Personal protective equipment related skin reactions in healthcare professionals during COVID‐19

Since the outbreak of COVID‐19 pandemic, clinicians have had to use personal protective equipment (PPE) for prolonged periods. This has been associated with detrimental effects, especially in relation to the skin health. The present study describes a comprehensive survey of healthcare workers (HCWs) to describe their experiences using PPE in managing COVID‐19 patients, with a particular focus on adverse skin reactions. A 24‐hour prevalence study and multi‐centre prospective survey were designed to capture the impact of PPE on skin health of hospital staff. Questionnaires incorporated demographics of participants, PPE type, usage time, and removal frequency. Participants reported the nature and location of any corresponding adverse skin reactions. The prevalence study included all staff in intensive care from a single centre, while the prospective study used a convenience sample of staff from three acute care providers in the United Kingdom. A total of 108 staff were recruited into the prevalence study, while 307 HCWs from a variety of professional backgrounds and demographics participated in the prospective study. Various skin adverse reactions were reported for the prevalence study, with the bridge of the nose (69%) and ears (30%) being the most affected. Of the six adverse skin reactions recorded for the prospective study, the most common were redness blanching (33%), itchiness (22%), and pressure damage (12%). These occurred predominantly at the bridge of the nose and the ears. There were significant associations (P < .05) between the adverse skin reactions with both the average daily time of PPE usage and the frequency of PPE relief. The comprehensive study revealed that the use of PPE leads to an array of skin reactions at various facial locations of HCWs. Improvements in guidelines are required for PPE usage to protect skin health. In addition, modifications to PPE designs are required to accommodate a range of face shapes and appropriate materials to improve device safety.     

Enolase 1 of Candida albicans binds human CD4+ T cells and modulates naïve and memory responses

To obtain a better understanding of the biology behind life-threatening fungal infections caused by Candida albicans, we recently conducted an in silico screening for fungal and host protein interaction partners. We report here that the extracellular domain of human CD4 binds to the moonlighting protein enolase 1 (Eno1) of C. albicans as predicted bioinformatically. By using different anti-CD4 monoclonal antibodies, we determined that C. albicans Eno1 (CaEno1) primarily binds to the extracellular domain 3 of CD4. Functionally, we observed that CaEno1 binding to CD4 activated lymphocyte-specific protein tyrosine kinase (LCK), which was also the case for anti-CD4 monoclonal antibodies tested in parallel. CaEno1 binding to naïve human CD4⁺ T cells skewed cytokine secretion toward a Th2 profile indicative of poor fungal control. Moreover, CaEno1 inhibited human memory CD4⁺ T-cell recall responses. Therapeutically, CD4⁺ T cells transduced with a p41/Crf1-specific T-cell receptor developed for adoptive T-cell therapy were not inhibited by CaEno1 in vitro. Together, the interaction of human CD4⁺ T cells with CaEno1 modulated host CD4⁺ T-cell responses in favor of the fungus. Thus, CaEno1 mediates not only immune evasion through its interference with complement regulators but also through the direct modulation of CD4⁺ T-cell responses.     

Development and in Vitro Evaluation of Systems to Protect Peptide Drugs from Aminopeptidase N

Purpose. Develop and evaluate systems to prevent aminopeptidase N caused enzymatic degradation of perorally administrated peptide drugs. Methods. Bacitracin was covalently bound to the unabsorbable carrier matrix poly(acrylic acid) (paa) in order to avoid any dilution effects of the inhibitor in the intestine as well as systemic toxic side effects. The inhibitory effect of this conjugate, of neutralized paa and N-acetylcysteine was evaluated using a brush border membrane model. Results. Whereas within 6 h of incubation 65.3 ± 3.7 mol/1 of the substrate (L-leucine p-nitroanilide) was hydrolyzed under our assay conditions, this metabolism was reduced to 44.5 ± 6.3 mol/1 and 49.0 ± 8.8 mol/1 (n = 3–5; ± S.D.) using 1.5% bacitracin-polymer conjugate and 0.5% N-acetylcysteine, respectively. The same amount of bacitracin as immobilized to the polymer exhibited a comparably weaker inhibitory effect. Neutralized paa did not inhibit membrane bound aminopeptidase N. Covering the membrane with a thin mucus layer led to a significantly lowered inhibitory effect of all tested agents. Conclusions. The immobilization of enzyme inhibitors to a carrier matrix and the use of N-acetylcysteine as a novel inhibitor are promising strategies in order to overcome the enzymatic barrier caused by membrane bound peptidases. However the use of effective mucolytic agents seems to be a prerequisite.     

Application of eye drops to the medial canthus

Background: Our purpose was to investigate the efficacy of instillation of eye drops in the medial canthus with the lids closed at the time of application. Methods: The pupils of 50 healthy volunteers were dilated with tropicamide 0.125%. The effect of the drug on pupillary dilatation when instilled in one eye with the lids closed was compared to its effect when instilled in the conventional mode in the other eye. Results: Maximal mydriasis achieved was 2.75 ± 0.76 mm in the eye with closed lids and 2.8 ± 0.77 mm in the eye in which eye drops were instilled in the conventional mode. Conclusion: Eye drop instillation in the medial canthus with the lids closed at the time of application seems to be an effective means of ophthalmic drug delivery.     

Teaching participants with developmental disabilities to comply with self-instructions

Four adults with mild mental retardation were taught to sort based on what two pictures had in common and to name each object and common features of two pairs as well as to comply with a series of instructions to sort the pictures selectively. The criterion task was to inspect a sample pair, sort through a deck of 15 pictures to find those showing what the sample pair had in common, and to repeat a series of pairs. They failed this task and continued to fail even after a supposedly relevant self-instruction. After being taught to act on what they told themselves, they self-instructed correctly and sorted accordingly. Imperfect generalization by 2 participants was remediated by revoking self-instructions. They were taught to act on what they told themselves; thereafter, they self-instructed correctly and sorted accordingly. Imperfect generalization by 2 participants was remediated by re-evoking the relevant self-instructions.     

Retinal pigment epithelial cells from Royal College of Surgeons dystrophic rats can take up melanin granules

· Background: Many successful pigment epithelium transplantation studies involving pink-eyed Royal College of Surgeons (RCS) dystrophic rats showed highly pigmented transplanted cells forming a double layer with slightly pigmented cells, attached to Bruch’s membrane. Since it is not clear whether transplanted pigmented cells can displace retinal pigment epithelial (RPE) host cells from Bruch’s membrane, we suggested that RPE cells of RCS dystrophic rats can phagocytize melanin granules, possibly derived from perished transplanted cells. · Methods: In a series of three experiments, RPE cells of nine pink-eyed, 2-month-old RCS dystrophic rats were isolated by trypsinization and mechanical dissection and cultivated in Dulbecco’s modified Eagles’ medium. These cells were then fed with melanin granules, isolated from bovine RPE cells, double-trypsinized after phagocytosis and viewed by light and electron microscopy. We also transplanted iris pigment epithelial (IPE) cells of 20-day-old Long-Evans rats into the subretinal space of pink-eyed RCS dystrophic rats of the same age, shown in light-microscopic photography after 42 days. · Results: Living RPE cells were heavily pigmented after feeding with isolated melanin granules in all three experiments as viewed by light microscopy. In addition, we identified melanin granules phagocytized by dystrophic RPE cells in electron microscopy. After transplantation of pigmented IPE cells into the subretinal space of pink-eyed RCS dystrophic rats’ eyes, a layer of slightly pigmented cells was seen on Bruch’s membrane below the transplanted IPE cells, shown in light microscopy. · Conclusion: We have shown by phagocytosis assay that dystrophic RPE cells can take up melanin granules in vitro. Our results assume that pigmented cells in transplantation studies, found as a monolayer, attached to Bruch’s membrane, cannot automatically be identified as transplanted cells. Instead, the possibility of perished transplanted cells serving as melanin donors for RPE host cells must be taken into consideration. Received: 11 March 1998 Revised version received: 5 May 1998 Accepted: 26 May 1998     

β-Lactam antibiotics in the treatment of neuroborreliosis in children: Preliminary results

Summary In vitro -lactam antibiotics like ceftriaxone and penicillin G sodium have been shown to be active againstBorrelia burgdorferi. Results of quantitative determinations of both antibiotic substances in the CSF for children are limited. Seventy-five children (median age 96 months, range 10 to 176 months) with probable or definite neuroborreliosis were treated with ceftriaxone (1×50–90 mg/kg/day) or penicillin G sodium (4×80,000–120,000 IU/kg/day) intravenously. On day 10 of therapy levels of penicillin G sodium (1, 1.5, 2, 3, 4, 5, or 6 h after i.v. administration), and ceftriaxone (1, 2, 4, 6, 12 or 24 h after i.v. administration) in serum and CSF were measured with a micro agar diffusion bioassay. Results demonstrate that after 5 h penicillin G sodium in CSF was above the minimal inhibitory concentration (MIC) but after 6 h penicillin G sodium levels were below the determination limit in 60% of the cases. All ceftriaxone results in CSF — even after 24 h — were above MIC. Penicillin G sodium serum values ranged from 46.6 to 0.1 mg/l (1 to 6 h post dose) and ceftriaxone serum values from 261 to 5 mg/l (1 to 24 h post dose). The role of penicillin G sodium and ceftriaxone and administration intervals of both antibiotics in the therapy of neuroborreliosis in children are discussed.

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-Lactam Antibiotika zur Behandlung der Neuroborreliose im Kindesalter: Vorläufige Ergebnisse

Zusammenfassung Ceftriaxon und Natrium-Penicillin G sind gegenBorrelia burgdorferi in vitro wirksam. Zur Pharmakokinetik beider Substanzen im Liquor cerebrospinalis von Kindern ist hingegen wenig bekannt. 75 Kinder im Alter von 10 bis 176 Monaten (Median 96) mit einer definitiven oder möglichen Neuroborreliose wurden intravenös mit Ceftriaxon (1×50–90 mg/kg/Tag) oder Penicillin G (4×80000–120000 I.E./kg/Tag) behandelt. Am 10. Therapietag wurden die Liquor-Spiegel von Penicillin G (1, 1.5, 2, 3, 4, 5, oder 6 Stunden nach Gabe) bzw. Ceftriaxon (1, 2, 4, 6, 12, oder 24 Stunden nach Gabe) in Serum und Liquor aus gepaarten Proben mittels einer Mikroagar Diffusions-Methode gemessen. Die Ergebnisse zeigen, daß Penicillin G 5 Stunden nach Gabe noch über der minimalen Hemmkonzentration lag, daß aber 6 Stunden nach Gabe die Konzentration des Antibiotikums in 60% der Liquorproben bereits unterhalb der Meßgrenze lag. Die Ceftriaxon Liquorspiegel lagen durchwegs über der MHK — auch noch 24 Stunden nach der letzten Gabe. Die Serumkonzentrationen von Penicillin G lagen zwischen 46,6 und 0.1 mg/l, die Serumkonzentrationen von Ceftriaxon zwischen 261 und 5 mg/l. Die vorgestellten Ergebnisse werden im Hinblick auf den Stellenwert der beiden Antibiotika in der Therapie der Neuroborreliose im Kindesalter diskutiert.