Extending the phenotypes associated with TRIO gene variants in a cohort of 25 patients and review of the literature

The TRIO gene encodes a rho guanine exchange factor, the function of which is to exchange GDP to GTP, and hence to activate Rho GTPases, and has been described to impact neurodevelopment. Specific genotype-to-phenotype correlations have been established previously describing striking differentiating features seen in variants located in specific domains of the TRIO gene that are associated with opposite effects on RAC1 activity. Currently, 32 cases with a TRIO gene alteration have been published in the medical literature. Here, we report an additional 25, previously unreported individuals who possess heterozygous TRIO variants and we review the literature. In addition, functional studies were performed on the c.4394A > G (N1465S) and c.6244-2A > G TRIO variants to provide evidence for their pathogenicity. Variants reported by the current study include missense variants, truncating nonsense variants, and an intragenic deletion. Clinical features were previously described and included developmental delay, learning difficulties, microcephaly, macrocephaly, seizures, behavioral issues (aggression, stereotypies), skeletal problems including short, tapering fingers and scoliosis, dental problems (overcrowding/delayed eruption), and variable facial features. Here, we report clinical features that have not been described previously, including specific structural brain malformations such as abnormalities of the corpus callosum and ventriculomegaly, additional psychological and dental issues along with a more recognizable facial gestalt linked to the specific domains of the TRIO gene and the effect of the variant upon the function of the encoded protein. This current study further strengthens the genotype-to-phenotype correlation that was previously established and extends the range of phenotypes to include structural brain abnormalities, additional skeletal, dental, and psychiatric issues.     

Malaria infection through multiorgan donation: an update from Spain.

During the last years, immigration has increased and, consequently, the pool of foreign donors and associated infectious diseases from exotic countries (especially from the tropics) has also increased. Only a few cases of malaria transmitted via different donation sources have been published. In the present report, a Plasmodium vivax transmitted through a multiorgan donation is reported. In conclusion, we discuss the features related with the diagnosis, the treatment, and the special characteristics of a case in which the liver and not any other organ is the reservoir of the plasmodium.     

Factors related to refuse antiretroviral therapy in prison

INTRODUCTION: Despite the benefits of highly-active antiretroviral therapy (HAART) on morbidity and mortality, some seropositive patients refuse to accept this treatment. Prisons provide easier access to this population. OBJECTIVE: To determine the psychosocial characteristics of prisoners who refuse HAART. METHODS: We performed a cross-sectional study in 580 seropositive prisoners in 3 hospitals in Andalusia (Spain). The dependent variable was being under treatment or refusal to be so. The independent variables were sociodemographic and psychosocial factors related to the prison environment and clinical factors related to health status and drug addiction. A logistic regression analysis was performed to determine which factors were related with refusal to accept HAART. RESULTS: HAART was recommended to 73.1% of seropositive prisoners. This treatment was refused by 23.1% of these prisoners and was accepted by 76.9%. The factors related to refusal to accept HAART were high viral load, worse self-perceived health status, a greater number of stays in prison, and being visited by persons other than relatives. CONCLUSIONS: There is a group of prisoners with specific characteristics that refuse HAART. Specific interventions should be performed in these prisoners to make them aware of the effects of their decision on the course of their disease.     

Antioxidant responses in the nereidid Laeonereis acuta (Annelida, Polychaeta) after cadmium exposure

The objective of this study was to evaluate the effects of the exposure to cadmium on the antioxidant responses in the polychaeta Laeonereis acuta. The worms were submitted to 0, 5, and 100 microg of Cd/L during a period of test of 7 days. Cadmium was significantly (p<0.05) accumulated in L. acuta in both concentrations assayed, but the concentration of reactive oxygen and nitrogen species (RONS) increased (p<0.05) only in the group submitted to the highest concentration of cadmium (100 microg/L). At this concentration, a decrease in the activity of the superoxide dismutase and an increase of glutathione-S-transferase activity (p<0.05) was observed. The levels of both lipid peroxides and the activities of catalase and glutathione peroxidase were not affected (p>0.05) by the exposition to cadmium. Thus, cadmium can augment RONS levels and can interfere with the antioxidant defense system of the polychaete L. acuta, although cadmium does not directly induce oxidative stress unlike copper and iron.     

Basal cell carcinoma with matrical differentiation: expression of beta-catenin [corrected] and osteopontin

Basal cell carcinoma with matrical differentiation is an extremely rare variant. To date, only 12 cases have been described in the literature. This tumor is a typical basal cell carcinoma with basaloid nests containing shadow cells identical to those of pilomatricoma and pilomatrical carcinoma. We present two additional cases and have investigated the immunoprofile of .-catenin and osteopontin with the aim of determining both their biological significance and possible diagnostic utility. The morphological and immunohistochemical features of these cases that we have found suggest that basal cell carcinomas with matrical differentiation belong to a spectrum of lesions deriving from hair follicles in which .-catenin plays an important role in the tumor development, differentiation, and behavior.