Treatment with metformin is indicated in all hyperinsulinaemic overweight patients with PCOS, especially in those with NAFLD. These data appear even more interesting considering their increased risk to develop metabolic and hepatic complications.
For the first time, we have identified a genetic variant that is strongly associated with PCOS in an isolated population. These results, if confirmed in other cohorts, may provide the opportunity to test the S312N genotype at the LHCGR locus in fertile women to assess the risk of PCOS. The avoidance of triggering factors like weight increase may improve the reproductive outcome of potentially at-risk subjects.
This work was supported by the National Fund for Scientific and Technological Development of Chile (FONDECYT), grant no. 1120176 (A.C.). The authors declare that no conflicting interests exist.
Adolescents with Type 1 diabetes had lower levels of serum oestrogenic activity, and these were lower than expected based on their serum oestradiol levels. We postulate that changes in the serum milieu of oestrogens in patients with Type 1 diabetes may explain their decreased oestrogenic activity and may play a role in their adverse metabolic profile.
The tendency of organic contaminants
(OCs) to partition
between
different phases is a key set of properties that underlie their human
and ecological health impacts and the success of remediation efforts.
A significant challenge associated with these efforts is the need
for accurate partitioning data for an ever-expanding list of OCs and
breakdown products. All-atom molecular dynamics (MD) simulations have
the potential to help generate these data, but existing studies have
applied these techniques only to a limited variety of OCs. Here, we
use established MD simulation approaches to examine the partitioning
of 82 OCs, including many compounds of critical concern, at the water–air
interface. Our predictions of the Henry’s law constant (K
H) and interfacial adsorption coefficients (K
iw, K
ia) correlate
strongly with experimental results, indicating that MD simulations
can be used to predict K
H, K
iw, and K
ia values with mean
absolute deviations of 1.1, 0.3, and 0.3 logarithmic units after correcting
for systematic bias, respectively. A library of MD simulation input
files for the examined OCs is provided to facilitate future investigations
of the partitioning of these compounds in the presence of other phases.
DAX-1 [dosage-sensitive sex reversal-adrenal hypoplasia congenital (AHC) critical region on the X chromosome gene 1; NR0B1] is an orphan nuclear receptor that acts as a transcriptional repressor in adrenal/gonadal development, steroidogenesis and probably spermatogenesis. An alternatively spliced form called DAX-1A (NR0B1A) has been described in several tissues including the testis, and in vitro studies have shown an inhibitory effect on DAX-1 transcriptional function. We aimed to study the mRNA and protein expression of DAX-1 in testicular tissues of 65 men with primary spermatogenic failure [complete Sertoli cell only syndrome (SCOS), focal SCOS, maturation arrest and mixed atrophy] compared with 33 controls with normal spermatogenesis. As a novel finding, we observed intense immunostaining, not only in the nucleus of Sertoli cells, but also in pachytene spermatocytes and round spermatids. The quantitative mRNA expression of DAX-1 and DAX-1A was similar between cases and controls and was not associated with the levels of gonadotrophins and steroids. Moreover, DAX-I transcript expression level was ∼750-fold higher than DAX-1A, and there was a strong positive correlation between them (r = 0.52; P< 0.001). We conclude that, in addition to Sertoli cells, DAX-1/DAX-1A is expressed in germ cells from spermatogonia to round spermatids. Besides, the similar mRNA expression of DAX-I and DAX-IA in testicular tissues from cases and controls does not support the involvement of DAX-1 in the etiology of primary spermatogenic failure. Finally, the low level of expression of the alternative transcriptional variant DAX-1A would not support its putative inhibitory function in vivo.
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