Characterization of Xenopus laevis guanine deaminase reveals new insights for its expression and function in the embryonic kidney.

BACKGROUND: The mammalian guanine deaminase (GDA), called cypin, is important for proper neural development, by regulating dendritic arborization through modulation of microtubule (MT) dynamics. Additionally, cypin can promote MT assembly in vitro. However, it has never been tested whether cypin (or other GDA orthologs) binds to MTs or modulates MT dynamics. Here, we address these questions and characterize Xenopus laevis GDA (Gda) for the first time during embryonic development. RESULTS: We find that exogenously expressed human cypin and Gda both display a cytosolic distribution in primary embryonic cells. Furthermore, while expression of human cypin can promote MT polymerization, Xenopus Gda has no effect. Additionally, we find that the tubulin-binding collapsin response mediator protein (CRMP) homology domain is only partially conserved between cypin and Gda. This likely explains the divergence in function, as we discovered that the cypin region containing the CRMP homology and PDZ-binding domain is necessary for regulating MT dynamics. Finally, we observed that gda is strongly expressed in the kidneys during late embryonic development, although it does not appear to be critical for kidney development. CONCLUSIONS: Together, these results suggest that GDA has diverged in function between mammals and amphibians, and that mammalian GDA plays an indirect role in regulating MT dynamics. Developmental Dynamics 248:296-305, 2019. © 2019 Wiley Periodicals, Inc.

Effects of Palliative Care for Progressive Neurologic Diseases: A Systematic Review and Meta-Analysis.

OBJECTIVES: To determine the association of palliative care for progressive neurologic diseases with patient- and caregiver-centered outcomes. DESIGN: Systematic review and meta-analysis of randomized controlled trials and quasi-experimental studies, including pilot studies. SETTING AND PARTICIPANTS: Adults with progressive neurologic diseases (dementia, multiple sclerosis, Parkinson's disease, motor neuron disease, multiple system atrophy, and progressive supranuclear palsy) and their caregivers. METHODS: MEDLINE, EMBASE, CINAHL PLUS, Cochrane CENTRAL, and PubMed were searched from inception to September 2021. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Cochrane risk of bias tools. Narrative synthesis was conducted. Patient quality of life (QoL), symptom burden, caregiver burden, and satisfaction with care were meta-analyzed using a random-effects model. RESULTS: Fifteen trials provided data on 3431 patients (mean age, 73.9 years). Compared with usual care, palliative care was statistically significantly associated with lower symptom burden [standardized mean difference (SMD), -0.34 (95% Cl, -0.59 to -0.09)] and higher caregiver satisfaction [SMD, 0.41 (95% Cl, 0.12 to 0.71)] and patient satisfaction [SMD, 0.43 (95% Cl, -0.01 to 0.87)]. However, the associations were not significant after excluding studies with high risk of bias. Insignificant associations of palliative care with caregiver burden [SMD, -0.09 (95% Cl, -0.21 to 0.03)] and patient QoL [SMD, 0.19 (95% Cl, -0.07 to 0.44)] were observed. CONCLUSIONS AND IMPLICATIONS: Palliative care is likely to improve symptom burden and satisfaction with care among patients with progressive neurologic diseases and their caregivers, while its effects on QoL and caregiver burden remains inconclusive. Specific intervention components including interdisciplinary team, palliative care physicians, home visits, and spiritual care appeared to be associated with increased effects on improving palliative outcomes. More rigorous designed studies are warranted to examine the effects of neuropalliative care, effective intervention components, optimal timing, and symptom triggers of palliative care referrals.