Coexistence of a Classical Nodoventricular Accessory Pathway With a Left-Sided Mahaim Accessory Pathway.

The coexistence of 2 Mahaim pathways represents a diagnostic challenge. We present a case in which the SH/HA intervals were useful for identifying concealed nodoventricular or His-ventricular pathways.

Nanoscrolls of Janus Monolayer Transition Metal Dichalcogenides.

Tubular structures of transition metal dichalcogenides (TMDCs) have attracted attention in recent years due to their emergent physical properties, such as the giant bulk photovoltaic effect and chirality-dependent superconductivity. To understand and control these properties, it is highly desirable to develop a sophisticated method to fabricate TMDC tubular structures with smaller diameters and a more uniform crystalline orientation. For this purpose, the rolling up of TMDC monolayers into nanoscrolls is an attractive approach to fabricating such a tubular structure. However, the symmetric atomic arrangement of a monolayer TMDC generally makes its tubular structure energetically unstable due to considerable lattice strain in curved monolayers. Here, we report the fabrication of narrow nanoscrolls by using Janus TMDC monolayers, which have an out-of-plane asymmetric structure. Janus WSSe and MoSSe monolayers were prepared by the plasma-assisted surface atom substitution of WSe2 and MoSe2 monolayers, respectively, and then were rolled by solution treatment. The multilayer tubular structures of Janus nanoscrolls were revealed by scanning transmission electron microscopy observations. Atomic resolution elemental analysis confirmed that the Janus monolayers were rolled up with the Se-side surface on the outside. We found that the present nanoscrolls have the smallest diameter of about 5 nm, which is almost the same as the value predicted by the DFT calculation. The difference in work functions between the S- and Se-side surfaces was measured by Kelvin probe force microscopy, which is in good agreement with the theoretical prediction. Strong interlayer interactions and anisotropic optical responses of the Janus nanoscrolls were also revealed by Raman and photoluminescence spectroscopy.

pCO2 decrement through alkalinity enhancement and biological production in a shallow-water ecosystem constructed using steelmaking slag.

Ocean-based carbon dioxide removal has gained immense attention as a countermeasure against climate change. The enhancement of ocean alkalinity and the creation of new blue carbon ecosystems are considered effective approaches for this. To evaluate the function of steelmaking slag from the viewpoints of CO2 reduction and creation of new blue carbon ecosystems, we conducted a comparative experiment using two mesocosms that replicated tidal-flats and shallow-water ecosystems. Initially, approximately 20 seagrasses (Zostera marina) were transplanted into the shallow-water area in the mesocosm tanks. The use of steelmaking slag is expected to increase the pH by releasing calcium and mitigate turbidity by solidifying dredged soil. In the experimental tank, where dredged soil and steelmaking slag were utilized as bed materials, the pH remained higher throughout the experimental period compared with the control tank, which utilized only dredged soil. As a result, pCO2 remained consistently lower in the experimental tank due to mainly its alkaline effect (March 2019: -10 ± 6 µatm, September 2019: -130 ± 47 µatm). The light environment in the control tank deteriorated due to high turbidity, whereas the turbidity in the experimental tank remained low throughout the year. The number of seagrass shoots in the experimental tank was consistently approximately 20, which was higher than that in the control tank. Additionally, more seaweed and benthic algae were observed in the experimental tank, indicating that it was more conducive to the growth of primary producers. In conclusion, tidal-flat and shallow-water ecosystems constructed using dredged soil and steelmaking slag are expected to enhance CO2 uptake and provide a habitat for primary producers that is superior to those constructed using dredged soil only.

Structural Diversity of Single-Walled Transition Metal Dichalcogenide Nanotubes Grown via Template Reaction.

Monolayers of transition metal dichalcogenides (TMDs) are an ideal 2D platform for studying a wide variety of electronic properties and potential applications due to their chemical diversity. Similarly, single-walled TMD nanotubes (SW-TMDNTs)-seamless cylinders of rolled-up TMD monolayers-are 1D materials that can exhibit tunable electronic properties depending on both their chirality and composition. However, much less has been explored about their geometrical structures and chemical variations due to their instability under ambient conditions. Here, the structural diversity of SW-TMDNTs templated by boron nitride nanotubes (BNNTs) is reported. The outer surfaces and inner cavities of the BNNTs promote and stabilize the coaxial growth of SW-TMDNTs with various diameters, including few-nanometers-wide species. The chiral indices (n,m) of individual SW-MoS2 NTs are assigned by high-resolution transmission electron microscopy, and statistical analyses reveals a broad chirality distribution ranging from zigzag to armchair configurations. Furthermore, this methodology can be applied to the synthesis of various TMDNTs, such as selenides and alloyed Mo1- x Wx S2 . Comprehensive microscopic and spectroscopic analyses also suggest the partial formation of Janus MoS2(1- x ) Se2 x nanotubes. The BNNT-templated reaction provides a universal platform to characterize the chirality-dependent properties of 1D nanotubes with various electronic structures.

Abrupt increased serum creatinine in a hyperferritinemia patient treated with deferoxamine after cord blood transplantation: a case report with literature review.

BACKGROUND: Erythrocyte transfusion is an indispensable component of supportive care after hematopoietic stem cell transplantation (HSCT). However, HSCT recipients are susceptible to the development of acute kidney injury (AKI) with multifactorial causes. We report a case of a rapid elevation in serum creatinine associated with deferoxamine after cord blood transplantation (CBT). CASE PRESENTATION: A 36-year-old Japanese male diagnosed with relapsed Philadelphia-positive acute lymphoblastic leukemia received CBT. At day 88 post-CBT, multidrug-resistant Pseudomonas aeruginosa (MDRP) was isolated from urine culture. Subsequently, colistin 200 mg/day was administered parenterally for treatment of epididymitis from day 91 to 117 post-CBT. Despite concomitant administration of potential nephrotoxic agents such as piperacillin-tazobactam, acyclovir, and liposomal amphotericin B, no development of AKI was observed during this period. At day 127 post-CBT, MDRP was detected in blood and urine cultures, and colistin 200 mg/day was re-started parenterally. Due to extremely higher ferritin level, deferoxamine was administered intravenously at day 133 post-CBT. While serum creatinine was 1.03 mg/dL before starting deferoxamine, the level increased to 1.36 mg/dL one day after commencing deferoxamine (day 134 post-CBT), and further increased to 2.11 mg/dL at day 141. Even though colistin was discontinued at day 141 post-CBT, serum creatinine continued to increase. Deferoxamine was withdrawn at day 145 post-CBT, when serum creatinine peaked at 2.70 mg/dL. In addition, no cylinduria is observed during the period of development of AKI. In adverse drug reaction (ADR) assessment using Naranjo probability score, the scores of 3 in deferoxamine and 2 in colistin, respectively, indicated "possible" ADR. However, while colistin-associated AKI manifested early onset, recovery time within 2 weeks after discontinuation and development of cylinduria, this case was discordant with the properties. Furthermore, in the literature review, development of AKI within 1 day, including sudden increase in serum creatinine or abrupt reduction in urine volume, was reported in 3 identified cases. CONCLUSIONS: We considered the rapid creatinine elevation to be the result of deferoxamine rather than ADR caused by colistin. Therefore, careful monitoring of kidney function is required in recipients of HSCT treated with deferoxamine.

Is higher lymphocyte count a potential strategy for preventing chronic kidney disease in patients receiving long-term dasatinib treatment?

BACKGROUND: Dasatinib, which is used to treat treating chronic myeloid leukemia, induces increases in blood lymphocytes during the treatment. In addition, neutrophil-lymphocyte count ratio (NLR) is associated with the related to development of chronic kidney disease (CKD). However, it has not been reported whether development of CKD during long-term dasatinib treatment is related to lymphocyte count or NLR. This study aimed to reveal the relationship between CKD and lymphocyte count or NLR during long-term dasatinib treatment. METHODS: A retrospective study was conducted in patients treated with dasatinib for 6 months or longer. Risk factors for CKD development were explored using multivariate analysis. Changes in maximal lymphocyte count and NLR over time were examined separately. RESULTS: A total of 33 patients in CKD group (n = 8) and No CKD group (n = 25) who received dasatinib were enrolled. In univariate analysis, significant differences between the groups were observed in maximal lymphocyte count, lymphocytosis, age, and estimated glomerular filtration rate at baseline. As the factor independently associated with the development of CKD, maximal lymphocyte count (odds ratio 0.999, 95% confidence interval: 0.999-1.000, p = 0.033) was identified. In this analysis, age had borderline significance (odds ratio 1.073, 95% CI: 0.999-1.153, p = 0.054)]. After 6 months of dasatinib therapy, lymphocyte count was significantly lower in CKD group [median (range), 2184 (878‒3444)/µL] than in the No CKD group [3501 (966‒7888)/µL] (p = 0.020). However, no significant difference in lymphocyte count was observed between the groups at the last follow-up. During the study period, the median NLR in the No CKD group fluctuated between 1.11 and 1.42, and median NLR in CKD group was increased from 1.13 to 2.24 between after 6 months of dasatinib therapy and the last follow-up. CONCLUSIONS: The development of CKD during dasatinib therapy was associated with lower maximal lymphocyte counts. In contrast, the higher levels of lymphocytes induced during dasatinib treatment may prevent CKD progression.

Health Care Cost Analysis of PPI or P-CAB-First Treatment in Patients With Gastroesophageal Reflux Disease.

GOALS: The aim was to examine actual health care cost in patients with gastroesophageal reflux disease (GERD) who were initiated on proton pump inhibitor (PPI) or potassium-competitive acid blocker (P-CAB) as first-line therapy in Japanese real-world clinical settings. BACKGROUND: To date, cost-utility evaluation of acid-suppressants treatment in Japan has only been conducted by model analysis. STUDY: A cost utilization analysis was performed using a Japanese nationwide hospital-based claim database by extracting patients with GERD initiated on either PPI or P-CAB (242,102 pairs) and esomeprazole (EPZ) or P-CAB (241,825 pairs). Health care costs were compared in each comparison cohort with propensity-score matched pairs. The switching rates of initial acid-suppressants were also examined. RESULTS: Baseline characteristics were well-balanced after matching. The 3-year mean cumulative GERD-related and hospitalization costs per patient were ¥142,620 and ¥122,444 in PPI-first and P-CAB-first treatment groups, and ¥105,263 and ¥121,958 in EPZ-first and P-CAB-first treatment groups, respectively. Most hospitalization costs were non-GERD related in all the groups. The switching rates of PPI to P-CAB and P-CAB to PPI in 12 months were 7.5% and 20.2%, respectively. CONCLUSIONS: In this propensity-score matched analysis, health care cost was higher in patients with GERD initiated on PPI than in those initiated on P-CAB mainly owing to non-GERD-related hospitalization cost, whereas it was lower in those initiated on EPZ than in those initiated on P-CAB. When considering health care costs except hospitalization costs, PPI-first treatment was less expensive than P-CAB-first treatment. Low switching rate from PPI to P-CAB in the real-world practice may partially explain the discrepancy.

Fabrication of near-invisible solar cell with monolayer WS2.

Herein, we developed a near-invisible solar cell through a precise control of the contact barrier between an indium tin oxide (ITO) electrode and a monolayer tungsten disulfide (WS2), grown by chemical vapor deposition (CVD). The contact barrier between WS2 and ITO was controlled by coating various thin metals on top of ITO (Mx/ITO) and inserting a thin layer of WO3 between Mx/ITO and the monolayer WS2, which resulted in a drastic increase in the Schottky barrier height (up to 220 meV); this could increase the efficiency of the charge carrier separation in our Schottky-type solar cell. The power conversion efficiency (PCE) of the solar cell with the optimized electrode (WO3/Mx/ITO) was more than 1000 times that of a device using a normal ITO electrode. Large-scale fabrication of the solar cell was also investigated, which revealed that a simple size expansion with large WS2 crystals and parallel long electrodes could not improve the total power (PT) obtained from the complete device even with an increase in the device area; this can be explained by the percolation theory. This problem was addressed by reducing the aspect ratio (width/channel length) of the unit device structure to a value lower than a critical threshold. By repeating the experiments on this optimized unit device with an appropriate number of series and parallel connections, PT could be increased up to 420 pW from a 1-cm2 solar cell with a very high value (79%) of average visible transmission (AVT).

Clinical value of the HATCH score for predicting adverse outcomes in patients with heart failure.

The HATCH score is employed as a risk assessment tool for atrial fibrillation (AF) development. However, the impact of the HATCH score on the long-term adverse outcomes in patients with acute heart failure (AHF) remains unknown. We investigated the clinical value of the HATCH score in patients with AHF. From a multicenter AHF registry, we retrospectively evaluated 1543 consecutive patients who required hospitalization owing to AHF (median age, 78 [69-85] years; 42.3% women) from January 2012 to December 2019. These patients were divided into five risk groups based on their HATCH score at admission (scores 0, 1, 2, 3, and 4-7). The correlation between the HATCH score and the composite outcome, including all-cause mortality and re-hospitalization due to HF, was analyzed using Kaplan-Meier and Cox proportional-hazard analyses. The median HATCH score was 2 [1-3], and the median age was 78 years (69-85 years). During the follow-up period (median, 16.8 months), the composite endpoint occurred in 691 patients (44.8%), including 416 (27%) patients who died (with 65 [4.2%] in-hospitalization deaths) and 455 (29.5%) patients requiring re-hospitalizations due to HF. The Kaplan-Meier analysis showed a significant increase in the composite endpoint with an increasing HATCH score (log-rank, p < 0.001). The multivariate Cox regression model revealed that the HATCH score was an independent predictor of the composite endpoint (hazard ratio [HR] 1.181; 95% confidence interval [CI]: 1.111-1.255; p < 0.001) with all-cause mortality (HR 1.153, 95% CI 1.065-1.249; p < 0.001) and re-hospitalizations due to HF (HR 1.21; 95% CI 1.124-1.303; p < 0.001) in patients with AHF, regardless of the presence or absence of AF, ejection fraction, and etiology. The HATCH score is an independent predictor of adverse outcomes in patients with AHF.

Comparative study of fractional flow reserve and diastolic pressure ratio using a guidewire with a sensor for measuring intravascular pressure.

PURPOSE: This study aimed to evaluate the correlation and diagnostic agreement between diastolic pressure ratio (dPR) and fractional flow reserve (FFR) in a Japanese real-world setting. DESIGN: Prospective multicenter observational study. METHODS: This study included 100 patients with intermediate coronary artery stenosis at 4 Japanese hospitals. For these lesions, FFR and dPR were measured using a guidewire with a sensor and a monitor to measure intravascular pressure. The correlation and diagnostic agreement between FFR and dPR were assessed. When both FFR and dPR were negative or positive, the results were considered to be concordant. When one was positive and the other was negative, the result was regarded as discordant (positive discordance, FFR > 0.80 and dPR ≤ 0.89; negative discordance, FFR ≤ 0.80 and dPR > 0.89). RESULTS: Overall, the FFR and dPR were well-correlated (R = 0.841). FFR and dPR were concordant in 89% of cases (concordant normal, 43%; concordant abnormal, 46%) and discordant in 11% (positive discordance, 7%; negative discordance, 4%). No significant difference was observed in the rate of concordant results between patients with and without diabetes mellitus. The diagnostic concordance rate was significantly different among the 3 coronary arteries (right coronary artery, 93.3%; left anterior descending artery, 93.2%; and left circumflex artery, 58.3%; P = .001). Additionally, the rate of concordant results tended to be higher when using intravenous administration of adenosine than when using intracoronary bolus injection of nicorandil (adenosine, 95.1%; nicorandil, 84.7%; P = .103). CONCLUSION: We found that dPR was highly correlated with FFR, and diagnostic discordance was observed in 11% of the lesions. Several factors, including lesion location and medication for hyperemia, may cause the diagnostic discordance between dPR and FFR.

Non-classical nucleation in vapor-liquid-solid growth of monolayer WS2 revealed by in-situ monitoring chemical vapor deposition.

The very early nucleation stage of a transition metal dichalcogenide (TMD) was directly observed with in-situ monitoring of chemical vapor deposition and automated image analysis. Unique nucleation dynamics, such as very large critical nuclei and slow to rapid growth transitions, were observed during the vapor-liquid-solid (VLS) growth of monolayer tungsten disulfide (WS2). This can be explained by two-step nucleation, also known as non-classical nucleation, in which metastable clusters are formed through the aggregation of droplets. Subsequently, nucleation of solid WS2 takes place inside the metastable cluster. Furthermore, the detailed nucleation dynamics was systematically investigated from a thermodynamic point of view, revealing that the incubation time of metastable cluster formation follows the traditional time-temperature transformation diagram. Quantitative phase field simulation, combined with Bayesian inference, was conducted to extract quantitative information on the growth dynamics and crystal anisotropy from in-situ images. A clear transition in growth dynamics and crystal anisotropy between the slow and rapid growth phases was quantitatively verified. This observation supports the existence of two-step nucleation in the VLS growth of WS2. Such detailed understanding of TMD nucleation dynamics can be useful for achieving perfect structure control of TMDs.

Reliability and validity of D-dimer monitoring for pulmonary thromboembolism in patients with unresectable, advanced or recurrent colorectal cancer treated with bevacizumab.

Pulmonary thromboembolism (PTE) is one of the leading causes of death among cancer outpatients. The aim of the present study was to investigate the reliability and validity of D-dimer monitoring for PTE in patients with unresectable, advanced or recurrent colorectal cancer treated with bevacizumab. A total of 25 patients with advanced colorectal cancer who received bevacizumab combination chemotherapy as primary treatment were retrospectively reviewed. The selection criteria included that D-dimer tests were performed repetitively, and that chest and abdominal contrast-enhanced CT scans were completed. The D-dimer levels and the presence or absence of PTE on CT images were retrospectively examined. Four cases (16%) were detected as having asymptomatic PTE. The D-dimer values at the onset of PTE were 14.2, 4.6, 1.1 and 0.9 µg/ml. The negative predictive value was 90.5% when 3.0 µg/ml was set as the D-dimer level cutoff value. The incidence of PTE, including asymptomatic PTE, in the present study was higher compared with that reported in previous studies on various types of cancer, of various stages and treated with different chemotherapy regimens. In patients with bevacizumab-treated unresectable, advanced or recurrent colorectal cancer, the D-dimer test was found to be less useful for exclusion diagnosis; however, along with chest CT, it may be useful in the detection and diagnosis of PTE. However, the determination of the optimal reference values and appropriate measurement timing of D-dimer testing requires further study.

Clinical impact of heart rate change in patients with acute heart failure in the early phase.

AIMS: Patients with acute heart failure (AHF) often present with an increased heart rate (HR), and the HR changes dramatically after initial treatment for AHF. However, the HR change after admission and the relationship between HR change in the early phase and prognosis have not been fully elucidated. METHODS AND RESULTS: From a multicentre AHF registry, we retrospectively evaluated 1527 consecutive patients admitted with AHF. HR change (%) was calculated by [HR (at admission) - HR (24 h after admission)] × 100∕HR (at admission). The median HR change was 15.1% (range, 2.0-28.4%). The HR decreased most in the first 24 h and then gradually thereafter [admission: 98 (81-117) b.p.m., 24 h: 80 (70-92) b.p.m., 48 h: 78 (68-90) b.p.m., and 72 h: 77 (67-88) b.p.m.]. In Kaplan-Meier analysis, the cumulative event-free rates in the composite endpoint of death and rehospitalization due to AHF showed better according to larger HR change (P = 0.012, log rank). Cox proportional hazards analysis showed that HR change was a prognostic factor for composite endpoint adjusted by age and sex [hazard ratio, 0.995; 95% confidence interval (CI), 0.991-0.998; P = 0.006]. HR change was associated with outcome adjusted by age and sex in patients with sinus rhythm (hazard ratio, 0.993; 95% CI, 0.988-0.999; P = 0.015), but not in patients with atrial fibrillation (hazard ratio, 0.996; 95% CI, 0.990-1.002; P = 0.15). CONCLUSIONS: A decrease in HR in the first 24 h after admission indicates better prognosis in patients with AHF, although the prognostic influence may differ between patients with sinus rhythm and those with atrial fibrillation.

Role of mitochondrial complex III/IV in the activation of transcription factor Rst2 in Schizosaccharomyces pombe.

Mitochondria play essential roles in eukaryotic cells for glucose metabolism to produce ATP. In Schizosaccharomyces pombe, transcription factor Rst2 can be activated upon glucose deprivation. However, the link between Rst2 and mitochondrial function remains elusive. Here, we monitored Rst2 transcriptional activity in living cells using a Renilla luciferase reporter system, and found that inhibition of mitochondrial complex III/IV caused cells to produce reactive oxygen species (ROS) and nitric oxide (NO), which in turn activated Rst2. Furthermore, Rst2-GFP was observed to translocate from cytoplasm to nucleus upon mitochondrial complex III/IV inhibitors treatment, and deletion of genes associated with complex III/IV resulted in delayed process of Rst2-GFP nuclear exportation under glucose-rich condition. In particular, we found that Rst2 was phosphorylated following the treatment of complex III/IV inhibitors or SNAP. Altogether, our findings suggest that mitochondrial complex III/IV participates in the activation of Rst2 through ROS and NO generation in Schizosaccharomyces pombe.

Prognostic value of leucine/phenylalanine ratio as an amino acid profile of heart failure.

Heart failure (HF) causes a hypercatabolic state that enhances the catabolic activity of branched-chain amino acids (BCAA; leucine, isoleucine, and valine) in the heart and skeletal muscles and reduces protein synthesis in the liver. Consequently, free plasma aromatic amino acids (AAA, tyrosine and phenylalanine) are increased. To date, we have reported the prognostic value of the BCAA/AAA ratio (Fischer's ratio) in patients with HF. However, the leucine/phenylalanine ratio, which is a simpler index than the Fischer's ratio, has not been examined. Therefore, the prognostic value of the leucine/phenylalanine ratio in patients with HF was investigated. Overall 157 consecutive patients hospitalized for worsening HF (81 men, median age 78 years) were enrolled in the study. Plasma amino acid levels were measured when the patients were stabilized at discharge. Cardiac events were defined as a composite of cardiac death and hospitalization for worsening HF. A total of 46 cardiac events occurred during the median follow-up period of 238 (interquartile range 93-365) days. The median leucine/phenylalanine ratio was significantly lower in patients with cardiac events than in those without cardiac events (1.4 vs. 1.8, P < 0.001). The best cutoff value of the leucine/phenylalanine ratio was determined as 1.7 in the receiver operating characteristic (ROC) curve for cardiac events. Following a Kaplan-Meier survival analysis, the low group (leucine/phenylalanine ratio < 1.7, n = 72) had more cardiac events than the high group (leucine/phenylalanine ratio ≥ 1.7, n = 85) (log-rank, P < 0.001). Multivariate Cox proportional hazards regression analysis showed that the leucine/phenylalanine ratio was an independent predictor of cardiac events. Furthermore, on comparing the prognostic values for cardiac events based on ROC curves of leucine levels, BCAA levels, Fischer's ratio, and leucine/phenylalanine ratio, the leucine/phenylalanine ratio was the most accurate in predicting future cardiac events (area under the curve 0.763,; sensitivity 0.783,; specificity 0.676,; P < 0.001). The leucine/phenylalanine ratio could be a useful predictor of future cardiac events in patients with HF, reflecting an imbalance in amino acid metabolism.

Evaluation Methods for the Measurement of Lower Leg Edema in Healthy Young Adults.

BACKGROUND: In recent years, objective quantitative evaluations have become particularly important. Both qualitative and quantitative evaluations are also available for edema. It is thought that the technical problem of quantitative evaluation can be solved by using a simple and reproducible method. Several studies have evaluated various methods for measuring edema. Limitations, such as weaknesses, measurement complexity, and errors, have been identified. Therefore, this study aimed to consider a simple and effective measurement method for the quantitative evaluation of edema. METHODS: This study was a prospective, observational study. The subjects were 15 healthy adults (2 male and 13 female). Measurements were performed on the subjects' right lower leg once in the morning and once in the afternoon, with a minimum interval of 4 hours. RESULTS: The actual volume of the lower leg was correlated with all indices except the ultrasonic echo findings for subcutaneous tissue. The intra-subject and inter-subject reliabilities for the indices using digital images were very high. The lower leg volume was greater significantly in the afternoon from the morning. CONCLUSION: The leg circumference was measured by utilizing a tape, while the width and volume were measured by utilizing digital imaging suitable for quantitatively evaluating edema. Furthermore, swelling of the lower leg with time can occur in the absence of daily exercise.

Prognostic Value of Delirium in Patients With Acute Heart Failure in the Intensive Care Unit.

BACKGROUND: Delirium is a common adverse event observed in patients admitted to the intensive care unit (ICU). However, the prognostic value of delirium and its determinants have not been thoroughly investigated in patients with acute heart failure (AHF). METHODS: We investigated 408 consecutive patients with AHF admitted to the ICU. Delirium was diagnosed by means of the Confusion Assessment Method for ICU tool and evaluated every 8 hours during the patients' ICU stays. RESULTS: Delirium occurred in 109 patients (26.7%), and the in-hospital mortality rate was significantly higher in patients with delirium (13.8% vs 2.3%; P < 0.001). Multivariate logistic regression analysis showed that delirium independently predicted in-hospital mortality (odds ratio [OR] 4.33, confidence interval [CI] 1.62-11.52; P = 0.003). Kaplan-Meier analysis showed that the 12-month mortality rate was significantly higher in patients with delirium compared with those without (log-rank test: P < 0.001), and Cox proportional hazards analysis showed that delirium remained an independent predictor of 12-month mortality (hazard ratio 2.19, 95% CI 1.49-3.25; P < 0.001). The incidence of delirium correlated with severity of heart failure as assessed by means of the Get With The Guidelines-Heart Failure risk score (chi-square test: P = 0.003). Age (OR 1.05, 95% CI 1.02-1.09; P = 0.003), nursing home residential status (OR 3.32, 95% CI 1.59-6.94; P = 0.001), and dementia (OR 5.32, 95% CI 2.83-10.00; P < 0.001) were independently associated with the development of delirium. CONCLUSIONS: Development of delirium during ICU stay is associated with short- and long-term mortality and is predicted by the severity of heart failure, nursing home residential, and dementia status.

AMPKα Subunit Ssp2 and Glycogen Synthase Kinases Gsk3/Gsk31 are involved in regulation of sterol regulatory element-binding protein (SREBP) activity in fission yeast.

Sterol regulatory element-binding protein (SREBP), a highly conserved family of membrane-bound transcription factors, is an essential regulator for cellular cholesterol and lipid homeostasis in mammalian cells. Sre1, the homolog of SREBP in the fission yeast Schizosaccharomyces pombe (S. pombe), regulates genes involved in the transcriptional responses to low sterol as well as low oxygen. Previous study reported that casein kinase 1 family member Hhp2 phosphorylated the Sre1 N-terminal transcriptional factor domain (Sre1N) and accelerated Sre1N degradation, and other kinases might exist for regulating the Sre1 function. To gain insight into the mechanisms underlying the Sre1 activity and to identify additional kinases involved in regulation of Sre1 function, we developed a luciferase reporter system to monitor the Sre1 activity through its binding site called SRE2 in living yeast cells. Here we showed that both ergosterol biosynthesis inhibitors and hypoxia-mimic CoCl2 caused a dose-dependent increase in the Sre1 transcription activity, concurrently, these induced transcription activities were almost abolished in Δsre1 cells. Surprisingly, either AMPKα Subunit Ssp2 deletion or Glycogen Synthase Kinases Gsk3/Gsk31 double deletion significantly suppressed ergosterol biosynthesis inhibitors- or CoCl2-induced Sre1 activity. Notably, the Δssp2Δgsk3Δgsk31 mutant showed further decreased Sre1 activity when compared with their single or double deletion. Consistently, the Δssp2Δgsk3Δgsk31 mutant showed more marked temperature sensitivity than any of their single or double deletion. Moreover, the fluorescence of GFP-Sre1N localized at the nucleus in wild-type cells, but significantly weaker nuclear fluorescence of GFP-Sre1N was observed in Δssp2, Δgsk3Δgsk31, Δssp2Δgsk3, Δssp2Δgsk31 or Δssp2Δgsk3Δgsk31 cells. On the other hand, the immunoblot showed a dramatic decrease in GST-Sre1N levels in the Δgsk3Δgsk31 or the Δssp2Δgsk3Δgsk31 cells but not in the Δssp2 cells. Altogether, our findings suggest that Gsk3/Gsk31 may regulate Sre1N degradation, while Ssp2 may regulate not only the degradation of Sre1N but also its translocation to the nucleus.

A program of exercise, brain training, and lecture to prevent cognitive decline.

OBJECTIVE: We examined the benefits of a community-based program combining physical exercise, cognitive training, and education on dementia and lifestyle habits. METHODS: This crossover open-label trial included 141 community-dwelling elderly people with suspected mild cognitive decline (MCD). Subjects were assigned to a 6-month intervention-first/6-month observation-second (INT-OBS) group or an OBS-INT group. The 6-month intervention consisted of 2 h of physical exercise, cognitive training, and classroom study or rest once weekly. Primary outcome was change in Touch Panel-type Dementia Assessment Scale (TDAS) score. RESULTS: TDAS score improved significantly during the intervention period compared with the observation period for all subjects (P < 0.05). Some physical functions also improved significantly during the intervention period compared with the observation period in the OBS-INT group (P < 0.05). INTERPRETATION: This community-based program improved both cognitive and physical function in elderly people with suspected MCD.