Distinct roles of glycinergic and GABAergic inhibition in coordinating locomotor-like rhythms in the neonatal mouse spinal cord.

The primary objective of our study was to examine the role of the inhibitory neurotransmitters glycine and GABA in modulating spontaneous activity and coordinating neurochemically induced locomotor-like rhythms in the mouse spinal cord. Motor outputs were recorded in lumbar ventral roots of 1-4-day old neonatal mice, and the function of glycinergic and GABAergic synapses in regulating spontaneous and induced activities was examined by suppressing synaptic inhibition using selective glycine or GABAA receptor antagonists. Strychnine (0.5 microM), a glycine receptor antagonist, did not change the pattern of spontaneous activity that consisted of random single spikes and discharges of variable durations and intervals. In contrast, blocking GABAA receptors with either picrotoxin (10 microM) or bicuculline (5 microM) triggered bilaterally synchronous, non-rhythmic discharges. These findings suggested that GABAergic synapses suppressed excitatory synapses, and their disinhibition synchronized spontaneous discharges between the two sides of the spinal cord. Locomotor-like rhythms alternating between the two sides of the spinal cord were triggered by the neurotransmitter agonists 5-HT, N-methyl-D,L-aspartic acid and dopamine. Blocking glycine receptors increased tonic discharges, and in most preparations it reduced the phase correlation between the alternating rhythms. Inhibiting GABAA receptor-mediated synapses synchronized the onset and prolonged the duration of rhythmic discharges. Intraburst alternating peaks were evident and those were suppressed by strychnine, suggesting that they were mediated via glycinergic synapses. Our findings indicated that GABAergic and glycinergic synapses played different roles in modulating neurochemically induced locomotion rhythms. GABAergic inhibition regulated the onset and duration of neurochemically induced locomotor-like rhythms, and glycinergic inhibition stabilized the pattern of the alternating rhythms.

Make no mistake-errors can be controlled.

Traditional quality control methods identify "variation" as the enemy. However, the control of variation by itself can never achieve the remarkably low non-conformance rates of world class quality leaders. Because the control of variation does not achieve the highest levels of quality, an inordinate focus on these techniques obscures key quality improvement opportunities and results in unnecessary pain and suffering for patients, and embarrassment, litigation, and loss of revenue for healthcare providers. Recent experience has shown that mistakes are the most common cause of problems in health care as well as in other industrial environments. Excessive product and process complexity contributes to both excessive variation and unnecessary mistakes. The best methods for controlling variation, mistakes, and complexity are each a form of mistake proofing. Using these mistake proofing techniques, virtually every mistake and non-conformance can be controlled at a fraction of the cost of traditional quality control methods.

Defining the best quality-control systems by design and inspection.

Not all of the many approaches to quality control are equally effective. Nonconformities in laboratory testing are caused basically by excessive process variation and mistakes. Statistical quality control can effectively control process variation, but it cannot detect or prevent most mistakes. Because mistakes or blunders are frequently the dominant source of nonconformities, we conclude that statistical quality control by itself is not effective. I explore the 100% inspection methods essential for controlling mistakes. Unlike the inspection techniques that Deming described as ineffective, the new "source" inspection methods can detect mistakes and enable corrections before nonconformities are generated, achieving the highest degree of quality at a fraction of the cost of traditional methods. Key relationships between task complexity and nonconformity rates are also described, along with cultural changes that are essential for implementing the best quality-control practices.

Dipotassium tetramethyl osmate: a stain for electron microscopy.

Methanol solutions of dipotassium tetramethyl osmate (DTMO) have been found to be useful as general stains in electron microscopic studies of plant and fungal ultrastructure. The stain solutions are easy to prepare, stable when anhydrous and convenient to use. Although generally similar in staining to lead citrate stains, some elements of cell ultrastructure appear different with dipotassium tetramethyl osmate staining, particularly the outer cell walls of fungi. Indications of specific precipitate-producing reactions in cell storage areas are observed.