Service provision of genetics health care in Portugal.

In recent decades, genetics has undergone important technological advances. The rapid shift to genomics has made a strong impact on health systems around the world. In Portugal, this huge increase in consultations and typologies of genetic tests has joined the serious limitations of the few existing genetics services. The following study aims to characterize the current state of the network of genetics services in Portugal regarding its functioning, main challenges, and opportunities. Five semi-structured interviews were conducted, corresponding to 83.33% of the directors of the public genetics services of the National Health Service. Four thematic categories emerged from the analysis: (1) specialty and technical developments, (2) structural difficulties, (3) potentialities, and (4) future directions. The developments are due to the emergence of more comprehensive genetic applications, specific protocols and patient referral standards, and accreditation of services. The main difficulties encountered in the functioning of the services were difficulty in obtaining funding, lack of human resources, service overload, and lack of exclusive time for training and research. The potentialities mentioned were the establishment of multidisciplinary teams and the best articulation with specialists from other areas. Among the various future directions pointed out, better management of patients' waiting lists, the importance of research, the simplification of test request procedures, and the creation of specialized units inside the genetic services, were reported. The results showed several gaps in the practice of medical genetics that should be addressed with the development of public policies for the recognition and restructuring of medical genetics in health care.

Antagonistic regulation of spermatogonial differentiation in zebrafish (Danio rerio) by Igf3 and Amh.

Fsh-mediated regulation of zebrafish spermatogenesis includes modulating the expression of testicular growth factors. Here, we study if and how two Sertoli cell-derived Fsh-responsive growth factors, anti-Müllerian hormone (Amh; inhibiting steroidogenesis and germ cell differentiation) and insulin-like growth factor 3 (Igf3; stimulating germ cell differentiation), cooperate in regulating spermatogonial development. In dose response and time course experiments with primary testis tissue cultures, Fsh up-regulated igf3 transcript levels and down-regulated amh transcript levels; igf3 transcript levels were more rapidly up-regulated and responded to lower Fsh concentrations than were required to decrease amh mRNA levels. Quantification of immunoreactive Amh and Igf3 on testis sections showed that Fsh increased slightly Igf3 staining but decreased clearly Amh staining. Studying the direct interaction of the two growth factors showed that Amh compromised Igf3-stimulated proliferation of type A (both undifferentiated [Aund] and differentiating [Adiff]) spermatogonia. Also the proliferation of those Sertoli cells associated with Aund spermatogonia was reduced by Amh. To gain more insight into how Amh inhibits germ cell development, we examined Amh-induced changes in testicular gene expression by RNA sequencing. The majority (69%) of the differentially expressed genes was down-regulated by Amh, including several stimulators of spermatogenesis, such as igf3 and steroidogenesis-related genes. At the same time, Amh increased the expression of inhibitory signals, such as inha and id3, or facilitated prostaglandin E2 (PGE2) signaling. Evaluating one of the potentially inhibitory signals, we indeed found in tissue culture experiments that PGE2 promoted the accumulation of Aund at the expense of Adiff and B spermatogonia. Our data suggest that an important aspect of Fsh bioactivity in stimulating spermatogenesis is implemented by restricting the different inhibitory effects of Amh and by counterbalancing them with stimulatory signals, such as Igf3.

The weighted average reference montage.

In this article we describe the implementation of a linearly weighted average reference montage. This montage differs from the commonly used source derivation montage in that the reference includes all the scalp electrodes of the 10-20 system; and it differs from all other montages implemented thus far in that the weighting of the reference electrodes is based on directly measured interelectrode distances. Using EEG and computer generated signals we have been able to demonstrate that the weighted average reference montage combines topographic selectivity and accuracy in the display of both focal and regional background changes. In comparison to the source derivation montage, ectopic peaks and troughs of localized potential fields are less prominent and interhemispheric symmetry is better preserved. In comparison to the common average reference montage the frequent prominent ectopic displacement of high amplitude (e.g., vertex waves) or widespread potentials (e.g., alpha background activity) is suppressed. We believe that the spatial filtering characteristics of the weighted average reference montage, which are intermediate between those of the common average reference montage and the source derivation and Laplacian montages, will make it a useful alternative for topographic analysis. Our results also indicate that actual scalp measurements should be used to calculate reference electrode weighting factors because such measurements yield values that are substantially different from those derived from other methods of estimation presented thus far. A weighted average montage derived from pooled scalp measurements can be easily implemented using the weighting factors provided herein.