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.     

Bi-allelic pathogenic variations in DNAJB11 cause Ivemark II syndrome,a renal-hepatic-pancreatic dysplasia

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A literature-based treatment algorithm for low-grade neuroendocrine liver metastases

BackgroundThe optimal timing of treatment of liver metastases from low-grade neuroendocrine tumors (LG-NELM) varies significantly due to numerous treatment modalities and the literature supporting various treatment(s). This study sought to create and validate a literature-based treatment algorithm for LG-NELM.MethodsA treatment algorithm to maximize overall survival (OS) was designed using peer-reviewed articles evaluating treatment of LG-NELM. This algorithm was retrospectively applied to patients treated for LG-NELM at our institution. Deviation was determined based on whether or not a patient received treatment consistent with that recommended by the algorithm. Patients who did and did not deviate from the algorithm were compared with respect to OS and number of treatments.ResultsApplying our algorithm to a 149-patient cohort, 57 (38%) deviated from recommended treatment. Deviation occurred in the form of alternative (28, 49%) versus additional procedures (29, 51%). Algorithm deviators underwent significantly more procedures than non-deviators (median 1 vs. 2, p < 0.001). Cox model indicated no difference in OS associated with algorithm deviation (HR 1.19, p = 0.58) when controlling for age and tumor characteristics.ConclusionThis literature-based algorithm helps standardize treatment protocols in patients with LG-NELM and can reduce cost and risk by minimizing unnecessary procedures. Prospective implementation and validation is required.     

A survey of internists’ recommendations for aspirin in older adults and barriers to evidence-based use

Journal of Thrombosis and Thrombolysis - Recent trials suggest that aspirin for primary prevention may do more harm than good for some, including adults over 70&nbsp;years of age. We sought to...     

Construct validity of the Eating Assessment Tool (EAT-10)

Abstract

Purpose: We aimed to evaluate the construct validity of the Eating Assessment Tool (EAT-10) by determining its dimensionality, rating scale integrity, item-person match, precision and relationship with the degree of airway invasion and functional oral intake.

Methods: We conducted a retrospective analysis of patients’ EAT-10 scores. We used the Rasch rating scale model. We investigated correlations between the EAT-10 and scores on the Penetration-Aspiration Scale (PAS) and Functional Oral Intake Scale (FOIS).

Results: The median score of the EAT-10 from 127 patients was 16 of 40 (range 0–40). Confirmatory factor analysis supported unidimensionality. The 5-point rating scale categories met published criteria. Two items misfit the Rasch model and two other items displayed differential item functioning. Rasch person reliability was 0.79. Our patient cohort was divided into three person-strata. Correlations between the EAT-10 and the PAS and FOIS were weak to moderate in strength (respectively: r?=?0.26, p?=?0.0036; r?=??0.27, p?=?0.0027).

Conclusions: Our analyses identified deficits in the construct validity of the EAT-10 suggestive of a need to improve the EAT-10 to support its frequent use in clinical practice and research.

• Implications for Rehabilitation

• Swallowing disorders are associated with severe complications, such as pneumonia and malnutrition, and impose both social and psychological burdens on patients.

• The Eating Assessment Tool is a self-report instrument developed to estimate initial dysphagia severity and monitor change in patient-reported dysphagia symptoms as a response to treatment.

• This study shows that the Eating Assessment Tool has deficits in its construct validity and a need to improve the instrument to support its frequent use in clinical practice and research.

     

Grappling with complexity: Medical students’ reflective writings about challenging patient encounters as a window into professional identity formation

Aim: Clerkship-specific interactive reflective writing (IRW)-enhanced reflection may enhance professional identity formation (PIF), a fundamental goal of medical education. PIF process as revealed in students? reflective writing (RW) has been understudied.

Methods: The authors developed an IRW curriculum within a Family Medicine Clerkship (FMC) and analyzed students? reflections about challenging/difficult patient encounters using immersion-crystallization qualitative analysis.

Results: The qualitative analysis identified 26 unique emergent themes and five distinct thematic categories (1. Role of emotions, 2. Role of cognition, 3. Behaviorally responding to situational context, 4. Patient factors, and 5. External factors) as well as an emergent PIF model from a directed content analysis. The model describes students? backgrounds, emotions and previous experiences in medicine merging with external factors and processed during student?patient interactions. The RWs also revealed that processing often involves polarities (e.g. empathy/lack of empathy or encouragement/disillusionment) as well as dissonance between idealized visions and lived reality.

Conclusions: IRW facilitates and ideally supports grappling with the lived reality of medicine; uncovering a “positive hidden curriculum” within medical education. The authors propose engaging learners in guided critical reflection about complex experiences for meaning-making within a safe learning climate as a valuable way to cultivate reflective, resilient professionals with “prepared” minds and hearts for inevitable challenges of healthcare practice.     

Patient preferences on the use of technology in cancer surveillance after curative surgery: A cross-sectional analysis

Background

Advances in communication technology have enabled new methods of delivering test results to cancer survivors. We sought to determine patient preferences regarding the use of newer technology in delivering test results during cancer surveillance.