Modified full-face snorkeling mask for thoracic surgery and otolaryngology surgical use: comfort and usability assessment during the COVID-19 pandemic

Background:A worldwide personal protection equipment (PPE) shortage has emerged during COVID-19 pandemic, contributing to the high incidence of SARS-CoV-2 infection among health care providers. To address this lack of PEE, new solutions have been researched. Among those, full-face snorkeling masks demonstrated to be an interesting option. Among surgical specialties otolaryngologists and thoracic surgeons are at high risk of infection, due to the close contact with airway secretions.Objectives:We tested the comfort and usability of a modified full-face snorkeling mask (Ocean Reef Mask Aria QR+) as a protective device for otolaryngologic and thoracic surgeries.Methods:The mask was customized with a 3D-printed adaptor supporting many industrial filter types, including FFP3 and heat and moisture exchangers (HME). We evaluated surgical performances of the mask, both subjectively, with a questionnaire filled in by the surgeons, as well as objectively, monitoring transcutaneous PCO₂ and PO₂ values of surgeons during surgical procedures.Results:The modified full-face snorkeling mask was tested during 9 otolaryngologic and 15 thoracic surgery procedures. The device demonstrated very good overall vision quality with some limitations regarding lateral vision and almost no difficulties in usability. Water condensation into the mask was absent in almost every case. Both PO₂ and PCO₂ parameters remained within normal ranges during every procedure.Discussion:The modified full-face snorkeling mask can be an innovative PPE. In the current COVID-19 pandemic scenario, the worldwide shortage of protective masks and goggles may exploit this ready-to-use and low-cost solution, especially for high-risk surgical procedures.     

An image-based modeling framework for patient-specific computational hemodynamics

We present a modeling framework designed for patient-specific computational hemodynamics to be performed in the context of large-scale studies. The framework takes advantage of the integration of image processing, geometric analysis and mesh generation techniques, with an accent on full automation and high-level interaction. Image segmentation is performed using implicit deformable models taking advantage of a novel approach for selective initialization of vascular branches, as well as of a strategy for the segmentation of small vessels. A robust definition of centerlines provides objective geometric criteria for the automation of surface editing and mesh generation. The framework is available as part of an open-source effort, the Vascular Modeling Toolkit, a first step towards the sharing of tools and data which will be necessary for computational hemodynamics to play a role in evidence-based medicine.     

Retinoids in embryonal development

The key role of vitamin A in embryonal development is reviewed. Special emphasis is given to the physiological action of retinoids, as evident from the retinoid ligand knockout models. Retinoid metabolism in embryonic tissues and teratogenic consequences of retinoid administration at high doses are presented. Physiological and pharmacological actions of retinoids are outlined and explained on the basis of their interactions as ligands of the nuclear retinoid receptors. Immediate target genes and the retinoid response elements of their promoters are summarized. The fundamental role of homeobox genes in embryonal development and the actions of retinoids on their expression are discussed. The similarity of the effects of retinoid ligand knockouts to effects of compound retinoid receptor knockouts on embryogenesis is presented. Although much remains to be clarified, the emerging landscape offers exciting views for future research.     

Difenoxin and loperamide: studies on possible mechanisms of intestinal antisecretory action

Summary Experiments have been performed to determine whether the antisecretory (antidiarrhoeal) actions of difenoxin and loperamide are mediated by enteric neurones. An iso-osmotic perfusion solution was circulated around the lumen of the jejunum of anaesthetised rats. Vasoactive intestinal peptide was infused intra-arterially to induce net fluid secretion which was inhibited by difenoxin (ED₅₀, 0.23 mg/kg) and loperamide (ED₅₀, 0.5 mg/kg). However, neither were able to restore the fluid transport rate to the control level of absorption.The antisecretory effects of difenoxin (0.77 mg/kg) and loperamide (0.6 mg/kg) were blocked by the opiate receptor antagonist naloxone (2 mg/kg). Their effects were also abolished by pretreatment with the 5-HT synthesis inhibitor p-chlorophenylalanine (PCPA; 200 mg/kg; with desmethylimipramine given beforehand to protect noradrenergic nerves and enhance 5-HT depletion). The effect of difenoxin was blocked with methiothepin (1 mg/kg) and methysergide (30 g/kg) but not ketanserin (30 g/kg), ritanserin (30 mg/kg), ondansetron (10 g/kg) or ICS 205-930 (3 mg/kg). None of the above 5-HT receptor antagonists modified the antisecretory effect of loperamide. The antisecretory effect of difenoxin but not loperamide was prevented by phentolamine (2 mg/kg) and by pretreatment with 6-hydroxydopamine (150 mg/kg) total.It is concluded that both difenoxin and loperamide inhibit net fluid secretion by indirect mechanisms. It is proposed that the initial action is on enteric -opiate receptors and that this results in the release of 5-HT. In the case of difenoxin, the 5-HT may act on 5-HT₁-like receptors to release noradrenaline. However, the major difference in the mechanism of action of loperamide compared to difenoxin is that it does not utilize noradrenaline as the final mediator of its antisecretory action.Correspondence to A. De Luca at the above address     

Molecular design, synthesis, and antiinflammatory activity of a series of beta-aminoxypropionic acids

Previous experimental and theoretical studies carried out on the mechanism of action of adrenergic drugs have shown that the (methyleneaminoxy)methyl moiety (C = NOCH2, MAOMM) can be considered as a "bioisostere" of an aryl group (Ar). On this basis, a series of substituted beta-aminoxypropionic acids (AOPAs) were synthesized as analogues of antiinflammatory arylacetic acids (ArAAs), in which the Ar portion is substituted by the MAOMM, with the aim of evaluating whether any antiinflammatory activity could be obtained from this class of drugs after the substitution of the Ar with the MAOMM. The antiinflammatory activity of the AOPAs synthesized was determined by carageenan-induced rat paw edema, using diclofenac as the reference drug. The pharmacological data showed that most of the AOPAs examined exhibit a significant antiinflammatory activity, which in the case of the (E)-3-(benzylideneaminoxy)propionic acid (7q) is very close to that of the reference drug. Structural and theoretical studies were carried out in order to compare the conformation and the molecular reactivity of the AOPAs with those of the ArAAs. Pharmacological results showed that the ArAAs also generally exhibit an antiinflammatory activity after the substitution of the Ar with the MAOMM, thus supporting the hypothesis of a bioisosterelike relationship between these two moieties in this class of NSAIDs.     

Involvement of cholecystokinin receptors in the control of striatal dopamine autoreceptors

Summary The interaction of locally perfused cholecystokinin-8 (sulphated) with systemically administered apomorphine was studied on the release of dopamine and its metabolites using microdialysis in the neostriatum of the halothane-anaesthetized male rat. Dialysate levels of dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid were assayed by high performance liquid chromatography in combination with electrochemical detection. Perfusion with cholecystokinin-8 (100 M but not 1 M or 10 nM) increased the dialysate levels of dopamine without affecting those of DOPAC or HVA. At low concentrations (1 M and 10 nM but not 1 nM), cholecystokinin-8 counteracted the inhibitory effect of apomorphine (0.05 mg/kg, s. c.) on dopamine release. This counteraction was antagonized by perfusion with the cholecystokinin-8 antagonist proglumide (3 M). At this concentration, proglumide perfused alone was without effect on basal or apomorphine-reduced levels of dopamine. The results indicate a facilitatory effect of cholecystokinin-8 on dopamine release in rat neostriatum only at high concentrations. At lower concentrations, cholecystokinin-8 appears to modulate dopamine release by an inhibitory effect on dopamine autoreceptors possibly involving an intramembrane interaction between presynaptic cholecystokinin-8 receptors and dopamine autoreceptors. Send offprint requests to K. Fuxe at the above address     

De novo germline mutations of the p53 gene in young children with sarcomas

Germline p53 mutations are associated with cancer predisposition in Li-Fraumeni families as well as in individuals with component tumors of the syndrome. In the majority of cases these mutations have been shown to be inherited rather than de novo. We screened 59 children with primary bone or soft tissue sarcomas. Germline p53 mutations were identified in 2 patients. Interestingly, analysis revealed that both mutations were de novo. Although the frequency of germline p53 mutations in primary pediatric sarcoma patients is low, there is evidence for the importance of considering pediatric patients for testing for de novo mutations.     

The effects of visual input on open-loop and closed-loop postural control mechanisms

In an earlier posturographic investigation (Collins and De Luca 1993) it was proposed that open-loop and closed-loop control mechanisms are involved in the regulation of undisturbed, upright stance. In this study, stabilogram-diffusion analysis was used to examine how visual input affects the operational characteristics of these control mechanisms. Stabilogram-diffusion analysis leads to the extraction of repeatable center-of-pressure (COP) parameters that can be directly related to the resultant steady-state behavior and functional interaction of the neuromuscular mechanisms underlying the maintenance of erect posture. Twenty-five healthy male subjects (aged 19–30 years) were included in the study. An instrumented force platform was used to measure the time-varying displacements of the COP under each subject's feet during quiet standing. The subjects were tested under eyes-open and eyes-closed conditions. The COP trajectories were analyzed as one-dimensional and two-dimensional random walks, according to stabilogram-diffusion analysis. Using this technique, it was found that visual input affects the performance of the postural control system in one of two different ways — either it significantly modifies the steady-state behavior of the open-loop postural control mechanisms, or it significantly alters the characteristics of the other closed-loop feedback mechanisms that are involved in balance control. This result is interpreted as an indication that the visual system is integrated into the postural control system in one of two different ways. The experimental population was roughly evenly divided between these two schemes. For the first group (13 of 25 subjects), visual input principally caused a decrease in the effective stochastic activity of the open-loop control mechanisms in both the mediolateral and anteroposterior directions. For the second group (12 of 25 subjects), visual input caused an increase in the effective stochastic activity and uncorrelated behavior of the closed-loop control mechanisms in the anteroposterior direction only. On the basis of these results, it is hypothesized that visual input, in both schemes, serves to decrease the stiffness of the musculoskeletal system. In the former case, this may be accomplished by decreasing the level of muscular activity across the joints of the lower limb, whereas, in the latter case, reduced stiffness may be achieved by reducing the gain(s) of the other postural feedback mechanisms, i.e., the proprioceptive and/or vestibular systems. Using stabilogram-diffusion analysis, it was also found that the two groups of subjects behaved similarly under eyes-closed conditions. This result suggests that the open-loop postural control mechanisms and reflex-based feedback systems, respectively, of healthy, young individuals are organized in functionally equivalent ways.     

Stereoselective effects of mexiletine enantiomers on sodium currents and excitability characteristics of adult skeletal muscle fibers

The effects of the enantiomers of mexiletine were tested on sodium currents of frog skeletal muscle fibers recorded by means of the three vaseline gap voltage clamp method and compared with the effects produced by tocainide enantiomers. The R-( – ) mexiletine produced a tonic block of the sodium current, elicited by single depolarizing test pulses from the holding potential of – 100 mV to – 20 mV, with an IC₅₀ of 43.9 ± 1 M, whereas the corresponding S-( + ) enantiomer produced the same effects at about twofold higher concentrations. A similar stereoselectivity was observed with tocainide enantiomers, but at about 5 fold higher concentrations. Both the R-( – ) and S-( + ) enantiomers of mexiletine and tocainide produced a further use-dependent block of sodium currents when the test pulse was applied repetitively at a frequency of 2 Hz. The use dependent behaviour led to a significant lowering of the IC₅₀ values with respect to the tonic block but the eudismic ratios ([IC₅₀S-( + )]/[IC₅₀R( – )]) and the relative potency between mexiletine and tocainide were maintained. All the tested compounds produced a left shift of the steady state inactivation curves (h) , suggesting a high-affinity interaction with the inactivated sodium channels. Again a stronger potency of R-( – ) vs. S-( + ) enantiomers and of mexiletine vs. tocainide was observed. The excitability characteristics recorded from the semitendinosus muscle by the two microelectrode technique were modified by the tested drugs in agreement with their ability to block sodium current. Thus a concentration-related increase in the threshold current required to elicit an action potential was observed along with a decrease in the amplitude and a shortening of the latency of action potential and a decrease in the firing capability of the membrane. Again the R-( – ) isomers were more potent than the S-( + ) ones and mexiletine was more effective than tocainide. These data corroborate the presence of a stereospecific site for these drugs on adult skeletal muscle sodium channels. The constant eudismic ratios between the enantiomers during both tonic and use-dependent block suggest that the increase in the apparent affinity of the receptor during statedependent conformational changes of the channel does not enhance its stereospecificity. The decrease in effective concentration upon high frequency stimulation supports the potential usefulness of low doses of R-( – ) mexiletine in the treatment of the abnormal hyperexcitability of the myotonic muscles, with a likely reduction of unwanted side effects.     

Vitamin A-sensitive tissues in transgenic mice expressing high levels of human cellular retinol-binding protein type I are not altered phenotypically.

The suggested function of cellular retinol-binding protein type I [CRBP(I)] is to carry retinol to esterifying or oxidizing enzymes. The retinyl esters are used in storage or transport, whereas oxidized forms such as all-trans or 9-cis retinoic acid are metabolites used in the mechanism of action of vitamin A. Thus, high expression of human CRBP(I) [hCRBP(I)] in transgenic mice might be expected to increase the production of retinoic acid in tissues, thereby inducing a phenotype resembling vitamin A toxicity. Alternatively, a vitamin A-deficient phenotype could also be envisioned as a result of an increased accumulation of vitamin A in storage cells induced by a high hCRBP(I) level. Signs of vitamin A toxicity or deficiency were therefore examined in tissues from transgenic mice with ectopic expression of hCRBP(I). Testis and intestine, the tissues with the highest expression of the transgene, showed normal gross morphology. Similarly, no abnormalities were observed in other tissues known to be sensitive to vitamin A status such as cornea and retina, and the epithelia in the cervix, trachea and skin. Furthermore, hematologic variables known to be influenced by vitamin A status such as the hemoglobin concentration, hematocrits and the number of red blood cells were within normal ranges in the transgenic mice. In conclusion, these transgenic mice have normal function of vitamin A despite high expression of hCRBP(I) in several tissues.