Behavioural adjustments of predators and prey to wind speed in the boreal forest.

Wind speed can have multifaceted effects on organisms including altering thermoregulation, locomotion, and sensory reception. While forest cover can substantially reduce wind speed at ground level, it is not known if animals living in forests show any behavioural responses to changes in wind speed. Here, we explored how three boreal forest mammals, a predator and two prey, altered their behaviour in response to average daily wind speeds during winter. We collected accelerometer data to determine wind speed effects on activity patterns and kill rates of free-ranging red squirrels (n = 144), snowshoe hares (n = 101), and Canada lynx (n = 27) in Kluane, Yukon from 2015 to 2018. All 3 species responded to increasing wind speeds by changing the time they were active, but effects were strongest in hares, which reduced daily activity by 25%, and lynx, which increased daily activity by 25%. Lynx also increased the number of feeding events by 40% on windy days. These results highlight that wind speed is an important abiotic variable that can affect behaviour, even in forested environments.

[The COVID-19 funeral. A director of an ethical reflection space and a funeral guide look at the upheaval of funeral rites during the health crisis]. / Les funérailles à l'épreuve de la pandémie de COVID-19. Regards croisés d'un directeur d'espace de réflexion éthique et d'un guide de funérailles sur le bouleversement des rites funéraires lors de la crise sanitaire.

The pandemic has severely affected social cohesion and the traditional landmarks of our fellow citizens. In addition to suffering related to the loss of a loved one, disorganization of the funeral and the experience of confiscation of the funeral deeply affected the psychic life of the bereaved. Despite the adaptation of funeral laws during the pandemic, an anthropological discontinuity has emerged. This anthropological break prevented the dynamic of mourning and burial of COVID-19 deaths, all the while affecting the ritualization of people leaving at the end of life, the orderliness of feelings through funeral rites as well as the resilience of caregivers and families facing an unprecedented wave of deaths. This has resulted in both a pandemic-related mortality and funeral crisis and a human crisis revealed by the COVID-19 viral storm.

The rs2108622 polymorphism is related to the early risk of ischemic stroke in non-valvular atrial fibrillation subjects under oral anticoagulation.

Oral anticoagulant treatments, such as vitamin K antagonists (VKAs), are the main treatments administered to atrial fibrillation (AF) patients in order to prevent ischemic stroke (IS). However, the genes involved in the VKA metabolism can undergo variations in a single nucleotide (SNP). These SNPs may then affect the VKA target enzyme (VKORC1), VKA degradation enzyme (CYP2C9), and vitamin K bioavailability enzyme (CYP4F2). We genotyped these SNPs in a cohort of patients with non-valvular AF who were under VKA treatment after suffering an IS. Clinical variables, CHADS2-VASC score and data about the international normalized ratio (INR) within the therapeutic range were all recorded. DNA was extracted from blood and genotyping was carried out by DNA sequencing. The main endpoint was the time from VKA onset to IS. Of a total of 356 consecutive IS patients monitored, 33 were included in the study. The median time to the event was 2248.0 days (interquartile range [IQR] 896.3-3545.3). The median CHADS2-VASC score was 4.0 (IQR 3.0-6.0). When we considered the risk of IS within 2 years under VKA treatment, we found that only the rs2108622 AA genotype was significantly associated with this endpoint (early IS) (hazard ratio 6.81, 95% CI 1.37-33.92, p = 0.019). Kaplan-Meier curve analysis also showed a significant relationship between early IS and rs2108622 AA genotype (Log rank p = 0.022). The CYP4F2 gene rs2108622 polymorphism was associated with a risk of early IS in NV-AF patients under VKA treatment.

The determination of copeptin levels helps management decisions among transient ischaemic attack patients.

BACKGROUND: Most approaches to transient ischaemic attack (TIA) triage use clinical scores and vascular imaging; however, some biomarkers have been suggested to improve the prognosis of TIA patients. METHODS: Serum levels of copeptin, adiponectin, neopterin, neuron-specific enolase, high-sensitivity C-reactive protein, IL-6, N-terminal pro-B-type natriuretic peptide, S100ß, tumour necrosis factor-alpha and IL-1α as well as clinical characteristics were assessed on consecutive TIA patients during the first 24 h of the onset of symptoms. RESULTS: Among 237 consecutive TIA patients, 12 patients (5%) had a stroke within 7 days and 15 (6%) within 90 days. Among all candidate biomarkers analysed, only copeptin was significantly increased in patients with stroke recurrence (SR) within 7 days (P = 0.026) but not within 90 days. A cut-off point of 13.8 pmol/l was established with a great predictive negative value (97.4%). Large artery atherosclerosis (LAA) [hazard ratio (HR) 12.7, 95% CI 3.2-50.1, P < 0.001] and copeptin levels ≥13.8 pmol/l (HR 3.9, 95% CI 1.01-14.4, P = 0.039) were independent predictors of SR at the 7-day follow-up. LAA was the only predictor of 90-day SR (HR 7.4, 95% CI 2.5-21.6, P < 0.001). ABCD3I was associated with 7- and 90-day SRs (P = 0.025 and P = 0.034, respectively). The association between copeptin levels and LAA had a diagnostic accuracy of 90.3%. CONCLUSIONS: Serum copeptin could be an important prognostic biomarker to guide management decisions among TIA patients. Therefore, TIA patients with copeptin levels below 13.8 pmol/l and without LAA have an insignificant risk of 7-day SR and could be managed on an outpatient basis.

Prevalence and correlates of disturbed dreaming in children.

Relatively little is known about nightmares and other forms of disturbed dreaming in children. This article reviews the literature on the prevalence and correlates of nightmares in children and highlights key methodological issues in the field. Results show that regardless of how they are defined and measured, nightmares affect a significant proportion of children of all ages and there is some evidence to suggest that nightmare frequency may peak around the age of 10. Gender differences in nightmare frequency, with girls reporting more nightmares than do boys, tend to appear between the ages of 10 and 15. Although nightmares are associated with a range of psychosocial difficulties (e.g., stress, behavioural problems), elevated anxiety and concomitant sleep-related disorders (e.g., sleepwalking) are among the most robust correlates of nightmares. Very few studies have examined nightmare treatment in children, but promising results have been obtained with imagery rehearsal therapy. Overall, research in the field has been hampered by inconsistent definitions for nightmares, by extensive variability in questionnaire items used to measure nightmare frequency, and by a lack of awareness of how using parents versus children as respondents may impact results. Longitudinal studies are needed to better understand how nightmares and their correlates evolve during childhood and adolescence, to delineate their clinical significance, and to develop effective and age-appropriate treatment strategies.

Generation of high-titer neutralizing antibodies against botulinum toxins A, B, and E by DNA electrotransfer.

Botulinum neurotoxins are known to be among the most toxic known substances. They produce severe paralysis by preventing the release of acetylcholine at the neuromuscular junction. Thus, new strategies for efficient production of safe and effective anti-botulinum neurotoxin antisera have been a high priority. Here we describe the use of DNA electrotransfer into the skeletal muscle to enhance antiserum titers against botulinum toxin serotypes A, B, and E in mice. We treated animals with codon-optimized plasmid DNA encoding the nontoxic but highly immunogenic C-terminal heavy chain fragment of the toxin. By employing both codon optimization and the electrotransfer procedure, the immune response and corresponding neutralizing antiserum titers were markedly increased. The cellular localization of the antigen and the immunization regimens were also shown to increase neutralizing titers to >100 IU/ml. This study demonstrates that DNA electrotransfer is an effective procedure for raising neutralizing antiserum titers to remarkably high levels.

Widespread biochemical correction of murine mucopolysaccharidosis type VII pathology by liver hydrodynamic plasmid delivery.

Mucopolysaccharidosis type VII (MPS VII) is a lysosomal storage disease caused by a deficiency of the acid hydrolase beta-glucuronidase. MPS VII mice develop progressive lysosomal accumulation of glycosaminoglycans (GAGs) within multiple organs, including the brain. Using this animal model, we compared two plasmid gene administration techniques: muscle electrotransfer and liver-directed transfer using hydrodynamic injection. We have evaluated both the expression kinetics and the biodistribution of beta-glucuronidase activity after gene transfer, as well as the correction of biochemical abnormalities in various organs. This study shows that MPS VII mice treated with a plasmid-bearing mouse beta-glucuronidase cDNA, acquire the ability to produce the beta-glucuronidase enzyme for an extended period of time. The liver seemed to be more appropriate than the muscle as a target organ to enable enzyme secretion into the systemic circulation. A beneficial effect on the MPS VII pathology was also observed, as liver-directed gene transfer led to the correction of secondary enzymatic elevations and to the reduction of GAGs storage in peripheral tissues and brain, as well as to histological correction in many tissues. This work is one of the first examples showing that non-viral plasmid DNA delivery can lead to improvements in both peripheral and brain manifestations of MPS VII disease. It confirms the potential of non-viral systemic gene transfer strategy in neurological lysosomal disorders.

Anionic pH-sensitive pegylated lipoplexes to deliver DNA to tumors.

Anionic pegylated lipoplexes have been prepared from the combined formulation of cationic lipoplexes and pegylated anionic liposomes. To this end, two original (bis- and tetra-) carboxylated cholesterol derivatives have been synthesised. Titration of the particle surface charge was realised to determine the ratio between anionic and cationic lipids that would give pH-sensitive complexes. This ratio has been optimised to form particles sensitive to pH change in the range 5.5-6.5. Compaction of DNA into these newly formed anionic complexes was checked by DNA accessibility to picogreen and DNA electrophoresis on an agarose gel. Gene expression of the formulated gene was similar for the cationic formulation taken as a control and the anionic formulations prepared. The pH-sensitive properties of these formulations was shown in vitro using bafilomycin, a vacuolar H(+)ATPase inhibitor. The efficiency of the new formulations to deliver DNA to the tumor was compared with cholesteryl hemisuccinate (CHEMS) formulations. The tetracarboxylated compound gave the most efficient formulations for tumor delivery in vivo.

[Near a biological diagnosis of Alzheimer's disease and related disorders]. / Vers un diagnostic biologique de la maladie d'Alzheimer et des syndromes apparentés.

PURPOSE: To review the current concepts in the biological diagnosis of Alzheimer's disease (AD) and related disorders. CURRENT KNOWLEDGE AND KEY POINTS: As new therapeutics specific of AD may be available soon, early diagnosis of AD in the context of mild cognitive impairment (MCI) or dementia appears to be challenging. The high amount of atypical clinical forms of AD leads to develop new tools allowing in vivo diagnosis. New CerebroSpinal Fluid (CSF) biomarkers seem to reflect specific aspects of deep neuropathological changes observed in AD, i.e. amyloid deposits and neurofibrillary tangles. Amyloid beta-peptide 1-42 (Abeta(1-42)) and hyperphosphorylated tubulin associated unit (tau) isoforms appear to be the most sensitive and specific CSF biomarkers, the combination of these biomarkers depicting the best diagnosis value for AD. These molecules are also efficient in the prediction of the conversion from the MCI state to the dementia state of AD. Combined to clinical and neuro-imaging information, CSF biomarkers appear thus to be highly relevant in improving the early etiological diagnosis of dementia. FUTURE PROSPECTS AND PROJECTS: The current research focalises on the development of new molecules coming from Abeta and tau protein families, in the CSF and in the serum, as well as molecules reflecting other pathological metabolism changes, as alpha-synuclein in Lewy Body Disease. The diagnosis value of CSF biological markers is so promising that they have been recently included in the research diagnosis criteria of AD.

Assessment of the targeting specificity of a fluorescent albumin conceived as a preclinical agent of the liver function.

In the context of increasing liver diseases, no contrast agent is currently available in Europe and the United States to directly assess the liver function. Only neolactosylated human serum albumin is being clinically used in Asia. In order to perform preclinical studies in the context of liver diseases, we conceived a fluorescent lactosylated albumin for the quantification of liver functional cells (l-Cyal). Precise characterization was achieved in order to determine the amounts of lactose and Cyanine 5 (Cy5) coupled to the albumin. In addition, potential aggregation was characterized by asymmetrical flow field-flow fractionation hyphenated to multi-angle light scattering (AF4-MALS). The optimal functionalized albumin exhibited a mass greater than 87 kDa which corresponds to the addition of 34 lactose moieties per protein and 1-2 Cy5 labels. Also, no significant formation of aggregates could be identified due to the modification of the native albumin. In healthy mice, the accumulation of l-Cyal in the liver and its selectivity for hepatocyte cells were shown by optical imaging and flow cytometry. Administration of l-Cyal to mice bearing liver metastases showed a reduced signal in the liver related to a decrease in the number of hepatocytes. The l-Cyal bioimaging contrast agent could be particularly useful for assessing the state of liver related diseases.

[A systematic review of the characteristics and prognosis of subjects who suffer an embolic stroke of undetermined source]. / Revision sistematica de las caracteristicas y pronostico de los sujetos que sufren un ictus criptogenico no lacunar de mecanismo embolico.

INTRODUCTION: The concept of embolic stroke of undetermined source (ESUS) has recently appeared to better characterise patients with cryptogenic stroke. PATIENTS AND METHODS: A systematic review of studies published since 2014 was performed to evaluate the epidemiology, clinical features and prognosis of patients with ESUS and their proportion among patients with cryptogenic stroke. RESULTS: Ten studies were identified with a total of 14,810 patients. The frequency of ESUS varied between 6% and 42%. We observed a high percentage of patients with cryptogenic stroke who met ESUS criteria (37-82%). The mean age of these patients was 65-68 years. The mean severity of the stroke, as measured using the National Institutes of Health Stroke Scale, was found to be 3-7 points. A high degree of variability was seen in the proportion of atrial fibrillation (detected during follow-up) related to the electrocardiogram monitoring technique. In five studies, some minor source of cardioembolism was observed in one out of every two patients, the most frequent being the persistence of patent foramen ovale. The risk of recurrence was 5-14.5%. CONCLUSION: The application of the new ESUS criteria provides a better definition of patients with cryptogenic stroke. Applying the concept of ESUS requires not only adequate electrocardiogram monitoring, but also routine complementary examinations to rule out the presence of minor sources of cardioembolism and other sources of embolism other than atrial fibrillation.

TITLE: Revision sistematica de las caracteristicas y pronostico de los sujetos que sufren un ictus criptogenico no lacunar de mecanismo embolico.Introduccion. Recientemente ha surgido el concepto de ictus criptogenico no lacunar de mecanismo embolico ­del ingles embolic stroke of undetermined source (ESUS)­ para caracterizar mejor a los pacientes con ictus criptogenico. Pacientes y metodos. Se realiza una revision sistematica de los estudios publicados desde 2014 hasta la actualidad, valorando la epidemiologia, las caracteristicas clinicas y el pronostico de los pacientes con ESUS y su proporcion entre los pacientes con ictus criptogenico. Resultados. Se identificaron 10 estudios con un total de 14.810 pacientes. La frecuencia de ESUS vario entre el 6 y el 42%. Se observo un porcentaje elevado de pacientes con ictus criptogenico que cumplian los criterios de ESUS (37-82%). La edad media de estos pacientes era de 65-68 años. La gravedad media del ictus, medida por la National Institutes of Health Stroke Scale, se establecio en 3-7 puntos. Se observo una alta variabilidad en la proporcion de fibrilacion auricular (detectada durante el seguimiento) relacionada con la tecnica de monitorizacion del electrocardiograma. En cinco estudios, hasta en uno de cada dos pacientes se observo alguna fuente de cardioembolismo menor, la mas frecuente, la persistencia del foramen oval permeable. El riesgo de recurrencia fue del 5-14,5%. Conclusion. La aplicacion de los nuevos criterios de ESUS define mejor a los pacientes con ictus criptogenico. La aplicacion del concepto de ESUS exige no solo una monitorizacion de electrocardiograma adecuada, sino exploraciones complementarias de rutina para descartar la presencia de fuentes de cardioembolismo menor y de otras fuentes de embolismo diferentes a la fibrilacion auricular.

Optical imaging of luminescence for in vivo quantification of gene electrotransfer in mouse muscle and knee.

BACKGROUND: Optical imaging is an attractive non-invasive way to evaluate the expression of a transferred DNA, mainly thanks to its lower cost and ease of realization. In this study optical imaging was evaluated for monitoring and quantification of the mouse knee joint and tibial cranial muscle electrotransfer of a luciferase encoding plasmid. Optical imaging was applied to study the kinetics of luciferase expression in both tissues. RESULTS: The substrate of luciferase (luciferin) was injected either intraperitonealy (i.p.) or in situ into the muscle or the knee joint. Luminescence resulting from the luciferase-luciferin reaction was measured in vivo with a cooled CCD camera and/or in vitro on tissue lysate. Maximal luminescence of the knee joint and muscle after i.p. (2.5 mg) or local injection of luciferin (50 microg in the knee joint, 100 microg in the muscle) were highly correlated. With the local injection procedure adopted, in vivo and in vitro luminescences measured on the same muscles significantly correlated. Luminescence measurements were reproducible and the signal level was proportional to the amount of plasmid injected. In vivo luciferase activity in the electrotransfered knee joint was detected for two weeks. Intramuscular electrotransfer of 0.3 or 3 microg of plasmid led to stable luciferase expression for 62 days, whereas injecting 30 microg of plasmid resulted in a drop of luminescence three weeks after electrotransfer. These decreases were partially associated with the development of an immune response. CONCLUSION: A particular advantage of the i.p. injection of substrate is a widespread distribution at luciferase production sites. We have also highlighted advantages of local injection as a more sensitive detection method with reduced substrate consumption. Besides, this route of injection is relatively free of uncontrolled parameters, such as diffusion to the target organ, crossing of biological barriers and evidencing variations in local enzymatic kinetics, probably related to the reaction medium in the targeted organ. Optical imaging was shown to be a sensitive and relevant technique to quantify variations of luciferase activity in vivo. Further evaluation of the effective amount of luciferase in a given tissue by in vivo optical imaging relies on conditions of the enzymatic reaction and light absorption and presently requires in vitro calibration for each targeted organ.

Interrelations Between Maternal Smoking During Pregnancy, Birth Weight and Sociodemographic Factors in the Prediction of Early Cognitive Abilities.

Maternal prenatal smoking, birth weight and sociodemographic factors were investigated in relation to cognitive abilities of 1544 children (aged 3.5 years) participating in the Québec Longitudinal Study of Children's Development. The Peabody Picture Vocabulary Test (PPVT) was used to assess verbal ability, the Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R) block design test to assess visuospatial ability, and the Visually Cued Recall (VCR) task to assess short-term memory. Prenatal smoking was related to performance on the WPPSI-R, the PPVT, and the VCR, although it did not independently predict any cognitive ability after maternal education was taken into account. Birth weight was a more robust predictor of all outcome measures and independently predicted VCR-performance. Birth weight interacted significantly with family income and maternal education in predicting visuospatial ability, indicating a greater influence of birth weight under relatively poor socio-economic conditions. Parenting and family functioning mediated associations between maternal education/family income and cognitive task performance under different birth weight conditions, although there were indications for stronger effects under relatively low birth weight. We conclude that investigations of moderating and mediating effects can provide insights into which children are most at risk of cognitive impairment and might benefit most from interventions.

[Update on post-stroke depression: posing new challenges in patients with a minor stroke or transient ischaemic attack]. / Actualizacion de la depresion postictus: nuevos retos en pacientes con ictus minor o ataque isquemico transitorio.

INTRODUCTION: Stroke is a leading cause of disability in adults. The development of depressive symptoms is the most common emotional complication. To date, most studies of post-stroke depression have excluded patients who have suffered a minor stroke or transient ischaemic attack (TIA), although they are equally vulnerable subgroups of this sickness. AIM: We present a review of published studies of post-stroke depression to elucidate aspects that have already been widely demonstrated and those who need more evidence. DEVELOPMENT: The post-stroke depression is both frequent in patients with established stroke and minor stroke or TIA. Although there are discrepancies in the definition used, in up to one out of three patients will develop this complication. We have identified risk factors of post-stroke depression with a broad scientific background (female, history of depression or other psychiatric disorders, stroke severity, functional impairment) and other without it (quality of life, cognitive impairment and neuroimaging biomarkers). The main methodological limitations found are: confusion between post-stroke depression and depressive symptoms; variability in rating scales used; and temporal variability in the time of the evaluation of mood. To date very few studies focused on minor stroke or TIA. CONCLUSIONS: Further studies are required with improved design in order to help establish the risk of post-stroke depression at different times after the stroke, minor stroke or TIA and the importance of all the factors described above.

TITLE: Actualizacion de la depresion postictus: nuevos retos en pacientes con ictus minor o ataque isquemico transitorio.Introduccion. El ictus es una de las principales causas de discapacidad en la poblacion adulta. El desarrollo de sintomas depresivos es la complicacion afectiva mas frecuente. Hasta ahora, en la mayoria de los estudios sobre depresion postictus se ha excluido a los pacientes que han sufrido un ictus minor o un ataque isquemico transitorio (AIT), si bien es un subgrupo igualmente vulnerable a esta enfermedad. Objetivo. Revisar los estudios publicados de depresion postictus para dilucidar los aspectos que ya se han demostrado ampliamente y los que necesitan mayor evidencia. Desarrollo. La depresion postictus es frecuente tanto en los pacientes con ictus establecido como en los pacientes con ictus minor o AIT. Aunque existen discrepancias en la definicion utilizada, aproximadamente uno de cada tres pacientes desarrollara esta complicacion. Se han identificado factores de riesgo de depresion postictus con un amplio respaldo cientifico (sexo femenino, antecedentes de depresion u otros trastornos psiquiatricos, gravedad del ictus y afectacion funcional) y otros sin el (calidad de vida, deterioro cognitivo y biomarcadores de neuroimagen). Las principales limitaciones metodologicas halladas son la confusion entre depresion postictus y sintomatologia depresiva, la variabilidad en las escalas de evaluacion usadas y la variabilidad en el momento temporal de la evaluacion del estado de animo. Hasta ahora son muy pocos los estudios en el ictus minor o el AIT. Conclusiones. Se necesitan nuevos estudios con mejor diseño que ayuden a establecer el riesgo de depresion postictus a diferentes tiempos tras el ictus, el ictus minor o el AIT, y establecer la importancia de los factores descritos previamente.

1H-NMR on line monitoring of water activity during lipase catalysed esterification.

1H-NMR spectroscopy is used to determine simultaneously the water activity (aw) and the time course of an esterification reaction catalysed by a lipase. Chemical shifts signals of hydroxylic hydrogens in fast exchange (i.e the average hydroxylic signal of acid, alcohol and water) varies with water activity and ester content. Calibration curves have been established from model media composed of the substrates and various ester contents, at different water activities, in order to mimic a reaction medium. One relationship is established between water activity, hydroxylic hydrogen signal chemical shift and ester content. In order to estimate the water activity evolution as a function of time, this last relationship is applied to the hydroxylic hydrogen chemical shift measured in a reaction medium where the Rhizomucor miehei lipase in a powder form is suspended in the liquid substrates. This alternative way of determining the water activity based on hydroxylic hydrogen chemical shift presents some advantages over more classical means, i.e. time saved and inaccuracies avoided by monitoring without handling the sample.

Intramuscular plasmid DNA electrotransfer: biodistribution and degradation.

We have studied radiolabelled plasmid DNA biodistribution and degradation in the muscle at different times after injection, with or without electrotransfer using previously defined conditions. Radiolabelled plasmid progressively left the muscle and was degraded as soon as 5 min after plasmid injection, with or without electrotransfer. Autoradiography showed that the major part of injected radioactivity was detected in the interfibrilar space of a large proportion of the muscle. Large zones of accumulation of radioactivity, which seems to be contained in some fibres (more than 20 microm), were identified as soon as 5 min after electrotransfer. Such structures were never observed on slices of non-electrotransferred muscles. However, these structures were not frequent and probably lesional. The surprising fact is that despite the amount of intact plasmid having been greatly reduced between 5 min and 3 h after injection, the level of transfection remains unchanged whether electric pulses were delivered 20 s or 3 h after injection. Such a behavior was similarly observed when injecting 0.3, 3 or 30 microg of plasmid DNA. Moreover, the transfection level was correlated to the amount of plasmid DNA injected. These results suggest that as soon as it is injected, plasmid DNA is proportionally partitioned between at least two compartments. While a major part of plasmid DNA is rapidly cleared and degraded, the electrotransferable pool of plasmid DNA represents a very small part of the amount injected and belongs to another compartment where it is protected from endogenous DNAses.

Intramyocardial distribution of hydroquinidine in the dog.

Hydroquinidine concentrations were measured simultaneously in the plasma and in right atrial and ventricular biopsy samples of four dogs in the steady state after eight days of oral sustained release hydroquinidine administration. The right ventricular concentrations were greater than the plasma concentrations in all samples (ratio 5.02(2.2)). In necropsy samples the ventricular concentrations were higher than the atrial concentrations, (ratio 1.54(0.36); p less than 0.01) and than the concentration in the sinus node region (7.72(1.85) ng.g-1 vs 4.21(2.6) ng.g-1). This study shows that intramyocardial pharmacokinetic measurements are possible and may help towards a better understanding of antiarrhythmic agents, particularly those with cumulative myocardial effect.

Minor physical anomalies and family adversity as risk factors for violent delinquency in adolescence.

OBJECTIVE: Minor physical anomalies are considered indicators of disruption in fetal development. They have been found to predict behavioral problems and psychiatric disorders. This study examined the extent to which minor physical anomalies, family adversity, and their interaction predict violent and nonviolent delinquency in adolescence. METHOD: Minor physical anomalies were assessed in a group of 170 adolescent boys from low socioeconomic status neighborhoods of Montréal. The boys had been enrolled in a longitudinal study since their kindergarten year, when an assessment of family adversity had been made on the basis of familial status and the parents' occupational prestige, age at the birth of the first child, and educational level. Adolescent delinquency was measured by using self-reported questionnaires and a search of official crime records. RESULTS: Results from logistic regression analyses indicated that both the total count of minor physical anomalies and the total count of minor physical anomalies of the mouth were significantly associated with an increased risk of violent delinquency in adolescence, beyond the effects of childhood physical aggression and family adversity. Similar findings were not found for nonviolent delinquency. CONCLUSIONS: Children with a higher count of minor physical anomalies, and especially a higher count of anomalies of the mouth, could be more difficult to socialize for different and additive reasons: they may have neurological deficits, and they may have feeding problems in the first months after birth. Longitudinal studies of infants with minor physical anomalies of the mouth are needed to understand the process by which they fail to learn to inhibit physical aggression.

Ascorbyl free radical: a noninvasive marker of oxidative stress in human open-heart surgery.

To assess the development of oxidative stress in cardiac ischemia/reperfusion, the resulting depletion of plasma ascorbate was monitored by electron spin resonance spectroscopic detection of ascorbyl free radical (AFR) in a homogeneous group of 12 patients undergoing aortic valve replacement. Dimethyl sulfoxide (DMSO) was used as an enhancer and stabilizer for AFR in plasma separated from blood samples collected 15 min before incision, 10 min before aortic declamping, and sequentially during the initial 30 min of reperfusion. Plasma DMSO/AFR levels of patients were found to be significantly lower than in healthy subjects (-25%), further decreased upon ischemia (-35%), dropped to their lowest values within the first 10 min of reperfusion (-46%), and did not recover their initial values within 30 min following reflow. Cardiac index measurements revealed a still depressed heart function 4 h postdeclamping and a more delayed tissue injury was evidenced by cardiac myosin and myoglobin release in plasma. DMSO/AFR levels at early reperfusion were slightly (+ 12%) higher in plasma obtained from coronary sinus samples than in plasma from peripheral blood, suggesting an extra ascorbate release from the injured heart tissue. The close analogy between these results and the reported measurements of other plasma markers of oxidative stress, including ascorbate, indicates that the present method could be of great value in clinical practice.