Identifying Novel Inhibitors of Workplace Support and the Importance of Value Congruence and Feeling Valued in General Surgery Residency Training.

OBJECTIVE: To explore residents' perceptions of workplace support inhibitors and their relationship to resident wellbeing. We aim to provide evidence-based targets to inform future work operationalizing support in surgical training. DESIGN: This is a 2-part mixed-methods cross-sectional study. Part 1 analyzed qualitative data from focus groups (April 2021-May 2022). Part 2 comprised an online survey (informed by findings in Part 1, May 2022) to assess the association between perceived workplace support (e.g. feeling valued and value congruence) and poor individual global wellbeing (e.g. languishing). SETTING: National multi-center study including 16 ACGME-accredited academic programs. PARTICIPANTS: General surgery residents at all training levels, both clinical and research years. RESULTS: 28 residents participated in the focus groups which revealed three major themes around perceived inhibitors of workplace support: lack of trust in residency program (e.g. ulterior motives), poor communication from leadership (e.g. lack of transparency, ineffective dialogue), and unfair systems in residency training (e.g. exploitation of residents, paternal leave policies). These themes emphasized the importance of feeling valued and value congruence, with the latter reflected in the form of trust and communication with leadership, a key element of worker-workplace alignment. 251 residents responded to the survey (response rate 31%, 50.6% women) which revealed that a lower sense of feeling valued and lower perceived value congruence were significantly associated with languishing. CONCLUSIONS: Our findings suggest feeling valued and value congruence (specifically, having trust and communication with leadership) are important targets for increasing workplace support in surgical training, offering evidence-based targets for future work to operationalize support in surgical training.

Investigating Workplace Support and the Importance of Psychological Safety in General Surgery Residency Training.

OBJECTIVE: Workplace interventions that increase support can mitigate burnout, improve workplace satisfaction, and increase well-being. Our aim is to provide evidence-based targets to inform future work for operationalizing support in general surgery residency. DESIGN: This is a 2-part mixed-methods cross-sectional study. Part 1 analyzed qualitative data from focus groups (April 2021-May 2022). Part 2 comprised an online survey (informed by findings in Part 1) in May 2022 to assess the association between perceived psychological safety (PS) and flourishing, as well as PS and languishing. SETTING: National multi-center study including 16 ACGME-accredited academic programs. PARTICIPANTS: General surgery residents at various training levels, in both clinical and research. RESULTS: A total of 28 residents participated in the focus groups which revealed both enhancers and inhibitors of support pertaining to PS in the workplace. Enhancers of support included those currently implemented (i.e., allyship of mentors) and those proposed by residents (i.e., nonpunitive analysis of mistakes). Inhibitors of support included both systems (i.e., wellness initiatives as a 'band-aid' for systems issues) and culture (i.e., indefatigability, stoicism). About 251 residents (31%) responded to the survey which revealed higher perception of PS was significantly associated with flourishing at the level of residency program and departmental leadership. Lower perception of PS was significantly associated with languishing at the level of residency program leadership only. CONCLUSION: Our findings highlight the promotion of PS, such as expansion of mentorship to include advocacy (advocating on a resident's behalf, recognition when mistreated) and affirmation (i.e., soliciting opinions on controversial social matters/events, recognizing different life experiences), cultural acceptance of asking for help (without being perceived as weak), formal help navigating interpersonal dynamics (i.e., guidance from senior residents), and leadership presentations and modeling to destigmatize asking for help, as a means of operationalizing workplace support to increase flourishing and decrease languishing.

Investigating First Year Surgery Residents' Expectations of Demand, Control, and Support During Training.

OBJECTIVE: To provide a more granular understanding of the expectations of general surgery interns regarding workplace demand, control, and support prior to starting training. SUMMARY/BACKGROUND DATA: General surgery (GS) interns are at highest risk for burnout and attrition. Maslach frames burnout as resulting from a mismatch between workplace expectations and reality. Occupational science demonstrates workplace demand, control, and support (DCS) as strong influencers of job strain. GS interns' realistic expectations of demands are associated with decreased likelihood of attrition, but their expectations regarding this factor are poorly understood. METHODS: Semi-structured interviews were conducted with 14 incoming surgical residents at UCSF: University of California, San Francisco (57% women, 71% non-White), exploring expectations regarding workplace DCS. Transcripts were uploaded to analytic software and coded in dyads using an iterative approach to consensus. Transcripts were thematically analyzed using inductive and deductive reasoning, applying job-demand-resource theory frameworks, and following a published 6-step approach. RESULTS: Four main themes emerged: past experiences, expected rewards, anticipated challenges, and the desire to belong. Past experiences describes the expectation to successfully cope with future stressors via self-reliance. Rewards such as professional mastery, personal growth, and sense of meaning were expected outcomes seen as balancing anticipated challenges. Anticipated challenges included low control, toxic cultural elements, and discrimination. Desire to belong (i.e., earned recognition as a peer, inclusion in an elite culture) emerged as a powerful motivator, with survival connotations for women and non-Whites. CONCLUSION: Our results suggest incoming interns overestimate the efficacy of self-reliance for coping; count on specific rewards; express realistic expectations regarding challenges; and see inclusion among surgeons as an aspiration that off-sets prolonged effort. Further study is warranted to understand expectation-reality mismatch and potential interventions to target dissonance. MINI-ABSTRACT: In this institutional study of general surgery interns, we provide a more granular understanding of the expectations of general surgery interns regarding workplace demand, control, and support prior to starting training, and how we might target "expectations-reality" mismatch and the "desire to belong" as a means of mitigating burnout and minimizing attrition from training.

Mindfulness Based Interventions for Surgeons: A Scoping Review.

OBJECTIVE: To review the evidence on mindfulness-based interventions (MBIs) for surgeons. BACKGROUND: Healthcare professionals have alarmingly high rates of burnout, yet little is known about psychological factors that support resilience. MBIs, which involve codified training in specific skills such as self-awareness, emotional regulation, and perspective-taking, have shown benefit to professionals in high stress environments, but have had limited implementation in the healthcare workplace and in surgery. To our knowledge, there has not been a scoping review of MBIs in surgery to date. METHODS: We conducted a scoping review of the evidence for the feasibility and effectiveness of MBIs for surgeons, including evidence on interventions that explicitly train mindfulness, which spans multiple cohorts and settings, utilizing different methodologies and outcome measures. RESULTS: This scoping review yielded 24 studies, including two mixed method/qualitative studies, nine randomized control trials, three non-randomized interventional studies, and eight single-arm interventional studies. CONCLUSIONS: We find that MBIs in surgery 1) are feasible in surgical contexts, with implementation science providing insights on sustainability; 2) increase mindfulness, 3) improve well-being in terms of burnout and both psychological and neurophysiological measures of stress, and 4) enhance performance as measured in executive function, surgical skills, and communication skills. These conclusions are supported by psychometric measures, observations of technical skills, and neurophysiological evidence. Future directions include studying MBIs in larger and more diverse populations, and iteratively tailoring mindfulness-based interventions to other healthcare contexts.

Flourishing and the Prioritization of Workplace Elements in General Surgery Residents.

INTRODUCTION: To explore and begin to operationalize workplace elements that influence general surgery (GS) resident wellbeing. Tailoring workplace wellbeing interventions is critical to their success. Occupational science has revealed that a person-centered approach to identifying positive and negative workplace influences can inform tailoring while accounting for individual differences. To our knowledge, this approach has not been applied to the surgical training environment. METHODS: A national sample of GS residents from 16 Accreditation Council for Graduate Medical Education training programs ranked the importance of workplace elements via an anonymous survey. Latent profile analysis was performed to identify shared patterns of workplace element prioritization and their relation to levels of flourishing, a measure of global wellbeing. RESULTS: GS trainee respondents (n = 300, 34% response rate - average for studies with this sample population) expressed a hierarchy of workplace element importance which differed by gender and race. "Skills to manage stress" and "a team you feel a part of" were prioritized higher by non-males than males. Residents of color and residents underrepresented in medicine, respectively, prioritized "recognition of work/effort" and "skills to manage stress" more than White and overrepresented in medicine residents. Flourishing prevalence varied by 40% with small differences in the specific profile of workplace element prioritization. CONCLUSIONS: Differences in prioritization of workplace elements reveal subtle but important differences that may guide the design of wellbeing interventions for different populations within surgery.

Operationalizing the Culture of Burnout and Well-Being: Multicenter Study of Value Congruence and Flourishing in General Surgery Residency.

BACKGROUND: Value congruence (VC) is the degree of alignment between worker and workplace values and is strongly associated with reduced job strain and retention. Within general surgery residency, the impact of VC and how to operationalize it to improve workplace well-being remain unclear. STUDY DESIGN: This 2-part mixed-methods study comprised 2 surveys of US general surgery residents and qualitative interviews with program directors. In Part 1, January 2021, mixed-level surgical residents from 16 ACGME-accredited general surgery residency programs participated in survey #1. This survey was used to identify shared or conflicting perspectives on VC concerning well-being initiatives and resources. In April 2021, interviews from 8 institutions were conducted with 9 program directors or their proxies. In Part 2, May to June 2022, a similar cohort of surgical residents participated in survey #2. Unadjusted logistic and linear regression models were used in this survey to assess the association between VC and individual-level global well-being (ie flourishing), respectively. RESULTS: In survey #1 (N = 300, 34% response rate), lack of VC was an emergent theme with subthemes of inaccessibility, inconsiderateness, inauthenticity, and insufficiency regarding well-being resources. Program directors expressed variable awareness of and alignment with these perceptions. In survey #2 (N = 251, 31% response rate), higher VC was significantly associated with flourishing (odds ratio 1.91, 95% CI 1.44 to 2.52, p < 0.001). CONCLUSIONS: Exploring the perceived lack of VC within general surgery residency reveals an important cultural variable for optimizing well-being and suggests open dialogue as a first step toward positive change. Future work to identify where and how institutional actions diminish perceived VC is warranted.

When the absence of evidence is not the evidence of absence: Nasa (Loasaceae) rediscoveries from Peru and Ecuador, and the contribution of community science networks.

Documentation of plant taxa has long been subject to the temporal and spatial selectivity of professional research expeditions, especially in tropical regions. Therefore, rare and/or narrowly endemic species are sometimes known only from very few and very old herbarium specimens. However, these taxa are very important from a conservation perspective. The lack of observations of living plants and confirmation of the actual occurrence of taxa hinders the planning and implementation of effective conservation measures. Community science networks have recently made tremendous contributions to documenting biodiversity in many regions across the globe. The rediscovery of six species of Nasa (Loasaceae) from Peru and Ecuador primarily via the platform iNaturalist, is reported.

Understanding climate change impacts on biome and plant distributions in the Andes: Challenges and opportunities.

Aim: Climate change is expected to impact mountain biodiversity by shifting species ranges and the biomes they shape. The extent and regional variation in these impacts are still poorly understood, particularly in the highly biodiverse Andes. Regional syntheses of climate change impacts on vegetation are pivotal to identify and guide research priorities. Here we review current data, knowledge and uncertainties in past, present and future climate change impacts on vegetation in the Andes. Location: Andes. Taxon: Plants. Methods: We (i) conducted a literature review on Andean vegetation responses to past and contemporary climatic change, (ii) analysed future climate projections for different elevations and slope orientations at 19 Andean locations using an ensemble of model outputs from the Coupled Model Intercomparison Project 5, and (iii) calculated changes in the suitable climate envelope area of Andean biomes and compared these results to studies that used species distribution models. Results: Future climatic changes (2040-2070) are projected to be stronger at high-elevation areas in the tropical Andes (up to 4°C under RCP 8.5), while in the temperate Andes temperature increases are projected to be up to 2°C. Under this worst-case scenario, temperate deciduous forests and the grasslands/steppes from the Central and Southern Andes are predicted to show the greatest losses of suitable climatic space (30% and 17%-23%, respectively). The high vulnerability of these biomes contrasts with the low attention from researchers modelling Andean species distributions. Critical knowledge gaps include a lack of an Andean wide plant checklist, insufficient density of weather stations at high-elevation areas, a lack of high-resolution climatologies that accommodates the Andes' complex topography and climatic processes, insufficient data to model demographic and ecological processes, and low use of palaeo data for distribution modelling. Main conclusions: Climate change is likely to profoundly affect the extent and composition of Andean biomes. Temperate Andean biomes in particular are susceptible to substantial area contractions. There are, however, considerable challenges and uncertainties in modelling species and biome responses and a pressing need for a region-wide approach to address knowledge gaps and improve understanding and monitoring of climate change impacts in these globally important biomes.

Geographic distribution, conservation status and lectotypification of Pedersenia weberbaueri (Suess.) Holub (Amaranthaceae), an endemic and highly threatened shrub from the Marañón valley of Peru

The present study analyses the geographical distribution, conservation status, and nomenclature of Peruvian endemic Pedersenia weberbaueri. The species distribution was modelled using MaxEnt based on occurrence data and bioclimatic variables. The conservation status of the species was assessed against the categories and criteria of the IUCN Red List, and nomenclatural and typification issues were resolved. The potential distribution map of P. weberbaueri shows that the species is restricted to the seasonally dry tropical forests of the Marañón valley within a narrow latitudinal, longitudinal, and elevational range. Consequently, we propose to categorise the species as Endangered (EN) and provide the necessary information for its inclusion in the IUCN Red List. Finally, we resolve nomenclatural issues and designate a lectotype. The results contribute to the biological knowledge of P. weberbaueri and support subsequent conservation management plans.

El presente estudio analiza la distribución geográfica, el estado de conservación y la nomenclatura de la endémica peruana Pedersenia weberbaueri. La distribución de especies se modeló usando MaxEnt con base en datos de ocurrencia y variables bioclimáticas. Se evaluó el estado de conservación de la especie frente a las categorías y criterios de la Lista Roja de la UICN y se resolvieron cuestiones de nomenclatura y tipificación. El mapa de distribución potencial de P. weberbaueri muestra que la especie está restringida a los bosques tropicales estacionalmente secos del valle del Marañón dentro de un estrecho rango latitudinal, longitudinal y altitudinal. En consecuencia, proponemos categorizar a la especie como En Peligro (EN) y brindar la información necesaria para su inclusión en la Lista Roja de la UICN. Finalmente, resolvemos cuestiones de nomenclatura y designamos un lectotipo. Los resultados contribuyen al conocimiento biológico de P. weberbaueri y respaldan los planes de manejo de conservación posteriores.

Validity evidence for flourishing as a measure of global wellbeing: a national multicenter study of academic general surgery residents.

Purpose: Physician wellbeing is critical to high-quality sustainable healthcare and optimal patient experience. Few objective measures exist to assay wellbeing (as opposed to just pathology) in surgery, or to evaluate the efficacy of wellbeing interventions. Flourishing (as measured by the Mental Health Continuum, MHC) has been suggested as a concise measure of global wellbeing in surgeons. We aimed to establish validity evidence for flourishing in a large national sample of surgical trainees, explore differences by gender and race, and confirm support for the underlying constructs. Methods: This cross-sectional study of all General Surgery residents at 16 ACGME-accredited academic programs included an online survey of published measures distributed in February 2021. The Mental Health Continuum (MHC), a three-factor model, assesses emotional, social, and psychological wellbeing and is an established metric of psychosocial thriving in non-physicians. A global score cut-off exists for flourishing which represents high wellbeing. Correlation between flourishing and established measures of risk and resilience in surgery were assessed for validity evidence. Differences by gender and race were explored. A confirmatory factor analysis (CFA) was performed to confirm the three-factor structure in surgical trainees. Results: 300 residents (60% non-male, 41% non-white) responded to the survey. For the overall group, flourishing was significantly positively correlated with all wellbeing resilience factors and negatively correlated with all risk factors. This held true for race and gender subgroups based on interaction analyses. CFA and sensitivity analysis results supported the three-factor structure. Conclusions: Our findings offer validity evidence for flourishing as a measure of global wellbeing and confirm the three-factor structure of emotional, social, and psychological wellbeing in surgical trainees. Thus, the MHC may be a concise tool for assaying wellbeing, within and across subgroups, and for assessing wellbeing intervention effectiveness within the surgery.

[In vitro study of the effect of three commercial solvents on gutta-percha cones used for the cold and thermoplastic technique]. / Estudio in vitro del efecto de tres solventes comerciales sobre conos de gutapercha utilizados para técnica en frío y termoplastificada.

The objective of this research was to compare the solvent action of orange oil, eucalyptol and experimental lemongrass oil on gutta-percha cones for cold technique and thermoplastic technique. Methodology: The sample consisted of 80 gutta-percha cones No. 80 Endomedic and F3 ProTaper Universal. The cones were divided into 4 groups (n = 20) according to the type of solvent, and each one was divided into two subgroups (n = 10) according to the exposure time (5 min and 10 min). The cones were immersed in the respective solvent for 5 or 10 minutes. Then, they were washed with 5 ml of alcohol for 5 minutes and rinsed with water. Finally, after drying at room temperature for one hour, the solvent action was recorded in grams (g) of weight loss. The results were analyzed and compared using Tukey's test (p<0.05). Results: The Endomedic cone exposed for 5 min to eucalyptol obtained the lowest average weight (0.0625 ± 0.0009 g), followed by Lemongrass oil (0.0629 ± 0.0003 g) and orange oil (0.0629 ± 0.0010 g), although not a significant difference (p > 0.05) was found between each one. Conclusion: The experimental solvent of Lemongrass, eucalyptol and orange oil presented a similar solvent effect on the guta-percha cone for cold and thermoplastic technique. At a clinical level, the three solvents studied could be used in endodontic retreatment as alternative solutions with a similar solvent effect.

Successful Modified Therapy in a Patient with Probable Infection-Associated Hemophagocytic Lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a rare, hyperinflammatory syndrome characterized by clinical signs and symptoms of extreme inflammation. In adults, HLH is typically a complication of infections, autoimmune diseases, and malignancies. While the disease is often fatal, classic management of HLH revolves around early diagnosis and initiation of protocolized therapy. We present a case of a previously healthy 56-year-old female who developed distributive shock requiring intubation, vasopressors, and continuous venovenous hemofiltration. In the setting of multiple infectious syndromes, severe cytopenias, and rising direct hyperbilirubinemia, her diagnosis of HLH was confirmed. Therapy was initiated with dexamethasone and two doses of reduced-intensity etoposide based on the patient's clinical course. Over the next few weeks, she continued to improve on dexamethasone monotherapy and has maintained remission up to the present with complete resolution of her cytopenias and return of baseline renal function. Our case highlights the variability in the management of probable infection-associated HLH (IHLH) with a good patient outcome. We demonstrate the potential to treat IHLH with partial protocols and minimal chemotherapeutics.

Plinabulin, an inhibitor of tubulin polymerization, targets KRAS signaling through disruption of endosomal recycling.

Constitutive activation of Kirsten rat sarcoma viral oncogene homolog (KRAS) is the most common oncogenic event in certain types of human cancer and is associated with poor patient survival. Small molecule signaling inhibitors have improved the clinical outcomes of patients with various cancer types but attempts to target KRAS have been unsuccessful. Plinabulin represents a novel class of agents that inhibit tubulin polymerization with a favorable safety profile in clinical trials. In the present study, the potency of plinabulin to inhibit tubulin polymerization and growth of KRAS-driven cancer cells was characterized. In vivo efficacy of plinabulin was tested in two different mouse models; one being the RCAS/t-va gene transfer system and the other being a xenograft model. In vitro cell culture tubulin polymerization assays were used to complement the mouse models. There was improved survival in a KRAS-driven mouse gene transfer glioma model, but lack of benefit in a similar model, without constitutively active KRAS, which supports the notion of a KRAS-specific effect. This survival benefit was mediated, at least in part, by the ability of plinabulin to inhibit tubulin polymerization and disrupt endosomal recycling. It was proposed a mechanism of compromised endosomal recycling of displaced KRAS through targeting microtubules that yields inhibition of protein kinase B, but not extracellular signal regulated kinase (ERK) signaling, therefore lending rationale to combination treatments of tubulin- and ERK-targeting agents in KRAS-driven cancer.

Estrategias de problematización e intervención de Kinesiología / Fisioterapia para un paciente con una afección ventilatoria crónica reagudizada / Problematizing strategies and intervention of Kinesiology / Physiotherapy for a patient with aggravated chronic ventilatory condition

La Clasificación Internacional del Funcionamiento, de la Discapacidad y de la Salud (CIF), permite organizar la información mediante un lenguaje trans-disciplinario. Al respecto, es fundamental complementarlo con una epistemología propia para generar prácticas clínicas eficientes. La enfermedad pulmonar obstructiva crónica (EPOC), se ha convertido en una condicionante negativa de función, movimiento y salud en la población. Proponemos un modelo de razonamiento en kinesiología/fisioterapia para disfunciones del movimiento humano aplicado a una fase crónica ventilatoria irreversible. Paciente de 74 años con EPOC. Plantea como necesidad, la "mínima asistencia para realizar su aseo personal", lo que se estableció como contexto funcional crítico (CFC). Se entrenó progresivamente, según velocidad, por 36 sesiones, de 30 minutos. La espirometría no presentó cambios. Mejoró la capacidad de trabajo físico, calidad de vida y el CFC se hizo independiente. La intervención derivada del diagnóstico mediante estrategias de problematización permitió una mejora clínica eficiente de los indicadores evaluados.

The International Classification of Functioning, Disability and Health (CIF), make it possible to organize information through a trans-disciplinary language. In this regard, it is essential to complement it with an own epistemology to generate efficient clinical practices. Chronic obstructive pulmonary disease (COPD) has become a negative condition of function, movement and health in the population. We propose a model of reasoning in kinesiology/ physiotherapy for dysfunctions of human movement applied to an irreversible chronic ventilatory phase. Patient of 74 years old patient with COPD. As a necessity, it poses the "minimum assistance to perform personal hygiene", which was established as a critical functional context (CFC). He trained progressively, according to speed, for 36 sessions of 30 min. The spirometry did not change. The capacity for physical work, quality of life improved, and the CFC became independent. The intervention derived from the diagnosis by problematizing strategies allowed an efficient clinical improvement of the evaluated indicators.

Vascular flora and phytogeographical links of the Carabaya Mountains, Peru / Flora vascular y conexiones fitogeográficas de las montañas Carabaya, Perú

Studies of floristic composition and plant species richness in tropical mountains support their recognition as areas of high biological diversity, and therefore of their importance for plant conservation. Here, we present data on the flora of the high Andes of eight sites centered in the Carabaya mountains, and also provide a floristic comparison with nine other floras within Peru and northern Bolivia. The study area includes 506 species of vascular plants, grouped in 203 genera and 66 families. The highest species richness was found in two families: Asteraceae and Poaceae, which collectively encompass 37% of all species. Other important families were Caryophyllaceae, Fabaceae, Malvaceae, Brassicaceae, Caprifoliaceae, Gentianaceae, Plantaginaceae and Cyperaceae. The most diverse genera wereSenecio, Calamagrostis, Poa and Nototriche. Perennial herbs were the dominant growth form. The vascular flora of the Carabaya Mountains is closely related to those of other regions of southern Peru. Also, more than half of all vascular plants registered for the Carabaya Mountain occur in the Andean region of Bolivia, which shows the undoubted geophysical and phytogeographical connection of the Carabaya and the Bolivian Apolobamba Mountains. This study also shows that there is still a need for more extensive plant collecting and future exploration, since the Carabaya, as other parts of Peru’s high Andes are subject of dramatic change that may threaten these plant populations.

Los estudios sobre la composición florística y riqueza de especies en montañas tropicales apoyan su reconocimiento como áreas de alta diversidad biológica, y, por tanto, de su importancia para la conservación. En este trabajo presentamos datos sobre la flora altoandina de ocho sitios localizados en la Cordillera de Carabaya, proveemos también una comparación florística con otros nueve lugares tanto en Perú como en el norte de Bolivia. El área de estudio incluye 506 especies de plantas vasculares, reconocidas en 203 géneros y 66 familias. Las tasas más altas de riqueza de especies se hallan en dos familias: Asteraceae y Poaceae, que colectivamente abarcan el 37% de todas las especies. Otras familias importantes fueron Caryophyllaceae, Fabaceae, Malvaceae, Brassicaceae, Caprifoliaceae, Gentianaceae, Plantaginaceae y Cyperaceae. Los géneros más diversos fueron Senecio, Calamagrostis, Poa y Nototriche. La forma de crecimiento predominante fueron las hierbas perennes. La flora vascular de la Cordillera Carabaya está muy relacionada con otras regiones del sur de Perú. Además, más de la mitad de todas las plantas vasculares registradas para la Cordillera Carabaya se encuentran en la región andina de Bolivia, lo que demuestra la indudable conexión geofísica y fitogeográfica entre las cordilleras Carabaya y Apolobamba de Bolivia. Este estudio también demuestra la necesidad de una extensa colección botánica y futura exploración, desde que Carabaya, como otras partes de los altos Andes del Perú, están sujetos a cambios dramáticos que amenazan las poblaciones de esas plantas.

MR Imaging of Cardiac Masses.

Cardiac masses present a diagnostic challenge given their relative rarity and the overall difficulty imaging the heart. With the increasing frequency and quality of imaging in general, however, the incidental discovery of cardiac masses is increasing. Cardiac masses seldom produce symptoms, and they are more commonly found during imaging for noncardiac indications. While echocardiography is useful in the initial evaluation of a suspected mass, cardiac magnetic resonance (MR) imaging is the best imaging modality to characterize cardiac tumors due to its superior tissue characterization and its higher contrast resolution. Due to the risk of embolization and arrhythmia, most benign cardiac tumors are removed, and imaging plays an important role in treatment planning. While primary resection remains the mainstay of treatment, new treatment strategies may prolong survival and slow the growth of metastases. A fundamental knowledge of common cardiac masses is vital to all radiologists, and here, we discuss the most pertinent imaging approach to cardiac masses emphasizing MR imaging.

Everolimus Implicated in Case of Severe Gastrointestinal Hemorrhage.

Breast cancer remains the leading cause of cancer and the third leading cause of cancer related deaths among our population with an estimated number of 246,660 new cases and 40,450 deaths in 2016. With treatment advancements, including targeted agents such as Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, survivability and quality of life continue to improve. However, with the use of these agents come adverse effects, some of which are still being characterized. Our case demonstrates recurrent episodes of gastrointestinal bleeding in a 60-year-old woman being treated with Everolimus for progressive metastatic breast cancer. On endoscopy, bleeding was secondary to erosive gastritis. Previous case reports have described bleeding due to gastric antral vascular ectasia (GAVE), which was described in two prior reported cases. In our case, bleeding also occurred on a reduced dose of Everolimus compared to what is previously reported (5 mg versus 10 mg). As a result of her gastrointestinal bleeding, she required multiple endoscopic interventions including argon plasma coagulation and multipolar heater probe to achieve hemostasis. This is the first case reported of gastrointestinal bleeding not consistent with GAVE and occurring while being on a reduced dose of Everolimus. It is important to document our case so that the Gastroenterology and Hematology communities can be educated and made aware for their patient populations on Everolimus.

Targeting polo-like kinase 1, a regulator of p53, in the treatment of adrenocortical carcinoma.

BACKGROUND: Adrenocortical carcinoma (ACC) is an aggressive cancer with a 5 year survival rate of 20-30 %. Various factors have been implicated in the pathogenesis of ACC including dysregulation of the G2/M transition and aberrant activity of p53 and MDM2. Polo-like kinase 1 (PLK-1) negatively modulates p53 functioning, promotes MDM2 activity through its phosphorylation, and is involved in the G2/M transition. Gene expression profiling of 44 ACC samples showed that increased expression of PLK-1 in 29 % of ACC. Consequently, we examined PLK-1's role in the modulation of the p53 signaling pathway in adrenocortical cancer. METHODS: We used siRNA knock down PLK-1 and pharmacological inhibition of PLK-1 and MDM2 ACC cell lines SW-13 and H295R. We examined viability, protein expression, p53 transactivation, and induction of apoptosis. RESULTS: Knocking down expression of PLK-1 with siRNA or inhibition of PLK-1 by a small molecule inhibitor, BI-2536, resulted in a loss of viability of up to 70 % in the ACC cell lines H295R and SW-13. In xenograft models, BI-2536 demonstrated marked inhibition of growth of SW-13 with less inhibition of H295R. BI-2536 treatment resulted in a decrease in mutant p53 protein in SW-13 cells but had no effect on wild-type p53 protein levels in H295R cells. Additionally, inhibition of PLK-1 restored wild-type p53's transactivation and apoptotic functions in H295R cells, while these functions of mutant p53 were restored only to a smaller extent. Furthermore, inhibition of MDM2 with nutlin-3 reduced the viability of both the ACC cells and also reactivated wild-type p53's apoptotic function. Inhibition of PLK-1 sensitized the ACC cell lines to MDM2 inhibition and this dual inhibition resulted in an additive apoptotic response in H295R cells with wild-type p53. CONCLUSIONS: These preclinical studies suggest that targeting p53 through PLK-1 is an attractive chemotherapy strategy warranting further investigation in adrenocortical cancer.

Synthesis of improved lysomotropic autophagy inhibitors.

Autophagy is a conserved cellular pathway used to recycle nutrients through lysosomal breakdown basally and under times of stress (e.g., nutrient deprivation, chemotherapeutic treatment). Oncogenes are known to induce autophagy, which may be exploited by cancers for cell survival. To identify autophagy inhibitors with potential therapeutic value for cancer, we screened a panel of antimalarial agents and found that quinacrine (QN) had 60-fold higher potency of autophagy inhibition than chloroquine (CQ), a well-known autophagy inhibitor that functions by disrupting lysosomal activity. Despite desirable autophagy inhibiting properties, QN showed considerable cytotoxicity. Therefore, we designed and synthesized a novel series of QN analogs and investigated their effects on autophagy inhibition and cell viability. Notably, we found two compounds (33 and 34), bearing a backbone of 1,2,3,4-tetrahydroacridine, had limited cytotoxicity yet strong autophagy inhibition properties. In conclusion, these improved lysomotropic autophagy inhibitors may have use as anticancer agents in combination with conventional therapies.

Four new non-spiny Solanum (Solanaceae) species from South America.

Four new species of "non-spiny" Solanum from South America are described. Solanumlongifilamentum Särkinen & P.Gonzáles, sp. nov. (Morelloid clade) is widespread from Ecuador to Bolivia and is most similar to Solanummacrotonum Dunal from Central and northern South America. Solanumantisuyo Särkinen & S.Knapp, sp. nov. (Morelloid clade) is found on the eastern Andean slopes in Ecuador, Peru and Bolivia and is most similar to the widespread lower elevation species Solanumpolytrichostylum Bitter. Solanumarenicola Särkinen & P.Gonzáles, sp. nov. (Morelloid clade) is found in low elevation habitats on the eastern Andean slopes and in Amazonia of Peru and Bolivia and is most similar to the higher elevation species Solanumaloysiifolium Dunal of Bolivia and Argentina. Solanummariae Särkinen & S.Knapp, sp. nov. (Potato clade) is endemic to Cajamarca Department in Peru, and is most similar to the widespread Solanumcaripense Dunal. Complete descriptions, distributions and preliminary conservation assessments of all new species are given.

ResumenSe describen cuatro species nuevas de Solanum de América del Sur. Solanumlongifilamentum Särkinen & P. Gonzáles, sp. nov. (clado Morelloide) se encuentra de Ecuador a Bolivia y es muy similar a Solanummacrotonum Bitter de Centroamerica y la parte norte de América del Sur. Solanumantisuyo Särkinen & S.Knapp, sp. nov. (clado Morelloide) se encuentra en las vertientes orientales de los Andes en Ecuador, Peru y Bolivia y es similar a Solanumpolytrichostylum Bitter, una especie de amplia distribución de elevaciones menores. Solanumarenicola Särkinen & P. Gonzáles, sp. nov. (clado Morelloide) se encuentra en las vertientes orientales de los Andes y la selva baja de Peru y Bolivia, es muy parecida a una especie que se encuentra a mayor altitud en Bolivia y Argentina, Solanumaloysiifolium Dunal. Solanummariae Särkinen & S.Knapp, sp. nov. (clado Potato) es endémica del departamento de Cajamarca (Perú), y es similar a Solanumcaripense Dunal, una especie de amplia distribución en los Andes. Se presenta descripciones completas, mapas de distribuciones y evaluaciones preliminares de conservación de todas las especies descritas aquí.