People can use the placement of objects to infer communicative goals.

Beyond words and gestures, people have a remarkable capacity to communicate indirectly through everyday objects: A hat on a chair can mean it is occupied, rope hanging across an entrance can mean we should not cross, and objects placed in a closed box can imply they are not ours to take. How do people generate and interpret the communicative meaning of objects? We hypothesized that this capacity is supported by social goal inference, where observers recover what social goal explains an object being placed in a particular location. To test this idea, we study a category of common ad-hoc communicative objects where a small cost is used to signal avoidance. Using computational modeling, we first show that goal inference from indirect physical evidence can give rise to the ability to use object placement to communicate. We then show that people from the U.S. and the Tsimane'-a farming-foraging group native to the Bolivian Amazon-can infer the communicative meaning of object placement in the absence of a pre-existing convention, and that people's inferences are quantitatively predicted by our model. Finally, we show evidence that people can store and retrieve this meaning for use in subsequent encounters, revealing a potential mechanism for how ad-hoc communicative objects become quickly conventionalized. Our model helps shed light on how humans use their ability to interpret other people's behavior to embed social meaning into the physical world.

Social inferences from physical evidence via bayesian event reconstruction.

Humans can make remarkable social inferences by watching each other's behavior. In many cases, however, people can also make social inferences about agents whose behavior they cannot see, based only on the physical evidence left behind. We hypothesized that this capacity is supported by a form of mental event reconstruction. Under this account, observers derive social inferences by reconstructing the agent's behavior, based on the physical evidence that revealed their presence. We present a computational model of this idea, embedded in a Bayesian framework for action understanding, and show that its predictions match human inferences with high quantitative accuracy. Specifically, Experiment 1 shows that people can infer where an agent came from and which goal they pursued in a room, all from a small pile of cookie crumbs. Experiment 2 shows that people can explicitly reconstruct the actions that the agent took, and these reconstructed trajectories can predict the entry point and goal inferences from Experiment 1. Finally, Experiment 3 shows that people can also infer whether one or two agents were in a room based on the position of two piles of cookie crumbs. Our results shed light on how people extract social information from the physical world. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Nanostructured calcium silicate hydrate seeds accelerate concrete hardening: a combined assessment of benefits and risks.

Nanotechnology creates new possibilities to control and improve material properties for civil infrastructure. Special focus in this area is put on Portland cement and gypsum. Together their annual production is by far larger than for any other material worldwide. Nanomodification of these materials can be done during the few hours between dissolution and hardening, especially by nucleation of the re-crystallization with suitable colloids. Here we report first results in homogeneous seeding of the precipitation of calcium silicate hydrates within a real Portland cement composition. The occupational safety during the production phase and during mixing of concrete paste is addressed in detail by in vivo testing. We perform 5-day inhalation with 21-day recovery in rats and analyze organ-specific toxicity and 71 endpoints from bronchoalveolar lavage (BALF) and blood. In BALF parameters, no test-related changes were observed, indicating the generally low toxicity of the test material. Some mild lesions were observed in larynx level. In the lungs, all animals of the 50 mg/m³ concentration group revealed a minimal to mild increase in alveolar macrophages, which recovered back to control level.

Mexiletine and lidocaine suppress the excitability of dorsal horn neurons.

BACKGROUND: Spinal sensitization and facilitatory processes in dorsal horn neurons after nerve injury alter spinal outflow leading to enhanced pain perception and chronic pain syndromes. Clinically used Na+ channel blockers at doses which do not block conduction can relieve such chronic pain. Although much attention has been paid to their effect upon afferents, less work has been done with their effect on the excitability of central sensory neurons. Thus, we investigated the effects of the Na+ channel blockers mexiletine and lidocaine on sensory spinal dorsal horn neurons. METHODS: Patch-clamp recordings were directly performed in visualized neurons of the substantia gelatinosa in the spinal cord of young rats to investigate the effect of mexiletine and lidocaine in different types of dorsal horn neurons (tonically firing, adapting-firing, and single spike neurons). RESULTS: All three different types of neurons responded dose-dependently to mexiletine and lidocaine. Both local anesthetics reversibly inhibited Na+ and K+ currents. The half-maximal inhibitory concentration for Na+ conductance block was 89 +/- 2 or 54 +/- 6 microM and for delayed-rectifier K+ conductance block was 582 +/- 36 or 398 +/- 14 microM for lidocaine and mexiletine, respectively. The inhibition of Na+ and K+ currents consecutively altered the properties of single action potentials and reduced the firing rate of tonically firing and adapting-firing neurons. CONCLUSIONS: In clinically relevant concentrations, lidocaine and mexiletine reduced the excitability of sensory dorsal horn neurons via a blockade of Na+ and K+ channels. Our work confirms that, in addition to the peripheral effects of lidocaine and mexiletine, modulation of voltage-gated ion channels in the central nervous system contributes to the antinociceptive effects of these drugs used in pain therapy.

How much water does calcined gypsum contain?

Ordered water: Gypsum has been used for construction for millennia. The structure and water content of calcined gypsum, CaSO(4)0.5 H(2)O, has been under discussion until now: single-crystal structure analysis (see picture: S yellow, Ca gray, O blue, H red) provides an ordered model that is confirmed by DFT calculations.

Increased seroprevalence of parvovirus B 19 IgG in complex regional pain syndrome is not associated with antiendothelial autoimmunity.

The etiology of complex regional pain syndrome (CRPS) is unclear yet. Recently autoantibodies and antecedent viral infections have been discussed to be involved in the pathogenesis of CRPS. We investigated sera from 39 CRPS patients and healthy controls for parvovirus B19 IgG and the occurrence of antiendothelial autoantibodies (AECA). CRPS patients showed a higher seroprevalence of parvovirus B19 IgG than controls (p < 0.01). All CRPS 2 patients were positive. 10.2% of the CRPS patients and 10.0% of the controls had AECA (n.s.) and AECA were not associated with parvovirus B19 seropositivity. Our findings suggest the involvement of parvovirus B19, but not autoantibody-mediated endothelial cell damage, in the pathogenesis of CRPS.

Impact of TASK-1 in human pulmonary artery smooth muscle cells.

The excitability of pulmonary artery smooth muscle cells (PASMC) is regulated by potassium (K+) conductances. Although studies suggest that background K+ currents carried by 2-pore domain K+ channels are important regulators of resting membrane potential in PASMC, their role in human PASMC is unknown. Our study tested the hypothesis that TASK-1 leak K+ channels contribute to the K+ current and resting membrane potential in human PASMC. We used the whole-cell patch-clamp technique and TASK-1 small interfering RNA (siRNA). Noninactivating K+ current performed by TASK-1 K+ channels were identified by current characteristics and inhibition by anandamide and acidosis (pH 6.3), each resulting in significant membrane depolarization. Moreover, we showed that TASK-1 is blocked by moderate hypoxia and activated by treprostinil at clinically relevant concentrations. This is mediated via protein kinase A (PKA)-dependent phosphorylation of TASK-1. To further confirm the role of TASK-1 channels in regulation of resting membrane potential, we knocked down TASK-1 expression using TASK-1 siRNA. The knockdown of TASK-1 was reflected by a significant depolarization of resting membrane potential. Treatment of human PASMC with TASK-1 siRNA resulted in loss of sensitivity to anandamide, acidosis, alkalosis, hypoxia, and treprostinil. These results suggest that (1) TASK-1 is expressed in human PASMC; (2) TASK-1 is hypoxia-sensitive and controls the resting membrane potential, thus implicating an important role for TASK-1 K+ channels in the regulation of pulmonary vascular tone; and (3) treprostinil activates TASK-1 at clinically relevant concentrations via PKA, which might represent an important mechanism underlying the vasorelaxing properties of prostanoids and their beneficial effect in vivo.

Ketamine impairs excitability in superficial dorsal horn neurones by blocking sodium and voltage-gated potassium currents.

Ketamine shows, besides its general anaesthetic effect, a potent analgesic effect after spinal administration. We investigated the local anaesthetic-like action of ketamine and its enantiomers in Na+ and K+ channels and their functional consequences in dorsal horn neurones of laminae I-III, which are important neuronal structures for pain transmission receiving most of their primary sensory input from Adelta and C fibres. Combining the patch-clamp recordings in slice preparation with the 'entire soma isolation' method, we studied action of ketamine on Na+ and voltage-activated K+ currents. The changes in repetitive firing behaviour of tonically firing neurones were investigated in current-clamp mode after application of ketamine. Concentration-effect curves for the Na+ peak current revealed for tonic block half-maximal inhibiting concentrations (IC50) of 128 microM and 269 microM for S(+) and R(-)-ketamine, respectively, showing a weak stereoselectivity. The block of Na+ current was use-dependent. The voltage-dependent K+ current (K(DR)) was also sensitive to ketamine with IC50 values of 266 microM and 196 microM for S(+) and R(-)-ketamine, respectively. Rapidly inactivating K+ currents (K(A)) were less sensitive to ketamine. The block of K(DR) channels led to an increase in action potential duration and, as a consequence, to lowering of the discharge frequency in the neurones. We conclude that ketamine blocks Na+ and K(DR) channels in superficial dorsal horn neurones of the lumbar spinal cord at clinically relevant concentrations for local, intrathecal application. Ketamine reduces the excitability of the neurones, which may play an important role in the complex mechanism of its action during spinal anaesthesia.

Lidocaine and octanol have different modes of action at tetrodotoxin-resistant Na(+) channels of peripheral nerves.

UNLABELLED: Local anesthetics and alcohols block impulse conduction in peripheral nerves by inhibiting Na(+) currents. In small peripheral nerve fibers, tetrodotoxin-resistant (TTX-r) Na(+) channels play an important role in impulse generation. We investigated the effects of lidocaine and the alcohol octanol on TTX-r Na(+) channels. Currents were recorded with the whole-cell patch-clamp method from enzymatically isolated rat dorsal root ganglion cells (data evaluation: nonlinear least-squares fitting). Lidocaine and octanol blocked the TTX-r Na(+) current in a reversible and concentration-dependent manner (50% inhibitory concentration values: 177 +/- 25 and 455 +/- 25 microM, respectively). Lidocaine additionally produced a strong use-dependent block. Both drugs showed a strong dynamic block (i.e., block developed during the time course of current activation and inactivation). Double-pulse protocols showed a slow dissociation of lidocaine from the channel during repolarization (time constant: 1763 +/- 63 ms; 300 microM). The dissociation of octanol was too quick to be distinguished from normal current repriming kinetics of 2.2 ms. Lidocaine and octanol acted noncompetitively in the Na(+) channel. Lidocaine and octanol have different blocking properties on the TTX-r Na(+) current and bind to different channel sites. IMPLICATIONS: Lidocaine and octanol have different inhibitory effects on the function of tetrodotoxin-resistant Na(+) channels in rat dorsal root ganglion cells, as well as noncompetitive modes of action, as investigated by the whole-cell patch-clamp method, and therefore are likely to have different binding sites on the channel.

Local anaesthetics block hyperpolarization-activated inward current in rat small dorsal root ganglion neurones.

(1) Hyperpolarizing voltage steps evoke slowly activating inward currents in a variety of neurones and in cardiac cells. This hyperpolarization-activated inward current (I(h)) is thought to play a significant role in cell excitability, firing frequency, or in setting of the resting membrane potential in these cells. We studied the effects of lidocaine, mepivacaine, QX-314 and bupivacaine as well as its enantiomers on I(h) in the membrane of dorsal root ganglion neurones (DRG). (2) The patch-clamp technique was applied to small dorsal root ganglion neurones identified in 200 micro M thin slices of young rat DRGs. Under voltage-clamp conditions, the whole-cell I(h) current was recorded in the presence of different concentrations of the local anaesthetics. In current-clamp mode the resting membrane potential and the voltage response of DRG neurones to injected current pulses were investigated. (3) I(h) was reversibly blocked by bupivacaine, lidocaine and mepivacaine applied externally in clinically relevant concentrations. Concentration-response curves gave half-maximum inhibiting concentrations of 55, 99 and 190 micro M, respectively. Bupivacaine block of the I(h) current was not stereoselective. No significant effect was observed when QX-314 was applied to the external surface of the membrane. (4) In current-clamp experiments 60 micro M bupivacaine slightly hyperpolarized the membrane. The membrane stimulation by low-amplitude current pulses in the presence of bupivacaine showed an increase of the hyperpolarizing responses. (5) Our findings suggest an important role of the I(h)-block by local anaesthetics in the complex mechanism of drug action during epidural and spinal anaesthesia.

A combined stage 1 and 2 repair for hypoplastic left heart syndrome: anaesthetic considerations.

Therapy of hypoplastic left heart syndrome (HLHS) consists of the staged Norwood procedure or cardiac transplantation. Stenting the ductus arteriosus and subsequent banding of the pulmonary arteries allows the combination of neoaortic reconstruction with the establishment of a bidirectional cavopulmonary connection (combined stage 1 and 2 procedure) in a later session. We report the anaesthetic management in eight infants ranging from 107 to 195 days undergoing a combined stage 1 and 2 procedure. Nonselective pulmonary vasodilators and nitric oxide were needed in all cases to improve oxygen saturation in the postbypass period. Phosphodiesterase inhibitors and epinephrine were required in all patients for inotropic support during and after weaning off cardiopulmonary bypass. The procedure was successful in seven patients. One patient died intraoperatively because of right heart failure. The physiological changes of this new surgical strategy for palliation of HLHS offers a challenge for the anaesthetist primarily in the early postbypass period.

Enhancement of delayed-rectifier potassium conductance by low concentrations of local anaesthetics in spinal sensory neurones.

Combining the patch-clamp recordings in slice preparation with the 'entire soma isolation' method we studied action of several local anaesthetics on delayed-rectifier K(+) currents in spinal dorsal horn neurones. Bupivacaine, lidocaine and mepivacaine at low concentrations (1 - 100 microM) enhanced delayed-rectifier K(+) current in intact neurones within the spinal cord slice, while exhibiting a partial blocking effect at higher concentrations (>100 microM). In isolated somata 0.1 - 10 microM bupivacaine enhanced delayed-rectifier K(+) current by shifting its steady-state activation characteristic and the voltage-dependence of the activation time constant to more negative potentials by 10 - 20 mV. Detailed analysis has revealed that bupivacaine also increased the maximum delayed-rectifier K(+) conductance by changing the open probability, rather than the unitary conductance, of the channel. It is concluded that local anaesthetics show a dual effect on delayed-rectifier K(+) currents by potentiating them at low concentrations and partially suppressing at high concentrations. The phenomenon observed demonstrated the complex action of local anaesthetics during spinal and epidural anaesthesia, which is not restricted to a suppression of Na(+) conductance only.