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BACKGROUND: Impella (Abiomed, Danvers, MA, USA) is a percutaneous ventricular assist device commonly used in cardiogenic shock, providing robust hemodynamic support, improving the systemic circulation, and relieving pulmonary congestion. Maintaining adequate left ventricular (LV) filling is essential for optimal hemodynamic support by Impella. This study aimed to investigate the impact of pulmonary vascular resistance (PVR) and right ventricular (RV) function on Impella-supported hemodynamics in severe biventricular failure using cardiovascular simulation. METHODS: We used Simulink® (Mathworks, Inc., Natick, MA, USA) for the simulation, incorporating pump performance of Impella CP determined using a mock circulatory loop. Both systemic and pulmonary circulation were modeled using a 5-element resistance-capacitance network. The four cardiac chambers were represented by time-varying elastance with unidirectional valves. In the scenario of severe LV dysfunction (LV end-systolic elastance set at a low level of 0.4â¯mmHg/mL), we compared the changes in right (RAP) and left atrial pressures (LAP), total systemic flow, and pressure-volume loop relationship at varying degrees of RV function, PVR, and Impella flow rate. RESULTS: The simulation results showed that under low PVR conditions, an increase in Impella flow rate slightly reduced RAP and LAP and increased total systemic flow, regardless of RV function. Under moderate RV dysfunction and high PVR conditions, an increase in Impella flow rate elevated RAP and excessively reduced LAP to induce LV suction, which limited the increase in total systemic flow. CONCLUSIONS: PVR is the primary determinant of stable and effective Impella hemodynamic support in patients with severe biventricular failure.
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In middle to late 2023, a sublineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron XBB, EG.5.1 (a progeny of XBB.1.9.2), is spreading rapidly around the world. We performed multiscale investigations, including phylogenetic analysis, epidemic dynamics modeling, infection experiments using pseudoviruses, clinical isolates, and recombinant viruses in cell cultures and experimental animals, and the use of human sera and antiviral compounds, to reveal the virological features of the newly emerging EG.5.1 variant. Our phylogenetic analysis and epidemic dynamics modeling suggested that two hallmark substitutions of EG.5.1, S:F456L and ORF9b:I5T are critical to its increased viral fitness. Experimental investigations on the growth kinetics, sensitivity to clinically available antivirals, fusogenicity, and pathogenicity of EG.5.1 suggested that the virological features of EG.5.1 are comparable to those of XBB.1.5. However, cryo-electron microscopy revealed structural differences between the spike proteins of EG.5.1 and XBB.1.5. We further assessed the impact of ORF9b:I5T on viral features, but it was almost negligible in our experimental setup. Our multiscale investigations provide knowledge for understanding the evolutionary traits of newly emerging pathogenic viruses, including EG.5.1, in the human population.
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BACKGROUND: Left ventricular stroke work index (LVSWI) and cardiac power index (CPI) account for the haemodynamic load of the left ventricle and are promising prognostic values in cardiogenic shock. However, accurately and non-invasively measuring these parameters during veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is challenging and potentially biased by the extracorporeal circulation. This study aimed to investigate, in an ovine model of cardiogenic shock, whether Pressure-Strain Product (PSP), a novel speckle-tracking echocardiography parameter, (1) can correlate with pressure-volume catheter-based LVSWI and CPI, and (2) can be load-independent during the flow modification of V-A ECMO. METHODS: Nine Dorset-cross ewes (51 ± 4 kg) were included. After cardiogenic shock was induced, full support V-A ECMO (X L/min based on 60 mL/kg/min) commenced. At seven time points during 24-h observation, echocardiographic parameters as well as pressure-volume catheter-based LVSWI and CPI were simultaneously measured with X and following X-1 L/min of ECMO flow. PSP was calculated by multiplying global circumferential strain or global radial strain, and mean arterial pressure, for PSPcirc or PSPrad, respectively. RESULTS: PSPcirc showed a stronger correlation with LVSWI (correlation coefficient, CC = .360, p < .001) and CPI (CC = .283, p < .001) than other echocardiographic parameters. The predictability of PSPcirc for pressure-volume catheter-based LVSWI (AUC .82) and CPI (AUC .80) was also higher than other echocardiographic parameters. No statistically significant differences were identified between the two ECMO flow variations in PSPcirc (p = .558). CONCLUSIONS: A novel echocardiographic parameter, PSP, may non-invasively predict pressure-volume catheter-based LVSWI and CPI in a load-independent manner in a cardiogenic shock supported by V-A ECMO.
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BACKGROUND: Left ventricular (LV) unloading by Impella, an intravascular microaxial pump, has been shown to exert dramatic cardioprotective effects in acute clinical settings of cardiovascular diseases. Total Impella support (no native LV ejection) is far more efficient in reducing LV energetic demand than partial Impella support, but the manual control of pump speed to maintain stable LV unloading is difficult and impractical. We aimed to develop an Automatic IMpella Optimal Unloading System (AIMOUS), which controls Impella pump speed to maintain LV unloading degree using closed-feedback control. We validated the AIMOUS performance in an animal model. METHODS: In dogs, we identified the transfer function from pump speed to LV systolic pressure (LVSP) under total support conditions (n = 5). Using the transfer function, we designed the feedback controller of AIMOUS to keep LVSP at 40 mmHg and examined its performance by volume perturbations (n = 9). Lastly, AIMOUS was applied in the acute phase of ischemia-reperfusion in dogs. Four weeks after ischemia-reperfusion, we assessed LV function and infarct size (n = 10). RESULTS: AIMOUS maintained constant LVSP, thereby ensuring a stable LV unloading condition regardless of volume withdrawal or infusion (±8 ml/kg from baseline). AIMOUS in the acute phase of ischemia-reperfusion markedly improved LV function and reduced infarct size (No Impella support: 13.9 ± 1.3 vs. AIMOUS: 5.7 ± 1.9%, P < 0.05). CONCLUSIONS: AIMOUS is capable of maintaining optimal LV unloading during periods of unstable hemodynamics. Automated control of Impella pump speed in the acute phase of ischemia-reperfusion significantly reduced infarct size and prevented subsequent worsening of LV function.
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Coração Auxiliar , Hemodinâmica , Infarto do Miocárdio , Função Ventricular Esquerda , Cães , Animais , Hemodinâmica/fisiologia , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/terapia , Função Ventricular Esquerda/fisiologia , Masculino , Modelos Animais de Doenças , AutomaçãoRESUMO
BACKGROUND: The commonest echocardiographic measurement, left ventricular ejection fraction, can not necessarily predict mortality of recipients following heart transplantation potentially due to afterload dependency. Afterload-independent left ventricular stroke work index (LVSWI) is alternatively recommended by the current guideline; however, pulmonary artery catheters are rarely inserted in organ donors in most jurisdictions. We propose a novel non-invasive echocardiographic parameter, Pressure-Strain Product (PSP), as a potential surrogate of catheter-based LVSWI. This study aimed to investigate if PSP could correlate with catheter-based LVSWI in an ovine model of brain stem death (BSD) donors. The association between PSP and myocardial mitochondrial function in the post-transplant hearts was also evaluated. METHODS: Thirty-one female sheep (weight 47 ± 5 kg) were divided into two groups; BSD (n = 15), and sham neurologic injury (n = 16). Echocardiographic parameters including global circumferential strain (GCS) and global radial strain (GRS) and pulmonary artery catheter-based LVSWI were simultaneously measured at 8-timepoints during 24-h observation. PSP was calculated as a product of GCS or GRS, and mean arterial pressure for PSPcirc or PSPrad, respectively. Myocardial mitochondrial function was evaluated following 6-h observation after heart transplantation. RESULTS: In BSD donor hearts, PSPcirc (n = 96, rho = .547, p < .001) showed the best correlation with LVSWI among other echocardiographic parameters. PSPcirc returned AUC of .825 to distinguish higher values of cardiomyocyte mitochondrial function (cut-off point; mean value of complex 1,2 O2 Flux) in post-transplant hearts, which was greater than other echocardiographic parameters. CONCLUSIONS: PSPcirc could be used as a surrogate of catheter-based LVSWI reflecting mitochondrial function.
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[This corrects the article DOI: 10.3389/fmicb.2020.575255.].
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Introduction: Intra-operative hypotension is a common complication of surgery under general anesthesia in dogs and humans. Computer-controlled closed-loop infusion systems of norepinephrine (NE) have been developed and clinically applied for automated optimization of arterial pressure (AP) and prevention of intra-operative hypotension in humans. This study aimed to develop a simple computer-controlled closed-loop infusion system of NE for the automated control of the mean arterial pressure (MAP) in dogs with isoflurane-induced hypotension and to validate the control of MAP by the developed system. Methods: NE was administered via the cephalic vein, whereas MAP was measured invasively by placing a catheter in the dorsal pedal artery. The proportional-integral-derivative (PID) controller in the negative feedback loop of the developed system titrated the infusion rate of NE to maintain the MAP at the target value of 60 mmHg. The titration was updated every 2 s. The performance of the developed system was evaluated in six laboratory Beagle dogs under general anesthesia with isoflurane. Results: In the six dogs, when the concentration [median (interquartile range)] of inhaled isoflurane was increased from 1.5 (1.5-1.5)% to 4 (4-4)% without activating the system, the MAP was lowered from 95 (91-99) to 41 (37-42) mmHg. In contrast, when the concentration was increased from 1.5 (1.0-1.5)% to 4 (4-4.8)% for a 30-min period and the system was simultaneously activated, the MAP was temporarily lowered from 92 (89-95) to 47 (43-49) mmHg but recovered to 58 (57-58) mmHg owing to the system-controlled infusion of NE. If the acceptable target range for MAP was defined as target MAP ±5 mmHg (55 ≤ MAP ≤65 mmHg), the percentage of time wherein the MAP was maintained within the acceptable range was 96 (89-100)% in the six dogs during the second half of the 30-min period (from 15 to 30 min after system activation). The median performance error, median absolute performance error, wobble, and divergence were - 2.9 (-4.7 to 1.9)%, 2.9 (2.0-4.7)%, 1.3 (0.8-1.8)%, and - 0.24 (-0.34 to -0.11)%·min-1, respectively. No adverse events were observed during the study period, and all dogs were extubated uneventfully. Conclusion: This system was able to titrate the NE infusion rates in an accurate and stable manner to maintain the MAP within the predetermined target range in dogs with isoflurane-induced hypotension. This system can be a potential tool in daily clinical practice for the care of companion dogs.
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BACKGROUND: Although several SARS-CoV-2-related coronaviruses (SC2r-CoVs) were discovered in bats and pangolins, the differences in virological characteristics between SARS-CoV-2 and SC2r-CoVs remain poorly understood. Recently, BANAL-20-236 (B236) was isolated from a rectal swab of Malayan horseshoe bat and was found to lack a furin cleavage site (FCS) in the spike (S) protein. The comparison of its virological characteristics with FCS-deleted SARS-CoV-2 (SC2ΔFCS) has not been conducted yet. METHODS: We prepared human induced pluripotent stem cell (iPSC)-derived airway and lung epithelial cells and colon organoids as human organ-relevant models. B236, SARS-CoV-2, and artificially generated SC2ΔFCS were used for viral experiments. To investigate the pathogenicity of B236 in vivo, we conducted intranasal infection experiments in hamsters. FINDINGS: In human iPSC-derived airway epithelial cells, the growth of B236 was significantly lower than that of the SC2ΔFCS. A fusion assay showed that the B236 and SC2ΔFCS S proteins were less fusogenic than the SARS-CoV-2 S protein. The infection experiment in hamsters showed that B236 was less pathogenic than SARS-CoV-2 and even SC2ΔFCS. Interestingly, in human colon organoids, the growth of B236 was significantly greater than that of SARS-CoV-2. INTERPRETATION: Compared to SARS-CoV-2, we demonstrated that B236 exhibited a tropism toward intestinal cells rather than respiratory cells. Our results are consistent with a previous report showing that B236 is enterotropic in macaques. Altogether, our report strengthens the assumption that SC2r-CoVs in horseshoe bats replicate primarily in the intestinal tissues rather than respiratory tissues. FUNDING: This study was supported in part by AMED ASPIRE (JP23jf0126002, to Keita Matsuno, Kazuo Takayama, and Kei Sato); AMED SCARDA Japan Initiative for World-leading Vaccine Research and Development Centers "UTOPIA" (JP223fa627001, to Kei Sato), AMED SCARDA Program on R&D of new generation vaccine including new modality application (JP223fa727002, to Kei Sato); AMED SCARDA Hokkaido University Institute for Vaccine Research and Development (HU-IVReD) (JP223fa627005h0001, to Takasuke Fukuhara, and Keita Matsuno); AMED Research Program on Emerging and Re-emerging Infectious Diseases (JP21fk0108574, to Hesham Nasser; JP21fk0108493, to Takasuke Fukuhara; JP22fk0108617 to Takasuke Fukuhara; JP22fk0108146, to Kei Sato; JP21fk0108494 to G2P-Japan Consortium, Keita Matsuno, Shinya Tanaka, Terumasa Ikeda, Takasuke Fukuhara, and Kei Sato; JP21fk0108425, to Kazuo Takayama and Kei Sato; JP21fk0108432, to Kazuo Takayama, Takasuke Fukuhara and Kei Sato; JP22fk0108534, Terumasa Ikeda, and Kei Sato; JP22fk0108511, to Yuki Yamamoto, Terumasa Ikeda, Keita Matsuno, Shinya Tanaka, Kazuo Takayama, Takasuke Fukuhara, and Kei Sato; JP22fk0108506, to Kazuo Takayama and Kei Sato); AMED Research Program on HIV/AIDS (JP22fk0410055, to Terumasa Ikeda; and JP22fk0410039, to Kei Sato); AMED Japan Program for Infectious Diseases Research and Infrastructure (JP22wm0125008 to Keita Matsuno); AMED CREST (JP21gm1610005, to Kazuo Takayama; JP22gm1610008, to Takasuke Fukuhara; JST PRESTO (JPMJPR22R1, to Jumpei Ito); JST CREST (JPMJCR20H4, to Kei Sato); JSPS KAKENHI Fund for the Promotion of Joint International Research (International Leading Research) (JP23K20041, to G2P-Japan Consortium, Keita Matsuno, Takasuke Fukuhara and Kei Sato); JST SPRING (JPMJSP2108 to Shigeru Fujita); JSPS KAKENHI Grant-in-Aid for Scientific Research C (22K07103, to Terumasa Ikeda); JSPS KAKENHI Grant-in-Aid for Scientific Research B (21H02736, to Takasuke Fukuhara); JSPS KAKENHI Grant-in-Aid for Early-Career Scientists (22K16375, to Hesham Nasser; 20K15767, to Jumpei Ito); JSPS Core-to-Core Program (A. Advanced Research Networks) (JPJSCCA20190008, to Kei Sato); JSPS Research Fellow DC2 (22J11578, to Keiya Uriu); JSPS Research Fellow DC1 (23KJ0710, to Yusuke Kosugi); JSPS Leading Initiative for Excellent Young Researchers (LEADER) (to Terumasa Ikeda); World-leading Innovative and Smart Education (WISE) Program 1801 from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) (to Naganori Nao); Ministry of Health, Labour and Welfare (MHLW) under grant 23HA2010 (to Naganori Nao and Keita Matsuno); The Cooperative Research Program (Joint Usage/Research Center program) of Institute for Life and Medical Sciences, Kyoto University (to Kei Sato); International Joint Research Project of the Institute of Medical Science, the University of Tokyo (to Terumasa Ikeda and Takasuke Fukuhara); The Tokyo Biochemical Research Foundation (to Kei Sato); Takeda Science Foundation (to Terumasa Ikeda and Takasuke Fukuhara); Mochida Memorial Foundation for Medical and Pharmaceutical Research (to Terumasa Ikeda); The Naito Foundation (to Terumasa Ikeda); Hokuto Foundation for Bioscience (to Tomokazu Tamura); Hirose Foundation (to Tomokazu Tamura); and Mitsubishi Foundation (to Kei Sato).
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COVID-19 , Quirópteros , SARS-CoV-2 , Animais , SARS-CoV-2/genética , SARS-CoV-2/fisiologia , Humanos , COVID-19/virologia , Quirópteros/virologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Glicoproteína da Espícula de Coronavírus/genética , Organoides/virologia , Organoides/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/virologia , Cricetinae , Furina/metabolismo , Células Epiteliais/virologia , Células Vero , Chlorocebus aethiopsAssuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/epidemiologia , COVID-19/virologiaRESUMO
Low body weight and advanced age are among the best predictors of osteoporosis. Osteoporosis Self-Assessment Tool (OST) values are calculated by a simple formula [(body weight in kilograms - age in years) × 0.2] to identify patients at increased risk of osteoporosis. In our recent single-center study, we demonstrated an association between OST and poor outcomes in postmenopausal women after transcatheter aortic valve replacement (TAVR). We aimed to investigate the impact of osteoporotic risk in men with aortic stenosis who underwent TAVR in a large cohort. In this multi-center study, 1,339 men who underwent TAVR between April 2010 and July 2023 were retrospectively analyzed. Women were excluded from the present study. All patients were deemed appropriate for TAVR after a review by a multidisciplinary team. Baseline characteristics of patients were compared by dividing patients into three tertiles, based on the OST value: ≤ - 6.16, - 6.16 to - 4.14, and - 4.14 < for tertiles 1, 2, and 3, respectively. Primary endpoint was all-cause mortality after TAVR. Tertile 1 (patients with the lowest OST values) included older patients with smaller body mass index, lower hemoglobin and albumin levels. In addition, they had greater clinical frailty scale, slower 5-meter walk test, weaker hand grip strength, and more cognitive impairment, indicating increased frailty. They were more severely symptomatic, with lower ejection fractions, smaller aortic valve areas, and more tricuspid regurgitation than were patients in the other two groups. Multivariate analysis revealed that OST tertiles 3 was associated with decreased risk of all-cause mortality (hazard ratio, 0.66; 95% confidence interval, 0.48-0.90), compared with OST tertile 1 as a reference. For OST tertiles 1, 2, and 3, the estimated 1-year survival rates of all-cause mortality post-TAVR were 83.6% ± 1.9%, 91.1% ± 1.4%, and 93.1% ± 1.3%, respectively, (log-rank, p < 0.001).ãIn conclusions, in men as same as women, osteoporotic risk assessed by OST values was overlapped with increased frailty. The simple OST formula was useful for predicting all-cause mortality in patients undergoing TAVR in large registry datasets.
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Nitric oxide (NO) inhalation improves pulmonary hemodynamics in participants with pulmonary arterial hypertension (PAH). Although it can reduce pulmonary vascular resistance (PVR) in PAH, its impact on the dynamic mechanics of pulmonary arteries and its potential difference between control and participants with PAH remain unclear. PA impedance provides a comprehensive description of PA mechanics. With an arterial model, PA impedance can be parameterized into peripheral pulmonary resistance (Rp), arterial compliance (Cp), characteristic impedance of the proximal arteries (Zc), and transmission time from the main PA to the reflection site. This study investigated the effects of inhaled NO on PA impedance and its associated parameters in control and monocrotaline-induced pulmonary arterial hypertension (MCT-PAH) male rats (6/group). Measurements were obtained at baseline and during NO inhalation at 40 and 80 ppm. In both groups, NO inhalation decreased PVR and increased the left atrial pressure. Notably, its impact on PA impedance was frequency dependent, as revealed by reduced PA impedance modulus in the low-frequency range below 10 Hz, with little effect on the high-frequency range. Furthermore, NO inhalation attenuated Rp, increased Cp, and prolonged transmission time without affecting Zc. It reduced Rp more pronouncedly in MCT-PAH rats, whereas it increased Cp and delayed transmission time more effectively in control rats. In conclusion, the therapeutic effects of inhaled NO on PA impedance were frequency dependent and may differ between the control and MCT-PAH groups, suggesting that the effect on the mechanics differs depending on the pathological state.NEW & NOTEWORTHY Nitric oxide inhalation decreased pulmonary arterial impedance in the low-frequency range (<10 Hz) with little impact on the high-frequency range. It reduced peripheral pulmonary resistance more pronouncedly in pulmonary hypertension rats, whereas it increased arterial compliance and transmission time in control rats. Its effect on the mechanics of the pulmonary arteries may differ depending on the pathological status.
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Óxido Nítrico , Artéria Pulmonar , Resistência Vascular , Animais , Masculino , Óxido Nítrico/metabolismo , Artéria Pulmonar/fisiopatologia , Artéria Pulmonar/efeitos dos fármacos , Administração por Inalação , Resistência Vascular/efeitos dos fármacos , Monocrotalina , Ratos , Ratos Sprague-Dawley , Modelos Animais de Doenças , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Arterial Pulmonar/fisiopatologia , Hipertensão Arterial Pulmonar/tratamento farmacológico , Hipertensão Arterial Pulmonar/induzido quimicamente , Pressão Arterial/efeitos dos fármacosRESUMO
Monitoring in vivo viral dynamics can improve our understanding of pathogenicity and tissue tropism. Because the gene size of RNA viruses is typically small, NanoLuc is the primary choice for accommodation within viral genome. However, NanoLuc/Furimazine and also the conventional firefly luciferase/D-luciferin are known to exhibit relatively low tissue permeability and thus less sensitivity for visualization of deep tissue including lungs. Here, we demonstrated in vivo sufficient visualization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using the pair of a codon-optimized Akaluc and AkaLumine. We engineered the codon-optimized Akaluc gene possessing the similar GC ratio of SARS-CoV-2. Using the SARS-CoV-2 recombinants carrying the codon-optimized Akaluc, we visualized in vivo infection of respiratory organs, including the tissue-specific differences associated with particular variants. Additionally, we could evaluate the efficacy of antivirals by monitoring changes in Akaluc signals. Overall, we offer an effective technology for monitoring viral dynamics in live animals.
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A primary reason for the ongoing spread of coronavirus disease 2019 (COVID-19) is the continuous acquisition of mutations by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the mechanism of acquiring mutations is not fully understood. In this study, we isolated SARS-CoV-2 from an immunocompromized patient persistently infected with Omicron strain BF.5 for approximately 4 months to analyze its genome and evaluate drug resistance. Although the patient was administered the antiviral drug remdesivir (RDV), there were no acquired mutations in RDV binding site, and all isolates exhibited susceptibility to RDV. Notably, upon analyzing the S protein sequence of the day 119 isolate, we identified mutations acquired by mutant strains emerging from the BF.5 variant, suggesting that viral genome analysis in persistent COVID-19 patients may be useful in predicting viral evolution. These results suggest mutations in SARS-CoV-2 are acquired during long-term viral replication rather than in response to antiviral drugs.
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Bedside ultrasound represents a well-suited diagnostic and monitoring tool for patients on extracorporeal membrane oxygenation (ECMO) who may be too unstable for transport to other hospital areas for diagnostic tests. The role of ultrasound, however, starts even before ECMO initiation. Every patient considered for ECMO should have a thorough ultrasonographic assessment of cardiac and valvular function, as well as vascular anatomy without delaying ECMO cannulation. The role of pre-ECMO ultrasound is to confirm the indication for ECMO, identify clinical situations for which ECMO is not indicated, rule out contraindications, and inform the choice of ECMO configuration. During ECMO cannulation, the use of vascular and cardiac ultrasound reduces the risk of complications and ensures adequate cannula positioning. Ultrasound remains key for monitoring during ECMO support and troubleshooting ECMO complications. For instance, ultrasound is helpful in the assessment of drainage insufficiency, hemodynamic instability, biventricular function, persistent hypoxemia, and recirculation on venovenous (VV) ECMO. Lung ultrasound can be used to monitor signs of recovery on VV ECMO. Brain ultrasound provides valuable diagnostic and prognostic information on ECMO. Echocardiography is essential in the assessment of readiness for liberation from venoarterial (VA) ECMO. Lastly, post decannulation ultrasound mainly aims at identifying post decannulation thrombosis and vascular complications. This review will cover the role of head-to-toe ultrasound for the management of adult ECMO patients from decision to initiate ECMO to the post decannulation phase.
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Oxigenação por Membrana Extracorpórea , Sistemas Automatizados de Assistência Junto ao Leito , Humanos , Oxigenação por Membrana Extracorpórea/métodos , Adulto , Ultrassonografia/métodos , Ecocardiografia/métodosRESUMO
BACKGROUND: PlMERS-CoV is a coronavirus known to cause severe disease in humans, taxonomically classified under the subgenus Merbecovirus. Recent findings showed that the close relatives of MERS-CoV infecting vespertillionid bats (family Vespertillionidae), named NeoCoV and PDF-2180, use their hosts' ACE2 as their entry receptor, unlike the DPP4 receptor usage of MERS-CoV. Previous research suggests that this difference in receptor usage between these related viruses is a result of recombination. However, the precise location of the recombination breakpoints and the details of the recombination event leading to the change of receptor usage remain unclear. METHODS: We used maximum likelihood-based phylogenetics and genetic similarity comparisons to characterise the evolutionary history of all complete Merbecovirus genome sequences. Recombination events were detected by multiple computational methods implemented in the recombination detection program. To verify the influence of recombination, we inferred the phylogenetic relation of the merbecovirus genomes excluding recombinant segments and that of the viruses' receptor binding domains and examined the level of congruency between the phylogenies. Finally, the geographic distribution of the genomes was inspected to identify the possible location where the recombination event occurred. RESULTS: Similarity plot analysis and the recombination-partitioned phylogenetic inference showed that MERS-CoV is highly similar to NeoCoV (and PDF-2180) across its whole genome except for the spike-encoding region. This is confirmed to be due to recombination by confidently detecting a recombination event between the proximal ancestor of MERS-CoV and a currently unsampled merbecovirus clade. Notably, the upstream recombination breakpoint was detected in the N-terminal domain and the downstream breakpoint at the S2 subunit of spike, indicating that the acquired recombined fragment includes the receptor-binding domain. A tanglegram comparison further confirmed that the receptor binding domain-encoding region of MERS-CoV was acquired via recombination. Geographic mapping analysis on sampling sites suggests the possibility that the recombination event occurred in Africa. CONCLUSION: Together, our results suggest that recombination can lead to receptor switching of merbecoviruses during circulation in bats. These results are useful for future epidemiological assessments and surveillance to understand the spillover risk of bat coronaviruses to the human population.
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Quirópteros , Infecções por Coronavirus , Coronavírus da Síndrome Respiratória do Oriente Médio , Animais , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Filogenia , Funções Verossimilhança , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/epidemiologia , Recombinação Genética , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismoRESUMO
Paired Ga sites represented by the Ga-O-Si-O-Ga sequence were firstly formed intentionally in CHA-type zeolite frameworks via the transcription of pre-formed paired Ga species in a Ga-rich amorphous silica-gallia under seed-assisted hydrothermal conditions. Such paired Ga sites behaved as ion-exchange sites for capturing divalent cation, Co2+.
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The ongoing vaccination efforts and exposure to endemic and emerging coronaviruses can shape the population's immunity against this group of viruses. In this study, we investigated neutralizing immunity against endemic and emerging coronaviruses in 200 Tanzanian frontline healthcare workers (HCWs). Despite low vaccination rates (19.5%), we found a high SARS-CoV-2 seroprevalence (94.0%), indicating high exposure in these HCWs. Next, we determined the neutralization capacity of antisera against human coronavirus NL63, and 229E, SARS-CoV-1, MERS-CoV and SARS-CoV-2 (including Omicron subvariants: BA.1, BQ.1.1 and XBB.1.5) using pseudovirus neutralization assay. We observed a broad range of neutralizing activity in HCWs, but no neutralization activity detected against MERS-CoV. We also observed a strong correlation between neutralizing antibody titers for SARS-CoV-2 and SARS-CoV-1, but not between other coronaviruses. Cross-neutralization titers against the newer Omicron subvariants, BQ.1.1 and XBB.1.5, was significantly reduced compared to BA.1 and BA.2 subvariants. On the other hand, the exposed vaccinated HCWs showed relatively higher median cross-neutralization titers against both the newer Omicron subvariants and SARS-CoV-1, but did not reach statistical significance. In summary, our findings suggest a broad range of neutralizing potency against coronaviruses in Tanzanian HCWs with detectable neutralizing immunity against SARS-CoV-1 resulting from SARS-CoV-2 exposure.