Acute upper limb infections in a regional Scottish plastic surgery unit during COVID-19: Lessons learned.

Acute upper limb infections represent a large proportion of on-call referrals and emergency theatre time in plastic surgery. To enable us to maintain effective service provision despite reallocation of hospital resources as a result of COVID-19, and to minimise patient exposure in a hospital setting during the pandemic, we introduced a walk-in clinic and dedicated local anaesthetic (LA) operating theatre for these infections. In this work, we sought to analyse our service changes and resulting patient outcomes. Using electronic records, data from patients presenting with upper extremity infections was collected before the pandemic from 1st January to 30th March 2020, then for a period of three months from 30th March until 30th June 2020, after our changes were implemented. Seventy-two patients were included before 30th March 2020, and 49 patients after. Prior to our changes, most patients underwent surgery (n = 58, 80.6%), requiring overnight admission (n = 64, 88.9%), following mainly general anaesthetic procedures (n = 56, 96.6%). After our service changes, a similar percentage of patients were treated operatively (n = 41, 83.7%), but these procedures mostly utilised LA (n = 37, 90.2%) in the outpatient setting (n = 25, 51.0%). Despite this shift in management approach, no statistically significant difference in readmission rates was calculated between the two groups (p = 0.556) and post-operative complications were fewer in absolute terms. Our results suggest that in many instances, these infections can be managed in an outpatient setting without the need for inpatient care. Selective admission with strict follow-up of patients may be feasible, improving patient experience and reducing resource burden.

Capture of Perfluorooctanoic Acid Using Oil-Filled Graphene Oxide-Silica Hybrid Capsules.

Fluorinated hydrocarbon (FHC) contamination has attracted global attention recently because of persistence within the environment and ecosystems of many types of FHC. The surfactant perfluorooctanoic acid (PFOA) is particularly commonly found in contaminated sites, and thus, urgent action is needed for its removal from the environment. In this study, water dispersible hybrid capsules were successfully prepared from an oil-in-water emulsion stabilized by graphene oxide and including a silicate precursor to grow a strong, mesoporous capsule shell surrounding the droplets. These capsules were decorated with amine groups to present a positively charged outer corona that attracts negative PFOA molecules. The aminated capsules were effectively applied as a novel technology to adsorb and sequester PFOA contamination in water. It was confirmed that PFOA removal by the capsules was pH and PFOA concentration dependent, with adsorption efficiencies of >60 mg g-1 under ideal conditions. PFOA removal kinetics followed using high-performance liquid chromatography and liquid chromatography-mass spectrometry showed that capture of PFOA by the capsules reached a maximum of >99.9% in 2-3 days.

Graphene oxide-silica hybrid capsules for sustained fragrance release.

Encapsulation of active or valuable cargoes has become one of the most important methods for controlled delivery and release. However, many existing capsule technologies suffer from scalability issues, and capsules from surfactant- or polymer-stabilised emulsions tend to have weak shells or limited stability. Here we present a robust and scalable method for the surfactant-free preparation of silica hybrid capsules templated from Pickering emulsions stabilised by graphene oxide. These capsules are produced using a single step, undemanding formulation process with cheap and scalable precursors. The mechanical and chemical stability provided by the silica shell grown around these droplets is explored using surface pressure measurements and atomic force microscopy, demonstrating that a rigid and robust capsule is produced from higher loadings of silica precursor. In order to demonstrate the utility of these capsules, the sustained release of a fragrance molecule (vanillin) from the capsules is monitored, and compared to release from unencapsulated vanilla oil. It is seen that the capsules retain the fragrance for multiple weeks, offering new pathways for scalable encapsulation systems for the delivery of valuable actives.

Sphingosine kinase 2-deficiency mediated changes in spinal pain processing.

Chronic pain is one of the most burdensome health issues facing the planet (as costly as diabetes and cancer combined), and in desperate need for new diagnostic targets leading to better therapies. The bioactive lipid sphingosine 1-phosphate (S1P) and its receptors have recently been shown to modulate nociceptive signaling at the level of peripheral nociceptors and central neurons. However, the exact role of S1P generating enzymes, in particular sphingosine kinase 2 (Sphk2), in nociception remains unknown. We found that both sphingosine kinases, Sphk1 and Sphk2, were expressed in spinal cord (SC) with higher levels of Sphk2 mRNA compared to Sphk1. All three Sphk2 mRNA-isoforms were present with the Sphk2.1 mRNA showing the highest relative expression. Mice deficient in Sphk2 (Sphk2(-/-)) showed in contrast to mice deficient in Sphk1 (Sphk1(-/-)) substantially lower spinal S1P levels compared to wild-type C57BL/6 mice. In the formalin model of acute peripheral inflammatory pain, Sphk2(-/-) mice showed facilitation of nociceptive transmission during the late response, whereas responses to early acute pain, and the number of c-Fos immunoreactive dorsal horn neurons were not different between Sphk2(-/-) and wild-type mice. Chronic peripheral inflammation (CPI) caused a bilateral increase in mechanical sensitivity in Sphk2(-/-) mice. Additionally, CPI increased the relative mRNA expression of P2X4 receptor, brain-derived neurotrophic factor and inducible nitric oxide synthase in the ipsilateral SC of wild-type but not Sphk2(-/-) mice. Similarly, Sphk2(-/-) mice showed in contrast to wild-type no CPI-dependent increase in areas of the dorsal horn immunoreactive for the microglia marker Iba-1 and the astrocyte marker Glial fibrillary acidic protein (GFAP). Our results suggest that the tightly regulated cell signaling enzyme Sphk2 may be a key component for facilitation of nociceptive circuits in the CNS leading to central sensitization and pain memory formation.

Oxidative stress decreases functional airway mannose binding lectin in COPD.

We have previously established that a defect in the ability of alveolar macrophages (AM) to phagocytose apoptotic cells (efferocytosis) and pathogens is a potential therapeutic target in COPD. We further showed that levels of mannose binding lectin (MBL; required for effective macrophage phagocytic function) were reduced in the airways but not circulation of COPD patients. We hypothesized that increased oxidative stress in the airway could be a cause for such disturbances. We therefore studied the effects of oxidation on the structure of the MBL molecule and its functional interactions with macrophages. Oligomeric structure of plasma derived MBL (pdMBL) before and after oxidation (oxMBL) with 2,2'-azobis(2-methylpropionamidine)dihydrochroride (AAPH) was investigated by blue native PAGE. Macrophage function in the presence of pd/oxMBL was assessed by measuring efferocytosis, phagocytosis of non-typeable Haemophilus influenzae (NTHi) and expression of macrophage scavenger receptors. Oxidation disrupted higher order MBL oligomers. This was associated with changed macrophage function evident by a significantly reduced capacity to phagocytose apoptotic cells and NTHi in the presence of oxMBL vs pdMBL (eg, NTHi by 55.9 and 27.0% respectively). Interestingly, oxidation of MBL significantly reduced macrophage phagocytic ability to below control levels. Flow cytometry and immunofluorescence revealed a significant increase in expression of macrophage scavenger receptor (SRA1) in the presence of pdMBL that was abrogated in the presence of oxMBL. We show the pulmonary macrophage dysfunction in COPD may at least partially result from an oxidative stress-induced effect on MBL, and identify a further potential therapeutic strategy for this debilitating disease.

Alpha-tocopheryl phosphate: a novel, natural form of vitamin E.

We have detected alpha-tocopheryl phosphate in biological tissues including liver and adipose tissue, as well as in a variety of foods, suggesting a ubiquitous presence in animal and plant tissue. Alpha-tocopheryl phosphate is a water-soluble molecule that is resistant to both acid and alkaline hydrolysis, making it undetectable using standard assays for vitamin E. A new method was therefore developed to allow the extraction of both alpha-tocopheryl phosphate and alpha-tocopherol from a single specimen. We used ESMS to detect endogenous alpha-tocopheryl phosphate in biological samples that also contained alpha-tocopherol. Due to the significance of these findings, further proof was required to unequivocally demonstrate the presence of endogenous alpha-tocopheryl phosphate in biological samples. Four independent methods of analysis were examined: HPLC, LCMS, LCMS/MS, and GCMS. Alpha-tocopherol phosphate was identified in all instances by comparison between standard alpha-tocopheryl phosphate and extracts of biological tissues. The results show that alpha-tocopheryl phosphate is a natural form of vitamin E. The discovery of endogenous alpha-tocopheryl phosphate has implications for the expanding knowledge of the roles of alpha-tocopherol in biological systems.