Metabolic profiling of polycystic ovary syndrome reveals interactions with abdominal obesity.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common reproductive disorder associated with metabolic disturbances including obesity, insulin resistance and diabetes mellitus. Here we investigate whether changes in the metabolic profile of PCOS women are driven by increased tendency to obesity or are specific features of PCOS related to increased testosterone levels. DESIGN AND METHODS: We conducted an NMR metabolomics association study of PCOS cases (n=145) and controls (n=687) nested in a population-based birth cohort (n=3127). Subjects were 31 years old at examination. The main analyses were adjusted for waist circumference (WC) as a proxy measure of central obesity. Subsequently, metabolite concentrations were compared between cases and controls within pre-defined WC strata. In each stratum, additional metabolomics association analyses with testosterone levels were conducted separately among cases and controls. RESULTS: Overall, women with PCOS showed more adverse metabolite profiles than the controls. Four lipid fractions in different subclasses of very low density lipoprotein (VLDL) were associated with PCOS, after adjusting for WC and correction for multiple testing (P<0.002). In stratified analysis the PCOS women within large WC strata (⩾98 cm) had significantly lower high density lipoprotein (HDL) levels, Apo A1 and albumin values compared with the controls. Testosterone levels were significantly associated with VLDL and serum lipids in PCOS cases with large WC but not in the controls. The higher testosterone levels, adjusted for WC, associated adversely with insulin levels and HOMA IR in cases but not in the controls. CONCLUSIONS: Our findings show that both abdominal obesity and hyperandrogenism contribute to the dyslipidaemia and other metabolic traits of PCOS which all may negatively contribute to the long-term health of women with PCOS.

[Neonatal death of a newborn twin]. / Le décès d'un jumeau en réanimation néonatale. La place que le psychiatre peut prendre.

In France, in 2001, 33,000 children were born from multiple pregnancies (4.2% of births). Lately, with the stimulated fertilization improvement, this number has strongly increased. These pregnancies are pretty often difficult and the hospitalizations of the twins (or other multiples) in a neonatal intensive care unit are more frequent than in a single pregnancy (48 vs. 5.3%). Newborn twin death leads the parents to face a tough mourning because of the surviving twin presence. The psychiatrist's function is crucial with the parents, the deceased child, the surviving child and the pediatric staff. Therefore, as much as possible, the psychiatrist (or the psychologist) has to gather and work through the confused feelings of the parents. Several splittings occur in this situation. Some of these splittings concern the medical staff, some others affect the children, the dead one and the living one, either rejected and disinvested or idealized and overprotected. The child psychiatrist is a preferred recipient for the different projections of the parents.The hospital staff as a whole has to understand their full significance and their important psychic sparing for the couple. As the deceased child, the psychiatrist may look bad and unsatisfying, for instance: "he doesn't answer as we would like", "he doesn't come up to the couple's expectations", "he doesn't talk enough", "he's leaving too soon", etc.In addition, the psychiatrist may be attacked as the representative of the pediatric staff, in order to preserve in a better way the others medical protagonists, still essential for the survival of the alive child. These parents are in mourning and the psychiatrist must help them in this process in order to improve the specific investment of the surviving child, the attachment and the communication with him.

Improved techniques for the identification of pseudogenes.

MOTIVATION: Pseudogenes are the remnants of genomic sequences of genes which are no longer functional. They are frequent in most eukaryotic genomes, and an important resource for comparative genomics. However, pseudogenes are often mis-annotated as functional genes in sequence databases. Current methods for identifying pseudogenes include methods which rely on the presence of stop codons and frameshifts, as well as methods based on the ratio of non-silent to silent nucleotide substitution rates (dN/dS). A recent survey concluded that 50% of human pseudogenes have no detectable truncation in their pseudo-coding regions, indicating that the former methods lack sensitivity. The latter methods have been used to find sets of genes enriched for pseudogenes, but are not specific enough to accurately separate pseudogenes from expressed genes. RESULTS: We introduce a program called pseudogene inference from loss of constraint (PSILC) which incorporates novel methods for separating pseudogenes from functional genes. The methods calculate the log-odds score that evolution along the final branch of the gene tree to the query gene has been according to the following constraints: A neutral nucleotide model compared to a Pfam domain encoding model (PSILC(nuc/dom)); A protein coding model compared to a Pfam domain encoding model (PSILC(prot/dom)). Using the manual annotation of human chromosome 6, we show that both these methods result in a more accurate classification of pseudogenes than dN/dS when a Pfam domain alignment is available. AVAILABILITY: PSILC is available from http://www.sanger.ac.uk/Software/PSILC