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For photoelectrochemical water splitting, tungsten trioxide (WO3) films with a monoclinic structure were synthesized on fluorine-doped tin oxide coated glass substrates with a vacuum evaporation method. To control the WO3 film thickness from 0.42 to 5.6 μm, the crystal orientation was intergraded from the (200) crystal plane to the (002) one. In x-ray diffraction measurements, the intensity ratio of the (002) crystal plane to the (200) one was defined as rp. In the WO3 photoelectrode with higher (002)-preferred orientation, the photocurrent continued to flow even when the incident light against the photoelectrode was completely blocked after the irradiation for 60 s. This suggests that hydrogen continues to be produced owing to the electrons charged by the formation of a hydrogen tungsten bronze (HxWO3) phase. After 72 s, the photocurrent density of the WO3 photoelectrode with rp = 42 became one-tenth of the value before the incident light was blocked. This charge release time was remarkably long compared to those of the WO3 photoelectrodes with (200)-preferred orientation and non-orientation. Therefore, it was considered that the hydrogen ion diffusion through the defects in the WO3 crystals tends to occur in the [002] crystal direction. However, the improvement in the (002)-preferred orientation can facilitate the structural change from the WO3 phase to the HxWO3 one for the entire film. [ABSTRACT FROM AUTHOR]

Objectives Artemisinin-resistant Plasmodium falciparum malaria is currently spreading globally, including in Africa. Artemisinin resistance also leads to resistance to partner drugs used in artemisinin-based combination therapies. Sequencing of kelch13 , which is associated with artemisinin resistance, culture-based partner drug susceptibility tests, and ELISA-based growth measurement are conventionally used to monitor resistance; however, their application is challenging in resource-limited settings. Methods An experimental package for field studies with minimum human/material requirements was developed. Results First, qPCR-based SNP assay was applied in artemisinin resistance screening, which can detect mutations within 1 h and facilitate sample selection for subsequent processes. It had 100% sensitivity and specificity compared with DNA sequencing in the detection of the two common artemisinin resistance mutations in Uganda, C469Y and A675V. Moreover, in the partner drug susceptibility test, the cultured samples were dry-preserved on a 96-well filter paper plate and shipped to the central laboratory. Parasite growth was measured by ELISA using redissolved samples. It well reproduced the results of direct ELISA, reducing significant workload in the field (Pearson correlation coefficient: 0.984; 95% CI: 0.975–0.990). Conclusions Large-scale and sustainable monitoring is required urgently to track rapidly spreading drug-resistant malaria. In malaria-endemic areas, where research resources are often limited, simplicity and feasibility of the procedure is especially important. Our approach combines a qPCR-based rapid test, which is also applicable to point-of-care diagnosis of artemisinin resistance and centralized analysis of ex vivo culture. The approach could improve efficiency of field experiments and accelerate global drug resistance surveillance. [ABSTRACT FROM AUTHOR]

WO3 thin films with (002)-preferred orientation showing superior electron storage capacity were prepared using a vacuum evaporation system. The electron storage capacity of the WO3 photoelectrode can be improved by controlling the crystallographic orientation of the WO3 crystals. In photoelectrochemical water splitting, the TiO2/WO3 photoelectrode exhibited a significantly higher increment in current density than the pristine WO3 photoelectrode. The charging and discharging capacities of the preferentially oriented WO3 layer can be derived in full value to introduce a TiO2 layer with a porous morphology. Moreover, because a difference in the crystal facet results in a slight change in the energy of the valence and conduction bands, it can be speculated that better separation of electron–hole pairs is achieved, leading to exposure of the (002) dominant crystal facet of WO3. [ABSTRACT FROM AUTHOR]

In this study, using enteric methane emissions, we investigated the metabolic characteristics of Japanese Black cattle. Their methane emissions were measured at early (age 13 months), middle (20 months), and late fattening phases (28 months). Cattle with the highest and lowest methane emissions were selected based on the residual methane emission values, and their liver transcriptome, blood metabolites, hormones, and rumen fermentation characteristics were analyzed. Blood β-hydroxybutyric acid and insulin levels were high, whereas blood amino acid levels were low in cattle with high methane emissions. Further, propionate and butyrate levels differed depending on the enteric methane emissions. Hepatic genes, such as SERPINI2, SLC7A5, ATP6, and RRAD, which were related to amino acid transport and glucose metabolism, were upregulated or downregulated during the late fattening phase. The above mentioned metabolites and liver transcriptomes could be used to evaluate enteric methanogenesis in Japanese Black cattle. [ABSTRACT FROM AUTHOR]

Aims and objectives: The present study investigated whether morning or afternoon activity is more effective at increasing the high‐frequency (HF) index, a parasympathetic index, in patients with cardiovascular risk factors. Background: A decreased HF index, a heart rate variability (HRV) parameter, is a well‐established marker of poor cardiovascular prognosis. Because blood pressure and sympathetic tone are higher in the morning, physical activity and exercise in the afternoon has been recommended for patients with cardiovascular diseases. However, there have been no reports concerning the superior effects of afternoon exercise on parasympathetic activity and sleep. Design: This observational study was a post hoc comparison. Methods: Patients' physical activity was measured for 1 month to determine their habits. Patients' HF index was measured by 24‐h Holter electrocardiography. The study enrolled 56 patients. Each patient's morning step count (before lunch) and afternoon step count (between lunch and dinner) were compared. We adhered to the STROBE guidelines in the present study. Results: Thirty‐one patients took more steps in the morning, and 25 patients took more steps in the afternoon. The present study showed that those who took more steps in the afternoon had a significantly higher HF index during the first hour after sleep onset and during sleep than those who took more steps in the morning (p =.003,.047). Conclusions: The present study showed that those who took more steps in the afternoon had a significantly higher HF index during the first hour after sleep onset and a higher HF index during sleep than those who took more steps in the morning. Relevance to clinical practice: Exercise in the afternoon may improve the prognosis in patients with cardiovascular disease by not only preventing excessive blood pressure, afterload, and sympathetic tone but also positively influencing the parasympathetic system and sleep. [ABSTRACT FROM AUTHOR]

Aim: The purpose of the present study was to elucidate the relationship between high-frequency heart rate variability (HF HRV) and continuous daytime sitting time in patients with cardiovascular risk factors such as mild hypertension and/or stable angina pectoris. Background: Decreased HF HRV precedes the progression and worsening of cardiovascular diseases. Continuous sitting behavior is a major risk factor for developing metabolic syndrome and is associated with cardiovascular disease, diabetes mellitus, renal failure, sarcopenia and osteoporosis. Risk factors for cardiovascular disease can be affected by continuous daytime sitting behaviors. Design: The present study design was a post-hoc comparison. Methods: Patients treated at two different primary care clinics from 2014 to 2018 were enrolled in this study (n = 53). We assessed HF HRV and continuous sitting time using 24-hour Holter electrocardiography and an activity meter at baseline and 6 months. HF HRV was calculated during sleep. Results: Sitting time had decreased in 22 patients (decreased group) and increased in 31 patients (increased group) after 6 months. The mean patient ages were 73.1 and 72.0 years in the decreased and increased sitting time groups, respectively (p = 0.503). HF HRV during sleep had increased after 6 months in the decreased sitting time group. Compared with the increased group, the decreased group showed significantly higher HF HRV during sleep after 6 months by two-way repeated-measures ANOVA after adjustment for age, sex and change in activity (p = 0.045). Conclusion: These results suggest that a decrease in sitting time might induce parasympathetic activity during sleep. Therefore, reducing continuous sitting time during the day might contribute, in part, to improving the prognosis of patients with cardiovascular risk factors not only by avoiding muscle loss but also by providing positive influences on parasympathetic tone during sleep. [ABSTRACT FROM AUTHOR]

Elucidation of the mechanisms of drug resistance in malaria parasites is crucial for combatting the emergence and spread of resistant parasites, which can be achieved by tracing resistance-associated mutations and providing useful information for drug development. Previously, we produced a novel genetic tool, a Plasmodium berghei mutator (PbMut), whose base substitution rate is 36.5 times higher than that of wild-type parasites. Here, we report the isolation of a mutant with reduced susceptibility to piperaquine (PPQ) from PbMut under PPQ pressure by sequential nine-cycle screening and named it PbMut-PPQ-R-P9. The ED50 of PbMut-PPQ-R-P9 was 1.79 times higher than that of wild-type parasites, suggesting that its PPQ resistance is weak. In the 1st screen, recrudescence occurred in the mice infected with PbMut but not in those infected with wild-type parasites, suggesting earlier emergence of PPQ-resistant parasites from PbMut. Whole-genome sequence analysis of PbMut-PPQ-R-P9 clones revealed that eight nonsynonymous mutations were conserved in all clones, including N331I in PbCRT , the gene encoding chloroquine resistance transporter (CRT). The PbCRT(N331I) mutation already existed in the parasite population after the 2nd screen and was predominant in the population after the 8th screen. An artificially inserted PbCRT(N331I) mutation gave rise to reduced PPQ susceptibility in genome-edited parasites (PbCRT-N331I). The PPQ susceptibility and growth rates of PbCRT-N331I parasites were significantly lower than those of PbMut-PPQ-R-P9, implying that additional mutations in the PbMut-PPQ-R9 parasites could compensate for the fitness cost of the PbCRT(N331I) mutation and contribute to reduced PPQ susceptibility. In summary, PbMut could serve as a novel genetic tool for predicting gene mutations responsible for drug resistance. Further study on PbMut-PPQ-R-P9 could identify genetic changes that compensate for fitness costs owing to drug resistance acquisition. [ABSTRACT FROM AUTHOR]

Hole-transport material-free perovskite solar cells were prepared by utilizing a spin-coating method. To optimize the dropping conditions of the toluene as an antisolvent in the nitrogen atmosphere, the CH3NH3PbI3/TiO2/fluorine-doped tin oxide (FTO)/glass specimen consisted of a high-density tissue, and crystal faults such as voids and cracks were not observed on its surface. By controlling the thickness of the mesoporous TiO2 layer with the rotation speed (x) of a spin coater, it was speculated that the thicker mesoporous TiO2 layer enables not only an efficient electron extraction from the CH3NH3PbI3 perovskite layer but also a smooth transition of electrons to the FTO electrode. Moreover, the precursor solution for CH3NH3PbI3 perovskite crystals was optimized for its molar concentration (y). The energy conversion efficiency (η) gradually increased from η = 5.8% to 9.6% with an increase in y to 2.6 M above which it decreased. The reason to obtain a superior energy conversion efficiency is so that the larger interface between the mesoporous TiO2 and perovskite layers is able to extract photoexcited electrons effectively. The above facts show for that the perovskite solar cells that have a larger area are synthesized with good reproducibility. [ABSTRACT FROM AUTHOR]

The rapid and aggressive spread of artemisinin-resistant Plasmodium falciparum carrying the C580Y mutation in the kelch13 gene is a growing threat to malaria elimination in Southeast Asia, but there is no evidence of their spread to other regions. We conducted cross-sectional surveys in 2016 and 2017 at two clinics in Wewak, Papua New Guinea (PNG) where we identified three infections caused by C580Y mutants among 239 genotyped clinical samples. One of these mutants exhibited the highest survival rate (6.8%) among all parasites surveyed in ring-stage survival assays (RSA) for artemisinin. Analyses of kelch13 flanking regions, and comparisons of deep sequencing data from 389 clinical samples from PNG, Indonesian Papua and Western Cambodia, suggested an independent origin of the Wewak C580Y mutation, showing that the mutants possess several distinctive genetic features. Identity by descent (IBD) showed that multiple portions of the mutants' genomes share a common origin with parasites found in Indonesian Papua, comprising several mutations within genes previously associated with drug resistance, such as mdr1, ferredoxin, atg18 and pnp. These findings suggest that a P. falciparum lineage circulating on the island of New Guinea has gradually acquired a complex ensemble of variants, including kelch13 C580Y, which have affected the parasites' drug sensitivity. This worrying development reinforces the need for increased surveillance of the evolving parasite populations on the island, to contain the spread of resistance. Author summary: Artemisinin is the most widely used drug against Plasmodium falciparum malaria. In southeast Asia, parasites have evolved genetic changes making them resistant to artemisinin. The elimination of resistant strains is a global priority, since their global spread could result in massive loss of lives. In Papua New Guinea, we found three patients infected with parasites carrying the most widespread resistant variant in southeast Asia, and they were confirmed to be artemisinin resistant. We established that the mutations were not imported from southeast Asia, and found other drug resistance variants in their genetic background, including some shared with parasites in Indonesia. This indicates that artemisinin resistance has emerged in New Guinea separately from southeast Asia, not by a chance event, but by a gradual process of evolution which may still be ongoing undetected on the island. These resistant strains could undermine malaria local control efforts, and constitute a global threat. [ABSTRACT FROM AUTHOR]

This study evaluated the effect of increased physical activity on high-frequency (HF) heart rate variability (HRV) during the first hour after sleep onset in patients with hypertension and/or stable angina pectoris. Physical activity and HF were measured using activity monitors and 24-hour Holter monitors at baseline and 6 months later. The physical activity increased in 28 patients (increase group) and decreased in 20 patients (decrease group) after 6 months. In this study, after 6 months, compared to the decreased physical activity group, the increased physical activity group showed a significant increase in the HF index during the first hour after sleep onset. Therefore, the increase in the HF index may have been due to the increase in physical activity. An increase in physical activity suggests that the quality of sleep early in the sleep cycle may be improved, which may affect the patient's prognosis. [ABSTRACT FROM AUTHOR]

Background: Usage of chloroquine was discontinued from the treatment of Plasmodium falciparum infection in almost all endemic regions because of global spread of resistant parasites. Since the first report in Malawi, numerous epidemiological studies have demonstrated that the discontinuance led to re-emergence of chloroquine-susceptible P. falciparum, suggesting a possible role in future malaria control. However, most studies were cross-sectional, with few studies looking at the persistence of chloroquine recovery in long term. This study fills the gap by providing, for a period of at least 6 years, proof of persistent re-emergence/stable recovery of susceptible parasite populations using both molecular and phenotypic methods. Methods: Ex vivo drug-susceptibility assays to chloroquine (n = 319) and lumefantrine (n = 335) were performed from 2013 to 2018 in Gulu, Northern Uganda, where chloroquine had been removed from the official malaria treatment regimen since 2006. Genotyping of pfcrt and pfmdr1 was also performed. Results: Chloroquine resistance (≥ 100 nM) was observed in only 3 (1.3%) samples. Average IC50 values for chloroquine were persistently low throughout the study period (17.4–24.9 nM). Parasites harbouring pfcrt K76 alleles showed significantly lower IC50s to chloroquine than the parasites harbouring K76T alleles (21.4 nM vs. 43.1 nM, p-value = 3.9 × 10−8). Prevalence of K76 alleles gradually increased from 71% in 2013 to 100% in 2018. Conclusion: This study found evidence of stable persistence of chloroquine susceptibility with the fixation of pfcrt K76 in Northern Uganda after discontinuation of chloroquine in the region. Accumulation of similar evidence in other endemic areas in Uganda could open channels for possible future re-use of chloroquine as an option for malaria treatment or prevention. [ABSTRACT FROM AUTHOR]

Utilizing a pulsed laser deposition method, silver-copper (Ag–Cu) nanoparticles have been synthesized by irradiating the laser light of λ=248 nm on Ag and Cu plates under the pressure below 1×10-4 Pa. The peak absorption attributed to surface plasmon resonance (SPR) of the Ag–Cu nanoparticles appeared at 763 nm, which was approximately 200 nm higher wavelength than that of Ag nanoparticles. With increase in the annealing temperature from 300 to 548 K, the peak absorption attributed to SPR of the Ag–Cu nanoparticles shifted continuously from 763 to 437 nm. This fact proved that the peak absorption attributed to SPR can be tuned in the whole visible region by changing the annealing temperature only. Moreover, from the results of atomic force microscopy and grazing angle x-ray diffraction, the SPR wavelength tuning is conjectured due not to the change in the surface morphology of the Ag–Cu nanoparticles but to the increase in the electric conductivity of the nanoparticles induced by the precipitation of Cu atoms. [ABSTRACT FROM AUTHOR]

Introduction: Cardiac memory is recognized as altered T‐waves when the sinus rhythm resumes after an abnormal myocardial activation period that recovers slowly over several weeks. The T‐wave changes after ablation of frequent premature ventricular contractions (PVCs) as cardiac memory was not known. Objective: This study identified whether cardiac memory exists after successful ablation of PVCs from the right ventricular outflow tract (RVOT). Methods: We investigated 45 patients who underwent successful ablation of PVCs from RVOT and 10 patients who underwent unsuccessful ablation. We analyzed the amplitude of the T‐wave, QT intervals, and QRST time‐integral values of a 12‐lead electrocardiogram before ablation and 1 day, 3 days, and 1 month after ablation. Results: In the successful ablation group, the amplitude of the T‐wave and QRST time‐integral values of lead II, III, aVR, aVL, and aVF significantly changed after ablation and gradually normalized within 1 month. In addition, if the number of pre‐ablation PVCs was small, then the corresponding impact was also small. However, the greater the number of pre‐ablation PVCs, the more prominent the changes. Significant changes were not observed in the unsuccessful ablation group. Conclusion: When ablation of PVCs from RVOT was successful, primary T‐wave changes because of cardiac memory and the gradual normalization of the amplitude of the T‐wave were observed. No significant T‐wave changes were detected after unsuccessful ablation. [ABSTRACT FROM AUTHOR]

Heart rate variability (HRV), especially increased high frequency (HF), has been reported to provide clinically useful prognostic information regarding cardiovascular disease. Napping is an excellent sleep management strategy in older adults. This study was conducted to clarify the effect of napping on HRV in older adult patients with cardiovascular risk factors. The patients were divided into two groups: one group of 32 patients who reported napping (nap group) and another group of 45 patients who did not report napping (nonnap group). The HRV was calculated in terms of the HF component over 24 hr during wakefulness, sleep, and 1 hr after sleep onset. The HF in the nap group was significantly higher than that in the nonnap group during all times measured. In addition, napping was a significant predictor of increased HF. This study shows the effectiveness of napping in the daily lives of patients with cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Background Although several prognostic factors of atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) have been investigated, the accurate prediction of AF recurrence remains difficult. We propose an electrocardiogram (ECG) index, the P-wave force (PWF), which is the product of the amplitude of the negative terminal phase of the P wave in the V1 electrode and the filtered P-wave duration, obtained by a signal-averaged P-wave analysis. This study was conducted to evaluate the impact of the PWF on the recurrence of AF after PVI. Methods We retrospectively evaluated 79 paroxysmal AF patients (64 ± 9 years, 56 males) who underwent PVI by cryoballoon ablation. Standard 12-lead ECG and a P-wave signal-averaged electrocardiogram (SAECG) were recorded the day before and 1 month after the PVI procedure. Results During the mean follow-up of 10.2 months, AF recurred in 11 (14%) patients. The PWF 1 month after ablation was significantly higher in the recurrence group compared to that in the nonrecurrence group (8.8 ± 3.1 mVms vs 6.5 ± 2.9 mVms, P = 0.017). The patients with a PWF value ≥9.3 mVms had a significantly greater risk of recurrence after the ablation compared to the patients with a PWF value <9.3 mVms (log-rank test, P < 0.001). Conclusion Higher PWF after cryoballoon ablation was associated with poor prognosis during follow-up. The PWF may be a useful and noninvasive marker to predict the recurrence of AF. [ABSTRACT FROM AUTHOR]

The relationship between body mass index (BMI) and the prognosis of elderly patients with atrial fibrillation (AF) is unknown. We aimed to examine the association of body weight with the clinical outcomes among Japanese elderly patients with a history of documented AF. This observational study of AF patients from an outpatients clinic in Nagoya University Hospital included 413 patients ≥70 years old (99 obese: BMI ≥25 kg/m; 256 normal weight: BMI 18.5-24.9 kg/m; and 58 underweight patients: BMI <18.5 kg/m). The mean age was 77.5 ± 5.6 years. During a mean follow-up of 19.0 months, all-cause death occurred in 23 patients (obese 1 %, normal weight 5.1 %, and underweight 16 %). The major adverse events including all-cause death, stroke or transient ischemic attack, heart failure requiring admission, and acute coronary syndrome were observed in 53 patients (obese 5.1 %, normal weight 13 %, and underweight 26 %). After adjusting for confounding factors, the underweight group had a significantly greater risk for all-cause death [hazard ratio (HR) 2.91, 95 % confidence interval (CI) 1.12-7.60, p = 0.029], and major adverse events (HR 2.45, 95 % CI 1.25-4.78, p = 0.009) than the normal weight group. In contrast, the obese group had a better prognosis in major adverse events compared with the normal weight group (HR 0.34, 95 % CI 0.13-0.89, p = 0.029). In conclusion, lower BMI was independently associated with poor outcomes among older AF patients. The association between obesity and better prognosis in elderly AF patients was also found. [ABSTRACT FROM AUTHOR]

Background Little is known about the association between B-type natriuretic peptide (BNP) levels and catheter ablation of atrial fibrillation (AF) in patients with heart failure. This study aimed to examine the impact of elimination of AF by catheter ablation on BNP levels in patients with left ventricular systolic dysfunction. Methods Fifty-four AF patients with left ventricular ejection fraction (LVEF) ≤ 50%, who underwent radiofrequency catheter ablation therapy of AF, were included. BNP sampling was performed at baseline, 3 days, and 1 month after ablation. Results After a follow-up period of 6 months, the BNP levels decreased significantly in the nonrecurrence group (n = 35; median 126.3 [interquartile 57.2-206.5] pg/mL, 63.5 [23.9-180.2] pg/mL, and 45.9 [21.9-160.3] pg/mL, P < 0.001, respectively), but not in the recurrence group (n = 19; 144.7 [87.1-217.3] pg/mL, 88.8 [12.9-213.2] pg/mL, and 118.5 [51.6-298.2] pg/mL, P = 0.368, respectively). The patients in the nonrecurrence group had a higher percentage relative reduction in BNP levels from baseline to 1 month after ablation than those in the recurrence group (56.5 [−9.0-77.4]% vs −2.4 [−47.1-60.9]%, P = 0.027). Additionally, a relative reduction in BNP levels significantly correlated with an increase in LVEF after ablation (r = 0.486, P < 0.001). Conclusions Plasma BNP levels decreased significantly with successful catheter ablation of AF in patients with impaired LVEF. The decrease in BNP levels might be associated with early recovery of cardiac function and subsequent maintenance of sinus rhythm at follow-up. [ABSTRACT FROM AUTHOR]

Although artemisinin combination therapies have been deployed as a first-line treatment for uncomplicated malaria in almost all endemic countries, artemisinin-resistant parasites have emerged and have gradually spread across the Greater Mekong subregions. There is growing concern that the resistant parasites may migrate to or emerge indigenously in sub-Saharan Africa, which might provoke a global increase in malaria-associated morbidity and mortality. Therefore, development of molecular markers that enable identification of artemisinin resistance with high sensitivity is urgently required to combat this issue. In 2014, a potential artemisinin-resistance responsible gene, Plasmodium falciparum kelch13, was discovered. Here, we review the genetic features of P. falciparum kelch13 and discuss its related resistant mechanisms and potential as a molecular marker. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to examine the association between body mass index (BMI) and prognosis in heart failure patients after cardiac resynchronization therapy-defibrillator (CRT-D) implantation. Methods: We retrospectively investigated 125 patients (33 overweight [BMI ≥25 kg/m], 75 normal weight [BMI 18.5-24.9 kg/m], and 17 underweight patients [BMI <18.5 kg/m]) who underwent CRT-D implantation. The clinical outcome endpoints were all-cause death and appropriate shock therapy. Results: During the follow-up period (mean 3.1 ± 1.8 years), 23 patients died (1 [3.0 %] overweight, 17 [22.7 %] normal weight, and 5 [29.4 %] underweight patients), and appropriate shock events were observed in 14 patients (2 [6.1 %] overweight, 10 [13.3 %] normal weight, and 2 [11.8 %] underweight patients). All patients survived shock therapy. After adjusting for confounding factors, overweight patients had significantly fewer outcomes relating to all-cause death and appropriate shock events (hazard ratio 0.27, 95 % confidence interval 0.08-0.91, p = 0.034) than normal weight patients. However, the prognostic difference between overweight and normal weight patients could be diminished as a result of the successful shock therapies ( p = 0.067). Additionally, prognosis did not differ between overweight and normal weight patients among the responders, but did differ among the non-responders. The underweight patients had a poorer prognosis after CRT-D implantation compared with the other groups. Conclusions: Although high BMI was associated with better outcomes among heart failure patients with CRT-D implantations, the difference in the prognosis between overweight and normal weight patients was reduced because of defibrillator therapy and the improvement in cardiac function provided by CRT-D implantation. [ABSTRACT FROM AUTHOR]

Introduction Apixaban, a factor Xa (FXa) inhibitor, is a new oral anticoagulant for stroke prevention in atrial fibrillation (AF). However, little is known about its efficacy and safety as a periprocedural anticoagulant therapy for patients who had undergone catheter ablation (CA) for AF. Methods and Results We evaluated 342 consecutive patients who underwent CA for AF between April 2013 and March 2014 and received apixaban (n = 105) and warfarin (n = 237) for uninterrupted periprocedural anticoagulation. We retrospectively investigated the occurrence of bleeding and thromboembolic complications during the procedural period and compared them between the apixaban group (AG) and warfarin group (WG). Thromboembolic complications occurred in one (0.4%) patient in the WG. Major and minor bleeding complications occurred in one (1%) and four (4%) patients in the AG, and three (1%) and 12 (5%) patients in the WG. No significant difference in complications was observed between the AG and WG. Of importance, adverse event rates did not differ between the two groups after adjusting by a propensity score analysis. In preoperative tests of blood coagulation, there were significant differences in the prothrombin time, activated partial thromboplastin time, FXa activity, and prothrombin fragment 1 + 2 (F1+2) levels between the AG and WG. Conclusion The use of apixaban during the periprocedural period of AF ablation seemed as efficacious and safe as warfarin. [ABSTRACT FROM AUTHOR]

Background Patients with greater improvement of cardiac function after cardiac resynchronization therapy (CRT) implantation are identified as 'super-responders.' However, it remains unclear which kind of preimplant assessments could accurately predict outcomes after CRT. Thus, we aimed to examine the essential predicting factors for super-response to CRT, and to construct an accurate predictable model. Methods We retrospectively analyzed the CRT patients who underwent implantation at Nagoya University Hospital. Super-responders are defined as those who show a relative reduction in left ventricular end-systolic volume ≥30% after 6 months of CRT. Results Eighty patients (mean age, 67.8 ± 10.2 years) were included. Twenty-two patients received upgrading procedure to CRT implantation. Six months after the implantation, 29 patients (36%) were super-responders. Multiple logistic regression analysis shows that consistent right ventricular pacing with a previous device (odds ratio [OR] 7.28, 95% confidence interval [CI] 1.52-34.9; P = 0.013), lack of prior history of ventricular arrhythmia (OR 5.32, 95% CI 1.52-18.6; P = 0.009), and smaller left atrial diameter (LAD) (OR 0.92, 95% CI 0.86-0.98; P = 0.014) are independent predictors for CRT super-responders. The use of a combination of these predictive factors could increase the certainty with which a greater response to CRT is predicted and the presence of such a combination could improve prognosis. Conclusion Greater response to biventricular pacing occurs more frequently in patients with consistent right ventricular pacing, lack of prior history of ventricular arrhythmia, and smaller LAD. An association between patient background characteristics and a super-response to CRT was also identified. [ABSTRACT FROM AUTHOR]

Plasmodium falciparum malaria imposes a serious public health concern throughout the tropics. Although genetic tools are principally important to fully investigate malaria parasites, currently available forward and reverse tools are fairly limited. It is expected that parasites with a high mutation rate can readily acquire novel phenotypes/traits; however, they remain an untapped tool for malaria biology. Here, we generated a mutator malaria parasite (hereinafter called a ‘malaria mutator’), using site-directed mutagenesis and gene transfection techniques. A mutator Plasmodium berghei line with a defective proofreading 3′ → 5′ exonuclease activity in DNA polymerase δ (referred to as PbMut) and a control P. berghei line with wild-type DNA polymerase δ (referred to as PbCtl) were maintained by weekly passage in ddY mice for 122 weeks. High-throughput genome sequencing analysis revealed that two PbMut lines had 175–178 mutations and a 86- to 90-fold higher mutation rate than that of a PbCtl line. PbMut, PbCtl, and their parent strain, PbWT, showed similar course of infection. Interestingly, PbMut lost the ability to form gametocytes during serial passages. We believe that the malaria mutator system could provide a novel and useful tool to investigate malaria biology. [ABSTRACT FROM PUBLISHER]

Aims and objectives To determine the effects on heart rate variability of home-based daily activity in patients with mild hypertension and/or stable angina pectoris and to clarify the relationship between daily activity and sympathovagal balance. Background Several prior studies have assessed the ability of exercise training to improve functional capacity and produce beneficial effects on mortality and physical capacity in patients with cardiovascular disease. Design A non-randomised six-month prospective longitudinal study. Methods This study consisted of 41 patients (59-83 years old) with mild hypertension and/or stable angina pectoris. The home-based daily activity and heart rate variability were measured at the start of the study ( BASE) and six months after the start of the study (6MoA). At 6MoA, the active mass increased in 23 patients (the IC group), while it decreased in the remaining 18 patients (the DC group). Results There were significant increases in the high-frequency component in the IC group between the data at BASE and 6MoA. There were significant decreases in the low frequency to high-frequency ratio (low frequency/high-frequency) during sleep in the IC group between the data at BASE and 6MoA. The active mass was classified into life activities and walk activities in terms of intensity of activity. In a multivariate model, increased life activitiesrevealed a trend towards an association with increased high-frequency. Conclusions In patients with mild hypertension and/or stable angina pectoris, an increase in active mass improved heart rate variability outcomes with increased high-frequency and decreased low frequency/high-frequency during sleep. To increase life activitiesmight improve heart rate variability and prognosis in patients. Relevance to clinical practice This study demonstrated that the potential importance of low-intensity daily activities in patients with mild hypertension and/or stable angina pectoris. [ABSTRACT FROM AUTHOR]

Although IL-12 is believed to contribute to protective immune responses, the role played by IL-23 (a member of the IL-12 family) in malaria is elusive. Here, we show that IL-23 is produced during infection with Plasmodium berghei NK65. Mice deficient in IL-23 (p19 KO) had higher parasitemia and died earlier than wild-type ( WT) controls. Interestingly, p19 KO mice had lower numbers of IL-17-producing splenic cells than their WT counterparts. Furthermore, mice deficient in IL-17 (17 KO) suffered higher parasitemia than the WT controls, indicating that IL-23-mediated protection is dependent on induction of IL-17 during infection. We found that macrophages were responsible for IL-17 production in response to IL-23. We observed a striking reduction in splenic macrophages in the p19 KO and 17 KO mice, both of which became highly susceptible to infection. Thus, IL-17 appears to be crucial for maintenance of splenic macrophages. Adoptive transfer of macrophages into macrophage-depleted mice confirmed that macrophage-derived IL-17 is required for macrophage accumulation and parasite eradication in the recipient mice. We also found that IL-17 induces CCL2/7, which recruit macrophages. Our findings reveal a novel protective mechanism whereby IL-23, IL-17, and macrophages reduce the severity of infection with blood-stage malaria parasites. [ABSTRACT FROM AUTHOR]

Recent studies show that some human malaria parasite species Plasmodium falciparum and P.vivax parasitize erythroblasts; however, the biological and clinical significance of this is unclear. To investigate further, we generated a rodent malaria parasite (P. yoelii 17XNL) expressing GFP-ovalbumin (OVA). Its infectivity to erythroblasts was confirmed and parasitized erythroblasts were capable of initiating malaria infections. Experiments showed that MHC class I molecules were highly expressed on parasitized erythroblasts. As CD8+ T cells recognize MHC class I and peptide complexes on target cells and are involved in protection or pathology against malaria, we examined whether erythroblasts are targeted by CD8+ T cells. Purified non-parasitized erythroblasts pulsed with OVA peptides were recognized by OVA-specific CD8+ T cells. Crucially, parasitized erythroblasts isolated from GFP-OVA-, but not GFP- infected-mice, activated OT-I CD8+ T cells, indicating that CD8+ T cells recognize parasitized erythroblasts in an antigen-specific manner. [ABSTRACT FROM AUTHOR]

General cellular functions of proteasomes occur through protein degradation, whereas the specific function of immunoproteasomes is the optimization of antigen processing associated with MHC class I. We and others previously reported that deficiency in subunits of immunoproteasomes impaired the activation of antigen-specific CD8+ T cells, resulting in higher susceptibility to tumor and infections. We demonstrated that CD8+ T cells contributed to protection against malaria parasites. In this study, we evaluated the role of immunoproteasomes in the course of infection with rodent malaria parasites. Unexpectedly, Plasmodium yoelii infection of mice deficient in LMP7, a catalytic subunit of immunoproteasomes, showed lower parasite growth in the early phase of infection and lower lethality compared with control mice. The protective characteristics of LMP7-deficient mice were not associated with enhanced immune responses, as the mutant mice showed comparable or diminished activation of innate and acquired immunity. The remarkable difference was observed in erythrocytes instead of immune responses. Parasitized red blood cells (pRBCs) purified from LMP7-deficient mice were more susceptible to phagocytosis by macrophages compared with those from wild-type mice. The susceptibility of pRBC to phagocytosis appeared to correlate with deformity of the membrane structures that were only observed after infection. Our results suggest that RBCs of LMP7-deficient mice were more likely to deform in response to infection with malaria parasites, presumably resulting in higher susceptibility to phagocytosis and in the partial resistance to malaria. [ABSTRACT FROM AUTHOR]

Although the circadian variation of catecholamine has been reported, that of the pulse wave velocity (PWV) has not. Brachial ankle (ba) PWV is associated with well-established indices of central stiffness. It is not known whether arterial stiffness is associated with catecholamine. The aim of the present study was to evaluate the changes in baPWV and those on the plasma epinephrine and norepinephrine levels in the morning and evening in hypertensive patients (HPs) and normotensive subjects (NSs). The baPWV and blood pressure (BP) were measured in 14 NSs (14 males, 39 ± 5 years) and 10 HPs (9 males and 1 female, 55 ± 13 years) at 06:00 h, noon, 18:00 h, and midnight, respectively. The plasma epinephrine and norepinephrine levels were measured in 14 NSs and 5 HPs at 06:00 h and 18:00 h, respectively. There was no significant difference in BPs at 06:00 h, noon, 18:00 h, and midnight in either NSs or HPs. The baPWV at 06:00 h was significantly lower than that at noon, 18:00 h, and midnight in NSs ( P = 0.01, 0.04, and 0.0008, respectively). The plasma epinephrine and norepinephrine levels at 06:00 h were markedly lower than those at 18:00 h in NSs ( P = 0.002 and 0.003, respectively). There were no significant changes in the baPWV of HPs at 06:00 h, noon, 18:00 h, or midnight. The plasma epinephrine and norepinephrine levels at 06:00 h were notably lower than those at 18:00 h in HPs ( P = 0.004 and 0.01, respectively). Only NSs showed a significant reduction in the baPWV with a decrease in the plasma catecholamine levels in the morning, suggesting that the baPWV of NSs may be correlated with the variation of the plasma catecholamine levels. [ABSTRACT FROM AUTHOR]

It is generally accepted that the mitochondria play central roles in energy production of most eukaryotes. In contrast, it has been thought that Plasmodium spp., the causative agent of malaria, rely mainly on cytosolic glycolysis but not mitochondrial oxidative phosphorylation for energy production during blood stages. However, Plasmodium spp. possesses all genes necessary for the tricarboxylic acid (TCA) cycle and most of the genes for electron transport chain (ETC) enzymes. Therefore, it remains elusive whether oxidative phosphorylation is essential for the parasite survival. To elucidate the role of TCA metabolism and ETC in malaria parasites, we deleted the gene for flavoprotein (Fp) subunit, Pbsdha, one of four components of complex II, a catalytic subunit for succinate dehydrogenase activity. The Pbsdha(-) parasite grew normally at blood stages in mouse. In contrast, ookinete formation of Pbsdha(-) parasites in the mosquito stage was severely impaired. Finally, Pbsdha(-) ookinetes failed in oocyst formation, leading to complete malaria transmission blockade. These results suggest that malaria parasite may switch the energy metabolism from glycolysis to oxidative phosphorylation to adapt to the insect vector where glucose is not readily available for ATP production. [ABSTRACT FROM AUTHOR]

Objectives: To differentiate acute from chronic damage to the myocardium in patients with myocardial infarction (MI) using DE and T2w MR. Methods: Short-axis T2w and DE MR images were acquired twice after the onset of MI in 36 patients who successfully underwent emergency coronary revascularisation. The areas of infarct and oedema were measured. The oedema-infarct ratio (O/I) of the left ventricular area was calculated by dividing the oedema by the infarct area. Results: The oedema size on T2w MR was significantly larger than the infarct size on DE MR in the acute phase. Both the oedema size on T2w MR and the infarct size on DE MR in the acute phase were significantly larger than those in the chronic phase. The O/I was significantly greater in the acute phase compared with that in the chronic phase ( P < 0.05). An analysis of relative cumulative frequency distributions revealed an O/I of 1.4 as a cut-off value for differentiating acute from chronic myocardial damage with the sensitivity, specificity, and accuracy of 85.1%, 82.7% and 83.9%, respectively. Conclusion: The oedema-infarct ratio may be a useful index in differentiating acute from chronic myocardial damage in patients with MI. Key Points • MR can differentiate reversible from irreversible myocardial damage after myocardial infarction. • MR is a useful modality to noninvasively differentiate the infarct stages. • The O/I is an important index to decide therapeutic strategies. [ABSTRACT FROM AUTHOR]

Aims Atrial fibrillation (AF) is a common arrhythmia frequently associated with hypertension. This study was designed to test the hypothesis that lowering blood pressure by angiotensin II-receptor blockers (ARB) has more beneficial effects than by conventional calcium channel blockers (CCB) on the frequency of paroxysmal AF with hypertension. Methods and results The Japanese Rhythm Management Trial II for Atrial Fibrillation (J-RHYTHM II study) is an open-label randomized comparison between an ARB (candesartan) and a CCB (amlodipine) in the treatment of paroxysmal AF associated with hypertension. Using daily transtelephonic monitoring, we examined asymptomatic and symptomatic paroxysmal AF episodes during a maximum 1 year treatment. The primary endpoint was the difference in AF frequency between the pre-treatment period and the final month of the follow-up. The secondary endpoints included cardiovascular events, development of persistent AF, left atrial dimension, and quality-of-life (QOL). The study enrolled 318 patients (66 years, male/female 219/99, 158 in the ARB group and 160 in the CCB group) treated at 48 sites throughout Japan. At baseline, the frequency of AF episodes (days/month) was 3.8 ± 5.0 in the ARB group vs. 4.8 ± 6.3 in the CCB group (not significant). During the follow-up, blood pressure was significantly lower in the CCB group than in the ARB group (P < 0.001). The AF frequency decreased similarly in both groups, and there was no significant difference in the primary endpoint between the two groups. There were no significant differences between the two groups in the development of persistent AF, changes in left atrial dimension, occurrence of cardiovascular events, or changes in QOL. Conclusions In patients with paroxysmal AF and hypertension, treatment of hypertension by candesartan did not have an advantage over amlodipine in the reduction in the frequency of paroxysmal AF (umin CTR C000000427). [ABSTRACT FROM PUBLISHER]

SERA gene sequences were newly determined from 11 primate Plasmodium species including two human parasites, P. ovale and P. malariae, and the evolutionary history of SERA genes was analyzed together with 7 known species. All have one each of Group I to III cysteine-type SERA genes and varying number of Group IV serine-type SERA genes in tandem cluster. Notably, Group IV SERA genes were ascertained in all mammalian parasite lineages; and in two primate parasite lineages gene events such as duplication, truncation, fragmentation and gene loss occurred at high frequency in a manner that mimics the birth-and-death evolution model. Transcription profile of individual SERA genes varied greatly among rodent and monkey parasites. Results support the lineage-specific evolution of the Plasmodium SERA gene family. These findings provide further impetus for studies that could clarify/provide proof-of-concept that duplications of SERA genes were associated with the parasites' expansion of host range and the evolutionary conundrums of multigene families in Plasmodium. [ABSTRACT FROM AUTHOR]

Fertilization is one of the most important processes in all organisms utilizing sexual reproduction. In a previous study, we succeeded in identifying a novel male gametic transmembrane protein GCS1 (GENERATIVE CELL SPECIFIC 1), also called HAP2 (HAPLESS 2) in the male-sterile Arabidopsis thaliana mutants, as a factor critical to gamete fusion in flowering plants. Interestingly, GCS1 is highly conserved among various eukaryotes covering plants, protists and invertebrates. Of these organisms, Chlamydomonas (green alga) and Plasmodium (malaria parasite) GCS1s similarly show male gametic expression and gamete fusion function. Since it is generally believed that protein factors controlling gamete fusion have rapidly evolved and different organisms utilize species-specific gamete fusion factors, GCS1 may be an ancient fertilization factor derived from the common ancestor of those organisms above. And therefore, its molecular structure and function are important to understanding the common molecular mechanics of eukaryotic fertilization. In this study, we tried to detect the central functional domain(s) of GCS1, using complementation assay of ArabidopsisGCS1 mutant lines expressing modified GCS1. As a result, the positively-charged C-terminal sequence of this protein is dispensable for gamete fusion, while the highly conserved N-terminal domain is critical to GCS1 function. In addition, in vitro fertilization assay of Plasmodium berghei (mouse malaria parasite) knock-in lines expressing partly truncated GCS1 showed similar results. Those findings above indicate that the extracellular N-terminus alone is sufficient for GCS1-based gamete fusion. [ABSTRACT FROM AUTHOR]

Aims: Identification of arrhythmogenic pulmonary veins (PVs) initiating atrial fibrillation is helpful for catheter ablation. The aim of this study was to examine the possibility to recognize the arrhythmogenic PV using Holter ECG. [ABSTRACT FROM PUBLISHER]