Backgrounds: Several studies have shown the serum high sensitive cardiac troponin I (hs-TnI) a biomarker of myocardium injury, and C-reactive protein (CRP), a biomarker of inflammation, are associated with worse cardiovascular outcomes. We evaluated the relationship between the hs-TnI level in patients with paroxysmal atrial fibrillation (PAF) after pulmonary vein isolation (PVI) and atrial fibrillation (AF) recurrence. Methods and Results:We enrolled 263 consecutive PAF patients who underwent PVI from May 2017 to April 2018. We investigated the difference in the relationship between the myocardial injury marker (serum hs-TnI), inflammatory marker (CRP, white blood cell) at 36 to 48 hours after the PVI, and early or late recurrence of AF (ERAF; <3 months and LRAF; from 3 months to 1 year) between the radiofrequency ablation group (R group) and cryoballoon ablation group (C group). The R group consisted of 147 patients and the C groups consisted of 116 patients. The serum hs-TnI level in R group was significantly lower than in the C group (2.33 vs 5.08 ng/mL; P < .001), while the CRP was significantly higher in the R group than C group (2.02 vs 1.10 mg/dL; P < .001). The incidences of an ERAF/LRAF were similar between the two groups.Conclusion: Cryoballoon ablation may cause more myocardial injury than radiofrequency catheter ablation, on the contrary, radiofrequency catheter ablation, may cause more inflammation than cryoballoon ablation. However, these phenomena may not affect the recurrence of AF after the PVI in patient with PAF. K E Y W O R D Shigh-sensitive cardiac troponin-T, inflammation, myocardial injury, paroxysmal atrial fibrillation, pulmonary vein isolation, recurrence of AF

Various characteristics of complex gene regulatory networks (GRNs) have been discovered during the last decade, e.g., redundancy, exponential indegree distributions, scale-free outdegree distributions, mutational robustness, and evolvability. Although progress has been made in this field, it is not well understood whether these characteristics are the direct products of selection or those of other evolutionary forces such as mutational biases and biophysical constraints. To elucidate the causal factors that promoted the evolution of complex GRNs, we examined the effect of fluctuating environmental selection and some intrinsic constraining factors on GRN evolution by using an individual-based model. We found that the evolution of complex GRNs is remarkably promoted by fixation of beneficial gene duplications under unpredictably fluctuating environmental conditions and that some internal factors inherent in organisms, such as mutational bias, gene expression costs, and constraints on expression dynamics, are also important for the evolution of GRNs. The results indicate that various biological properties observed in GRNs could evolve as a result of not only adaptation to unpredictable environmental changes but also non-adaptive processes owing to the properties of the organisms themselves. Our study emphasizes that evolutionary models considering such intrinsic constraining factors should be used as null models to analyze the effect of selection on GRN evolution.

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Cancer chemotherapy-induced peripheral neuropathy (CIPN) often results in discontinuation of treatment with potentially useful anticancer drugs and may deteriorate the patient's quality of life. This study investigated the effect of contact needle therapy (CNT) on CIPN caused by responsible chemotherapeutic agents as taxanes and oxaliplatin. Six patients with CIPN were treated with CNT. The severity of CIPN was evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) version 4 and FACT/GOG-Ntx before and after CNT. After the treatment, all of the patients showed some improvement. Four patients showed apparent improvement in breakthrough pain. One of the cases had difficulty in walking because of CIPN in lower extremities, but after 2 times of CNT, he could walk without pain and could continue the chemotherapy. Although its putative mechanisms remain elusive, CNT has strong potential as an adjunctive therapy in CIPN. Well-designed clinical trials with adequate sample size and power are necessary to confirm the findings of this study.

Background An association between uric acid (UA) and cardiovascular diseases, including heart failure (HF), has been reported. However, whether UA is a causal risk factor for HF is controversial. In particular, the prognostic value of lowering UA in patients with HF with preserved ejection fraction (HFpEF) is unclear. Methods and Results We enrolled patients with HFpEF from the PURSUIT‐HFpEF (Prospective Multicenter Observational Study of Patients With Heart Failure With Preserved Ejection Fraction) registry. We investigated whether UA was correlated with the composite events, including all‐cause mortality and HF rehospitalization, in patients with hyperuricemia and HFpEF (UA >7.0 mg/dL). Additionally, we evaluated whether lowering UA for 1 year (≥1.0 mg/dL) in them reduced mortality or HF rehospitalization. We finally analyzed 464 patients with hyperuricemia. In multivariable Cox regression analysis, UA was an independent determinant of composite death and rehospitalization (hazard ratio [HR], 1.15 [95% CI, 1.03–1.27], P =0.015). We divided them into groups with severe and mild hyperuricemia according to median estimated value of serum UA (8.3 mg/dL). Cox proportional hazards models revealed the incidence of all‐cause mortality was significantly higher in the group with severe hyperuricemia than in the group with mild hyperuricemia (HR, 1.73 [95% CI, 1.19–2.25], P =0.004). The incidence of all‐cause mortality was significantly decreased in the group with lowering UA compared with the group with nonlowering UA (HR, 1.71 [95% CI, 1.02–2.86], P =0.041). The incidence of urate‐lowering therapy tended to be higher in the group with lowering UA than in the group with nonlowering UA (34.9% versus 24.6%, P =0.06). Conclusions UA is a predictor for the composite of all‐cause death and HF rehospitalization in patients with hyperuricemia and HFpEF. In these patients, lowering UA, including the use of urate‐lowering therapy, may improve prognosis.