Structure, Dynamics and Functional Implications of the Eukaryotic Vault Complex.

Vault ribonucleoprotein particles are naturally designed nanocages, widely found in the eukaryotic kingdom. Vaults consist of 78 copies of the major vault protein (MVP) that are organized in 2 symmetrical cup-shaped halves, of an approximate size of 70x40x40 nm, leaving a huge internal cavity which accommodates the vault poly(ADP-ribose) polymerase (vPARP), the telomerase-associated protein-1 (TEP1) and some small untranslated RNAs. Diverse hypotheses have been developed on possible functions of vaults, based on their unique capsular structure, their rapid movements and the distinct subcellular localization of the particles, implicating transport of cargo, but they are all pending confirmation. Vault particles also possess many attributes that can be exploited in nanobiotechnology, particularly in the creation of vehicles for the delivery of multiple molecular cargoes. Here we review what is known about the structure and dynamics of the vault complex and discuss a possible mechanism for the vault opening process. The recent findings in the characterization of the vaults in cells and in its natural microenvironment will be also discussed.

P-wave characteristics as electrocardiographic markers of atrial abnormality in prediction of incident atrial fibrillation - The Malmö Preventive Project.

BACKGROUND: P-wave indices reflect atrial abnormalities contributing to atrial fibrillation (AF). We aimed to assess a comprehensive set of P-wave characteristics for prediction of incident AF in a population-based setting. METHODS: Malmö Preventative Project (MPP) participants were reexamined in 2002-2006 with electrocardiographic (ECG) and echocardiographic examinations and followed for 5 years. AF-free subjects (n = 983, age 70 ± 5 years, 38% females) with sinus rhythm ECGs were included in the study. ECGs were digitally processed using the Glasgow algorithm. P-wave duration, axis, dispersion, P-terminal force in lead V1 and interatrial block (IAB) were evaluated. ECG risk score combining the morphology, voltage and length of P-wave (MVP score) was calculated. New-onset diagnoses of AF were obtained from nation-wide registers. RESULTS: During follow up, 66 patients (7%) developed AF. After adjustment for age and gender, the independent predictors of AF were abnormal P-wave axis > 75° (HR 1.63 CI95% 1.95-11.03) and MVP score 4 (HR 6.17 CI 95% 1.76-21.64), both correlated with LA area: Person r - 0.146, p < 0.001 and 0.192, p < 0.001 respectively. Advanced IAB (aIAB) with biphasic P-wave morphology in leads III and aVF was the most prevalent variant of aIAB and predicted AF in a univariate model (HR 2.59 CI 95% 1.02-6.58). CONCLUSION: P-wave frontal axis and MVP score are ECG-based AF predictors in the population-based cohort. Our study provides estimates for prevalence and prognostic importance of different variants of aIAB, providing a support to use biphasic P-wave morphology in lead aVF as the basis for aIAB definition.

Comparison between oral dydrogesterone versus micronized vaginal progesterone gel in clinical outcome within the first HRT-FET cycle: a retrospective analysis.

OBJECTIVE: The purpose of this study is to compare the clinical efficacy of oral dydrogesterone and micronized vaginal progesterone (MVP) gel during the first HRT-FET cycle. METHODS: A retrospective cohort study based on a total of 344 women undergoing their first HRT-FET cycles without Gonadotropin-Releasing Hormone agonist (GnRH-a) pretreatment was conducted. All the cycles were allocated to two groups in the reproductive medical center at the University of Hong Kong-Shenzhen Hospital. One group (n = 193) received oral dydrogesterone 30 mg/d before embryo transfer, while the other group (n = 151) received MVP gel 180 mg/d. RESULTS: The demographics and baseline characteristics of two groups were comparable. We found no statistically significant difference in live birth rate (24.35% vs. 31.13%, P = 0.16), clinical pregnancy rate (34.72% vs. 36.42%, P = 0.74), embryo implantation rate (25.09% vs. 28.36%, P = 0.43), positive pregnancy rate (42.49% vs 38.41%, P = 0.45), miscarriage rate (9.33% vs 3.97%, P = 0.05), or ectopic pregnancy rate (0.52% vs. 0.66%, P = 0.86) between the oral dydrogesterone group and MVP gel group. In the multivariate logistic regression analysis for covariates, medication used for luteal support was not associated with live birth rate (OR = 0.73, 95% CI: 0.32-1.57, P = 0.45). And the different luteal support medication did not have a significant positive association with the live birth rate in the cycles with day 2 embryo transferred (OR = 1.39, 95% CI:0.66-2.39, P = 0.39) and blastocyst transferred (OR = 1.31 95% CI:0.64-2.69, P = 0.46). CONCLUSION: 30 mg/d oral dydrogesterone and 180 mg/d MVP gel revealed similar reproductive outcomes in HRT-FET cycles in the study.

[MVP Risk score and new atrial fibrillation diagnosis: Prospective cohort PREFATE study]. / MVP Risk score y nuevo diagnóstico de fibrilación auricular: estudio de cohorte prospectivo PREFATE.

OBJECTIVE: To assess the association between electrocardiogram (ECG) patterns according to the MVP ECG risk score (morphology-voltage-P-wave duration) and a diagnosis of Atrial Fibrillation (AF). DESIGN: Prospective observational cohort study (1/01/2023-31/12/2024). SITE: Primary care. PARTICIPANTS: Randomized sample of 150 patients aged 65-85 years without prior diagnosis of AF, stroke, or current anticoagulant treatment; high risk of future AF; CHA2DS2-VASc ≥2; and ability to use the FibricheckR application (App). MEASUREMENTS: At baseline, a standard ECG, MVP risk score assessment, and cardiac rhythm monitoring for 15 days using the FibricheckR App were performed. The dependent variables were the presence of P-wave patterns on the electrocardiogram according to MVP risk score and a new diagnosis of AF. RESULTS: The diagnosis of AF was confirmed in 14 cases (9.3%, 95% CI 5.6-15.1), 3 men and 11 women. In 3 cases, the arrhythmia was diagnosed on the baseline ECG, and in 11 cases by Holter after being reported as possible AF by the FibricheckR App. A higher prevalence of atypical advanced interatrial block (A-AIB) (p 0.007) was detected among participants with AF, as well as the prevalence of P-wave <0.1mV. (p=0.006). All new diagnoses of AF were made at scores ≥4 in the MVP risk score. CONCLUSIONS: Using scales for identifying ECG patterns in high-risk subjects in primary care can facilitate the diagnosis of unknown AF.

Same-day discharge following catheter ablation and venous closure with VASCADE MVP: A postmarket registry.

INTRODUCTION: Early and safe ambulation can facilitate same-day discharge (SDD) following catheter ablation, which can reduce resource utilization and healthcare costs and improve patient satisfaction. This study evaluated procedure success and safety of the VASCADE MVP venous vascular closure system in patients with atrial fibrillation (AF). METHODS: The AMBULATE SDD Registry is a two-stage series of postmarket studies in patients with paroxysmal or persistent AF undergoing catheter ablation followed by femoral venous access-site closure with VASCADE MVP. Efficacy endpoints included SDD success, defined as the proportion of patients discharged the same day who did not require next-day hospital intervention for procedure/access site-related complications, and access site sustained success within 15 days of the procedure. RESULTS: Overall, 354 patients were included in the pooled study population, 151 (42.7%) treated for paroxysmal AF and 203 (57.3%) for persistent AF. SDD was achieved in 323 patients (91.2%) and, of these, 320 (99.1%) did not require subsequent hospital intervention based on all study performance outcomes. Nearly all patients (350 of 354; 98.9%) achieved total study success, with no subsequent hospital intervention required. No major access-site complications were recorded. Patients who had SDD were more likely to report procedure satisfaction than patients who stayed overnight. CONCLUSION: In this study, 99.7% of patients achieving SDD required no additional hospital intervention for access site-related complications during follow-up. SDD appears feasible and safe for eligible patients after catheter ablation for paroxysmal or persistent AF in which the VASCADE MVP is used for venous access-site closure.

Pitfalls of mitral regurgitation assessment in the presence of mitral valve prolapse.

Adequate grading of mitral regurgitation (MR) in patients with mitral valve prolapse (MVP) in the presence of mid-late systolic jets can represent a major challenge. In this entity, jets are commonly overestimated by echocardiography. Correct quantification is crucial and highly relevant for the further management and prognosis of these oftentimes young patients. This case points out potential pitfalls and underlines the importance to systematically include qualitative, quantitative, and semi-quantitative parameters into the echocardiographic assessment.

Increased incidence of mitral valve prolapse in children with pectus chest wall deformity.

BACKGROUND: Pectus anomalies constitute 95% of chest anomalies. Pectus carinatum (PC) and excavatum (PE) are often asymptomatic in childhood. However, symptoms and signs such as chest pain, dyspnea, and mitral valve prolapse (MVP) can be seen in pectus anomalies. Demographic characteristics and accompanying cardiac signs in children with pectus deformity were investigated. METHODS: In this study, the clinical findings for children with pectus deformity, and the incidence of MVP and other concomitant heart diseases detected in echocardiographic examinations were evaluated. RESULTS: Eighty-two children with PE, 27 with PC, and 107 healthy children were included in this study. In the echocardiographic examination of PE, PC patients, and healthy children, MVP was detected with frequencies of 25%, 33%, and 2% respectively. CONCLUSIONS: The study showed that pectus anomalies were associated with an increased incidence of MVP. All patients with pectus deformity should therefore undergo a screening echocardiogram in adolescence to assess for the presence of MVP.

Successful Use of Neurovascular Plug for Embolization of Scalp Arteriovenous Fistula: A Novel Technique.

PURPOSE: We report a case of a pediatric patient developing a delayed-onset scalp arteriovenous fistula (AVF) and pseudoaneurysm managed with a new technique. TECHNIQUE: A 10-year-old boy presented to the outpatient clinic complaining of a growing pulsatile mass in the right side of the skull after head trauma 6 months ago. He had no neurological deficits. Imaging studies revealed scalp AVF with pseudoaneurysm. The arterial feeding was from the right temporal artery, while the blood was drained into the superior sagittal sinus and the facial vein. The fistula was occluded successfully by a microvascular plug (MVP). Follow-up angiography 1 year later showed that the AVF was no longer seen with complete embolization of pseudoaneurysm, total occlusion of the abnormal vessels, and the absence of MVP migration. CONCLUSION: To the best of our knowledge, we report the first case of successfully using MVP to treat scalp AVF. The MVP is a novel technique with its unique ability to achieve rapid, safe, effective, and permanent vascular occlusion through a single device. Besides, the possibility of delayed-onset traumatic vascular injuries should be considered in a patient with head or facial trauma.

Analysis of Multiple Drug Resistance Mechanism in Different Types of Soft Tissue Sarcomas: Assessment of the Expression of ABC-Transporters, MVP, YB-1, and Analysis of Their Correlation with Chemosensitivity of Cancer Cells.

Chemotherapy of soft tissue sarcomas (STS) is restricted by low chemosensitivity and multiple drug resistance (MDR). The purpose of our study was the analysis of MDR mechanism in different types of STS. We assessed the expression of ABC-transporters, MVP, YB-1, and analyzed their correlation with chemosensitivity of cancer cells. STS specimens were obtained from 70 patients without metastatic disease (2018-2020). Expression level of MDR-associated genes was estimated by qRT-PCR and cytofluorimetry. Mutations in ABC-transporter genes were captured by exome sequencing. Chemosensitivity (SI) of STS to doxorubicin (Dox), ifosfamide (Ifo), gemcitabine (Gem), and docetaxel (Doc) was analyzed in vitro. We found strong correlation in ABCB1, ABCC1, and ABCG2 expression. We demonstrated strong negative correlations in ABCB1 and ABCG2 expression with SI (Doc) and SI (Doc + Gem), and positive correlation of MVP expression with SI (Doc) and SI (Doc + Gem) in undifferentiated pleomorphic sarcoma. Pgp expression was shown in 5 out of 44 STS samples with prevalence of synovial sarcoma relapses and it is strongly correlated with SI (Gem). Mutations in MDR-associated genes were rarely found. Overall, STS demonstrated high heterogeneity in chemosensitivity that makes reasonable in vitro chemosensitivity testing to improve personalized STS therapy, and classic ABC-transporters are not obviously involved in MDR appearance.

A case of variant parachute mitral valve associated with mitral annular disjunction arrhythmic syndrome.

Parachute mitral valve (PMV) is a rare congenital cardiac valvular anomaly often associated with other congenital cardiac defects, particularly Shone's complex, but may infrequently occur in isolation. PMV and its variants are predominantly associated with mitral stenosis (MS) or rarely mitral regurgitation (MR). We present the case of a middle-aged female who was evaluated for a syncopal episode and found to have an atypical variant PMV with disproportionately long anterior mitral leaflet, bileaflet mitral valve prolapse, and mitral annular disjunction, without associated MS or MR. This is the first case report to highlight this particular constellation of findings.

The usefulness of morphology-voltage-P wave duration ECG score for predicting early left atrial dysfunction in hypertensive patients.

OBJECTIVE: Left atrial (LA) function is an important predictor of adverse cardiovascular outcomes in patients with hypertension (HT). Therefore, recognition of subtle LA dysfunction in the early stages of HT is essential for controlling modifiable variables. Several electrocardiographic and echocardiographic parameters have been studied to show early LA dysfunction. The goal of this study was to investigate the relationship between newly defined morphology-voltage-P wave duration electrocardiography (MVP ECG) score and early LA dysfunction in hypertensive patients. MATERIALS AND METHODS: Eighty-nine hypertensive patients were included in this study. Based on speckle tracking echocardiography results, the patients were divided into two groups: 67 patients with normal LA function were included in Group 1, and 22 patients with abnormal LA function in Group 2. RESULTS: Age, diabetes mellitus history, duration of HT history, left ventricular mass index, E/Em, and MVP ECG score values were statistically significant between the two groups. Based on the results of the multivariate logistic regression test, duration of HT history, E/Em, and MVP ECG score were determined as independent predictive parameters for early LA dysfunction in hypertensive patients. CONCLUSION: In conclusion, MVP ECG score assessment could be a novel approach to detect early LA dysfunction in hypertensive patients.

MVP Expression Facilitates Tumor Cell Proliferation and Migration Supporting the Metastasis of Colorectal Cancer Cells.

Cancer cells show significant dysregulation of genes expression, which may favor their survival in the tumor environment. In this study, the cellular vault's components MVP (major vault protein), TEP1 (telomerase-associated protein 1) and vPARP (vault poly(ADP-ribose) polymerase) were transiently or completely inhibited in U2OS cells (human bone osteosarcoma epithelial cells) to evaluate their impact on the cell proliferative and migratory capacity as well as on the development of their resistance to the drug vinorelbine. Comparative analysis of MVP protein expression level in normal colon tissue, primary colorectal tumor, and metastasis showed that the expression of this protein does not increase significantly in the primary tumor, but its expression increases in metastatic cells. Further comparative molecular analysis using the whole transcriptome microarrays for MVP-positive and MVP-negative cells showed that MVP is involved in regulating proliferation and migration of cancer cells. MVP may facilitate metastasis of colon cancer due to its impact on cell migration. Moreover, two vault proteins, MVP and TEP1, contribute the resistance to vinorelbine, while vPARP does not.

Diminished distractor exclusion for magnocellular features near the hand.

The modulated visual pathway (MVP) hypothesis attempts to explain a range of differences observed in the processing of objects in the proximal as compared to the distal region of the hand. However, there has been no account of how 'hand proximity' interacts with task relevance within the MVP framework. In the present study, we used a visual search task to test whether the task relevance of a unique feature (motion in Expt. 1, and color in Expt. 2) influences its processing with respect to the hand. The feature was either relevant (Expt. 1a and 2a) or irrelevant (Expt. 1b and 2b) to the search task. The hand proximity effect was observed only in the experiments in which the unique feature was task irrelevant. However, the effect of hand proximity was overridden when the unique feature was predictive of the target location. We propose that it is difficult to accomplish active distractor rejection of magnocellular features near the hand. Similarly, there is improved active distractor rejection of parvocellular features in the distal region of the hand. Overall, the results suggest that processes involving active distractor rejection may drive the attentional effect of hand proximity.

Usefulness of Morphology-Voltage-P-wave duration (MVP) score as a predictor of atrial fibrillation recurrence after pulmonary vein isolation.

BACKGROUND: Atrial fibrillation (AF) is known to be the most common arrhythmia, and the successful rate of long-term ablation can vary comparatively. Therefore, a clinical scoring system to predict rhythm outcome remains a critical unmet need. The electrocardiographic (ECG) risk score which is named Morphology-Voltage-P-wave duration (MVP) score was reported to be useful for predicting new-onset AF. The goal of the current study was to investigate whether the MVP score was a useful scheme in the prediction of rhythm outcome following pulmonary vein isolation (PVI) in paroxysmal atrial fibrillation (PAF). METHODS: We retrospectively analyzed baseline characteristics, risk scores, and rates of AF recurrence 12 months postablation in the medical records of 207 consecutive patients with PAF undergoing PVI in General Hospital of Ningxia medical University from 2010 to 2018. RESULTS: Two hundred and seven patients (71 females, median age 58.7 years) with symptomatic PAF underwent PVI. From the cohort, 32.3% (67) had a recurrence of AF within 1 year of the PVI. The area of the MVP score under the curve in the receiver operating characteristics (ROC) analysis was 0.789 (95% CI 0.730-0.840, p < .001). A score cut-off value of >3 showed the best predictive ability for AF recurrence within 1 year after PVI, with sensitivity (53.03%) and specificity (89.87%). CONCLUSIONS: The results of our study suggest that the easy-to-measure ECG MVP score can be used to predict recurrence of PAF after PVI.

AV hysteresis causing initiation of recurrent atrial arrhythmias.

A 73-year-old male with dual-chamber implantable cardioverter defibrillator (Teligen, Boston Scientific, Marlborough, MA, USA) had multiple episodes of automatic mode switch (AMS) during clinical follow-up. Over 50% of these demonstrated a similar pattern of initiation. AV Search+ in combination with sensor rate pacing can cause short-coupled atrial paced intervals that can be proarrhythmic. After programming changes were made AMS burden has significantly decreased.

Edwardsiella ictaluri type III secretion system (T3SS) effector EseN is a phosphothreonine lyase that inactivates ERK1/2.

EseN is a type III secretion system (T3SS) effector that is encoded on the Edwardsiella ictaluri chromosome and is homologous to a family of T3SS effector proteins with phosphothreonine lyase (PTL) activity, including OspF from Shigella and SpvC from Salmonella. A yeast-2-hybrid system was used to identify the major vault protein (MVP) as a specific host-cell binding partner for EseN, and the proximity ligation assay (PLA) confirmed the interaction. Similar to other pathogens, E. ictaluri invasion activates extracellular signal-regulated kinases 1 and 2 (ERK1/2) early in the infection, which are subsequently inactivated by EseN. Structurally, EseN contains a highly conserved docking motif that is required for specific binding to mitogen-activated protein kinases, such as ERK1/2, and a motif that is essential for PTL activity. Immunoblotting and immunofluorescence analyses indicate that EseN inactivates ERK1/2 by dephosphorylation in vivo in the head kidney of infected fish and ex vivo in head kidney derived macrophages. Interaction of EseN with phosphorylated ERK1/2 (pERK1/2) was also confirmed using PLA, suggesting that MVP serves as a signaling scaffold for ERK1/2 and EseN. Channel catfish Ictalurus punctatus infected with E. ictaluri strains lacking the eseN gene had reduced numbers of E. ictaluri in the tissues following infection and reduced mortality compared to fish infected with the wild-type. Our results indicate that eseN encodes a PTL domain that interacts with MVP as a possible scaffold protein and inactivates pERK1/2 to ERK1/2, resulting in increased proliferation of E. ictaluri and, ultimately, death of the host.

Arterial embolizations with microvascular plug in extracranial and intracranial districts: technical results.

PURPOSE: A new detachable microvascular plug (MVP, Reverse Medical®, Irvine, CA, USA) has been recently developed; three models are available according to the size (MVP3-MVP5-MVP7). MVP3 and MVP5 are released through a 0.027″ microcatheter, MVP7 through a 4 Fr catheter. This series aims to describe an initial single-center experience examining intraprocedural safety and technical success of MVP. MATERIALS AND METHODS: Ten patients (mean age 55.1 years) have been treated for arterial embolization using MVP; eight extracranial and two intracranial arterial embolizations have been performed. The embolizations were because of: four bleedings, three aneurysms, two pseudoaneurysms, and one presurgical nephrectomy. RESULTS: MVP3 was used in five cases, MVP5 in four cases, and MVP 7 once. In all cases, the MVP was successfully released in < 1 min. In six patients, the MVP was the sole embolizing agent employed, while in four subjects, it was positioned complementary after coils. The technical and clinical success was obtained in 100%; hemorrhages were interrupted and aneurysms and pseudoaneurysms did not show recanalization at follow-up. CONCLUSIONS: MVP seems to be a safe embolizing device that interventional radiologists should consider when facing arterial embolization of both body and neuroarterial districts; the main advantage is related to MVP3 and MVP5 models that can be adopted for distal embolization thanks to the precise release through 0.027″ microcatheter.

Covidien micro vascular plug in congenital heart diseases and vascular anomalies: A new kid on the block for premature babies and older patients.

OBJECTIVES: To evaluate the safety, feasibility, and efficacy of the MVP™ microvascular plug(Covidien) for closure of vascular anomalies in patients with congenital heart diseases (CHD). BACKGROUND: The MVP™ is a novel device with PTFE integrated. The device has been recently introduced in the radiological field and reported exclusively for neurological anomalies. METHODS: All CHD patients receiving the device from April 2015 until July 2015 were included in the study and followed up clinically as well as by transthoracic echocardiography. Standard safety and follow-up such as vascular complications, embolization rate, and residual shunting were assessed. RESULTS: Twelve patients with a median age of 2.6-years (0.03-12.6 years) and a mean weight of 13 kg (2.8-34.2 kg) were included. Devices were delivered from the femoral artery in 10 and from the femoral vein in 2 patients. Devices were used for closure of patent ductus arteriosus (PDA) closure (n = 5), aorto-pulmonary collaterals or Blalock-Taussig shunt (n = 5), veno-venous fistula (n = 1), and coronary fistula (n = 1). One device was retrieved before release due to inappropriate size estimation (PDA spasm). The PDA was successfully closed using a PDA device (Lifetech, Medtronic). Immediate angiographic evaluation showed minimal or no shunt in 90% (10/11 patients) and 100% occlusion rate after a mean follow-up of 3.2-months. There was no device embolization, hemolysis, or any other complication following closure. CONCLUSIONS: The delivery of new MVP™ micro vascular plug system (Covidien) is safe and effective in patients with CHD for closure of a variety of vascular abnormalities. The low profile of the device and the sheathless nature of the procedure make it particularly interesting for PDA closure in premature babies. © 2016 Wiley Periodicals, Inc.

Functional atrial undersensing associated with device algorithm promoting AV conduction.

A 58-year-old woman received a dual chamber pacemaker (Medtronic) for sick sinus syndrome. Given intact AV conduction the Managed Ventricular Pacing mode algorithm (MVP) was programmed. The day after, she suffered from palpitations. Her ECG showed a possible loss of atrial capture accompanied by atrial undersensing. Telemetry-supported pacemaker control confirmed the loss of capture. Undersensing of atrial signal was functional, related to long atrial refractory period in MVP mode algorithm. Device algorithms could induce false suspicions. Awareness about the different pacing algorithms can be useful in order to avoid erroneous interpretations and to correct potential malfunctioning.