AICAR prevents heat-induced sudden death in RyR1 mutant mice independent of AMPK activation.

Mice with a knock-in mutation (Y524S) in the type I ryanodine receptor (Ryr1), a mutation analogous to the Y522S mutation that is associated with malignant hyperthermia in humans, die when exposed to short periods of temperature elevation (≥37 °C). We show here that treatment with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) prevents this heat-induced sudden death in this mouse model. The protection by AICAR is independent of AMP-activated protein kinase (AMPK) activation and results from a newly identified action of the compound on mutant Ryr1 to reduce Ca(2+) leak from the sarcoplasmic reticulum to the sarcoplasm. AICAR thus prevents Ca(2+)-dependent increases in the amount of both reactive oxygen species (ROS) and reactive nitrogen species (RNS) that act to further increase resting Ca(2+) concentrations. If unchecked, the temperature-driven increases in resting Ca(2+) concentrations and the amounts of ROS and RNS create an amplifying cycle that ultimately triggers sustained muscle contractions, rhabdomyolysis and death. Although antioxidants are effective in reducing this cycle in vitro, only AICAR prevents heat-induced death in vivo. Our findings suggest that AICAR is probably effective in prophylactic treatment of humans with enhanced susceptibility to exercise- and/or heat-induced sudden death associated with RYR1 mutations.

The effect of the coupling between the top plate and the fingerboard on the acoustic power radiated by a classical guitar (L).

An experimental investigation on the coupling between the fingerboard and the top plate of a classical guitar at low frequencies is presented. The study was carried out using a finished top plate under fixed boundary conditions and a commercial guitar. Radiated sound power was determined in one-third octave bands up to the band of 1 kHz based on measurements of sound intensity. The results provide evidence that the way in which the fingerboard and top plate are coupled is not a relevant factor in the radiated acoustic power of the classical guitar in the studied frequency range.

A resonance shift prediction based on the Boltzmann-Ehrenfest principle for cylindrical cavities with a rigid sphere.

An investigation on the resonance frequency shift for a plane-wave mode in a cylindrical cavity produced by a rigid sphere is reported in this paper. This change of the resonance frequency has been previously considered as a cause of oscillational instabilities in single-mode acoustic levitation devices. It is shown that the use of the Boltzmann-Ehrenfest principle of adiabatic invariance allows the derivation of an expression for the resonance frequency shift in a simpler and more direct way than a method based on a Green's function reported in literature. The position of the sphere can be any point along the axis of the cavity. Obtained predictions of the resonance frequency shift with the deduced equation agree quite well with numerical simulations based on the boundary element method. The results are also confirmed by experiments. The equation derived from the Boltzmann-Ehrenfest principle appears to be more general, and for large spheres, it gives a better approximation than the equation previously reported.

Removal of FKBP12 enhances mTOR-Raptor interactions, LTP, memory, and perseverative/repetitive behavior.

FK506-binding protein 12 (FKBP12) binds the immunosuppressant drugs FK506 and rapamycin and regulates several signaling pathways, including mammalian target of rapamycin (mTOR) signaling. We determined whether the brain-specific disruption of the FKBP12 gene in mice altered mTOR signaling, synaptic plasticity, and memory. Biochemically, the FKBP12-deficient mice displayed increases in basal mTOR phosphorylation, mTOR-Raptor interactions, and p70 S6 kinase (S6K) phosphorylation. Electrophysiological experiments revealed that FKBP12 deficiency was associated with an enhancement in long-lasting hippocampal long-term potentiation (LTP). The LTP enhancement was resistant to rapamycin, but not anisomycin, suggesting that altered translation control is involved in the enhanced synaptic plasticity. Behaviorally, FKBP12 conditional knockout (cKO) mice displayed enhanced contextual fear memory and autistic/obsessive-compulsive-like perseveration in several assays including the water maze, Y-maze reversal task, and the novel object recognition test. Our results indicate that FKBP12 plays a critical role in the regulation of mTOR-Raptor interactions, LTP, memory, and perseverative behaviors.

Transfer of angular momentum to matter from acoustical vortices in free space.

An experimental demonstration of the mechanical transfer of orbital angular momentum to matter from acoustical vortices in free field is presented. Vortices with topological charges l=+/-1 and l=+/-2 were generated and a torsion pendulum was used to study the angular momentum transfer to hanging disks of several sizes. This allowed us to make a comparative study of the effective acoustical torque in terms of topological charge of the vortex, the disk radius, and its position along the main propagation axis. A theoretical discussion of the generated sound fields is also provided.

[Noise conditions inside waiting rooms of primary care clinics]. / Ruido en salas de espera de unidades médicas.

OBJECTIVES: to explore the acoustic noise conditions of the waiting rooms in primary care facilities and to evaluate whether the ambient noise level was within the recommended levels for these facilities. METHODOLOGY: the waiting rooms of four primary care clinics located in the south of Mexico City were tested. Several recording points homogeneously distributed and close to the seats of the users were chosen. In each recording point, four recordings of the ambient noise were carried out in intervals of 20 to 40 minutes; this was done during the provision of care. The day in which the recordings were made was randomly selected. The values of the specifications used in the analysis of the ambient noise levels were determined in the laboratory. RESULTS: the ambient noise level of the waiting rooms in each of the four clinics was above 55 dB-A. This level is considered as the threshold of annoyance. In one of the clinics, the level exceeded 65 dB-A. The chief contributors to the noise were the conversations of the people that were at the waiting room or in adjacent rooms, and in some cases the sound from the TV sets. CONCLUSIONS: the study showed that the ambient noise level passed the upper limits indicated by The American National Standard Institute. It is appropriate to define criteria to guarantee suitable noise conditions inside health care facilities and to revise current Mexican standards.