Exploring Novel Intradialytic Techniques to Identify & Ameliorate of Hemodialysis-induced Myocardial Ischemic Injury

Patients with chronic kidney disease requiring hemodialysis to sustain life have extremely high rates of cardiovascular morbidity/mortality. This is both a consequence of the disease process and treatment. Hemodialysis induces systemic circulatory stress is largely due to the extracorporeal circuit and volume removal. The stress induced by intermitted hemodialysis is repetitive with cumulative cardiovascular effect and is the principal driver of heart failure and sudden death in this vulnerable population. The insults imposed by hemodialysis result in left ventricular regional wall motion abnormalities and lead to myocardial stunning with permanent damage to the vasculature and myocardium. Currently, the adversity caused by hemodialysis remains under appreciated and largely ignored. The aim of this thesis is to explore intradialytic methods to detect and ameliorate hemodialysis-induced circulatory stress (myocardial stunning). The utility of a non-invasive intradialytic hemodynamic monitoring system using photoplethysmography to detect hemodialysis-induced circulatory stress through the skin was explored. In this first thesis project, we determined that pulse strength, an output generated by PPG technology was associated with the development of myocardial stunning. Building on this initial finding, the second thesis project supported the significance of the pulse strength variable as a signal to the development of regional wall motion abnormalities/myocardial stunning during hemodialysis. Additionally, we determined that intradialytic changes in cutaneous perfusion were detected earlier in treatment and were directly associated with direct measures of global cardiac perfusion using intravenous contract/computerized tomography imaging. Both findings were associated with rates of ultrafiltration/fluid removal during dialysis (previously identified as principal drivers of hemodialysis-induced acute cardiac injury). Exercise pre-conditioning, a phenomenon that is cardio-protective against ischemic-reperfusion injury was explored, in the form of intradialytic exercise. In the third project, we found there to be a reduction in the number of treatment-induced regional wall motion abnormalities at the peak of hemodialysis stress when intradialytic exercise was incorporated into treatment. Moreover, any amount of exercise had an immediate influence with no detrimental effect on treatment tolerability. This work describes the utility and benefit of non-invasive microcirculatory monitoring for the early detection of hemodialysis-induced circulatory stress and demonstrates the pre-conditioning benefit that intradialytic exercise has on the reduction of myocardial stunning in the hemodialysis populatio

Earthquake-related stressors associated with suicidality, depression, anxiety and post-traumatic stress in adolescents from Muisne after the earthquake 2016 in Ecuador

Background The Ecuadorian earthquake in April 16th was the second strongest and deadliest in 2016 worldwide, with approximately one million people affected. In this paper, we analyzed the psychological impact and the relationship between mental health events and various earthquake-related stressors related to the earthquake, 9 months after the event. Methods We conducted an analytical cross-sectional study, applying an anonymous survey to 316 adolescents (13-19 years old) from Muisne, Ecuador. Suicidal tendency, depression, anxiety and post-traumatic stress (PTSD) were evaluated via the Child PTSD Symptom Scale (CPSS), Spence Children's Anxiety Scale, Okasha Suicidality Scale, and the Center for Epidemiologic Studies Depression Scale (CES-D) and the adapted seven-questions earthquake-related stressors survey. Results We found a high prevalence of suicidal ideations and behavior, posttraumatic stress, depression and anxiety compared to international studies. Even though adolescents currently living in shelters had higher levels of anxiety, their suicidal tendency was significantly lower than those living in their own or their relatives' home. Finally, the earthquake-related stressors were not associated with suicidality and mental health events, with the exception of economic damage suffered by the family. Conclusions High levels of depression, post-traumatic stress and anxiety among high-school students were found, especially among those who have suffered serious economic damage. The economic impact in their families and high unemployment rates among their parents seems to be related to lack of hope and favorable perspectives for their future, situation that might lead to lead to emotional disturbances and psychological disorders. Although prolonged homelessness experience in shelters may be a stressful occurrence, might also be related with spiritual growth among adolescents, and may work as a protective factor against suicidal ideations and attempts

The Reliability of the Factor Structure of the Pediatric Daytime Sleepiness Scale in both a Spanish-Colombian and French-Canadian Version

Daytime sleepiness is characterized by an increased likelihood of falling asleep and adversely impacts youth’s academic performance, behavior, and mood. The National Sleep Foundation Sur­vey (2006) found almost 50% of youth sleep 1 to 2 hours less than the recommended 9 hours per night and 60% report daytime sleepiness. The Pediatric Daytime Sleepiness Scale (PDSS; Drake et al., 2003) is a self-report questionnaire used to evaluate the likelihood of youth falling asleep in various everyday situations. The original PDSS was developed with an English-speaking American sample (Mage=11.8; SD=.6 years), and the measure was thought to assess a uni-dimensional construct: day­time sleepiness. The PDSS has previously been translated into a Spanish version for an Argentinean sample (Mage=13.3; SD=1.5 years)

Non-invasive intradialytic percutaneous perfusion monitoring: a view to the heart through the skin

IntroductionThe life-sustaining treatment of hemodialysis (HD) induces recurrent and cumulative systemic circulatory stress resulting in cardiovascular injury. These recurrent insults compound preexisting cardiovascular sequalae leading to the development of myocardial injury and resulting in extremely high morbidity/mortality. This is largely a consequence of challenged microcirculatory flow within the myocardium (evidenced by detailed imaging-based studies). Currently, monitoring during HD is performed at the macrovascular level. Non-invasive monitoring of organ perfusion would allow the detection and therapeutic amelioration of this pathophysiological response to HD. Non-invasive percutaneous perfusion monitoring of the skin (using photoplethysmography—PPG) has been shown to be predictive of HD-induced myocardial stunning (a consequence of segmental ischemia). In this study, we extended these observations to include a dynamic assessment of skin perfusion during HD compared with directly measured myocardial perfusion during dialysis and cardiac contractile function.MethodsWe evaluated the intradialytic microcirculatory response in 12 patients receiving conventional HD treatments using continuous percutaneous perfusion monitoring throughout HD. Cardiac echocardiography was performed prior to the initiation of HD, and again at peak-HD stress, to assess the development of regional wall motion abnormalities (RWMAs). Myocardial perfusion imaging was obtained at the same timepoints (pre-HD and peak-HD stress), utilizing intravenous administered contrast and a computerized tomography (CT)-based method. Intradialytic changes in pulse strength (derived from PPG) were compared with the development of HD-induced RWMAs (indicative of myocardial stunning) and changes in myocardial perfusion.ResultsWe found an association between the lowest pulse strength reduction (PPG) and the development of RWMAs (p = 0.03) and also with changes in global myocardial perfusion (CT) (p = 0.05). Ultrafiltration rate (mL/kg/hour) was a significant driver of HD-induced circulatory stress [(associated with the greatest pulse strength reduction (p = 0.01), a reduction in global myocardial perfusion (p = 0.001), and the development of RWMAs (p = 0.03)].DiscussionPercutaneous perfusion monitoring using PPG is a useful method of assessing intradialytic hemodynamic stability and HD-induced circulatory stress. The information generated at the microcirculatory level of the skin is reflective of direct measures of myocardial perfusion and the development of HD-induced myocardial stunning. This approach for the detection and management of HD-induced cardiac injury warrants additional evaluation

Stock-Specific Movement and Distribution of Juvenile Chinook Salmon, Oncorhynchus tshawytscha, in Sandy Beach Surf Zones of Oregon and Washington, USA

Sandy beach surf zones serve as alternative nursery habitats for juvenile Chinook salmon (0 age) during their early marine residency, a period considered critical due to high and variable mortality rates. Despite the importance of early marine residence, the extent of juvenile salmon surf zone use and movement along sandy beaches is not well understood. Juvenile Chinook salmon distribution and movement were studied in shallow surf zone habitats by sampling from 2006 to 2010 with a beach seine 11 beaches adjacent and distant to four estuary mouths in Oregon and Washington, USA. The estuary of origin of each juvenile was determined using genetic stock identification methods and coded wire tags. Surf zones sampled were within littoral cells, which are stretches of the coastline bordered by rocky headlands, and included estuaries with and without Chinook salmon populations. Juvenile salmonids were only collected at littoral cells with Chinook-inhabited watersheds. Most juveniles (95 %) were present at sandy beaches adjacent (<500 m from estuary mouth) to their estuary of origin. Few Chinook salmon (5 %) were collected at littoral cells that contained non-natal estuaries. These results indicate that juvenile Chinook salmon inhabiting surf zones mostly use beaches adjacent to their estuaries of origin, but some juveniles may reside in beaches distant from their point of ocean entry.Keywords: Habitat use, Juvenile Chinook salmon, Movement, Sandy beach surf zones, Genetic stockKeywords: Habitat use, Juvenile Chinook salmon, Movement, Sandy beach surf zones, Genetic stoc

MidA is a putative methyltransferase that is required for mitochondrial complex I function

10 páginas, 6 figuras.-- et al.Dictyostelium and human MidA are homologous proteins that belong to a family of proteins of unknown function called DUF185. Using yeast two-hybrid screening and pull-down experiments, we showed that both proteins interact with the mitochondrial complex I subunit NDUFS2. Consistent with this, Dictyostelium cells lacking MidA showed a specific defect in complex I activity, and knockdown of human MidA in HEK293T cells resulted in reduced levels of assembled complex I. These results indicate a role for MidA in complex I assembly or stability. A structural bioinformatics analysis suggested the presence of a methyltransferase domain; this was further supported by site-directed mutagenesis of specific residues from the putative catalytic site. Interestingly, this complex I deficiency in a Dictyostelium midA- mutant causes a complex phenotypic outcome, which includes phototaxis and thermotaxis defects. We found that these aspects of the phenotype are mediated by a chronic activation of AMPK, revealing a possible role of AMPK signaling in complex I cytopathology.This work was supported by grants BMC2006-00394 and BMC2009-09050 to R.E. from the Spanish Ministerio de Ciencia e Innovación; to P.R.F. from the Thyne Reid Memorial Trusts and the Australian Research Council; to A.V. and O.G. from the Spanish National Bioinformatics Institute (www.inab.org), a platform of Genome Spain; to R.G. from the Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain (PI070167) and from the Comunidad de Madrid (GEN-0269/2006). S.C. is supported by a research contract from Consejería de Educación de la Comunidad de Madrid y del Fondo Social Europeo (FSE).Peer Reviewe

Search for New Physics with Jets and Missing Transverse Momentum in pp collisions at sqrt(s) = 7 TeV

A search for new physics is presented based on an event signature of at least three jets accompanied by large missing transverse momentum, using a data sample corresponding to an integrated luminosity of 36 inverse picobarns collected in proton--proton collisions at sqrt(s)=7 TeV with the CMS detector at the LHC. No excess of events is observed above the expected standard model backgrounds, which are all estimated from the data. Exclusion limits are presented for the constrained minimal supersymmetric extension of the standard model. Cross section limits are also presented using simplified models with new particles decaying to an undetected particle and one or two jets

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE