Using a Novel Connected Device for the Collection of Puffing Topography Data for the Vuse Solo Electronic Nicotine Delivery System in a Real-World Setting: Prospective Ambulatory Clinical Study.

BACKGROUND: Over the last decade, the use of electronic nicotine delivery systems (ENDSs) has risen, whereas studies that describe how consumers use these products have been limited. Most studies related to ENDS use have involved study designs focused on use in a central location environment or attempted to measure use outcomes through subjective self-reported end points. The development of accurate and reliable tools to collect data in a naturalistic real-world environment is necessary to capture the complexities of ENDS use. Using connected devices in a real-world setting provides a convenient and objective approach to collecting behavioral outcomes with ENDS. OBJECTIVE: The Product Use and Behavior instrument was developed and used to capture the use of the Vuse Solo ENDS in an ambulatory setting to best replicate real-world use behavior. This study aims to determine overall mean values for topography outcomes while also providing a definition for an ENDS use session. METHODS: A prospective ambulatory clinical study was performed with the Product Use and Behavior instrument. Participants (n=75) were aged between 21 and 60 years, considered in good health, and were required to be established regular users of ENDSs. To better understand use behavior within the population, the sample was sorted into percentiles with bins based on daily puff counts. To frame these data in the relevant context, they were binned into low-, moderate-, and high-use categories (10th to 40th, 40th to 70th, and 70th to 100th percentiles, respectively), with the low-use group representing the nonintense category, the high-use group representing the intense category, and the moderate-use group being reflective of the average consumer. RESULTS: Participants with higher daily use took substantially more puffs per use session (6.71 vs 4.40) and puffed more frequently (interpuff interval: 32.78 s vs 61.66 s) than participants in the low-use group. Puff duration remained consistent across the low-, moderate­, and high-use groups (2.10 s, 2.18 s, and 2.19 s, respectively). The moderate-use group had significantly shorter session lengths (P<.001) than the high- and low-use groups, which did not differ significantly from each other (P=.16). CONCLUSIONS: Using connected devices allows for a convenient and robust approach to the collection of behavioral outcomes related to product use in an ambulatory setting. By using the variables captured with these tools, it becomes possible to move away from predefined periods of use to better understand topography outcomes and define use sessions. The data presented here offer a possible method to define these sessions. These data also begin to frame international standards used for the analytical assessments of ENDSs in the correct context and begin to shed light on the differences between standardized testing regimens and actual use behavior. TRIAL REGISTRATION: Clinicaltrials.gov NCT04226404; https://clinicaltrials.gov/study/NCT04226404.

Training in a cooperative bimanual skilled reaching task, the popcorn retrieval task, improves unimanual function after motor cortical infarcts in rats.

Disuse of the paretic hand after stroke is encouraged by compensatory reliance on the nonparetic hand, to exacerbate impairment and potentially constrain motor rehabilitation efficacy. Rodent stroke model findings support that learning new unimanual skills with the nonparetic forelimb diminishes functional improvements that can be driven by rehabilitative training of the paretic forelimb. The influence of learning new ways of skillfully using the two hands together on paretic side function is much less clear. To begin to explore this, we developed a new cooperative bimanual skilled reaching task for rats, the Popcorn Retrieval Task. After motor cortical infarcts impaired an established unimanual reaching skill in the paretic forelimb, rats underwent a 7 week period of de novo bimanual training (BiT) or no-training control procedures (Cont). Probes of paretic forelimb unimanual performance revealed significant improvements during and after the training period in BiT vs. Cont. We additionally observed a striking change in the bimanual task strategy over training days: a switch from the paretic to the nonparetic forelimb for initiating reach-to-grasp sequences. This motivated another study to test whether rats that established the bimanual skill prior to the infarcts would similarly switch handedness, which they did not, though paretic paw use for manipulative movements diminished. These results indicate that unimanual function of the paretic side can be improved by novel bimanual skill practice, even when it involves compensatory reliance on the nonparetic hand. They further support the suitability of the Popcorn Retrieval Task for studying bimanual skill learning effects in rats.

Combining Enriched Environment, Progesterone, and Embryonic Neural Stem Cell Therapy Improves Recovery after Brain Injury.

Millions of persons every year are affected by traumatic brain injury (TBI), and currently no therapies have shown efficacy in improving outcomes clinically. Recent research has suggested that enriched environments (EE), embryonic neural stem cells (eNSC), and progesterone (PROG) improve functional outcomes after TBI, and further, several investigators have suggested that a polytherapuetic approach may have greater efficacy than a single therapy. The purpose of the current study was to determine if varying combinations of post-injury EE, progesterone therapy, or eNSC transplantation would improve functional outcomes over just a single therapy. A controlled cortical impact was performed in rats to create a lesion in the medial frontal cortex. The rats were then placed in either EE or standard environments and administered 10 mg/kg progesterone or vehicle injections 4 h post-injury and every 12 h for 72 h after the initial injection. Seven days after the surgery, rats were transplanted with either eNSCs or media. Rats were then tested on the open field test, Barnes maze, Morris water maze, and Rotor-Rod tasks. Improved functional outcomes were shown on a majority of the behavioral tasks in animals that received a combination of therapies. This effect was especially prominent with therapies that were combined with EE. Immunohistochemistry showed that the transplanted eNSCs survived, migrated, and displayed neural phenotypes. These data suggest that a poly-therapeutic approach after TBI improves functional recovery to a greater magnitude. Moreover, when polytherapies are combined with EE, the effects on recovery are enhanced, leading to greater recovery of function.

Pre and post-injury environmental enrichment effects functional recovery following medial frontal cortical contusion injury in rats.

The rodent has been the preferred research model for evaluating the mechanisms related to, and potential treatments for, traumatic brain injury (TBI). Many therapies previously determined to be effective in pre-clinical investigations have failed to show the same effectiveness in clinical trials. The environment a rodent is housed in plays an important role in brain and behavioral development. Housing rodents in non-enriched environments significantly alters the development of the rodent brain and its behavioral profile, negatively impacting the ecological validity of the rodent model. This investigation employed 113 male Long-Evans rats assigned to either an enriched environment (EE) or standard environment (SE) from post-natal day 25. At four months of age, rats received either a controlled cortical impact (CCI) to the medial frontal cortex (mFC) or sham injury. Rats assigned to EE or SE pre-injury were re-assigned to remain in, or switch to, EE or SE post-injury. The open-field test (OFT), vermicelli handling test (VHT) Morris water maze (MWM), and rotor-rod (RR), were used to evaluate the animals response to TBI. The data from the current investigation indicates that the performance of TBI rats assigned to pre-injury EE was improved on the MWM compared to the TBI rats assigned to pre-injury SE. However, those that were reared in the EE performed better on the MWM if placed into a SE post-injury as compared to those placed into the EE after insult. The TBI and sham groups that were raised, and remained, in the SE performed worse than any of the EE groups on the RR. TBI rats that were placed in the EE had larger cortices and more cells in the hippocampus than the TBI rats housed in the SE. These data strongly suggest that the pre-injury housing environment should be considered as investigators refine pre-clinical models of TBI.