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Mucopolysaccharidosis type IIIA (MPS IIIA, Sanfilippo A syndrome) is a single gene (SGSH) childhood onset neurodegenerative disease for which gene therapy is in clinical trial. Theoretically, the transfer of a working gene should enable functional expression of the defective protein and rescue the phenotype when administered before the onset of irreversible disease. Recombinant adeno-associated virus (AAV) is being used as a vehicle for a number of gene therapy applications and the neurotropism of serotype 9 affords utility for monogenetic neurological disorders. Ferrostatin-1 To assess the efficacy of restoring the underlying biochemistry in the MPS IIIA brain, tail vein injections of self-complementary AAV9 human N-sulfoglucosamine sulfohydrolase (scAAV9.U1A.hSGSH) at 3 × 1013 vg/kg were administered to 6- and 16-week-old MPS IIIA mice. Heparan sulfate (HS) and GM2 and GM3 gangliosides were cleared from the cortex, hippocampus and subcortex with residual storage remaining in the brain stem and cerebellum. SGSH activity increased in the brain of the MPS IIIA-treated mice, but remained significantly reduced compared with wild-type. Motor activity as assessed in an open-field arena, and gait length, improved in MPS IIIA mice treated at both 6 and 16 weeks of age. However, functional assessment of cognition in the water cross-maze test, as well as gait width, normalized in mice treated at 6 weeks of age only, with mice treated at 16 weeks performing similar to untreated MPS IIIA mice. Astrogliosis was reduced in mice treated at 6 and 16 weeks of age compared to untreated MPS IIIA mice. These results demonstrate that the gene product is actively clearing primary HS and secondary ganglioside accumulation in MPS IIIA mice, but in older mice, neurocognitive impairments remain. This is likely due to secondary downstream consequences of HS affecting neurological functions that are not reversible upon substrate clearance.

To elaborate on early survival in patients with mitral valve replacement requiring temporary extracorporeal life support system (ECLS).

We analyzed survival, significant bleeding, wound infection, and ECLS duration in 421 from 14,400 patients with postoperative need for ECLS from January 2008 to December 2017 at our institution. Finally, patients were stratified according to the type of surgery performed the mitral group (mitral valve replacement)

 = 63 and the control group (any cardiac surgery excluding the mitral valve)

 = 358. In order to adjust for preoperative patient characteristics, a propensity matching analysis was performed. Differences in in-hospital mortality were analyzed accordingly.

In-hospital mortality was significantly higher in the mitral group as compared to the control group before and after adjustment (

 < 0.001). Median duration of ECLS was 4 days in both groups. Perioperative bleeding (

 < 0.001) and wound infection (

 < 0.001) also showed significant worse outcome parameters in the mitral group. The main causes of death in the mitral group were multiorgan failure,

 = 48 (76%), stroke,

 = 7 (12%), and intracardiac thrombus formation,

 = 5 (10%).

ECLS is associated with a high in-hospital mortality rate in patients after mitral valve replacement.

ECLS is associated with a high in-hospital mortality rate in patients after mitral valve replacement.

There is a growing body of qualitative studies examining parents' experiences of caring for a child with a life-limiting condition, coinciding with recent evidence that indicates an increasing incidence of paediatric life-limiting conditions. However, research focusing on fathers' needs remains sparse and is often diluted among a predominant 'mother's voice', raising questions about whether practices in clinical settings meet fathers' needs.

To provide an in-depth assembly of the current state of knowledge around fathers' experiences of caring for their children diagnosed with life-limiting conditions and understand the implications for healthcare services and policies.

A meta-ethnography was conducted to synthesise findings from existing qualitative studies exploring fathers' experiences of caring.

Four electronic databases (PubMed, PsycINFO, CINAHL and Science Direct) were searched up until April 2020. Qualitative studies exploring fathers' care experience and published in English language were included. The Critical Appraisal Skills Programme (CASP) checklist was employed for study quality appraisal. No temporal limits were used.

Sixty-three studies met the inclusion criteria. Thirty life-limiting conditions were included. Based on responses from 496 fathers, a conceptual model was developed which translates key experiences within the fathers' caregiving journeys. The overarching concepts identified were

and

. These and associated sub-concepts are discussed, with recommendations for future research and practice provided.

The findings indicate the value of a family-oriented approach to develop psychosocial interventions and support channels for fathers, thus empowering them whilst reducing the care-giving burden on the family unit.

The findings indicate the value of a family-oriented approach to develop psychosocial interventions and support channels for fathers, thus empowering them whilst reducing the care-giving burden on the family unit.The predominant tool used to predict outcomes after traumatic spinal cord injury (SCI) is the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI), in association with the American Spinal Injury Association (ASIA) Impairment Scale (AIS). These measures have evolved based on analyses of large amounts of longitudinal neurological recovery data published in numerous separate studies. This article reviews and synthesizes published data on neurological recovery from multiple sources, only utilizing data in which the sacral sparing definition was applied for determination of completeness. Conversion from a complete to incomplete injury is more common in tetraplegia than paraplegia. The majority of AIS conversion and motor recovery occurs within the first 6-9 months, with the most rapid rate of motor recovery occurring in the first three months after injury. Motor score changes, as well as recovery of motor levels, are described with the initial strength of muscles as well as the levels of the motor zone of partial preservation influencing the prognosis.