Network approaches for modeling the effect of drugs and diseases.

The network approach is quickly becoming a fundamental building block of computational methods aiming at elucidating the mechanism of action (MoA) and therapeutic effect of drugs. By modeling the effect of drugs and diseases on different biological networks, it is possible to better explain the interplay between disease perturbations and drug targets as well as how drug compounds induce favorable biological responses and/or adverse effects. Omics technologies have been extensively used to generate the data needed to study the mechanisms of action of drugs and diseases. These data are often exploited to define condition-specific networks and to study whether drugs can reverse disease perturbations. In this review, we describe network data mining algorithms that are commonly used to study drug's MoA and to improve our understanding of the basis of chronic diseases. These methods can support fundamental stages of the drug development process, including the identification of putative drug targets, the in silico screening of drug compounds and drug combinations for the treatment of diseases. We also discuss recent studies using biological and omics-driven networks to search for possible repurposed FDA-approved drug treatments for SARS-CoV-2 infections (COVID-19).

Collection of peripheral blood stem cells in new patients with myeloma receiving minimal or no prior cytoreductive therapy.

The aim of the study was to evaluate whether adequate stem cells (CD34+) could be harvested at presentation in myeloma patients such that high dose melphalan (HDM) with autologous stem cell rescue can be offered as primary therapy. The regimes either involved no prior cytoreductive chemotherapy (steroids only, n = 31) or a single course of VAD (n = 22). The median number of CD34 cells collected with steroids was 1.3 x 10(6) (0.2-5.6) compared to 4.6 x 10(6) (0.3-19.2) cells/kg with VAD (P < 0.0001). We conclude that it is possible to collect stem cells from myeloma patients at presentation with minimal prior therapy. Using this strategy, of a single prior course of chemotherapy followed by immediate harvest, it is feasible to offer early high-dose therapy in clinical situations where this is important.

Validation of electrode placement in neonatal electrogastrography.

Electrogastrography (EGG) is the transcutaneous measurement of gastric electrical activity. The aims of this study were to validate the electrode placement position in neonatal electrogastrography using ultrasonography to localise the stomach, and to describe the observed EGG frequency characteristics. Fifteen neonates with no known abdominal disorder were studied. Two bipolar EGG recordings were obtained from each subject, the first from electrodes placed at sites localized by ultrasound and the second from electrodes placed at the currently recommended sites. Paired sample t tests were used to compare electrode positioning and electrogastrographic data. There were 15 subjects with a mean age of 36 days (range 1-95). While there was a significant difference in the position of electrodes at each site, the EGG recordings did not differ. The 3-cycle/minute (2.6-3.7cpm) activity ranged from 30% to 84% of recorded time (mean at sites localized with ultrasound was 53%, and at currently recommended sites it was 50%; difference not significant, P = 0.155). Bradygastria (<2.6 cpm) was observed in the range of 2-29% of recorded time (mean at sites localised with ultrasound was 12.9%, and at currently recommended sites it was 11.7%; difference not significant, P = 0.40). Tachygastria (3.2-10 cpm) was shown to be in the range of 10-58% of recorded time (mean at sites localized with ultrasound was 33.3%, and at currently recommended sites it was 38.7%; difference not significant; P = 0.044). In conclusion, there was no significant difference between EGG recordings taken from electrode sites localized by ultrasound and those recommended by manufacturers of the electrogastrogram, thus confirming the validity of the manufacturer's recommended electrode positioning. The pattern of electrical control activity in the normal neonatal stomach appears to be different from that demonstrated in adults. Bradygastria and tachygastria are seen more frequently, with fewer periods of 3 cpm activity.

Hot spots, indicator taxa, complementarity and optimal networks of taiga.

If hot spots for different taxa coincide, priority-setting surveys in a region could be carried out more cheaply by focusing on indicator taxa. Several previous studies show that hot spots of different taxa rarely coincide. However, in tropical areas indicator taxa may be used in selecting complementary networks to represent biodiversity as a whole. We studied beetles (Coleoptera), Heteroptera, polypores or bracket fungi (Polyporaceae) and vascular plants of old growth boreal taiga forests. Optimal networks for Heteroptera maximized the high overall species richness of beetles and vascular plants, but these networks were least favourable options for polypores. Polypores are an important group indicating the conservation value of old growth taiga forests. Random selection provided a better option. Thus, certain groups may function as good indicators for maximizing the overall species richness of some taxonomic groups, but all taxa should be examined separately.

[Congenital toxoplasmosis with delayed immune response]. / Konnatale Toxoplasmose mit verzögerter Immunantwort.

In typical cases the diagnosis "toxoplasmosis connata" is based on clinical symptoms and positive serological findings. When the infection of the fetus occurred a short time before birth the neonate seems still normal and the disease develops in the postnatal period. In such cases the specific antibody production may be delayed. We present a case report with well documented first infection of the mother between the 15th and 30th gestational week but with no specific treatment. The baby was born without clinical signs of a toxoplasmosis infection and developed the disease 2-3 weeks later; the serological test (complement fixation test, KBR) was negative at the 24th postnatal day. Specific antimicrobial therapy could be started after serological conversion between the 4th and 5th postnatal week. Problems of diagnostics and delayed therapy are discussed.