Multisystem screening reveals SARS-CoV-2 in neurons of the myenteric plexus and in megakaryocytes.

SARS-CoV-2, the causative agent of COVID-19, typically manifests as a respiratory illness, although extrapulmonary involvement, such as in the gastrointestinal tract and nervous system, as well as frequent thrombotic events, are increasingly recognised. How this maps onto SARS-CoV-2 organ tropism at the histological level, however, remains unclear. Here, we perform a comprehensive validation of a monoclonal antibody against the SARS-CoV-2 nucleocapsid protein (NP) followed by systematic multisystem organ immunohistochemistry analysis of the viral cellular tropism in tissue from 36 patients, 16 postmortem cases and 16 biopsies with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 status from the peaks of the pandemic in 2020 and four pre-COVID postmortem controls. SARS-CoV-2 anti-NP staining in the postmortem cases revealed broad multiorgan involvement of the respiratory, digestive, haematopoietic, genitourinary and nervous systems, with a typical pattern of staining characterised by punctate paranuclear and apical cytoplasmic labelling. The average time from symptom onset to time of death was shorter in positively versus negatively stained postmortem cases (mean = 10.3 days versus mean = 20.3 days, p = 0.0416, with no cases showing definitive staining if the interval exceeded 15 days). One striking finding was the widespread presence of SARS-CoV-2 NP in neurons of the myenteric plexus, a site of high ACE2 expression, the entry receptor for SARS-CoV-2, and one of the earliest affected cells in Parkinson's disease. In the bone marrow, we observed viral SARS-CoV-2 NP within megakaryocytes, key cells in platelet production and thrombus formation. In 15 tracheal biopsies performed in patients requiring ventilation, there was a near complete concordance between immunohistochemistry and PCR swab results. Going forward, our findings have relevance to correlating clinical symptoms with the organ tropism of SARS-CoV-2 in contemporary cases as well as providing insights into potential long-term complications of COVID-19. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Polythiophene Doping of the Cu-Based Metal-Organic Framework (MOF) HKUST-1 Using Innate MOF-Initiated Oxidative Polymerization.

The copper-based metal-organic framework (MOF) HKUST-1 adsorbs organic molecules into its pores. When loaded with electron-rich oligothiophenes, the resulting system reacts under heat to initiate oxidative polymerization without the use of any other oxidant or catalyst. This reaction is not observed in the non-redox-active MOF MIL-100(Al). We have characterized the composites by optical and nanoscale microscopy, vibrational and UV-vis spectroscopy, X-ray photoelectron spectroscopy, N2 sorption analysis, and thermogravimetric analysis/residual gas analysis. Unsubstituted oligothiophenes polymerize within MOF pores, while 3,4-ethylenedioxythiophene forms a coating on the MOF surface. MOF composites with conjugated polymer dopants trapped inside their pores undergo profound shifts in the composite electronic structure. Reasoning from time-dependent density functional theory calculations of an HKUST-1 model system bound to monomers, we rationalize the observed reactivity and propose an initiation mechanism based on a ligand-to-metal charge-transfer state.

Positional Differences in Running and Nonrunning Activities During Elite American Football Training.

Ward, PA, Ramsden, S, Coutts, AJ, Hulton, AT, and Drust, B. Positional differences in running and nonrunning activities during elite American football training. J Strength Cond Res XX(X): 000-000, 2017-The aim of this investigation was to describe differences in training loads between position groups within professional American football. Integrated micro technology data were collected on 63 NFL football players during an American football training camp. Five key metrics (total distance, high-speed distance, player load (PL), PL per minute, and total inertial movement analysis [IMA]) served to quantify both running and nonrunning activities. Players were classified into position groups (defensive back [DB], defensive linemen [DL], linebacker, offensive linemen [OL], quarterback, running back, tight end, and wide receiver [WR]). Training sessions were identified by their relationship to the upcoming match (e.g., -4, -3, and -2). Running and nonrunning activities varied between position groups relative to the training day. Differences in total distance between DB and WR were observed to be unclear across the 3 training days (game day [GD] -4: 74 ± 392 m; GD -3: -122 ± 348 m; and GD -2: -222 ± 371 m). However, moderate to large differences were observed between these 2 positions and the other positional groups. A similar relationship was observed in PL and PL per minute, with the DB and WR groups performing greater amounts of load compared with other positional groups. Differences in high-speed distance varied across positional groups, indicating different outputs based on ergonomic demands. The OL and DL groups ran less but engaged in a higher amount of nonrunning activities (total IMA) with differences ranging from moderate to large across the 3 training days. Total IMA differences between offensive and defensive linemen were unclear on GD -4 (-4 ± 9) and GD -2 (-2 ± 8) and likely moderate on GD -3 (-9 ± 9). Positional differences with regard to running and nonrunning activities highlight the existence of position-specific training within a training microcycle. In addition, total IMA provides a useful metric for quantifying sport-specific movements within the game of American football.

Synthesis, characterization, and reversible hydrogen sorption study of sodium-doped fullerene.

Herein is presented a novel, straightforward route to the synthesis of an alkali metal-doped fullerene as well as a detailed account of its reversible and enhanced hydrogen sorption properties in comparison to pure C60. This work demonstrates that a reaction of sodium hydride with fullerene (C60) results in the formation of a sodium-doped fullerene capable of reversible hydrogen sorption via a chemisorption mechanism. This material not only demonstrated reversible hydrogen storage over several cycles, it also showed the ability to reabsorb over three times the amount of hydrogen (relative to the hydrogen content of NaH) under optimized conditions. The sodium-doped fullerene was hydrogenated on a pressure composition temperature (PCT) instrument at 275 °C while under 100 bar of hydrogen pressure. The hydrogen desorption behavior of this sodium-doped fullerene hydride was observed over a temperature range up to 375 °C on the PCT and up to 550 °C on the thermogravimetric analysis (TGA). Powder x-ray diffraction verifies the identity of this material as being Na6C60. Characterization of this material by thermal decomposition analysis (e.g. PCT and TGA methods), as well as FT-IR and mass spectrometry, indicates that the hydrogen sorption activity of this material is due to the reversible formation of a hydrogenated fullerene (fullerane). However, the reversible formation of fullerane was found to be greatly enhanced by the presence of sodium. It was also demonstrated that the addition of a catalytic amount of titanium (via TiO2 or Ti(OBu)4) further enhances the hydrogen sorption process of the sodium-doped fullerene material.

Synthesis and characterization of a lithium-doped fullerane (Li(x)-C60-H(y)) for reversible hydrogen storage.

Herein, we present a lithium-doped fullerane (Li(x)-C(60)-H(y)) that is capable of reversibly storing hydrogen through chemisorption at elevated temperatures and pressures. This system is unique in that hydrogen is closely associated with lithium and carbon upon rehydrogenation of the material and that the weight percent of H(2) stored in the material is intimately linked to the stoichiometric ratio of Li:C(60) in the material. Characterization of the material (IR, Raman, UV-vis, XRD, LDI-TOF-MS, and NMR) indicates that a lithium-doped fullerane is formed upon rehydrogenation in which the active hydrogen storage material is similar to a hydrogenated fullerene. Under optimized conditions, a lithium-doped fullerane with a Li:C(60) mole ratio of 6:1 can reversibly desorb up to 5 wt % H(2) with an onset temperature of ~270 °C, which is significantly less than the desorption temperature of hydrogenated fullerenes (C(60)H(x)) and pure lithium hydride (decomposition temperature 500-600 and 670 °C respectively). However, our Li(x)-C(60)-H(y) system does not suffer from the same drawbacks as typical hydrogenated fullerenes (high desorption T and release of hydrocarbons) because the fullerene cage remains mostly intact and is only slightly modified during multiple hydrogen desorption/absorption cycles. We also observed a reversible phase transition of C(60) in the material from face-centered cubic to body-centered cubic at high levels of hydrogenation.

Airway Management: The Current Role of Videolaryngoscopy.

Airway management is usually an uncomplicated and safe intervention; however, when problems arise with the primary airway technique, the clinical situation can rapidly deteriorate, resulting in significant patient harm. Videolaryngoscopy has been shown to improve patient outcomes when compared with direct laryngoscopy, including improved first-pass success at tracheal intubation, reduced difficult laryngeal views, reduced oxygen desaturation, reduced airway trauma, and improved recognition of oesophageal intubation. The shared view that videolaryngoscopy affords may also facilitate superior teaching, training, and multidisciplinary team performance. As such, its recommended role in airway management has evolved from occasional use as a rescue device (when direct laryngoscopy fails) to a first-intention technique that should be incorporated into routine clinical practice, and this is reflected in recently updated guidelines from a number of international airway societies. However, currently, overall videolaryngoscopy usage is not commensurate with its now widespread availability. A number of factors exist that may be preventing its full adoption, including perceived financial costs, inadequacy of education and training, challenges in achieving deliverable decontamination processes, concerns over sustainability, fears over "de-skilling" at direct laryngoscopy, and perceived limitations of videolaryngoscopes. This article reviews the most up-to-date evidence supporting videolaryngoscopy, explores its current scope of utilisation (including specialist techniques), the potential barriers preventing its full adoption, and areas for future advancement and research.

Spectroscopic investigation of the electronic and excited state properties of para-substituted tetraphenyl porphyrins and their electrochemically generated ions.

Porphyrins play pivotal roles in many crucial biological processes including photosynthesis. However, there is still a knowledge gap in understanding electronic and excited state implications associated with functionalization of the porphyrin ring system. These effects can have electrochemical and spectroscopic signatures that reveal the complex nature of these somewhat minor substitutions, beyond simple inductive or electronic effect correlations. To obtain a deeper insight into the influences of porphyrin functionalization, four free-base, meso-substituted porphyrins: tetraphenyl porphyrin (TPP), tetra(4-hydroxyphenyl) porphyrin (THPP), tetra(4-carboxyphenyl) porphyrin (TCPP), and tetra(4-nitrophenyl) porphyrin (TNPP), were synthesized, characterized, and investigated. The influence of various substituents, (-hydroxy,-carboxy, and -nitro) in the para position of the meso-substituted phenyl moieties were evaluated by spectroelectrochemical techniques (absorption and fluorescence), femtosecond transient absorption spectroscopy, cyclic and differential pulse voltammetry, ultraviolet photoelectron spectroscopy (UPS), and time-dependent density functional theory (TD-DFT). Spectral features were evaluated for the neutral porphyrins and differences observed among the various porphyrins were further explained using rendered frontier molecular orbitals pertaining to the relevant transitions. Electrochemically generated anionic and cationic porphyrin species indicate similar absorbance spectroscopic signatures attributed to a red-shift in the Soret band. Emissive behavior reveals the emergence of one new fluorescence decay pathway for the ionic porphyrin, distinct from the neutral macrocycle. Femtosecond transient absorption spectroscopy analysis provided further analysis of the implications on the excited-state as a function of the para substituent of the free-base meso-substituted tetraphenyl porphyrins. Herein, we provide an in-depth and comprehensive analysis of the electronic and excited state effects associated with systematically varying the induced dipole at the methine bridge of the free-base porphyrin macrocycle and the spectroscopic signatures related to the neutral, anionic, and cationic species of these porphyrins.

Closo-Borate Gel Polymer Electrolyte with Remarkable Electrochemical Stability and a Wide Operating Temperature Window.

A major challenge in the pursuit of higher-energy-density lithium batteries for carbon-neutral-mobility is electrolyte compatibility with a lithium metal electrode. This study demonstrates the robust and stable nature of a closo-borate based gel polymer electrolyte (GPE), which enables outstanding electrochemical stability and capacity retention upon extensive cycling. The GPE developed herein has an ionic conductivity of 7.3 × 10-4  S cm-2 at room temperature and stability over a wide temperature range from -35 to 80 °C with a high lithium transference number ( tLi+$t_{{\rm{Li}}}^ + $ = 0.51). Multinuclear nuclear magnetic resonance and Fourier transform infrared are used to understand the solvation environment and interaction between the GPE components. Density functional theory calculations are leveraged to gain additional insight into the coordination environment and support spectroscopic interpretations. The GPE is also established to be a suitable electrolyte for extended cycling with four different active electrode materials when paired with a lithium metal electrode. The GPE can also be incorporated into a flexible battery that is capable of being cut and still functional. The incorporation of a closo-borate into a gel polymer matrix represents a new direction for enhancing the electrochemical and physical properties of this class of materials.

Surgical Tracheostomy Outcomes in COVID-19-Positive Patients.

OBJECTIVE: The aim of this case series was to demonstrate that surgical tracheostomy can be undertaken safely in critically ill mechanically ventilated patients with coronavirus disease 2019 (COVID-19) and that it is an effective weaning tool. STUDY DESIGN: Retrospective case series. SETTING: Single academic teaching hospital in London. METHODS: All adult patients admitted to the adult intensive care unit (AICU), diagnosed with severe COVID-19 infection and requiring surgical tracheostomy between the March 10, 2020, and May 1, 2020, were included. Data collection focused upon patient demographics, AICU admission data, tracheostomy-specific data, and clinical outcomes. RESULTS: Twenty patients with COVID-19 underwent surgical tracheostomy. The main indication for tracheostomy was to assist in respiratory weaning. Patients had undergone mechanical ventilation for a median of 16.5 days prior to surgical tracheostomy. Tracheostomy remained in situ for a median of 12.5 days. Sixty percent of patients were decannulated at the end of the data collection period. There were no serious immediate or short-term complications. Surgical tracheostomy facilitated significant reduction in intravenous sedation at 48 hours after tracheostomy formation. There was no confirmed COVID-19 infection or reported sickness in the operating surgical or anesthetic teams. CONCLUSION: Surgical tracheostomy has been demonstrated to be an effective weaning tool in patients with severe COVID-19 infection.

Emergency Tracheal Intubation in Patients with COVID-19: Experience from a UK Centre.

This retrospective observational case series describes a single centre's preparations and experience of 53 emergency tracheal intubations in patients with COVID-19 respiratory failure. The findings of a contemporaneous online survey exploring technical and nontechnical aspects of airway management, completed by intubation team members, are also presented. Preparations included developing a COVID-19 intubation standard operating procedure and checklist, dedicated airway trolleys, a consultant-led mobile intubation team, and an airway education programme. Tracheal intubation was successful in all patients. Intubation first-pass success rate was 85%, first-line videolaryngoscopy use 79%, oxygen desaturation 49%, and hypotension 21%. Performance was consistent across all clinical areas. The main factor impeding first-pass success was larger diameter tracheal tubes. The majority of intubations was performed by consultant anaesthetists. Nonconsultant intubations demonstrated higher oxygen desaturation rates (75% vs. 45%, p=0.610) and lower first-pass success (0% vs. 92%, p < 0.001). Survey respondents (n = 29) reported increased anxiety at the start of the pandemic, with statistically significant reduction as the pandemic progressed (median: 4/5 very high vs. 2/5 low anxiety, p < 0.001). Reported procedural/environmental challenges included performing tasks in personal protective equipment (62%), remote-site working (48%), and modification of normal practices (41%)-specifically, the use of larger diameter tracheal tubes (21%). Hypoxaemia was identified by 90% of respondents as the most challenging patient-related factor during intubations. Our findings demonstrate that a consultant-led mobile intubation team can safely perform tracheal intubation in critically ill COVID-19 patients across all clinical areas, aided by thorough preparation and training, despite heightened anxiety levels.