Reversal of Opioid-Induced Respiratory Depression in Healthy Volunteers: Comparison of Intranasal Nalmefene and Intranasal Naloxone.

An open-label, randomized, crossover study in healthy volunteers compared the reversal of remifentanil-induced respiratory depression by intranasal (IN) naloxone hydrochloride (4 mg) to IN nalmefene (2.7 mg) (NCT04828005). Subjects were administered a hypercapnic gas mixture which produces an elevation in minute ventilation (MV), a result of the ventilatory response to hypercapnia. Subjects breathed a hypercapnic gas mixture through a tight-fitting mask for an initial period of 46 min prior to a series of mask "holidays" introduced to reduce subject discomfort and encourage study completion. Ten minutes after initiating the hypercapnic gas mixture, a remifentanil bolus was administered, and an infusion continued for the study duration. Subjects were administered either naloxone or nalmefene 15 min after initiating the remifentanil infusion and MV monitored for 21 min followed by a mask holiday. Both nalmefene and naloxone produced a time-dependent reversal of remifentanil-induced reductions in MV measured 2.5-20 min post administration. At the primary endpoint (5 min post administration), nalmefene increases in MV (5.75 L/min) were nearly twice that produced by naloxone (3.01 L/min) (P < .0009); the point estimate favors nalmefene, demonstrating non-inferiority and superiority. In this model of opioid-induced respiratory depression, nalmefene has a more rapid onset of action than naloxone, which required 20 min to achieve a comparable reversal of respiratory depression. Both nalmefene and naloxone were well tolerated by healthy volunteers. This rapid onset of action may prove particularly valuable in an era when over 90% of fatalities are linked to synthetic opioid overdose.

Optical coherence tomography angiography in primary eye care.

Optical coherence tomography angiography (OCT-A) is a non-invasive imaging modality for assessing the vasculature within ocular structures including the retina, macula, choroid and optic nerve. OCT-A has a wide range of clinical applications in various optometric conditions which have been independently reported in the literature. This paper aims to present a review of the current literature on the clinical application of OCT-A in optometric practice as well as to analyse and evaluate the quality of the available evidence. This review included 78 articles from a literature search conducted on 26 May 2019 across the following databases: Cochrane Library of Systematic Reviews, Medline, Scopus and Web of Science. Primary ocular pathologies discussed in this review include glaucoma, diabetic retinopathy, age-related macular degeneration, myopia, acquired and congenital macular dystrophies, epiretinal membrane, retinal vein occlusion, retinitis pigmentosa, choroidal melanoma, uveitis, central serous chorioretinopathy, amblyopia and optic neuropathies. Primary outcome variables included vessel density, foveal avascular zone area and diameter, flow velocity and flow index. This review aims to evaluate the evidence available for OCT-A applications in diagnosis and prognosis of ocular conditions in an optometric setting.

Correction: Sexual dichromatism in the neotropical genus Mannophryne (Anura: Aromobatidae).

[This corrects the article DOI: 10.1371/journal.pone.0223080.].

Sexual dichromatism in the neotropical genus Mannophryne (Anura: Aromobatidae).

Recent reviews on sexual dichromatism in frogs included Mannophryne trinitatis as the only example they could find of dynamic dichromatism (males turn black when calling) within the family Aromobatidae and found no example of ontogenetic dichromatism in this group. We demonstrate ontogenetic dichromatism in M. trinitatis by rearing post-metamorphic froglets to near maturity: the throats of all individuals started as grey coloured; at around seven weeks, the throat became pale yellow in some, and more strongly yellow as development proceeded; the throats of adults are grey in males and variably bright yellow in females, backed by a dark collar. We demonstrated the degree of throat colour variability by analysing a large sample of females. The red: green (R:G) ratio ranged from ~1.1 to 1.4, reflecting variation from yellow to yellow/orange, and there was also variation in the tone and width of the dark collar, and in the extent to which the yellow colouration occurred posterior to the collar. Female M. trinitatis are known to be territorial in behaviour. We show a positive relationship between throat colour (R:G ratio) and escape performance, as a proxy for quality. Our field observations on Tobago's M. olmonae showed variability in female throat colour and confirmed that males in this species also turn black when calling. Our literature review of the 20 Mannophryne species so far named showed that all females have yellow throats with dark collars, and that male colour change to black when calling has been reported in eight species; in the remaining 12 species, descriptions of males calling are usually lacking so far. We predict that both dynamic and ontogenetic sexual dichromatism are universal in this genus and provide discussion of the ecological role of dichromatism in this genus of predominantly diurnal, non-toxic frogs, with strong paternal care of offspring.

Simultaneous in vivo measurement of dopamine, serotonin and ascorbate in the striatum of experimental rats using voltammetric microprobe.

The in vivo performance of a voltammetric microprobe based on overoxidized poly(1,2-phenylenediamine) coated carbon fiber microelectrode (OPPD/CFME), developed in our laboratory, is presented. For this purpose, an OPPD microprobe was stereotaxicaly implanted in the striatum of a deeply anesthetized Wistar rat for the simultaneous measurement of dopamine, serotonin and ascorbate. Furthermore, the post mortem levels of these physiologically important compounds were monitored after the rats were terminated with an overdose of anesthetic introduced through an indwelling jugular catheter. Using cyclic (CV) and square-wave (SWV) voltammetry, the OPPD/CFME was demonstrated to exhibit efficient separation of the voltammetric signals of dopamine, serotonin and ascorbate in the presence of biological matrix, with the SWV mode allowing more convenient detection regarding both sensitivity and selectivity. Explicit proof of in vivo dopamine detection at the OPPD/CFME was achieved via the absence of the dopamine signal in rats with unilateral lesions of nigrostriatal dopaminergic neurons, which was induced by the use of the selective dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA). In stark contrast to non-treated rats, where a strong signal corresponding to 1.2 micro M dopamine was measured at ca. 90 s after the rats' death, the signal for dopamine in dopamine-depleted striatum of 6-OHDA rats was absent. A critical comparison of the in vivo performance of the OPPD/CFME to that of bare and Nafion-coated carbon fiber microelectrodes, often used in neurophysiological studies, clearly showed a significant advantage of the former microprobe. The OPPD/CFME allowed multiple and repetitive in vivo measurements, along with pre- and post-measurement external calibration, with no loss in selectivity and an acceptable loss in sensitivity, indicating that the active sensing sites were not adversely blocked by the components of the extracellular fluid, thus affirming the great practical in vivo applicability of the OPPD microprobe.

Amperometric microsensor for direct probing of ascorbic acid in human gastric juice.

This article reports on a novel microsensor for amperometric measurement of ascorbic acid (AA) under acidic conditions (pH 2) based on a carbon fiber microelectrode (CFME) modified with nickel oxide and ruthenium hexacyanoferrate (NiO-RuHCF). This sensing layer was deposited electrochemically in a two-step procedure involving an initial galvanostatic NiO deposition followed by a potentiodynamic RuHCF deposition from solutions containing the precursor salts. Several important parameters were examined to characterize and optimize the NiO-RuHCF sensing layer with respect to its current response to AA by using cyclic voltammetry, and scanning electron microscopy-energy dispersive X-ray spectroscopy methods. With the NiO-RuHCF coated CFME, the AA oxidation potential under acidic conditions was shifted to a less positive value for about 0.2 V (E(p) of ca. 0.23 V vs. Ag/AgCl) as compared to a bare CFME, which greatly improves the electrochemical selectivity. Using the hydrodynamic amperometry mode, the current vs. AA concentration in 0.01 M HCl, at a selected operating potential of 0.30 V, was found to be linear over a wide range of 10-1610 µM (n=22, r=0.999) with a calculated limit of detection of 1.0 µM. The measurement repeatability was satisfactory with a relative standard deviation (r.s.d.) ranging from 4% to 5% (n=6), depending on the AA concentration, and with a sensor-to-sensor reproducibility (r.s.d.) of 6.9% at 100 µM AA. The long-term reproducibility, using the same microsensor for 112 consecutive measurements of 20 µM AA over 11 h of periodic probing sets over 4 days, was 16.1% r.s.d., thus showing very good stability at low AA levels and suitability for use over a prolonged period of time. Moreover, using the proposed microsensor, additionally coated with a protective cellulose acetate membrane, the calibration plot obtained in the extremely complex matrix of real undiluted gastric juice was linear from 10 to 520 µM (n=14, r=0.998). These results demonstrated the unique featuring of the proposed NiO-RuHCF microsensor under acidic conditions with enhanced sensitivity and stability and proved its promising potentiality for direct amperometric probing of AA at physiological levels in real gastric juice environments.

Bismuth film electrode for anodic stripping voltammetric determination of tin.

The bismuth film electrode (BiFE), in combination with anodic stripping voltammetry, offers convenient measurement of low concentrations of tin. The procedure involves simultaneous in situ formation of the bismuth film electrode on a glassy carbon substrate electrode, together with electrochemical deposition of tin, in a non-deaerated model solution containing bismuth ions, catechol as complexing agent and the metal analyte, followed by an anodic stripping scan. The BiFE is characterized by an attractive electroanalytical performance, with two distinct voltammetric stripping signals corresponding to tin, accompanied with low background contributions. Several experimental parameters were optimized, such as concentration of bismuth ions and catechol, deposition potential, deposition time and pH of the model solution. In addition, a critical comparison is given with bare glassy carbon and mercury film electrodes, revealing the superior characteristics of BiFE for measurement of tin. BiFE exhibited highly linear behavior in the examined concentration range from 1 to 100 microg L(-1) of tin (R2=0.997), an LoD of 0.26 microg L(-1) tin, and good reproducibility with a calculated R.S.D. of 7.3% for 10 microg L(-1) tin (n=10). As an example, the practical applicability of BiFE was tested with the measurement of tin in a real sample of seawater.

Validation of bismuth film electrode for determination of cobalt and cadmium in soil extracts using ICP-MS.

A study is presented on the use of the bismuth film electrode (BiFE) operated in the anodic stripping and the cathodic adsorptive stripping voltammetry (ASV, CAdSV) modes, for the determination of two trace heavy metals (Cd and Co, respectively), in soil extract samples. Two types of BiFE were examined in this study: the in situ prepared BiFE, which was employed in ASV determination of Cd, and the ex situ prepared BiFE, which was used in CAdSV of Co with dimethylglyoxime (DMG) as complexing agent. A series of unpretreated soil extracts with varying Cd and Co concentrations were analyzed, and the results obtained compared to those determined using inductively coupled plasma-mass spectrometry (ICP-MS). The results revealed the suitability of stripping analysis at the BiFE for determination of mugl(-1) levels of heavy metals in soil extracts. The promising results obtained here, coupled with the non-toxic nature of bismuth (in comparison to commonly used mercury electrodes employed in stripping analysis), offer great promise in centralized and decentralized analysis of trace heavy metals in complex environmental matrices.