Effect of real-time remote-based cardiac rehabilitation on subjective satisfaction and objective performance during the coronavirus disease 2019 pandemic

Background: Real-time remote-based cardiac rehabilitation (CR) programmes improve exercise capacity. However, satisfaction and performance improvements after remote-based CR remain unclear. In addition to physical function, subjective satisfaction and objective performance may be adversely affected during the coronavirus disease 2019 pandemic. Purpose(s): This study aimed to compare the effectiveness of real-time remote-based CR versus hospital-based CR in improving physical function, subjective satisfaction, and objective performance (i.e., activity limitations and participation restrictions). Method(s): We conducted a quasi-randomised controlled trial and recruited 38 patients with cardiovascular disease (CVD). The patients participated in 4 weeks of hospital-based CR, followed by 12 weeks of remote or hospitalbased CR based on quasi-randomised allocation. We assessed the participants at baseline and after 12 weeks of remote or hospital-based CR using the shortened version of the World Health Organization Quality of Life scale (WHOQOL-BREF) for subjective satisfaction, the World Health Organization Disability Assessment Schedule (WHODAS 2.0) for objective performance, and peak oxygen uptake (peak VO2) using the cardiopulmonary exercise test, for physical function. We evaluated individual results by measuring baseline to post-CR changes (i.e., delta [DELTA]) (paired t-test) and then compared the remote and hospital-based CR programmes (unpaired t-test). Result(s): Sixteen patients (72.2+/-10.4 years) completed remote-based CR and fifteen patients (77.3+/-4.8 years) completed hospital-based CR. Seven patients were excluded owing to other health complications (n=2) and inability to attend hospital based-CR (n=5). In the remote-based CR group, the peak VO2 (before: 12.0+/-2.7 mL min-1 kg-1;after: 14.9+/-3.9 mL min-1 kg-1;p<0.05) and the WHOQOL-BREF score (before: 77.4+/-12.8 points;after: 93.9+/-12.9 points;p<0.001) were significantly higher, whereas the WHODAS 2.0 score was significantly lower (before: 19.9+/-13.2 points;after: 11.3+/-6.8 points;p<0.05) after rehabilitation than at baseline. The post- CR physical function differed significantly between the two groups (DELTApeak VO2, remote: 2.8+/-3.0 mL min-1 kg-1;hospital: 0.84+/-1.8 mL min-1 kg-1;p<0.05). The post-CR change in the WHOQOL-BREF score was not significantly different between the groups. The post-CR change in the WHODAS 2.0 score was significantly lower in the remote-based CR group than in the hospital-based CR group. (DELTAWHODAS 2.0 score, remote: -8.56+/-14.2 points;hospital: 2.14+/-7.6 points;p<0.01). Conclusion(s): Remote-based CR significantly improved physical function and objective performance in patients with CVD. Remote-based CR could be an effective treatment for stable patients who are unable to visit the hospital during the coronavirus disease 2019 pandemic. In the future, risk stratification according to severity of illness is needed.

Augmented Humoral Response to a Third And Fourth Dose of Mrna Sars-Cov-2 Vaccines in Lung Transplant Recipients

Lung transplant recipients (LTRs) are at the greatest risk for mortality of COVID-19 among recipients of solid organ transplantation. However, LTRs have been shown to have impaired humoral response (0-40%) to the two doses of mRNA SARS-CoV-2 vaccine. In this study, we aimed to assess the humoral response to a third and fourth dose of SARS-CoV-2 mRNA vaccines in LTRs. This was a prospective observational study of 45 LTRs without a history of SARS-CoV-2 infection, who received two or more doses of the BNT162b2 or mRNA-1273 vaccines between April and October 2022. Among these, 11, 26 and 8 LTRs received 2, 3 and 4 doses of the vaccine, respectively. The levels of antibodies to SARS-CoV-2 spike protein were tested by quantitative immunochromatographic assay. LTRs with antibody titers of 250 AU/mL or higher were defined as responders, which corresponds to two-fold the LD50 concentration level in vitro. The median age of the LTRs was 50 years (interquartile range [IQR], 34-59), and 77% of the LTRs were female. The median time from transplantation to anti-SARS-CoV-2 IgG test was 82 months (IQR, 35-124), and the median time from the last dose to anti-SARS-CoV-2 IgG test was 101 days (IGR, 60-158). The maintenance immunosuppression included calcineurin inhibitors (100%), mycophenolate mofetil (95%), and corticosteroids (100%). The humoral responses were detected in 0%, 31%, and 50% of LTRs and the median titers of anti-SARS-CoV-2 IgG were 0.01 AU/ml (IQR, 0.01-0.01), 0.01 AU/ml (IQR, 0.01-335.25), and 1429.48 AU/mL (IQR, 32.06-8195.91) after the second, third and fourth vaccination, respectively. The response rate and the levels of antibodies significantly increased with the numbers of vaccinations (p = 0.027). No patient had acute rejection or serious adverse events within the study period. Augmented humoral response was achieved in the LTRs after the third and fourth vaccine dose. Repeated vaccination may be beneficial to enhance humoral immunity even in the LTRs. [ FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Relacao Entre O Indice Rdw, Gravidade E Mortalidade De Pacientes Internados Com Covid-19 No Municipio De Uberaba-Mg

Objetivo: Avaliar os indices RDW de pacientes hospitalizados por COVID-19 no municipio de Uberaba-MG e estabelecer uma relacao com a gravidade e mortalidade durante o periodo de internacao. Material e Metodos: Este estudo foi aprovado pelo Comite de Etica em Pesquisa do Hospital de Clinicas da Universidade Federal do Triangulo Mineiro (CAAE ndegree 31328220.8.0000.8667). Foram levantados os dados epidemiologicos de 337 pacientes que estiveram internados em 3 unidades hospitalares do municipio de Uberaba-MG no periodo de maio de 2020 a junho de 2021. Foram coletados os seguintes dados: idade, sexo e desfecho. A classificacao de gravidade foi estabelecida de acordo com os criterios determinados no COVID-19 Clinical Management Living Guidance - World Health Organization, 2021. Os dados coletados foram compilados em uma planilha no programa Excel e posteriormente analisados por meio do programa GraphPad Prism© versao 8.4.3. A variavel continua foi descrita por media+/-desvio padrao. As variaveis quantitativas foram descritas por meio dos testes: Kolmogorov-Smirnov para verificacao da normalidade e as comparacoes entre os grupos por meio dos testes Mann-Whitney e Kruskal-Wallis. Os resultados foram considerados significativos quando p < 0,05. Resultados: Dos 337 pacientes analisados, 61,2% eram homens com idade media de 58,2 anos (DP +/- 15,6). Em relacao ao desfecho foi observado um aumento estatisticamente significante do indice RDW (p < 0,0001) no grupo que de pacientes que foram a obito (mediana 14,71%) quando comparado ao grupo que teve alta (mediana 13,32%). Quanto a gravidade foi verificado um aumento estatisticamente significante do indice RDW (p < 0,0001) de acordo com a gravidade do caso, quanto mais grave maior o indice. Foram observadas diferencas estatisticas entre os grupos leve e grave (p < 0,0001) e moderado e grave (p < 0,0001). As pacientes do sexo feminino tinham em media 60,8 anos (DP +/- 18) e corresponderam a 38,8% dos casos analisados. Em relacao ao desfecho foi observado um aumento significativo do indice RDW (p < 0,0001) no grupo de pacientes que foram a obito (mediana 14,56%) comprado ao grupo de pacientes que tiveram alta (mediana 13,63%). Em relacao a gravidade tambem foi visto um aumento do indice RDW em casos moderados e graves (p<0,001). Foram observadas diferencas significativas entre os grupos leve e grave (p < 0,05) e moderado e grave (p < 0,05). Discussao: O indice RDW tem sido apontado como um potencial marcador prognostico e de desfecho no curso da COVID-19. Ja foi demonstrado um aumento do indice RDW em pacientes com doencas infecciosas graves. Esse estudo demonstrou o aumento dos indices RDW em pacientes homens e mulheres conforme a progressao da gravidade. Os casos moderados, graves e os pacientes que foram a obito, independente do sexo, demonstraram maiores indices. Conclusao: O indice RDW tem grande potencial como marcador prognostico e de monitoramento do curso da evolucao da COVID-19 em pacientes de ambos os sexos, pois quanto maior o indice RDW maiores as chances de severidade e obito. Copyright © 2022

Perfil Clinico-Epidemiologico De Individuos Com Covid-19 Atendidos Em Unidades Hospitalares Do Municipio De Uberaba - Mg

Objetivo: Descrever o perfil clinico-epidemiologico de pacientes com COVID-19 atendidos em hospitais de Uberaba - MG. Material e Metodos: Trabalho aprovado pelo Comite de Etica em Pesquisa do Hospital de Clinicas da Universidade Federal do Triangulo Mineiro (CAAE ndegree 31328220.8.0000.8667). Foram coletados dados de 371 individuos com COVID-19, atendidos entre maio/2020 e junho/2021. As variaveis analisadas foram: genero, idade, sintomatologia, comorbidades, medicamentos e desfecho (alta/obito). Utilizou-se o programa SPSS, versao 20.0 para o tratamento dos dados coletados. Considerou-se estatisticamente significantes valores de p < 0,05. Resultados: Dentre os 371 pacientes, 39,9% eram mulheres e 60,1%, homens. Os sintomas predominantes foram dispneia (70%), tosse (60%) e febre (50%). Acerca das comorbidades, HAS (44,6% M e 49,8% H), DM (29% M e 24,7% H) e obesidade (16,2% M e 12,1% H) foram as mais prevalentes. Os medicamentos mais utilizados foram heparina (87,2% M e 86,1% H) e corticoide (81,1% M e 80,7% H). Houve pior desfecho entre os pacientes mais velhos;sendo a presenca de comorbidades e o tempo de internacao significativamente maiores para homens que foram a obito se comparados aos que receberam alta (p = 0,004 e p = 0,002, respectivamente). Discussao: No presente estudo, houve um predominio de pacientes do sexo masculino, o que diverge de um estudo realizado no estado de Pernambuco, que relatou um predominio do sexo feminino. Por outro lado, esse mesmo estudo aponta achados semelhantes aos nossos em relacao aos sintomas apresentados pelos pacientes, como dispneia, tosse e febre sendo os mais frequentes nos dois estudos, demonstrando um comportamento semelhante da sintomatologia da doenca no Brasil. Alem disso, a literatura tambem vem demonstrando que a presenca de comorbidades, em especial HAS e DM, sao importantes fatores de risco para o agravamento e pior prognostico em individuos com COVID-19. No presente trabalho, a prevalencia de comorbidades foi maior no grupo de individuos do sexo masculino que foram a obito e observamos maior incidencia de hipertensao, diabetes e obesidade em toda a nossa casuistica, corroborando os dados da literatura. No tocante a medicacao, foi observado o uso de heparina e corticoide, independentemente da gravidade. Estudos demonstram que o tratamento com corticosteroides reduz o risco de morte em pacientes graves, incluindo aqueles em ventilacao mecanica. Em relacao a heparina, um ensaio clinico demonstrou que o farmaco reduz o risco de mortes por complicacoes da doenca, se administrada aos primeiros sinais de insuficiencia respiratoria. Conclusao: Conclui-se que a idade mais avancada e comorbidades previas estao relacionadas a um pior prognostico em individuos infectados pelo SARS-CoV-2 na amostra analisada. Copyright © 2022

Investigacao Do Gene Nr3c1 Em Pacientes Com Covid-19

Objetivo: O presente trabalho tem por objetivo investigar o gene NR3C1, que codifica os receptores de Glicocorticoide (GCs), em individuos com COVID-19. Material e Metodos: Foram analisadas 58 amostras de pacientes com COVID-19, atendidos em hospitais do municipio de Uberaba - MG entre maio de 2020 a junho de 2021. Este projeto foi aprovado pelo Comite de Etica em Pesquisa do Hospital de Clinicas da Universidade Federal do Triangulo Mineiro e todos os participantes assinaram o Termo de Consentimento Livre e Esclarecido. A amostra foi agrupada de acordo com o desfecho (alta ou obito) e gravidade da doenca (leve, moderada ou grave). A determinacao de gravidade dos casos foi realizada segundo os criterios estabelecidos no Manual de Manejo Clinico da COVID-19 da Organizacao Mundial de Saude. Foram coletados um tubo de 04 mL de sangue periferico na admissao do paciente e a quantificacao relativa do gene NR3C1 foi realizada por PCR em tempo real, utilizando o equipamento 7500 (Applied BiosystemsTM). O gene ACTB foi utilizado como controle endogeno. Os dados quantitativos foram submetidos ao teste de normalidade de Kolmogorov-Smirnov e as comparacoes estatisticas entre dois grupos realizadas com emprego do teste de Mann-Whitney. A significancia estatistica foi definida como p<0,05. Resultados: A idade mediana dos pacientes foi de 64,5 anos (min. 29, max. 100 anos). Dos 58 pacientes analisados, 26 eram mulheres e 32 homens. Em relacao ao desfecho, 31 obtiveram alta (17 mulheres 14 homens) e 27 evoluiram para obito (9 mulheres e 18 homens). Em relacao a gravidade, 13 pacientes tiveram quadro clinico leve (07 mulheres e 06 homens), 16 moderado (08 mulheres e 08 homens) e 29 grave (11 mulheres e 18 homens). Nao foi observada diferenca estatisticamente significativa na expressao do gene NR3C1 quanto ao desfecho ou gravidade (p=0,49 e p=0,25, respectivamente). Discussao: Acredita-se que a genetica humana tenha um importante papel na determinacao da resposta clinica ao SARS-CoV-2, no entanto, o estabelecimento dos mecanismos geneticos envolvidos na suscetibilidade ou resistencia a infeccao ainda nao sao completamente conhecidos. Os GCs inibem rapidamente a transcricao de citocinas pro-inflamatorias, como a IL-6. Essa citocina, por sua vez, esta envolvida num fenomeno denominado "tempestade de citocinas", em que ha uma exacerbacao da resposta imunologica. Na COVID-19 as manifestacoes de doenca grave e morte nao se apresentam exclusivamente pelos danos induzidos pelo virus nos pulmoes, mas tambem devido aos niveis elevados de citocinas, particularmente IL-6, que podem ser inibidas por GCs. Apesar do presente estudo nao ter observado diferenca na expressao do gene NR3C1 em relacao ao desfecho e gravidade, os receptores de GCs tem importante desempenho na supressao da "tempestade de citocinas". Alem disso, ja foi demonstrado que o uso de glicocorticoides em doses baixas e medias por ate oito dias e seguro e benefico para pacientes com COVID-19 grave. Conclusao: O presente estudo conclui que nao ha relacao entre a expressao do gene NR3C1 com o agravamento ou pior desfecho em pacientes com COVID-19. Copyright © 2022

Assessment of the Influence of Prf1 and Gzmb Genes in Relation to Severity and Outcome in Patients with Covid-19

Objective: This study aimed to evaluate the role of genes encoding perforin (PRF1) and granzyme B (GZMB) in SARS-CoV-2 infection. Material(s) and Method(s): This is a cohort study in which the expression of the PRF1 and GZMB genes was quantified by qPCR, as well as the investigation of the rs35947132 and rs885822 polymorphisms in the PRF1 gene in 86 patients with COVID-19 treated in hospitals from Uberaba/MG, Brazil. Result(s): Patients who died had significantly lower PRF1 gene expression than those who survived. As for the severity of the disease, the expression was significantly lower of both genes in those patients with more severe clinical conditions. Characteristics such as sex, age and presence of comorbidities did not show differences in the expression of the PRF1 gene. Regarding the presence of polymorphisms, no differences were observed in relation to the parameters evaluated, such as outcome, severity, sex, age and presence of comorbidities, indicating that these alterations do not seem to directly influence these aspects. Despite this, it was observed that those who were homozygous for the rs885822 polymorphism had higher expression of the PRF1 gene when compared to patients with heterozygous or homozygous wild-type alleles. Discussion(s): The difference in the expression of the perforin gene regarding the outcome and severity may be due to greater activation of lymphocytes and consequently an increase in the expression of these genes, leading to a better prognosis. It is necessary to investigate whether patients who died and those who developed more severe manifestations of the disease have some immune deficiency related to cytotoxic lymphocytes. When it comes to the analysis of polymorphisms, the results found to differ from the literature, which considers that the presence of the rs35947132 polymorphism is more prevalent in patients with severe forms of COVID-19. The literature demonstrates that individuals with the polymorphic allele rs35947132 express less perforin, but the studies analyzed were performed using different techniques. A limitation of the present study is the sample size. We believe that the increase in the number of cases evaluated can provide us with a better understanding of this topic. Regarding the rs885822 polymorphism, the higher expression of the perforin gene contradicts the initial hypothesis of the work. However, one of the possible explanations for this fact would be the existence of other polymorphisms in linkage unbalance that trigger an increase in the expression of the PRF1 gene. Conclusion(s): The present study concludes that the PRF1 gene was less expressed in patients with more severe COVID-19 and in those who died. Furthermore, in the analysis of perforin gene variants presence, no association was observed between the polymorphisms and the severity or outcome of individuals with COVID-19. Copyright © 2022

DUV-LED packaging using high density TSV in silicon cavity and laser-glass-frit-bonded UV transmitting glass cap

This paper reports an improved deep ultraviolet LED (DUV-LED) packaging based on Si Micro-Electro-Mechanical Systems (MEMS) process technology. The Si package (Si-PKG) consists of a cavity formed by Si crystalline anisotropic wet etching and through-silicon vias (TSVs) filled with electroplated Cu. The Si-PKG is hermetically sealed by laser local heating of screen-printed glass frit. This technology allows for the use of a DUV-transparent glass substrate, which has an unmatched coefficient of thermal expansion (CTE). Using a high-density array of TSV capped with AuSn solder bumps, the cooling performance of the DUV-LED has been greatly improved. And the contribution by the Si (111) side reflection of Si-PKG to the total light output was confirmed 13 %. As a result, an optical output of 114 % (50 mW) and a volumetric light power density of 380 % (14 mW/mm3) were recorded compared with the conventional AlN-packaged device. The developed compact low-cost Si-PKG is promising for wider applications of the DUV-LED including the disinfection of the new coronaviruses. © 2022 Elsevier B.V.

ASSOCIAÇÃO ENTRE GRUPO SANGUÍNEO ABO, GRAVIDADE E MORTALIDADE POR COVID-19

Objetivo: Avaliar a relação entre o sistema ABO e os índices de gravidade e mortalidade em pacientes hospitalizados por COVID-19 no município de Uberaba-MG. Material e métodos: Participaram deste estudo 343 pacientes atendidos em unidades hospitalares do município de Uberaba – MG. Foram determinadas as fenotipagens eritrocitárias por prova reversa em todas as amostras de sangue periférico e coletados os dados clínicos e epidemiológicos de cada paciente. A análise estatística dos resultados foi realizada de forma descritiva e inferencial. Para variáveis quantitativas, utilizaram-se medidas de posição ou centralidade (média) e medidas de dispersão e variabilidade (desvio padrão). As variáveis categóricas foram analisadas por meio do software SPSS, versão 20.0, bem como análise de associação em tabelas de contingências χ2. Os valores foram considerados estatisticamente significativos quando p ≤ 0,05. Resultados: Dos 343 pacientes avaliados no período de maio a novembro de 2020, 80,17% foram diagnosticados com COVID-19 e 19,83% negativos para a doença. Os pacientes positivos tinham idade média de 60,32 anos (DP ± 17,17) e a maioria eram homens (60%). Foram observadas comorbidades em 81% dos pacientes infectados. Quanto à tipagem sanguínea ABO nos casos positivos, não foram encontradas diferenças estatísticas entre os grupos analisados (χ2 = 3,24, p = 0,37), sendo 31,8% pacientes positivos do tipo A, 2% do tipo AB, 10,3% do tipo B e 55,9% do tipo O. Em relação a gravidade foi observado que 51,2% dos casos foram considerados graves (UTI entubados), 19,3% considerados moderados (UTI sem entubação) e 29,5% considerados leves (enfermaria), e quanto a mortalidade, 51,6% tiveram alta e 48,4% foram a óbito. Não foram encontradas diferenças estatisticamente significantes entre a relação de gravidade dos pacientes positivos para COVID-19 e o tipo sanguíneo ABO (χ2 = 4,781, p = 0,57). Quando realizada a comparação entre a mortalidade por COVID-19 e a tipagem sanguínea também não foram encontradas diferenças estatísticas (χ2 = 6,088, p = 0,11). Discussão: Recentemente foi sugerida correlação entre o tipo sanguíneo e a infecção por SARS-CoV-2. Alguns estudos apontaram o tipo sanguíneo A como o mais suscetível a infecções graves. Embora tenhamos realizado a determinação da tipagem sanguínea apenas por prova reversa, nossos resultados foram semelhantes ao de outros estudos em que não houve nenhuma relação entre os tipos sanguíneos, gravidade e mortalidade por COVID-19. Conclusão: De acordo com os dados encontrados nessas análises, o tipo sanguíneo ABO não parece estar associado a gravidade e a mortalidade da COVID-19, portanto, o sistema ABO não deve ser considerado como marcador biológico prognóstico para a COVID-19.

Collective residue interactions in trimer complexes of SARS-CoV-2 spike proteins analyzed by fragment molecular orbital method

In large biomolecular systems such as protein complexes, there are huge numbers of combinations of inter-residue interactions whose comprehensive analyses are often beyond the intuitive processing by researchers. Here we propose a computational method to allow for a systematic analysis of these interactions based on the fragment molecular orbital calculations, in which the inter-fragment interaction energies are comprehensively processed by the singular value decomposition. For a trimer complex of SARS-CoV-2 spike protein, three-body interactions among residues belonging to three chains are analyzed to elicit a small number of essential interaction modes or networks crucial for the structural stability of the complex.

Fragment molecular orbital based interaction analyses on complexes between SARS-CoV-2 RBD variants and ACE2

The SARS-CoV-2 virus initiates infection of human cells by recognizing the human angiotensin-converting enzyme 2 (ACE2) with the receptor binding domain (RBD) of the viral spike protein. Thus, the variant of concern (VOC) with mutations on RBD is of special interest. Here, we present a series of interaction analyses for the RBD-ACE2 complex of the wild-type (PDB ID: 6M0J) and those of B.1.1.7 (alpha), B.1.351 (beta) and P.1 (gamma) VOCs, based on the fragment molecular orbital (FMO) calculations. The results revealed that the RBD variants have a higher affinity for ACE2 than the wild type does.

Umami: an alternative Japanese approach to reducing sodium while enhancing taste desirability

COVID-19 has highlighted the underlying global burden from non-communicable diseases (NCDs) and the lack of resiliency in health systems to tackle highly preventable risk factors, which have left populations vulnerable to acute health crises. The persistent issue of unhealthy behaviors, particularly those related to a high-sodium diet, suggests inadequate policy attention and insufficient funding for public health and behavioral research. This year, Japan will host the Tokyo Nutrition for Growth (N4G) Summit 2021. The summit is being held in the era of COVID-19, offering a historic opportunity to make a difference on the global health agenda for food and nutrition and to reaffirm the global commitment to prevent future health crises by addressing the growing burden of NCDs and building better prepared and more resilient health systems. This perspective article suggests that we, global health researchers and decision-makers, should rethink the value of using "Umami" substances as candidates for a practical salt-reducing alternative that originated in Japan (while maintaining the affordability, accessibility, availability, and desirability of healthy food). Reduced salt intake will help address the global syndemic of COVID-19 pandemic and high rates of hypertension, heart diseases, diabetes, and other NCDs. By addressing these issues, it will make countries more resilient to future pandemic threats.

A SARS-CoV-2-neutralizing ACE2 decoy shows high affinity for N501Y and L452R variants

Background: SARS-CoV-2 infects the host by binding of its spike receptor binding domain (S RBD) to angiotensin converting enzyme 2 (ACE2) on the surface of cells in the respiratory tract and gut;thus therapeutics that prevent this interaction are of interest because they have the potential to inhibit propagation of infection. A recombinant 'ACE2 Decoy' that competitively binds S RBD and neutralizes SARS-CoV-2 infection represents such a therapeutic approach. The impact of S RBD mutations found in the rapidly spreading UK, South African, and California SARS-CoV-2 variants on ACE2 Decoy affinity is an important factor in design. Here, we identified a high-affinity SARS-CoV-2-neutralizing ACE2 Decoy that maintains its high affinity against RBD with mutations found in emerging variants. Methods: We used Molecular Dynamic (MD) simulation of S RBD-ACE2 interactions to predict ACE2 residues that if mutated, might increase affinity for S RBD and thus successfully compete with endogenous ACE2 for binding. Recombinant ACE2-IgG1Fc and-IgAFc fusion proteins expressing mutations predicted to increase S RBD binding affinity were produced, purified, and screened for binding affinities against wild type S RBD and S RBD expressing E484K, K417N, N501Y, or L452R alone and in combinations of: K417N/N501Y;E484K/N501Y;K417N/E484K;and K417N/E484K/N501Y (found in the South African variant). The ability of the Decoy with the highest affinity to neutralize SARS-CoV-2 infection was determined by a live virus assay using Vero E6 cells. An additional mutation (H374N) to inhibit enzymatic activity of ACE2 was added to the Decoy with the highest affinity from mutation screening. Results: Eleven of the ACE2 mutations predicted to increase affinity for S RBD were tested, revealing the ACE2 Decoy with T27Y and H34A mutations to have the highest S RBD affinity and the ability to neutralize SARS-CoV-2 infection of cells. Both the ACE2 wild type (WT)-IgG1Fc and the ACE2(T27Y/H34A/H374N)-IgG1Fc Decoys showed enhanced binding affinity for S RBD with either N501Y and L452R mutations alone. Interestingly, the South African variant K417N mutation alone decreased affinity, but not in combination with the N501Y mutation. Conclusion: The potential efficacy of the ACE2 (T27Y/H34A/H374N)-IgG1FC Decoy is not decreased by the UK, South African, or California variant mutations and will undergo testing in animal models likely by expression using a human adenovirus (hAd5) construct to enhance stability.

Financial literacy and exercise behavior: Evidence from japan

Lack of exercise, which increases the risk of many serious physical and mental illness, has been a common health issue in Japan. Recent studies confirm that financial literacy discourages irrational behavior like gambling and smoking. We therefore investigate how financial literacy, as a rational decision-making instrument, relates to peoples’ exercise behavior in Japan. We hypothesize that financial literacy encourages people to exercise regularly. Using Osaka University’s Preference Parameters Study (PPS) for 2010, we categorized respondents into two groups: those who exercise regularly or at least once a week and those who do not. Our probit estimation results show that financial literacy is positively related with exercise behavior, meaning that financially literate people are more likely to exercise regularly. As the COVID-19 health pandemic seems to exacerbate peoples’ physical inactivity, the results of our study show an alternative approach to encourage exercise. We therefore recommend that governments implement a financial literacy improvement policy to alleviate the lack of exercise. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Statistical interaction analyses between SARS-CoV-2 main protease and inhibitor N3 by combining molecular dynamics simulation and fragment molecular orbital calculation

A combination of classical molecular dynamics (MD) simulation and ab initio fragment molecular orbital (FMO) calculation was applied to a complex formed between the main protease of the new coronavirus and the inhibitor N3 to calculate interactions within the complex while incorporating structural fluctuations mimicking physiological conditions. Namely, a statistical evaluation of interaction energies between N3 and amino acid residues was performed by processing a thousand of structure samples. It was found that relative importance of each residue is altered by the structural fluctuation. The MD-FMO combination should be promising to simulate protein related systems in a more realistic way. (c) 2021 The Japan Society of Applied Physics