A pilot study evaluating stress factors during and after the COVID-19 pandemic in Viennese families who have the suspicion of child maltreatment or abuse.

The global population was affected by the unprecedented coronavirus COVID-19 pandemic. The impact of the pandemic on children who suffer child maltreatment has not been explored sufficiently. Child abuse is known to increase in stressful circumstances, and therefore potentially during this pandemic.We aimed to identify and measure the impact of pandemic-related stress in families with a suspicion or confirmed child maltreatment. In addition, other parameters were determined, including resilience factors and family dynamics.We conducted a pilot study at the Medical University of Vienna, Forensic Examination Centre for Children and Adolescents (FOKUS Safeguarding team). Parents, carers and legal guardians of children who were referred for potential child abuse (study group) participated by completing two questionnaires, one year apart, covering the following periods: pre-COVID, during-COVID and post-COVID. Simultaneously, a control group was devised with patients who presented to the Paediatric Emergency Department with unrelated conditions (other than child maltreatment concerns). The questionnaires addressed psychological stress factors and were completed face-to-face and/or via telephone. A total of 35 carers participated, with almost equal numbers in both intervention and control groups.Results show that there was statistically significantly higher stress level perception before and during the pandemic period in the study group. Several families in this group commented on the positive effect of support received from health professionals, especially after the pandemic.

Upregulation of elastase proteins results in aortic dilatation in mucopolysaccharidosis I mice.

Mucopolysaccharidosis I (MPS I), known as Hurler syndrome in the severe form, is a lysosomal storage disease due to alpha-L-iduronidase (IDUA) deficiency. It results in fragmentation of elastin fibers in the aorta and heart valves via mechanisms that are unclear, but may result from the accumulation of the glycosaminoglycans heparan and dermatan sulfate. Elastin fragmentation causes aortic dilatation and valvular insufficiency, which can result in cardiovascular disease. The pathophysiology of aortic disease was evaluated in MPS I mice. MPS I mice have normal elastic fiber structure and aortic compliance at early ages, which suggests that elastin assembly is normal. Elastin fragmentation and aortic dilatation are severe at 6 months, which is temporally associated with marked increases in mRNA and enzyme activity for two elastin-degrading proteins, matrix metalloproteinase-12 (MMP-12) and cathepsin S. Upregulation of these genes likely involves activation of STAT proteins, which may be induced by structural stress to smooth muscle cells from accumulation of glycosaminoglycans in lysosomes. Neonatal intravenous injection of a retroviral vector normalized MMP-12 and cathepsin S mRNA levels and prevented aortic disease. We conclude that aortic dilatation in MPS I mice is likely due to degradation of elastin by MMP-12 and/or cathepsin S. This aspect of disease might be ameliorated by inhibition of the signal transduction pathways that upregulate expression of elastase proteins, or by inhibition of elastase activity. This could result in a treatment for patients with MPS I, and might reduce aortic aneurism formation in other disorders.

Correction of clinical manifestations of canine mucopolysaccharidosis I with neonatal retroviral vector gene therapy.

Mucopolysaccharidosis I (MPS I) (Hurler syndrome) is due to deficient alpha-L-iduronidase (IDUA) activity and is the most common of the MPS disorders. Neonatal MPS I dogs were injected intravenously (IV) with a gamma retroviral vector containing a complete long-terminal repeat (LTR) and an internal human alpha(1)-antitrypsin (hAAT) promoter upstream of the canine IDUA complementary DNA (cDNA). This resulted in stable serum IDUA activity of 366 +/- 344 units (U)/ml (28-fold normal) for up to 1.8 years, which likely derived primarily from secretion of IDUA by transduced liver cells. Retroviral vector (RV)-treated dogs had >18% of normal IDUA activity in organs and had decreased severity and/or incidence of hernias, chest deformities, joint disease, facial dysmorphia, corneal clouding, valvular heart disease, and aortic dilatation as compared with untreated MPS I dogs. The marked reduction that was observed in lysosomal storage in the brain of RV-treated dogs may have been due in part to expression from the LTR of the vector in cells in the brain. This possibility will be explored in future studies, because the potential for insertional mutagenesis has raised concerns about using vectors with an intact LTR. If proven safe, this gene therapy technique may be utilized in treating children with Hurler syndrome.