The Global Anesthesia Workforce Survey: Updates and Trends in the Anesthesia Workforce.

Background: There is a large global deficit of anesthesia providers. In 2016, the World Federation of Societies of Anaesthesiologists (WFSA) conducted a survey to count the number of anesthesia providers worldwide. Much work has taken place since then to strengthen the anesthesia health workforce.

Effects of Hydrostatic-Pressure on Muscle Contraction: A Look Back on Some Experimental Findings.

Findings from experiments that used hydrostatic pressure changes to analyse the process of skeletal muscle contraction are re-examined. The force in resting muscle is insensitive to an increase in hydrostatic pressure from 0.1 MPa (atmospheric) to 10 MPa, as also found for force in rubber-like elastic filaments.

The Location and Rate of the Phosphate Release Step in the Muscle Cross-Bridge Cycle.

It is controversial whether the phosphate (Pi) release step in the cross-bridge cycle occurs before or after the first tension-generating step and whether it is fast or slow. We have therefore modified our previous model of the frog cross-bridge cycle by including a Pi release step either before (model A) or after (model B) the first tension-generating step and refined the two models by downhill simplex runs against experimental data for the force-velocity relation and the tension transients after length steps. Pi release step was initially made slow (70 s), but after refinement, it became fast (∼500 s for model A and ∼6000 s for model B).

Mechanotransduction is required for establishing and maintaining mature inner hair cells and regulating efferent innervation.

In the adult auditory organ, mechanoelectrical transducer (MET) channels are essential for transducing acoustic stimuli into electrical signals. In the absence of incoming sound, a fraction of the MET channels on top of the sensory hair cells are open, resulting in a sustained depolarizing current. By genetically manipulating the in vivo expression of molecular components of the MET apparatus, we show that during pre-hearing stages the MET current is essential for establishing the electrophysiological properties of mature inner hair cells (IHCs).

Temperature Effects on Force and Actin⁻Myosin Interaction in Muscle: A Look Back on Some Experimental Findings.

Observations made in temperature studies on mammalian muscle during force development, shortening, and lengthening, are re-examined. The isometric force in active muscle goes up substantially on warming from less than 10 °C to temperatures closer to physiological (>30 °C), and the sigmoidal temperature dependence of this force has a half-maximum at ~10 °C. During steady shortening, when force is decreased to a steady level, the sigmoidal curve is more pronounced and shifted to higher temperatures, whereas, in lengthening muscle, the curve is shifted to lower temperatures, and there is a less marked increase with temperature.

The force-generation process in active muscle is strain sensitive and endothermic: a temperature-perturbation study.

In experiments on active muscle, we examined the tension decline and its temperature sensitivity at the onset of ramp shortening and at a range of velocities. A segment (∼1.5 mm long) of a skinned muscle fibre isolated from rabbit psoas muscle was held isometrically (sarcomere length ∼2.

Reinterpretation of the Tension Response of Muscle to Stretches and Releases.

We have reexamined the experimental time courses of tension in frog muscle after rapid length steps. The early tension recoveries are biexponential. After 3 nm/hs stretches and releases, the rates of the immediate rapid tension changes are similar but the subsequent tension fall after a stretch is much slower than the rise after a release.

The endothermic ATP hydrolysis and crossbridge attachment steps drive the increase of force with temperature in isometric and shortening muscle.

The isometric tetanic tension of skeletal muscle increases with temperature because attached crossbridge states bearing a relatively low force convert to those bearing a higher force. It was previously proposed that the tension-generating step(s) in the crossbridge cycle was highly endothermic and was therefore itself directly targeted by changes in temperature. However, this did not explain why a rapid rise in temperature (a temperature jump) caused a much slower rate of rise of tension than a rapid length step.

A cross-bridge cycle with two tension-generating steps simulates skeletal muscle mechanics.

We examined whether cross-bridge cycle models with one or two tension-generating steps can account for the force-velocity relation of and tension response to length steps of frog skeletal muscle. Transition-state theory defined the strain dependence of the rate constants. The filament stiffness was non-Hookean.

Mechanism of force enhancement during and after lengthening of active muscle: a temperature dependence study.

The aim of the present study was to examine the temperature dependence of active force in lengthening and shortening muscle. Experiments were done, in vitro, on bundles of intact fibres (fibre length L(0) ~2 mm; sarcomere length ~2.5 μm) isolated from a rat fast muscle (flexor hallucis brevis) and a ramp length change of 5-7% L(0) was applied on the plateau of an isometric tetanic contraction.

Position-dependent patterning of spontaneous action potentials in immature cochlear inner hair cells.

Spontaneous action potential activity is crucial for mammalian sensory system development. In the auditory system, patterned firing activity has been observed in immature spiral ganglion and brain-stem neurons and is likely to depend on cochlear inner hair cell (IHC) action potentials. It remains uncertain whether spiking activity is intrinsic to developing IHCs and whether it shows patterning.

Crossbridge and filament compliance in muscle: implications for tension generation and lever arm swing.

The stiffness of myosin heads attached to actin is a crucial parameter in determining the kinetics and mechanics of the crossbridge cycle. It has been claimed that the stiffness of myosin heads in the anterior tibialis muscle of the common frog (Rana temporaria) is as high as 3.3 pN/nm, substantially higher than its value in rabbit muscle (~1.

Crossbridge mechanism(s) examined by temperature perturbation studies on muscle.

An overall view of the contractile process that has emerged from -temperature-studies on active muscle is outlined. In isometric muscle, a small rapid temperature-jump (T-jump) enhances an early, pre-phosphate release, step in the acto-myosin (crossbridge) ATPase cycle and induces a characteristic rise in force indicating that crossbridge force generation is endothermic (force rises when heat is absorbed). Sigmoidal temperature dependence of steady force is largely due to the endothermic nature of force generation.

Crossbridge and non-crossbridge contributions to force in shortening and lengthening muscle.

Analysis of tension responses to ramp length changes in muscle can provide important information about the crossbridge cycle. During a ramp length change, the force response of an active muscle shows an early change in slope (the P₁ transition) followed by a later, gradual change in slope (the P₂ transition). Modeling shows that the first transition reflects the tension change associated with the crossbridge power stroke in shortening and with its reversal in lengthening; the reduction in slope at the second transition occurs when most of the crossbridges (myosin heads) that were attached at the start of the ramp become detached; the steady tension during shortening is borne mainly by post-stroke heads whereas tension during lengthening is borne mostly by pre-stroke heads.

Force and power generating mechanism(s) in active muscle as revealed from temperature perturbation studies.

The basic characteristics of the process of force and power generation in active muscle that have emerged from temperature studies are examined. This is done by reviewing complementary findings from temperature-dependence studies and rapid temperature-jump (T-jump) experiments and from intact and skinned fast mammalian muscle fibres. In isometric muscle, a small T-jump leads to a characteristic rise in force showing that crossbridge force generation is endothermic (heat absorbed) and associated with increased entropy (disorder).

Temperature jump induced force generation in rabbit muscle fibres gets faster with shortening and shows a biphasic dependence on velocity.

We examined the tension responses to ramp shortening and rapid temperature jump (<0.2 ms, 3-4 degrees C T-jump) in maximally Ca(2+)-activated rabbit psoas muscle fibres at 8-9 degrees C (the fibre length (L(0)) was approximately 1.5 mm and sarcomere length 2.

Probing muscle myosin motor action: x-ray (m3 and m6) interference measurements report motor domain not lever arm movement.

The key question in understanding how force and movement are produced in muscle concerns the nature of the cyclic interaction of myosin molecules with actin filaments. The lever arm of the globular head of each myosin molecule is thought in some way to swing axially on the actin-attached motor domain, thus propelling the actin filament past the myosin filament. Recent X-ray diffraction studies of vertebrate muscle, especially those involving the analysis of interference effects between myosin head arrays in the two halves of the thick filaments, have been claimed to prove that the lever arm moves at the same time as the sliding of actin and myosin filaments in response to muscle length or force steps.

Muscle fatigue examined at different temperatures in experiments on intact mammalian (rat) muscle fibers.

In experiments on small bundles of intact fibers from a rat fast muscle, in vitro, we examined the decline in force in repeated tetanic contractions; the aim was to characterize the effect of shortening and of temperature on the initial phase of muscle fatigue. Short tetanic contractions were elicited at a control repetition rate of 1/60 s, and fatigue was induced by raising the rate to 1/5 s for 2-3 min, both in isometric mode (no shortening) and in shortening mode, in which each tetanic contraction included a ramp shortening at a standard velocity. In experiments at 20 degrees C (n = 12), the force decline during a fatigue run was 25% in the isometric mode but was significantly higher (35%) in the shortening mode.

Aminoglycoside-induced phosphatidylserine externalization in sensory hair cells is regionally restricted, rapid, and reversible.

The aminophospholipid phosphatidylserine (PS) is normally restricted to the inner leaflet of the plasma membrane. During certain cellular processes, including apoptosis, PS translocates to the outer leaflet and can be labeled with externally applied annexin V, a calcium-dependent PS-binding protein. In mouse cochlear cultures, annexin V labeling reveals that the aminoglycoside antibiotic neomycin induces rapid PS externalization, specifically on the apical surface of hair cells.

An analysis of the temperature dependence of force, during steady shortening at different velocities, in (mammalian) fast muscle fibres.

We examined, over a wide range of temperatures (10-35 degrees C), the isometric tension and tension during ramp shortening at different velocities (0.2-4 L(0)/s) in tetanized intact fibre bundles from a rat fast (flexor hallucis brevis) muscle; fibre length (L(0)) was 2.2 mm and sarcomere length approximately 2.