A Cost Model for Neurological Diseases in Puerto Rico: Parkinson's Disease, Alzheimer's Disease and Huntington's Disease.

OBJECTIVE: This article proposes an engineering-economics model to determine the total cost of a neurological disease along its temporal progression. The objective was to develop a planning tool faithful to the reality of this type of ailment as well as to that of Puerto Rico (PR). METHODS: The proposed model organizes a given neurological disease into 3 progressive phases of deterioration; in each, the model collects the typical associated costs and adjusts them based on their value over time. This way, the total cost of the ailment is calculated and its present day dollar value expressed. Model verification was carried out using data from Puerto Rico related to Parkinson's, Alzheimer's, and Huntington's diseases. RESULTS: The method demonstrated here considered Parkinson's disease in PR. Our model calculated a total annual cost of $64,915 for a patient at the medium stage. This figure is larger than estimates from other authors, which fall between $41,689 and $51,600 for the USA. This difference is partially due to the proposed model considering the individual's opportunity cost of the loss of productive years, an original contribution of our work. CONCLUSION: A neurological disease is one in which an individual goes through progressive phases of deterioration that will require significant economic resources. The model proposed here is designed across the commonalities between Alzheimer's, Parkinson's, and Huntington's diseases and illustrated using costs from PR. As an additional contribution, it allows the consideration of the opportunity cost of lost productivity, a characteristic that makes it more realistic.

In vivo tracking of KCC2b expression during early brain development.

The neuronal chloride (Cl-) exporter, KCC2, regulates neuron excitability and development and undergoes a stereotypical pattern of delayed upregulation as neurons mature. KCC2 upregulation favors neural inhibition by establishing a negative Cl- gradient, ensuring GABA-induced Cl- currents are inward and inhibitory. We developed a zebrafish fluorescent reporter line, KCC2b:mCitrine, to track KCC2 expression in vivo during early brain development. KCC2b:mCitrine was first detected at 16 h postfertilization and by day 6 labeled most central and peripheral neurons and processes. At 20 h, expression was greatest in the soma-dense basal neuroepithelium but largely absent in apical and mantle zones where differentiation and migration primarily occur, and time lapse imaging at this stage supports a postmigration upregulation of KCC2b. Central dopamine neurons showed low KCC2b expression as observed in other species. KCC2b:mCitrine fluorescence was stable over minutes in most neurons, but brightness transients observed in single cells fit our expectation for real-time tracking of KCC2b upregulation in new neurons. To further assess whether fluorescence brightness tracks KCC2b expression, zebrafish embryos were exposed to bisphenol-A (BPA), which is known to suppress KCC2 expression. Fluorescence decreased after 6 days of BPA exposure but not after 2 or 4 days, suggesting that it is an accurate but delayed indicator of KCC2b expression. KCC2b:mCitrine zebrafish present a new method for visualizing KCC2b's complex dynamics during brain development, and potentially screening compounds aimed at modulating KCC2 expression.

Nanoscale organization of rotavirus replication machineries.

Rotavirus genome replication and assembly take place in cytoplasmic electron dense inclusions termed viroplasms (VPs). Previous conventional optical microscopy studies observing the intracellular distribution of rotavirus proteins and their organization in VPs have lacked molecular-scale spatial resolution, due to inherent spatial resolution constraints. In this work we employed super-resolution microscopy to reveal the nanometric-scale organization of VPs formed during rotavirus infection, and quantitatively describe the structural organization of seven viral proteins within and around the VPs. The observed viral components are spatially organized as five concentric layers, in which NSP5 localizes at the center of the VPs, surrounded by a layer of NSP2 and NSP4 proteins, followed by an intermediate zone comprised of the VP1, VP2, VP6. In the outermost zone, we observed a ring of VP4 and finally a layer of VP7. These findings show that rotavirus VPs are highly organized organelles.