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Objective-Collateral artery growth (arteriogenesis) is an important adaptive response to hampered arterial perfusion.It is unknown whether preventive physical exercise before limb ischemia can improve arteriogenesis and modulate mononuclear cell function. This study aimed at investigating the effects of endurance exercise before arterial occlusion on MNC function and collateral artery growth. Approach and Results-After 3 weeks of voluntary treadmill exercise, ligation of the right femoral artery was performed in mice. Hindlimb perfusion immediately after surgery did not differ from sedentary mice. However, previous exercise improved perfusion restoration ≤7 days after femoral artery ligation, also when exercise was stopped at ligation. This was accompanied by an accumulation of peri-collateral macrophages and increased expression of endothelial nitric oxide synthase and inducible nitric oxide synthase (iNOS) in hindlimb collateral and in MNC of blood and spleen. Systemic monocyte and macrophage depletion by liposomal clodronate but not splenectomy attenuated exercise-induced perfusion restoration, collateral artery growth, peri-collateral macrophage accumulation, and upregulation of iNOS. iNOS-deficient mice did not show exercise-induced perfusion restoration. Transplantation of bone marrow-derived MNC from iNOSdeficient mice into wild-type animals inhibited exercise-induced collateral artery growth. In contrast to sedentary controls, thrice weekly aerobic exercise training for 6 months in humans increased peripheral blood MNC iNOS expression. Conclusions-Circulating mononuclear cell-derived inducible nitric oxide is an important mediator of exercise-induced collateral artery growth.

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Aims:We aimed at developing a structured study protocol utilizing the bibliographic web-application science performance evaluation (SciPE) to perform comprehensive scientometric analyses.Methods and results: Metadata related to publications derived from online databases were processed and visualized by transferring the information to an undirected multipartite graph and distinct partitioned sets of nodes. Also, institutionspecific data was normalized and merged allowing precise geocoordinate positioning, to enable heatmapping and valid identification. As a result, verified, processed data regarding articles, institutions, journals, authors gender, nations and subject categories can be obtained. We recommend including the total number of publications, citations, the population, research institutions, gross domestic product, and the country-specific modified Hirsch-Index and to form corresponding ratios (e.g. population/publication). Also, our approach includes implementation of bioinformatical methods such as heatmapping based on exact geocoordinates, simple chord diagrams, and the central implementation of specific ratios with plain visualization techniques. Conclusion:This protocol allows precise conduction of contemporaneous scientometric analyses based on bioinformatic and meta-analytical techniques allowing to evaluate and contextualize scientific efforts. Data presentation with the depicted visualization techniques are mandatory for transparent and consistent analyses of research output across different nations and topics. Research performance can then be discussed in a synopsis of all findings.

Background The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has instigated immediate and massive worldwide research efforts. Rapid publication of research data may be desirable but also carries the risk of quality loss. Objective This analysis aimed to correlate the severity of the COVID-19 outbreak with its related scientific output per country. Methods All articles related to the COVID-19 pandemic were retrieved from Web of Science and analyzed using the web application SciPE (science performance evaluation), allowing for large data scientometric analyses of the global geographical distribution of scientific output. Results A total of 7185 publications, including 2592 articles, 2091 editorial materials, 2528 early access papers, 1479 letters, 633 reviews, and other contributions were extracted. The top 3 countries involved in COVID-19 research were the United States, China, and Italy. The confirmed COVID-19 cases or deaths per region correlated with scientific research output. The United States was most active in terms of collaborative efforts, sharing a significant amount of manuscript authorships with the United Kingdom, China, and Italy. The United States was China’s most frequent collaborative partner, followed by the United Kingdom. Conclusions The COVID-19 research landscape is rapidly developing and is driven by countries with a generally strong prepandemic research output but is also significantly affected by countries with a high prevalence of COVID-19 cases. Our findings indicate that the United States is leading international collaborative efforts.

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Objective: Renal denervation (RDN) can reduce sympathetic activity and blood pressure (BP) in hypertensive patients, which both have an impact on atrial fibrillation. We performed a systematic meta-analysis on the effects of renal denervation (RDN) in addition to pulmonary vein isolation (PVI) in patients with atrial fibrillation. Methods: All published randomized controlled trials investigating the effects of RDN as adjunctive treatment to PVI for rhythm control of atrial fibrillation were included. Primary endpoint was recurrence of atrial fibrillation after 12 months on average. Results: A total of six randomized controlled studies including 689 patients with hypertension and symptomatic atrial fibrillation were included. In five studies, patients had uncontrolled BP despite prescription of an average of three antihypertensive agents. PVI was performed with irrigated radio-frequency catheters in 387 patients, and in 302 with cryoballoon. Cardiac ablation catheters were used for RDN in 78% of all cases. In the remaining 22%, RDN was performed using a designated, nonirrigated radio-frequency catheter system. After 12 months, the mean odds ratio for recurrence of atrial fibrillation for PVI with RDN compared with PVI alone was 0.43 (95% confidence interval 0.32–0.59). After RDN, BP was reduced significantly whereas no changes were reported in the PVI-only groups. No relevant complications associated to RDN were documented. Conclusion: This meta-analysis supports the concept of RDN as an adjunctive treatment for atrial fibrillation. Further studies with standardized PVI and RDN procedures are needed.

Purpose Hypertension represents the most common cardiovascular risk factor for premature death worldwide. Hydrochlorothiazide (HCTZ) is one of the most commonly used antihypertensive and diuretic drug worldwide. Recently, pharmacoepidemiologic studies associated the use of HCTZ with increased risk of skin cancer. As a result, prescriptions of HCTZ decreased, leading to worsening of blood pressure therapy in a significant proportion of patients. However, whether HCTZ causes skin cancer remains elusive. We aimed to examine the photosensitive potential of HCTZ in vivo. To further enlighten the pathophysiologic mechanisms of carcinogenesis and phototoxicity caused by HCTZ in vitro, we conducted a series of laboratory experiments. Methods This randomized, double-blinded, placebo-controlled clinical trial assessed the phototoxic properties of HCTZ. We randomly assigned 30 healthy adult volunteers in a 2:1 ratio to either HCTZ 25 mg daily or placebo once daily for 15 days. Skin photosensitivity by phototesting for UV-A and UV-B radiation, office blood pressure, serum-vitamin-D status and urinary excretion of thymidine-dimers were measured. To further assess the pathophysiologic mechanisms of possibly HCTZ induced photosensitivity, human keratinocytes (HaCaT) were incubated with HCTZ and then irradiated with UV-B radiation (311 nm one burst of 100 J/cm2). rt-PCR-testing and western blots were performed to analyze reactive oxygen species, inflammation and carcinogenesis. Results All 30 participants were adherent to the protocol, as confirmed by toxicological analysis of serum and urine. Skin photosensitivity to exposure of UV-A and UV-B radiation remained unchanged in both groups (UVB-MED: HCTZ Δ = 0.0 J/cm2 vs. placebo Δ = −0.2 J/cm2; p=0.06). No thymidine-dimers were detected in urine of either group. Systolic blood pressure decreased in both groups but was not different between HCTZ and placebo (HCTZ Δ = −5.2 mmHg vs. placebo Δ = −5.4 mmHg; p=0.94). The same was found for diastolic blood pressure (HCTZ Δ = −1.9 mmHg vs. placebo Δ = −4.3 mmHg; p=0.34). Serum-vitamin-D increased in both groups (HCTZ Δ = +2.7 ng/ml vs. placebo Δ = 0.9 ng/ml; p=0.56). In addition, combination of HCTZ and a high intensity burst of UV-B radiation did not increase expression of inflammatory proteins or increase formation of reactive oxygen species (SOD-1, SOD-2, and catalase). Conclusions HCTZ did not significantly increase photosensitivity for UV-A or UV-B radiation in healthy volunteers compared with placebo. Moreover, no relevant DNA-damages were detected in either group. HCTZ alone did not increase inflammation, formation of reactive oxygen species or carcinogenesis in human keratinocytes. Furthermore, the combination of a UV-B burst of 100 J/cm2 and HCTZ was not associated with additive effects on inflammation, reactive oxygen species or carcinogenisis. HCTZ in a cumulative dose of 375 did not increase photosensitivity or DNA-damages in vivo. Funding Acknowledgement Type of funding sources: None.