTS are presented and discussed during the sessions of the task force. Debate concerning the interpretation of identified variants and the content of the final report constitutes a major part of the task force's work. Furthermore, issues related to bioethics, genetic counseling, quality control, and reimbursement are also addressed. CONCLUSIONS: This multidisciplinary task force has enabled us to create a platform for regular exchanges between all involved experts in order to deal with the multiple complex issues related to HTS in clinical practice and to continuously improve the diagnostic use of HTS. In addition, this task force was instrumental to formally approve the reimbursement of HTS for molecular diagnosis of Mendelian disorders in Switzerland.

Reference range for thyrotropin. Post hoc assessment.

UNLABELLED: Setting the reference range for thyrotropin (TSH) remains a matter of ongoing controversy. PATIENTS, METHODS: We used an indirect method to determine the TSH reference range post hoc in a large sample. A total of 399 well characterised subjects showing no evidence of thyroid dysfunction were selected for definition of the TSH reference limits according to the method of Katayev et al.. To this end, the cumulative frequency was plotted against the individual logarithmic TSH values. Reference limits were calculated by extrapolating the middle linear part of the regression line to obtain the cut-offs for the 95% confidence interval. We also examined biological variation in a sample of 65 subjects with repeat measurements to establish reference change values (RCVs). RESULTS: Based on these, the reference interval obtained by the novel technique was in close agreement with the conventionally established limits, but differed significantly from earlier recommendations. DISCUSSION: Following unverified recommendations could result in a portion of patients with subclinical thyroid dysfunctions being missed, an important consideration in a setting with a high prevalence of thyroid autonomy. CONCLUSION: Indirect post hoc verification of reference intervals from a large retrospective sample is a modern approach that gives plausible results. The method seems particularly useful to assess the adequacy and performance of reference limits reported or established by others in a particular setting. The present data should encourage re-evaluation of reference systems on a broader scale.

Risk factors associated with the presence of Varroa destructor in honey bee colonies from east-central Argentina.

Varroa destructor is considered one of the major threats for worldwide apiculture. Damage caused by varroa mite includes body weight loss, malformation and weakening of the bees. It was also suggested as the main cause associated with colony winter mortality and as an important vector for several honey bee viruses. Little is known about multiple factors and their interaction affecting V. destructor prevalence in apiaries from South America. The aim of this study was to identify risk factors associated with V. destructor prevalence in east-central Argentina. Parasitic mite infestation level and colony strength measures were evaluated in 63 apiaries distributed in 4 different regions in east-central Argentina in a cross sectional study. Data regarding management practices in each apiary were collected by means of a questionnaire. A mixed-effects logistic regression model was constructed to associate management variables with the risk of achieving mite infestation higher than 3%. Colonies owned by beekeepers who indicated that they did not monitor colonies after mite treatment (OR=2.305; 95% CI: 0.944-5.629) nor disinfect hives woodenware material (OR=2.722; 95% CI: 1.380-5.565) were associated with an increased risk of presenting high intensity infestation with V. destructor (>3%). On the other hand, beekeepers who reported replacing more than 50% of the queens in their operation (OR=0.305; 95% CI: 0.107-0.872), feeding colonies protein substitute containing natural pollen (OR=0.348; 95% CI: 0.129-0.941) and feeding colonies High Fructose Corn Syrup (HFCS) (OR=0.108; 95% CI: 0.032-0.364), had colonies that were less likely to have V. destructor infestations above 3%, than beekeepers who did not report using these management practices. Further research should be conducted considering that certain management practices were associated to mite infestation level in order to improve the sanitary condition in the colonies. Epidemiological studies provide key information to design surveillance programs against one the major threat to worldwide beekeeping.

[Trophoblastic diseases: a multidisciplinary approach, a first Swiss center]. / Maladies trophobtastiques: une prise en charge pluridisciplinaire, un premier centre suisse.

Trophoblastic diseases are rare and complex. The Center for trophoblastic diseases, the first in Switzerland, was founded in Geneva in January 2009 to formalize the collaboration between obstetricians-gynecologists, pathologists, geneticists, radiologists and oncologists. At the physician's request and with patient consent, an integrative diagnosis is proposed after centralized review of the histological slides, anti-p57KIP2 immunohistochemistry, and ploidy analysis by QF-PCR (Quantitative fluorescent polymerase chain reaction). The referring physician receives treatment and beta-hCG dosage recommendations. This pluridisciplinary diagnostic and therapeutic approach allows optimal surveillance and treatment of patients.

Increased methylation of glucocorticoid receptor gene (NR3C1) in adults with a history of childhood maltreatment: a link with the severity and type of trauma.

Childhood maltreatment, through epigenetic modification of the glucocorticoid receptor gene (NR3C1), influences the hypothalamic-pituitary-adrenal axis (HPA axis). We investigated whether childhood maltreatment and its severity were associated with increased methylation of the exon 1(F) NR3C1 promoter, in 101 borderline personality disorder (BPD) and 99 major depressive disorder (MDD) subjects with, respectively, a high and low rate of childhood maltreatment, and 15 MDD subjects with comorbid post-traumatic stress disorder (PTSD). Childhood sexual abuse, its severity and the number of type of maltreatments positively correlated with NR3C1 methylation (P=6.16 × 10(-8), 5.18 × 10(-7) and 1.25 × 10(-9), respectively). In BPD, repetition of abuses and sexual abuse with penetration correlated with a higher methylation percentage. Peripheral blood might therefore serve as a proxy for environmental effects on epigenetic processes. These findings suggest that early life events may permanently impact on the HPA axis though epigenetic modifications of the NR3C1. This is a mechanism by which childhood maltreatment may lead to adulthood psychopathology.

Specific language impairment as the prominent feature in a patient with a low-level trisomy 21 mosaicism.

BACKGROUND: The extent and severity of the disabilities is variable among individuals with Down syndrome, although generally characterized by a range of physical and intellectual conditions, including language impairment. Whether the language deficit is due to the intellectual disability (ID) or associated to the supernumerary or portion of chromosome 21 is still debated. METHODS: Karyotyping was performed on blood lymphocyte and skin fibroblasts. Fluorescence in situ hybridization analysis was performed on cultured lymphocytes and buccal smear cells. RESULTS: The trisomy 21 (T21) mosaicism was characterized by 0.7-10% of mosaic cells in the different tissues, in a 14-year-old girl presenting an intellectual development within the normal range and specific language impairment (SLI) as the only prominent feature. CONCLUSION: This case illustrates the wide range of phenotypical abnormalities possibly associated with T21 mosaicism. We propose that SLI is indeed a phenotypic trait specific to Down syndrome rather than subsequent to the ID most often associated to the syndrome.

Six cases of cryptic subtelomeric translocations in four families: the use of subtelomeric FISH probes as a diagnostic tool.

Finding the diagnosis in children with mental retardation and a normal karyotype, whether or not associated with dysmorphic features, is important for defining an eventual syndrome and for genetic counselling of the families. Telomeric re-arrangements may be a common and underestimated-to-date cause of non-syndromic mental retardation. Using a FISH-based approach combining subtelomeric probes, we report the detection of 4 cases of cryptic translocations t(2;10)(p25.3;q26.3), t(4;17)(p16.2;q25), t(4;20)(p16.2;q13) and t(5;7)(p15.3;q36) associated with MR and dysmorphic features. We discuss the usefulness of subtelomeric FISH in children with unexplained delayed psychomotor development, when the genetic cause remains unknown and the karyotype is normal.

The role of DMDs in the maintenance of epigenetic states.

An important aspect of genome reprogramming is the establishment and maintenance of gamete-specific DNA methylation patterns that distinguish the parental alleles of imprinted genes. Disrupting the accurate transmission of genomic imprints by interfering with these methylation patterns causes severe defects in fetal growth and development. The inheritance of sex-specific DNA methylation patterns from both parents is thus a fundamental molecular definition of genomic imprinting. The other cardinal aspect is the regulation of imprinted gene expression over a long genomic distance, spanning a few clustered imprinted genes. There is converging experimental evidence that differentially methylated domains (DMDs), located in non-coding regions of imprinted genes, are involved in both processes. As such, DMDs are the imprinting backbone upon which the fundamental processes of sex-specific methylation and imprinted gene expression are built.

[A conflict within the genome, the battle of the sexes?]. / Empreinte génomique, la bataille des sexes?

It is estimated that 100 to 200 genes in the human genome are imprinted. These are expressed only from one parental allele, although having the same DNA sequence. Several of the known imprinted genes have been shown to be involved in fetal and placental growth, and imprinting defects can lead to embryonic, developmental defects as well as cancer. This mechanism of gene regulation probably emerged 150 million years ago in mammals. The reasons for the appearance and maintenance of this phenomenon throughout evolution are still controversial.

Parenteral nutrition practices in hospital pharmacies in Switzerland, France, and Belgium.

OBJECTIVE: Important changes in administering total parenteral nutrition (PN) admixtures have occurred over the past decade. This study describes hospital pharmacists' practices in France (F), Switzerland (CH), and Belgium (B). METHODS: From the responses received using a standardized questionnaire, (n = 378) we determined the origin, types of container used, and choice of PN formula (standard versus tailor-made) and the type of quality control and the existence of nutrition support teams. RESULTS: The mean response rates were 55.6% (CH), 30.5% (F), and 24.5% (B). Standard formulas were used mainly for adult patients (CH, 86%; F, 79%; B, 86%), whereas approximately 50% of tailor-made PN bags were used for children. Single-compartment or multicompartment bags or glass bottles contained standard formulas. Most standard formulas were provided by industry, apart from (B), where 50% of PN solutions were compounded by hospital pharmacies. Single-compartment bags contained generally tailor-made formulas produced exclusively by hospital pharmacies in (CH) and (B), whereas 33% were provided by industry in (F). Quality controls were mostly visual and occurred in 75% to 95% of hospitals. Nutrition support teams were present in 32% to 45% of hospitals. CONCLUSION: The choice, origin, and type of container used for PN formulas were highly variable among countries. However, the use of standard formulas in bags was predominant in (CH) and (B). The function of nutrition support teams was similar in (F), (CH), and (B).

Genomic interactions with disease and nutrition.

The putative influence of genomic factors on the responsiveness to nutrient intake is a newly developed field of research. As well, there is growing interest for determining the interactions between nutrient, inflammation and aging and the possible impact on lifespan and disease development. Inflammation adversely affects health in many diseases with an inflammatory basis, such as atherosclerosis, obesity and type 2 diabetes mellitus. The metabolic effects of inflammation are mediated by pro-inflammatory cytokines. Metabolic effects include insulin insensitivity, hyperlipidemia, muscle protein loss and oxidant stress. Aging is also characterized by an increase in inflammatory stress and contains some of the hallmarks of inflammatory disease. It is also a phase of life when inflammatory diseases rise in incidence. Evidence is accumulating that the individual level of cytokine production is influenced by single nucleotide polymorphisms (SNPs) in cytokine genes. The combination of SNPs might control the relative level of inflammatory stress following inflammatory stimuli and diseases. These genomic characteristics might therefore influence lifespan, morbidity and mortality in diseases with an infectious or inflammatory basis.Recent studies indicate that genotypic factors may influence the effectiveness of such immunonutrients as anti-oxidants and n-3 polyunsaturated fatty acids. A better understanding of this aspect of nutrient gene interactions and of the genomic factors which influence the intensity of inflammation in disease will help in the targeting of nutritional therapy.

Genetics and nutrition.

The understanding of the role of nutrients on DNA stability, repair and on the different gene expression processes recently became more prominent in nutritional science. Nutrients and the genomics interact at two levels. Nutrients can induce gene expression thereby altering individual phenotype. Conversely single nucleotide polymorphisms, in a range of genes important in inflammation and lipid metabolism, alter the bioactivity of important metabolic pathways and mediators and influence the ability of nutrients to interact with them. The study on single effects of nutrients on the individual's phenotype as well as the serial analyses of gene expression patterns in response to specific nutrients will help us to understand how metabolic homeostasis is maintained. Considering that there is wide variation in the ability of nutritional factors to modulate the expression of detrimental or protective proteins at an individual level, the concept of diet-medication could be developed in the light of a better understanding of nutrient-gene interactions. In this way, 'good responders' and 'poor responders' to diet therapy can be identified. Furthermore, as several vitamins participate in DNA protection and genomic stabilisation, diet-linked therapies could become part of cancer prevention and other treatments with relevant consequences for human health.

Pregnancy outcome of 30 fetuses with cystic hygroma diagnosed during the first 15 weeks of gestation.

The goal of the study was to assess the prognostic value of ultrasound finding of fetal cystic hygromas. Thirty cases of septated cystic hygromas were diagnosed at 10-15 weeks gestation by transabdominal ultrasound and followed through pregnancy. The rate of abnormal karyotype was found to be 61% and the global rate of unfavorable outcome, independently of karyotype result, as high as 96%. These data suggest that cautious genetic counselling should be offered when such cystic hygromas are noticed during the first 15 weeks of gestation, even with a normal karyotype.

A case of (X;15) translocation diagnosed as a paracentric inversion of Xp: diagnostic revision with FISH.

In 1990 we reported the case of a 17 years old girl with growth retardation, overweight and primary amenorrhea, presenting a de novo chromosomal rearrangement cytogenetically characterized as a paracentric inversion of the short arm of X chromosome. The FISH analyses that were recently performed, revealed that in fact our patient presented a case of unbalanced translocation, 46,X, t(X;15)(p11.2; q15).