A cross-institutional analysis of the effects of broadening trainee professional development on research productivity.

PhD-trained scientists are essential contributors to the workforce in diverse employment sectors that include academia, industry, government, and nonprofit organizations. Hence, best practices for training the future biomedical workforce are of national concern. Complementing coursework and laboratory research training, many institutions now offer professional training that enables career exploration and develops a broad set of skills critical to various career paths. The National Institutes of Health (NIH) funded academic institutions to design innovative programming to enable this professional development through a mechanism known as Broadening Experiences in Scientific Training (BEST). Programming at the NIH BEST awardee institutions included career panels, skill-building workshops, job search workshops, site visits, and internships. Because doctoral training is lengthy and requires focused attention on dissertation research, an initial concern was that students participating in additional complementary training activities might exhibit an increased time to degree or diminished research productivity. Metrics were analyzed from 10 NIH BEST awardee institutions to address this concern, using time to degree and publication records as measures of efficiency and productivity. Comparing doctoral students who participated to those who did not, results revealed that across these diverse academic institutions, there were no differences in time to degree or manuscript output. Our findings support the policy that doctoral students should participate in career and professional development opportunities that are intended to prepare them for a variety of diverse and important careers in the workforce.

ß-Lactam allergy delabeling is safe and saves costs in Primary Care.

OBJECTIVE: To determine whether the ß-lactam allergy delabeling was safe and cost-saving in Primary Care (PC) patients. DESIGN: We have conducted a retrospective chart review of PC patients with ß-lactam allergy label evaluated in our Allergy Unit between 2017 and 2022. SITE: Allergy Department. Hospital Virgen del Rocio (Sevilla). PARTICIPANTS: A total of 391 patients labeled for ß-lactam allergy in PC were studied. MAIN MEASUREMENTS: (a) Outcome evaluation of a ß-lactam allergy delabeling procedure. (b) A ratio between the total e-prescribed antibiotic cost and the number of treatment days (the experimental daily antibiotic cost or EDAC) before and after delabeling was analyzed in delabeled and truly allergic patients. RESULTS: The results of skin testing were positive in 9.2% of the reported cases (36 of 391 patients). The reactions to oral provocation challenge (OPC) occurred in 2.14% of the patients who underwent negative skin testing to offending ß-lactam (in 15 of 699 OPC). A total of 307 patients (78.5%) were delabeled; 70 (17.9%) had a ß-lactam selective response and 14 (3.59%) reacted to both penicillin and cephalosporin. The EDAC before and after the procedure in delabeled patients was significantly lower (0.88 € vs 0.62 €, p<10-3), than that observed in truly allergic group (0.87 € vs. 0.76 €, p=not significant). CONCLUSION: To delabel ß-lactam allergy in Primary Care patients is safe in most patients, cost-saving in antibioticotherapy, and allows identify the main clinical ß-lactam allergy phenotypes that benefit from this procedure.

Down-Regulation of CK2α Leads toUp-Regulation of the Cyclin-Dependent Kinase Inhibitor p27KIP1 in Conditions Unfavorable for the Growth of Myoblast Cells.

BACKGROUND/AIMS: Compelling evidence indicates that CK2α, which is one of the two catalytic isoforms of protein kinase CK2, is required for cell viability and plays an important role in cell proliferation and differentiation. While much is known on CK2 in the context of disease states, particularly cancer, its critical role in non-cancerous cell growth has not been extensively investigated. METHODS: In the present study, we have employed a cell line derived from rat heart with inducible down-regulation of CK2α and CK2α-knockout mouse tissue to identify CK2-mediated molecular mechanisms regulating cell growth. For this, we have performed Incucyte® live-cell analysis and applied flow cytometry, western blot, immunoprecipitation, immunohistochemistry, RT-qPCR and luciferase-based methods. RESULTS: Here, we show that lack of CK2α results in significantly delayed cell cycle progression through G1, inhibition of cyclin E-CDK2 complex, decreased phosphorylation of Rb protein at S795, and inactivation of E2F transcription factor. These events are accompanied by nuclear accumulation and up-regulation of the cyclin-dependent kinase inhibitor p27KIP1 in cells and CK2α-knockout mouse tissues. We found that increased levels of p27KIP1 are mainly attributable to post-translational modifications, namely phosphorylation at S10 and T197 amino acid residues catalyzed by Dyrk1B and AMPK, respectively, as silencing of FoxO3A transcription factor, which activates CDKN1B the gene coding for p27KIP1, does not result in markedly decreased expression levels of the corresponding protein. Interestingly, simultaneous silencing of CK2α and p27KIP1 significantly impairs cell cycle progression without increasing cell death. CONCLUSION: Taken together, our study sheds light on the molecular mechanisms controlling cell cycle progression through G1 phase when myoblasts proliferation potential is impaired by CK2α depletion. Our results suggest that elevated levels of p27KIP1, which follows CK2α depletion, contribute to delay the G1-to-S phase transition. Effects seen when p27KIP1 is down-regulated are independent of CK2α and reflect the protective role exerted by p27KIP1 under unfavorable cell growth conditions.

Specific inhibition of GPCR-independent G protein signaling by a rationally engineered protein.

Activation of heterotrimeric G proteins by cytoplasmic nonreceptor proteins is an alternative to the classical mechanism via G protein-coupled receptors (GPCRs). A subset of nonreceptor G protein activators is characterized by a conserved sequence named the Gα-binding and activating (GBA) motif, which confers guanine nucleotide exchange factor (GEF) activity in vitro and promotes G protein-dependent signaling in cells. GBA proteins have important roles in physiology and disease but remain greatly understudied. This is due, in part, to the lack of efficient tools that specifically disrupt GBA motif function in the context of the large multifunctional proteins in which they are embedded. This hindrance to the study of alternative mechanisms of G protein activation contrasts with the wealth of convenient chemical and genetic tools to manipulate GPCR-dependent activation. Here, we describe the rational design and implementation of a genetically encoded protein that specifically inhibits GBA motifs: GBA inhibitor (GBAi). GBAi was engineered by introducing modifications in Gαi that preclude coupling to every known major binding partner [GPCRs, Gßγ, effectors, guanine nucleotide dissociation inhibitors (GDIs), GTPase-activating proteins (GAPs), or the chaperone/GEF Ric-8A], while favoring high-affinity binding to all known GBA motifs. We demonstrate that GBAi does not interfere with canonical GPCR-G protein signaling but blocks GBA-dependent signaling in cancer cells. Furthermore, by implementing GBAi in vivo, we show that GBA-dependent signaling modulates phenotypes during Xenopus laevis embryonic development. In summary, GBAi is a selective, efficient, and convenient tool to dissect the biological processes controlled by a GPCR-independent mechanism of G protein activation mediated by cytoplasmic factors.

Integrating the basic sciences in medical curricula: focus on the basic scientists.

Basic science educators are not trained as clinicians, yet are expected to adjust their content to mesh appropriately with its clinical application. While achievable, this is a challenge that requires intentional effort on the part of the basic science educators. A practical solution to facilitate curricular integration is to create experiential opportunities for basic scientists to observe the clinical application of their content and to pair these initiatives with training in effective medical education practices.

Mitofusins 1 and 2 are essential for postnatal metabolic remodeling in heart.

RATIONALE: At birth, there is a switch from placental to pulmonary circulation and the heart commences its aerobic metabolism. In cardiac myocytes, this transition is marked by increased mitochondrial biogenesis and remodeling of the intracellular architecture. The mechanisms governing the formation of new mitochondria and their expansion within myocytes remain largely unknown. Mitofusins (Mfn-1 and Mfn-2) are known regulators of mitochondrial networks, but their role during perinatal maturation of the heart has yet to be examined. OBJECTIVE: The objective of this study was to determine the significance of mitofusins during early postnatal cardiac development. METHODS AND RESULTS: We genetically inactivated Mfn-1 and Mfn-2 in midgestational and postnatal cardiac myocytes using a loxP/Myh6-cre approach. At birth, cardiac morphology and function of double-knockout (DKO) mice are normal. At that time, DKO mitochondria increase in numbers, appear to be spherical and heterogeneous in size, but exhibit normal electron density. By postnatal day 7, the mitochondrial numbers in DKO myocytes remain abnormally expanded and many lose matrix components and membrane organization. At this time point, DKO mice have developed cardiomyopathy. This leads to a rapid decline in survival and all DKO mice die before 16 days of age. Gene expression analysis of DKO hearts shows that mitochondria biogenesis genes are downregulated, the mitochondrial DNA is reduced, and mitochondrially encoded transcripts and proteins are also reduced. Furthermore, mitochondrial turnover pathways are dysregulated. CONCLUSIONS: Our findings establish that Mfn-1 and Mfn-2 are essential in mediating mitochondrial remodeling during postnatal cardiac development, a time of dramatic transitions in the bioenergetics and growth of the heart.

Two distinct phosphorylation events govern the function of muscle FHOD3.

Posttranslational modifications such as phosphorylation are universally acknowledged regulators of protein function. Recently we characterised a striated muscle-specific isoform of the formin FHOD3 that displays distinct subcellular targeting and protein half-life compared to its non-muscle counterpart and which is dependent on phosphorylation by CK2 (formerly casein kinase 2). We now show that the two isoforms of FHOD3 are already expressed in the vertebrate embryonic heart. Analysis of CK2 alpha knockout mice showed that phosphorylation by CK2 is also required for proper targeting of muscle FHOD3 to the myofibrils in embryonic cardiomyocytes in situ. The localisation of muscle FHOD3 in the sarcomere varies depending on the maturation state, being either broader or restricted to the Z-disc proper in the adult heart. Following myofibril disassembly, such as that in dedifferentiating adult rat cardiomyocytes in culture, the expression of non-muscle FHOD3 is up-regulated, which is reversed once the myofibrils are reassembled. The shift in expression levels of different isoforms is accompanied by an increased co-localisation with p62, which is involved in autophagy, and affects the half-life of FHOD3. Phosphorylation of three amino acids in the C-terminus of FHOD3 by ROCK1 is sufficient for activation, which results in increased actin filament synthesis in cardiomyocytes and also a broader localisation pattern of FHOD3 in the myofibrils. ROCK1 can directly phosphorylate FHOD3, and FHOD3 seems to be the downstream mediator of the exaggerated actin filament formation phenotype that is induced in cardiomyocytes upon the overexpression of constitutively active ROCK1. We conclude that the expression of the muscle FHOD3 isoform is characteristic of the healthy mature heart and that two distinct phosphorylation events are crucial to regulate the activity of this isoform in thin filament assembly and maintenance.

[Epidemiology of febrile neutropenia in adult patients with acute leukemia and lymphoma: Cohort study of public and private hospital of Santiago, Chile]. / Epidemiología de neutropenia febril en pacientes adultos con leucemia aguda y linfoma: Estudio de cohorte en hospitales público y privado de Santiago, Chile.

INTRODUCTION: Febrile neutropenia (FN) is a common complication of patients undergoing chemotherapy (QMT). Clinical presentation is varied, from mild fever to severe sepsis with invasive bacterial infection (IBI) or invasive fungal infection (IFI), with great impact on prognosis and patient mortality. PATIENTS AND METHODS: Prospective cohort study of FN episodes in adult patients with acute leukemia (AL) or lymphoma (L), diagnosed and treated at the Hospital Clínico Universidad Católica and Hospital Dr. Sótero del Río in Santiago from April 2010 to January 2012. RESULTS: 130 patients were included with 105 episodes of NF, with an incidence of 0.65 per 100 days of observation, higher in AL than L (1.31 vs 0.25, p = 0.001). Etiology or clinical focus was documented in 67 (63.8%) episodes, with IBI in 33 (31.4%) and IFI in 21 (20%) cases. Mortality related to infection occurred in 4 (6.2%) patients. CONCLUSIONS: This study reports that the FN incidence and frequency of IBI and IFI during episodes are higher in AL vs. L. It is necessary to evaluate the impact of interventions to reduce its incidence, including the benefit and risk of using antibacterial and antifungal prophylaxis in high-risk subgroups.

A multicriteria decision analysis for selecting rainwater harvesting systems in rural areas: a tool for developing countries.

Global water provision challenges have promoted decentralized water supply alternatives such as rainwater harvesting systems (RWHS). RWHS sustainability demands involve social, technical, and economic criteria in planning. Generally, in rural areas, water provision is more complex due to multiple uses of water, scattering of households, and low economies of scale. This research proposes a multicriteria tool for selecting RWHS in rural areas, considering social, technical, and economic criteria. The tool was developed by systematically identifying subcriteria and their hierarchization through the analytical hierarchy process (AHP), the technique for order of preference by similarity to ideal solution (TOPSIS), and a case study validation. Seven subcriteria were identified. The hierarchy of criteria was social (49.7%), technical (26.4%), and economic (23.9%). The tool involved: (i) users' consultation about the perceived ease of use and availability of water sources other than rainwater; (ii) system dimensioning to establish supply size, maintenance requirements, and required water quality; and (iii) costs and benefits estimation. Tool validation in a rural area included the evaluation of the alternatives proposed: (a) alternative 1: potable domestic uses (PD) and non-potable (NPD); (b) alternative 2: PD and NPD, irrigation of crops and chicken farming for self-consumption; and alternative 3: PD and NPD and chicken farming for profit sale. The sensitivity analysis showed the tool's consistency and robustness. Tool validation highlights the importance of integrating the three dimensions in selecting RWHS. The study provides a systematic methodology to assess and prioritize RWHS, appealing to policymakers, engineers, and practitioners facilitating water management and supply processes in rural areas.

Effect of agricultural activities on surface water quality from páramo ecosystems.

Páramos are high mountain ecosystems strategic for water provision in South America. Currently, páramos are under threat due to agricultural intensification that impairs surface water sources. This research analyzed the effect of agriculture (spring onion-Allium fistulosum, potato-Solanum tuberosum, and livestock farming) on water quality in páramo ecosystems. A Hydrographic Unit upstream of the Jordan river catchment (Colombia) was selected and monitored in two different rainfall regimes, following the paired catchments and upstream-downstream approaches to compare water quality from natural and anthropic areas. Twenty-two parameters related to agricultural activities were analyzed (nutrients, salts, organic matter, sediments, and pathogens). The studied agricultural activities increased loads of surface water in quality in nitrates (0.02 to 2.56 mg N-NO3/L), potassium (0.13 to 1.24 mg K/L), and Escherichia coli (63 to 2718 FCU/100 mL), generating risks on the human health and promoting eutrophication. Total nitrogen and organic matter in the rainy season were higher than dry. BOD5, COD, turbidity, and E. coli were above international standards for direct human consumption. However, water could be used for irrigation, livestock watering, and aquatic life ambient freshwater. The results show that a small land-use change of almost 15% from natural páramo vegetation to agricultural uses in these ecosystems impairs water quality, limiting its uses, and the need to harmonize small-scale livelihoods in the páramo with the sustainability of ecosystem service provision.

Predictive functional, statistical and structural analysis of CSNK2A1 and CSNK2B variants linked to neurodevelopmental diseases.

Okur-Chung Neurodevelopmental Syndrome (OCNDS) and Poirier-Bienvenu Neurodevelopmental Syndrome (POBINDS) were recently identified as rare neurodevelopmental disorders. OCNDS and POBINDS are associated with heterozygous mutations in the CSNK2A1 and CSNK2B genes which encode CK2α, a serine/threonine protein kinase, and CK2ß, a regulatory protein, respectively, which together can form a tetrameric enzyme called protein kinase CK2. A challenge in OCNDS and POBINDS is to understand the genetic basis of these diseases and the effect of the various CK2⍺ and CK2ß mutations. In this study we have collected all variants available to date in CSNK2A1 and CSNK2B, and identified hotspots. We have investigated CK2⍺ and CK2ß missense mutations through prediction programs which consider the evolutionary conservation, functionality and structure or these two proteins, compared these results with published experimental data on CK2α and CK2ß mutants, and suggested prediction programs that could help predict changes in functionality of CK2α mutants. We also investigated the potential effect of CK2α and CK2ß mutations on the 3D structure of the proteins and in their binding to each other. These results indicate that there are functional and structural consequences of mutation of CK2α and CK2ß, and provide a rationale for further study of OCNDS and POBINDS-associated mutations. These data contribute to understanding the genetic and functional basis of these diseases, which is needed to identify their underlying mechanisms.

The influence between gestational age and postural control, a systematic review.

The central nervous system (CNS) of preterm infants might have some peculiarities which distinguish it from that of full term infants. The difficulties associated with prematurity are the main cause of deaths all over the world during the new-born period after community-acquired pneumonia, and the second cause of deaths worldwide in children under five years old. Early recognition of signs indicating fragile postural control in premature infants can support understanding and help prevent and early intervention on possible future neuromotor dysfunctions in these subjects. The purpose of this paper is to determine if there is a qualitatively different development of postural control in premature infants without neurological involvement and infants born at term. We conducted a systematic review of longitudinal and cross-sectional case-control studies published between 2010 and March 2020 on this topic. The evaluation of parameters related to postural control was also included. The methodological quality of the selected works was evaluated using the CASPe critical reading programme for cases and controls. PRISMA guidelines for systematic reviews were followed for prematurity and postural control. 16 articles were included. The total sample amounted to 3,460 participants, of which 1,860 in the preterm group, and 1,600 in the control group. All the studies found show a poorer postural control by the group of children born preterm compared to the group of children born at term and one study indicating more limited postural control with higher prematurity. Regarding the methodological quality according to CASPe, those studies exceeding half of the total score were considered of adequate quality.

Impact of a Primary Care Antimicrobial Stewardship Program on Bacterial Resistance Control and Ecological Imprint in Urinary Tract Infections.

Antimicrobial stewardship programs (ASPs) are a central component in reducing the overprescription of unnecessary antibiotics, with multiple studies showing benefits in the reduction of bacterial resistance. Less commonly, ASPs have been performed in outpatient settings, but there is a lack of available data in these settings. We implemented an ASP in a large regional outpatient setting to assess its feasibility and effectiveness. Over a 5-year post-implementation period, compared to the pre-intervention period, a significant reduction in antibiotic prescription occurred, with a reduction in resistance in E. coli urinary isolates. ASP activities also were found to be cost-effective, with a reduction in medication prescription.

CK2α is essential for embryonic morphogenesis.

CK2 is a highly conserved serine-threonine kinase involved in biological processes such as embryonic development, circadian rhythms, inflammation, and cancer. Biochemical experiments have implicated CK2 in the control of several cellular processes and in the regulation of signal transduction pathways. Our laboratory is interested in characterizing the cellular, signaling, and molecular mechanisms regulated by CK2 during early embryonic development. For this purpose, animal models, including mice deficient in CK2 genes, are indispensable tools. Using CK2α gene-deficient mice, we have recently shown that CK2α is a critical regulator of mid-gestational morphogenetic processes, as CK2α deficiency results in defects in heart, brain, pharyngeal arch, tail bud, limb bud, and somite formation. Morphogenetic processes depend upon the precise coordination of essential cellular processes in which CK2 has been implicated, such as proliferation and survival. Here, we summarize the overall phenotype found in CK2α (-/- ) mice and describe our initial analysis aimed to identify the cellular processes affected in CK2α mutants.

Clinical characteristics and outcomes of people living with HIV hospitalized with COVID-19: a nationwide experience.

In this prospective, multicentric, observational study, we describe the clinical characteristics and outcomes of people living with HIV (PLHIV) requiring hospitalization due to COVID-19 in Chile and compare them with Chilean general population admitted with SARS-CoV-2. Consecutive PLHIV admitted with COVID-19 in 23 hospitals, between 16 April and 23 June 2020, were included. Data of a temporally matched-hospitalized general population were used to compare demography, comorbidities, COVID-19 symptoms, and major outcomes. In total, 36 PLHIV subjects were enrolled; 92% were male and mean age was 44 years. Most patients (83%) were on antiretroviral therapy; mean CD4 count was 557 cells/mm3. Suppressed HIV viremia was found in 68% and 56% had, at least, one comorbidity. Severe COVID-19 occurred in 44.4%, intensive care was required in 22.2%, and five patients died (13.9%). No differences were seen between recovered and deceased patients in CD4 count, HIV viral load, or time since HIV diagnosis. Hypertension and cardiovascular disease were associated with a higher risk of death (p = 0.02 and 0.006, respectively). Compared with general population, the HIV cohort had significantly more men (OR 0.15; IC 95% 0.07-0.31) and younger age (OR 8.68; IC 95% 2.66-28.31). In PLHIV, we found more intensive care unit admission (OR 2.31; IC 95% 1.05-5.07) but no differences in the need for mechanical ventilation or death. In this cohort of PLHIV hospitalized with COVID-19, hypertension and cardiovascular comorbidities, but not current HIV viro-immunologic status, were the most important risk factors for mortality. No differences were found between PLHIV and general population in the need for mechanical ventilation and death.

Cultural Competence and Cultural Sensitivity Education in University Nursing Courses. A Scoping Review.

When assessing the fragility that characterizes the health of an immigrant person, a culturally competent transformation of the nurse-patient teaching-learning process is necessary. Therefore, it is considered essential to incorporate cultural competence and intercultural communication in higher nursing education. OBJECTIVE: To determine the content and knowledge of cultural competence and intercultural communication offered in higher education in nursing courses. DESIGN: The Campinha-Bacote model of cultural competence was used as the primary reference. METHOD: A scoping review was conducted about studies published in the period 2003 and 2020. The research was conducted between May and October 2020. More than a hundred documents (books, chapters, articles, conference proceedings) have been consulted. RESULTS: Undergraduate nursing courses and postgraduate education move toward promoting cultural competence and sensitivity through teaching strategies. CONCLUSIONS: Teaching projects that combine multiple competencies are more effective, including teacher training. A predominant element is a need for continuous and transversal projects. University nursing education must adapt culturally competent curricula.

Dynamic expression of a LEF-EGFP Wnt reporter in mouse development and cancer.

We have characterized a transgenic mouse line in which enhanced green fluorescent protein (EGFP) is expressed under the control of multimerized LEF-1 responsive elements. In embryos, EGFP was detected in known sites of Wnt activation, including the primitive streak, mesoderm, neural tube, somites, heart, limb buds, mammary placodes, and whisker follicles. In vitro cultured transgenic embryonic fibroblasts upregulated EGFP expression in response to activation of Wnt signaling by GSK3beta inhibition. Mammary tumor cell lines derived from female LEF-EGFP transgenic mice treated with the carcinogen 7, 12-dimethylbenz[a]anthracene (DMBA) also express EGFP. Thus, this transgenic line is useful for ex vivo and in vitro studies of Wnt signaling in development and cancer.

Beta-arrestin and casein kinase 1/2 define distinct branches of non-canonical WNT signalling pathways.

Recent advances in understanding beta-catenin-independent WNT (non-canonical) signalling suggest an increasing complexity, raising the question of how individual non-canonical pathways are induced and regulated. Here, we examine whether intracellular signalling components such as beta-arrestin (beta-arr) and casein kinases 1 and 2 (CK1 and CK2) can contribute to determining signalling specificity in beta-catenin-independent WNT signalling to the small GTPase RAC-1. Our findings indicate that beta-arr is sufficient and required for WNT/RAC-1 signalling, and that casein kinases act as a switch that prevents the activation of RAC-1 and promotes other non-canonical WNT pathways through the phosphorylation of dishevelled (DVL, xDSH in Xenopus). Thus, our results indicate that the balance between beta-arr and CK1/2 determines whether WNT/RAC-1 or other non-canonical WNT pathways are activated.

Developing a Practical Medical Educator Training Program: Meeting A Need in Faculty Development.

This article was migrated. The article was marked as recommended. Faculty who teach in medical schools typically do so because of their knowledge and expertise in their field, yet few receive training in best practices in teaching. Educator development programs that help faculty enhance their teaching skills while continuing to fulfill their existing professional responsibilities can help address this gap. Such programs may be developed and implemented locally by individuals within the institution. This guide is intended for individuals who are interested in developing educator training programs but who lack experience in program development. The article describes practical strategies for designing, implementing, and evaluating a collaborative program to teach skills and best practices in medical education. Key themes in program design, program implementation, and program evaluation and dissemination include appropriate goal setting, setting clear expectations, strong communication, and the benefits of diversity in collaboration. Educator training programs provide enhanced teaching skills and opportunities for career advancement for participants at all career stages, which in turn benefits the institution and the medical profession.

An exaggerated increase in blood pressure with exercise does not predict mortality or severe cardiovascular events in women referred for exercise echocardiography for clinical reasons. / Un incremento exagerado de la presión arterial con el ejercicio no predice mortalidad ni eventos cardiovasculares graves en mujeres referidas a ecocardiografía de ejercicio por razones clínicas.

BACKGROUND AND OBJECTIVES: The association between an exaggerated systolic blood pressure increase with exercise (EBPIE) and the probability of cardiovascular events is controversial and poorly studied in the female population. Our aim was to determine the possible association between EBPIE on one hand and mortality and cardiovascular events on the other in women referred for exercise echocardiography due to known or suspected coronary artery disease. PATIENTS AND METHODS: A total of 3942 women with known or suspected coronary artery disease underwent exercise echocardiography. We defined EBPIE as a ≥70mm Hg increase in systolic blood pressure with exercise. The study endpoints were overall and cardiac mortality, acute myocardial infarction (MI), stroke and coronary revascularisation procedures. RESULTS: A total of 332 women developed EBPIE during the test. During the follow-up, 458 deaths (162 of cardiac origin), 212 MIs, 89 strokes and 345 coronary revascularisation procedures were recorded. The annual rates of overall and cardiac mortality were lower in the patient subgroup with EBPIE (0.15% vs. 2.3%, P=.02 and 0.01% vs. 0.2%, P=.015, respectively). There were no significant differences in the rates of MI, stroke and the need for coronary revascularisation procedures, which occurred in 1.1%, 0.43% and 2.24% of the patients with EBPIE, respectively, and occurred in 0.09%, 0.05% and 0.13% of the women without EBPIE (P=.66; P=.57; P=.19, respectively). After a multivariate adjustment, EBPIE was not a predictor of mortality or cardiovascular events. CONCLUSIONS: EBPIE is not associated with mortality or severe cardiovascular events in women with known or suspected coronary artery disease.