Opioid-Sparing Pain Management in Upper Extremity Surgery: Part 1: Role of the Surgeon and Anesthesiologist.

A multimodal pain management strategy combines complementary medications and techniques, targeting unique pathways, to improve overall analgesic effect and reduce opioid requirements. In this 2-part review, we examine the literature identifying nonopioid analgesic modalities and their targets in the pain pathway as well as anesthetic techniques found to be opioid-sparing in the practice of upper extremity surgery. First, we focus on operative anesthesia and analgesia and areas for future research specific to upper extremity surgery. In part 2, we discuss the nonopioid options available after surgery.

Opioid-Sparing Pain Management in Upper Extremity Surgery: Part 2: Surgeon as Prescriber.

A multimodal pain management strategy combines complementary medications and techniques, targeting unique pathways, to improve overall analgesic effect and reduce opioid requirements. In this 2-part review, we examine the literature identifying nonopioid analgesic modalities and their targets in the pain pathway as well as anesthetic techniques found to be opioid sparing in the practice of upper extremity surgery. Part 1 focused on operative anesthesia and analgesia. In part 2, we discuss the nonopioid options available after surgery and explore areas for future investigation specific to upper extremity surgery.

Selective reactions to different killer whale call categories in two delphinid species.

The risk of predation is often invoked as an important factor influencing the evolution of social organization in cetaceans, but little direct information is available about how these aquatic mammals respond to predators or other perceived threats. We used controlled playback experiments to examine the behavioral responses of short-finned pilot whales (Globicephala macrorhynchus) off Cape Hatteras, NC, USA, and Risso's dolphins (Grampus griseus) off the coast of Southern California, USA, to the calls of a potential predator, mammal-eating killer whales. We transmitted calls of mammal-eating killer whales, conspecifics and baleen whales to 10 pilot whales and four Risso's dolphins equipped with multi-sensor archival acoustic recording tags (DTAGs). Only playbacks of killer whale calls resulted in significant changes in tagged animal heading. The strong responses observed in both species occurred only following exposure to a subset of killer whale calls, all of which contained multiple non-linear properties. This finding suggests that these structural features of killer whale calls convey information about predatory risk to pilot whales and Risso's dolphins. The observed responses differed between the two species; pilot whales approached the sound source while Risso's dolphins fled following playbacks. These divergent responses likely reflect differences in anti-predator response mediated by the social structure of the two species.

Benefits of Meeting the Healthy People 2030 Youth Sports Participation Target.

INTRODUCTION: Healthy People 2030, a U.S. government health initiative, has indicated that increasing youth sports participation to 63.3% is a priority in the U.S. This study quantified the health and economic value of achieving this target. METHODS: An agent-based model developed in 2023 represents each person aged 6-17 years in the U.S. On each simulated day, agents can participate in sports that affect their metabolic and mental health in the model. Each agent can develop different physical and mental health outcomes, associated with direct and indirect costs. RESULTS: Increasing the proportion of youth participating in sports from the most recent participation levels (50.7%) to the Healthy People 2030 target (63.3%) could reduce overweight/obesity prevalence by 3.37% (95% CI=3.35%, 3.39%), resulting in 1.71 million fewer cases of overweight/obesity (95% CI=1.64, 1.77 million). This could avert 352,000 (95% CI=336,200, 367,500) cases of weight-related diseases and gain 1.86 million (95% CI=1.86, 1.87 million) quality-adjusted life years, saving $22.55 billion (95% CI=$22.46, $22.63 billion) in direct medical costs and $25.43 billion (95% CI= $25.25, $25.61 billion) in productivity losses. This would also reduce depression/anxiety symptoms, saving $3.61 billion (95% CI=$3.58, $3.63 billion) in direct medical costs and $28.38 billion (95% CI=$28.20, $28.56 billion) in productivity losses. CONCLUSIONS: This study shows that achieving the Healthy People 2030 objective could save third-party payers, businesses, and society billions of dollars for each cohort of persons aged 6-17 years, savings that would continue to repeat with each new cohort. This suggests that even if a substantial amount is invested toward this objective, such investments could pay for themselves.

Synaptotagmin: Mechanisms of an electrostatic switch.

Synaptic transmission relies on the fast, synchronous fusion of neurotransmitter filled vesicles with the presynaptic membrane. Synaptotagmin is the Ca2+ sensor that couples the Ca2+ influx into nerve terminals following an action potential with this fast, synchronous vesicle fusion. Over two decades of synaptotagmin research has provided many clues as to how Ca2+ binding by synaptotagmin may lead to vesicle fusion. In vitro studies of molecular binding interactions are essential for elucidating potential mechanisms. However, an in vivo system to evaluate the postulated mechanisms is required to determine functional significance. The neuromuscular junction (NMJ) has long been an indispensable tool for synaptic research and studies at the NMJ will undoubtedly continue to provide key insights into synaptotagmin function.

The C2A domain of synaptotagmin is an essential component of the calcium sensor for synaptic transmission.

The synaptic vesicle protein, synaptotagmin, is the principle Ca2+ sensor for synaptic transmission. Ca2+ influx into active nerve terminals is translated into neurotransmitter release by Ca2+ binding to synaptotagmin's tandem C2 domains, triggering the fast, synchronous fusion of multiple synaptic vesicles. Two hydrophobic residues, shown to mediate Ca2+-dependent membrane insertion of these C2 domains, are required for this process. Previous research suggested that one of its tandem C2 domains (C2B) is critical for fusion, while the other domain (C2A) plays only a facilitatory role. However, the function of the two hydrophobic residues in C2A have not been adequately tested in vivo. Here we show that these two hydrophobic residues are absolutely required for synaptotagmin to trigger vesicle fusion. Using in vivo electrophysiological recording at the Drosophila larval neuromuscular junction, we found that mutation of these two key C2A hydrophobic residues almost completely abolished neurotransmitter release. Significantly, mutation of both hydrophobic residues resulted in more severe deficits than those seen in synaptotagmin null mutants. Thus, we report the most severe phenotype of a C2A mutation to date, demonstrating that the C2A domain is absolutely essential for synaptotagmin's function as the electrostatic switch.

The role of the C2A domain of synaptotagmin 1 in asynchronous neurotransmitter release.

Following nerve stimulation, there are two distinct phases of Ca2+-dependent neurotransmitter release: a fast, synchronous release phase, and a prolonged, asynchronous release phase. Each of these phases is tightly regulated and mediated by distinct mechanisms. Synaptotagmin 1 is the major Ca2+ sensor that triggers fast, synchronous neurotransmitter release upon Ca2+ binding by its C2A and C2B domains. It has also been implicated in the inhibition of asynchronous neurotransmitter release, as blocking Ca2+ binding by the C2A domain of synaptotagmin 1 results in increased asynchronous release. However, the mutation used to block Ca2+ binding in the previous experiments (aspartate to asparagine mutations, sytD-N) had the unintended side effect of mimicking Ca2+ binding, raising the possibility that the increase in asynchronous release was directly caused by ostensibly constitutive Ca2+ binding. Thus, rather than modulating an asynchronous sensor, sytD-N may be mimicking one. To directly test the C2A inhibition hypothesis, we utilized an alternate C2A mutation that we designed to block Ca2+ binding without mimicking it (an aspartate to glutamate mutation, sytD-E). Analysis of both the original sytD-N mutation and our alternate sytD-E mutation at the Drosophila neuromuscular junction showed differential effects on asynchronous release, as well as on synchronous release and the frequency of spontaneous release. Importantly, we found that asynchronous release is not increased in the sytD-E mutant. Thus, our work provides new mechanistic insight into synaptotagmin 1 function during Ca2+-evoked synaptic transmission and demonstrates that Ca2+ binding by the C2A domain of synaptotagmin 1 does not inhibit asynchronous neurotransmitter release in vivo.

Developing cultural competence in caring for LGBTQI+ patients.

Evidence demonstrates that subconscious and intentional discrimination against lesbian, gay, bisexual, transgender, queer or questioning, and intersex (LGBTQI+) people continues to exist in the UK healthcare system. Surveys have indicated significant health inequalities in LGBTQI+ populations, including high rates of mental health issues and suboptimal healthcare experiences. This article explores these issues and encourages nurses to reflect on their unique and privileged position to champion the rights of vulnerable people, as well as their role in improving the healthcare experience of LGBTQI+ patients in the future. It also discusses safety issues and special considerations for LGBTQI+ patients, including those related to sexual health, mental health and intellectual disabilities.

Interresponse time structures in variable-ratio and variable-interval schedules.

The interresponse-time structures of pigeon key pecking were examined under variable-ratio, variable-interval, and variable-interval plus linear feedback schedules. Whereas the variable-ratio and variable-interval plus linear feedback schedules generally resulted in a distinct group of short interresponse times and a broad distribution of longer interresponse times, the variable-interval schedules generally showed a much more continuous distribution of interresponse times. The results were taken to indicate that a log survivor analysis or double exponential fit of interresponse times may not be universally applicable to the task of demonstrating that operant behavior can be dichotomized into bouts of engagement and periods of disengagement.

Hidden Markov models reveal complexity in the diving behaviour of short-finned pilot whales.

Diving behaviour of short-finned pilot whales is often described by two states; deep foraging and shallow, non-foraging dives. However, this simple classification system ignores much of the variation that occurs during subsurface periods. We used multi-state hidden Markov models (HMM) to characterize states of diving behaviour and the transitions between states in short-finned pilot whales. We used three parameters (number of buzzes, maximum dive depth and duration) measured in 259 dives by digital acoustic recording tags (DTAGs) deployed on 20 individual whales off Cape Hatteras, North Carolina, USA. The HMM identified a four-state model as the best descriptor of diving behaviour. The state-dependent distributions for the diving parameters showed variation between states, indicative of different diving behaviours. Transition probabilities were considerably higher for state persistence than state switching, indicating that dive types occurred in bouts. Our results indicate that subsurface behaviour in short-finned pilot whales is more complex than a simple dichotomy of deep and shallow diving states, and labelling all subsurface behaviour as deep dives or shallow dives discounts a significant amount of important variation. We discuss potential drivers of these patterns, including variation in foraging success, prey availability and selection, bathymetry, physiological constraints and socially mediated behaviour.

Drosophila studies support a role for a presynaptic synaptotagmin mutation in a human congenital myasthenic syndrome.

During chemical transmission, the function of synaptic proteins must be coordinated to efficiently release neurotransmitter. Synaptotagmin 2, the Ca2+ sensor for fast, synchronized neurotransmitter release at the human neuromuscular junction, has recently been implicated in a dominantly inherited congenital myasthenic syndrome associated with a non-progressive motor neuropathy. In one family, a proline residue within the C2B Ca2+-binding pocket of synaptotagmin is replaced by a leucine. The functional significance of this residue has not been investigated previously. Here we show that in silico modeling predicts disruption of the C2B Ca2+-binding pocket, and we examine the in vivo effects of the homologous mutation in Drosophila. When expressed in the absence of native synaptotagmin, this mutation is lethal, demonstrating for the first time that this residue plays a critical role in synaptotagmin function. To achieve expression similar to human patients, the mutation is expressed in flies carrying one copy of the wild type synaptotagmin gene. We now show that Drosophila carrying this mutation developed neurological and behavioral manifestations similar to those of human patients and provide insight into the mechanisms underlying these deficits. Our Drosophila studies support a role for this synaptotagmin point mutation in disease etiology.

An Event-Related Potential Study on the Effects of Cannabis on Emotion Processing.

The effect of cannabis on emotional processing was investigated using event-related potential paradigms (ERPs). ERPs associated with emotional processing of cannabis users, and non-using controls, were recorded and compared during an implicit and explicit emotional expression recognition and empathy task. Comparisons in P3 component mean amplitudes were made between cannabis users and controls. Results showed a significant decrease in the P3 amplitude in cannabis users compared to controls. Specifically, cannabis users showed reduced P3 amplitudes for implicit compared to explicit processing over centro-parietal sites which reversed, and was enhanced, at fronto-central sites. Cannabis users also showed a decreased P3 to happy faces, with an increase to angry faces, compared to controls. These effects appear to increase with those participants that self-reported the highest levels of cannabis consumption. Those cannabis users with the greatest consumption rates showed the largest P3 deficits for explicit processing and negative emotions. These data suggest that there is a complex relationship between cannabis consumption and emotion processing that appears to be modulated by attention.

Neuropilar projections of the anterior gastric receptor neuron in the stomatogastric ganglion of the Jonah crab, Cancer borealis.

Sensory neurons provide important feedback to pattern-generating motor systems. In the crustacean stomatogastric nervous system (STNS), feedback from the anterior gastric receptor (AGR), a muscle receptor neuron, shapes the activity of motor circuits in the stomatogastric ganglion (STG) via polysynaptic pathways involving anterior ganglia. The AGR soma is located in the dorsal ventricular nerve posterior to the STG and it has been thought that its axon passes through the STG without making contacts. Using high-resolution confocal microscopy with dye-filled neurons, we show here that AGR from the crab Cancer borealis also has local projections within the STG and that these projections form candidate contact sites with STG motor neurons or with descending input fibers from other ganglia. We develop and exploit a new masking method that allows us to potentially separate presynaptic and postsynaptic staining of synaptic markers. The AGR processes in the STG show diversity in shape, number of branches and branching structure. The number of AGR projections in the STG ranges from one to three simple to multiply branched processes. The projections come in close contact with gastric motor neurons and descending neurons and may also be electrically coupled to other neurons of the STNS. Thus, in addition to well described long-loop pathways, it is possible that AGR is involved in integration and pattern regulation directly in the STG.

The effects of climate change on harp seals (Pagophilus groenlandicus).

Harp seals (Pagophilus groenlandicus) have evolved life history strategies to exploit seasonal sea ice as a breeding platform. As such, individuals are prepared to deal with fluctuations in the quantity and quality of ice in their breeding areas. It remains unclear, however, how shifts in climate may affect seal populations. The present study assesses the effects of climate change on harp seals through three linked analyses. First, we tested the effects of short-term climate variability on young-of-the year harp seal mortality using a linear regression of sea ice cover in the Gulf of St. Lawrence against stranding rates of dead harp seals in the region during 1992 to 2010. A similar regression of stranding rates and North Atlantic Oscillation (NAO) index values was also conducted. These analyses revealed negative correlations between both ice cover and NAO conditions and seal mortality, indicating that lighter ice cover and lower NAO values result in higher mortality. A retrospective cross-correlation analysis of NAO conditions and sea ice cover from 1978 to 2011 revealed that NAO-related changes in sea ice may have contributed to the depletion of seals on the east coast of Canada during 1950 to 1972, and to their recovery during 1973 to 2000. This historical retrospective also reveals opposite links between neonatal mortality in harp seals in the Northeast Atlantic and NAO phase. Finally, an assessment of the long-term trends in sea ice cover in the breeding regions of harp seals across the entire North Atlantic during 1979 through 2011 using multiple linear regression models and mixed effects linear regression models revealed that sea ice cover in all harp seal breeding regions has been declining by as much as 6 percent per decade over the time series of available satellite data.

Stimulus control in fixed interfood intervals.

The control exerted by various portions of fixed-time and fixed-interval schedules was assessed with a trace-conditioning procedure. The intervals were segmented into 10 bins. In all but 1 of those bins, the stimuli were presented in different random orders on each trial. In 1 bin, the stimulus was the same on each trial. The position of this trace stimulus was varied across phases. The results indicated that a trace stimulus can come to control behavior and that differential control can extend to even the second tenth of an interfood interval. The results were interpreted as indicating that traditional explanations of the rate loss in earlier portions of an interfood interval are inadequate and that models such as Palya's (1993) bipolar model or Miller and Schachtman's (1985) comparator model may provide a principled framework with which to understand within-trial effects.