A Doppler ultrasound self-monitoring approach for detection of relevant individual decompression stress in scuba diving.

Observing modern decompression protocols alone cannot fully prevent diving injuries especially in repetitive diving. Professional audio Doppler bubble measurements are not available to sports scuba divers. If those non-professionals were able to learn audio Doppler self-assessment for bubble grading, such skill could provide significant information on individual decisions with respect to diving safety. We taught audio Doppler self-assessment of subclavian and precordial probe position to 41 divers in a 45-min standardized, didactically optimized training. Assessment before and after air dives within sports diving limits was made through 684 audio Doppler measurements in dive-site conditions by both trained divers and a medical professional, plus additional 2D-echocardiography reference. In all dives (average maximum depth 22 m; dive time 44 min), 33% of all echocardiography measurements revealed bubbles. The specificity of audio bubble detection in combination of both detection sites was 95%, and sensitivity over all grades was 40%, increasing with higher bubble grades. Dive-site audio-Doppler-grading underestimated echo-derived bubble grades. Bubble detection sensitivity of audio Doppler self-assessments, compared to an experienced examiner, was 62% at subclavian and 73% at precordial position. 6 months after the training and 4.5 months after the last measurement, the achieved Doppler skill level remained stable. Audio Doppler self-assessment can be learned by non-professionals in a single teaching intervention. Despite accurate bubble grading is impossible in dive-site conditions, relevant high bubble grades can be detected by non-professionals. This qualitative information can be important in self-evaluating decompression stress and assessing measures for increased diving safety.

Sonographic Estimation Rather Than Quantification of Fluid Status Using Inferior Vena Cava and Other Major Vessel Parameters in a Non-Bleeding Fluid Loss and Centralization Model.

OBJECTIVE: A well-accepted step in emergency sonography is the estimation of a fluid deficit through Inferior Vena Cava (IVC) diameter variability with known cut-offs especially in bleeding. We sought to answer, whether a non-bleeding fluid deficit can be quantified through sonographic assessment of IVC diameter variability and related aortic parameters. Sport divers were used as human hypovolemic vasoconstriction models since immersion is known to cause relevant volume depletion through vasoconstriction and induced diuresis. MATERIALS AND METHODS: Forty-one sport divers performed 342 single and repetitive dives to account for intra- and interindividual variability and were assessed for inferior Vena Cava and neighboring aortic diameters as well as their cardiac/respiratory variations. Dive-related weight loss was measured together with sonographic vessel diameter changes inferior to the right atrium. RESULTS: Highest correlation with dive-related weight loss of max. 2.9 kg per an average 47 minutes dive was found with r=0.34 for the difference of IVC maximum diameter related to minimum Aortic diameter. Single or combined parameters, as well as Collapsibility Index, showed lower or no correlations. Vascular parameters were able to explain 7.5% of the variance of fluid losses, whereas interindividual effects explained 10%. The remaining 82.5% is of mixed intraindividual counterregulatory effects. CONCLUSION: IVC diameter changes in immersion-induced hypovolemic centralization provides qualitative information on relevant fluid loss only. Confounding factors like inter and intraindividual variability prevent a sufficient correlation for useful quantification of the experienced non-bleeding fluid deficit in the clinical setting.

Estimating Inert Gas Bubbling from Simple SCUBA Diving Parameters.

Inert gas bubbles frequently occur in SCUBA divers' vascular systems, eventually leading to decompression accidents. Only in professional settings, dive profiles can be adjusted on individual basis depending on bubble grades detected through ultrasonography. A total of 342 open-circuit air dives following sports diving profiles were assessed using echocardiography. Subsequently, (Eftedal-Brubakk) bubble grades were correlated with dive and individual parameters. Post-dive cardiac bubbles were observed in 47% of all dives and bubble grades were significantly correlated with depth (r=0.46), air consumption (r=0.41), age (r=0.25), dive time (r=0.23), decompression diving (r=0.19), surface time (r=- 0.12). Eftedal-Brubakk categorical bubble grades for sports diving with compressed air can be approximated by bubble grade = (age*50-1 - surface time*150-1+maximum depth*45-1+air consumption*4500-1)2 (units in years, hours, meter, and bar*liter; R2=0.31). Thus, simple dive and individual parameters allow reasonable estimation of especially relevant medium to higher bubble grades for information on relevant decompression stress after ascent. Echo bubble grade 0 is overestimated by the formula derived. However, echo might fail to detect minor bubbling only. The categorical prediction of individual decompression stress with simple bio and dive data should be evaluated further to be developed towards dive computer included automatic ex-post information for decision-making on individual safety measures.

Kinetic profiling an abundantly expressed planarian serotonergic GPCR identifies bromocriptine as a perdurant antagonist.

The diversity and uniqueness of flatworm G protein coupled receptors (GPCRs) provides impetus for identifying ligands useful as tools for studying flatworm biology, or as therapeutics for treating diseases caused by parasitic flatworm infections. To catalyse this discovery process, technologies optimized for mammalian GPCR high throughput screening need be transposed for screening flatworm GPCRs. Here, we demonstrate the utility of a genetically encoded cAMP biosensor for resolving the properties of an abundantly expressed planarian serotonergic GPCR (S7.1R). Application of this methodology resolved the real time kinetics of GPCR modulation by ligands and demonstrated a marked difference in the kinetic action of antagonists at S7.1R. Notably, bromocriptine caused a protracted inhibition of S7.1R activity in vitro and a protracted paralysis of planarian movement, replicating the effect of S7.1R in vivo RNAi. The lengthy inhibition of function caused by bromocriptine at this abundantly expressed GPCR provides a useful tool to ablate serotonergic signaling in vivo, and is a noteworthy feature for exploitation as an anthelmintic vulnerability.

Ergot Alkaloids (Re)generate New Leads as Antiparasitics.

Praziquantel (PZQ) is a key therapy for treatment of parasitic flatworm infections of humans and livestock, but the mechanism of action of this drug is unresolved. Resolving PZQ-engaged targets and effectors is important for identifying new druggable pathways that may yield novel antiparasitic agents. Here we use functional, genetic and pharmacological approaches to reveal that serotonergic signals antagonize PZQ action in vivo. Exogenous 5-hydroxytryptamine (5-HT) rescued PZQ-evoked polarity and mobility defects in free-living planarian flatworms. In contrast, knockdown of a prevalently expressed planarian 5-HT receptor potentiated or phenocopied PZQ action in different functional assays. Subsequent screening of serotonergic ligands revealed that several ergot alkaloids possessed broad efficacy at modulating regenerative outcomes and the mobility of both free living and parasitic flatworms. Ergot alkaloids that phenocopied PZQ in regenerative assays to cause bipolar regeneration exhibited structural modifications consistent with serotonergic blockade. These data suggest that serotonergic activation blocks PZQ action in vivo, while serotonergic antagonists phenocopy PZQ action. Importantly these studies identify the ergot alkaloid scaffold as a promising structural framework for designing potent agents targeting parasitic bioaminergic G protein coupled receptors.