Purpose of Review This commentary summarizes recent literature pertaining to healthcare challenges and needs during the current pandemic among refugees and asylum seekers residing in a host country. We conducted a literature review to identify barriers to shielding these structurally marginalized populations from the impact of the COVID-19 pandemic. Recent Findings Many populations, including refugees, migrants, and asylum seekers, endure structural vulnerabilities in refugee camps and during their resettlement. These structural vulnerabilities include fear of contacting the healthcare system, cultural differences, housing insecurity, food insecurity, discrimination, lack of health insurance, health illiteracy and lack of readily available, and culturally appropriate educational materials. During pandemics, displaced persons suffer disproportionately from poorly managed chronic diseases, economic hardships isolation, and mental illnesses, in addition to the threats posed by the infectious agent. Summary Underserved groups, including refugee populations, shoulder a disproportionate burden of disease during pandemics. In order to mitigate the impact of preventable chronic illnesses and also reduce the spread of COVID-19 and other easilytransmissible and deadly viruses during pandemics, governments and public health authorities need to implement policies that allow refugees, asylum seekers, and displaced persons to be fully incorporated into their respective healthcare systems, so that they can be supported and protected and to reduce the amplifying networks of transmission.

As a single polypeptide, cytochrome P450 BM3 fuses oxidase and reductase domains and couples each domain's function to perform catalysis with exceptional activity upon binding of substrate for hydroxylation. Mutations introduced into the enzyme to change its substrate specificity often decrease coupling efficiency between the two domains, resulting in unproductive consumption of cofactors and formation of water and/or reactive species. This phenomenon can correlate with leakage, in which P450 BM3 uses electrons from NADPH to reduce oxygen to water and/or reactive species even without bound substrate. The physical basis for leakage is not yet well understood in this particular member of the cytochrome P450 family. To clarify the relationship between leakage and coupling, we used simulations to illustrate how different combinations of kinetic parameters related to substrate-free consumption of NADPH and substrate hydroxylation can lead to either minimal effects on coupling or a dramatic decrease in coupling as a result of leakage. We explored leakage in P450 BM3 by introducing leakage-enhancing mutations and combining these mutations to assess whether doing so increases leakage further. The variants in this study provide evidence that while a transition to high spin may be vital for coupled hydroxylation, it is not required for enhanced leakage; substrate binding and the consequent shift in spin state are not necessary as a redox switch for catalytic oxidation of NADPH. Additionally, the variants in this study suggest a tradeoff between leakage and stability and thus evolvability, as the mutations we Abbreviations: P450 BM3, cytochrome P450 monooxygenase from B. megaterium; P450 cam, cytochrome P450 monooxygenase from P. putida; WT, wild type; k cat , R-H, turnover rate constant with respect to hydroxylation; K m , R-H, Michaelis constant with respect to hydroxylation; k cat , leakage, turnover rate constant with respect to leakage; K m , leakage, Michaelis constant with respect to leakage; K d , dissociation equilibrium constant; k on , association rate constant; k off , dissociation rate constant; T 50 , incubation temperature at which half of protein becomes denatured after 10 min; NADPH, nicotinamide adenine dinucleotide phosphate; ROS, reactive oxygen species; H 2 O 2 , hydrogen peroxide; O 2 2 , superoxide; IPTG, isopropyl b-d-1-thiogalactopyranoside; KPi, potassium phosphate; HRP, horseradish peroxidase; ABTS, 2,2 0 -azino-bis(3-ethylbenzothiazoline-6-sulphonic acid); CO, carbon monoxide; Tris, tris(hydroxyl)aminomethane; SDS, sodium dodecyl sulfate; PAGE, polyacrylamide gel electrophoresis Additional Supporting Information may be found in the online version of this article. Published by Wiley-Blackwell. V C 2015 The Protein Society investigated were far more deleterious than other mutations that have been used to change substrate specificity.

Background: Microsurgical breast reconstruction following mastectomy represents a high-risk patient group for venous thromboembolism (VTE), but there is limited consensus on postoperative prophylaxis duration. The aim of this study was to characterize the risk of VTE after microsurgical breast reconstruction, the risk reduction associated with postoperative outpatient VTE prophylaxis, the clinical factors associated with VTE events, and surgeon prescribing patterns regarding outpatient VTE prophylaxis. Methods: A commercially available database of 53 million unique patients, PearlDiver, was used to identify patients with breast cancer who underwent microsurgical breast reconstruction. Patients were grouped into those receiving any form of outpatient VTE prophylaxis at discharge and those who did not. Probability of VTE within 90 days was calculated for each group followed by absolute risk reduction and number needed to treat. A logistic regression, assuming binomial distribution, was performed to determine clinical factors associated with VTE events after surgery. Results: A total of 22,606 patients underwent microsurgical breast reconstruction from 2010 to 2020. Of these patients, 356 (1.6%) were discharged with VTE prophylaxis and 22,250 (98.4%) were discharged without. No patients developed a VTE in the prophylaxis group, and 403 (1.8%) developed a VTE in the group without prophylaxis. The number needed to prevent one VTE was 55.25 patients. Most VTE events occurred after postoperative day 10 (71.3%). Conclusions: Outpatient chemoprophylaxis following breast reconstruction is underused despite the majority of VTE events occurring after the acute postoperative period. Breast microsurgeons should consider routine outpatient chemoprophylaxis as part of their postoperative care pathway to optimize VTE prevention. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.