Bumblebee resilience to climate change, through plastic and adaptive responses.

Bumblebees are ubiquitous, cold-adapted eusocial bees found worldwide from subarctic to tropical regions of the world. They are key pollinators in most temperate and boreal ecosystems, and both wild and managed populations are significant contributors to agricultural pollination services. Despite their broad ecological niche at the genus level, bumblebee species are threatened by climate change, particularly by rising average temperatures, intensifying seasonality and the increasing frequency of extreme weather events. While some temperature extremes may be offset at the individual or colony level through temperature regulation, most bumblebees are expected to exhibit specific plastic responses, selection in various key traits, and/or range contractions under even the mildest climate change. In this review, we provide an in-depth and up-to-date review on the various ways by which bumblebees overcome the threats associated with current and future global change. We use examples relevant to the fields of bumblebee physiology, morphology, behaviour, phenology, and dispersal to illustrate and discuss the contours of this new theoretical framework. Furthermore, we speculate on the extent to which adaptive responses to climate change may be influenced by bumblebees' capacity to disperse and track suitable climate conditions. Closing the knowledge gap and improving our understanding of bumblebees' adaptability or avoidance behaviour to different climatic circumstances will be necessary to improve current species climate response models. These models are essential to make correct predictions of species vulnerability in the face of future climate change and human-induced environmental changes to unfold appropriate future conservation strategies.

Acoustomechanically activatable liposomes for ultrasonic drug uncaging.

Ultrasound-activatable drug-loaded nanocarriers enable noninvasive and spatiotemporally-precise on-demand drug delivery throughout the body. However, most systems for ultrasonic drug uncaging utilize cavitation or heating as the drug release mechanism and often incorporate relatively exotic excipients into the formulation that together limit the drug-loading potential, stability, and clinical translatability and applicability of these systems. Here we describe an alternate strategy for the design of such systems in which the acoustic impedance and osmolarity of the internal liquid phase of a drug-loaded particle is tuned to maximize ultrasound-induced drug release. No gas phase, cavitation, or medium heating is necessary for the drug release mechanism. Instead, a non-cavitation-based mechanical response to ultrasound mediates the drug release. Importantly, this strategy can be implemented with relatively common pharmaceutical excipients, as we demonstrate here by implementing this mechanism with the inclusion of a few percent sucrose into the internal buffer of a liposome. Further, the ultrasound protocols sufficient for in vivo drug uncaging with this system are achievable with current clinical therapeutic ultrasound systems and with intensities that are within FDA and society guidelines for safe transcranial ultrasound application. Finally, this current implementation of this mechanism should be versatile and effective for the loading and uncaging of any therapeutic that may be loaded into a liposome, as we demonstrate for four different drugs in vitro, and two in vivo. These acoustomechanically activatable liposomes formulated with common pharmaceutical excipients promise a system with high clinical translational potential for ultrasonic drug uncaging of myriad drugs of clinical interest.

Noninvasive ultrasonic induction of cerebrospinal fluid flow enhances intrathecal drug delivery.

Intrathecal drug delivery is routinely used in the treatment and prophylaxis of varied central nervous system conditions, as doing so allows drugs to directly bypass the blood-brain barrier. However, the utility of this route of administration is limited by poor brain and spinal cord parenchymal drug uptake from the cerebrospinal fluid. We demonstrate that a simple noninvasive transcranial ultrasound protocol can significantly increase influx of cerebrospinal fluid into the perivascular spaces of the brain, to enhance the uptake of intrathecally administered drugs. Specifically, we administered small (~1 kDa) and large (~155 kDa) molecule agents into the cisterna magna of rats and then applied low, diagnostic-intensity focused ultrasound in a scanning protocol throughout the brain. Using real-time magnetic resonance imaging and ex vivo histologic analyses, we observed significantly increased uptake of small molecule agents into the brain parenchyma, and of both small and large molecule agents into the perivascular space from the cerebrospinal fluid. Notably, there was no evidence of brain parenchymal damage following this intervention. The low intensity and noninvasive approach of transcranial ultrasound in this protocol underscores the ready path to clinical translation of this technique. In this manner, this protocol can be used to directly bypass the blood-brain barrier for whole-brain delivery of a variety of agents. Additionally, this technique can potentially be used as a means to probe the causal role of the glymphatic system in the variety of disease and physiologic processes to which it has been correlated.

Signals of adaptation to agricultural stress in the genomes of two European bumblebees.

Human-induced environmental impacts on wildlife are widespread, causing major biodiversity losses. One major threat is agricultural intensification, typically characterised by large areas of monoculture, mechanical tillage, and the use of agrochemicals. Intensification leads to the fragmentation and loss of natural habitats, native vegetation, and nesting and breeding sites. Understanding the adaptability of insects to these changing environmental conditions is critical to predicting their survival. Bumblebees, key pollinators of wild and cultivated plants, are used as model species to assess insect adaptation to anthropogenic stressors. We investigated the effects of agricultural pressures on two common European bumblebees, Bombus pascuorum and B. lapidarius. Restriction-site Associated DNA Sequencing was used to identify loci under selective pressure across agricultural-natural gradients over 97 locations in Europe. 191 unique loci in B. pascuorum and 260 in B. lapidarius were identified as under selective pressure, and associated with agricultural stressors. Further investigation suggested several candidate proteins including several neurodevelopment, muscle, and detoxification proteins, but these have yet to be validated. These results provide insights into agriculture as a stressor for bumblebees, and signal for conservation action in light of ongoing anthropogenic changes.

The Psychosocial Impact of Compounding Humanitarian Crises Caused by War and COVID-19 Informing Future Disaster Response.

The coronavirus disease 2019 (COVID-19) pandemic has caused the greatest global loss of life and economic impact due to a respiratory virus since the 1918 influenza pandemic. While health care systems around the world faced the enormous challenges of managing COVID-19 patients, health care workers in the Republic of Armenia were further tasked with caring for the surge of casualties from a concurrent, large-scale war. These compounding events put a much greater strain on the health care system, creating a complex humanitarian crisis that resulted in significant psychosocial consequences for health care workers in Armenia.

Reliability and Feasibility of Extended Field of View Ultrasound Imaging Techniques for Measuring the Limb Muscle Cross-Sectional Area.

Purpose: Panoramic ultrasound imaging (pUSI) is an extended field of view (FOV) imaging technique that enables visualization of larger muscles; however, it is not available in all ultrasound systems. Using an acoustic standoff pad that is compatible with any ultrasound system may be an alternative method to increase FOV, but it has not been used to evaluate limb muscles. The purpose of this study was to evaluate the reliability and feasibility of using pUSI and an acoustic standoff pad to measure the limb muscle cross-sectional area (mCSA). Method: A cross-sectional study was conducted. Using pUSI and an acoustic standoff pad, we obtained B-mode ultrasound images of the rectus femoris, biceps brachii, and lateral gastrocnemius muscles of 26 healthy participants on two occasions 7-10 days apart. The agreement between the two methods was determined using intra-class correlation coefficients (ICCs) and Bland-Altman plots. Test-retest reliability was assessed using ICCs and standard error of measurement (SEM). The feasibility of acquiring and analyzing the images was evaluated using a Likert scale. Results: The acoustic standoff pad and pUSI demonstrated strong agreement (ICC[3,3] > 0.85); however, the mCSAs were different (p < 0.05). Test-retest reliability for each technique was high for all muscles (ICC[3,3] > 0.85; SEM = 0.6-1.5 cm2). Image acquisition was highly feasible, but there were some limitations in analyzing the images. Conclusions: pUSI and an acoustic standoff pad are two reliable techniques for measuring mCSA, but the measurements are not directly comparable. Future studies should evaluate the accuracy of the acoustic standoff pad compared with gold-standard methods.

Objectif : l'imagerie panoramique (IP) est une technique à champ étendu (CÉ) qui permet de visualiser les grands muscles, mais qui n'est pas offerte dans tous les systèmes d'échographie. Un panneau acoustique autonome compatible avec les autres systémes d'échographie peut être utilisé pour accroître l'étendue du champ, mais il n'a pas été utilisé pour évaluer les muscles des membres. La présente étude visait à évaluer la fiabilité de l'IP et la faisabilité de l'utiliser comme panneau acoustique autonome pour mesurer la surface transversale du muscle (STM) du membre. Méthodologie : les chercheurs ont réalisé une étude transversale. Ils ont obtenu des images d'échographie en mode B du muscle droit antérieur de la cuisse, du biceps brachial et des muscles gastrocnémiens latéraux à l'aide de l'IP et d'un panneau acoustique autonome chez 26 sujets en santé à deux reprises (à sept à dix jours d'écart). Ils ont établi la concordance entre les deux méthodes à l'aide des coefficients de corrélation intraclasse (CCI) et des courbes de Bland-Altman. Ils ont évalué la fiabilité test-retest à l'aide des CCI et de l'écart-type de mesure standard (ÉTM). Ils ont évalué la faisabilité d'acquérir et d'analyser les images à l'aide de l'échelle de Likert. Résultats : Le panneau acoustique autonome et l'IP présentaient une forte concordance (CCI[3,3] > 0,85), mais les STM étaient différentes (p < 0,05). La fiabilité test-retest de chaque technique était élevée pour tous les muscles (CCI[3,3] > 0,85; ÉTM = 0,6 à 1,5 cm2). Il était hautement faisable d'acquérir les images, mais il y avait certaines limites à les analyser. Conclusions : Un IP et un panneau acoustique autonome sont deux techniques fiables pour mesurer la STM, mais les mesures ne sont pas directement comparables. De futures études devront évaluer la précision du panneau acoustique autonome par rapport aux méthodes de référence.

A dignitary medicine curriculum developed using a modified Delphi methodology.

BACKGROUND: Dignitary medicine is an emerging field of training that involves the specialized care of diplomats, heads of state, and other high-ranking officials. In an effort to provide guidance on training in this nascent field, we convened a panel of experts in dignitary medicine and using the Delphi methodology, created a consensus curriculum for training in dignitary medicine. METHODS: A three-round Delphi consensus process was performed with 42 experts in the field of dignitary medicine. Predetermined scores were required for an aspect of the curriculum to advance to the next round. The scores on the final round were used to determine the components of the curriculum. Scores below the threshold to advance were dropped in the subsequent round. RESULTS: Our panel had a high degree of agreement on the required skills needed to practice dignitary medicine, with active practice in a provider's baseline specialty, current board certification, and skills in emergency care and resuscitation being the highest rated skills dignitary medicine physicians need. Skills related to vascular and emergency ultrasound and quality improvement were rated the lowest in the Delphi analysis. No skills were dropped from consideration. CONCLUSIONS: The results of our work can form the basis of formal fellowship training, continuing medical education, and publications in the field of dignitary medicine. It is clear that active medical practice and knowledge of resuscitation and emergency care are critical skills in this field, making emergency medicine physicians well suited to practicing dignitary medicine.