Genome instability can drive aging in many organisms. The ribosomal RNA gene (rDNA) cluster is one of the most unstable regions in the genome and the stability of this region impacts replicative ...lifespan in budding yeast. To understand the underlying mechanism, we search for yeast mutants with stabler rDNA and longer lifespans than wild-type cells. We show that absence of a transcription elongation factor, Spt4, results in increased rDNA stability, reduced levels of non-coding RNA transcripts from the regulatory E-pro promoter in the rDNA, and extended replicative lifespan in a SIR2-dependent manner. Spt4-dependent lifespan restriction is abolished in the absence of non-coding RNA transcription at the E-pro locus. The amount of Spt4 increases and its function becomes more important as cells age. These findings suggest that Spt4 is a promising aging factor that accelerates cellular senescence through rDNA instability driven by non-coding RNA transcription.
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•Identification of candidate senescence factors that act by altering rDNA stability•Spt4 induces rDNA instability by promoting non-coding RNA transcription in the rDNA•Spt4-mediated rDNA destabilization accelerates cellular senescence•The function of Spt4 becomes more important as cells age
In budding yeast, rDNA stability can impact cellular senescence. Yokoyama et al. report that the transcription elongation factor Spt4 activates transcription of non-coding RNA in the rDNA, which induces rDNA instability and accelerates cellular senescence.
Background
Mesopancreas excision in pancreatoduodenectomy is technically complicated because of the anatomical complexity of the mesopancreas with the inferior peripancreatic blood vessels which is ...caused by intestinal rotation in fetal life. We have developed a novel artery-first approach (the intestinal derotation procedure) for facilitating mesopancreas excision. The aim of this study was to clarify the vascular anatomy of the mesopancreas after derotation.
Methods
The right-sided colon and small intestine are mobilized from the retroperitoneum, and the intestinal loop is then derotated. In 136 cases of pancreatoduodenectomy employing the derotation procedure, we analyzed the vascular anatomy of the mesopancreas.
Results
After derotation, the anatomy was simplified. The mesopancreas extended from the right aspect of the superior mesenteric artery (SMA), forming a horizontal plane. The first jejunal trunk (FJT) was situated in parallel with the second jejunal artery and was anterior (91%) or posterior (9%) to the SMA. The inferior pancreaticoduodenal vein (IPDV) entered the right side of the FJT (83%) or the superior mesenteric vein (17%). Besides the IPDV, 1–4 tributaries entered the right wall of the FJT, in 89% of cases. The inferior pancreaticoduodenal artery was observed to originate from the right wall of the SMA, sharing a common stem with the first jejunal artery (70%) or branching directly from the SMA (29%).
Conclusions
Intestinal derotation simplifies the mesopancreas anatomy and reveals the anatomical details of the inferior peripancreatic blood vessels in pancreatoduodenectomy.
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.
While phrenic nerve palsy (PNP) due to cryoballoon pulmonary vein isolation (PVI) of atrial fibrillation (AF) was transient in most cases, no studies have reported the results of the long-term ...follow-up of PNP. This study aimed to summarize details and the results of long-term follow-up of PNP after cryoballoon ablation. A total of 511 consecutive AF patients who underwent cryoballoon ablation was included. During right-side PVI, the diaphragmatic compound motor action potential (CMAP) was reduced in 46 (9.0%) patients and PNP occurred in 29 (5.7%) patients (during right-superior PVI in 20 patients and right-inferior PVI in 9 patients). PNP occurred despite the absence of CMAP reduction in 0.6%. The PV anatomy, freezing parameters and the operator's proficiency were not predictors of PNP. While PNP during RSPVI persisted more than 4 years in 3 (0.6%) patients, all PNP occurred during RIPVI recovered until one year after the ablation. However, there was no significant difference in the recovery duration from PNP between PNP during RSPVI and RIPVI. PNP occurred during cryoballoon ablation in 5.7%. While most patients recovered from PNP within one year after the ablation, PNP during RSPVI persisted more than 4 years in 0.6% of patients.
The optimal ablation strategy for persistent atrial fibrillation (PsAF) remains to be defined. We sought to compare very long-term outcomes between linear ablation and electrogram (EGM)-guided ...ablation for PsAF. In a retrospective analysis, long-term arrhythmia-free survival compared between two propensity-score matched cohorts, one with pulmonary vein isolation (PVI) and linear ablation including roof/mitral isthmus line (LINE-group, n = 52) and one with PVI and EGM-guided ablation (EGM-group; n = 52). Overall, 99% of patients underwent successful PVI. Complete block following linear ablation was achieved for 94% of roof lines and 81% of mitral lines (both lines blocked in 75%). AF termination by EGM-guided ablation was accomplished in 40% of patients. Non-PV foci were targeted in 7 (13%) in the LINE-group and 5 (10%) patients in the EGM-group (p = 0.76). During 100 ± 28 months of follow-up, linear ablation was associated with superior arrhythmia-free survival after the initial and last procedure (1.8 ± 0.9 procedures) compared with EGM-group (Logrank test: p = 0.0001 and p = 0.045, respectively). In multivariable analysis, longer AF duration and EGM-guided ablation remained as independent predictors of atrial arrhythmia recurrence. Linear ablation might be a more effective complementary technique to PVI than EGM-guided ablation for PsAF ablation.
Background: Pulmonary vein stenosis (PVS) after PV isolation (PVI) for atrial fibrillation (AF) is a severe complication that requires angioplasty. This study aimed to compare the reduction of the ...cross-sectional PV area (PVA) and the incidence of PVS after cryoballoon (CB)-PVI, hot balloon (HB)-PVI, or laser balloon (LB)-PVI.Methods and Results: A total of 320 patients who underwent an initial catheter ablation procedure for AF using a CB, HB, or LB in 2 hospitals were included. They underwent contrast-enhanced multidetector CT before and 3 months after the procedure. In all 4 PVs, the reduction in PVA was more significant in the LB group than in the CB or HB groups, respectively. Moderate (50–75%) and severe (>75%) PVS were observed in 5.3% and 0.5% of the PVs, respectively. Although moderate PVS was more frequently observed in the LB group than in the CB or HB groups (8.2%, 3.8%, and 5.0%; P=0.03), the incidence of severe PVS was similar in the LB, CB, and HB groups (0.3%, 0.5%, and 1.0%; P=0.46). Symptomatic PVS requiring intervention occurred in 1 (0.3%) patient.Conclusions: Although the reduction in cross-sectional PVA and the incidence of moderate PVS after LB-PVI was more significant than after CB-PVI or HB-PVI, it rarely led to severe PVS. Symptomatic PVS requiring intervention was rare after the balloon ablation of AF.
The “pre-freezing” technique was a method in which a fully inflated balloon after the start of freezing was pressed against the pulmonary vein (PV) during cryoballoon ablation and has been applied ...especially in large-size PVs. Of 556 patients who underwent cryoballoon ablation for atrial fibrillation (AF), the pre-freezing technique was applied to 48 patients. The resulting 2:1 propensity score-matched data set included 120 patients. Using the pre-freezing technique, all left-superior PVs, all left-inferior PVs, and 95% of right-superior PVs were successfully isolated. In most right-inferior PVs, complete sealing using the pre-freezing technique was challenging, and this technique was not applied. Procedure time was similar between the two groups. In the pre-freezing group, the percentage of the left atrial posterior wall isolated was larger (47.6 ± 10.3 vs. 42.8 ± 15.7%,
P
= 0.006), and the postoperative reduction of diaphragmatic compound motor action potentials tended to occur less frequently (2.5 vs. 12.5%,
P
= 0.07), and the reduction of the cross-sectional LSPV area was smaller (17.5 ± 12.2 vs. 27.2 ± 19.8%,
P
= 0.03) than the conventional group. The AF-free rate of the two groups was similar between the two groups (
P
= 0.15). The pre-freezing technique was a simple method that can isolate a wider surface area during cryoballoon PV isolation. While the postoperative AF recurrence was comparable, the postoperative reduction in the cross-sectional PV area was less than that of the conventional method, which may reduce the risk of PV stenosis.
The aims of the present study are to clarify the changes in clinicopathologic features, diagnosis and treatment for hepatolithiasis, and propose an appropriate management strategy in Japan. The ...research group conducted nationwide surveys seven times in the past over a period of 40 years. Furthermore, a cohort was followed up in 2010. We analyzed the clinical features, diagnosis tools, treatment procedures, outcomes, and predictive factors for cholangiocarcinoma. Surgery was the primary method for hepatolithiasis up to 1998, and the frequency of its use has decreased since then. In 2011, 66.7% of hepatolithiasis patients were treated using nonsurgical approaches. In addition, endoscopic retrograde cholangiography (ERC) with stone extraction was the most frequently performed procedure (22.7%). However, the incidences of residual stone and recurrent stone after ERC with stone extraction were higher than those after percutaneous transhepatic cholangioscopic lithotomy and surgery. Bile duct stricture and dilatation during follow up were significant risk factors for stone recurrences. In the cohort study, stone removal only and age >65 years were significant factors for the development of cholangiocarcinoma. In patients without a history of cholangioenterostomy, left‐lobe‐type stones were a risk factor, and hepatectomy reduced the risk of the development of cholangiocarcinoma significantly. Nonsurgical treatment may be performed as the first‐line treatment for hepatolithiasis. Surgery should be performed on patients who were treated incompletely after nonsurgical treatment. However, hepatectomy may be recommended for patients with left‐lobe‐type stones and without a history of cholangioenterostomy.
A series of 2‐methylpyrimidine skeleton‐based electron‐transporting derivatives (BPyMPM) are designed and synthesized to investigate the influence of substituted pyridine rings on the physical ...properties and electron mobilities (μe). The only structural difference is the position of substituted pyridine rings. The melting point (Tm) of B4PyMPM is estimated to be ca. 50 °C higher than that of B3PyMPM, and ca. 120 °C higher than that of B2PyMPM. The ionization potential is observed to increase in the order B2PyMPM (6.62 eV) < B3PyMPM (6.97 eV) < B4PyMPM (7.30 eV), measured using ultraviolet photoelectron spectroscopy. Furthermore, time‐of‐fight measurements of vacuum‐deposited films demonstrate that the μe at 298 K of B4PyMPM is 10 times higher than that of B3PyMPM and 100 times higher than that of B2PyMPM. To extract the charge transport parameters, the temperature and field dependencies of μe are investigated. Using Bässler's disorder formalism, the degree of energetic disorder is estimated to decrease in the order B2PyMPM (91 meV) > B3PyMPM (88 meV) > B4PyMPM (76 meV), and the positional disorder is 2.7 for B2PyMPM, and < 1.5 for B3PyMPM and B4PyMPM.
The influence of substituted pyridine rings on the physical properties and electron mobilities (μe) of 2‐methylpyrimidine skeleton‐based electron‐transporters is investigated. Although the structural difference is very small, the difference in μe is found to be quite large. At 298 K, the μe of B4PyMPM is measured to be 10 times higher than that of B3PyMPM and 100 times higher than that of B2PyMPM.
Although antiarrhythmic drugs have long been used for the suppression of various types of arrhythmias, their prior use before the onset of ventricular arrhythmia with hemodynamic collapse and the ...effect on prognosis is not well known. Data from 1004 consecutive patients with cardiovascular shock in the Japanese Circulation Society’s Shock Registry were analyzed. Eighty-four cases of ventricular arrhythmia-induced shock and ROSC (return of spontaneous circulation) were divided into the prior amiodarone or β-blockers use group (Aβ group,
n
= 27) and the non-amiodarone and non-β-blockers use group (non-Aβ group;
n
= 57) based on treatment before the onset of those arrhythmias. Clinical outcomes related to hemodynamic collapse such as OHCA (out-of-hospital cardiovascular arrest) was less in the Aβ group Aβ group, 11/26 (42%) vs. non-Aβ group, 41/56 (73%);
p
= 0.007. Similarly, syncope was less common in the Aβ group than in the non-Aβ group Aβ group 4/27 (15%) vs. non-Aβ group 27/57 (47%);
p
= 0.004. Furthermore, prior amiodarone or β-blockers use before the onset of ventricular arrhythmias was strongly associated with both survival at discharge (odds ratio 3.19; 95% confidence interval 1.06–9.67;
p
= 0.040) and neurological outcomes at discharge (odds ratio 3.96; 95% confidence interval 1.32–11.85;
p
= 0.014) based on multivariate logistic regression analysis. Prior amiodarone or β-blockers use before the onset of malignant ventricular arrhythmia and maintaining appropriate blood concentrations in advance is associated with a good survival rate and better neurological outcomes after recovery from ventricular arrhythmia with hemodynamic collapse.
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