Murine MPDZ-linked hydrocephalus is caused by hyperpermeability of the choroid plexus.

Though congenital hydrocephalus is heritable, it has been linked only to eight genes, one of which is MPDZ Humans and mice that carry a truncated version of MPDZ incur severe hydrocephalus resulting in acute morbidity and lethality. We show by magnetic resonance imaging that contrast medium penetrates into the brain ventricles of mice carrying a Mpdz loss-of-function mutation, whereas none is detected in the ventricles of normal mice, implying that the permeability of the choroid plexus epithelial cell monolayer is abnormally high. Comparative proteomic analysis of the cerebrospinal fluid of normal and hydrocephalic mice revealed up to a 53-fold increase in protein concentration, suggesting that transcytosis through the choroid plexus epithelial cells of Mpdz KO mice is substantially higher than in normal mice. These conclusions are supported by ultrastructural evidence, and by immunohistochemistry and cytology data. Our results provide a straightforward and concise explanation for the pathophysiology of Mpdz-linked hydrocephalus.

A Survey of Perianesthesia Nursing Electronic Documentation.

PURPOSE: Electronic health records have become a common part of the perianesthesia care workflow, particularly for data gathering and documentation. The purpose of this survey of perianesthesia nurses was to examine patterns of adoption of electronic health records and their effect on clinical documentation and patient care. DESIGN: A survey was sent to nurses who are members of the American Society of Perianesthesia Nursing (ASPAN). METHODS: The electronic documentation survey was sent to the e-mail addresses of 13,339 ASPAN members representing various practice environments across the United States. Results were examined through descriptive statistics. FINDINGS: About two thirds (66.02%) of the respondents indicated that they could capture 80% of their clinical interactions with the patient. Few nurses indicated that adoption of the EHR was done using a standardized terminology. Respondents (63.99%) overwhelmingly indicated that they spent less time interacting with patients and families because of electronic documentation demands. CONCLUSIONS: The results pertaining to the impact of the EHR on their practice were fairly mixed with some indication that there was greater access to important patient data, but with a trade-off of less satisfaction and efficiency. Improvements and evaluation of clinical documentation are being done, but ongoing optimization and improvements to the EHR based on the knowledge needs of nurses will help realize the promise of greater quality, safety, and access to data.

Neuron loss and degeneration in the progression of TDP-43 in frontotemporal lobar degeneration.

Frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) is associated with the accumulation of pathological neuronal and glial intracytoplasmic inclusions as well as accompanying neuron loss. We explored if cortical neurons detected by NeuN decreased with increasing TDP-43 inclusion pathology in the postmortem brains of 63 patients with sporadic and familial FTLD-TDP. Semi-automated quantitative algorithms to quantify histology in tissue sections stained with antibodies specific for pathological or phosphorylated TDP-43 (pTDP-43) and NeuN were developed and validated in affected (cerebral cortex) and minimally affected (cerebellar cortex) brain regions of FTLD-TDP cases. Immunohistochemistry (IHC) for NeuN and other neuronal markers found numerous neurons lacking reactivity, suggesting NeuN may reflect neuron health rather than neuron loss in FTLD. We found three patterns of NeuN and pTDP-43 reactivity in our sample of cortical tissue representing three intracortical region-specific stages of FTLD-TDP progression: Group 1 showed low levels of pathological pTDP-43 and high levels NeuN, while Group 2 showed increased levels of pTDP-43, and Group 3 tissues were characterized by reduced staining for both pTDP-43 and NeuN. Comparison of non-C9orf72/GRN FTLD-TDP with cases linked to both GRN mutations and C9orf72 expansions showed a significantly increased frequency of Group 3 histopathology in the latter cases, suggesting more advanced cortical disease. Hence, we propose that IHC profiles of pTDP-43 and NeuN reflect the burden of pTDP-43 and its deleterious effects on neuron health.