Vivaria housing conditions expose sex differences in brain oxidation, microglial activation, and immune system states in aged hAPOE4 mice.

Apolipoprotein E ε4 allele (APOE4) is the predominant genetic risk factor for late-onset Alzheimer's disease (AD). APOE4 mouse models have provided advances in the understanding of disease pathogenesis, but unaccounted variables like rodent housing status may hinder translational outcomes. Non-sterile aspects like food and bedding can be major sources of changes in rodent microflora. Alterations in intestinal microbial ecology can cause mucosal barrier impairment and increase pro-inflammatory signals. The present study examined the role of sterile and non-sterile food and housing on redox indicators and the immune status of humanized-APOE4 knock-in mice (hAPOe4). hAPOE4 mice were housed under sterile conditions until 22 months of age, followed by the transfer of a cohort of mice to non-sterile housing for 2 months. At 24 months of age, the redox/immunologic status was evaluated by flow cytometry/ELISA. hAPOE4 females housed under non-sterile conditions exhibited: (1) higher neuronal and microglial oxygen radical production and (2) lower CD68+ microglia (brain) and CD8+ T cells (periphery) compared to sterile-housed mice. In contrast, hAPOE4 males in non-sterile housing exhibited: (1) higher MHCII+ microglia and CD11b+CD4+ T cells (brain) and (2) higher CD11b+CD4+ T cells and levels of lipopolysaccharide-binding protein and inflammatory cytokines in the periphery relative to sterile-housed mice. This study demonstrated that sterile vs. non-sterile housing conditions are associated with the activation of redox and immune responses in the brain and periphery in a sex-dependent manner. Therefore, housing status may contribute to variable outcomes in both the brain and periphery.

Decoding signaling pathways involved in prolactin-induced neuroprotection: A review.

It has been well recognized that prolactin (PRL), a pleiotropic hormone, has many functions in the brain, such as maternal behavior, neurogenesis, and neuronal plasticity, among others. Recently, it has been reported to have a significant role in neuroprotection against excitotoxicity. Glutamate excitotoxicity is a common alteration in many neurological and neurodegenerative diseases, leading to neuronal death. In this sense, several efforts have been made to decrease the progression of these pathologies. Despite various reports of PRL's neuroprotective effect against excitotoxicity, the signaling pathways that underlie this mechanism remain unclear. This review aims to describe the most recent and relevant studies on the molecular signaling pathways, particularly, PI3K/AKT, NF-κB, and JAK2/STAT5, which are currently under investigation and might be implicated in the molecular mechanisms that explain the PRL effects against excitotoxicity and neuroprotection. Remarkable neuroprotective effects of PRL might be useful in the treatment of some neurological diseases.

Mesenchymal stromal cells in the regeneration of radiation-induced organ sequelae: will they make the difference?

Mesenchymal stromal cells (MSCs) are a stem cell product with good safety that demonstrate significant clinical efficacy in the treatment of different pathologies, including radiation diseases (e.g. radiological burns, pelvic radiation disease). While the first results for some first human applications for the treatment of radiation disease suggest benefit, larger trials with clinically important endpoints are needed before definitive conclusions can be drawn. However, the supply and cost of MSCs remain the two main limitations for this innovative therapeutic product. Exosomes (EXOs), a stem cell product associated with MSC therapy, have shown promising efficacy and safety in humans. MSC-EXO therapeutics represent a promising next-generation approach for treating radiation diseases involving a primary (major) inflammatory component. Provided that conditions for MSC-EXO production and bio-banking are agreed in the near future, the transition to industrial production of MSC-EXOs will be possible, and this is required to initiate well-controlled clinical trials for approval by the European Medicines Agency (EMA) and US Food and Drug Administration (FDA).

Regional disparity of HIV incidence and prevalence among men who have sex with men.

BACKGROUND: HIV incidence can be estimated with cross-sectional studies using clinical, serological, and molecular data. Worldwide, HIV incidence data in only men who have sex with men (MSM) are scarce and principally focus on those with healthcare or under treatment. However, better estimates can be obtained through studies with national representativeness. The objective was to estimate the prevalence, incidence, and factors associated with acquiring HIV in a national sample of MSM who attend meeting places, considering geographical regions. METHODS: A nationally representative survey of MSM attending meeting places was performed in Mexico. Participants answered a questionnaire, and a dried blood spot (DBS) was collected. Samples were classified as recent infections using an algorithm with HIV status, antiretroviral therapy, and the result of BED-EIA assay. Parameters were analysed considering regions and demographic and sexual behaviour characteristics. RESULTS: The national HIV prevalence was 17.4% with regional differences; the highest prevalence (20.7%) was found in Mexico City, and the lowest prevalence was found in the West region (11.5%). The incidence was 9.4 per 100 p/y, with regional values from 6.2 to 13.2 for the Northeast and the Centre regions, respectively. Age, age at sexual debut, low wealth index, and rewarded sex were associated with HIV prevalence. Centre region, use of private clinics as health services, and having sex exclusively with men were associated with recent HIV infections. CONCLUSIONS: The incidence and prevalence showed regional differences, suggesting a difference in the dynamics of HIV transmission; some regions have a greater case accumulation, and others have a greater rate of new infections. Understanding this dynamic will allow developing health programs focused on HIV prevention or treating people already living with HIV.

Ultrasonographic and hemodynamic characteristics of patients with symptomatic carotid near-occlusion: results from a multicenter registry study.

PURPOSE: The ultrasonographic and hemodynamic features of patients with carotid near-occlusion (CNO) are still not well known. Our aim was to describe the ultrasonographic and hemodynamic characteristics of a cohort of patients with CNO. METHODS: A prospective, observational, nationwide, and multicenter study was conducted from January/2010 to May/2016. Patients with digital subtraction angiography (DSA)-confirmed CNO were included. We collected information on clinical and demographic characteristics, carotid and transcranial ultrasonography and DSA findings, presence of full-collapse, collateral circulation, and cerebrovascular reactivity (CVR). RESULTS: One hundred thirty-five patients were analyzed. Ultrasonographic and DSA diagnosis of CNO were concordant in only 44%. This disagreement was related to the presence/absence of full-collapse: 45% of patients with CNO with full-collapse were classified as a complete carotid occlusion, and 40% with a CNO without full-collapse were interpreted as severe stenosis (p < 0.001). Mean velocities (mV) and pulsatility indexes (PIs) were significantly lower in the ipsilateral middle cerebral artery compared with the contralateral (43 cm/s vs 58 cm/s, p < 0.001; 0.80 vs 1.00, p < 0.001). Collateral circulation was identified in 92% of patients, with the anterior communicating artery (73%) being the most frequent. CVR was decreased or exhausted in 66% of cases and was more frequent in patients with a poor or absent collateral network compared with patients with ≥ 2 collateral arteries (82% vs 56%, p = 0.051). CONCLUSION: The accuracy of carotid ultrasonography in the diagnosis of CNO seems to be limited, with significant discrepancies with DSA. Decreased ipsilateral mV, PI, and CVR suggest a hemodynamic compromise in patients with CNO.

The risk of recurrent stroke at 24 months in patients with symptomatic carotid near-occlusion: results from CAOS, a multicentre registry study.

BACKGROUND AND PURPOSE: The risk of recurrent stroke amongst patients with symptomatic carotid near-occlusion (SCNO) has not been clearly established, and its management remains controversial. The aim was to define the 24-month risk of recurrent stroke and to analyse the effect of the different treatment modalities (medical treatment and revascularization) in a population of patients with SCNO. METHODS: A multicentre, nationwide, prospective study from January 2010 to May 2016 was performed. Patients with angiography-confirmed SCNO were included. The primary end-point was ipsilateral ischaemic stroke including periprocedural events within 24 months following the presenting event. Revascularization results and periprocedural complications, ipsilateral transient ischaemic attack, disabling or fatal stroke, and mortality were also noted. RESULTS: The study population comprised 141 patients from 17 Spanish centres. Seventy patients (49.6%) were treated by revascularization (carotid stenting in 47, endarterectomy in 23). Complete revascularization was achieved in 58 patients (83%). Periprocedural stroke or death occurred in 5.7%. The 24-month cumulative incidence of the primary end-point was 11.1% (95% confidence interval 5.8-16.4; n = 15), 12% in the medical treatment group and 10.2% in the revascularization group, log-rank P = 0.817. The cumulative rates of ipsilateral ischaemic stroke or transient ischaemic attack, disabling or fatal stroke, and mortality, were 17%, 4.5% and 7.5%, respectively. CONCLUSIONS: The rate of ipsilateral ischaemic stroke in patients with SCNO seems to be lower than the known rate associated with severe carotid stenosis without near-occlusion. The potential benefit of revascularization in the prevention of stroke in patients with SCNO may be influenced by the effectiveness and safety of the procedure.

Mature teratoma of the pineal region in the paediatric age group: A case report and review of the literature.

INTRODUCTION: Intracranial teratomas account for 0.5% of all intracranial tumours and 2-4% of intracranial tumours in children. However, in terms of tumours of the pineal area, the exact incidence is not ascertained. Although, it is noted that 50-60% of central nervous system (CNS) germ cell tumours are found in the pineal gland. The degree of difficulty in the sampling of lesions in the pineal gland during biopsy emphasizes the importance of correlating the imaging studies, histopathologic findings, and serum and cerebrospinal fluid (CSF) tumour markers. CASE REPORT: This case report is that of a 9-year-old male who presented with frontal headache of eight days, with associated photophobia, nausea and vomiting, and diplopia. Biopsy with intraoperative navigation was done and the specimen was referred for histopathologic evaluation. The biopsy showed findings consistent with a mature teratoma with no histologic findings of an immature component or secondary somatic malignancy. Comparison of the pre-operative and post-operative multiaxial cranial CT scan showed findings that was consistent with a residual lesion. This was correlated with the pre-operative serum tumour markers which showed alpha-fetoprotein of 22.5 ng/mL and beta-HCG of 1.0 mIU/mL(IU/L), and the post-operative tumour markers of the cerebrospinal fluid that showed alpha-fetoprotein of 3.28 ng/mL and beta-HCG of 18.9 mIU/mL (IU/L). CONCLUSION: A review of the literature and comparison with current case in relation to the histopathologic, serum and CSF findings, and imaging studies was done to better understand the mechanism of this lesion.

Thermodynamic sorption analysis and glass transition temperature of faba bean (Vicia faba L.) protein.

Freeze-dried faba bean (Vicia faba L.) protein adsorption isotherms were determined at 25, 35 and 40 °C and fitted with the Guggenheim-Anderson-de Boer model. The pore radius of protein was in the range of 0.87-6.44 nm, so that they were considered as micropores and mesopores. The minimum integral entropy ranged between 4.33 and 4.44 kg H2O/100 kg d.s., was regarded as the point of maximum of stability. The glass transition temperature of the protein equilibrated at the different conditions of storage was determined, showing that the protein remained in glassy state for all cases. The protein showed compact and rigid structures, evidenced by microscopy analysis.

Preterm birth: the role of knowledge transfer and exchange.

BACKGROUND: Preterm birth (PTB) is the leading cause of death in children under age five. Healthcare policy and other decision-making relevant to PTB may rely on obsolete, incomplete or inapplicable research evidence, leading to worsened outcomes. Appropriate knowledge transfer and exchange (KTE) strategies are an important component of efforts to reduce the global PTB burden. We sought to develop a 'landscape' analysis of KTE strategies currently used in PTB and related contexts, and to make recommendations for optimising programmatic implementation and for future research. METHODS: In the University of California, San Francisco's Preterm Birth Initiative, we convened a multidisciplinary working group and examined KTE frameworks. After selecting a widely-used, adaptable, theoretically-strong framework we reviewed the literature to identify evidence-based KTE strategies. We analysed KTE approaches focusing on key PTB stakeholders (individuals, families and communities, healthcare providers and policymakers). Guided by the framework, we articulated KTE approaches that would likely improve PTB outcomes. We further applied the KTE framework in developing recommendations. RESULTS: We selected the Linking Research to Action framework. Searches identified 19 systematic reviews, including two 'reviews of reviews'. Twelve reviews provided evidence for KTE strategies in the context of maternal, neonatal and child health, though not PTB specifically; seven reviews provided 'cross-cutting' evidence that could likely be generalised to PTB contexts. For individuals, families and communities, potentially effective KTE strategies include community-based approaches, 'decision aids', regular discussions with providers and other strategies. For providers, KTE outcomes may be improved through local opinion leaders, electronic reminders, multifaceted strategies and other approaches. Policy decisions relevant to PTB may best be informed through the use of evidence briefs, deliberative dialogues, the SUPPORT tools for evidence-informed policymaking and other strategies. Our recommendations for research addressed knowledge gaps in regard to partner engagement, applicability and context, implementation strategy research, monitoring and evaluation, and infrastructure for sustainable KTE efforts. CONCLUSIONS: Evidence-based KTE, using strategies appropriate to each stakeholder group, is essential to any effort to improve health at the population level. PTB stakeholders should be fully engaged in KTE and programme planning from its earliest stages, and ideally before planning begins.

Positive influence of a dental anaesthesia simulation model on the perception of learning by Mexican dental students.

INTRODUCTION: This study evaluated the influence of three-repetition training with a dental anaesthesia simulation model (DASM) on the perception of learning by dental students. MATERIALS AND METHODS: Dental students who had never used a dental anaesthesia technique were randomly divided into two groups that were taught the anterior superior alveolar nerve infiltrative anaesthesia technique. Group 1 (G1; N = 10) followed a three-stage learning method: (i) theoretical lecture, (ii) clinical demonstration and (iii) DASM training, including three repetitions of the anaesthesia technique. Group 2 (G2; N = 10) followed only the 1st and 2nd stages. The students in both groups then performed the anaesthesia technique. The perception of the students was evaluated by four learning concepts. Each was evaluated with a 5-point Likert scale questionnaire. The average score of each item of the questionnaire for G1 was compared with that of G2. Statistically significant differences were identified with the Mann-Whitney test. The average working time of each group was timed and compared by Student's t-test to identify possible statistically significant differences. RESULTS: Students in G1 showed higher average scores of perception in controlling the handling of the dental syringe and confidence in performing the injection (P < 0.05) and showed an average working time shorter than that of the students in G2 (P < 0.05). CONCLUSION: The DASM positively influenced the perception learning of the dental students; it increased their confidence and syringe handling ability, as well as skills to perform the injection of anaesthesia more quickly.

Desigualdad social y tendencias de mortalidad por diabetes.

OBJECTIVE: To identify the trend of national diabetes mortality by level of marginality at the state and municipal levels. METHOD: A descriptive study was conducted with records of deaths from diabetes in over 20 years from 1990 to 2013. The national mortality rate was calculated standardized by age according to the 2000 world population and the state level 2013 saw the projected naational population by join point analysis for trend analysis was performed. RESULTS: For the general population, the annual percentage change between 1990 and 1996 was 2.2, from 1996 to 2005 was 4.3, and from 2005 to 2013 was 0.1. The largest increase among women occurred between 1998 and 2005 while among men occurred between 1995 and 2006. At the state level was found higher annual percentage change between the towns with the highest degree of marginalization. CONCLUSIONS: The mortality of diabetes in women shows a significant decrease since 2004, among men, the mortality with a continuous upward trend, consistent with the trend that the disease has had in recent years.

Endovascular treatment of cerebral venous sinus thrombosis (CVST): Is a complete recanalization required for a good clinical outcome?

The usual therapy in cerebral venous sinus thrombosis (CVST) is based on anticoagulant treatment with adjusted-dose unfractionated heparin. When medical treatment fails, endovascular techniques, such as mechanical thrombectomy, are available. We report a case of a 21-year-old woman with a diagnosis of left CVST, treated by a neurointerventional approach with mechanical thrombectomy using the Penumbra(®) System. Despite the fact that only incomplete recanalization was achieved, a gradual resolution of the thrombus and a progressive clinical improvement occurred.

Are the clinical guideline recommendations on gastroprotection being followed? A review in patients taking nonsteroidal anti-inflammatory drugs. / ¿Qué tanto se siguen las recomendaciones de las guías clínicas sobre gastroprotección? Una revisión en enfermos que consumen antiinflamatorios no esteroideos.

INTRODUCTION AND AIMS: The chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) can cause complications in the gastrointestinal tract. The use of proton pump inhibitors (PPIs) is recommended in high-risk patients to prevent them. OBJECTIVE: The aim of this article was to evaluate the gastroprotection measures taken in persons with chronic NSAID use. MATERIALS AND METHODS: A descriptive cross-sectional study was conducted. The clinical records were reviewed of patients seen as outpatients at the Rheumatology Department over a 4-month period, choosing those with chronic NSAID use, and intentionally looking for gastroprotection measures according to the recommendations published by the American College of Gastroenterology. RESULTS: A total of 417 patients (347 women; mean age: 48.12±14.2 years) were included. The most frequent diagnosis was rheumatoid arthritis (65%). Nine patients (2.1%) had a history of peptic ulcer, 48 (11.5%) patients were 65 years of age or older, 26 (6.2%) patients took NSAIDs and aspirin, and 130 (31.2%) took NSAIDs with steroids. Tests for Helicobacter pylori infection were done in just 53 cases, and there were positive results in only 9 (16%). Some risk for gastrointestinal toxicity was established in 211 cases and only 65 (30.8%) received gastroprotection. In contrast, 31 (15%) patients received gastroprotection when there was no indication for it. CONCLUSION: Prophylaxis with PPIs in chronic NSAID users was inadequately employed. It was not prescribed in the majority of patients (69.2%) and it was used with no justification in others (15%).

[Treatment of postpartum hemorrhage with intrauterine hydrostatic condom]. / Tratamiento de la hemorragia posparto con condón hidrostático intrauterine.

OBJECTIVE: To report of experience of intrauterine hydrostatic condom to control obstetric hemorrhage. MATERIAL AND METHOD: Descriptive, retro-prospective study. The method was use in patients who had obstetric hemorrhage and do not responded to medical management during the period from March 1st to August27, 2015 in a rural facility. RESULTS: 955 patients that had a vaginal delivery were identified, 40 (4.1%) of which needed the application of the method. The method was unsuccessful in 2 of 40 patients (5%), one requiring emergency obstetric hysterectomy and other exploratory laparotomy with conservative measures. 11 of 40 patients (2 7.5%) required at least 1-3 globular packs transfusion. None of the 38 patients (95%) who responded to the method presented endometritis in the postpartum follow up or complications associated with the use of hydrostatic condom. CONCLUSION: The use of intrauterine hydrostatic condom is an effective method to control postpartum obstetric hemorrhage secondary to uterine atony unresponsive to medical management.

First approach to characterize tilts through multiple pistons in the classical Ronchi test.

In this work, it is shown how a tilt can be introduced into a segmented surface through several piston terms, by using the classical Ronchi test. We have developed tilt error simulations by adding multiple constant terms to each point on the sagitta surface of a segment using ray tracing. Thereby a comparison between simulated Ronchigrams for piston and tilt has been performed for two adjacent segments, so that it is possible to appreciate the tilt and piston effects on the shape of the patterns. As a result, we show the behavior of the central maximum of the fringes in the presence of tilt and/or piston. Additionally we present evidence of introducing tilting without changing the surface shape by adding multiple pistons, and a description of how to characterize both piston and tilt using the Ronchi test.

Lipopolysaccharide-Induced Ionized Hypocalcemia and Acute Kidney Injury in Carotid Chemo/Baro-Denervated Rats.

The acute kidney injury (AKI) observed during sepsis is due to an uncontrolled release of inflammatory mediators. Septic patients develop electrolytic disturbances and one of the most important is ionized hypocalcemia. AKI adversely affects the function of other organs and hypocalcemia is associated with cardiovascular and respiratory dysfunctions. Since carotid body chemoreceptors modulate the systemic inflammatory response during sepsis syndromes, we used pentobarbitone-anesthetized male Sprague-Dawley rats in control condition (SHAM surgery) and after bilateral carotid neurotomy (carotid chemo/baro-denervated, BCN). We evaluate serum creatinine (CRE), serum neutrophil gelatinase-associated lipocaline (NGAL), ionized calcium (iCa) and cardiac Troponin I (cTnI) 90 min after the IP administration of 15 mg/kg lipopolysaccharide (LPS) or saline. In the SHAM group, LPS failed to induce significant changes CRE, NGAL, or iCa, and increased cTnI. Conversely, in the BCN group LPS increased CRE and NGAL, decreased iCa, and enhanced the increase of cTnI. Our results suggest that carotid chemo/baro-receptors might contribute to the regulation of both renal function and calcemia during sepsis. In addition, results imply that the carotid chemo-baroreceptors serve as an immunosensory organ.

Cryptomphalus aspersa mollusc eggs extract promotes migration and prevents cutaneous ageing in keratinocytes and dermal fibroblasts in vitro.

BACKGROUND: The search of substances that minimize cutaneous ageing has increased in the last few years. Previous studies have described the regenerative properties of the secretion of the mollusc Cryptomphalus aspersa (C. aspersa) when applied topically. OBJECTIVE: We evaluate the in vitro effects of a new product derived from the eggs of C. aspersa, IFC-CAF, on cell proliferation, migration, distribution of cytoskeletal proteins, production of extracellular components as well as its ability to prevent cutaneous ageing because of intrinsic or extrinsic factors (exposure to UVB) by determination of ageing markers. METHODS: We have used the human keratinocyte cell line (HaCaT cells), primary dermal fibroblasts (HDF) and senescent dermal fibroblasts (SHDF). The effects of the compound on cell proliferation and on the cell cycle were determined by the MTT colorimetric assay, estimation of total protein and/or trypan blue test and by flow cytometry, respectively. We also studied cell migration using the wound-healing migration assay, whereas ELISA assays, Western Blot and immunofluorescence microscopy were carried out to test the expression of proteins related to cytoskeleton, extracellular matrix and with ageing. RESULTS: We have found that IFC-CAF does not promote proliferation but induces migration of HaCaT, HDF and SHDF in a time- and dose-dependent manner; a better organization of cytoskeletal proteins (F-actin and vimentin) and promotes the production of extracellular components (fibronectin, collagen 1 and MMPs) and the adhesion to cell-substrate vinculin protein. IFC-CAF also prevents cutaneous ageing. The treatment decreases the expression of the ageing-related markers b-Gal, p53 and p16INK4 in SDDF cells, and improves cell survival after UVB irradiation and nuclear repair in HaCaT cells. CONCLUSION: IFC-CAF has regenerative properties and protects against ageing factors being, therefore, a potential therapeutic agent for treating or preventing skin ageing.

Salivary Urease and ADS Enzymatic Activity as Endogenous Protection against Dental Caries in Children.

UNLABELLED: The aim of this cross sectional study was to evaluate the ureolytic and arginolytic activities of saliva in children and associate them with their caries status. STUDY DESIGN: 65, 8 year old children, were randomly selected. The ureolytic and arginolytic activity of non stimulated saliva was studied and associated with DMFT and dmft index. Saliva of children were sampled under fasting conditions; Children refrained from any oral hygiene procedures during the 12 hours that preceded the sample collection. Caries activity was scored and divided in 3 groups: Group A: Index zero: without lesions; Group B: Moderate Index: 1 to 3 enamel caries lesions; and Group C: High Index: more than 4 dentin caries lesions. RESULTS: DMFT scores were moderate: 0.4(±0.79) and dmft: 2.78(±2.45). Results expressed in µmol/min/mg/protein, for urease activity were statistically significant (p=0.048): Group A= 0.69 (±0.7); Group B= 0.45 (±0.43); and Group C= 0.39 (±0.55). The arginine deiminase activity was not statistically significant (p=0.16): Group A= 2.53 (±1.42), Group B= 2.31 (±1.57) and Group C= 1.97 (±2.0). CONCLUSION: Higher levels of ureolytic (statistically significant) and arginolytic activity (trend) in saliva were associated with lower DMFT/dmft scores in 8 year old children. There was a higher production of ammonia from the arginine deiminase system than the urease enzyme in saliva (p>0.05).

Regadenoson in Europe: first-year experience of regadenoson stress combined with submaximal exercise in patients undergoing myocardial perfusion scintigraphy.

PURPOSE: Regadenoson was approved for clinical use in Europe in 2011. Since then, it has become the default form of stress at our institution. We have assessed the side-effect profile and tolerability of regadenoson in patients undergoing clinically indicated myocardial perfusion scintigraphy between July 2011 and July 2012. METHODS: Clinical, stress and imaging data were recorded prospectively. Symptoms during stress were recorded and defined as mild, moderate or severe. An adverse event was defined as any symptom that persisted for more than 30 min or that required investigation or treatment. RESULTS: Of 1,764 consecutive patients, 1,581 (90%) received regadenoson combined with submaximal exercise unless contraindicated. Symptoms were common (63%) but transient and well-tolerated. The severity of symptoms was recorded in most patients as mild (84%). Dyspnoea (36%) and chest discomfort (12%) were the commonest side effects. Adverse events were reported in eight patients (0.5%), thought to be vasovagal in seven of these. All patients recovered fully without sequelae. There were no deaths, myocardial infarction or hospital admissions. Regadenoson stress was performed in 206 patients (12%) with asthma or chronic obstructive pulmonary disease (COPD) without bronchospasm or any other major side effect. CONCLUSION: We studied the symptom profile of regadenoson in the largest European cohort to date. Regadenoson combined with submaximal exercise was well tolerated, notably also in patients with asthma or COPD. The majority of regadenoson-related adverse events were vasovagal episodes without sequelae.