The 10th Biennial Hatter Cardiovascular Institute workshop: cellular protection—evaluating new directions in the setting of myocardial infarction, ischaemic stroke, and cardio-oncology

Due to its poor capacity for regeneration, the heart is particularly sensitive to the loss of contractile cardiomyocytes. The onslaught of damage caused by ischaemia and reperfusion, occurring during an acute myocardial infarction and the subsequent reperfusion therapy, can wipe out upwards of a billion cardiomyocytes. A similar program of cell death can cause the irreversible loss of neurons in ischaemic stroke. Similar pathways of lethal cell injury can contribute to other pathologies such as left ventricular dysfunction and heart failure caused by cancer therapy. Consequently, strategies designed to protect the heart from lethal cell injury have the potential to be applicable across all three pathologies. The investigators meeting at the 10th Hatter Cardiovascular Institute workshop examined the parallels between ST-segment elevation myocardial infarction (STEMI), ischaemic stroke, and other pathologies that cause the loss of cardiomyocytes including cancer therapeutic cardiotoxicity. They examined the prospects for protection by remote ischaemic conditioning (RIC) in each scenario, and evaluated impasses and novel opportunities for cellular protection, with the future landscape for RIC in the clinical setting to be determined by the outcome of the large ERIC-PPCI/CONDI2 study. It was agreed that the way forward must include measures to improve experimental methodologies, such that they better reflect the clinical scenario and to judiciously select combinations of therapies targeting specific pathways of cellular death and injury

Tratamiento quirúrgico de las enfermedades de transición cervicotorácica

OBJETIVO: avaliar o resultado do tratamento cirúrgico de pacientes portadores de doenças na transição cervicotorácica da coluna vertebral. MÉTODOS: foram avaliados, retrospectivamente, 20 pacientes: nove (45%) apresentavam lesões traumáticas, sete (35%) lesões neoplásicas e quatro (20%) doenças degenerativas. No grupo de pacientes com lesões traumáticas, foi realizada fixação posterior em cinco deles (55,5%), fixação anterior em um (11,1%) e abordagem combinada (anterior e posterior) em três (33,3%). Dos sete pacientes com lesões tumorais, quatro (57,1%) foram submetidos ao tratamento cirúrgico pela abordagem combinada e três (42,8%) pela abordagem posterior isolada. No grupo de pacientes com doenças degenerativas da coluna vertebral, três (75%) foram tratados pela abordagem posterior e um (25%) de forma combinada. Todos os pacientes foram avaliados por meio de parâmetros clínicos (dor e déficit neurológico), radiológicos (manutenção da redução, soltura ou quebra dos implantes) e funcionais (SF-36, escala de dor e trabalho de Denis). RESULTADOS: os 20 pacientes foram seguidos por um período que variou de seis meses a 11 anos (média de 44,6 meses ± 29,02). Dos 13 pacientes que apresentavam déficit neurológico, oito apresentaram melhora do nível na escala de Frankel (61,5%) e cinco pacientes (38,4%) permaneceram com o quadro inalterado. Como complicações um paciente (5%) apresentou soltura do implante e quatro pacientes evoluíram com infecção pós-operatória (20%). Segundo as escalas de dor e trabalho de Denis, 80% dos pacientes apresentavam pouca ou nenhuma dor (P1 e P2) e 70% dos pacientes tinham retornado ao trabalho (W1, W2 e W3). Os pacientes que não apresentavam déficit neurológico (Frankel E) obtiveram escores mais altos de qualidade de vida pelo questionário SF-36, quando comparados aos escores dos pacientes que mantinham alterações neurológicas (Frankel A-D). CONCLUSÃO: o tratamento das doenças da transição cervicotorácica da coluna vertebral apresenta detalhes adicionais aos demais segmentos da coluna vertebral. Na vigência de tratamento cirúrgico, existem pontos a serem respeitados como a anatomia relacionada ao acesso cirúrgico, as características anatômicas peculiares das vértebras e a biomecânica singular desse segmento da coluna vertebral.OBJECTIVE: to assess the results of the surgical treatment of patients with disease in the cervicothoracic junction of the spine. METHODS: twenty patients were retrospectively evaluated. Nine patients (45%) had traumatic lesions, seven (35%) neoplasic lesions and four (20%) degenerative arthropathies. In the group of patients with traumatic lesions it has been accomplished the posterior fixation in five patients (55.5%), anterior fixation in one patient (11.1%) and the combined approach (anterior and posterior) in three patients (33.3%). In the seven patients with neoplasic lesions, four (57.1%) underwent to the surgical treatment through the combined approach and 3 (42.8%) through the posterior approach. In the group of patients with spinal degenerative disease, three (75%) were treated through the posterior approach and one (25%) in a combined way. The patients were evaluated on the basis of clinical (pain and neurological deficit), radiological (reduction maintenance and implant loosening or break) and functional parameters (SF-36, Denis scale of work and pain). RESULTS: twenty patients were followed-up for a period of time ranging from six months to 11 years (44.6 months ± 29.02). From 13 patients which presented neurological deficit, eight patients presented improvement in Frankel scale level (61.5%) and five patients (38.5%) remained with the same level. As complications, one patient (5%) presented implant loosening and four patients presented postoperative infection (20%). In pain and work assessment, 80% of the patients presented few or no pain (P1 and P2) through Denis scale of pain, and 70% of the patients had returned to work (W1, W2 and W3) through Denis scale of work. The patients without neurological deficit (Frankel E) presented higher scores of life quality through the SF-36 questionnaire compared to the patients who had neurological deficit (Frankel A-D). CONCLUSION: the treatment of the diseases of the cervicothoracic junction of the spine presents additional details compared to the others segments of the spine. The surgical treatment has aspects to be respected as the anatomy related to the surgical access, the peculiar anatomic characteristics of the vertebrae and the unique biomechanics of this spinal segment.OBJETIVO: evaluar el resultado del tratamiento quirúrgico de pacientes portadores de enfermedades de transición cervicotorácica de la columna vertebral. MÉTODOS: fueron retrospectivamente evaluados veinte pacientes. Nueve pacientes (45%) presentaron lesiones traumáticas, 7 (35%) lesiones neoplásicas y 4 enfermedades degenerativas (20%). En el grupo de pacientes con lesiones traumáticas fue realizada una fijación posterior en 5 pacientes (55.5%), una fijación anterior en 1 paciente (11,1%) y abordaje combinado (anterior y posterior) en 3 pacientes (33.3%). De los 7 pacientes con lesiones tumorales, cuatro (57.1%) fueron sometidos al tratamiento quirúrgico por abordaje combinado y 3 (42.8%) por abordaje posterior aislado. En el grupo de pacientes con enfermedades degenerativas de la columna vertebral, tres (75%) fueron tratados por abordaje posterior y uno de forma combinada (25%). Todos los pacientes fueron evaluados por medio de parámetros clínicos (dolor y déficit neurológico), radiológicos (mantenimiento de la reducción, soltura o quiebra de los implantes) y funcionales (SF-36, escala de dolor y trabajo de Denis). RESULTADOS: los veinte pacientes fueron seguidos por um periodo que varió de 6 meses a 11 años (promedio de 44.6 meses ± 29.02). De los 13 pacientes que presentaron déficit neurológico, ocho presentaron una mejora en el nivel de la escala de Frankel (61.5%) y cinco pacientes (38.4%) permanecieron con un cuadro inalterado. Como complicaciones un paciente (5%) presentó soltura del implante y cuatro pacientes evolucionaron con infección postoperatoria (20%). Según las escalas de dolor y el trabajo de Denis, el 80% de los pacientes presentaron poco o nada de dolor (P1 y P2) y el 70% de los pacientes regresaron al trabajo (W1, W2 y W3). Los pacientes que no presentaron déficit neurológico (Frankel E) tuvieron escores mas altos de calidad de vida por el cuestionario SF-36, cuando comparados con los pacientes con alteraciones neurológicas (Frankel A-D). CONCLUSIÓN: el tratamiento de las enfermedades de la transición cervicotorácica de la columna vertebral presenta detalles adicionales a los demás segmentos de la columna vertebral. En la vigencia al acceso quirúrgico existen puntos a ser respetados como la anatomía relacionada al acceso quirúrgico, las características anatómicas peculiares de las vértebras y biomecánica singular de ese segmento de la columna vertebral

Effect of resource spatial correlation and Hunter-Fisher-Gatherer mobility on social cooperation in Tierra del Fuego

This article presents an agent-based model designed to explore the development of cooperation in hunter-fisher-gatherer societies that face a dilemma of sharing an unpredictable resource that is randomly distributed in space. The model is a stylised abstraction of the Yamana society, which inhabited the channels and islands of the southernmost part of Tierra del Fuego (Argentina-Chile). According to ethnographic sources, the Yamana developed cooperative behaviour supported by an indirect reciprocity mechanism: whenever someone found an extraordinary confluence of resources, such as a beached whale, they would use smoke signals to announce their find, bringing people together to share food and exchange different types of social capital. The model provides insight on how the spatial concentration of beachings and agents’ movements in the space can influence cooperation. We conclude that the emergence of informal and dynamic communities that operate as a vigilance network preserves cooperation and makes defection very costly.MICINN http://www.idi.mineco.gob.es/ CSD2010-00034 (SimulPast CONSOLIDER-INGENIO 2010) and HAR2009-06996; the government of Castilla y Leónhttp://www.jcyl.es/ GREX251-2009; the Argentine CONICET http://www.conicet.gov.ar/PIP-0706; and the Wenner-Gren Foundation for Anthropological Researchhttp://www.wennergren.org/ "Social Aggregation: A Yamana Society's Short Term Episode to Analyse Social Interaction, Tierra del Fuego, Argentina". The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscrip

Phosphate concentration and arbuscular mycorrhizal colonisation influence the growth, yield and expression of twelve PHT1 family phosphate transporters in foxtail millet (Setaria italica)

Phosphorus (P) is an essential element which plays several key roles in all living organisms. Setaria italica (foxtail millet) is a model species for panacoid grasses including several millet species widely grown in arid regions of Asia and Africa, and for the bioenergy crop switchgrass. The growth responses of S. italica to different levels of inorganic phosphate (Pi) and to colonisation with the arbuscular mycorrhizal fungus Funneliformis mosseae (syn. Glomus mosseae) were studied. Phosphate is taken up from the environment by the PHT1 family of plant phosphate transporters, which have been well characterized in several plant species. Bioinformatic analysis identified 12 members of the PHT1 gene family (SiPHT1;1-1;12) in S. italica, and RT and qPCR analysis showed that most of these transporters displayed specific expression patterns with respect to tissue, phosphate status and arbuscular mycorrhizal colonisation. SiPHT1;2 was found to be expressed in all tissues and in all growth conditions tested. In contrast, expression of SiPHT1;4 was induced in roots after 15 days growth in hydroponic medium of low Pi concentration. Expression of SiPHT1;8 and SiPHT1;9 in roots was selectively induced by colonisation with F. mosseae. SiPHT1;3 and SiPHT1;4 were found to be predominantly expressed in leaf and root tissues respectively. Several other transporters were expressed in shoots and leaves during growth in low Pi concentrations. This study will form the basis for the further characterization of these transporters, with the long term goal of improving the phosphate use efficiency of foxtail millet

Evaluating the drivers of and obstacles to the willingness to use cognitive enhancement drugs: the influence of drug characteristics, social environment, and personal characteristics

Sattler S, Mehlkop G, Graeff P, Sauer C. Evaluating the drivers of and obstacles to the willingness to use cognitive enhancement drugs: the influence of drug characteristics, social environment, and personal characteristics. Substance Abuse Treatment, Prevention, and Policy. 2014;9(1): 8.Background The use of cognitive enhancement (CE) by means of pharmaceutical agents has been the subject of intense debate both among scientists and in the media. This study investigates several drivers of and obstacles to the willingness to use prescription drugs non-medically for augmenting brain capacity. Methods We conducted a web-based study among 2,877 students from randomly selected disciplines at German universities. Using a factorial survey, respondents expressed their willingness to take various hypothetical CE-drugs; the drugs were described by five experimentally varied characteristics and the social environment by three varied characteristics. Personal characteristics and demographic controls were also measured. Results We found that 65.3% of the respondents staunchly refused to use CE-drugs. The results of a multivariate negative binomial regression indicated that respondents’ willingness to use CE-drugs increased if the potential drugs promised a significant augmentation of mental capacity and a high probability of achieving this augmentation. Willingness decreased when there was a high probability of side effects and a high price. Prevalent CE-drug use among peers increased willingness, whereas a social environment that strongly disapproved of these drugs decreased it. Regarding the respondents’ characteristics, pronounced academic procrastination, high cognitive test anxiety, low intrinsic motivation, low internalization of social norms against CE-drug use, and past experiences with CE-drugs increased willingness. The potential severity of side effects, social recommendations about using CE-drugs, risk preferences, and competencies had no measured effects upon willingness. Conclusions These findings contribute to understanding factors that influence the willingness to use CE-drugs. They support the assumption of instrumental drug use and may contribute to the development of prevention, policy, and educational strategies

Popliteal lymph node dissection for metastatic squamous cell carcinoma: a case report of an uncommon procedure for an uncommon presentation

Lymph node metastasis from cutaneous squamous cell carcinoma is uncommon. The popliteal fossa is rarely involved with metastasis. Popliteal lymph node dissection is uncommonly performed and not frequently discussed in the literature. We present a case of squamous cell carcinoma of the heel with popliteal and inguinal metastasis. This is followed by a description of the relevant anatomy of the popliteal fossa and the technique of popliteal lymphadenectomy

Epidemiologic evidence for asthma and exposure to air toxics: linkages between occupational, indoor, and community air pollution research.

Outdoor ambient air pollutant exposures in communities are relevant to the acute exacerbation and possibly the onset of asthma. However, the complexity of pollutant mixtures and etiologic heterogeneity of asthma has made it difficult to identify causal components in those mixtures. Occupational exposures associated with asthma may yield clues to causal components in ambient air pollution because such exposures are often identifiable as single-chemical agents (e.g., metal compounds). However, translating occupational to community exposure-response relationships is limited. Of the air toxics found to cause occupational asthma, only formaldehyde has been frequently investigated in epidemiologic studies of allergic respiratory responses to indoor air, where general consistency can be shown despite lower ambient exposures. The specific volatile organic compounds (VOCs) identified in association with occupational asthma are generally not the same as those in studies showing respiratory effects of VOC mixtures on nonoccupational adult and pediatric asthma. In addition, experimental evidence indicates that airborne polycyclic aromatic hydrocarbon (PAH) exposures linked to diesel exhaust particles (DEPs) have proinflammatory effects on airways, but there is insufficient supporting evidence from the occupational literature of effects of DEPs on asthma or lung function. In contrast, nonoccupational epidemiologic studies have frequently shown associations between allergic responses or asthma with exposures to ambient air pollutant mixtures with PAH components, including black smoke, high home or school traffic density (particularly truck traffic), and environmental tobacco smoke. Other particle-phase and gaseous co-pollutants are likely causal in these associations as well. Epidemiologic research on the relationship of both asthma onset and exacerbation to air pollution is needed to disentangle effects of air toxics from monitored criteria air pollutants such as particle mass. Community studies should focus on air toxics expected to have adverse respiratory effects based on biological mechanisms, particularly irritant and immunological pathways to asthma onset and exacerbation

Model for in vivo progression of tumors based on co-evolving cell population and vasculature

With countless biological details emerging from cancer experiments, there is a growing need for minimal mathematical models which simultaneously advance our understanding of single tumors and metastasis, provide patient-personalized predictions, whilst avoiding excessive hard-to-measure input parameters which complicate simulation, analysis and interpretation. Here we present a model built around a co-evolving resource network and cell population, yielding good agreement with primary tumors in a murine mammary cell line EMT6-HER2 model in BALB/c mice and with clinical metastasis data. Seeding data about the tumor and its vasculature from in vivo images, our model predicts corridors of future tumor growth behavior and intervention response. A scaling relation enables the estimation of a tumor's most likely evolution and pinpoints specific target sites to control growth. Our findings suggest that the clinically separate phenomena of individual tumor growth and metastasis can be viewed as mathematical copies of each other differentiated only by network structure