A case of suicide by self-injection of adrenaline.

Adrenaline (epinephrine) auto-injectors provide life-saving pre-hospital treatment for individuals experiencing anaphylaxis in a community setting. Errors in handling adrenaline auto-injectors, particularly by children and healthcare professionals, have been reported. Reports of adrenaline overdoses are limited in the medical literature. In most of these cases, accidental adrenaline administration results from medical error. Exogenous administration of catecholamine is responsible for cardiovascular and metabolic responses, which may cause supraventricular tachycardia, ventricular dysrhythmias and myocardial ischemia. The authors present a unique autopsy case involving a 34 year-old woman who intentionally self-injected adrenaline using an adrenaline auto-injector as part of a suicide plan. Catecholamines and metanephrines were measured in peripheral and cardiac blood as well as urine and vitreous humor. Based on the results of all postmortem investigations, the cause of death was determined to be cardiac dysrhythmia and cardiac arrest following adrenaline self-injection.

Neuro-mechanical determinants of repeated treadmill sprints - Usefulness of an "hypoxic to normoxic recovery" approach.

To improve our understanding of the limiting factors during repeated sprinting, we manipulated hypoxia severity during an initial set and examined the effects on performance and associated neuro-mechanical alterations during a subsequent set performed in normoxia. On separate days, 13 active males performed eight 5-s sprints (recovery = 25 s) on an instrumented treadmill in either normoxia near sea-level (SL; FiO2 = 20.9%), moderate (MH; FiO2 = 16.8%) or severe normobaric hypoxia (SH; FiO2 = 13.3%) followed, 6 min later, by four 5-s sprints (recovery = 25 s) in normoxia. Throughout the first set, along with distance covered [larger sprint decrement score in SH (-8.2%) compared to SL (-5.3%) and MH (-7.2%); P < 0.05], changes in contact time, step frequency and root mean square activity (surface electromyography) of the quadriceps (Rectus femoris muscle) in SH exceeded those in SL and MH (P < 0.05). During first sprint of the subsequent normoxic set, the distance covered (99.6, 96.4, and 98.3% of sprint 1 in SL, MH, and SH, respectively), the main kinetic (mean vertical, horizontal, and resultant forces) and kinematic (contact time and step frequency) variables as well as surface electromyogram of quadriceps and plantar flexor muscles were fully recovered, with no significant difference between conditions. Despite differing hypoxic severity levels during sprints 1-8, performance and neuro-mechanical patterns did not differ during the four sprints of the second set performed in normoxia. In summary, under the circumstances of this study (participant background, exercise-to-rest ratio, hypoxia exposure), sprint mechanical performance and neural alterations were largely influenced by the hypoxia severity in an initial set of repeated sprints. However, hypoxia had no residual effect during a subsequent set performed in normoxia. Hence, the recovery of performance and associated neuro-mechanical alterations was complete after resting for 6 min near sea level, with a similar fatigue pattern across conditions during subsequent repeated sprints in normoxia.

The role of geography and ecology in shaping repeated patterns of morphological and genetic differentiation between European minnows (Phoxinus phoxinus) from the Pyrenees and the Alps

Neutral and selective processes c an drive repeated patterns of evolu tion in dif ferent groups of populationsexp eriencing similar ecol ogica l gradients. In this paper, we used a combinat ion of nucl ear and mitochondrialDNA markers, as well as geometric morphometrics, to investigate repeated patterns of morphological andgenetic divergence of E uropean minnows in two mountain ranges : the Pyrenees and the Al ps. Europeanminnows (Phoxinus phoxinus) are cyprinid fish i nha bitin g most freshwater bodies in Europe, including those indifferent mountain r anges that could act as major geographical barriers to gene flow. We explored patterns ofP. phoxinus phenotypic and genetic di versi fication along a gradi ent of alti tude common to the two mountainranges, and tested for isolation by distance (IBD), isolation by environment (IBE) and isolation by adaptation(IBA). The results indicated that populations from the Pyr enees a nd the Alps bel ong to two well differentiated,reciprocally monophyletic mt DNA lineages. Substantial genetic differentiation due to geographical isolationwithin and between populations from the Pyrenees and the Alps was also found using rapidly evolving AFLPsmarkers (isolation by distance or IBD), as well as morphological differences between mountain ranges. Als o,morphology varied strong ly with elevation and so did genetic differentiation to a lower extent. Despitemoderate evidence for IBE and IBA, and therefore of repeated evolution, substantial population heterogeneitywas found at the genetic level, suggesting that selection and population specific genetic drift act in concert toaffect genetic divergence.

Suicide par sulfure d'hydrogène et délai post mortem long : à propos d'un cas. [Suicide by hydrogen sulfide inhalation and significant post mortem delay: A case report].

L'hydrogène sulfuré (H2S) est un gaz toxique retrouvé à l'état naturel et dans certains milieux industriels, à l'origine d'intoxication accidentelle, mais pouvant être également et facilement synthétisé de manière domestique. Des cas de suicide par hydrogène sulfuré ont ainsi été décrits à partir de produits ménagers dans la littérature depuis 2009, aux États-Unis et au Japon. La plupart présentait des délais post mortem (DPM) courts (moins de 72 heures). En France, les intoxications aiguës à l'H2S demeurent rares et sont le plus souvent liées à des accidents du travail. Nous rapportons ici le cas d'un homme âgé de 37 ans découvert à son domicile, en état de décomposition avancée avec un DPM de deux mois. Compte tenu de la présence d'une importante signalétique avisant du danger potentiel d'exposition à l'H2S, des mesures de précaution ont été mises en oeuvre dès la découverte du corps et poursuivies jusqu'aux opérations d'autopsie. Les analyses toxicologiques ont confirmé la présence d'H2S au niveau des prélèvements de cerveau et de muscle. Le cas présenté constitue le premier cas de suicide avec un délai post mortem long à l'H2S rapporté en France. Dans la littérature, les constatations macroscopiques à l'autopsie ne sont pas spécifiques tandis que les analyses toxicologiques reposent essentiellement sur la recherche et la quantification d'H2S. En raison de leur redistribution post mortem, les résultats de ces analyses doivent être interprétés avec prudence, et encore plus en cas de délai post mortem long et de phénomènes de putréfaction qui peuvent également être une source de génération d'H2S post mortem. Hydrogen sulfide (H2S) which is a poisonous gas found either in the natural state or in industrial environments and potentially linked with accidental intoxication, can also be easily handmade. Several cases of suicide by inhaling H2S produced by mixing household products have been reported in the literature since 2009 in USA and Japan. Most of them involved short post mortem delays up to 72 hours. In France, acute H2S poisoning remains rare and mostly accidental. We report the case of a 37-year-old man found at home, in an advanced stage of decomposition with a 2-month post mortem delay. As numerous warning signs about a high risk of H2S exposure were present, some precautionary measures were taken from the discovery of the cadaver to the autopsy. Toxicological analyses confirmed the presence of H2S in brain and muscle samples. This observation is the first French case with a long post mortem delay. As macroscopic findings in such cases are described to be unspecific in literature, toxicological analysis must focus on the detection and the quantification of H2S. However, due to the phenomena of post mortem drug redistribution and neo-formation, their results should be interpreted with much more caution when the post mortem delay is long. The potential increase in such voluntary-intoxication-related-deaths in France, similar to the recent Japanese and American waves of suicides, requires for forensic scientists, a good knowledge of both thanatological and toxicological pictures, and precautionary measures to adopt in such situations.

Comparison of Four Sections for Analyzing Running Mechanics Alterations During Repeated Treadmill Sprints.

We compared different approaches to analyze running mechanics alterations during repeated treadmill sprints. Thirteen active male athletes performed five 5-second sprints with 25 seconds of recovery on an instrumented treadmill. This approach allowed continuous measurement of running kinetics/kinematics and calculation of vertical and leg stiffness variables that were subsequently averaged over 3 distinct sections of the 5-second sprint (steps 2-5, 7-10, and 12-15) and for all steps (steps 2-15). Independently from the analyzed section, propulsive power and step frequency decreased with fatigue, while contact time and step length increased (P < .05). Except for step frequency, all mechanical variables varied (P < .05) across sprint sections. The only parameters that highly depend on running velocity (propulsive power and vertical stiffness) showed a significant interaction (P < .05) between the analyzed sections, with smaller magnitude of fatigue-induced change observed for steps 2-5. Considering all steps or only a few steps during early, middle, or late phases of 5-second sprints provides similar mechanical outcomes during repeated treadmill sprinting, although acceleration induces noticeable differences between the sections studied. Furthermore, quantifying mechanical alterations from the early acceleration phase may not be readily detectable, and is not recommended.

Circadian variation of salivary immunoglobin A, alpha-amylase activity and mood in response to repeated double-poling sprints in hypoxia.

PURPOSE: To assess the circadian variations in salivary immunoglobin A (sIgA) and alpha-amylase activity (sAA), biomarkers of mucosal immune function, together with mood during 2 weeks of repeated sprint training in hypoxia (RSH) and normoxia (RSN). METHODS: Over a 2-week period, 17 competitive cross-country skiers performed six training sessions, each consisting of four sets of five 10-s bouts of all-out double-poling under either normobaric hypoxia (FiO2: 13.8 %, 3000 m) or normoxia. The levels of sIgA and sAA activity and mood were determined five times during each of the first (T1) and sixth (T6) days of training, as well as during days preceding (baseline) and after the training intervention (follow-up). RESULTS: With RSH, sIgA was higher on T6 than T1 (P = 0.049), and sAA was increased on days T1, T6, and during the follow-up (P < 0.01). With RSN, sIgA remained unchanged and sAA was elevated on day T1 only (P = 0.04). Similarly, the RSH group demonstrated reduced mood on days T1, T6, and during the follow-up, while mood was lowered only on T1 with RSN (P < 0.01). CONCLUSIONS: The circadian variation of sIgA and sAA activity, biomarkers of mucosal immune function, as well as mood were similar on the first day of training when repeated double-poling sprints were performed with or without hypoxia. Only with RSH did the levels of sIgA and sAA activity rise with time, becoming maximal after six training sessions, when mood was still lowered. Therefore, six sessions of RSH reduced mood, but did not impair mucosal immune function.

Repeated Whole-Genome Duplication, Karyotype Reshuffling, and Biased Retention of Stress-Responding Genes in Buckler Mustard.

Whole-genome duplication (WGD) is usually followed by gene loss and karyotype repatterning. Despite evidence of new adaptive traits associated with WGD, the underpinnings and evolutionary significance of such genome fractionation remain elusive. Here, we use Buckler mustard (Biscutella laevigata) to infer processes that have driven the retention of duplicated genes after recurrent WGDs. In addition to the β- and α-WGD events shared by all Brassicaceae, cytogenetic and transcriptome analyses revealed two younger WGD events that occurred at times of environmental changes in the clade of Buckler mustard (Biscutelleae): a mesopolyploidy event from the late Miocene that was followed by considerable karyotype reshuffling and chromosome number reduction and a neopolyploidy event during the Pleistocene. Although a considerable number of the older duplicates presented signatures of retention under positive selection, the majority of retained duplicates arising from the younger mesopolyploidy WGD event matched predictions of the gene balance hypothesis and showed evidence of strong purifying selection as well as enrichment in gene categories responding to abiotic stressors. Retention of large stretches of chromosomes for both genomic copies supported the hypothesis that cycles of WGD and biased fractionation shaped the genome of this stress-tolerant polypolyloid, promoting the adaptive recruitment of stress-responding genes in the face of environmental challenges.

Amiodarone biokinetics, the formation of its major oxidative metabolite and neurotoxicity after acute and repeated exposure of brain cell cultures.

The difficulty in mimicking nervous system complexity and cell-cell interactions as well as the lack of kinetics information has limited the use of in vitro neurotoxicity data. Here, we assessed the biokinetic profile as well as the neurotoxicity of Amiodarone after acute and repeated exposure in two advanced rodent brain cell culture models, consisting of both neurons and glial cells organized in 2 or 3 dimensions to mimic the brain histiotypic structure and function. A strategy was applied to evidence the abiotic processes possibly affecting Amiodarone in vitro bioavailability, showing its ability to adsorb to the plastic devices. At clinically relevant Amiodarone concentrations, known to induce neurotoxicity in some patients during therapeutic treatment, a complete uptake was observed in both models in 24h, after single exposure. After repeated treatments, bioaccumulation was observed, especially in the 3D cell model, together with a greater alteration of neurotoxicity markers. After 14days, Amiodarone major oxidative metabolite (mono-N-desethylamiodarone) was detected at limited levels, indicating the presence of active drug metabolism enzymes (i.e. cytochrome P450) in both models. The assessment of biokinetics provides useful information on the relevance of in vitro toxicity data and should be considered in the design of an Integrated Testing Strategy aimed to identify specific neurotoxic alerts, and to improve the neurotoxicity assay predictivity for human acute and repeated exposure.

High Altitude Increases Alteration in Maximal Torque but Not in Rapid Torque Development in Knee Extensors after Repeated Treadmill Sprinting.

We assessed knee extensor neuromuscular adjustments following repeated treadmill sprints in different normobaric hypoxia conditions, with special reference to rapid muscle torque production capacity. Thirteen team- and racquet-sport athletes undertook 8 × 5-s "all-out" sprints (passive recovery = 25 s) on a non-motorized treadmill in normoxia (NM; FiO2 = 20.9%), at low (LA; FiO2 = 16.8%) and high (HA; FiO2 = 13.3%) normobaric hypoxia (simulated altitudes of ~1800 m and ~3600 m, respectively). Explosive (~1 s; "fast" instruction) and maximal (~5 s; "hard" instruction) voluntary isometric contractions (MVC) of the knee extensors (KE), with concurrent electromyographic (EMG) activity recordings of the vastus lateralis (VL) and rectus femoris (RF) muscles, were performed before and 1-min post-exercise. Rate of torque development (RTD) and EMG (i.e., Root Mean Square or RMS) rise from 0 to 30, -50, -100, and -200 ms were recorded, and were also normalized to maximal torque and EMG values, respectively. Distance covered during the first 5-s sprint was similar (P > 0.05) in all conditions. A larger (P < 0.05) sprint decrement score and a shorter (P < 0.05) cumulated distance covered over the eight sprints occurred in HA (-8 ± 4% and 178 ± 11 m) but not in LA (-7 ± 3% and 181 ± 10 m) compared to NM (-5 ± 2% and 183 ± 9 m). Compared to NM (-9 ± 7%), a larger (P < 0.05) reduction in MVC torque occurred post-exercise in HA (-14 ± 9%) but not in LA (-12 ± 7%), with no difference between NM and LA (P > 0.05). Irrespectively of condition (P > 0.05), peak RTD (-6 ± 11%; P < 0.05), and normalized peak RMS activity for VL (-8 ± 11%; P = 0.07) and RF (-14 ± 11%; P < 0.01) muscles were reduced post-exercise, whereas reductions (P < 0.05) in absolute RTD occurred within the 0-100 (-8 ± 9%) and 0-200 ms (-10 ± 8%) epochs after contraction onset. After normalization to MVC torque, there was no difference in RTD values. Additionally, the EMG rise for VL muscle was similar (P > 0.05), whereas it increased (P < 0.05) for RF muscle during all epochs post-exercise, independently of the conditions. In summary, alteration in repeated-sprint ability and post-exercise MVC decrease were greater at high altitude than in normoxia or at low altitude. However, the post-exercise alterations in RTD were similar between normoxia and low-to-high hypoxia.

Running mechanical alterations during repeated treadmill sprints in hot versus hypoxic environments : a pilot study.

We determined if performance and mechanical running alterations during repeated treadmill sprinting differ between severely hot and hypoxic environments. Six male recreational sportsmen (team- and racket-sport background) performed five 5-s sprints with 25-s recovery on an instrumented treadmill, allowing the continuous (step-by-step) measurement of running kinetics/kinematics and spring-mass characteristics. These were randomly conducted in control (CON; 25°C/45% RH, inspired fraction of oxygen = 20.9%), hot (HOT; 38°C/21% RH, inspired fraction of oxygen = 20.9%; end-exercise core temperature: ~38.6°C) and normobaric hypoxic (HYP, 25°C/45% RH, inspired fraction of oxygen = 13.3%/simulated altitude of ~3600 m; end-exercise pulse oxygen saturation: ~84%) environments. Running distance was lower (P < 0.05) in HOT compared to CON and HYP for the first sprint but larger (P < 0.05) sprint decrement score occurred in HYP versus HOT and CON. Compared to CON, the cumulated distance covered over the five sprints was lower (P < 0.01) in HYP but not in HOT. Irrespective of the environmental condition, significant changes occurred from the first to the fifth sprint repetitions (all three conditions compounded) in selected running kinetics (mean horizontal forces, P < 0.01) or kinematics (contact and swing times, both P < 0.001; step frequency, P < 0.001) and spring-mass characteristics (vertical stiffness, P < 0.001; leg stiffness, P < 0.01). No significant interaction between sprint number and condition was found for any mechanical data. Preliminary evidence indicates that repeated-sprint ability is more impaired in hypoxia than in a hot environment, when compared to a control condition. However, as sprints are repeated, mechanical alterations appear not to be exacerbated in severe (heat, hypoxia) environmental conditions.