Neurexin 1 (NRXN1) splice isoform expression during human neocortical development and aging.

Neurexin 1 (NRXN1), a presynaptic cell adhesion molecule, is implicated in several neurodevelopmental disorders characterized by synaptic dysfunction including autism, intellectual disability and schizophrenia. To gain insight into NRXN1's involvement in human cortical development we used quantitative real-time PCR to examine the expression trajectories of NRXN1, and its predominant isoforms, NRXN1-α and NRXN1-ß, in prefrontal cortex from fetal stages to aging. In addition, we investigated whether prefrontal cortical expression levels of NRXN1 transcripts are altered in schizophrenia or bipolar disorder in comparison with non-psychiatric control subjects. We observed that all three NRXN1 transcripts were highly expressed during human fetal cortical development, markedly increasing with gestational age. In the postnatal dorsolateral prefrontal cortex, expression levels were negatively correlated with age, peaking at birth until ~3 years of age, after which levels declined markedly to be stable across the lifespan. NRXN1-ß expression was modestly but significantly elevated in the brains of patients with schizophrenia compared with non-psychiatric controls, whereas NRXN1-α expression was increased in bipolar disorder. These data provide novel evidence that NRXN1 expression is highest in human dorsolateral prefrontal cortex during critical developmental windows relevant to the onset and diagnosis of a range of neurodevelopmental disorders, and that NRXN1 expression may be differentially altered in neuropsychiatric disorders.

Cardiac hypertrophy: a matter of translation.

1. Left ventricular hypertrophy (LVH) of the heart is an adaptive response to sustained increases in blood pressure and hormone imbalances. Left ventricular hypertrophy is associated with programmed responses at the molecular and biochemical level in different subsets of cardiac cells, including the cardiac muscle cells (cardiomyocytes), fibroblasts, conductive tissue and coronary vasculature. 2. Regardless of the initiating cause, the actual increase in chamber enlargement is, in each case, due to an increase in size of a pre-existing cardiomyocyte population, with little or no change in their number; a process referred to as cellular hypertrophy. 3. An accelerated rate of global protein synthesis is the primary mechanism by which protein accumulation increases during cardiomyocyte hypertrophy. In turn, increased rates of synthesis are a result of increased translational rates of existing ribosomes (translational efficiency) and/or synthesis and recruitment of additional ribosomes (translational capacity). 4. The present review examines the relative importance of translational capacity and translational efficiency in the response of myocytes to acute and chronic demands for increased protein synthesis and the role of these mechanisms in the development of LVH.

Effect of routine pulse oximetry measurements on ED triage classification.

Pulse oximetry is commonly used to rapidly determine oxygen saturation and is incorporated in emergency triage as a screening for potential cardiopulmonary complications. This study examined the effect of routine pulse oximetry measurements on emergency department (ED) triage classification. Using a portable pulse oximeter, oxygen saturation of 1,235 adults presenting to a university-based, urban ED was obtained and each patient was assigned a classification of severity based on a standard 1-to-4 scale before and after the measurement. According to data obtained, a small but statistically significant group (2.8%) benefitted from the routine use of pulse oximetry in an emergency triage system and only 40% of these patients required admission or extended care. Although this group is small in number, the potential consequences of missing a hypoxic condition could be devastating for the individual patient. Since pulse oximetry is presently an inexpensive technology, it would seem to be a worthwhile screening tool for emergency triage.