What started as a cluster of patients with a mysterious respiratory illness in Wuhan, China, in December 2019, was later determined to be coronavirus disease 2019 (COVID-19). The pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel Betacoronavirus , was subsequently isolated as the causative agent. SARS-CoV-2 is transmitted by respiratory droplets and fomites and presents clinically with fever, fatigue, myalgias, conjunctivitis, anosmia, dysgeusia, sore throat, nasal congestion, cough, dyspnea, nausea, vomiting, and/or diarrhea. In most critical cases, symptoms can escalate into acute respiratory distress syndrome accompanied by a runaway inflammatory cytokine response and multiorgan failure. As of this article's publication date, COVID-19 has spread to approximately 200 countries and territories, with over 4.3 million infections and more than 290,000 deaths as it has escalated into a global pandemic. Public health concerns mount as the situation evolves with an increasing number of infection hotspots around the globe. New information about the virus is emerging just as rapidly. This has led to the prompt development of clinical patient risk stratification tools to aid in determining the need for testing, isolation, monitoring, ventilator support, and disposition. COVID-19 spread is rapid, including imported cases in travelers, cases among close contacts of known infected individuals, and community-acquired cases without a readily identifiable source of infection. Critical shortages of personal protective equipment and ventilators are compounding the stress on overburdened healthcare systems. The continued challenges of social distancing, containment, isolation, and surge capacity in already stressed hospitals, clinics, and emergency departments have led to a swell in technologically-assisted care delivery strategies, such as telemedicine and web-based triage. As the race to develop an effective vaccine intensifies, several clinical trials of antivirals and immune modulators are underway, though no reliable COVID-19-specific therapeutics (inclusive of some potentially effective single and multi-drug regimens) have been identified as of yet. With many nations and regions declaring a state of emergency, unprecedented quarantine, social distancing, and border closing efforts are underway. Implementation of social and physical isolation measures has caused sudden and profound economic hardship, with marked decreases in global trade and local small business activity alike, and full ramifications likely yet to be felt. Current state-of-science, mitigation strategies, possible therapies, ethical considerations for healthcare workers and policymakers, as well as lessons learned for this evolving global threat and the eventual return to a “new normal” are discussed in this article.
SARS-CoV-2 is a virus that is the cause of a serious life-threatening disease known as COVID-19. It was first noted to have occurred in Wuhan, China in November 2019 and the WHO reported the first case on December 31, 2019. The outbreak was declared a global pandemic on March 11, 2020 and by May 30, 2020, a total of 5 899 866 positive cases were registered including 364 891 deaths. SARS-CoV-2 primarily targets the lung and enters the body through ACE2 receptors. Typical symptoms of COVID-19 include fever, cough, shortness of breath and fatigue, yet some atypical symptoms like loss of smell and taste have also been described. 20% require hospital admission due to severe disease, a third of whom need intensive support. Treatment is primarily supportive, however, prognosis is dismal in those who need invasive ventilation. Trials are ongoing to discover effective vaccines and drugs to combat the disease. Preventive strategies aim at reducing the transmission of disease by contact tracing, washing of hands, use of face masks and government-led lockdown of unnecessary activities to reduce the risk of transmission.
The findings from this international comparison suggest that centralization of high-risk cancer surgery to centers of excellence with a high procedural volume translates into an improved clinical outcome. These findings should be factored into discussions regarding future service configuration of major cancer surgery in the United States.
Mononuclear MnIII–hydroxo and dinuclear (μ-oxo)dimanganese(III,III) complexes were prepared using derivatives of the pentadentate, amide-containing dpaq ligand (dpaq = 2-[bis(pyridin-2-ylmethyl)]amino-N-quinolin-8-yl-acetamidate). Each of these ligand derivatives (referred to as dpaq5R) contained a substituent R (where R = OMe, Cl, and NO2) at the 5-position of the quinolinyl group. Generation of the MnIII complexes was achieved by either O2 oxidation of MnII precursors (for [MnII(dpaq5OMe)]+ and [MnII(dpaq5Cl)]+ or PhIO oxidation (for [MnII(dpaq5NO2 )]+). For each oxidized complex, 1H NMR experiments provided evidence of a water-dependent equilibrium between paramagnetic [MnIII(OH)(dpaq5R)]+ and an antiferromagnetically coupled [MnIIIMnIII(μ-O)(dpaq5R)2]2+ species in acetonitrile, with the addition of water favoring the MnIII–hydroxo species. This conversion could also be monitored by electronic absorption spectroscopy. Solid-state X-ray crystal structures for each [MnIIIMnIII(μ-O)(dpaq5R)2](OTf)2 complex revealed a nearly linear Mn–O–Mn core (angle of ca. 177°), with short Mn–O distances near 1.79 Å, and a Mn···Mn separation of 3.58 Å. X-ray crystallographic information was also obtained for the mononuclear [MnIII(OH)(dpaq5Cl)](OTf) complex, which has a short Mn–O(H) distance of 1.810(2) Å. The influence of the 5-substituted quinolinyl moiety on the electronic properties of the [MnIII(OH)(dpaq5R)]+ complexes was demonstrated through shifts in a number of 1H NMR resonances, as well as a steady increase in the MnIII/II cyclic voltammetry peak potential in the order [MnIII(OH)(dpaq5OMe)]+ < [MnIII(OH)(dpaq)]+ < [MnIII(OH)(dpaq5Cl)]+ < [MnIII(OH)(dpaq5NO2 )]+. These changes in oxidizing power of the MnIII–hydroxo adducts translated to only modest rate enhancements for TEMPOH oxidation by the [MnIII(OH)(dpaq5R)]+ complexes, with the most reactive [MnIII(OH)(dpaq5NO2 )]+ complex showing a second-order rate constant only 9-fold larger than that of the least reactive [MnIII(OH)(dpaq5OMe)]+ complex. These modest rate changes were understood on the basis of density functional theory (DFT)-computed pK a values for the corresponding [MnII(OH2)(dpaq5R)]+ complexes. Collectively, the experimental and DFT results reveal that the 5-substituted quinolinyl groups have an inverse influence on electron and proton affinity for the MnIII–hydroxo unit.
Revascularization of the GSV strip track after stripping was found in 23 per cent of patients after 1 year; all of these had a postoperative haematoma in the track.
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