Previous data have indicated that T-type calcium channels (low-voltage activated T-channels) are potently inhibited by volatile anesthetics. Although the interactions of T-channels with a number of anesthetics have been described, the mechanisms by which these agents modulate channel activity, and the functional consequences of such interactions, are not well studied. Here, we used patch-clamp recordings to explore the actions of a prototypical volatile anesthetic, isoflurane (Iso), on recombinant human Ca V 3.1 and Ca V 3.2 isoforms of T-channels. We also performed behavioral testing of anesthetic endpoints in mice lacking Ca V 3.2. Iso applied at resting channel states blocked current through both isoforms in a similar manner at clinically relevant concentrations (1 minimum alveolar concentration, MAC). Inhibition was more prominent at depolarized membrane potentials (Ϫ65 versus Ϫ100 mV) as evidenced by hyperpolarizing shifts in channel availability curves and a 2.5-fold decrease in IC 50 values. Iso slowed recovery from inactivation and enhanced deactivation in both Ca V 3.1 and Ca V 3.2 in a comparable manner but caused a depolarizing shift in activation curves and greater use-dependent block of Ca V 3.2 channels. In behavioral tests, Ca V 3.2 knockout (KO) mice showed significantly decreased MAC in comparison with wild-type (WT) litter mates. KO and WT mice did not differ in loss of righting reflex, but mutant mice displayed a delayed onset of anesthetic induction. We conclude that state-dependent inhibition of T-channel isoforms in the central and peripheral nervous systems may contribute to isoflurane's important clinical effects.The effects of general anesthetics on ion channels have been the subject of intense research since studies describing specific interactions between anesthetics and proteins (Franks and Lieb, 1982, 1994). It is now known that some ligand-gated channels (e.g., GABA A ), voltage-gated channels, and background potassium channels display anesthetic sensitivity in vitro that is within the concentration range achieved during general anesthesia (Franks, 2008). These channels have overlapping physiological roles and pharmacological profiles, making it difficult to assign aspects of the anesthetic state to individual channel types. Thus, it has become clear that further study of anesthetic mechanisms of action on specific ion channels is needed.Low voltage-activated calcium channels activate with small depolarizations and allow calcium influx at resting potentials so that small differences in channel activity can result in large changes in cellular excitability and/or secondmessenger pathways. Recent molecular studies have indicated that at least three isoforms of T-channels exist: Ca V 3.1 (␣1G), Ca V 3.2 (␣1H), and Ca V 3.3 (␣1I) (Perez-Reyes, 2003). These channels are located throughout the spinothalamic pathway, in which nociceptive information passes from peripheral sensory neurons to the cortex. T-channels in smallsized dorsal root ganglia (DRG) neurons are believed to functi...

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Marijuana is the most widely consumed illicit substance in the United States, and an increasing number of states have legalized it for both medicinal and recreational purposes. As it becomes more readily available, there will be a concurrent rise in the number of users and, consequently, the number of motor vehicle operators driving under the influence. This article examines the cognitive and psychomotor effects of cannabis, as well as current policy concerning driving under the influence of drugs. The authors performed a MEDLINE search on the epidemiology of cannabis use, its cognitive and psychomotor effects, and policies regarding driving under the influence of drugs. Twenty-eight epidemiological studies, 16 acute cognitive and psychomotor studies, 8 chronic cognitive and psychomotor studies, and pertinent state and federal laws and policies were reviewed. These search results revealed that marijuana use is associated with significant cognitive and psychomotor effects. In addition, the legalization of marijuana varies from state to state, as do the laws pertaining to driving under the influence of drugs. Marijuana is a commonly found illicit substance in motor vehicle operators driving under the influence of drugs. Current evidence shows that blood levels of tetrahydrocannabinol do not correlate well with the level of impairment. In addition, although acute infrequent use of cannabis typically leads to cognitive and psychomotor impairment, this is not consistently the case for chronic heavy use. To establish the framework for driving under the influence of cannabis policy, we must review the current published evidence and examine existing policy at state and federal levels.

Objective Collate available evidence and provide guidance on whether to delay steroid injections after receiving a vaccine, and whether to delay vaccination if a recent steroid injection has been administered, leaving formal recommendations to various national societies. Methods A literature search was performed to identify information pertinent to steroid administration and the subsequent downstream effects on vaccine efficacy. The search was initiated on December 20, 2020, and the terms used were (steroid OR cortisone OR dexamethasone) AND (vaccine). The studies were limited to articles in the English language. Results Six studies specifically addressed the effect of steroids on vaccine efficacy. Three of the 6 studies indicated that steroids could be used during the peri‐vaccine period without significant suppression of the immune response. One study associated intra‐articular steroid injections with an increased risk of developing influenza even when vaccinated. The remaining 2 studies had mixed findings. One study showed that patients who received dexamethasone, but not prednisolone were able to mount an immune response resulting in increased IgG. Another study showed that vaccine efficacy was maintained if patients were on continuous steroids or steroids after vaccination, but not if they stopped steroids prior to vaccination. Conclusions Although there is no shared consensus in the studies reviewed, all but one study noted scenarios in which patients receiving steroids can still be successfully vaccinated.

Background: Lumbar spinal stenosis is a condition of progressive neurogenic claudication that can be managed with lumbar decompression surgery or less invasive interspinous process devices after failed conservative therapy. Popular interspinous process spacers include X-Stop, Vertiflex and Coflex, with X-Stop being taken off market due to its adverse events profile. Methods: A disproportionality analysis was conducted to determine whether a statistically significant signal exists in the three interspinous spacers and the reported adverse events using the Manufacturer and User Facility Device Experience (MAUDE) database maintained by the US Food and Drug Administration. Results: Statistically significant signals were found with each of the three interspinous spacer devices (Coflex, Vertiflex, and X-Stop) and each of the following adverse events: fracture, migration, and pain/worsening symptoms. Conclusions: Further studies such as randomized controlled trials are needed to validate the findings.