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Regulation of membrane protein integration involves molecular devices such as Sec-translocons or the insertase YidC. We have identified an integration-promoting factor in the inner membrane of Escherichia coli called membrane protein integrase (MPIase). Structural analysis revealed that, despite its enzyme-like name, MPIase is a glycolipid with a long glycan comprising N-acetyl amino sugars, a pyrophosphate linker, and a diacylglycerol (DAG) anchor. Additionally, we found that DAG, a minor membrane component, blocks spontaneous integration. In this review, we demonstrate how they contribute to Sec-independent membrane protein integration in bacteria using a comprehensive approach including synthetic chemistry and biophysical analyses. DAG blocks unfavorable spontaneous integrations by suppressing mobility in the membrane core, whereas MPIase compensates for this. Moreover, MPIase plays critical roles in capturing a substrate protein to prevent its aggregation, attracting it to the membrane surface, facilitating its insertion into the membrane, and delivering it to other factors. The combination of DAG and MPIase efficiently regulates the integration of membrane proteins.
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Escherichia coli , Glicolipídeos , Proteínas de Membrana , Glicolipídeos/metabolismo , Glicolipídeos/química , Proteínas de Membrana/metabolismo , Proteínas de Membrana/química , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/química , Membrana Celular/metabolismo , Diglicerídeos/metabolismo , Diglicerídeos/químicaRESUMO
A 10-year-old female patient experienced syncope while swimming, and electrocardiography revealed polymorphic ventricular tachycardia, leading to a diagnosis of catecholaminergic polymorphic ventricular tachycardia. No pathogenic variant was identified in RYR2. Additional comprehensive genetic testing revealed novel compound heterozygous variants in trans-2,3-enoyl-coenzyme A reductase-like gene, which caused a recessive form of catecholaminergic polymorphic ventricular tachycardia.
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A 77-year-old female patient with multiple pacemaker leads experienced hypotension and syncope during right heart catheterization. Imaging studies revealed a stenotic inferior vena cava with superior vena cava obstruction and well-developed retrograde collateral vessels, suggesting that balloon obstruction of the sole venous return site caused low cardiac output leading to syncope.
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BACKGROUND: The adaptive cardiac resynchronization therapy (aCRT) algorithm enables synchronized left ventricular pacing (sLVP) to achieve fusion with intrinsic right ventricular activation. Although sLVP presents benefits over biventricular pacing, the adequate sLVP rate for better clinical outcomes remains unclear. We aimed to assess the association between sLVP rates and clinical outcomes. METHODS: Our study cohort included 271 consecutive patients, who underwent CRT implantation between April 2016 and August 2021. RESULTS: We evaluated 63 patients on whom we applied the aCRT algorithm [48 men, mean age: 64⯱â¯14â¯years; median follow-up period: 316â¯days (interquartile range: 212-809â¯days)]. At the 6-month follow-up after CRT implantation, the frequency of CRT responders was 71â¯% (nâ¯=â¯45). The sLVP rate was significantly higher in responders than in non-responders (75⯱â¯30â¯% vs. 47⯱â¯40â¯%, pâ¯=â¯0.003). Receiver operating characteristics curve analysis revealed that the optimal cut-off value during the sLVP rate was 59.4â¯% for the prediction of CRT responders (area under the curve, 0.70; sensitivity, 80â¯%; specificity, 61â¯%; positive predictive value, 84â¯%; and negative predictive value, 55â¯%). Kaplan-Meier analysis demonstrated that the higher-sLVP group (sLVP â§59.4â¯%, nâ¯=â¯43) had a better prognosis (cardiac death and heart failure hospitalization) than the lower-sLVP group (sLVP <59.4â¯%, nâ¯=â¯20) (log-rank pâ¯<â¯0.001). Multivariate Cox hazard analysis revealed that a higher sLVP rate was associated with a good prognosis (pâ¯<â¯0.001). CONCLUSIONS: sLVP was associated with CRT response, and a higher sLVP rate (â§59.4â¯%) was important for good prognosis in patients with aCRT.
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Terapia de Ressincronização Cardíaca , Insuficiência Cardíaca , Humanos , Masculino , Terapia de Ressincronização Cardíaca/métodos , Feminino , Pessoa de Meia-Idade , Idoso , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/fisiopatologia , Algoritmos , Resultado do Tratamento , Ventrículos do Coração/fisiopatologia , Estudos Retrospectivos , Curva ROC , SeguimentosRESUMO
Biological membranes consist of integral and peripheral protein-associated lipid bilayers. Although constituent lipids vary among cells, membrane lipids are mainly classified as phospholipids, glycolipids, and sterols. Phospholipids are further divided into glycerophospholipids and sphingophospholipids, whereas glycolipids are further classified as glyceroglycolipids and sphingoglycolipids. Both glycerophospholipids and glyceroglycolipids contain diacylglycerol as the common backbone, but their head groups differ. Most glycerolipids have polar head groups containing phosphate esters or sugar moieties. However, trace components termed glycero-glycophospholipids, each possessing both a phosphate ester and a sugar moiety, exist in membranes. Recently, the unique biological activities of glycero-glycophospholipids have attracted considerable attention. In this review, we describe the structure, distribution, function, biosynthesis, and chemical synthetic approaches of representative glycero-glycophospholipids-phosphatidylglucoside (PtdGlc) and enterobacterial common antigen (ECA). In addition, we introduce our recent studies on the rare glycero-glyco"pyrophospho"lipid, membrane protein integrase (MPIase), which is involved in protein translocation across biomembranes.
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Membrane protein integrase (MPIase), an endogenous glycolipid in Escherichia coli (E. coli) membranes, is essential for membrane protein insertion in E. coli. We have examined Sec-independent membrane protein insertion mechanisms facilitated by MPIase using physicochemical analytical techniques, namely solid-state nuclear magnetic resonance, fluorescence measurements, and surface plasmon resonance. In this review, we outline the physicochemical characteristics of membranes that may affect membrane insertion of proteins. Subsequently, we introduce our results verifying the effects of membrane lipids on insertion and estimate the impact of MPIase. Although MPIase is a minor component of E. coli membranes, it regulates insertion by altering the physicochemical properties of the membrane. In addition, MPIase promotes insertion by interacting with substrate proteins. We propose comprehensive mechanisms for the membrane insertion of proteins involving MPIase, which provide a physicochemical basis for understanding the roles of glycolipids in protein translocation.
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The process of protein transport across membranes involves a variety of factors and has been extensively investigated. Traditionally, proteinaceous translocons and chaperones have been recognized as crucial factors in this process. However, recent studies have highlighted the significant roles played by lipids and a glycolipid present in biological membranes in membrane protein transport. Membrane lipids can influence transport efficiency by altering the physicochemical properties of membranes. Notably, our studies have revealed that diacylglycerol (DAG) attenuates mobility in the membrane core region, leading to a dramatic suppression of membrane protein integration. Conversely, a glycolipid in Escherichia coli inner membranes, named membrane protein integrase (MPIase), enhances integration not only through the alteration of membrane properties but also via direct interactions with membrane proteins. This review explores the mechanisms of membrane protein integration mediated by membrane lipids, specifically DAG, and MPIase. Our results, along with the employed physicochemical analysis methods such as fluorescence measurements, nuclear magnetic resonance, surface plasmon resonance, and docking simulation, are presented to elucidate these mechanisms.
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Membrana Celular , Escherichia coli , Glicolipídeos , Transporte Proteico , Glicolipídeos/metabolismo , Glicolipídeos/química , Escherichia coli/metabolismo , Membrana Celular/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Membrana/química , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/química , Diglicerídeos/metabolismo , Diglicerídeos/químicaRESUMO
BACKGROUND: Conflicting data are available on whether ventricular arrhythmia (VA) or shock therapy increases mortality. Although cardiac resynchronization therapy (CRT) reduces the risk of VA, little is known about the prognostic value of VA among patients with CRT devices. OBJECTIVES: The purpose of this study was to evaluate the implications of VA as a prognostic marker for CRT. METHODS: We investigated 330 CRT patients within 1 year after CRT device implantation. The primary endpoint was the composite endpoint of all-cause death or hospitalization for heart failure. RESULTS: Forty-three patients had VA events. These patients had a significantly higher risk of the primary endpoint, even among CRT responders (P = .009). Fast VA compared to slow VA was associated with an increased risk of the primary endpoint (hazard ratio [HR] 2.14; 95% confidence interval [CI] 1.06-4.34; P = .035). Shock therapy was not associated with a primary endpoint (shock therapy vs antitachycardia pacing: HR 1.49; 95% CI 0.73-3.03; P = .269). The patients with VA had a lower prevalence of response to CRT (23 [53%] vs 202 [70%]; P = .031) and longer left ventricular paced conduction time (174 ± 23 ms vs 143 ± 36 ms; P = .003) than the patients without VA. CONCLUSION: VA occurrence within 1 year was related to paced electrical delay and poor response to CRT. VA could be associated with poor prognosis among CRT patients.
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Terapia de Ressincronização Cardíaca , Insuficiência Cardíaca , Humanos , Terapia de Ressincronização Cardíaca/efeitos adversos , Resultado do Tratamento , Arritmias Cardíacas/terapia , PrognósticoRESUMO
This study aimed to investigate the association between hypertensive disorders of pregnancy (HDP) and subsequent risk of dementia using a systematic review and meta-analysis of cohort studies. We searched PubMed and Scopus for eligible studies that investigated the association between HDP and dementia risk. Using the random-effects model, pooled hazard ratio (HR) and 95% confidence interval (CI) of dementia risk in women with HDP were calculated. We applied the I2 statistic to measure heterogeneity across studies and the test for funnel plot asymmetry to evaluate publication bias. Six cohort studies were eligible: three from the United States, two from Sweden, and one from Denmark. When combined, HDP was associated with the risk of dementia: pooled HR (95% CI) = 1.31 (1.12, 1.53). The heterogeneity across studies was moderate (I2 = 47.3%, p-heterogeneity = 0.091), but no signs of publication bias were detected. The association of HDP with vascular dementia was stronger than that with Alzheimer's disease: pooled HRs (95% CIs) = 1.66 (1.13, 2.43) and 1.29 (0.97, 1.72), respectively. In conclusion, HDP was associated with a higher risk of dementia and this association was more prominent with vascular dementia.
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Doença de Alzheimer , Demência Vascular , Hipertensão Induzida pela Gravidez , Pré-Eclâmpsia , Gravidez , Humanos , Feminino , Hipertensão Induzida pela Gravidez/epidemiologia , Estudos de CoortesRESUMO
Background: Although the dynamic changes of atrial natriuretic peptide (ANP) expressions in a failing heart are well-documented, the clinical implications of detailed measurements of each ANP molecular form processed from proANP remain unclear. Methods: Patients screening was conducted on patients who were eligible for cardiac resynchronization therapy (CRT) between 2014 and 2019 in our institution. Blood samples and echocardiographic parameters were collected on the day before and six months after implantation. Total ANP, proANP, and N-terminal fragment of proANP (NT-proANP) were examined as predictive biomarkers for cardiac death, left ventricular assist device implantation, and heart failure hospitalization following CRT implantation. Results: A total of 86 subjects (mean age 70 years, 64 males) who underwent successful CRT implantation were enrolled. Plasma levels of total ANP, proANP, and NT-proANP were not normally distributed [25.8 pM (interquartile range: 11.1-53.1), 2.2 pM (1.0-5.4), and 4.1 nM (2.4-7.1), respectively]. Over a median follow-up of 2.7 years, 31 patients (2 deaths and 29 heart failure hospitalizations) reached the endpoints. Among the different ANP forms, only NT-proANP emerged as an independent predictor of the composite outcome (adjusted odds ratio of 2.542 in those with levels above vs. below the median, 95 % confidence interval 1.151-5.615, p = 0.021). NT-proANP levels were associated with left atrial volume and left diastolic functional parameters and decreased in response to echocardiographic improvements at six months post-implantation (16 ± 44 % decrease in responders vs 18 ± 60 % increase in non-responders, p = 0.005). Conclusion: Pre-implantation NT-proANP levels could serve as a predictive factor for clinical outcomes in recipients of CRT.
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Introduction: Cardiac implantable electronic devices are used in patients with cardiac rhythm disorders. Computed tomography irradiation is not prohibited for patients with cardiac implantable electronic devices, despite adverse events being reported. Hence, appropriate preparation and knowledge are required before computed tomography irradiation can be carried out in these patients. Since there is limited knowledge or literature about the influence of computed tomography irradiation in cases with recent cardiac implantable electronic devices, we aimed to evaluate the adverse events and elucidate the necessary and sufficient safety measures associated with this therapy. Methods and Results: We placed cardiac implantable electronic devices on an anthropomorphic phantom model and observed their electrical activity in electrograms, while various protocols of computed tomography irradiation were implemented and adverse events evaluated. Oversensing with pauses of up to 3.2 s was observed in standard computed tomography protocols, but ventricular tachyarrhythmia or other clinically significant events could not be confirmed. Oversensing with pauses of up to 8.0 s was observed and ventricular tachyarrhythmia was detected in the maximum-dose protocols. However, treatments such as antitachycardia pacing or shock therapy for ventricular tachyarrhythmia were not observed because of their absence. Conclusion: Computed tomography irradiation for patients using cardiac implantable electronic devices is highly unlikely to cause clinically significant adverse events with the device settings and computed tomography protocols currently being used. Changing or monitoring the device settings routinely before computed tomography irradiation is not necessarily required for most patients.
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Steviol glycosides obtained from Stevia rebaudiana leaves are increasingly used in the food industry as natural low-calorie sweeteners. Among them, the sweetness of major glycosides composed of glucose residues (e.g., stevioside and rebaudioside A) has been widely studied. However, the properties of minor natural products containing rhamnose or xylose residues are poorly investigated. In this study, five unreported steviol glycosides containing rhamnose or xylose were extracted from our developing stevia leaves, and their sweetness was evaluated. The highly glycosylated steviol glycosides were identified, and their structures were examined by fragmentation analysis using mass spectrometry. Chemical synthesis of these glycosides confirmed their structures and allowed sensory evaluation of minor steviol glycosides. Our study revealed that a xylose-containing glycoside, rebaudioside FX1, exhibits a well-balanced sweetness, and thus, it is a promising candidate for natural sweeteners used in the food industry.
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Diterpenos do Tipo Caurano , Stevia , Stevia/química , Ramnose , Xilose , Diterpenos do Tipo Caurano/química , Glicosídeos/química , Edulcorantes/química , Folhas de Planta/químicaRESUMO
We aimed to develop a platform to rapidly investigate the responses of agonists and antagonists to G-protein-coupled receptors (GPCRs) using native mass spectrometry (MS). We successfully observed the ligand-bound human ß2 adrenergic receptor (hß2AR); however, it was challenging to quantitatively discuss drug efficacy from MS data alone. Since ligand-bound GPCRs are stabilized by the Gα subunit of G proteins on the membrane, mini-Gs and nanobody80 (Nb80) that can mimic the Gα interface of the GPCR were utilized. Ternary complexes of hß2AR, ligand, and mini-Gs or Nb80 were prepared and subjected to native MS. We found a strong correlation between the hß2AR-mini-Gs or -Nb80 complex ratio observed in the mass spectra and agonist/antagonist efficacy obtained using a cell-based assay. This method does not require radioisotope labeling and would be applicable to the analysis of other GPCRs, facilitating the characterization of candidate compounds as GPCR agonists and antagonists.
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INTRODUCTION: Infection is one of the most important complications associated with cardiac implantable electronic device (CIED) therapy. The number of reports comparing the outcomes of transvenous lead extraction (TLE), surgical lead extraction, and conservative treatment for CIED infections using a real-world database is limited. This study investigated the association between the treatment strategies for CIED infections and their outcomes. METHODS: We performed a retrospective analysis of 3605 patients with CIED infections admitted to 681 hospitals using a nationwide claim-based database collected between April 2012 and March 2018. RESULTS: We divided the 3605 patients into TLE (n = 938 [26%]), surgical lead extraction (n = 182 [5.0%]), and conservative treatment (n = 2485 [69%]) groups. TLE was performed more frequently in younger patients and at larger hospitals (p for trend < .001 for both). The rate of TLE increased during the study period, whereas that of surgical lead extraction decreased (p for trend < .001 for both). TLE was associated with lower in-hospital mortality (vs. surgical lead extraction: odds ratio [OR], 0.20; 95% CI, 0.06-0.70; vs. conservative treatment: OR, 0.45; 95% CI: 0.22-0.94) and lower 30-day readmission rates (vs. surgical lead extraction: OR, 0.18; 95% CI: 0.06-0.56; vs. conservative treatment: OR, 0.06; 95% CI, 0.03-0.13) in propensity score-weighted analyses. CONCLUSIONS: Only 26% of patients hospitalized for CIED infections received TLE. TLE was associated with significantly lower in-hospital mortality and 30-day recurrence rates than surgical lead extraction and conservative treatment, suggesting that TLE should be more widely recommended as a first-line treatment for CIED infections.
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Desfibriladores Implantáveis , Cardiopatias , Marca-Passo Artificial , Humanos , Desfibriladores Implantáveis/efeitos adversos , Marca-Passo Artificial/efeitos adversos , Tratamento Conservador , Estudos Retrospectivos , Pontuação de Propensão , Remoção de Dispositivo , Resultado do TratamentoRESUMO
OBJECTIVE: Hormonal changes during menopause can disturb serum cholesterol which is closely associated with cardiovascular disease. This study investigated the prospective association between serum cholesterol and heart failure (HF) risk in postmenopausal women. METHODS: We analyzed data from 1,307 Japanese women, aged 55 to 94 years. All women had no history of HF, and their baseline brain natriuretic peptide (BNP) levels were less than 100 pg/mL. During the follow-ups conducted every 2 years, HF was diagnosed among women who developed BNP of 100 pg/mL or greater. Cox proportional hazard models were applied to calculate hazard ratios and 95% CI of HF for women per their baseline total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (HDL-C) levels. The Cox regression models were adjusted for age, body mass index, smoking, alcohol drinking, hypertension, diabetes, cardiac murmurs, arrhythmia, stroke or ischemic heart disease, chronic kidney disease, and lipid-lowering agent use. RESULTS: Within an 8-year median follow-up, 153 participants developed HF. In the multivariable-adjusted model, women with total cholesterol of 240 mg/dL or greater (compared with 160-199 mg/dL) and HDL-C of 100 mg/dL or greater (compared with 50-59 mg/dL) showed an increased risk of HF: hazard ratios (95% CI) = 1.70 (1.04-2.77) and 2.70 (1.10-6.64), respectively. The results remained significant after further adjusting for baseline BNP. No associations were observed with low-density lipoprotein cholesterol. CONCLUSIONS: Total cholesterol of 240 mg/dL or greater and HDL-C of 100 mg/dL or greater were positively associated with the risk of HF in postmenopausal Japanese women.
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Insuficiência Cardíaca , Peptídeo Natriurético Encefálico , Humanos , Feminino , Triglicerídeos , Pós-Menopausa , Estudos Prospectivos , Fatores de Risco , Insuficiência Cardíaca/epidemiologia , HDL-Colesterol , LDL-ColesterolRESUMO
BACKGROUND: High percent ventricular pacing maximizes cardiac resynchronization therapy (CRT) response. An effective CRT algorithm classifies each left ventricular (LV) pace as effective or ineffective on the basis of the detection of QS or QS-r morphology on the electrogram; however, the relationship between percent effective CRT pacing (%e-CRT) and responses is unclear. OBJECTIVE: We aimed to clarify the association between %e-CRT and clinical outcomes. METHODS: Of the 136 consecutive CRT patients, 49 using the adaptive and effective CRT algorithm with percent ventricular pacing > 90% were evaluated. The primary and secondary outcomes were heart failure (HF) hospitalization and prevalence of CRT responders, defined as patients with an improvement in LV ejection fraction of ≥10% or a reduction in LV end-systolic volume of ≥15% after CRT device implantation, respectively. RESULTS: We divided the patients into the effective group (n = 25) and the less effective group (n = 24) by the median value of %e-CRT (97.4% [93.7%-98.3%]). During the median follow-up period of 507 days (interquartile range 335-730 days), the effective group had a significantly lower risk of HF hospitalization than the less effective group as revealed by Kaplan-Meier analysis (log-rank, P = .016). Univariate analysis revealed %e-CRT ≥ 97.4% (hazard ratio 0.12; 95% confidence interval 0.01-0.95; P = .045) as a predictor of HF hospitalization. The effective group had a higher prevalence of CRT responders than the less effective group (23 [92%] vs 9 [38%]; P < .001). Univariate analysis revealed that %e-CRT ≥ 97.4% (odds ratio 19.20; 95% confidence interval 3.63-101.00; P < .001) was a predictor of CRT response. CONCLUSION: High %e-CRT is associated with high CRT responder prevalence and low HF hospitalization risk.
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Terapia de Ressincronização Cardíaca , Insuficiência Cardíaca , Humanos , Resultado do Tratamento , Dispositivos de Terapia de Ressincronização Cardíaca , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , AlgoritmosRESUMO
BACKGROUND: Alcohol consumption is a modifiable lifestyle, but its role in heart failure (HF) development is controversial. Herein, we investigated the prospective association between alcohol consumption and HF risk. METHODS: A total of 2,712 participants (1,149 men and 1,563 women) from the Suita Study were followed up every two years. Cox regression was applied to calculate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of HF risk for heavy drinking (≥46 g/day in men or ≥23 g/day in women) and never drinking compared to light drinking (<23 g/day in men or <11.5 g/day in women). Then, we combined the results of the Suita Study with those from other eligible prospective cohort studies in a meta-analysis using the random-effects model. RESULTS: In the Suita Study, within a median follow-up period of 8 years, 319 HF cases (162 in men and 157 in women) were detected. In men, but not women, never and heavy drinking carried a higher risk of HF than light drinking: HRs (95% CIs) = 1.65 (1.00, 2.73) and 2.14 (1.26, 3.66), respectively. Alike, the meta-analysis showed a higher risk of HF among heavy drinkers: HR (95% CI) = 1.37 (1.15, 1.62) and abstainers: HR (95% CI) = 1.18 (1.02, 1.37). CONCLUSION: We indicated a J-shaped association between alcohol consumption and HF risk among Japanese men. The results of the meta-analysis came in line with the Suita Study. Heavy-drinking men should be targeted for lifestyle modification interventions.
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Consumo de Bebidas Alcoólicas , Insuficiência Cardíaca , Masculino , Humanos , Fatores de Risco , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Estudos Prospectivos , Modelos de Riscos Proporcionais , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/etiologiaRESUMO
Background: Implantable cardiac monitors (ICMs) help investigate the cause of unexplained syncope, but the probability and predictors of needing a pacing device thereafter remain unclear. Methods: We retrospectively analyzed the data of patients who received ICM insertion for unexplained syncope with suspected arrhythmic etiology. The data were obtained from a nationwide database obtained between April 1, 2012 and March 31, 2020. Multivariable mixed-effects survival analysis was performed to identify predictors of pacing device implantation (PDI), and a risk score model was developed accordingly. Results: In total, 2905 patients (age: 72 years [range: 60-78]) implanted with ICMs to investigate the cause of syncope were analyzed. During the median follow-up period of 128 days (range: 68-209) days, 473 patients (16%) underwent PDI. Older age, history of atrial fibrillation, bundle branch block (BBB), and diabetes were independent predictors of PDI in multivariable analysis. A risk score model was developed with scores ranging from 0 to 32 points. When patients with the lowest quartile score (0-13 points) were used as a reference, those with higher quartiles had a higher risk of PDI (second quartile: 14-15 points, hazard ratio [HR]: 3.86, 95% confidence interval [CI]: 2.62-5.68; third quartile: 16-18 points, HR: 4.67, 95% CI: 3.14-6.94; fourth quartile: 19-32 points, HR: 6.59, 95% CI: 4.47-9.71). Conclusions: The 4 identified predictors are easily assessed during the initial evaluation of patients with syncope. They may help identify patients with a higher risk of requiring permanent PDI.
Contexte: Les moniteurs cardiaques implantables (MCI) aident à déterminer la cause d'une syncope inexpliquée, mais la probabilité et les facteurs prédictifs du besoin d'un dispositif de stimulation cardiaque par la suite demeurent incertains. Méthodologie: Nous avons analysé de façon rétrospective les données de patients s'étant fait implanter un MCI après une syncope inexpliquée et chez lesquels une étiologie d'arythmie était soupçonnée. Les données proviennent d'une base de données nationale et s'étendent du 1er avril 2012 au 31 mars 2020. Une analyse de survie multivariable à effets mixtes a été effectuée pour cibler les facteurs prédictifs de l'implantation d'un dispositif de stimulation cardiaque (IDSC), et un modèle de score de risque a été conçu en conséquence. Résultats: Au total, les cas de 2905 patients (âge : 72 ans [écart interquartile (ÉI) : 60-78]) ayant reçu un MCI pour déterminer la cause de la syncope ont été analysés. Durant la période de suivi médiane de 128 jours (ÉI : 68-209), 473 patients (16 %) ont subi une IDSC. L'âge avancé, les antécédents de fibrillation auriculaire, le bloc de branche et le diabète étaient des facteurs prédictifs indépendants de l'IDSC dans l'analyse multivariable. Un modèle de score de risque a été conçu, les scores allant de 0 à 32 points. Lorsque les patients ayant un score dans le quartile inférieur (0 à 13 points) étaient utilisés à titre de référence, ceux ayant un score dans les quartiles supérieurs avaient un risque plus élevé d'IDSC (deuxième quartile : 14-15 points, rapport des risques instantanés [RRI] : 3,86, intervalle de confiance [IC] à 95 % de 2,62 à 5,68; troisième quartile : 16-18 points, RRI : 4,67, IC à 95 % de 3,14 à 6,94; quatrième quartile : 19-32 points, RRI : 6,59, IC à 95 % de 4,47 à 9,71). Conclusions: Les quatre facteurs prédictifs ciblés sont faciles à évaluer durant l'évaluation initiale des patients ayant subi une syncope. Ils peuvent aider à repérer les patients présentant un risque plus élevé d'avoir besoin d'un dispositif de stimulation cardiaque permanent.
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MPIase is a glycolipid involved in membrane protein integration in the inner membrane of Escherichia coli. To overcome the trace amounts and heterogeneity of natural MPIase, we systematically synthesized MPIase analogs. Structure-activity relationship studies revealed the contribution of distinctive functional groups and the effect of the MPIase glycan length on membrane protein integration activity. In addition, both the synergistic effects of these analogs with the membrane chaperone/insertase YidC, and the chaperone-like activity of the phosphorylated glycan were observed. These results verified the translocon-independent membrane integration mechanism in the inner membrane of E. coli, in which MPIase captures the highly hydrophobic nascent proteins via its characteristic functional groups, prevents protein aggregation, attracts the proteins to the membrane surface, and delivers them to YidC in order to regenerate its own integration activity.