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2.
Artigo em Inglês | MEDLINE | ID: mdl-38556394

RESUMO

BACKGROUND: Considering the absence of reports validating the precision of the volume score and the relationship between the volume and Agatston scores, this study evaluated the accuracy of the volume score compared to the Agatston score for the quantitative measurement of aortic valve calcification (AVC) on non-electrocardiographic-gated computed tomography (CT). METHODS: We retrospectively analysed the AVC scores of 5385 patients who underwent transthoracic echocardiography between March 1, 2013 and December 26, 2019 â€‹at our institution, using non-contrast non-electrocardiographic-gated CT. The thresholds for significant aortic stenosis (AS) were computed using receiver operating characteristic curves based on the AVC scores. The area under the curve (AUC) of the Agatston and volume scores for significant AS were compared to evaluate the accuracy of the scoring method. RESULTS: All sex-specific AVC thresholds of the volume score for significant AS (moderate and high AS severity, moderate and high AS severity without discordance, discordant severe AS, and concordant severe AS) showed high sensitivity and specificity (AUC, 0.978-0.996; sensitivity, 94.2-98.4%; specificity, 90.1-100%). No significant differences in the AUC were observed between the Agatston and volume scores for significant AS in male and female patients. CONCLUSION: All volume score threshold values showed high sensitivity and specificity for identifying significant AS. The accuracy of the test for AVC thresholds of the volume score for significant AS was comparable to that of the Agatston score. Our findings raise questions about the significance of weighting calcium density in the Agatston score for assessing AS severity.

3.
Small ; 20(16): e2306325, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38032161

RESUMO

Due to the manufacturability of highly well-defined structures and wide-range versatility in its microstructure, SiO2 is an attractive template for synthesizing graphene frameworks with the desired pore structure. However, its intrinsic inertness constrains the graphene formation via methane chemical vapor deposition. This work overcomes this challenge by successfully achieving uniform graphene coating on a trimethylsilyl-modified SiO2 (denote TMS-MPS). Remarkably, the onset temperature for graphene growth dropped to 720 °C for the TMS-MPS, as compared to the 885 °C of the pristine SiO2. This is found to be mainly from the Si radicals formed from the decomposition of the surface TMS groups. Both experimental and computational results suggest a strong catalytic effect of the Si radicals on the CH4 dissociation. The surface engineering of SiO2 templates facilitates the synthesis of high-quality graphene sheets. As a result, the graphene-coated SiO2 composite exhibits a high electrical conductivity of 0.25 S cm-1. Moreover, the removal of the TMP-MPS template has released a graphene framework that replicates the parental TMS-MPS template on both micro- and nano- scales. This study provides tremendous insights into graphene growth chemistries as well as establishes a promising methodology for synthesizing graphene-based materials with pre-designed microstructures and porosity.

4.
Am J Physiol Heart Circ Physiol ; 325(4): H856-H865, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37594489

RESUMO

In addition to the classical actions of hemodynamic regulation, natriuretic peptides (NPs) interact with various neurohumoral factors that are deeply involved in the pathophysiology of cardiovascular diseases. However, their effects on the hypothalamic-pituitary-adrenal (HPA) axis, which is activated under acute high-stress conditions in acute coronary syndrome (ACS), remain largely unknown. We investigated the impact of plasma B-type NP (BNP) on plasma adrenocorticotropic hormone (ACTH)-cortisol levels during the acute phase of ACS ischemic attacks. The study population included 436 consecutive patients with ACS for whom data were collected during emergency cardiac catheterization. Among them, biochemical data after acute-phase treatment were available in 320 cases, defined as the ACS-remission phase (ACS-rem). Multiple regression analyses revealed that plasma BNP levels were significantly negatively associated with plasma ACTH levels only during ACS attacks (P < 0.001), but not in ACS-rem, whereas plasma BNP levels were not significantly associated with plasma cortisol levels at any point. Accordingly, covariance structure analyses were performed to clarify the direct contribution of BNP to ACTH by excluding other confounding factors, confirming that BNP level was negatively correlated with ACTH level only during ACS attacks (ß = -0.152, P = 0.002), whereas BNP did not significantly affect ACTH in ACS-rem. In conclusion, despite the lack of a significant direct association with cortisol levels, BNP negatively regulated ACTH levels during the acute phase of an ACS attack in which the HPA axis ought to be activated. NP may alleviate the acute stress response induced by severe ischemic attacks in patients with ACS.NEW & NOTEWORTHY BNP negatively regulates ACTH during a severe ischemic attack of ACS in which hypothalamic-pituitary-adrenal axis ought to be activated, indicating an important role of natriuretic peptides as a mechanism of adaptation to acute critical stress conditions in humans.


Assuntos
Síndrome Coronariana Aguda , Hormônios Peptídicos , Humanos , Hormônio Adrenocorticotrópico , Peptídeo Natriurético Encefálico , Sistema Hipotálamo-Hipofisário , Síndrome Coronariana Aguda/tratamento farmacológico , Hidrocortisona , Sistema Hipófise-Suprarrenal
5.
Heart Vessels ; 38(10): 1218-1227, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37318650

RESUMO

Several studies have investigated the association between P2Y12 reaction unit (PRU) value and major adverse cardiovascular events (MACEs) in patients with ischemic heart disease, but there is no well-established consensus on the utility of PRU value. Furthermore, the optimal PRU cut-off value varied with studies. One reason may be that the endpoints and observation periods differed, depending on the study. This study aimed to investigate the optimal cut-off and predictive ability of the PRU value for predicting cardiovascular events, while considering different endpoints and observation periods. We surveyed a total of 338 patients receiving P2Y12 inhibitors and measured PRU during cardiac catheterization. Using time-dependent receiver operating characteristic analysis, we evaluated the cut-off and area under curve (AUC) of the PRU value for two MACEs (MACE ①: composite of death, myocardial infarction, stent thrombosis, and cerebral infarction; MACE ②: composite of MACE ① and target vessel revascularization) at 6, 12, 24 and 36 months after cardiac catheterization. MACE ① occurred in 18 cases and MACE ② in 32 cases. The PRU cut-off values at 6, 12, 24, and 36 months were 257, 238, 217, and 216, respectively, for MACE ① and 250, 238, 209, and 204, respectively, for MACE ②. The AUCs at 6, 12, 24, and 36 months were 0.753, 0.832, 0.718, and 0.717, respectively, for MACE ① and 0.724, 0.722, 0.664, and 0.682, respectively, for MACE ②. The optimal cut-off and predictive ability of PRU values for cardiovascular events varied depending on different endpoints and duration of the observation periods. A relatively high PRU value is effective for short-term event suppression, but a low value is required for long-term event suppression.


Assuntos
Infarto do Miocárdio , Isquemia Miocárdica , Humanos , Inibidores da Agregação Plaquetária/farmacologia , Plaquetas , Estudos Prospectivos , Isquemia Miocárdica/complicações , Isquemia Miocárdica/diagnóstico , Resultado do Tratamento
6.
ESC Heart Fail ; 10(3): 1860-1870, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36942494

RESUMO

AIMS: Although the haemodynamic effects of angiotensin receptor-neprilysin inhibitor (ARNI) on patients with heart failure have been demonstrated, the effect on glucose metabolism has not been fully elucidated. We retrospectively investigated the effect of ARNI on abnormal glucose metabolism in patients with stable chronic heart failure using an additional structural equation model (SEM) analysis. METHODS: We analysed 34 patients who regularly visited to the outpatient department of our institute with heart failure from October 2021 and July 2022 and who were taking angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). Seventeen patients switched from ACE inhibitors or ARBs to an ARNI (ARNI group), and the other 17 patients continued treatment with ACE inhibitors or ARBs (control group). RESULTS: At baseline, although the ARNI group included fewer patients with heart failure with preserved ejection fraction in comparison with the control group (P = 0.004), patients with heart failure with mildly reduced ejection fraction, and heart failure with reduced ejection fraction were mostly biased towards the ARNI group (although not statistically significant). The baseline insulin resistance in the ARNI group was already significantly higher in comparison with the control group [fasting blood insulin, 9.7 (7.4, 11.6) vs. 7.8 (5.2, 9.2) µU/mL, P = 0.033; homoeostasis model assessment of insulin resistance (HOMA-IR), 3.10 (1.95, 4.19) vs. 2.02 (1.56, 2.42), P = 0.014]. Three months later, the fasting blood insulin and the HOMA-IR levels were both found to have decreased in comparison with the baseline values [baseline to 3 months: insulin, 9.7 (7.4, 11.6) to 7.3 (4.6, 9.4) µU/mL, P < 0.001; HOMA-IR, 3.10 (1.95, 4.19) to 1.96 (1.23, 3.09), P < 0.001]. An additional SEM analysis demonstrated that the initiation of ARNI had caused a reduction in the fasting blood insulin and the HOMA-IR levels at 3 months independently of the baseline fasting blood insulin and HOMA-IR levels, respectively. Similarly, the initiation of ARNI resulted in a significant reduction in serum uric acid levels (6.28 ± 0.35 to 5.80 ± 0.30 mg/dL, P = 0.008). CONCLUSIONS: In conclusion, even in a short period of only 3 months, the administration of ARNI improved insulin resistance and consequently reduced the serum uric acid levels in patients with stable chronic heart failure. Although the ARNI group already had high insulin resistance at baseline, an additional SEM analysis revealed that the decreased insulin resistance was truly due to the effect of ARNI.


Assuntos
Insuficiência Cardíaca , Resistência à Insulina , Insulinas , Disfunção Ventricular Esquerda , Humanos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Antagonistas de Receptores de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Anti-Hipertensivos , Glucose , Insuficiência Cardíaca/tratamento farmacológico , Neprilisina , Estudos Retrospectivos , Volume Sistólico , Resultado do Tratamento , Ácido Úrico
7.
Cardiovasc Interv Ther ; 38(3): 309-315, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36800064

RESUMO

The small-balloon technique used to retrieve a dislodged coronary stent is less studied. We investigated the small-balloon technique to study the capture force and retrieval rate of dislodged proximal or distal stents. We developed a retrieval model for stent dislodgement and performed bench tests to compare proximal and distal capture. We evaluated capture force by capture site in a fixed stent dislodgement model and capture force and retrieval rate by capture site using a retrieval model of stent dislodgement. Three-dimensional (3D)-micro-computed tomography (CT) was used to scan the captured conditions of the distal (DC) and proximal (PC) groups. Stent, balloon shaft, and guiding catheter (GC) diameters were measured. Retrieval areas within GC were calculated and compared. The force was significantly lower in the PC group than in the DC group (p < 0.01). Successful retrieval was achieved in 100% and 84.8% in the PC and DC groups, respectively. The force required to retrieve the dislodged stent was significantly lower in the PC group than that in the DC group (p < 0.01). The force was significantly lower in the successful cases in the DC group than in the unsuccessful cases (p < 0.01). The retrievable areas in the PC and DC groups were 67.5% and 32.7%, respectively, as calculated from the values measured from the 3D-CT images. The success rate of PC was higher than that of DC using the small-balloon technique. The smaller proximal stent gap in the PC method facilitated the retrieval of the dislodgement stent.


Assuntos
Angioplastia Coronária com Balão , Humanos , Angioplastia Coronária com Balão/métodos , Microtomografia por Raio-X , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/cirurgia , Cateterismo , Stents , Resultado do Tratamento
8.
Bioorg Med Chem Lett ; 83: 129175, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36758821

RESUMO

Bunyaviruses, including the Lassa virus (LASV), are known to cause hemorrhagic fever and have a high fatality rate among hospitalized patients, as there are few effective treatments. We focused on the fact that bunyaviruses use cap-dependent endonuclease (CEN) for viral replication, which is similar to influenza viruses. This led us to screen carbamoyl pyridone bicycle (CAB) compounds, which compose a series of baloxavir acid (BXA) derivatives, against lymphocytic choriomeningitis virus (LCMV) and Junin virus (JUNV) among the bunyaviruses. This led to the discovery of 1c, which has potent anti-bunyaviral activities. In SAR studies, we found that a large lipophilic side chain is preferred for the 1-position of the CAB scaffold, similar to the influenza CEN inhibitor, and that a small alkyl group for the 3-position shows high activity. Moreover, the 7­carboxyl group of the scaffold is essential for anti-bunyaviral activities, and the antiviral activity is reduced by conversion to various carboxylic acid bioisosteres. The SAR results are discussed using a binding model of 9d in the active center of the known LCMV CEN crystal structure. These compounds show promise as broad-spectrum anti-bunyavirus therapeutics, given their relatively favorable metabolic stability and PK profiles.


Assuntos
Influenza Humana , Orthomyxoviridae , Humanos , Relação Estrutura-Atividade , Antivirais/farmacologia , Antivirais/química , Endonucleases/metabolismo
9.
BMC Musculoskelet Disord ; 24(1): 148, 2023 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-36849957

RESUMO

BACKGROUND: The manual traditional anterior drawer test (ADT) is essential for deciding the treatment for chronic ankle instability, but it has been shown to have a comparatively low reproducibility and accuracy, especially in less experienced hands. To clarify the inter-examiner reproducibility, we compared the actual distance of anterior translation between junior and senior examiners in ADT. We also evaluated the diagnostic abilities of traditional ADT, and a novel modified ADT (supported ADT). METHODS: Thirty ankles were included in this study, and ankle instability was defined using stress radiography. All subjects underwent two methods of manual ADT by junior and senior examiners, and ankle instability was judged in a blinded fashion. The anterior drawer distance was calculated from the lengthening measured using a capacitance-type sensor device. RESULTS: The degree of anterior translation determined by the junior examiner was significantly lower than that determined by the senior examiner when traditional ADT was performed (3.3 vs. 4.5 mm, P = 0.016), but there was no significant difference in anterior translation between the two examiners when supported ADT was performed (4.6 vs. 4.1 mm, P = 0.168). The inter-examiner reliability of supported ADT was higher than that of traditional ADT. For the junior examiner, the diagnostic accuracy of supported ADT was higher than that of traditional ADT (sensitivity, 0.40 vs. 0.80; specificity, 0.75 vs. 0.80). CONCLUSION: Supported ADT may have the advantage of being a simple manual test of ankle instability with less error between examiners.


Assuntos
Tornozelo , Instabilidade Articular , Humanos , Reprodutibilidade dos Testes , Capacitância Elétrica , Mãos , Instabilidade Articular/diagnóstico
10.
Sleep ; 46(3)2023 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-36385326

RESUMO

STUDY OBJECTIVES: While caregiver-reported sleep disturbances are common in children and adolescents with autism spectrum disorder (['), few studies have measured objective sleep in ASD compared to controls, and their findings are mixed. We investigated (1) differences in sleep architecture, specifically slow-wave sleep (SWS) and rapid eye movement (REM) sleep, between ASD and typically developing controls (TD); and (2) if any observed differences in sleep were associated with core ASD symptoms. METHODS: We used ambulatory polysomnography (PSG) in 53 participants with ASD (ages 4-18) and 66 age-matched TD in their home sleeping environment. The primary outcome measures were SWS and REM sleep. Core behavioral ASD symptoms were assessed using the Autism Diagnostic Interview-Revised (ADI-R). Spectral power bands during sleep, and additional behavioral measures, were examined in exploratory analyses. RESULTS: Compared to TD, participants with ASD exhibited a higher SWS ratio and lower REM sleep ratio. Within the ASD group, higher SWS was associated with more severe symptoms on the Restricted, Repetitive, and Stereotyped Behaviors subscale of the ADI-R. No association was observed between REM sleep ratio and any ASD symptom. CONCLUSIONS: Increased SWS and reduced REM sleep ratio differentiated ASD from TD. However, only increased SWS was associated with more severe core ASD symptoms. Increased SWS may reflect neuronal immaturity specific to ASD in this age group. These findings may inform the underlying mechanisms of clinical symptoms observed in children and adolescents with ASD.


Assuntos
Transtorno do Espectro Autista , Sono de Ondas Lentas , Criança , Adolescente , Humanos , Pré-Escolar , Transtorno do Espectro Autista/complicações , Sono/fisiologia , Sono REM/fisiologia , Polissonografia
11.
ESC Heart Fail ; 10(2): 955-964, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36478404

RESUMO

AIMS: Pulmonary congestion, reduced cardiac output, neurohumoral factor activation, and decreased renal function associated with decreased cardiac function may have various effects on haemograms. The relationship between these factors and haemograms in patients with heart failure has not been sufficiently investigated. Recently, it was suggested that the lungs are an important site for platelet (Plt) biosynthesis and that it is necessary to study the relationship between pulmonary congestion and Plt count in heart failure in detail. In this study, we examined the relationship between various haemodynamic indicators and haemograms in detail using statistical analyses. METHODS AND RESULTS: A total of 345 patients who underwent cardiac catheterization for the evaluation of cardiac function between 1 January 2015 and 31 December 2020 were included in the study. Haemodynamic indices, including left ventricular end-diastolic pressure (LVEDP) and cardiac index (CI), were measured. Plasma noradrenaline (Nor) concentration, estimated glomerular filtration rate (eGFR), white blood cell (WBC) count, haemoglobin (Hb) level, and Plt count were measured using blood samples collected at the same time. Structural equation modelling (SEM) was used to examine the relationship between LVEDP, CI, plasma Nor concentration, eGFR, WBC count, Hb level, and Plt count. Bayesian inference using SEM was performed for Plt count. A total of 345 patients (mean age: 66.0 ± 13.2 years) were included in this study, and 251 (73%) patients were men. After simple and multiple regression analyses, path diagrams were drawn and analysed using SEM. LVEDP showed a significant negative relationship with Plt count (standardized estimate: -0.129, P = 0.015), and CI showed a significant negative relationship with Hb level (standardized estimate: -0.263, P < 0.001). Plasma Nor concentration showed a significant positive relationship with WBC count (standardized estimate: 0.165, P = 0.003) and Plt count (standardized estimate: 0.198, P < 0.001). The eGFR had a significant positive relationship with Hb level (standardized estimate: 0.274, P < 0.001). Bayesian inference using SEM revealed no relationship between LVEDP and Hb level or WBC count but a significant negative relationship between LVEDP and Plt count. CONCLUSIONS: LVEDP, CI, plasma Nor concentration, and eGFR were related to WBC count, Hb level, and Plt count in patients with heart failure. There was a strong relationship between elevated LVEDP and decreased Plt count, suggesting that pressure overload on the lungs may interfere with the function of the lung as a site of Plt biosynthesis.


Assuntos
Insuficiência Cardíaca , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Feminino , Teorema de Bayes , Hemodinâmica , Cateterismo Cardíaco , Circulação Pulmonar
12.
Int Psychogeriatr ; 35(8): 421-431, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-33118918

RESUMO

OBJECTIVES: (1) To delineate whether cognitive flexibility and inhibitory ability are neurocognitive markers of passive suicidal ideation (PSI), an early stage of suicide risk in depression and (2) to determine whether PSI is associated with volumetric differences in regions of the prefrontal cortex (PFC) in middle-aged and older adults with depression. DESIGN: Cross-sectional study. SETTING: University medical school. PARTICIPANTS: Forty community-dwelling middle-aged and older adults with depression from a larger study of depression and anxiety (NIMH R01 MH091342-05 PI: O'Hara). MEASUREMENTS: Psychiatric measures were assessed for the presence of a DSM-5 depressive disorder and PSI. A neurocognitive battery assessed cognitive flexibility, inhibitory ability, as well as other neurocognitive domains. RESULTS: The PSI group (n = 18) performed significantly worse on cognitive flexibility and inhibitory ability, but not on other neurocognitive tasks, compared to the group without PSI (n = 22). The group with PSI had larger left mid-frontal gyri (MFG) than the no-PSI group. There was no association between cognitive flexibility/inhibitory ability and left MFG volume. CONCLUSIONS: Findings implicate a neurocognitive signature of PSI: poorer cognitive flexibility and poor inhibitory ability not better accounted for by other domains of cognitive dysfunction and not associated with volumetric differences in the left MFG. This suggests that there are two specific but independent risk factors of PSI in middle- and older-aged adults.


Assuntos
Disfunção Cognitiva , Ideação Suicida , Humanos , Pessoa de Meia-Idade , Idoso , Adulto , Depressão/psicologia , Estudos Transversais , Cognição , Fatores de Risco
13.
Eur Radiol ; 33(2): 1243-1253, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36066729

RESUMO

OBJECTIVES: This study evaluated the association between aortic valve calcification (AVC) and aortic stenosis (AS) by scoring the AVC to determine the threshold scores for significant AS on non-electrocardiographic (ECG)-gated computed tomography (CT). METHODS: We retrospectively analyzed the AVC scores of 5385 patients on non-contrast non-ECG-gated CT, who underwent transthoracic echocardiography (TTE) from March 1, 2013, to December 26, 2019, at our institution. Multivariable logistic regression models were used to identify potential risk factors for significant AS. The thresholds for significant AS were computed using receiver operator characteristic (ROC) curves, based on the AVC scores after propensity score matching. RESULTS: A significant association was found between AS and age (p < 0.001; odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02-1.06), female sex (p < 0.001; OR, 4.5; 95% CI, 2.75-7.36), bicuspid aortic valve (p < 0.001; OR, 23.2; 95% CI, 7.35-72.9), and AVC score (AVC score/100) (p < 0.001; OR, 1.82; 95% CI, 1.71-1.95). All sex-specific AVC thresholds for significant AS (moderate and over AS severity, moderate and over AS severity without discordance, discordant severe AS, and concordant severe AS) showed high sensitivity and specificity (AUC, 0.939-0.968; sensitivity, 84.6-96%; specificity, 84.2-97.1%). CONCLUSIONS: We determined the optimal AVC threshold scores for significant AS, which may aid in diagnosing significant asymptomatic AS on incidental detection of AVC through non-ECG-gated CT for non-cardiac indications. KEY POINTS: • Increased frequency of non-electrocardiographic (ECG)-gated computed tomography (CT) for non-cardiac indications has led to the increased incidental identification of aortic valve calcification (AVC). • It is important to identify patients with significant aortic stenosis (AS) who require additional echocardiographic assessment on incidental detection of AVC via non-ECG-gated CT. • We determined the AVC thresholds with high sensitivity and specificity to identify significant AS on non-ECG-gated CT, which could lead to early diagnosis of asymptomatic significant AS and improved prognosis.


Assuntos
Estenose da Valva Aórtica , Valva Aórtica , Masculino , Humanos , Feminino , Valva Aórtica/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada Multidetectores/métodos , Estenose da Valva Aórtica/diagnóstico por imagem , Índice de Gravidade de Doença
14.
Intern Med ; 61(24): 3659-3666, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36198605

RESUMO

Objective Just before the Tokyo 2020 Olympic and Paralympic Games in Japan, the number of people infected with coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), started to increase at an unprecedented rate. This study investigated the effectiveness of vaccines in large-scale sporting events under difficult circumstances, such as during adherence to a bubble system and confinement inside the Olympic/Paralympic Village. Methods In collaboration with medical clinics inside and outside the Village, a prospective cohort study was conducted among overseas participants using the results of polymerase chain reaction (PCR) tests for SARS-CoV-2 upon leaving Japan. Results A total of 12,072 foreign participants were enrolled, 13 (0.11%) of whom had a positive PCR test result. None of these cases were broadcasters or members of the press, were tested outside the Olympic Village, or had a history of COVID-19 infection. The effectiveness of full vaccination and vaccination at least once (≥14 days ago) was 74% [95% confidence interval (CI): 6-93%] and 81% (95% CI: 30-95%), respectively. Three breakthrough infections with the Delta variant were observed in 6,485 fully vaccinated participants (0.05%). The positivity rate was 0.09% among adherents to the bubble system and 0.28% among non-adherents, but this difference was not significant. Conclusion These findings indicate that even huge sporting events such as the Olympic and Paralympic Games can proceed while pandemics are ongoing in the host country by combining countermeasures such as vaccination, frequent testing, social distancing, and adherence to a bubble system.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , Tóquio/epidemiologia , Estudos Prospectivos
15.
Proc Natl Acad Sci U S A ; 119(36): e2206104119, 2022 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-36037386

RESUMO

Viral hemorrhagic fevers caused by members of the order Bunyavirales comprise endemic and emerging human infections that are significant public health concerns. Despite the disease severity, there are few therapeutic options available, and therefore effective antiviral drugs are urgently needed to reduce disease burdens. Bunyaviruses, like influenza viruses (IFVs), possess a cap-dependent endonuclease (CEN) that mediates the critical cap-snatching step of viral RNA transcription. We screened compounds from our CEN inhibitor (CENi) library and identified specific structural compounds that are 100 to 1,000 times more active in vitro than ribavirin against bunyaviruses, including Lassa virus, lymphocytic choriomeningitis virus (LCMV), and Junin virus. To investigate their inhibitory mechanism of action, drug-resistant viruses were selected in culture. Whole-genome sequencing revealed that amino acid substitutions in the CEN region of drug-resistant viruses were located in similar positions as those of the CEN α3-helix loop of IFVs derived under drug selection. Thus, our studies suggest that CENi compounds inhibit both bunyavirus and IFV replication in a mechanistically similar manner. Structural analysis revealed that the side chain of the carboxyl group at the seventh position of the main structure of the compound was essential for the high antiviral activity against bunyaviruses. In LCMV-infected mice, the compounds significantly decreased blood viral load, suppressed symptoms such as thrombocytopenia and hepatic dysfunction, and improved survival rates. These data suggest a potential broad-spectrum clinical utility of CENis for the treatment of both severe influenza and hemorrhagic diseases caused by bunyaviruses.


Assuntos
Antivirais , Endonucleases , Orthobunyavirus , Animais , Antivirais/farmacologia , Avaliação Pré-Clínica de Medicamentos , Farmacorresistência Viral/efeitos dos fármacos , Farmacorresistência Viral/genética , Endonucleases/antagonistas & inibidores , Humanos , Camundongos , Orthobunyavirus/efeitos dos fármacos , Orthobunyavirus/genética , Orthobunyavirus/metabolismo , Replicação Viral/efeitos dos fármacos
16.
A A Pract ; 16(8): e01613, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35952341

RESUMO

Trauma is associated with debilitating acute and posttraumatic stress disorders, which have limited treatment options. We report on a patient undergoing surgical hand repair after a recent knife attack who experienced vivid dreaming and subsequent remission of acute stress disorder. After local anesthesia with propofol sedation she recalled a dream wherein she relived the attack, sought medical care, completed surgery, and returned home with a healed hand. While intraoperative dreaming is common, this case details potential associations between anesthetic state, dreaming, intraoperative electroencephalography, and remission of a psychiatric disorder. Our experience suggests a novel intervention for stress disorders.


Assuntos
Anestesia , Anestésicos , Transtornos Mentais , Propofol , Sonhos , Feminino , Humanos
17.
Mol Genet Metab Rep ; 31: 100858, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35782602

RESUMO

Aims: T1 mapping in cardiac magnetic resonance imaging enables us to distinguish various myocardial diseases showing left ventricular hypertrophy. Fabry disease is a lysosomal storage disorder causing the accumulation of glycosphingolipids into various organs, including the heart, which can be detected by native T1 values in T1 mapping. However, there is no report for the systematic evaluation of native T1 values in Fabry disease in Japan. Methods and results: We analyzed native T1 values of 30 Fabry disease patients (14 males and 16 females) obtained by 3-T cardiac magnetic resonance imaging. Averaged T1 values were significantly lower in male patients (septal T1: 1149.5 ± 63.3 ms; total T1: 1145.1 ± 59.5 ms) than in female patients (septal T1: 1210.5 ± 45.5 ms; total T1: 1198.8 ± 51.8 ms) (p < 0.01). We compared the native T1 values of Fabry disease patients with those obtained from 15 hypertrophic cardiomyopathy patients (9 males and 6 females). Native T1 values effectively differentiate Fabry disease from hypertrophic cardiomyopathy (septal T1: sensitivity 93.3% and specificity 80.0%; total T1: sensitivity 86.7% and specificity 73.3%). In addition, native T1 values had a significant negative correlation with the left ventricular mass index in male patients at the pre-hypertrophic stage (p < 0.05). In male and female patients without late-gadolinium enhancement, native T1 values also had a significant negative correlation with the left ventricular mass index (p < 0.05). Conclusion: These results suggest that native T1 values can be used to discriminate Fabry disease from hypertrophic cardiomyopathy and can reflect the accumulation of glycosphingolipids in cardiomyocytes.

18.
Circ J ; 86(8): 1229-1236, 2022 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-35786690

RESUMO

BACKGROUND: Pulmonary vein (PV) stenosis after atrial fibrillation (AF) ablation is rare; however, it remains a serious complication. PV angioplasty is reportedly an effective therapy; however, a dedicated device for PV angioplasty has not been developed, and the detailed procedural methods remain undetermined. This study describes the symptoms, indications, treatment strategies, and long-term outcomes for PV stenosis after AF ablation.Methods and Results: This study retrospectively analyzed 7 patients with PV stenosis after catheter ablation for AF and who had undergone PV angioplasty at our hospital during 2015-2021. PV stenosis occurred in the left superior (5 patients) and left inferior (2 patients) PV. Six patients had hemoptysis, chest pain, and dyspnea. Seven de novo lesions were treated using balloon angioplasty (BA) (3 patients), a bare metal stent (BMS) (3 patients), and a drug-coated balloon (DCB) (1 patient). The restenosis rate was 42.9% (n=3; 2 patients in the BA group and 1 patient in the DCB group). The repeat treatment rate was 28.6% (2 patients in the BA group). Stenting was performed as repeat treatment. One patient with subsequent repeat restenosis development underwent BA. Ten PV angioplasties were performed; there were no major complications. CONCLUSIONS: Regarding PV angioplasty after ablation therapy for AF, stenting showed superior long-term PV patency than BA alone; therefore, it should be considered as a standard first-line approach.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Estenose de Veia Pulmonar , Angioplastia/efeitos adversos , Angioplastia/métodos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Constrição Patológica/complicações , Humanos , Veias Pulmonares/cirurgia , Estudos Retrospectivos , Estenose de Veia Pulmonar/diagnóstico por imagem , Estenose de Veia Pulmonar/etiologia , Estenose de Veia Pulmonar/terapia , Resultado do Tratamento
19.
Heart Vessels ; 37(12): 2093-2100, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35842560

RESUMO

In the transcatheter aortic valve implantation (TAVI) era, the indications for balloon aortic valvuloplasty (BAV) are increasing. Previously, the INOUE-BALLOON® (IB) was used only for antegrade BAV, but recently, it has also been used for retrograde BAV. However, the safety and feasibility of retrograde BAV using an IB are not fully understood. In this study, we investigated the safety and feasibility of retrograde BAV using an IB in elderly Japanese patients with severe aortic stenosis (AS). We compared 39 cases of retrograde BAV using an IB performed from June 2018 to September 2020 and 34 cases of antegrade BAV using an IB performed from August 2013 to May 2018. The total number of complications was lower in retrograde BAV than in antegrade BAV (p = 0.020). The procedure time was significantly shorter in retrograde BAV than in antegrade BAV (p < 0.001), and the maximum balloon size and number of balloon inflations were smaller in retrograde BAV than in antegrade BAV (p = 0.002 and p < 0.001, respectively). There was no significant difference in the degree of improvement in the aortic valve area or ejection fraction between retrograde and antegrade BAV. In conclusion, the present study showed the safety and feasibility of retrograde BAV using an IB in elderly Japanese patients with severe AS compared with antegrade BAV using an IB.


Assuntos
Estenose da Valva Aórtica , Valvuloplastia com Balão , Substituição da Valva Aórtica Transcateter , Humanos , Idoso , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/cirurgia , Estudos de Viabilidade , Valvuloplastia com Balão/efeitos adversos , Resultado do Tratamento , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Estudos Retrospectivos
20.
Cureus ; 14(3): e22762, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35371876

RESUMO

A recent study suggested that angiotensin receptor/neprilysin inhibitor (ARNI; sacubitril/valsartan) can improve functional capacity and cardiac reverse remodeling in patients with heart failure with reduced ejection fraction (HFrEF). Another study suggested that ARNI reduced glycated hemoglobin (HbA1c) in patients with diabetes and HFrEF; however, the details of its efficacy are unknown. We herein report a case of HFrEF with abnormal glucose metabolism in which ARNI was initiated. On the 7th day of admission (before the initiation of ARNI), blood tests showed an abnormal glucose metabolism as follows: fasting blood glucose 134 mg/dL; and fasting blood insulin 11.4 µU/mL (homeostasis model assessment of insulin resistance (HOMA-IR) index 3.77; homeostasis model assessment of ß-cell function (HOMA-ß), 57.8%). On the 23rd day after the initiation of ARNI, even though the patient was not using hypoglycemic drugs, his fasting blood glucose markedly decreased to 70 mg/dL without hypoglycemic symptoms, and his fasting blood insulin decreased to 5.4 µU/mL (HOMA-IR decreased to 0.93, HOMA-ß increased to 277.7%). These results imply that ARNI has the potential to improve insulin resistance and the islet beta-cell function in patients with heart failure, in addition to the original effect of improving the hemodynamics, although the effect of improving the glucose metabolism is also considered to have been influenced by the improvement of the heart failure status and other drugs that the patient was taking.

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