Clinical significance of B cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) in acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

proliferation. We evaluated the correlation between serum concentration of BAFF or APRIL and severity of acute graft-versus-host disease (GVHD). METHODS: Fifteen patients who received allogeneic hematopoietic stem transplantation for leukemia and developed acute GVHD were enrolled. We determined serum concentrations of BAFF and APRIL at the onset of the first clinical manifestation of GVHD by enzyme-linked immunosorbent assay. RESULTS: Nine patients had grade 2 acute GVHD, and 6 had grade 3-4 acute GVHD. The BAFF serum concentration was higher in patients with grade 3-4 acute GVHD (1,093.42 in grade 2 vs. 2,171.99 pg/mL in grade 3-4), although the difference was not significant (P=0.077). However, the ratio of BAFF serum concentration to absolute lymphocyte count (ALC) (BAFF/ALC) was significantly higher in patients with grade 3-4 acute GVHD (P=0.045). The APRIL serum concentration and APRIL/ALC ratio showed similar results (P=0.077 and P=0.013, respectively). CONCLUSION: Patients with grade 3-4 acute GVHD had higher BAFF/ALC and APRIL/ALC ratios than patients with grade 2 acute GVHD. These findings suggest that B cells might play an important role in the development of acute GVHD, and that the BAFF and APRIL concentrations in serum might be significant predictive factors for estimating the severity of acute GVHD. Their clinical significance should be further evaluated in a larger patient populationope

Formyl-methionine as an N-degron of a eukaryotic N-end rule pathway

In bacteria, nascent proteins bear the pretranslationally generated N-terminal (Nt) formyl-methionine (fMet) residue. Nt-fMet of bacterial proteins is a degradation signal, termed fMet/N-degron. In contrast, proteins synthesized by cytosolic ribosomes of eukaryotes were presumed to bear unformylated Nt-Met. Here we found that the yeast formyltransferase Fmt1, although imported into mitochondria, could also produce Nt-formylated proteins in the cytosol. Nt-formylated proteins were strongly up-regulated in stationary phase or upon starvation for specific amino acids. This up-regulation strictly required the Gcn2 kinase, which phosphorylates Fmt1 and mediates its retention in the cytosol. We also found that the Nt-fMet residues of Nt-formylated proteins act as fMet/N-degrons, and identified the Psh1 ubiquitin ligase as the recognition component of this eukaryotic fMet/N-end rule pathway, which destroys Nt-formylated proteins

Impact of glycemic control on the progression of aortic stenosis: a single-center cohort study using a common data model

Background Diabetes mellitus (DM) is a well-established risk factor for the progression of degenerative aortic stenosis (AS). However, no study has investigated the impact of glycemic control on the rate of AS progression. We aimed to assess the association between the degree of glycemic control and the AS progression, using an electronic health record-based common data model (CDM). Methods We identified patients with mild AS (aortic valve [AV] maximal velocity [Vpeak] 2.0–3.0 m/sec) or moderate AS (Vpeak 3.0–4.0 m/sec) at baseline, and follow-up echocardiography performed at an interval of ≥ 6 months, using the CDM of a tertiary hospital database. Patients were divided into 3 groups: no DM (n = 1,027), well-controlled DM (mean glycated hemoglobin [HbA1c] < 7.0% during the study period; n = 193), and poorly controlled DM (mean HbA1c ≥ 7.0% during the study period; n = 144). The primary outcome was the AS progression rate, calculated as the annualized change in the Vpeak (△Vpeak/year). Results Among the total study population (n = 1,364), the median age was 74 (IQR 65–80) years, 47% were male, the median HbA1c was 6.1% (IQR 5.6–6.9), and the median Vpeak was 2.5 m/sec (IQR 2.2–2.9). During follow-up (median 18.4 months), 16.1% of the 1,031 patients with mild AS at baseline progressed to moderate AS, and 1.8% progressed to severe AS. Among the 333 patients with moderate AS, 36.3% progressed to severe AS. The mean HbA1c level during follow-up showed a positive relationship with the AS progression rate (β = 2.620; 95% confidence interval [CI] 0.732–4.507; p = 0.007); a 1%-unit increase in HbA1c was associated with a 27% higher risk of accelerated AS progression defined as △Vpeak/year values > 0.2 m/sec/year (adjusted OR = 1.267 per 1%-unit increase in HbA1c; 95% CI 1.106–1.453; p < 0.001), and HbA1c ≥ 7.0% was significantly associated with an accelerated AS progression (adjusted odds ratio = 1.524; 95% CI 1.010–2.285; p = 0.043). This association between the degree of glycemic control and AS progression rate was observed regardless of the baseline AS severity. Conclusion In patients with mild to moderate AS, the presence of DM, as well as the degree of glycemic control, is significantly associated with accelerated AS progression

Endoscopic Removal of Inflated Transected Sengstaken–Blakemore Tube Using Endoscopic Scissors

Balloon tamponade using Sengstaken–Blakemore (SB) tube is employed as a bridging therapy in cases in which endoscopic therapy fails to control esophageal variceal bleeding. Although SB tube insertion can lead to successful hemostasis, it is accompanied by numerous complications, with SB tube transection being one of the rarest complications. A 53-year-old man with liver cirrhosis and hepatocellular carcinoma presented with massive esophageal variceal bleeding. Therapeutic endoscopic variceal ligation failed, and SB tube was inserted. The SB tube was unexpectedly disconnected because of the patient’s irritability due to hepatic encephalopathy. The esophageal and gastric balloon of the SB tube remained inflated in the stomach. Whereas the use of other endoscopic instruments was ineffective, endoscopic removal was successfully accomplished using endoscopic scissors. In conclusion, we detected SB tube transection in a patient with hepatic encephalopathy and removed remnants of the inflated tube using endoscopic scissors

Controlling Ferromagnetic Easy Axis in a Layered MoS2 Single Crystal

We report the effective methods to induce weak ferromagnetism in pristine MoS2 persisting up to room temperature with the improved transport property, which would lead to new spintronics devices. The hydrogenation of MoS2 by heating at 300 degrees C for 1 h leads to the easy axis out of plane, while the irradiation of proton with a dose of 1 x 10(13) P/cm(2) leads to the easy axis in plane. The theoretical modeling supports such magnetic easy axes.open16

Impact of successful restoration of sinus rhythm in patients with atrial fibrillation and acute heart failure: Results from the Korean Acute Heart Failure registry

Background: Restoring and maintaining sinus rhythm (SR) in patients with atrial fibrillation (AF) failed to show superior outcomes over rate control strategies in prior randomized trials. However, there is sparse data on their outcomes in patients with acute heart failure (AHF).Methods: From December 2010 to February 2014, 5,625 patients with AHF from 10 tertiary hospitals were enrolled in the Korean Acute Heart Failure registry, including 1,961 patients whose initial electrocardiogram showed AF. Clinical outcomes of patients who restored SR by pharmacological or electrical cardioversion (SR conversion group, n = 212) were compared to those of patients who showed a persistent AF rhythm (AF persistent group, n = 1,662).Results: All-cause mortality both in-hospital and during the follow-up (median 2.5 years) were significantly lower in the SR conversion group than in the AF persistent group after adjustment for risk factors (adjusted hazard ratio [HR]; 95% confidence interval [CI] = 0.26 [0.08–0.88], p = 0.031 and 0.59 [0.43–0.82], p = 0.002, for mortality in-hospital and during follow-up, respectively). After 1:3 propensity score matching (SR conversion group = 167, AF persistent group = 501), successful restoration of SR was associated with lower all-cause mortality (HR [95% CI] = 0.68 [0.49–0.93], p = 0.015), heart failure rehospitalization (HR [95% CI] = 0.66 [0.45–0.97], p = 0.032), and composite of death and heart failure rehospitalization (HR [95% CI] = 0.66 [0.51–0.86], p = 0.002).Conclusions: Patients with AHF and AF had significantly lower mortality in-hospital and during follow-up if rhythm treatment for AF was successful, underscoring the importance of restoring SR in patients with AHF

Controlling ferromagnetic easy axis in a layered MoS2 single crystal

We report the effective methods to induce weak ferromagnetism in pristine MoS2 persisting up to room temperature with the improved transport property, which would lead to new spintronics devices. The hydrogenation of MoS2 by heating at 300 degrees C for 1 h leads to the easy axis out of plane, while the irradiation of proton with a dose of 1 x 10(13) P/cm(2) leads to the easy axis in plane. The theoretical modeling supports such magnetic easy axes.open116160Nsciescopu