Psychosis and Dandy-Walker syndrome: a case report and review of the literature

Dandy-Walker syndrome (DWS) is a group of brain malformations which sometimes present with psychotic symptoms. We present the case of a patient diagnosed with Dandy-Walker variant who presented with schizophrenia-like psychosis. A man in his 30s was admitted to an acute psychiatric unit presenting with persecutory delusions, auditory hallucinations and violent behaviour. The MRI performed showed the typical alterations of Dandy-Walker variant: vermian hypoplasia and cystic dilatation of the fourth ventricle. He also suffered from mild intellectual disability. After being treated with olanzapine 10 mg/d for a month, his psychotic symptoms greatly improved and he was discharged. In conclusion, DWS may cause psychosis through a dysfunction in the circuit connecting prefrontal, thalamic and cerebellar areas. The association between these two conditions may contribute to the understanding of the aetiopathogenesis of schizophrenia.     

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.     

Knee extensor strength differences in obese and healthy-weight 10-to 13-year-olds

The purpose of this study was to investigate if obese children have reduced knee extensor (KE) strength and to explore the relationship between adiposity and KE strength. An observational case–control study was conducted in three Australian states, recruiting obese [N = 107 (51 female, 56 male)] and healthy-weight [N = 132 (56 female, 76 male)] 10- to 13-year-old children. Body mass index, body composition (dual energy X-ray absorptiometry), isokinetic/isometric peak KE torques (dynamometry) and physical activity (accelerometry) were assessed. Results revealed that compared with their healthy-weight peers, obese children had higher absolute KE torques (P ≤ 0.005), equivocal KE torques when allometrically normalized for fat-free mass (FFM) (P ≥ 0.448) but lower relative KE torques when allometrically normalized for body mass (P ≤ 0.008). Adjustments for maternal education, income and accelerometry had little impact on group differences, except for isometric KE torques relative to body mass which were no longer significantly lower in obese children (P ≥ 0.013, not significant after controlling for multiple comparisons). Percent body fat was inversely related to KE torques relative to body mass (r = ?0.22 to ?0.35, P ≤ 0.002), irrespective of maternal education, income or accelerometry. In conclusion, while obese children have higher absolute KE strength and FFM, they have less functional KE strength (relative to mass) available for weight-bearing activities than healthy-weight children. The finding that FFM-normalized KE torques did not differ suggests that the intrinsic contractile properties of the KE muscles are unaffected by obesity. Future research is needed to see if deficits in KE strength relative to mass translate into functional limitations in weight-bearing activities.     

Phage phi29 protein p56 prevents viral DNA replication impairment caused by uracil excision activity of uracil-DNA glycosylase

Protein p56 encoded by the Bacillus subtilis phage 29 inhibits host uracil-DNA glycosylase (UDG) activity. In previous studies, we suggested that this inhibition is likely a defense mechanism developed by phage 29 to prevent the action of UDG if uracilation occurs in DNA either from deamination of cytosine or the incorporation of dUMP during viral DNA replication. In this work, we analyzed the ability of 29 DNA polymerase to insert dUMP into DNA. Primer extension analysis showed that viral DNA polymerase incorporates dU opposite dA with a catalytic efficiency only 2-fold lower than that for dT. Using the 29 DNA amplification system, we found that 29 DNA polymerase is also able to carry out the extension of the dA:dUMP pair and replicate past uracil. Additionally, UDG and apurinic-apyrimidinic endonuclease treatment of viral DNA isolated from 29-infected cells revealed that uracil residues arise in 29 DNA during replication, probably as a result of misincorporation of dUMP by the 29 DNA polymerase. On the other hand, the action of UDG on uracil-containing 29 DNA impaired in vitro viral DNA replication, which was prevented by the presence of protein p56. Furthermore, transfection activity of uracil-containing 29 DNA was significantly higher in cells that constitutively synthesized p56 than in cells lacking this protein. Thus, our data support a model in which protein p56 ensures an efficient viral DNA replication, preventing the deleterious effect caused by UDG when it eliminates uracil residues present in the 29 genome.     

Predictors of hepatitis B surface antigen loss,relapse and retreatment after discontinuation of effective oral antiviral therapy in noncirrhotic HBeAg‐negative chronic hepatitis B

Reliable predictors of outcomes after treatment discontinuation in HBeAg‐negative chronic hepatitis B (CHB) patients have not been established. We investigated the role of hepatitis B surface antigen (HBsAg), interferon‐inducible protein‐10 (IP10) and hepatitis B core‐related antigen (HBcrAg) serum levels as predictors of HBsAg loss, relapse and retreatment in noncirrhotic HBeAg‐negative CHB patients who discontinued long‐term antiviral therapy. All HBsAg‐positive (n = 57) patients of the prospective DARING‐B study were included and followed monthly for 3 months, every 2/3 months until month‐12 and every 3/6 months thereafter. HBsAg, IP10 and HBcrAg levels were measured by enzyme immunoassays, and SCALE‐B score was calculated. Twelve patients achieved HBsAg loss before retreatment with 18‐month cumulative incidence of 25%. Independent predictors of HBsAg loss were baseline HBsAg and month‐1 IP10 levels. Of 10 patients with baseline HBsAg ≤100 IU/mL, 70% cleared HBsAg and 10% required retreatment. Of 23 patients with baseline HBsAg >1000 IU/mL, 4% cleared HBsAg and 43% required retreatment. Of 24 patients with intermediate baseline HBsAg (100‐1000 IU/mL), 17% cleared HBsAg and 21% required retreatment; in this subgroup, month‐1 IP10 was significantly associated with HBsAg loss, which occurred in 30% and 7% of cases with IP10 >150 and ≤150 pg/mL, respectively. Baseline HBcrAg was undetectable in all patients who cleared HBsAg and was associated with retreatment. SCALE‐B was associated with HBsAg loss but not with relapse or retreatment. In conclusion, HBsAg, IP10 and HBcrAg serum levels can be useful for the decisions and management of treatment discontinuation in noncirrhotic Caucasian patients with HBeAg‐negative CHB.