The Society for Craniofacial Genetics and Developmental Biology 45th Annual Meeting

The Society for Craniofacial Genetics and Developmental Biology (SCGDB) held its 45th Annual Meeting at the Sanford Consortium for Regenerative Medicine at the University of California, San Diego on October 20th–21st, 2022. The meeting included presentation of the SCGDB Distinguished Scientists in Craniofacial Research Awards to Drs. Ralph Marcucio and Loydie Jerome-Majewska and four scientific sessions that highlighted new discoveries in signaling in craniofacial development, genomics of craniofacial development, human genetics of craniofacial development and translational and regenerative approaches in craniofacial biology. The meeting also included workshops on analysis of single cell RNA sequencing datasets and using human sequencing data from the Gabriella Miller Kids First Pediatric Research Program. There were 110 faculty and trainees in attendance that represent a diverse group of researchers from all career stages in the fields of developmental biology and genetics. The meeting, which also included outdoor poster presentations, provided opportunities for participant interactions and discussions, thus strengthening the SCGDB community.     

Selecting patients for early interdisciplinary rehabilitation during neurointensive care after moderate to severe traumatic brain injury

Background

Early interdisciplinary rehabilitation (EIR) in neurointensive care is a limited resource reserved for patients with moderate to severe traumatic brain injury (TBI) believed to profit from treatment. We evaluated how key parameters related to injury severity and patient characteristics were predictive of receiving EIR, and whether these parameters changed over time.

Methods

Among 1003 adult patients with moderate to severe TBI admitted over 72 h to neurointensive care unit during four time periods between 2005 and 2020, EIR was given to 578 and standard care to 425 patients. Ten selection criteria thought to best represent injury severity and patient benefit were evaluated (Glasgow Coma Scale, Head Abbreviated Injury Scale, New-Injury-Severity-Scale, intracranial pressure monitoring, neurosurgery, age, employment, Charlson Comorbidity Index, severe psychiatric disease, and chronic substance abuse).

Results

In multivariate regression analysis, patients who were employed (adjOR 1.99 [95% CI 1.41, 2.80]), had no/mild comorbidity (adjOR 3.15 [95% CI 1.72, 5.79]), needed neurosurgery, had increasing injury severity and were admitted by increasing time period were more likely to receive EIR, whereas receiving EIR was less likely with increasing age (adjOR 0.97 [95% CI 0.96, 0.98]) and chronic substance abuse. Overall predictive ability of the model was 71%. Median age and comorbidity increased while employment decreased from 2005 to 2020, indicating patient selection became less restrictive with time.

Conclusion

Injury severity and need for neurosurgery remain important predictors for receiving EIR, but the importance of age, employment, and comorbidity have changed over time. Moderate prediction accuracy using current clinical criteria suggest unrecognized factors are important for patient selection.     

Glutamate infusion associated with reduced rises of p-Copeptin after coronary surgery: Substudy of GLUTAMICS II

Background

Glutamate plays a key role for post-ischaemic recovery of myocardial metabolism. According to post hoc analyses of the two GLUTAMICS trials, patients without diabetes benefit from glutamate with less myocardial dysfunction after coronary artery bypass surgery (CABG). Copeptin reflects activation of the Arginine Vasopressin system and is a reliable marker of heart failure but available studies in cardiac surgery are limited. We investigated whether glutamate infusion is associated with reduced postoperative rises of plasma Copeptin (p-Copeptin) after CABG.

Methods

A prespecified randomised double-blind substudy of GLUTAMICS II. Patients had left ventricular ejection fraction ≤0.30 or EuroSCORE II ≥3.0 and underwent CABG ± valve procedure. Intravenous infusion of 0.125 M L-glutamic acid or saline at 1.65 mL/kg/h was commenced 10–20 min before the release of the aortic cross-clamp and then continued for another 150 min P-Copeptin was measured preoperatively and postoperatively on day one (POD1) and day three. The primary endpoint was an increase in p-Copeptin from the preoperative level to POD1. Postoperative stroke ≤24 h and mortality ≤30 days were safety outcomes.

Results

We included 181 patients of whom 48% had diabetes. The incidence of postoperative mortality ≤30 days (0% vs. 2.1%; p = .50) and stroke ≤24 h (0% vs. 3.2%; p = .25) did not differ between the glutamate group and controls. P-Copeptin increased postoperatively with the highest values recorded on POD1 without significant inter-group differences. Among patients without diabetes, p-Copeptin did not differ preoperatively but postoperative rise from preoperative level to POD1 was significantly reduced in the glutamate group (73 ± 66 vs. 115 ± 102 pmol/L; p = .02). P-Copeptin was significantly lower in the Glutamate group on POD1 (p = .02) and POD 3 (p = .02).

Conclusions

Glutamate did not reduce rises of p-Copeptin significantly after moderate to high-risk CABG. However, glutamate was associated with reduced rises of p-Copeptin among patients without diabetes. These results agree with previous observations suggesting that glutamate mitigates myocardial dysfunction after CABG in patients without diabetes. Given the exploratory nature of these findings, they need to be confirmed in future studies.     

Anästhesiologische Risikoevaluation und rechtssichere Aufklärung per Telemedizin – Sind wir bereit für einen Paradigmenwechsel?

Die Anaesthesiologie - In Deutschland werden pro Jahr 17 Millionen Narkosen und damit auch ungefähr so viele Narkosevorgespräche durchgeführt. Bis dato finden diese praktisch...     

Effects of antioxidant supplementation on bone mineral density,bone mineral content and bone structure in healthy men during 60 days of 6° head-down tilt bed rest: Results from a randomised controlled trial

Dietary countermeasures to mitigate detrimental spaceflight-induced effects on bone health would alleviate the requirements and the consequences imposed by other types of countermeasures for this risk. We hypothesised that antioxidant supplementation during 60 days of 6° head-down tilt bed rest (HDBR), an analogue of spaceflight, would have a protective effect on bone mineral density (BMD), content (BMC) and bone structure parameters. An exploratory, randomised, controlled, single-blind intervention trial was conducted in a parallel design with 20 healthy male volunteers (age 34 ± 8 y, weight 74 ± 6 kg). The study included 14 days of baseline data collection (BDC) before bed rest, followed by 60 days of HDBR and a 14-day recovery period. Ten subjects in the antioxidant group received a supplement (741 mg/d polyphenols, 2.1 g/d omega-3 fatty acids, 168 mg/d vitamin E and 80 μg/d selenium) daily. Ten subjects in the control group received no supplement. The diet was consistent with dietary reference intakes, individually tailored based on the subject's bodyweight and strictly controlled. We measured whole-body, lumbar spine and femur BMD and BMC, as well as BMD of the cortical and trabecular compartments of the distal radius and tibia, and cortical and trabecular thickness during BDC, HDBR and recovery. Data were analysed using linear mixed models. The supplementation of an antioxidant cocktail did not mitigate the deteriorating effects of HDBR on BMD, BMC and bone structure parameters. Our findings do not support a recommendation for antioxidant supplementation for astronauts.     

Expression of Human Secretory Group IIA Phospholipase A2 is Associated with Reduced Concentrations of Plasma Cholesterol in Transgenic Mice

It is well known that acute and chronic inflammatory reactions are accompanied by markedly decreased concentrations of plasma total cholesterol. However, the mechanisms underlying this hypocholesterolemia are not yet completely understood. To explore the question of whether an increased serum activity of secretory group IIA phospholipase A₂ (sPLA₂) may contribute to the development of hypocholesterolemia during inflammation, the lipids and lipoprotein patterns in the plasma of transgenic mice overexpressing the human sPLA₂ gene were studied and compared with those of nontransgenic controls. The mean plasma enzyme activities determined by using [¹⁴C]-oleate labeled Escherichia coli-membranes were found to be 331 ± 262 U/l in transgenic mice while the catalytic activity in plasma of controls was below the analytical sensitivity of the assay (0.5 U/l). Compared to nontransgenic littermates, sPLA₂-transgenic mice exhibited significantly lower plasma concentrations of total cholesterol (2.53 ± 0.37 mmol/l vs. 3.49 ± 0.44 mmol/l, p < 0.0001). The reduction of total cholesterol was due to decreased HDL and LDL cholesterol levels (1.21 ± 0.10 mmol/l vs. 1.78 ± 0.37 mmol/l, and 0.28 ± 0.02 mmol/l vs. 0.69 ± 0.23 mmol/l, respectively, p < 0.05). The analysis of lipoprotein composition indicated that the LDL of transgenic mice were selectively depleted in free and esterified cholesterol, whereas HDL of the two animal groups contained comparable percentages of cholesterol. The triglycerides were significantly enriched in LDL and HDL, but tended to be less in VLDL of transgenic mice. In conclusion, the results of the study have demonstrated that the expression of sPLA₂ may influence the metabolism of lipoproteins, possibly contributing to the development of hypocholesterolemia during inflammation.     

Quantification issues of in vivo 1H NMR spectroscopy of the rat brain investigated at 16.4 T

The accuracy and precision of the quantification of metabolite concentrations in in vivo ¹H NMR spectroscopy are affected by linewidth and signal‐to‐noise ratio (SNR). To study the effect of both factors in in vivo ¹H NMR spectra acquired at ultrahigh field, a reference spectrum was generated by summing nine in vivo ¹H NMR spectra obtained in rat brain with a STEAM sequence at 16.4 T. By progressive deterioration of linewidth and SNR, 6400 single spectra were generated. In an accuracy study, the variation in the mean concentrations of five metabolites was mainly dependent on SNR, whereas 11 metabolites were predominantly susceptible to the linewidth. However, the standard deviations of the concentrations obtained were dependent almost exclusively on the SNR. An insignificant correlation was found between most of the heavily overlapping metabolite peaks, indicating independent and reliable quantification. Two different approaches for the consideration of macromolecular signals were evaluated. The use of prior knowledge derived by parameterization of a metabolite‐nulled spectrum demonstrated improved fitting quality, with reduced Cramér–Rao lower bounds, compared to the calculation of a regularized spline baseline. Copyright © 2012 John Wiley & Sons, Ltd.