Tetanic Stimulation Leads to Increased Accumulation of Ca^(2+)/Calmodulin-Dependent Protein Kinase II via Dendritic Protein Synthesis in Hippocampal Neurons

mRNA for the ɑ-subunit of CaMKII is abundant in dendrites of neurons in the forebrain (Steward, 1997). Here we show that tetanic stimulation of the Schaffer collateral pathway causes an increase in the concentration of ɑ-CaMKII in the dendrites of postsynaptic neurons. The increase is blocked by anisomycin and is detected by both quantitative immunoblot and semiquantitative immunocytochemistry. The increase in dendritic ɑ-CaMKII can be measured 100-200 µm away from the neuronal cell bodies as early as 5 min after a tetanus. Transport mechanisms for macromolecules from neuronal cell bodies are not fast enough to account for this rapid increase in distal portions of the dendrites. Therefore, we conclude that dendritic protein synthesis must produce a portion of the newly accumulated CaMKII. The increase in concentration of dendritic CaMKII after tetanus, together with the previously demonstrated increase in autophosphorylated CaMKII (Ouyang et al., 1997), will produce a prolonged increase in steady-state kinase activity in the dendrites, potentially influencing mechanisms of synaptic plasticity that are controlled through phosphorylation by CaMKII

Impact of social complexity on outcomes in cystic fibrosis after transfer to adult care

Objective This study evaluates the roles of medical and social complexity in health care use outcomes in cystic fibrosis (CF) after transfer from pediatric to adult care. Methods Retrospective cohort design included patients with CF who were transitioned into adult care at Indiana University from 2005 to 2015. Predictor variables included demographic and comorbidity data, age at transition, treatment complexity score (TCS), and an objective scoring measure of their social complexity (Bob's Level of Social Support, BLSS). Outcome variables included outpatient visit rates and hospitalization rates. Pearson's correlations and linear regression were used to analyze the data. Results The median age of the patients (N = 133) at the time of transition was 20 (IQR 19‐23) years. The mean FEV1 % predicted at transition was 69 ± 24%. TCS correlated with outpatient visit rates (r = 0.3, P = 0.003), as well as hospitalization rates (r = 0.4, P < 0.001); while the BLSS only correlated with hospitalization rates (r = 0.7, P < 0.001). After adjusting for covariates, the strongest predictors of post‐transfer hospitalizations are BLSS (P < 0.0001) and pre‐transfer hospitalization rate (P < 0.0001). Conclusion Greater treatment complexity is associated with greater healthcare utilization overall, while greater social complexity is associated with increased hospitalizations (but not outpatient visits). Screening young adults for social complexity may identify high‐risk subpopulations and allow for patient centered interventions to support them and prevent avoidable health care use

Event History Regression with Pseudo-Observations: Computational Approaches and an Implementation in R

Due to tradition and ease of estimation, the vast majority of clinical and epidemiological papers with time-to-event data report hazard ratios from Cox proportional hazards regression models. Although hazard ratios are well known, they can be difficult to interpret, particularly as causal contrasts, in many settings. Nonparametric or fully parametric estimators allow for the direct estimation of more easily causally interpretable estimands such as the cumulative incidence and restricted mean survival. However, modeling these quantities as functions of covariates is limited to a few categorical covariates with nonparametric estimators, and often requires simulation or numeric integration with parametric estimators. Combining pseudo-observations based on non-parametric estimands with parametric regression on the pseudo-observations allows for the best of these two approaches and has many nice properties. In this paper, we develop a user friendly, easy to understand way of doing event history regression for the cumulative incidence and the restricted mean survival, using the pseudo-observation framework for estimation. The interface uses the well known formulation of a generalized linear model and allows for features including plotting of residuals, the use of sampling weights, and correct variance estimation

Aligning use of intensive care with patient values in the USA: past, present, and future.

For more than three decades, both medical professionals and the public have worried that many patients receive non-beneficial care in US intensive care units during their final months of life. Some of these patients wish to avoid severe cognitive and physical impairments, and protracted deaths in the hospital setting. Recognising when intensive care will not restore a person’s health, and helping patients and families embrace goals related to symptom relief, interpersonal connection, or spiritual fulfilment are central challenges of critical care practice in the USA. We review trials from the past decade of interventions designed to address these challenges, and present reasons why evaluating, comparing, and implementing these interventions have been difficult. Careful scrutiny of the design and interpretation of past trials can show why improving goal concordant care has been so elusive, and suggest new directions for the next generation of research

A Comparison of Lung Function Values Among a SCUBA Diver Population and in Comparison to a Non-diver Population

The purpose of this study was to investigate possible correlations between lung function values (PEF, IRV, ERV, and FVC) among a diver population, as well as in comparison to a non-diver population. Independent variables for both populations were biological sex, age, and weekly physical activity. Independent variables for the diver population were dive tenure, number of logged dives, certification level, and gas mixture used. A spirometry test was conducted to collect lung function values of both populations. Data from this study suggest a statistically significant relationship between diver and non-diver sex and FVC, diver age and ERV, diver sex and ERV, and non-diver FVC and weekly physical activity