The emotional impact of the COVID-19 pandemic on individuals with progressive multiple sclerosis

Journal of Neurology - Individuals with pre-existing chronic illness have shown increased anxiety and depression due to COVID-19. Here, we examine the impact of the COVID-19 pandemic on emotional...     

Expanding the clinical spectrum of STIP1 homology and U-box containing protein 1-associated ataxia

Journal of Neurology - STUB1 has been first associated with autosomal recessive (SCAR16, MIM# 615768) and later with dominant forms of ataxia (SCA48, MIM# 618093). Pathogenic variations in STUB1...     

Drug-resistant and immune-escape hepatitis B virus mutants, occult hepatitis B infection and coinfections in public hospital patients from Argentina

Virus Genes - Argentina exhibits low serological prevalence for Hepatitis B virus (HBV); however, occult hepatitis B infection (OBI) has been reported in blood donors, Amerindians and individuals...     

Deregulated cellular circuits driving immunoglobulins and complement consumption associate with the severity of COVID-19 patients

SARS-CoV-2 infection causes an abrupt response by the host immune system, which is largely responsible for the outcome of COVID-19. We investigated whether the specific immune responses in the peripheral blood of 276 patients were associated with the severity and progression of COVID-19. At admission, dramatic lymphopenia of T, B, and NK cells is associated with severity. Conversely, the proportion of B cells, plasmablasts, circulating follicular helper T cells (cTfh) and CD56^–CD16⁺ NK-cells increased. Regarding humoral immunity, levels of IgM, IgA, and IgG were unaffected, but when degrees of severity were considered, IgG was lower in severe patients. Compared to healthy donors, complement C3 and C4 protein levels were higher in mild and moderate, but not in severe patients, while the activation peptide of C5 (C5a) increased from the admission in every patient, regardless of their severity. Moreover, total IgG, the IgG1 and IgG3 isotypes, and C4 decreased from day 0 to day 10 in patients who were hospitalized for more than two weeks, but not in patients who were discharged earlier. Our study provides important clues to understand the immune response observed in COVID-19 patients, associating severity with an imbalanced humoral response, and identifying new targets for therapeutic intervention.     

Testing the inhibitory cascade model in the Middle Pleistocene Sima de los Huesos (Sierra de Atapuerca,Spain) hominin sample

The Middle Pleistocene Sima de los Huesos (SH) site has yielded more than 7.500 human fossil remains belonging to a minimum of 29 individuals. Most of these individuals preserve either the complete mandibular molar series or at least the first (M₁) and second (M₂) molars. The inhibitory cascade mathematical model was proposed by Kavanagh et al. (Nature, 449, 427–433 [2007]) after their experimental studies on the dental development of murine rodent species. The activator–inhibitor mechanism of this model has shown its ability for predicting evolutionary size patterns of mammalian teeth, including hominins. The main aim of this study is to test whether the size molar patterns observed in the SH hominins fit the inhibitory cascade model. With this purpose, we have measured the crown area of all SH molars in photographs, using a planimeter and following techniques used and well contrasted in previous works. Following one of the premises of the inhibitory cascade model, we expect that the central tooth (M₂ in our case) of a triplet would have the average size of the two outer teeth. The absolute difference between the observed and the expected values for the M₂s ranges from 0.23 to 8.46 mm² in the SH sample. In terms of percentage, the difference ranges between 0.25% and 10.34%, although in most cases, it is below 5%. The plot of the estimated M₃/M₁ and M₂/M₁ size ratios obtained in the SH hominins occupies a small area of the theoretical developmental morphospace obtained for rodent species. In addition, the majority of the values are placed near the theoretical line which defines the relationship predicted by the inhibitory cascade model in these mammals. The values of the slope and intercept of the reduced major regression obtained for the SH individuals do not differ significantly from those obtained for rodent species, thus confirming that the size of the molars of the SH hominins fits the inhibitory cascade model. We discuss these results in terms of dental development. Despite the promising results in the SH sample, we draw the attention to the fact that most Early Pleistocene Homo specimens exhibit a pattern (M₁ < M₂ > M₃), which is outside the expected theoretical morphospace predicted by the inhibitory cascade model. The shift from the M1 < M2 < M3 size relationship observed in early hominins (including H. habilis) to the M1 > M2 > M3 size relationship, which is predominant in modern humans, includes sequences that depart from predictions of the inhibitory cascade model. Additional studies are required to understand these deviations.     

Atrioventricular canal defect in patients with RASopathies

Congenital heart defects affect 60-85% of patients with RASopathies. We analysed the clinical and molecular characteristics of atrioventricular canal defect in patients with mutations affecting genes coding for proteins with role in the RAS/MAPK pathway. Between 2002 and 2011, 101 patients with cardiac defect and a molecularly confirmed RASopathy were collected. Congenital heart defects within the spectrum of complete or partial (including cleft mitral valve) atrioventricular canal defect were diagnosed in 8/101 (8%) patients, including seven with a PTPN11 gene mutation, and one single subject with a RAF1 gene mutation. The only recurrent mutation was the missense PTPN11 c.124 A>G change (T42A) in PTPN11. Partial atrioventricular canal defect was found in six cases, complete in one, cleft mitral valve in one. In four subjects the defect was associated with other cardiac defects, including subvalvular aortic stenosis, mitral valve anomaly, pulmonary valve stenosis and hypertrophic cardiomyopathy. Maternal segregation of PTPN11 and RAF1 gene mutations occurred in two and one patients, respectively. Congenital heart defects in the affected relatives were discordant in the families with PTPN11 mutations, and concordant in that with RAF1 mutation. In conclusion, our data confirm previous reports indicating that atrioventricular canal defect represents a relatively common feature in Noonan syndrome. Among RASopathies, atrioventricular canal defect was observed to occur with higher prevalence among subjects with PTPN11 mutations, even though this association was not significant possibly because of low statistical power. Familial segregation of atrioventricular canal defect should be considered in the genetic counselling of families with RASopathies.