Meiotic exchange and segregation in female mice heterozygous for paracentric inversions.

Inversion heterozygosity has long been noted for its ability to suppress the transmission of recombinant chromosomes, as well as for altering the frequency and location of recombination events. In our search for meiotic situations with enrichment for nonexchange and/or single distal-exchange chromosome pairs, exchange configurations that are at higher risk for nondisjunction in humans and other organisms, we examined both exchange and segregation patterns in 2728 oocytes from mice heterozygous for paracentric inversions, as well as controls. We found dramatic alterations in exchange position in the heterozygotes, including an increased frequency of distal exchanges for two of the inversions studied. However, nondisjunction was not significantly increased in oocytes heterozygous for any inversion. When data from all inversion heterozygotes were pooled, meiotic nondisjunction was slightly but significantly higher in inversion heterozygotes (1.2%) than in controls (0%), although the frequency was still too low to justify the use of inversion heterozygotes as a model of human nondisjunction.

Motor dysfunction and gliosis with preserved dopaminergic markers in human alpha-synuclein A30P transgenic mice.

Alpha-synuclein is a major component of Lewy bodies (LBs) in the substantia nigra and cortex in Parkinson's disease (PD) and dementia with Lewy bodies (DLB), and in glial inclusions in multiple systems atrophy (MSA). Mutations in alpha-synuclein have been associated with autosomal dominant forms of PD. We investigated the clinical and neuropathological effects of overexpression of human alpha-synuclein, alpha-synuclein A30P, and alpha-synuclein A53T under the control of the hamster prion protein (PrP) promoter; 5-15x endogenous levels of protein expression were achieved with widespread neuronal, including nigral, transgene expression. High expression of alpha-synuclein A30P in the Tg5093 line was associated with a progressive motor disorder with rigidity, dystonia, gait impairment, and tremor. Histological analysis of this line showed aberrant expression of the protein in cell soma and progressive CNS gliosis, but no discrete Lewy body-like alpha-synuclein inclusions could be identified. Biochemical analysis demonstrated alpha-synuclein fragmentation. Despite strong expression of the transgene in the nigra, there was no specific deterioration of the nigrostriatal dopaminergic system as assessed by quantitation of nigral tyrosine hydroxylase (TH) containing neurons, striatal TH immunoreactivity, dopamine levels, or dopamine receptor number and function. Lower expressing lines had no specific behavioral or histopathological phenotype. Thus, high expression of mutant human alpha-synuclein resulted in a progressive motor and widespread CNS gliotic phenotype independent of dopaminergic dysfunction in the Tg5093 line.

How well do emergency physicians document confirmation of endotracheal tube placement?

The authors' goal was to determine the rate at which emergency physicians document confirmation of endotracheal tube (ET) placement. The study was conducted in a 60 000-visit emergency department (ED) of an urban tertiary referral hospital. The authors' airway registry database was used to identify patients requiring airway management; 433 patients met study criteria, 281 (65%) were intubated in the ED, and 152 (35%) were intubated prior to arrival. ET confirmation was documented for 270 (96%) patients intubated in the ED and 52 (34%) patients intubated before arrival (P < .0001).The rate was higher for patients intubated by emergency medical services (40/64 [63%]) than for interhospital transfers (12/88 [14%]) (P < .0001). Documentation of ET placement has implications for patient care and safety. This study indicates that educational interventions are warranted to improve physicians' awareness of the importance of documenting correct tube placement.

Airway registry: a performance improvement surveillance project of emergency department airway management.

The aim of this study was to determine if use of a standardized airway data collection sheet can survey airway management practices in an emergency department. Success rates and trends from the authors' facility have been benchmarked against the National Emergency Airway Registry (NEAR). This study included all patients requiring invasive airway management during a 21-month period (July 1, 2005, through March 31, 2007). An audit form was developed and implemented to collect data on intubations. During the study period, 224 patients required invasive airway control. Of all airways managed by emergency medicine residents, the intubation success rate was 99% (200/203; 95% confidence interval [CI] = 96%-100%), with 3% of those (6/203; 95% CI = 1%-6%) requiring more than 3 attempts; 3 patients (1%; 95% CI = 0%-4%) could not be intubated and required a surgical airway. Use of an airway registry based on the NEAR registry as a benchmark of rates and types of successful intubation allows comparison of airway practices.

Improving emergency department door-to-electrocardiogram time in ST segment elevation myocardial infarction.

For patients presenting to emergency departments (ED) with a suspected acute coronary syndrome, time of arrival until an electrocardiogram is performed is an important quality metric. In our ED routine quality monitoring found that mean door-to-electrocardiogram (D2ECG) time did not meet our goal and national benchmark of 10 minutes. We describe the use of quality improvement tools to assess and decrease our D2ECG time. The ED quality improvement committee identified 2 main causes of D2ECG >10 minutes: (1) priority delay (eg, completing triage and registration data entry tasks before ECG), and (2) failure to recognize patients with nonchest pain ST Elevation Myocardial Infarction (STEMI) symptoms. Interventions included are-designed patient prioritization process for triage, staff assignment to provide immediate ECG testing, continuous feedback and a triage staff educational initiative to identify high risk patients. Mean time to ECG before intervention was 21.28 +/- 5.49 minutes. After the intervention period, the mean D2ECG for STEMI decreased to 9.47 +/- 2.48 minutes representing a 55% improvement. A D2ECG time of less than 10 minutes time can be achieved by the implementation of patient prioritization triage process changes, assigning specific personnel to obtain the ECG, continuous feedback by reviewing cases that fall outside the 10-minute goal and by ED staff education regarding STEMI symptoms other than chest pain.

Sex, not genotype, determines recombination levels in mice.

Recombination, the precise physical breakage and rejoining of DNA between homologous chromosomes, plays a central role in mediating the orderly segregation of meiotic chromosomes in most eukaryotes. Despite its importance, the factors that control the number and placement of recombination events within a cell remain poorly defined. The rate of recombination exhibits remarkable species specificity, and, within a species, recombination is affected by the physical size of the chromosome, chromosomal location, proximity to other recombination events (i.e., chiasma interference), and, intriguingly, the sex of the transmitting parent. To distinguish between simple genetic and nongenetic explanations of sex-specific recombination differences in mammals, we compared recombination in meiocytes from XY sex-reversed and XO females with that in meiocytes from XX female and XY male mice. The rate and pattern of recombination in XY and XO oocytes were virtually identical to those in normal XX females, indicating that sex, not genotype, is the primary determinant of meiotic recombination patterns in mammals.