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Metformin, a biguanide antihyperglycemic drug, can exert various beneficial effects in addition to its glucose-lowering effect. The effects of metformin are mainly mediated by AMP-activated protein kinase (AMPK)-dependent pathway. AMPK activation interferes with the action of the mammalian target of rapamycin complex 1 (mTORC1), and blockade of mTORC1 pathway suppresses pathological retinal angiogenesis. Therefore, in this study, we examined the effects of metformin on pathological angiogenesis and mTORC1 activity in the retinas of mice with oxygen-induced retinopathy (OIR). OIR was induced by exposing the mice to 80% oxygen from postnatal day (P) 7 to P10. The OIR mice were treated with metformin, rapamycin (an inhibitor of mTORC1), or the vehicle from P10 to P12 or P14. The formation of neovascular tufts, revascularization in the central avascular areas, expression of vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) 2, and phosphorylated ribosomal protein S6 (pS6), a downstream indicator of mTORC1 activity, were evaluated at P10, P13, or P15. Neovascular tufts and vascular growth in the central avascular areas were observed in the retinas of P15 OIR mice. The formation of neovascular tufts, but not the revascularization in the central avascular areas, was attenuated by metformin administration from P10 to P14. Metformin had no significant inhibitory effect on the expression of VEGF and VEGFR2, but it reduced the pS6 immunoreactivity in vascular cells at the sites of angiogenesis. Rapamycin completely blocked the phosphorylation of ribosomal protein S6 and markedly reduced the formation of neovascular tufts. These results suggest that metformin partially suppresses the formation of neovascular tufts on the retinal surface by blocking the mTORC1 signaling pathway. Metformin may exert beneficial effects against the progression of ocular diseases in which abnormal angiogenesis is associated with the pathogenesis. [ABSTRACT FROM AUTHOR]

The origin of intrinsic operational instability in organic field‐effect transistors (OFETs) is discussed by comparing bias stress effects of OFETs with unidirectionally aligned and unaligned active layers of two different semiconducting polymers under vacuum environment. By forming hydrophobic nano‐groove structures on gate dielectric surfaces, a high‐mobility donor–acceptor copolymer, poly[4‐(4,4‐dihexadecyl‐4H‐cyclopenta[1,2‐b:5,4‐b′]‐dithiophen‐2‐yl)‐alt‐[1,2,5]thiadiazolo[3,4‐c]pyridine] (PCDTPT) and a benchmark semicrystalline polymer, poly(2,5‐bis(3‐hexadecylthiophen‐2‐yl)thieno[3,2‐b]thiophene) (PBTTT‐C16), are successfully aligned. The mobilities of the PCDTPT‐OFETs are higher than those of the PBTTT‐OFETs, but the operational stabilities are lower. Moreover, for both semiconducting polymers, the aligned OFETs exhibit higher mobility but lower operational stability than the unaligned OFETs. These results indicate that an increase in mobility does not necessarily lead to an increase in operational stability. The interface trap density of states analysis reveals that the lower operational stability of PCDTPT‐OFETs is not due to the tail state change but primarily due to the much larger turn‐on voltage shift (ΔVon). The major mechanism causing ΔVon should be the charge carrier transfer from the channel to the gate dielectric. Since the energy barrier limiting the charge carrier transfer decreases with increasing ionization potential of the active layer, the lower operational stability of PCDTPT‐OFETs is attributed to the higher ionization potential of PCDTPT. [ABSTRACT FROM AUTHOR]

Glaucoma is one of the leading causes of acquired blindness and characterized by retinal ganglion cell (RGC) death. MicroRNAs are small noncoding RNAs that degrade their target mRNAs. Apoptosis is one of the common mechanisms leading to neuronal death in many neurodegenerative diseases, including glaucoma. In the present study, we identified microRNAs that modulate RGC death caused by the intravitreal injection of N-methyl-d-aspartic acid (NMDA). We found an upregulation of miR-29b and downregulation of miR-124 in the retina of the NMDA-injected eyes. The intravitreal injection of an miR-29b inhibitor 18 h before NMDA injection reduced RGC death and the downregulation of myeloid cell leukemia 1 (MCL-1), an anti-apoptotic factor, induced by intravitreal NMDA. The intravitreal injection of an miR-124 mimic 18 h before NMDA injection also reduced RGC death and the upregulation of B-cell/chronic lymphocytic leukemia lymphoma 2 (bcl-2)-associated X protein (Bax) and bcl-2 interacting protein (Bim), pro-apoptotic factors, induced by intravitreal NMDA. These data suggest that expressional changes in microRNA are involved in the excitotoxicity of RGCs, and that complement and/or inhibition of microRNA may be a potential therapeutic approach for the diseases related to the excitotoxicity of RGCs, such as glaucoma and retinal central artery occlusion. [ABSTRACT FROM AUTHOR]

Adeno‐associated virus (AAV) vector can efficiently transduce therapeutic genes in various tissue types with less side effects; however, owing to complex multistep processes during manufacture, there have been surges in the pricing of recently approved AAV vector‐based gene therapy products. This study aimed to develop a simple and efficient method for high‐quality purification of AAV vector via tangential flow filtration (TFF), which is commonly used for concentration and diafiltration of solutions during AAV vector purification. We established a novel purification method using TFF and surfactants. Treatment with two classes of surfactants (anionic and zwitterionic) successfully inhibited the aggregation of residual proteins separated from the AAV vector in the crude product by TFF, obtaining a clearance of 99.5% residual proteins. Infectivity of the AAV vector purified using the new method was confirmed both in vitro and in vivo, and no remarkable inflammation or tissue damage was observed in mouse skeletal muscle after local administration. Overall, our proposed method could be used to establish a platform for the purification of AAV vector. [ABSTRACT FROM AUTHOR]

In this study, the electrical conductivity of low‐volume samples was measured using a prototype microfluidic chip with electrodes. We were able to show the difference of electrical conductivity in the samples of saline solution (0.9w/v% NaCl solution) with sucrose. The correlation between the electrical conductivity and the viscosity evaluated by the capillary method was shown. This correlation was shown that it is possible to evaluate viscosity based on the Walden's rule with our chip. [ABSTRACT FROM AUTHOR]

We previously identified that NO derived from neuronal cells acts on glial cells and causes vasodilation in the healthy rat retina via the release of epoxyeicosatrienoic acids (EETs) and prostaglandins (PGs) by activation of the arachidonic acid cascade. However, it is not clear which PG types are involved in these responses. The aim of the present study was to identify prostanoid receptors involved in glial cell-derived vasodilation induced by NO in rat retina. Male Wistar rats were used to examine the effects of intravitreal pretreatment with indomethacin, a cyclooxygenase inhibitor; PF-04418948, a prostanoid EP2 receptor antagonist; and CAY10441, a prostanoid IP receptor antagonist, on the changes in the retinal arteriolar diameter induced by intravitreal administration of NOR3, an NO donor. Retinal arteriolar diameters were measured using ocular fundus images captured with a high-resolution digital camera in vivo. The increase in the retinal arteriolar diameter induced by intravitreal injection of NOR3 was significantly suppressed by intravitreal pretreatment with indomethacin and PF-04418948, but not by CAY10441. The dose of PF-04418948 and CAY10441 injected intravitreally in the present study significantly reduced the increase in the retinal arteriolar diameter induced by prostaglandin E2 (PGE2) and prostaglandin I2 (PGI2), respectively. These results suggest that activation of the arachidonic acid cascade and subsequent stimulation of prostanoid EP2 receptors are involved in rat retinal vasodilatory responses evoked by NO-induced glial cell stimulation. Therefore, glial cell-derived PGE2, similar to EETs, may play an important role in retinal vasodilatory mechanisms. [ABSTRACT FROM AUTHOR]

Introduction: Respiratory failure from acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is associated with high mortality. Direct hemoperfusion with polymyxin B-immobilized fiber column (PMX-DHP) has been reported to have beneficial effects on patients with AE-IPF. Whether patient characteristics influence the extent of this benefit remains unclear. Methods: We retrospectively examined the records of 30 patients with AE-IPF who underwent PMX-DHP. The favorable factors of survival were determined using Cox proportional hazards analyses. Results: The 1- and 12-month survival rates after PMX-DHP were 70.0% and 50.0%, respectively. The multivariate analysis revealed that low modified Gender-Age-Physiology (GAP) index (≤8 points) (hazard ratio [HR] 0.317, p = 0.015) and PMX-DHP received within 48 h of steroid pulse (HR 0.289, p = 0.012) were favorable factors. Notably, even in the patients with high modified GAP index (>8 points), that is, more advanced IPF, those who received PMX-DHP within 48 h of steroid pulse had a better prognosis than those who did after 48 h of the steroid pulse (p = 0.032). Conclusions: Early PMX-DHP initiation in patients with AE-IPF, specifically within 48 h after the steroid pulse therapy, may improve prognosis regardless of the severity of chronic phase of IPF before AE-IPF. [ABSTRACT FROM AUTHOR]

In this study, we newly considered the analysis of capillary flow under differential pressure, which extends the previous study and allows the independent measurement of relative viscosity and the product of relative surface tension and contact angle for low-volume samples. The theory of this method is explained, and it is demonstrated that relative viscosity and surface tension with contact angle can be obtained independently by measuring the capillary flow under differential pressure. We conducted capillary flow experiments with a small sample volume (less than 100 ÎĽ l) using a measurement system comprising a flow measurement unit, capillary chip, and differential pressure mechanism. The relative viscosities of pure water and dilute ethanol solutions obtained in the experiment were in one-to-one correspondence with the values in the Chemical Handbook. This also shows that relative surface tension can be determined using these measurement results and the separately measured contact angle values. [ABSTRACT FROM AUTHOR]

Although the 6 min walk test (6MWT) is well-established for assessing desaturation in patients with interstitial lung disease (ILD), it cannot be easily performed in primary healthcare settings. This retrospective observational study aimed to evaluate the usefulness of the 1 min sit-to-stand test (1STST) for assessing desaturation during 6MWT in ILD patients with normal resting blood oxygen levels. We included 116 patients, and the pulse oxygen saturation (SpO2) for both methods was analyzed. The SpO2 nadir during the 1STST and 6MWT correlated strongly (ρ = 0.82). The frequency of patients with nadir SpO2 < 90% was consistent for both tests (κ = 0.82). 1STST was superior to diffusing capacity for carbon monoxide in detecting desaturation during the 6MWT. These findings were similarly stratified according to performance status or dyspnea scale. The 1STST can easily measure exertional desaturation in ILD patients with normal resting blood oxygen levels and is an alternative to the 6MWT. [ABSTRACT FROM AUTHOR]

Mitochondrial aldehyde dehydrogenase 2 (ALDH2) detoxifies toxic aldehydes generated during ischemia/reperfusion (I/R) injury in ST-elevation myocardial infarction (STEMI). The deficient variant ALDH2 genotype (ALDH2*2) is prevalent among East Asians. Whether ALDH2*2 exacerbates I/R injury of in patients with STEMI is not known. The study subjects comprised 218 Japanese patients with STEMI (158 men and 60 women, mean age 67.9 ± 11.9) who underwent successful percutaneous coronary intervention. Of these, 120 (55.0%) were the carriers of variant ALDH2*2 and 98 (45.0%) those of wild ALDH2*1/*1 on genotyping. There were no differences in clinical characteristics between the ALDH2*2 and ALDH2*1/*1 group except lower alcohol habit (14.2% vs 46.3%, P < 0.001) in the ALDH2*2 group. The peak plasma levels of creatine phosphokinase myocardial binding (CKMB), a marker of myocardial injury, however, were significantly higher in the patients with ALDH2*2 than in those with ALDH2*1/*1 [a median 275.0 (175.8–407.5) vs 177.5 (126.9–344.3) U/L, P = 0.001] among men but not among women (P = 0.811). There was a significant interaction between men (male sex) and ALDH2*2 for I/R injury (χ2 = 4.425, P = 0.040). The variant ALDH2*2 was associated with more severe I/R injury than the wild ALDH2*1/*1 in STEMI patients in men with possible sex differences. [ABSTRACT FROM AUTHOR]

Although the 6 min walk test (6MWT) is well-established for assessing desaturation in patients with interstitial lung disease (ILD), it cannot be easily performed in primary healthcare settings. This retrospective observational study aimed to evaluate the usefulness of the 1 min sit-to-stand test (1STST) for assessing desaturation during 6MWT in ILD patients with normal resting blood oxygen levels. We included 116 patients, and the pulse oxygen saturation (SpO2) for both methods was analyzed. The SpO2 nadir during the 1STST and 6MWT correlated strongly (ρ = 0.82). The frequency of patients with nadir SpO2 < 90% was consistent for both tests (κ = 0.82). 1STST was superior to diffusing capacity for carbon monoxide in detecting desaturation during the 6MWT. These findings were similarly stratified according to performance status or dyspnea scale. The 1STST can easily measure exertional desaturation in ILD patients with normal resting blood oxygen levels and is an alternative to the 6MWT. [ABSTRACT FROM AUTHOR]

Percutaneous coronary intervention (PCI) has significantly advanced over the last 40 years, but it is not clear whether there have been any changes in prognosis in recent years. The Kumamoto Intervention Conference Study Real-World Registry is a multi-center registry that enrolls consecutive patients undergoing PCI in 17 centers in Kyushu, Japan. To elucidate the clinical impact of recent changes in treatment strategies, 8841 consecutive participants (historical PCI: n = 4038, enrolled between January 2013 and December 2014, and current PCI: n = 4803, between January 2015 and March 2017) with 1-year follow-up data were analyzed. The incidences of major adverse cardiovascular and other clinical events were comparable between historical PCI and current PCI, even though complex lesions were more frequent during the more recent period. During this period, the use of radial approaches, drug eluting stents, and coronary imaging was greater. The use of prasugrel was more frequent (P < 0.001) during the time periods. Comparable event rates were associated with the use of clopidogrel (52.7%) and prasugrel (47.3%). In the sub-analysis for acute coronary syndrome (n = 5047), similar clinical event rates were recorded for historical and current PCI. Although the lesions to be treated are becoming more severe and complex, equivalent clinical outcomes have been maintained in recent years, possibly due to advances in the devices and medication used. [ABSTRACT FROM AUTHOR]

Additive printing techniques have been widely investigated for fabricating multilayered electronic devices. In this work, a layer‐by‐layer printing strategy is developed to fabricate multilayered electronics including 3D conductive circuits and thin‐film transistors (TFTs) with low‐temperature catalyzed, solution‐processed SiO2 (LCSS) as the dielectric. Ultrafine, ultrasmooth LCSS films can be facilely formed at 90 °C on a wide variety of organic and inorganic substrates, offering a versatile platform to construct complex heterojunction structures with layer‐by‐layer fashion at microscale. The high‐resolution 3D conductive circuits formed with gold nanoparticles inside the LCSS dielectric demonstrate a high‐speed response to the transient voltage in less than 1 µs. The TFTs with semiconducting single‐wall carbon nanotubes can be operated with the accumulation mode at a low voltage of 1 V and exhibit average field‐effect mobility of 70 cm2 V−1 s−1, on/off ratio of 107, small average hysteresis of 0.1 V, and high yield up to 100% as well as long‐term stability, high negative‐gate bias stability, and good mechanical stability. Therefore, the layer‐by‐layer printing strategy with the LCSS film is promising to assemble large‐scale, high‐resolution, and high‐performance flexible electronics and to provide a fundamental understanding for correlating dielectric properties with device performance. [ABSTRACT FROM AUTHOR]

Background: In mice, a tri‐layered (superficial, intermediate, and deep) vascular structure is formed in the retina during the third postnatal week. Short‐term treatment of newborn mice with vascular endothelial growth factor (VEGF) receptor inhibitors delays the formation of superficial vascular plexus and this allows us to investigate the developmental process of superficial and deep vascular plexuses at the same time. Using this model, we examined the effect of pharmacological depletion of retinal neurons on the formation of superficial and deep vascular plexuses. Results: Neuronal cell loss induced by an intravitreal injection of N‐methyl‐d‐aspartic acid on postnatal day (P) 8 delayed vascular development in the deep layer but not in the superficial layer in mice treated with KRN633, a VEGF receptor inhibitor, on P0 and P1. In KRN633‐treated mice, neuronal cell loss decreased the number of vertical sprouts originating from the superficial plexus without affecting the number of angiogenic sprouts growing in front. Neuronal cell loss did not impair networks of fibronectin and astrocytes in the superficial layer. Conclusions: Our results suggest that inner retinal neurons play a crucial role in forming the deep vascular plexus by directing the sprouts from the superficial blood vessels to the deep layer. Key Findings: By interrupting the retinal superficial vascular growth in neonatal mice, it is possible to investigate the developmental process of superficial and deep vascular plexuses simultaneously.Neuronal cell loss decreases the number of vertical sprouts originating from the superficial plexus without affecting the number of angiogenic sprouts growing in front.Neuronal cells play a crucial role in forming the deep vascular plexus by directing the sprouts from the superficial blood vessels to the deep layer in the mouse retina. [ABSTRACT FROM AUTHOR]

Although there is accumulating evidence for the usefulness of imaging-guided percutaneous coronary intervention (PCI), there are few studies for acute coronary syndrome (ACS), and the impact of the frequency of use has not been well addressed. From the Kumamoto Intervention Conference Study; a Japanese registry comprising 17 institutions, consecutive patients undergoing successful PCI from April 2008 through March 2014 were enrolled. Subjects were divided into two groups: imaging-guided PCI and angiography-guided PCI. Clinical outcome was a composite of cardiac death, non-fatal myocardial infarction, and stent thrombosis within 1 year. A total of 6025 ACS patients were enrolled: 3613 and 2412 patients with imaging- and angiography-guided PCI, respectively. Adverse cardiac events were significantly lower in the imaging-guided PCI group (long-rank P < 0.001). Even after propensity-score matching, the event rates still showed significant differences between the two groups (log-rank P = 0.004). To assess the effects of frequency of imaging usage, we divided the 17 institutions into six low-, six moderate-, and five high-frequency groups. The event rates decreased depending on the frequency, seemingly driven by stepwise event suppression in angiography-guided PCI. In Japanese ACS patients, the incidence of adverse clinical events in patients treated with imaging-guided PCI were significantly lower than that in patients with angiography-guided PCI. Better clinical result was found in the institutions using intravascular imaging more frequently. University Hospital Medical Information Network (UMIN)-CTR (http://www.umin.ac.jp/ctr/). Identifier: KICS (UMIN000015397). [ABSTRACT FROM AUTHOR]

Misdirected vascular growth frequently occurs in the neovascular diseases in the retina. However, the mechanisms are still not fully understood. In the present study, we created capillary-free zones in the central and peripheral retinas in neonatal mice by pharmacological blockade of vascular endothelial growth factor (VEGF) signaling. Using this model, we investigated the process and mechanisms of revascularization in the central and peripheral avascular areas. After the completion of a 2-day treatment with the VEGF receptor tyrosine kinase inhibitor KRN633 on postnatal day (P) 4 and P5, revascularization started on P8 in the central avascular area where capillaries had been dropped out. The expression levels of VEGF were higher in the peripheral than in the central avascular area. However, the expansion of the vasculature in the peripheral avascular retina remained suppressed until revascularization had been completed in the central avascular area. Additionally, we found disorganized endothelial cell division, misdirected blood vessels with irregular diameters, and abnormal fibronectin networks at the border of the vascular front and the avascular retina. In the central avascular area, a slight amount of fibronectin as non-vascular component re-formed to provide a scaffold for revascularization. Mechanistic analysis revealed that higher levels of VEGF attenuated the migratory response of endothelial cells without decreasing the proliferative activity. These results suggest that the presence of concentration range of VEGF, which enhances both migration and proliferation of the endothelial cells, and the structurally normal fibronectin network contribute to determine the proper direction of angiogenesis. [ABSTRACT FROM AUTHOR]

Circulating catecholamines contribute to the regulation of retinal vascular tone. Our previous studies have demonstrated that the activation of large-conductance Ca2+-activated K+ (BKCa) channels is involved in the β2-adrenoceptor-mediated dilation of retinal arterioles in rats. The present study aimed to examine the role of Gi protein in the β2-adrenoceptor-mediated activation of BKCa channels in the retinal arterioles. Images of in vivo rat ocular fundi were captured, and the diameters of retinal arterioles were measured. Systemic blood pressure and heart rate were recorded continuously. Intravenous infusion of formoterol (0.01–0.3 μg/kg/min), a β2-adrenoceptor agonist, increased the diameter of retinal arterioles but decreased mean arterial pressure in a dose-dependent manner. Intravitreal injection of iberiotoxin (20 pmol/eye), an inhibitor of BKCa channels, significantly attenuated the formoterol-induced dilation of retinal arterioles. Similar results were obtained when salbutamol (0.03–3 μg/kg/min), another β2-adrenoceptor agonist, was used instead of formoterol. However, iberiotoxin had no significant effect on retinal vasodilator responses to intravenous infusion of denopamine (1–30 μg/kg/min; a β1-adrenoceptor agonist), CL316243 (0.3–10 μg/kg/min; a β3-adrenoceptor agonist), prostaglandin I2 (0.03–10 μg/kg/min; a prostanoid IP receptor agonist), and forskolin (1–10 μg/kg/min; an adenylyl cyclase activator). Intravitreal injection of pertussis toxin (66 ng/eye; a Gi protein inhibitor) significantly attenuated the dilation of retinal arterioles induced by formoterol but not by denopamine and CL316243. In the presence of pertussis toxin, iberiotoxin had no inhibitory effect on formoterol-induced dilation of retinal arterioles. These results suggest that stimulation of β2-adrenoceptors dilates retinal arterioles through pertussis toxin–sensitive Gi protein–dependent activation of BKCa channels in rats in vivo. [ABSTRACT FROM AUTHOR]

Air pollution causes hypertension, cardiovascular disease, and mortality. Asian dust (AD) reportedly induces asthma or acute myocardial infarction along with air pollution, but its impact on blood pressure (BP) is unknown. We investigated the association between short-term AD exposure and BP fluctuations in 300,952 individuals whose BP was measured during April 2005–March 2015 and divided them into AD and non-AD groups based on visitation for AD-related events. AD's occurrence, air pollutants' concentration (suspended particulate matter, SO2, NO2, photochemical oxidants), and meteorological variables (mean ambient temperature, relative humidity) were obtained from a monitoring station; AD events correlated with decreased visibility (< 10 km). We observed 61 AD days, with 3897 participants undergoing medical check-ups. Short-term AD exposure at lag day-0 was significantly associated with higher systolic BP (SBP), diastolic BP (DBP), and pulse rate (PR) risk (β = 1.85, 95% confidence interval (CI) 1.35–2.35 for SBP, β = 2.24, 95% CI 1.88–2.61 for DBP, β = 0.52, 95% CI 0.14–0.91 for PR) using multi-pollutant model. Population-attributable fractions exposed to AD were 11.5% for those with elevated SBP (SBP ≥ 120 mmHg) and 23.7% for those with hypertension (SBP ≥ 140 mmHg or DBP ≥ 90 mmHg). This study showed a strong association between short-term AD exposure and increased SBP and DBP. [ABSTRACT FROM AUTHOR]

In this paper, methods for measuring the viscosity and surface tension of low-volume liquid samples are proposed. Viscosity is measured by recording the motion of a liquid driven by surface tension through a horizontal glass capillary tube. Surface tension is determined by connecting a container of a constant volume to the distal end of the capillary tube and measuring the penetration distance of the liquid entering via the proximal end. Sucrose solutions of various concentrations (0–50 wt%) were measured as samples, and the determined viscosities were confirmed to be consistent with the tabulated values provided in the Handbook of Chemistry. The surface tension was found to be constant within the measurement sensitivity of the device regardless of the sucrose concentration. [ABSTRACT FROM AUTHOR]

Bias‐stress resistance of polymer‐based organic field‐effect transistors (OFETs) is considerably enhanced by coating the gate dielectric surface with an amorphous perfluoropolymer (CYTOP). In bottom‐gate (BG) OFETs offering a relatively simple fabrication process, the CYTOP coating causes a serious problem; that is, thin film formation of organic semiconducting polymers generally fails due to the lyophobic properties of CYTOP. This problem is solved by patterning the CYTOP coating layer with suitable designs. Here, a simple photo‐patterning method is established using CYTOP terminated with amidosilyl functional groups. This method is composed of self‐limited thinning process of CYTOP coating layers, exposure to vacuum ultraviolet light through a photomask, and development. BG/top‐contact OFET arrays are fabricated using poly(2,5‐bis(3‐hexadecylthiophene‐2‐yl)thieno[3,2‐b]thiophene) as the semiconducting polymer. The initial electrical properties and bias‐stress resistance are compared with those of OFETs with octadecyltrichlorosilane (ODTS)‐treated gate dielectrics. The CYTOP‐ and ODTS‐OFETs show approximately the same initial electrical properties with very small device‐to‐device variation, while the CYTOP‐OFETs exhibit much higher intrinsic bias‐stress resistance. Therefore, the spin‐coating combined with the simple photo‐patterning method is a promising technique that can form polymeric organic semiconductor layers on CYTOP layers and produce BG OFETs exhibiting very high operational stability. [ABSTRACT FROM AUTHOR]

Particulate matter from natural sources such as desert dust causes harmful effects for health. Asian dust (AD) increases the risk of acute myocardial infarction (AMI). However, little is known about the risk of myocardial infarction with nonobstructive coronary arteries (MINOCA), compared to myocardial infarction with coronary artery disease (MI-CAD). Using a time-stratified case-crossover design and conditional logistic regression models, the association between short-term exposure to AD whereby decreased visibility (< 10 km) observed at each monitoring station nearest to the hospitals was used for exposure measurements and admission for AMI in the spring was investigated using a nationwide administrative database between April 2012 and March 2016. According to presence of revascularization and coronary atherosclerosis, AMI patients (n = 30,435) were divided into 2 subtypes: MI-CAD (n = 27,202) or MINOCA (n = 3233). The single lag day-2 was used in AD exposure based on the lag effect analysis. The average level of meteorological variables and co-pollutants on the 3 days prior to the case/control days were used as covariates. The occurrence of AD events 2 days before the admission was associated with admission for MINOCA after adjustment for meteorological variables [odds ratio 1.65; 95% confidence interval (CI) 1.18–2.29], while the association was not observed in MI-CAD. The absolute risk difference of MINOCA admission was 1.79 (95% CI 1.21–2.38) per 100,000 person-year. These associations between AD exposure and the admission for MINOCA remained unchanged in two-pollutant models. This study provides evidence that short-term exposure to AD is associated with a higher risk of MINOCA, but not MI-CAD. [ABSTRACT FROM AUTHOR]

We present a case of double‐chambered right ventricle (DCRV) complicated by hypertrophic obstructive cardiomyopathy (HOCM) in KRAS mutation‐associated Noonan syndrome. The diagnosis was incidental and made during diagnostic testing for an intradural extramedullary tumour. Spinal compression, if not surgically treated, may cause paralysis of the extremities. We decided to pursue pharmacological therapy to control biventricular obstructions and reduce the perioperative complication rate. We initiated treatment with cibenzoline and bisoprolol; the doses were titrated according to the response. After 2 weeks, the peak pressure gradient of the two RV chambers decreased from 101 to 68 mmHg, and the LV peak pressure gradient decreased from 109 to 14 mmHg. Class 1A antiarrhythmic drugs and β‐blockers decreased the severe pressure gradients of biventricular obstructions caused by DCRV and HOCM. The patient was able to undergo surgery to remove the intradural extramedullary tumour, which was diagnosed as schwannoma. [ABSTRACT FROM AUTHOR]

Introduction: Mortality in hemodialysis patients is relatively high; thus, its risk stratification is very important. There are insufficient data describing the current status of the management of serum phosphate and calcium levels. Methods: We conducted a multicenter, prospective, registry study throughout the Kumamoto Prefecture in Japan. We enrolled 1993 patients at 58 facilities with complete explanatory data, including serum phosphate, corrected calcium, and intact parathyroid hormone levels. We categorized subjects into nine categories according to low, normal, and high levels of phosphate and corrected calcium levels. The endpoint was all‐cause mortality. Results: Of the total number of subjects, 56.1% of the patients were in the normal phosphate and calcium category, and 72% and 77.1% had controlled serum phosphate and calcium levels, respectively. Two hundred twenty‐six deaths occurred during the follow‐up period. In the nine categories, the highest mortality rates were observed in the highest corrected calcium and lowest phosphate categories. Stepwise backward multivariate regression analyses identified the serum corrected calcium level (OR, 1.38; 95% CI, 1.06–1.79; P = 0.016) and the serum phosphate level (OR, 1.26; 95% CI, 1.08–1.48; P = 0.003) as significant and independent predictors of all‐cause mortality. Conclusions: The corrected serum calcium and phosphate levels are associated with mortality in our dialysis population, with poorest survival in patients with high corrected serum calcium and low serum phosphorus. [ABSTRACT FROM AUTHOR]

BACKGROUND While there is a concern about the increase in the occurrence of acute aortic dissection (AAD) caused by the worsening of hypertension, mental stress, etc., there is a lack of data regarding the influence of disasters on this event. The aim of this study was to address this issue in the acute–subacute phase after the Kumamoto Earthquake occurred on 14 April 2016. METHODS We retrospectively investigated the impacts of the Kumamoto Earthquake on various cardiovascular diseases, including AAD, utilizing the medical records of patients in 16 hospitals in Kumamoto Prefecture during the period from 14 April to 30 June (78 days) in 2014, 2015, 2016, and 2017. RESULTS The occurrence of heart failure and venous thromboembolism increased significantly in the acute–subacute phase after the earthquake. When comparing the earthquake year (2016) to the non-earthquake years (2014, 2015, and 2017), the difference in the occurrences and mortalities of AADs were not significant. When other characteristics of the patients were compared between the earthquake year and the non-earthquake years, there were no differences. CONCLUSIONS It might be possible that the Kumamoto Earthquake did not affect the incidence of AAD or deaths from AAD, possibly because the climate was mild and the preventive efforts based on previous experience were successful. REGISTRATION University Hospital Medical Information Network (UMIN)-CTR (http://www.umin.ac.jp/ctr/). IDENTIFIER UMIN000023864. PUBLIC ACCESS INFORMATION Opt-out materials were available at the following website: http://www.kumadai-junnai.com/home/wp-content/uploads/shinsai.pdf. [ABSTRACT FROM AUTHOR]

We report the performances of planar organic photovoltaics (OPVs) using a low bandgap polymer (PTB7) as a donor (D) and three perylenetetracarboxylic diimide derivatives with different substituents on the nitrogen atoms, phenylethyl (PEPTC), (4-fluorophenyl)ethyl (4FPEPTC), and (4-methoxyphenyl)ethyl (4MeOPEPTC) as acceptors (A). These acceptors with different dipolar moments at the end group are expected to exhibit different interactions with the underlying PTB7 layer. An anomalous low open-circuit voltage (Voc) in the OPV with PTB7/4FPEPTC was obtained due to the orientation of dipolar moments at the D/A interfaces induced by the orientation of 4FPEPTC with 4-fluorophenyl groups. On the other hand, although the terminal 4-methoxyphenyl group in 4MeOPEPTC has a dipole moment in the opposite direction to the terminal 4-fluorophenyl group in 4FPEPTC, the expected large Voc was not obtained in the OPV with PTB7/4MeOPEPTC due to the disorientation of 4MeOPEPTC at the D/A interface. [ABSTRACT FROM AUTHOR]

An impairment of cellular interactions between the elements of the neurovascular unit contributes to the onset and/or progression of retinal diseases. The present study aims to examine how elements of the neurovascular unit are altered in a rat model of retinopathy of prematurity (ROP). Neonatal rats were treated subcutaneously with the vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor KRN633 (10 mg/kg) on postnatal day (P) 7 and P8 to induce ROP. Morphological assessments were performed of blood vessels, astrocytes and neuronal cells in the retina. Aggressive angiogenesis, tortuous arteries and enlarged veins were observed in the retinal vasculature of KRN633-treated (ROP) rats from P14 to P28, compared to age-matched control (vehicle-treated) animals. Morphological abnormalities in the retinal vasculature showed a tendency toward spontaneous recovery from P28 to P35 in ROP rats. Immunofluorescence staining for glial fibrillary acidic protein and Pax2 (astrocyte markers) revealed that morphological changes to and a reduction in the number of astrocytes occurred in ROP rats. The developmental cell death was slightly accelerated in ROP rats; however, no visible changes in the morphology of retinal layers were observed on P35. The abnormalities in astrocytes might contribute, at least in part, to the formation of abnormal retinal blood vessels and the pathogenesis of ROP. [ABSTRACT FROM AUTHOR]

Aims: The prediction of future heart failure (HF) in stable outpatients is often difficult for general practitioners and cardiologists. Recently, the H2FPEF score (0–9 points) has been proposed for the discrimination of HF with preserved ejection fraction from non‐cardiac causes of dyspnoea. The six clinical and echocardiographic variables that constitute the H2FPEF score include the following: (i) obesity (H); (ii) the use of ≥2 antihypertensive drugs (H); (iii) atrial fibrillation (F); (iv) pulmonary hypertension (P); (v) an age > 60 years (E); and (vi) E/e' > 9 (F). We performed an external validation study that investigated whether the H2FPEF score could predict future HF‐related events in stable outpatients with cardiovascular risk factor(s) in Japan. Methods and results: In this prospective cohort study, after exclusion of 195 from 551 consecutive, stable Japanese outpatients with at least one cardiovascular risk factor who were enrolled between September 2010 and July 2013, the remaining 356 outpatients (171 men, 185 women, mean age 73.2 years) were eligible for the analysis. We calculated the H2FPEF score (0–9 points), and followed up the patients for an average of 517 days. In all of the 356 patients, the mean H2FPEF score was 3.1 ± 1.8, and 15 developed HF‐related events during the follow‐up period, including cardiovascular death (n = 2) and hospitalization for HF decompensation (n = 13). Multivariate Cox proportional hazards analysis showed that the H2FPEF score was an independent predictor of future HF‐related events (P < 0.001 for all three models). Kaplan–Meier survival curves showed a significantly higher probability of HF‐related events in the outpatients with a high H2FPEF score (P < 0.001). In receiver operating characteristic (ROC) curve analysis, the H2FPEF score was significantly associated with the occurrence of future HF‐related events (P < 0.001). In ROC curve analysis, the sensitivity, specificity, and positive likelihood ratio of a H2FPEF score of 7 points to predict HF‐related events were 47%, 96%, and 11.4%, respectively. Conclusions: The H2FPEF score could provide useful information for future HF‐related events in stable outpatients with cardiovascular risk factor(s) in Japan. [ABSTRACT FROM AUTHOR]

Objectives: To compare the effects of hybrid iterative reconstruction (HIR) and model-based iterative reconstruction (MBIR) that incorporates a beam-hardening model for myocardial extracellular volume (ECV) quantification by cardiac CT using MRI as a reference standard.Methods: In this retrospective study, a total of 34 patients were evaluated using cardiac CT and MRI. Paired CT image sets were created using HIR and MBIR with a beam-hardening model. We calculated mean absolute differences and correlations between the global mid-ventricular ECV derived from CT and MRI via Pearson correlation analysis. In addition, we performed qualitative analysis of image noise and beam-hardening artifacts on postcontrast images using a four-point scale: 1 = extensive, 2 = strong, 3 = mild, and 4 = minimal.Results: The mean absolute difference between the ECV derived from CT and MRI for MBIR was significantly smaller than that for HIR (MBIR 3.74 ± 3.59%; HIR 4.95 ± 3.48%, p = 0.034). MBIR improved the correlation between the ECV derived from CT and MRI when compared with HIR (MBIR, r = 0.60, p < 0.001; HIR, r = 0.47, p = 0.006). In qualitative analysis, MBIR significantly reduced image noise and beam-hardening artifacts when compared with HIR ([image noise, MBIR 3.4 ± 0.7; HIR 2.1 ± 0.8, p < 0.001], [beam-hardening artifacts, MBIR 3.8 ± 0.4; HIR 2.6 ± 1.0, p < 0.001]).Conclusions: MBIR with a beam-hardening model effectively reduced image noise and beam-hardening artifacts and improved myocardial ECV quantification when compared with HIR using MRI as a reference standard.Key Points: • MBIR with a beam-hardening model effectively reduced image noise and beam-hardening artifacts. • The mean absolute difference between the global mid-ventricular ECV derived from CT and MRI for MBIR was significantly smaller than that for conventional HIR. • MBIR provided more accurate myocardial CT number and improved ECV quantification when compared with HIR. [ABSTRACT FROM AUTHOR]

Transient receptor potential vanilloid 4 (TRPV4) channel, a cation channel expressed in nearly all cell types, plays an important role in the regulation of vascular tone. In the present study, we examined the effect of GSK1016790A, an activator of TRPV4 channels, on the diameter of retinal blood vessels in rats and the underlying mechanisms. Ocular fundus images were captured with an original high-resolution digital fundus camera in vivo and diameters of retinal blood vessels were measured. Intravenous infusion of GSK1016790A (0.2–2 μg kg−1 min−1) increased retinal arteriolar diameter in a dose-dependent manner. The higher dose of GSK1016790A (2 μg kg−1 min−1) slightly decreased blood pressure. These responses to GSK1016790A were significantly attenuated by intravenous injection of GSK2193874 (0.3 mg/kg), an antagonist of TRPV4 channels. Intravitreal injection of Nω-nitro-L-arginine methyl ester, an inhibitor of nitric oxide (NO) synthase or iberiotoxin, an inhibitor of large-conductance Ca2+-activated K+ (BKCa) channel, significantly attenuated the GSK1016790A-induced increases in retinal arteriolar diameter. These results suggest that activation of TRPV4 channels dilates rat retinal arterioles through NO- and BKCa channel-dependent mechanisms in vivo. [ABSTRACT FROM AUTHOR]

Purpose: Retinopathy of prematurity (ROP) is characterized by morphological abnormalities in retinal blood vessels, but how an episode of ROP affects vascular function remains to be fully elucidated. The purpose of the present study was to assess the distribution of pericyte/smooth muscle in retinal blood vessels and retinal vasodilator responses in a rat model of ROP. Methods: ROP was induced in rats by the subcutaneous injection of the vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor KRN633 (10 mg/kg) on postnatal day (P) 7 and P8. The distribution of pericyte/smooth muscle in retinal blood vessels was examined on P14 and P35 by immunohistochemistry. Retinal vasodilator responses were assessed on P35 by measuring the diameter of retinal arterioles in fundus images. Results: In retinas of KRN633-treated (ROP) rats, progressive angiogenesis, tortuous arteries, enlarged veins, and enhanced expression of α-smooth muscle actin in pericytes on capillaries and veins were observed on P14. These abnormalities in retinal vasculature showed a tendency to normalize by P35. Vasodilation of retinal arterioles induced by acetylcholine, an endothelium-dependent vasodilator, was smaller in P35 ROP rats than age-matched controls, whereas retinal vasodilator responses to the nitric oxide (NO) donor NOR3 were unaltered. Conclusions: Phenotypic changes in pericytes occur in the ROP model rats and endothelium-dependent vasodilatory mechanisms in retinal blood vessels are impaired. The impaired vasodilator function may contribute to the progression and pathogenesis of ROP. [ABSTRACT FROM AUTHOR]

We report the anisotropic field-effect hole mobility of 30 nm-thick pentacene films deposited on 1.6 nm-thick polyimide photo-alignment layers with different in-plane anisotropy. To induce different in-plane anisotropy, the light exposure was varied up to 16 J/cm2. In this light exposure range, the long molecular axis of pentacene was standing with respect to the substrate surface (c*-axis oriented 'thin film phase'), and the pentacene molecular plane was oriented on average parallel to the average alignment direction of the underlying polyimide backbone structures. For light exposures of 6 and 11 J/cm2, the field-effect mobility for the current flow direction parallel (perpendicular) to the alignment direction of pentacene molecular plane was enhanced (suppressed) compared to that of the pentacene film deposited on non-aligned polyimide film. This field-effect mobility enhancement shows a positive effect of the in-plane alignment control of pentacene molecules. However, the field-effect mobility decreased at a light exposure of 16 J/cm2, even though the in-plane orientation order of the pentacene molecular plane slightly increased. The causes for the mobility enhancement at 6 and 11 J/cm2 and the mobility decrease at 16 J/cm2 were discussed. [ABSTRACT FROM AUTHOR]

We have succeeded in controlling the pretilt angle of liquid crystal (LC) molecules over the whole range of 0 to 90° by using photo-aligned blend films of two azobenzene-containing polyimides (Azo-PIs) with and without side-chains. The Azo-PIs were synthesized from pyromellitic dianhydride and a mixture of 4,4′-diaminoazobenzene and 4-(4′-propylbi(cyclohexan)-4-yl)phenyl 3,5-diaminobenzoate (PBCP-DABA). PBCP-DABA is a diamine to introduce a side-chain structure into the polyimide. Defect-free uniform LC alignment was obtained in the pretilt angle (θp) ranges of θp ≤ 11° and θp ≥ 78°. Previously, we reported that the pretilt angle can be controlled using pure photo-aligned films of Azo-PIs with different molar fractions of PBCP-DABA. For the pure photo-aligned films, the defect-free pretilt angle ranges were θp < 5° and θp ≥ 85°. These results suggest that the azimuthal anchoring strength of the blend Azo-PI film is stronger than that of the pure films of Azo-PIs with side-chains, at least for the pretilt angle range from 5 to 11°. We found that the defect-free pretilt angle range can be extended by using the blend Azo-PI films instead of the pure Azo-PI films. [ABSTRACT FROM AUTHOR]

We have fabricated organic field-effect transistors (OFETs) with a highly oriented active layer of poly[(9,9-dioctylfluorenyl-2,7-diyl)-co-bithiophene] (F8T2), which was formed with the help of a photoaligned polyimide film. Photoalignment is an attractive technique for integrating OFETs with aligned active layers on the same substrate, because of its potential capability of two-dimensional alignment patterning. The F8T2 layer formed on the photoaligned polyimide film showed an absorption dichroic ratio greater than 15 after annealing at 285 °C. Top-gate/bottom-contact-type OFETs with a parylene gate insulating layer exhibited an enhanced hole mobility (0.016 cm2 V-1 s-1) along the alignment direction of the F8T2 backbone structure and a suppressed one (0.002 cm2 V-1 s-1) along the perpendicular direction. This result shows that the photoaligned polyimide film is an attractive alignment layer for fabricating and integrating OFETs with aligned active layers. Current-direction-dependent bias stress effect was observed for those OFETs; when the current flowed parallel to the alignment direction of the F8T2 backbone structures, a larger negative threshold voltage shift was observed. This anisotropic bias stress effect was discussed on the basis of a microstructure model of aligned F8T2 films. [ABSTRACT FROM AUTHOR]

Polarized polymer-based light-emitting diodes (PLEDs) have been fabricated by inserting a very thin photoaligned polyimide film into the device structure. The photoaligned polyimide film was used to form a highly oriented layer of light-emitting polymer, poly (9,9-dioctylfluorenyl-2,7-diyl) (PFO). The polyimide contains azobenzene in the backbone structure, allowing us to control the alignment of its backbone structure by optical treatment. Since the photoalignment treatment is scratch-free, the thickness of the photoaligned film can be reduced below 4 nm without decreasing its alignment ability for PFO. Even though polyimide is a good insulator, such a very thin photoaligned film can be inserted into PLED structures. We examined the influence of the thickness of the photoaligned polyimide film and the light-emitting layer on the polarization ratio and the current efficiency of the polarized PLEDs. Using a 2.9 nm-thick polyimide photoalignment layer and a 101 nm-thick PFO light-emitting layer, we have succeeded in fabricating a polarized PLED with a current efficiency of 0.3 cd/A at 150 cd/m2 and polarization ratios of 46 at 434 nm, 27 at 460 nm, and 20 for integrated intensity from 400 to 600 nm. [ABSTRACT FROM AUTHOR]

We have investigated the pretilt angle of liquid crystal (LC) molecules induced by photoaligned films of a series of polyimides. The polyimides were random copolymers synthesized from pyromellitic dianhydride and a mixture of 4,4′-diaminoazobenzene and 4-[4′-propylbi(cyclohexan)-4-yl]phenyl 3,5-diaminobenzoate (PBCP-DABA). PBCP-DABA is a diamine to introduce a side-chain structure into polyimide. We found that the pretilt angle of LC molecules can be controlled from 0° to 90° by varying the molar fraction (x) of PBCP-DABA from 0 to 0.5. Defect-free uniform LC alignment was observed for x≤0.125 and x≥0.3, but threadlike textures appeared for 0.15≤x≤0.25. Since the interaction between the polyimide backbone structure and the LC molecule may be blocked by relatively dense side-chains, the appearance of threadlike texture is tentatively attributed to weak azimuthal anchoring strength of the photoaligned polyimide films with x≥0.15. [ABSTRACT FROM AUTHOR]

We have examined the in-plane orientation of liquid crystal (LC) molecules adsorbed on polyimide films as a function of coverage over a submonolayer range. In this study we used 12-nm-thick photoaligned films of polyimide containing azobenzene in the backbone structure (Azo-PI). The in-plane molecular order of the LC layer and the Azo-PI film was determined from the polarization angle dependence of infrared absorption. Even at ∼0.2 ML (monolayer) the orientational distribution of the LC molecules was anisotropic with an in-plane order parameter almost equal to that of the Azo-PI backbone structure in the underlying film. The in-plane order parameter of the LC molecules was constant up to 1 ML. This result indicates that the orientation of the LC molecules directly adsorbed on the polyimide film is determined by the interaction between the polyimide and LC molecules. The interaction among the LC molecules in the first monolayer was found to be negligibly weak compared with that between the polyimide and LC molecules. [ABSTRACT FROM AUTHOR]

We have investigated the inclined alignment of polyimide molecules (containing azobenzene in the backbone structure) induced by oblique angle irradiation of ultraviolet (UV) light. The UV irradiation was performed for a polyamic acid film, which then was thermally converted into a polyimide film. The orientation of the polyimide backbone structure was determined by measuring the polarized infrared absorption spectra as a function of the angle of incidence. We confirmed that inclined alignment of the polyimide backbone structures is obtained by oblique angle UV irradiation, and that this also induces tilted homogeneous liquid crystal (LC) alignment. For the UV irradiation conditions used in the present study, the average inclination angle of the polyimide backbone structure was about 4° from the surface plane. The pretilt angle of the LC molecules was 0.9°. [ABSTRACT FROM AUTHOR]

We have determined the relation between the in-plane anisotropy of the molecular orientation of a liquid crystal (LC) monolayer and the underlying polyimide film exposed to linearly polarized ultraviolet light (LPUVL). To evaluate the anisotropy of the LC monolayer and the polyimide film, the sample orientation dependence of the polarized infrared absorption spectrum was measured. The in-plane anisotropy of the LC monolayer was found to be proportional to that of the polyimide film, the proportionality factor being about 75%. This result strongly suggests that the alignment of the LC molecules in contact with the LPUVL-exposed polyimide film is induced by an interaction between the polyimide and LC molecules. [ABSTRACT FROM AUTHOR]

We have investigated the molecular orientation in the films of polyamic acid (PAA) with azobenzene units in the backbone structure. Anisotropic molecular orientation was induced by irradiation of linearly polarized ultraviolet light (LPUVL). The change in the molecular orientation caused by subsequent thermal imidization was also investigated. The orientation of the PAA and polyimide backbone structures was determined by measuring the polarized infrared absorption spectra of the films. When the PAA film was exposed to LPUVL of wavelength 365 to 400 nm at normal incidence, permanent orientational change of the PAA backbone structure occurred through repeated photoisomerization reactions of the azobenzene unit. The PAA backbone structure rotated toward the plane perpendicular to the polarization direction of LPUVL. In subsequent thermal imidization the molecular order increased significantly around the direction perpendicular to both the polarization direction of LPUVL and the surface normal. This enhancement of the molecular order was tentatively attributed to the crystallization of the film caused by thermal imidization. [ABSTRACT FROM AUTHOR]

We have investigated the anisotropic decomposition of polyimide molecules induced by irradiation of linearly polarized ultraviolet light (LPUVL). Three polyimides were examined: poly [4,4′-oxydiphenylene-pyromellitimide], poly [4,4′-oxydiphenylene-1,2,3,4-butanetetracarboximide] and poly [4,4′-oxydiphenylene-1,2,3,4-cyclobutanetetracarboximide] (CBDA-ODA). Anisotropic decomposition was monitored by measuring the polarized infrared absorption spectra of ∼10 nm thick films as a function of LPUVL exposure. Among the three polyimides, CBDA-ODA showed the largest anisotropy of decomposition in the initial stage of LPUVL exposure. This result suggests that CBDA-ODA is a suitable polyimide material for photoinduced liquid crystal alignment based on photodecomposition reactions. The details of the LPUVL exposure dependence of the film anisotropy are discussed. © 2001 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Determines the relation between the molecular orientation of a rubbed polyimide film and that of a very thin liquid crystal (LC) layer in contact with the polyimide film. Surface LC layer; Explanation for the orientational distribution of the LC molecules.

Background The H2FPEF score is recognized as a simple method to diagnose heart failure (HF) with preserved left ventricular ejection fraction (HFpEF). We investigated the value of the H2FPEF score in predicting subsequent cardiovascular events in HFpEF patients. Methods This study was a retrospective, single-center, observational study. We calculated the H2FPEF scores for 404 consecutive HFpEF patients. Subjects were subdivided into low- (0–3), intermediate- (4–6), and high-score (7–9) groups and followed for 50 months. The primary and secondary endpoints were composite cardiovascular/cerebrovascular events (cardiovascular death, nonfatal myocardial infarction, unstable angina pectoris, hospitalization for HF decompensation, and nonfatal stroke) occurrence and HF-related events (hospitalization for HF decompensation) occurrence at 50 months, respectively. Results Kaplan–Meier analyses demonstrated a significantly higher incidence of cardiovascular/cerebrovascular events among those with a higher H2FPEF score (log-rank test, P = 0.005). The HF-related event rate was higher in proportion to the H2FPEF score (log-rank test, P < 0.001). Multivariate Cox hazard analyses identified the H2FPEF score (per 1 point) as an independent predictor of cardiovascular and HF-related events (hazard ratio [HR], 1.179; 95% confidence interval [CI], 1.066–1.305; P = 0.001 and HR, 1.288; 95% CI, 1.134–1.463; P = 0.001, respectively). Receiver operating characteristic analysis showed that the H2FPEF significantly predicted cardiovascular events (area under the curve [AUC], 0.626; 95% CI, 0.557–0.693; P < 0.001) and HF-related events (AUC, 0.680; 95% CI, 0.600–0.759; P < 0.001). The cutoff H2FPEF score was 5.5 for the identification of cardiovascular and HF-related events. Conclusion The H2FPEF score might be a potentially useful marker for the prediction of cardiovascular and HF-related events in HFpEF patients. Clinical Trails Registration Trail Number UMIN000029600. [ABSTRACT FROM AUTHOR]

Background: In patients with idiopathic pulmonary fibrosis (IPF), continuing treatment with antifibrotic agents is crucial to decrease the reduction of forced vital capacity and mortality rate. However, predictive factors for the discontinuation of antifibrotic agents are unknown. This study aims to investigate the clinical characteristics and predictive factors for the discontinuation of antifibrotic agents in patients with IPF. Methods: This was a double-center retrospective study that enrolled patients with IPF treated with pirfenidone or nintedanib between 2009 and 2017. We compared clinical parameters between the medication-continuing group and the discontinued group. The predictive factors were determined using Cox proportional hazards analyses. Results: A total of 66 subjects were included: 43 received pirfenidone and 23 received nintedanib. At 1 year, 23 of 66 patients had discontinued due to adverse events (n = 12), disease progression (n = 9), or death (n = 2). The characteristics of the discontinuation group were poor performance status (PS) and delay from diagnosis to treatment. In the receiver operating characteristic (ROC) analysis associated with the discontinuation of antifibrotic agents, PS was the highest area under the ROC curve (AUC) value (cut-off value, 2; AUC, 0.83; specificity, 63%; sensitivity, 87%). This finding was consistent even when analyzing, except for examples of death and adjusting for the type of antifibrotic agent. The treatment persistence rate by PS was PS 0–1 = 90%, PS 2 = 65%, and PS 3 = 19%. Analysis of the relationship between PS and administration period of antifibrotic agents revealed that delays from diagnosis to treatment led to worsening of dyspnea, a decline in lung function, and deterioration of PS. Conclusions: PS may be informative for predicting discontinuation of medication. Our data reinforced the importance of early initiation of antifibrotic treatment, and we suggest PS should be used as a guide for starting antifibrotic agents in everyday practice. The reviews of this paper are available via the supplementary material section. [ABSTRACT FROM AUTHOR]

The article offers information on the clinical significance of brachial-ankle pulse wave velocity in patients with heart failure With Reduced Left Ventricular ejection fraction. Topics discussed include measurement of ankle-brachial pressure index (ABI) and baPWV values at stable condition after optimal therapy for HF in 201 consecutive HFrEF patients; and concludes that identifying complications of Peripheral arterial disease and measuring baPWV values in HFrEF patients were useful.

We examined the effect of probucol, an antihyperlipidemic drug with potent antioxidant properties, on cataract formation in streptozotocin (STZ)-induced hyperglycemic rats that were given 5% D-glucose as drinking water. Probucol treatment was initiated immediately after the induction of hyperglycemia was confirmed. Using full horizontal-plane lens images captured with an original digital camera system, the opacity of central region of lens was assessed by measuring the opaque area in the region. Central opacities were detected after 3 weeks of hyperglycemia, and progressed in a time-dependent manner. The majority of STZ-induced hyperglycemic rats developed severe cataracts after 9 weeks of hyperglycemia. Probucol slowed the progression of cataracts in a dose-dependent manner. Levels of sorbitol and protein carbonyls in lenses of STZ-induced hyperglycemic rats were higher than those of control rats. Probucol suppressed the increase in protein carbonyls, but not of sorbitol, in lenses of STZ-induced hyperglycemic rats. Probucol had no significant effect on increases in plasma concentrations of glucose, total cholesterol, and triglyceride observed in STZ-induced hyperglycemic rats. These results suggest that probucol slows the progression of sugar cataracts, independent of its lipid-lowering effects. The beneficial effect of probucol on cataracts is partially attributable to the attenuation of oxidative damage to lens proteins. [ABSTRACT FROM AUTHOR]