Short-Wavelength Sensitive Cone (S-cone) Testing as an Outcome Measure for NR2E3 Clinical Treatment Trials.

Recessively-inherited NR2E3 gene mutations cause an unusual retinopathy with abnormally-increased short-wavelength sensitive cone (S-cone) function, in addition to reduced rod and long/middle-wavelength sensitive cone (L/M-cone) function. Progress toward clinical trials to treat patients with this otherwise incurable retinal degeneration prompted the need to determine efficacy outcome measures. Comparisons were made between three computerized perimeters available in the clinic. These perimeters could deliver short-wavelength stimuli on longer-wavelength adapting backgrounds to measure whether S-cone vision can be quantified. Results from a cohort of normal subjects were compared across the three perimeters to determine S-cone isolation and test-retest variability. S-cone perimetry data from NR2E3-ESCS (enhanced S-cone syndrome) patients were examined and determined to have five stages of disease severity. Using these stages, strategies were proposed for monitoring efficacy of either a focal or retina-wide intervention. This work sets the stage for clinical trials.

Knowledge of evidence-based practices for PTSD among mental health court judges.

Mental health courts offer access to community-based care for defendants with psychiatric disorders, including posttraumatic stress disorder (PTSD). However, limited information is available on how judges make treatment decisions about evidence-based practices. In this qualitative study, we interviewed mental health court judges to evaluate: (1) perspectives toward the role of PTSD in criminal behavior; (2) knowledge about evidence-based practice for PTSD; (3) treatment decisions for defendants with PTSD; and (4) treatment decisions for defendants at risk for suicide, a common comorbidity with PTSD. We hypothesized that mental health court judges would report low familiarity with evidence-based practices for PTSD despite wide recognition of the impact of trauma on criminal behavior. Methods: Mental health court judges (N = 11, 60% women, 60% between 50-59 years) were recruited from 7 states in the US and completed a demographics questionnaire and semi-structured qualitative interview that was transcribed and double-coded. Results: Judges in mental health court unanimously agreed that PTSD is highly prevalent among their defendants, but that they had not having received formal education about evidence-based practices for PTSD. They reported relying on their team members to provide recommendations for treatment planning and viewed their role as the enforcer of the treatment teams' suggestions. Finally, judges also reported that suicide prevention is an important consideration and that there is a need for universal suicide risk assessments. Conclusions: These findings have implications for continuing education among judges in mental health court, and we recommend mandated training to increase awareness of evidence-based practices for PTSD and suicide prevention.

Defining hierarchical protein interaction networks from spectral analysis of bacterial proteomes.

Cellular behaviors emerge from layers of molecular interactions: proteins interact to form complexes, pathways, and phenotypes. We show that hierarchical networks of protein interactions can be defined from the statistical pattern of proteome variation measured across thousands of diverse bacteria and that these networks reflect the emergence of complex bacterial phenotypes. Our results are validated through gene-set enrichment analysis and comparison to existing experimentally derived databases. We demonstrate the biological utility of our approach by creating a model of motility in Pseudomonas aeruginosa and using it to identify a protein that affects pilus-mediated motility. Our method, SCALES (Spectral Correlation Analysis of Layered Evolutionary Signals), may be useful for interrogating genotype-phenotype relationships in bacteria.

Blue Cone Monochromacy Caused by the C203R Missense Mutation or Large Deletion Mutations.

Purpose: To compare the phenotype of blue cone monochromacy (BCM) caused by large deletion mutations with those having the C203R missense mutation. Methods: BCM patients with large deletion mutations (n = 21; age range, 5-60 years), and with the C203R missense mutation (n = 13; age range, 5-70 years), were studied with optical coherence tomography, visual acuity, and perimetric sensitivity in a retrospective observational case series. Perceptual estimates of spatial resolution driven by rods, S-cones, and L/M-cones were obtained by the choice of chromatic gratings presented on varied adapting conditions with a modified microperimeter. Results: Both genotypes had abnormal foveal photoreceptor structure early in life. Patients with the C203R mutation, however, had decades-longer persistence of foveal photoreceptor outer nuclear layer thickness and a slower rate of development of inner segment/outer segment defects than did patients with large deletion mutations. At late ages, both genotypes had comparably severe losses of central structure. At the rod-rich hot spot, there was no difference in structure between cohorts with age. Grating acuities in all BCM patients were driven by S-cones and rods; the foveal structural differences were not reflected in a difference between cohorts in visual sensitivity and spatial resolution. Conclusions: A difference in structural phenotype due to the C203R mutation versus large deletion mutations in BCM was detected as a more prolonged persistence of foveal photoreceptor structure in patients with the missense mutation. This should be taken into account in planning natural history studies, selecting outcomes for clinical trials, and defining the time window for possible therapies.