Interrelationships between Cellular Density,Mosaic Patterning,and Dendritic Coverage of VGluT3 Amacrine Cells

Amacrine cells of the retina are conspicuously variable in their morphologies, their population demographics, and their ensuing functions. Vesicular glutamate transporter 3 (VGluT3) amacrine cells are a recently characterized type of amacrine cell exhibiting local dendritic autonomy. The present analysis has examined three features of this VGluT3 population, including their density, local distribution, and dendritic spread, to discern the extent to which these are interrelated, using male and female mice. We first demonstrate that Bax-mediated cell death transforms the mosaic of VGluT3 cells from a random distribution into a regular mosaic. We subsequently examine the relationship between cell density and mosaic regularity across recombinant inbred strains of mice, finding that, although both traits vary across the strains, they exhibit minimal covariation. Other genetic determinants must therefore contribute independently to final cell number and to mosaic order. Using a conditional KO approach, we further demonstrate that Bax acts via the bipolar cell population, rather than cell-intrinsically, to control VGluT3 cell number. Finally, we consider the relationship between the dendritic arbors of single VGluT3 cells and the distribution of their homotypic neighbors. Dendritic field area was found to be independent of Voronoi domain area, while dendritic coverage of single cells was not conserved, simply increasing with the size of the dendritic field. Bax-KO retinas exhibited a threefold increase in dendritic coverage. Each cell, however, contributed less dendrites at each depth within the plexus, intermingling their processes with those of neighboring cells to approximate a constant volumetric density, yielding a uniformity in process coverage across the population.SIGNIFICANCE STATEMENT Different types of retinal neuron spread their processes across the surface of the retina to achieve a degree of dendritic coverage that is characteristic of each type. Many of these types achieve a constant coverage by varying their dendritic field area inversely with the local density of like-type neighbors. Here we report a population of retinal amacrine cells that do not develop dendritic arbors in relation to the spatial positioning of such homotypic neighbors; rather, this cell type modulates the extent of its dendritic branching when faced with a variable number of overlapping dendritic fields to approximate a uniformity in dendritic density across the retina.     

Living with the financial consequences of cancer: A life course perspective

Abstract

Purpose

Financial hardship can be a major cause of distress among persons with cancer, resulting in chronic stress and impacting physical and emotional health. This paper provides an analysis of the lived experience of cancer patients’ financial hardship from diagnosis to post-treatment.     

Theory-driven development of a mobile phone supported intervention for adolescents with perinatal depression

Purpose

This paper describes the design of a theory-informed pragmatic intervention for adolescent perinatal depression in primary care in Nigeria.

Methods

We conducted Focus Group Discussions (FGDs) among 17 adolescent mothers and 25 maternal health care providers with experience in the receipt and provision of care for perinatal depression. The Consolidated Framework for Implementation Research (CFIR) was used to systematically examine the barriers and facilitators affecting adolescent mothers' use of an existing intervention package for depression. The Theoretical Domain Framework (TDF) and the Capability, Opportunity, Motivation, Behaviour (COM-B) model were used to analyze the results of the data across the five CFIR domains.

Results

FGD analysis revealed that care providers lacked knowledge on approaches to engage young mothers in treatment. Young mothers had poor treatment engagement, low social support, and little interest in parenting. A main characteristic of the newly designed intervention is the inclusion of age-appropriate psychoeducation supported with weekly mobile phone calls, to address treatment engagement and parenting behaviours of young mothers. Also in the outer setting, low social support from relatives was addressed with education, “as need arises” phone calls, and the involvement of "neighborhood mothers”. In the inner settings, care providers’ behaviour is addressed with training to increase their capacity to engage young mothers in treatment.

Conclusion

A theory-based approach helped develop an age-appropriate intervention package targeting depression and parenting skills deficit among perinatal adolescents in primary maternal care and in which a pragmatic use of mobile phone was key.