Weyl-mediated helical magnetism in NdAlSi.

Emergent relativistic quasiparticles in Weyl semimetals are the source of exotic electronic properties such as surface Fermi arcs, the anomalous Hall effect and negative magnetoresistance, all observed in real materials. Whereas these phenomena highlight the effect of Weyl fermions on the electronic transport properties, less is known about what collective phenomena they may support. Here, we report a Weyl semimetal, NdAlSi, that offers an example. Using neutron diffraction, we found a long-wavelength helical magnetic order in NdAlSi, the periodicity of which is linked to the nesting vector between two topologically non-trivial Fermi pockets, which we characterize using density functional theory and quantum oscillation measurements. We further show the chiral transverse component of the spin structure is promoted by bond-oriented Dzyaloshinskii-Moriya interactions associated with Weyl exchange processes. Our work provides a rare example of Weyl fermions driving collective magnetism.

Thermodynamic Evidence of Proximity to a Kitaev Spin Liquid in Ag_{3}LiIr_{2}O_{6}.

Kitaev magnets are materials with bond-dependent Ising interactions between localized spins on a honeycomb lattice. Such interactions could lead to a quantum spin-liquid (QSL) ground state at zero temperature. Recent theoretical studies suggest two potential signatures of a QSL at finite temperatures, namely, a scaling behavior of thermodynamic quantities in the presence of quenched disorder, and a two-step release of the magnetic entropy. Here, we present both signatures in Ag_{3}LiIr_{2}O_{6} which is synthesized from α-Li_{2}IrO_{3} by replacing the interlayer Li atoms with Ag atoms. In addition, the dc susceptibility data confirm the absence of a long-range order, and the ac susceptibility data rule out a spin-glass transition. These observations suggest a closer proximity to the QSL in Ag_{3}LiIr_{2}O_{6} compared to its parent compound α-Li_{2}IrO_{3} that orders at 15 K. We discuss an enhanced spin-orbit coupling due to a mixing between silver d and oxygen p orbitals as a potential underlying mechanism.

Predictors of coronary artery disease in middle-aged Taiwanese women at premenopause, postmenopause and after undergoing hysterectomy.

AIMS AND OBJECTIVES: To examine the predictors of coronary artery disease among middle-aged women at various menopausal statuses. BACKGROUND: Few studies have explored coronary artery disease predictors among middle-aged women at various menopausal statuses, particularly with the inclusion of women who underwent a hysterectomy. DESIGN: A cross-sectional design was adopted. METHODS: Two hundred and twenty-five middle-aged women who were waiting for catheterisation examinations because of possible coronary artery disease were selected. These patients were divided into premenopausal (n = 41), postmenopausal (n = 143) and women who had undergone a hysterectomy groups (n = 41). The differences in the risk factors for coronary artery disease between patients with coronary artery disease (catheterisation results showing stenosis of >50% in at least one major coronary artery) and those without coronary artery disease in the three groups were compared. RESULTS: The participants were aged 56·8 ± 5·9 years. In the premenopausal group, the odds of coronary artery disease among ever or current smokers was 8·46 times the odds of coronary artery disease for the never smokers. In the postmenopausal group, the odds of coronary artery disease among diabetes patients was 2·89 times the odds of coronary artery disease for those without diabetes. Each additional point on the Chinese Beck Depression Inventory-II increased the risk of coronary artery disease by 5%. In the hysterectomy group, each additional increase in 1 mmHg in systolic blood pressure increased the risk of coronary artery disease by 4%. CONCLUSIONS: Smoking, diabetes, depression and systolic blood pressure are predictors of coronary artery disease in middle-aged women at premenopause, postmenopause and after undergoing hysterectomy respectively. RELEVANCE TO CLINICAL PRACTICE: These results are beneficial for middle-aged women at various menopausal stages to effectively implement prevention of coronary artery disease. These findings were among women being evaluated for possible coronary artery disease, we suggest the need for further study in lager, longitudinal studies.

Src contributes to IL6-induced vascular endothelial growth factor-C expression in lymphatic endothelial cells.

Formation of lymphatic capillaries by lymphatic endothelial cells (LECs) occurs both in normal tissues as well as in pathological processes including tumor metastasis. Interleukin-6 (IL-6), a potent pro-inflammatory cytokine, has been shown to be highly elevated in various cancers. IL-6 has also been shown to increase tumor lymphangiogenesis through vascular endothelial growth factor-C (VEGF-C) induction in tumor cells. Although lymphangiogenesis is associated with lymph node metastasis and also resistance to conventional therapy in various cancers, the precise mechanisms of lymphangiogenesis in LECs remain unclear. This study aimed to investigate the signaling cascade involved in IL-6-induced VEGF-C expression in murine LECs (SV-LEC). The VEGF-C mRNA and protein levels were increased in SV-LECs exposed to IL-6. IL-6 time-dependently induced Src phosphorylation and downstream phosphorylation of ERK1/2 and p38MAPK. In contrast, PP2, an inhibitor of Src signaling, abrogated IL-6's effects on ERK1/2 and p38MAPK phosphorylation. IL-6 exposure also led to increase in VEGF-C promoter-luciferase activity as well as C/EBPß- and κB-luciferase activities. VEGF-C promoter-, C/EBPß- and κB-luciferase activities were all suppressed by Src, ERK1/2 or p38MAPK signaling blockades despite presence of IL-6. Finally, C/EBPß and p65 binding to the VEGF-C promoter region were increased after IL-6 exposure in SV-LECs. Taken together, we report a Src-mediated ERK1/2 and p38MAPK activation resulting in C/EBPß and p65 binding to the promoter region of VEGF-C, leading to VEGF-C expression in IL-6-exposed SV-LECs.

Bipolar Disorder and Schizophrenia Present Different Risks of Atrial fibrillation: A Nationwide Population-Based Analysis.

BACKGROUND: Atrial fibrillation (AF) is increasingly prevalent in society, and can elevate cardiac morbidity and mortality. Psychosis and gender are known to play important roles in the genesis of AF. However, it is not clear whether gender modulates the impact of different psychoses on the occurrences of AF. METHODS: We identified patients suffering from bipolar disorder and schizophrenia, with and without AF, using the Taiwan National Health Insurance nationwide database. The identified patient population consisted of 927,915 subjects (463,050 males and 464,865 females) from 2001 to 2008, which included 2,963 (3.2 ‰) schizophrenia patients (1,650 males and 1,313 females) and 5,112 (5.5 ‰) bipolar-disorder patients (1,934 males and 3,178 females). RESULTS: The male and female bipolar-disorder patients had higher prevalences of AF than did male (16.5 ‰ vs. 2.4 ‰, p < 0.001) and female (12.9 ‰ vs. 2.3 ‰, p < 0.001) schizophrenia patients. Furthermore, male and female bipolar-disorder patients had higher AF prevalences than did males (8.5 ‰, p < 0.001) and females (7.2 ‰, p < 0.001) in the general population. Schizophrenia patients had lower AF prevalence than the general population in male, but not in female gender. Males had a higher AF prevalence than females. However, male and female bipolar disorder and schizophrenia patients had similar AF prevalences. Those patients with schizophrenia and bipolar-disorder patients with AF were older than those without AF. CONCLUSIONS: Differing risk factors for AF were identified in bipolar-disorder and schizophrenia patients. Compared to the general population, gender may have different impacts on the occurrence of AF in psychosis patients. KEY WORDS: Atrial fibrillation; Bipolar disorder; Population-based study; Schizophrenia.

Acute myocardial infarction risk prediction in emergency chest pain patients: An external validation study.

BACKGROUND: Chest pain is a common symptom that presents to the emergency department (ED), and its causes range from minor illnesses to serious diseases such as acute coronary syndrome. Accurate and timely diagnosis is essential for the efficient management and treatment of these patients. OBJECTIVE: This study aims to expand on a model previously developed by the Chi Mei Medical Group (CMMG) Emergency Department in 2020 to predict adverse cardiac events in patients with chest pain. The main goal is to evaluate the accuracy and generalizability of the model through external validation using data from other hospitals. METHODS: The initial model for this study was developed using data from three CMMG-affiliated hospitals in southern Taiwan. We utilized four supervised machine learning algorithms, namely random forest, logistic regression, support-vector clustering, and K-nearest neighbor, to predict the risk of acute myocardial infarction within a one month for emergency chest pain patients. The study used the model with the best area under the curve (AUC), recall and precision for external validation. The external validated data source was data collected from three hospitals associated with Taipei Medical University (TMU) in northern Taiwan. RESULTS: The original best model constructed by CMMG exhibited an AUC of 0.822, an accuracy of 0.740, a recall of 0.741, a precision of 0.566, a specificity of 0.740, and an NPV of 0.861. Subsequently, during the external validation phase, CMMG's top-performing model demonstrated acceptable validation result with TMU's data, achieving an AUC of 0.63, an accuracy of 0.661, a recall of 0.593, a precision of 0.243, a specificity of 0.691, and an NPV of 0.900. While the results indicate that the model's performance varied across different datasets and are not outstanding, the model is still acceptable for clinical application as a preliminary decision-support tool. CONCLUSION: This study highlights the importance of external validation to confirm the applicability of the previously developed predictive model in other hospital settings. Although the model shows potential in assessing chest pain patients in the ED, its broad clinical application requires further validation to ensure it can improve patient outcomes and optimize healthcare resource allocation.

Giant Hall Switching by Surface-State-Mediated Spin-Orbit Torque in a Hard Ferromagnetic Topological Insulator.

Topological insulators (TI) and magnetic topological insulators (MTI) can apply highly efficient spin-orbit torque (SOT) and manipulate the magnetization with their unique topological surface states (TSS) with ultrahigh efficiency. Here, efficient SOT switching of a hard MTI, V-doped (Bi,Sb)2Te3 (VBST), with a large coercive field that can prevent the influence of an external magnetic field, is demonstrated. A giant switched anomalous Hall resistance of 9.2 kΩ is realized, among the largest of all SOT systems, which makes the Hall channel a good readout and eliminates the need to fabricate complicated magnetic tunnel junction (MTJ) structures. The SOT switching current density can be reduced to 2.8 × 105 A cm-2, indicating its high efficiency. Moreover, as the Fermi level is moved away from the Dirac point by both gate and composition tuning, VBST exhibits a transition from edge-state-mediated to surface-state-mediated transport, thus enhancing the SOT effective field to (1.56 ± 0.12) × 10-6 T A-1 cm2 and the interfacial charge-to-spin conversion efficiency to 3.9 ± 0.3 nm-1. The findings establish VBST as an extraordinary candidate for energy-efficient magnetic memory devices.

Engineering Anomalously Large Electron Transport in Topological Semimetals.

Anomalous transport of topological semimetals has generated significant interest for applications in optoelectronics, nanoscale devices, and interconnects. Understanding the origin of novel transport is crucial to engineering the desired material properties, yet their orders of magnitude higher transport than single-particle mobilities remain unexplained. This work demonstrates the dramatic mobility enhancements result from phonons primarily returning momentum to electrons due to phonon-electron dominating over phonon-phonon scattering. Proving this idea, proposed by Peierls in 1932, requires tuning electron and phonon dispersions without changing symmetry, topology, or disorder. This is achieved by combining de Haas - van Alphen (dHvA), electron transport, Raman scattering, and first-principles calculations in the topological semimetals MX2 (M = Nb, Ta and X = Ge, Si). Replacing Ge with Si brings the transport mobilities from an order magnitude larger than single particle ones to nearly balanced. This occurs without changing the crystal structure or topology and with small differences in disorder or Fermi surface. Simultaneously, Raman scattering and first-principles calculations establish phonon-electron dominated scattering only in the MGe2 compounds. Thus, this study proves that phonon-drag is crucial to the transport properties of topological semimetals and provides insight to engineer these materials further.

Nonlinear optical diode effect in a magnetic Weyl semimetal.

Diode effects are of great interest for both fundamental physics and modern technologies. Electrical diode effects (nonreciprocal transport) have been observed in Weyl systems. Optical diode effects arising from the Weyl fermions have been theoretically considered but not probed experimentally. Here, we report the observation of a nonlinear optical diode effect (NODE) in the magnetic Weyl semimetal CeAlSi, where the magnetization introduces a pronounced directionality in the nonlinear optical second-harmonic generation (SHG). We demonstrate a six-fold change of the measured SHG intensity between opposite propagation directions over a bandwidth exceeding 250 meV. Supported by density-functional theory, we establish the linearly dispersive bands emerging from Weyl nodes as the origin of this broadband effect. We further demonstrate current-induced magnetization switching and thus electrical control of the NODE. Our results advance ongoing research to identify novel nonlinear optical/transport phenomena in magnetic topological materials and further opens new pathways for the unidirectional manipulation of light.

Analysis of 10-year nationwide population-based data on sex differences in hospitalization for heart failure.

Sex-related factors play an important role in the pathophysiology of heart failure (HF). However, trends in sex-related differences in hospital management for HF are not clear. We identified patients hospitalized for HF through a nationwide database (National Health Insurance in Taiwan), containing 722,272 subjects from 1999 to 2008. Higher incidences of diabetes mellitus (37 vs. 25 %, p < 0.001), thyroid dysfunction (2 vs. 0 %, p < 0.001), and transient cerebral ischemia (2 vs. 1 %, p < 0.05), as well as a lower incidence of chronic lung disease (14 vs. 22 %, p < 0.001) differentiated female HF patients from male HF patients. During this 10-year period, both percentage of HF hospitalization and age-adjusted HF rates significantly increased for total HF sample (1.92 vs. 2.49  ‰, p < 0.05, and 20.44 vs. 27.38/100,000, p < 0.05) and for female (1.76 vs. 2.86  ‰, p < 0.05, and 20.94 vs. 32.12/100,000, p < 0.05), but such changes did not occur among male patients (2.12 vs. 2.09  ‰, p > 0.05, and 19.93 vs. 22.51/100,000, p > 0.05). The age at the time of hospitalization and the length of the hospital stay increased significantly for all HF patients during the 10-year study period. However, the daily cost of hospitalization increased in males, but not in females. Compared to the survivors, patients who died were older and had a longer hospitalization and higher daily cost both in males and females. Through our analysis of the NHI database, we observed trends in factors related to hospitalization of HF patients in Taiwan that may be attributable to sex-related differences in the pathophysiology and treatment strategies for HF.

Analysis on key parameters in subretinal injection facilitating a predictable and automated robot-assisted treatment in gene therapy.

BACKGROUND: Subretinal injection (SRI) has become an important surgical method for treating vitreoretinal diseases. Nevertheless, the optimisation of bleb formation in SRI, for the attainment of desired therapeutic outcomes, still requires further investigation. METHODS: This study analysed the influence of surgical parameters on SRI using a robotic setup. The surgical procedure was automated using visual guidance. A predictive model for bleb formation was established through regression analysis. To validate the model, we compared the clinical data's target area with the simulated SRI's actual area using parameters determined by the predictive model. RESULTS: The insertion angle dominated the eccentricity and area of the bleb. The injection speed dominated the axial angle. Automated SRI increased success rate and produced predictable outcomes. CONCLUSIONS: We could provide accurate SRI on phantom models by adjusting surgical parameters based on the patient's clinical information. Automatic robot-assisted SRI is a promising surgical technique with highly predictable results.

Manipulating Topological Phases in Magnetic Topological Insulators.

Magnetic topological insulators (MTIs) are a group of materials that feature topological band structures with concurrent magnetism, which can offer new opportunities for technological advancements in various applications, such as spintronics and quantum computing. The combination of topology and magnetism introduces a rich spectrum of topological phases in MTIs, which can be controllably manipulated by tuning material parameters such as doping profiles, interfacial proximity effect, or external conditions such as pressure and electric field. In this paper, we first review the mainstream MTI material platforms where the quantum anomalous Hall effect can be achieved, along with other exotic topological phases in MTIs. We then focus on highlighting recent developments in modulating topological properties in MTI with finite-size limit, pressure, electric field, and magnetic proximity effect. The manipulation of topological phases in MTIs provides an exciting avenue for advancing both fundamental research and practical applications. As this field continues to develop, further investigations into the interplay between topology and magnetism in MTIs will undoubtedly pave the way for innovative breakthroughs in the fundamental understanding of topological physics as well as practical applications.

Emergent ferromagnetism with superconductivity in Fe(Te,Se) van der Waals Josephson junctions.

Ferromagnetism and superconductivity are two key ingredients for topological superconductors, which can serve as building blocks of fault-tolerant quantum computers. Adversely, ferromagnetism and superconductivity are typically also two hostile orderings competing to align spins in different configurations, and thus making the material design and experimental implementation extremely challenging. A single material platform with concurrent ferromagnetism and superconductivity is actively pursued. In this paper, we fabricate van der Waals Josephson junctions made with iron-based superconductor Fe(Te,Se), and report the global device-level transport signatures of interfacial ferromagnetism emerging with superconducting states for the first time. Magnetic hysteresis in the junction resistance is observed only below the superconducting critical temperature, suggesting an inherent correlation between ferromagnetic and superconducting order parameters. The 0-π phase mixing in the Fraunhofer patterns pinpoints the ferromagnetism on the junction interface. More importantly, a stochastic field-free superconducting diode effect was observed in Josephson junction devices, with a significant diode efficiency up to 10%, which unambiguously confirms the spontaneous time-reversal symmetry breaking. Our work demonstrates a new way to search for topological superconductivity in iron-based superconductors for future high Tc fault-tolerant qubit implementations from a device perspective.

Gender differences and the trend in the acute myocardial infarction: a 10-year nationwide population-based analysis.

It is not clear whether gender is associated with different hospitalization cost and lengths for acute myocardial infarction (AMI). We identified patients hospitalized for primary diagnosis of AMI with (STEMI) or without (NSTEMI) ST elevation from 1999 to 2008 through a national database containing 1,000,000 subjects. As compared to that in 1999~2000, total (0.35‰ versus 0.06‰, P < 0.001) and male (0.59‰ versus 0.07‰, P < 0.001) STEMI hospitalization percentages were decreased in 2007~2008, but female STEMI hospitalization percentages were not different from 1999 to 2008. However, NSTEMI hospitalization percentages were similar over the 10-year period. The hospitalization age for AMI, STEMI, and NSTEMI was increased over the 10-year period by 14, 9, and 7 years in male, and by 18, 18, and 21 years in female. The female and male hospitalization cost and lengths were similar in the period. As compared to nonmedical center, the hospitalization cost for STEMI in medical center was higher in male patients, but not in female patients, and the hospitalization cost for NSTEMI was higher in both male and female gender. We found significant differences between male and female, medical center and non-medical center, or STEMI and NSTEMI on medical care over the 10-year period.

Combination Biomarker of Immune Checkpoints Predict Prognosis of Urothelial Carcinoma.

In contrast to Western counties, the incidence of urothelial carcinoma (UC) remains mar-edly elevated in Taiwan. Regulatory T cells (Tregs) play a crucial role in limiting immune responses within the tumor microenvironment. To elucidate the relationship between immune checkpoints in the tumor immune microenvironment and UC progression, we utilize the Gene Expression Omnibus (GEO) to analyze a microarray obtained from 308 patients with UC. We observed that the expression level of CD276 or TIM-3 was positively correlated with late-stage UC and poor prognosis. Patients with simultaneously high CD276 and TIM-3 expression in tumors have significantly reduced both univariate and multivariate survival, indicating that mRNA levels of these immune checkpoints could be independent prognostic biomarkers for UC overall survival and recurrence. Our cohort study showed rare CD8+ cytotoxic T-cells and Tregs infiltration during early-stage UC-known as cold tumors. Approximately 30% of late-stage tumors exhibited highly infiltrated cytotoxic T cells with high PD-1 and FOXP3 expression, which implied that cytotoxic T cells were inhibited in the advanced UC microenvironment. Collectively, our findings provide a better prognosis prediction by combined immune checkpoint biomarkers and a basis for early-stage UC standard treatment to convert cold tumors into hot tumors, followed by immune checkpoint therapy.

Evidence of a coupled electron-phonon liquid in NbGe2.

Whereas electron-phonon scattering relaxes the electron's momentum in metals, a perpetual exchange of momentum between phonons and electrons may conserve total momentum and lead to a coupled electron-phonon liquid. Such a phase of matter could be a platform for observing electron hydrodynamics. Here we present evidence of an electron-phonon liquid in the transition metal ditetrelide, NbGe2, from three different experiments. First, quantum oscillations reveal an enhanced quasiparticle mass, which is unexpected in NbGe2 with weak electron-electron correlations, hence pointing at electron-phonon interactions. Second, resistivity measurements exhibit a discrepancy between the experimental data and standard Fermi liquid calculations. Third, Raman scattering shows anomalous temperature dependences of the phonon linewidths that fit an empirical model based on phonon-electron coupling. We discuss structural factors, such as chiral symmetry, short metallic bonds, and a low-symmetry coordination environment as potential design principles for materials with coupled electron-phonon liquid.

Exploring key factors in the choice of e-health using an asthma care mobile service model.

Asthma care mobile service (ACMS) is a care platform for asthma patients using mobile phones to monitor asthma patients' real-time conditions. The anticipated benefits and development of the healthcare network platform rely on people's adoptive willingness and behavioral intention. The goal of this study is to understand and predict patients' acceptance behavior for ACMS as an application of e-health. The study is based on the technology acceptance model and integrates "subjective norm" and "innovativeness" to understand and predict the patient's attitude and behavioral intention. Employing a convenience sampling method, valid questionnaire responses were obtained from 229 patients. A confirmatory factor analysis examined the reliability and validity of the measurement model, while the structural equation modeling technique was employed to interpret the causal model. The model was used in the study to explain and predict the utilization of ACMS with a high explanatory power as a good-fit model. The results indicated the most critical factor that affects behavioral intentions related to ACMS is user attitude, followed by perceived usefulness, subjective norm, perceived ease of use, and innovativeness. The results provide the government developing high-tech, preventive medicine strategies the necessary data to define an appropriate policy to use in attracting greater participation in the effort.

WMJ-S-001, a Novel Aliphatic Hydroxamate-Based Compound, Suppresses Lymphangiogenesis Through p38mapk-p53-survivin Signaling Cascade.

Background and purpose: Angiogenesis and lymphangiogenesis are major routes for metastatic spread of tumor cells. It thus represent the rational targets for therapeutic intervention of cancer. Recently, we showed that a novel aliphatic hydroxamate-based compound, WMJ-S-001, exhibits anti-angiogenic, anti-inflammatory and anti-tumor properties. However, whether WMJ-S-001 is capable of suppressing lymphangiogenesis remains unclear. We are thus interested in exploring WMJ-S-001's anti-lymphangiogenic mechanisms in lymphatic endothelial cell (LECs). Experimental approach: WMJ-S-001's effects on LEC proliferation, migration and invasion, as well as signaling molecules activation were analyzed by immunoblotting, flow-cytometry, MTT, BrdU, migration and invasion assays. We performed tube formation assay to examine WMJ-S-001's ex vivo anti-lymphangiogenic effects. Key results: WMJ-S-001 inhibited serum-induced cell proliferation, migration, invasion in murine LECs (SV-LECs). WMJ-S-001 reduced the mRNA and protein levels of survivin. Survivin siRNA significantly suppressed serum-induced SV-LEC invasion. WMJ-S-001 induced p53 phosphorylation and increased its reporter activities. In addition, WMJ-S-001 increased p53 binding to the promoter region of survivin, while Sp1 binding to the region was decreased. WMJ-S-001 induced p38 mitogen-activated protein kinase (p38MAPK) activation. p38MPAK signaling blockade significantly inhibited p53 phosphorylation and restored survivin reduction in WMJ-S-001-stimulated SV-LCEs. Furthermore, WMJ-S-001 induced survivin reduction and inhibited cell proliferation, invasion and tube formation of primary human LECs. Conclusions and Implications: These observations indicate that WMJ-S-001 may suppress lymphatic endothelial remodeling and reduce lymphangiogenesis through p38MAPK-p53-survivin signaling. It also suggests that WMJ-S-001 is a potential lead compound in developing novel agents for the treatment of lymphangiogenesis-associated diseases and cancer.

Vitamin D and bisphosphonates therapies for osteoporosis are associated with different risks of atrial fibrillation in women: A nationwide population-based analysis.

Osteoporosis and atrial fibrillation (AF) are common in post-menopausal women. Vitamin D and bisphosphonates are widely used to treat osteoporosis, and these may have different effects on the risk of AF.The goal of this study was to evaluate whether different agents for treating osteoporosis modulate the risk of AF in a population-based database.We identified 20,788 female patients suffering from osteoporosis who were or were not treated with vitamin D or bisphosphonates using the Taiwan National Health Insurance nationwide database from 2000 to 2008 and followed them up for 5 consecutive years to determine if they had a new diagnosis of AF after the diagnosis of osteoporosis.There were 14 (2.67%) new AF diagnoses in osteoporosis patients treated with bisphosphonates, one (0.28%) new AF diagnosis in patients treated with vitamin D, and 279 (1.40%) new AF diagnoses in patients who were not treated with vitamin D or bisphosphonates (neither group). Osteoporosis patients who received bisphosphonates showed a higher incidence of AF occurrence than those that were not treated with bisphosphonates (P = .015). In contrast, 1 patient who received vitamin D had a new diagnosis of AF during the study period; thus, the incidence was significantly lower than that in the patients treated with bisphosphonates (P = .007). In addition, the patients who were treated with vitamin D had a lower incidence of AF than did those who were not treated with either vitamin D or bisphosphonates (P = .074). Kaplan-Meier analysis also showed a significant difference in AF occurrence in different groups during the 5-year follow-up (P = .010).Different treatment for osteoporosis may carry diverse risks of AF occurrence. Vitamin D may have potential beneficial effects of reducing AF occurrence in osteoporosis patients.

Effects of the angiotensin II type 1 receptor antagonist valsartan on the expression of superoxide dismutase in hypertensive patients.

The role of oxidative stress in the pathogenesis of vascular diseases such as hypertension has been well recognized. Angiotensin (Ang) II is regarded as a pro-oxidant because it can stimulate the production of reactive oxygen species. The purpose of this study was to evaluate whether treatment with the Ang II type 1 (AT(1)) receptor antagonist valsartan has an antioxidant effect in patients with mild to moderate hypertension. A randomized, double-blind, placebo-controlled study was conducted in 48 stage I and II hypertensive subjects. Patients were followed every 4 weeks for 12 weeks after randomization to valsartan titrated to 80 to 160 mg once or twice daily or matching placebo. The erythrocyte superoxide dismutase (SOD) activity and expression of SOD-mRNA in polymorphonuclear leukocytes were measured before and after treatment. Valsartan showed concentration-dependent inhibition of reactive oxygen species generation in polymorphonuclear leukocytes from hypertensive patients. The erythrocyte superoxide dismutase activity before treatment was more than 2 times higher in hypertensive subjects compared to normal controls. Superoxide dismutase activity decreased significantly after 12 weeks of treatment with valsartan but did not change with placebo. The amount of SOD-mRNA in the polymorphonuclear leukocytes decreased progressively over 3 months in the hypertensive subjects receiving valsartan treatment but did not change in the placebo group. The production of reactive oxygen species is increased in hypertension, and superoxide dismutase activity is increased, presumably as a compensatory mechanism. Treatment with valsartan but not placebo resulted in a progressive down-regulation of SOD-mRNA expression and a reduction in superoxide dismutase activity, suggesting antioxidant activity and a reduction of reactive oxygen species generation. These findings imply that AT(1) receptor antagonists may provide benefits to hypertensive patients beyond blood pressure reduction.