Acoustically Detonated Biomolecules for Genetically Encodable Inertial Cavitation

Recent advances in molecular engineering and synthetic biology have made it possible for biomolecular and cell-based therapies to provide highly specific disease treatment. However, both the ability to spatially target the action of such therapies, and their range of effects on the target tissue remain limited. Here we show that biomolecules and cells can be engineered to deliver potent mechanical effects at specific locations inside the body under the direction of focused ultrasound. This capability is based on gas vesicles, a unique class of air-filled protein nanostructures derived from buoyant photosynthetic microbes. We show that low-frequency ultrasound can convert these nanoscale biomolecules into micron-scale cavitating bubbles, as demonstrated with acoustic measurements and ultrafast optical microscopy. This allows gas vesicles targeted to cell-surface receptors to serve as remotely detonated cell-killing agents. In addition, it allows cells genetically engineered to express gas vesicles to be triggered with ultrasound to lyse and release therapeutic payloads. We demonstrate these capabilities in vitro, in cellulo, and in vivo. This technology equips biomolecular and cellular therapeutics with unique capabilities for spatiotemporal control and mechanical action

Sonothrombolysis Of Porcine Blood Clots Using 1 MHz Pulsed Ultrasound

Blood clots block proper blood flow in vessels and often lead to fatal health conditions such as cardiac ischemia and stroke, especially in an aging population. Because ultrasonic fields can cause cavitation of fluids, administration of ultrasound and microbubble contrast agents can induce intravascular thrombolysis (dissolution of blood clots). Quantitative and qualitative data were collected on how a porcine blood clot dissolves when exposed to Definity™ microbubbles and 1 MHz pulsed ultrasound. In addition, bubble dynamics in response to the measured ultrasonic wave field were modeled using a modified Gilmore equation. The results allowed us to optimize parameters and better understand the interaction of the clot fibrin structure and the movement of microbubbles through it. Advances in the understanding of sonothrombolysis can help transform its clinical application in patients efficiently, especially in instances where life depends on rapid dissolution of a thrombus

Association of Sociodemographic Factors on the Presentation and Management of Unilateral Vocal Fold Immobility

To determine the association of social determinants of health (SDOH) on the presentation and management of unilateral vocal fold immobility (UVFI). Retrospective chart review of 207 adult UVFI patients evaluated at a tertiary-care hospital between 2018 and 2019 was performed. Sociodemographic factors including gender, median household income, preferred language, and insurance type were recorded. Confounding clinical factors including etiology of UVFI, Voice Handicap Index-10 (VHI-10) score, laryngoscopic findings, and intervention history were extracted from medical records. Multivariable logistic regression was performed using sociodemographic and clinical factors. Patient demographics and socioeconomic status were not associated with time to presentation. Patients presenting with glottic insufficiency and UVFI due to malignancy or recurrent laryngeal nerve (RLN) sacrifice had a shorter time to presentation. Higher household income was associated with greater number of interventions (p = 0.02), but neither income nor insurance type affected intervention type or timing. Female patients were less likely to undergo injection medialization laryngoplasty (odds ratio [OR] 0.25, p = 0.005). Older patients were more likely to undergo injection (OR 1.04, p = 0.027). Patients with large glottic gaps (OR 21.2, p = 0.014) and higher VHI-10 scores (OR 1.06, p = 0.047) were more likely to undergo surgery. Higher household income was associated with greater number of interventions and longer duration of care at a private tertiary-care hospital. RLN sacrifice, known malignancy, and glottic insufficiency significantly reduced the time to presentation. Type of intervention received was a complex interplay of both demographic and clinical factors. Large prospective studies should examine the role of SDOH in the presentation and management of UVFI. 4 Laryngoscope, 2023

Novel positive allosteric modulators of GABAA receptors with anesthetic activity.

GABAA receptors are the main inhibitory neurotransmitter receptors in the brain and are targets for numerous clinically important drugs such as benzodiazepines, anxiolytics and anesthetics. We previously identified novel ligands of the classical benzodiazepine binding pocket in α1β2γ2 GABAA receptors using an experiment-guided virtual screening (EGVS) method. This screen also identified novel ligands for intramembrane low affinity diazepam site(s). In the current study we have further characterized compounds 31 and 132 identified with EGVS as well as 4-O-methylhonokiol. We investigated the site of action of these compounds in α1β2γ2 GABAA receptors expressed in Xenopus laevis oocytes using voltage-clamp electrophysiology combined with a benzodiazepine site antagonist and transmembrane domain mutations. All three compounds act mainly through the two β+/α- subunit transmembrane interfaces of the GABAA receptors. We then used concatenated receptors to dissect the involvement of individual β+/α- interfaces. We further demonstrated that these compounds have anesthetic activity in a small aquatic animal model, Xenopus laevis tadpoles. The newly identified compounds may serve as scaffolds for the development of novel anesthetics

Reporting of Participants' Sex, Race, Ethnicity, and Socioeconomic Status in Pituitary Surgery Literature

Abstract Introduction Social determinants of health (SDOH) are associated with differential outcomes after pituitary tumor treatment. However, the specific impact of SDOH is not well characterized. One reason may be the lack of collection and reporting of sociodemographic variables in the literature. This study aims to evaluate the frequency of reporting and distribution of participants' sex, race, ethnicity, income, and education level within pituitary surgery literature. We will compare the reported clinical research population demographics to the 2020 U.S. census. Methods A systematic review was performed by searching PubMed, Cochrane, and Embase databases for pituitary surgery clinical research published between July 1, 2021 to June 30, 2022. We excluded studies that lacked a comparison group, were not original research (i.e., systematic reviews, meta-analysis), or included national databases and registry data. Results The final analysis included 92 studies. A total of 99% of studies collected data on subject sex. On average 49% (range: 14–100%) of study populations were male. Only 4% (n = 4) studies included racial demographic data. Two studies included information on participants' ethnicity and two included education background. No studies included income or insurance data. Four U.S. studies included demographic distribution, and the reported race and ethnicity percentages are similar to the U.S. 2020 census distribution. Conclusions Most clinical pituitary research collects and reports data on participant sex. However, very few studies collect and report data on other sociodemographic variables that can play a role in outcomes. The lack of sociodemographic information in clinical research literature makes it difficult to determine the role of SDOH on pituitary surgery outcomes