Updates in the perioperative and emergency management of non-vitamin K antagonist oral anticoagulants.

Perioperative management of patients treated with the non-vitamin K antagonist oral anticoagulants is an ongoing challenge. Due to the lack of good clinical studies involving adequate monitoring and reversal therapies, management requires knowledge and understanding of pharmacokinetics, renal function, drug interactions, and evaluation of the surgical bleeding risk. Consideration of the benefit of reversal of anticoagulation is important and, for some low risk bleeding procedures, it may be in the patient's interest to continue anticoagulation. In case of major intra-operative bleeding in patients likely to have therapeutic or supra-therapeutic levels of anticoagulation, specific reversal agents/antidotes would be of value but are currently lacking. As a consequence, a multimodal approach should be taken which includes the administration of 25 to 50 U/kg 4-factor prothrombin complex concentrates or 30 to 50 U/kg activated prothrombin complex concentrate (FEIBA®) in some life-threatening situations. Finally, further studies are needed to clarify the ideal therapeutic intervention.

No Accumulation of Transposable Elements in Asexual Arthropods.

Transposable elements (TEs) and other repetitive DNA can accumulate in the absence of recombination, a process contributing to the degeneration of Y-chromosomes and other nonrecombining genome portions. A similar accumulation of repetitive DNA is expected for asexually reproducing species, given their entire genome is effectively nonrecombining. We tested this expectation by comparing the whole-genome TE loads of five asexual arthropod lineages and their sexual relatives, including asexual and sexual lineages of crustaceans (Daphnia water fleas), insects (Leptopilina wasps), and mites (Oribatida). Surprisingly, there was no evidence for increased TE load in genomes of asexual as compared to sexual lineages, neither for all classes of repetitive elements combined nor for specific TE families. Our study therefore suggests that nonrecombining genomes do not accumulate TEs like nonrecombining genomic regions of sexual lineages. Even if a slight but undetected increase of TEs were caused by asexual reproduction, it appears to be negligible compared to variance between species caused by processes unrelated to reproductive mode. It remains to be determined if molecular mechanisms underlying genome regulation in asexuals hamper TE activity. Alternatively, the differences in TE dynamics between nonrecombining genomes in asexual lineages versus nonrecombining genome portions in sexual species might stem from selection for benign TEs in asexual lineages because of the lack of genetic conflict between TEs and their hosts and/or because asexual lineages may only arise from sexual ancestors with particularly low TE loads.

Evolution: the end of an ancient asexual scandal.

Bdelloid rotifers were believed to have persisted and diversified in the absence of sex. Two papers now show they exchange genes with each other, via horizontal gene transfers as known in bacteria and/or via other forms of non-canonical sex.

Une approche psychanalytique de la notion de dangerosité. Violence et subjectivation : le risque de la rencontre

Après avoir situé la question de la dangerosité dans les perspectives psychiatriques actuelles, l'auteur propose de penser cette notion complexe dans un renversement du paradigme couramment admis : ainsi la référence à la dangerosité témoignerait-elle, au premier plan, de la part non symbolisée de la rencontre de la violence. Cette proposition prend appui dans un premier temps sur les propositions esquissées par M. Foucault dans sa compréhension du rapport à la violence et à la dangerosité. Puis, le recours au concept psychanalytique d'identification projective permet de proposer une modélisation clinique de la dangerosité, qui sera discutée à partir de deux observatoires dans le champ des violences sexuelles : celui d'une recherche menée auprès d'adolescents engagés dans des agirs sexuels violents et celui d'une pratique d'expertise judiciaire. First the author proposes to situate dangerousness's question in actual psychiatric field. Then, he proposes to think this complex notion into a reversal of dangerousness's paradigm: the reference to dangerousness will be thought as the expression of non-symbolized part through violence's meeting. This proposition relies in a first time on M. Foucault's propositions about a comprehension of the relation with violence and dangerousness. In a second time, the psychoanalytic concept of projective identification allows to propose clinical comprehension of dangerousness's notion. Two clinical situations about sexual violences will be asked in this plan: a research with Young sexual offenders and practice of judiciary evaluation.

Men and women differ in their cardiovascular responses to affective pictures

Empirical evidence supports the hypothesis that emotional states might contribute to cardiovascular disease and health through multiple pathways. To the extent that the acute cardiovascular response to emotional events plays a role in cardiovascular health and disease, an essential step in order to understand this possible link is to define the hemodynamic response to affective challenges. This was the aim of the present study. We assessed blood pressure (BP), heart rate (HR), stroke volume (SV), cardiac output, and total peripheral resistance (TPR) in response to 13 picture series in 18 men and 19 women (mean age 26) in order to investigate their hemodynamic responses associated with activation of the appetitive and defensive motivational systems underlying emotional experience. The hemodynamic parameters were recorded by finger-cuff photoplethysmography with Finometer™ (FMS Finapres Medical Systems, Amsterdam) and electrocardiography with the Lifeshirt system (VivoMetrics Inc., Ventura, California). Participants rated self-perceived pleasantness and arousal for each series. In men, BP and SV, but not TPR, increased with increasing self-rated arousal both for appetitive and defensive activation, whereas in women these relationships were almost absent, especially, for defensive activation. HR decelerated more in response to negative than positive and neutral pictures, and more so in men than women. These findings indicate striking sex differences. In particular, it is suggested that the sympathetic inotropic effect to the heart increases with increasing self-rated arousal strongly in men but only weakly in women. Regardless of sex differences, the modulation of the cardiovascular response to affective pictures along the dimensions of pleasantness and arousal is primarily myocardial, and the pattern of cardiovascular response is consistent with a configuration of cardiac sympathetic-parasympathetic coactivation. One possible implication of the observed sex differences concerns the link between affective states and cardiovascular health and disease. Men have a higher incidence of cardiovascular diseases than premenopausal women, and exaggerated sympathetic reactivity to emotional events is a potential pathophysiological mechanism. These findings extend current knowledge showing that under several acute behavioral challenges men demonstrate stronger cardiovascular reactivity than women.

Copeptin Levels Remain Unchanged during the Menstrual Cycle.

BACKGROUND: Copeptin, a surrogate marker for arginin vasopressin production, is evaluated as an osmo-dependent stress and inflammatory biomarker in different diseases. We investigated copeptin during the menstrual cycle and its relationship to sex hormones, markers of subclinical inflammation and estimates of body fluid. METHODS: In 15 healthy women with regular menstrual cycles, blood was drawn on fifteen defined days of their menstrual cycle and was assayed for copeptin, progesterone, estradiol, luteinizing hormone, high-sensitive C-reactive protein, tumor necrosis factor-alpha and procalcitonin. Symptoms of fluid retention were assessed on each visit, and bio impedance analysis was measured thrice to estimate body fluid changes. Mixed linear model analysis was performed to assess the changes of copeptin across the menstrual cycle and the relationship of sex hormones, markers of subclinical inflammation and estimates of body fluid with copeptin. RESULTS: Copeptin levels did not significantly change during the menstrual cycle (p = 0.16). Throughout the menstrual cycle, changes in estradiol (p = 0.002) and in the physical premenstrual symptom score (p = 0.01) were positively related to copeptin, but changes in other sex hormones, in markers of subclinical inflammation or in bio impedance analysis-estimated body fluid were not (all p = ns). CONCLUSION: Although changes in estradiol and the physical premenstrual symptom score appear to be related to copeptin changes, copeptin does not significantly change during the menstrual cycle.

Lebenslauf und Regulation in Paarbeziehungen: Bestimmungsgründe der Ungleichheit familiarer Arbeitsteilung

On the basis of a recent survey of couples living together in Switzerland, classical and less classical explanatory factors of the un-equal division of family labour between the partners are explored. Resource-theoretical aspects are only modestly confirmed where-as the family cycle emerges as a strong con-dition that develops its effects concerning feminisation or equal distribution of family labour mainly through the female partner's occupational activity. An institutionalist ap-proach is proposed, based on the concept of sex-typed complementary master-statuses.

Post-genomic update on a classical candidate gene for coronary artery disease: ESR1.

BACKGROUND: After age, sex is the most important risk factor for coronary artery disease (CAD). The mechanism through which women are protected from CAD is still largely unknown, but the observed sex difference suggests the involvement of the reproductive steroid hormone signaling system. Genetic association studies of the gene-encoding Estrogen Receptor α (ESR1) have shown conflicting results, although only a limited range of variation in the gene has been investigated. METHODS AND RESULTS: We exploited information made available by advanced new methods and resources in complex disease genetics to revisit the question of ESR1's role in risk of CAD. We performed a meta-analysis of 14 genome-wide association studies (CARDIoGRAM discovery analysis, N=≈87,000) to search for population-wide and sex-specific associations between CAD risk and common genetic variants throughout the coding, noncoding, and flanking regions of ESR1. In addition to samples from the MIGen (N=≈6000), WTCCC (N=≈7400), and Framingham (N=≈3700) studies, we extended this search to a larger number of common and uncommon variants by imputation into a panel of haplotypes constructed using data from the 1000 Genomes Project. Despite the widespread expression of ERα in vascular tissues, we found no evidence for involvement of common or low-frequency genetic variation throughout the ESR1 gene in modifying risk of CAD, either in the general population or as a function of sex. CONCLUSIONS: We suggest that future research on the genetic basis of sex-related differences in CAD risk should initially prioritize other genes in the reproductive steroid hormone biosynthesis system.

Epithelial Na+ channel mutants causing Liddle's syndrome retain ability to respond to aldosterone and vasopressin.

Liddle's syndrome is a monogenic form of hypertension caused by mutations in the PY motif of the COOH terminus of beta- and gamma-epithelial Na+ channel (ENaC) subunits. These mutations lead to retention of active channels at the cell surface. Because of the critical role of this PY motif in the stability of ENaCs at the cell surface, we have investigated its contribution to the ENaC response to aldosterone and vasopressin. Mutants of the PY motif in beta- and gamma-ENaC subunits (beta-Y618A, beta-P616L, beta-R564stop, and gamma-K570stop) were stably expressed by retroviral gene transfer in a renal cortical collecting duct cell line (mpkCCDcl4), and transepithelial Na+ transport was assessed by measurements of the benzamil-sensitive short-circuit current (Isc). Cells that express ENaC mutants of the PY motif showed a five- to sixfold higher basal Isc compared with control cells and responded to stimulation by aldosterone (10(-6) M) or vasopressin (10(-9) M) with a further increase in Isc. The rates of the initial increases in Isc after aldosterone or vasopressin stimulation were comparable in cells transduced with wild-type and mutant ENaCs, but reversal of the effects of aldosterone and vasopressin was slower in cells that expressed the ENaC mutants. The conserved sensitivity of ENaC mutants to stimulation by aldosterone and vasopressin together with the prolonged activity at the cell surface likely contribute to the increased Na+ absorption in the distal nephron of patients with Liddle's syndrome.

Absolute height-specific thresholds to identify elevated blood pressure in children.

OBJECTIVE: : Identification of children with elevated blood pressure (BP) is difficult because of the multiple sex, age, and height-specific thresholds to define elevated BP. We propose a simple set of absolute height-specific BP thresholds and evaluate their performance to identify children with elevated BP in two different populations. METHODS: : Using the 95th sex, age, and relative-height BP US thresholds to define elevated BP in children (standard criteria), we derived a set of (non sex- and non age-specific) absolute height-specific BP thresholds for 11 height categories by 10 cm increments. Using data from large school-based surveys conducted in Switzerland (N = 5207; 2621 boys, 2586 girls; age range: 10.1-14.9 years) and in the Seychelles (N = 25 759; 13 048 boys, 12 711 girls; age range: 4.4-18.8 years), we evaluated the performance of these height-specific thresholds to identify children with elevated BP. We also derived sex-specific absolute height-specific BP thresholds and compared their performance. RESULTS: : In the Swiss and the Seychelles surveys, the prevalence of elevated BP (standard criteria) was 11.4 and 9.1%, respectively. The height-specific thresholds to identify elevated BP had a sensitivity of 80 and 84%, a specificity of 99 and 99%, a positive predictive value of 92 and 91%, and a negative predictive value of 97 and 98%, respectively. Performance of sex-specific absolute height-specific BP thresholds was similar. CONCLUSION: : A simple table of height-specific BP thresholds allowed identifying children with elevated BP with high sensitivity and excellent specificity.

Moderate to vigorous physical activity and sedentary time and cardiometabolic risk factors in children and adolescents.

CONTEXT: Sparse data exist on the combined associations between physical activity and sedentary time with cardiometabolic risk factors in healthy children. OBJECTIVE: To examine the independent and combined associations between objectively measured time in moderate- to vigorous-intensity physical activity (MVPA) and sedentary time with cardiometabolic risk factors. DESIGN, SETTING, AND PARTICIPANTS: Pooled data from 14 studies between 1998 and 2009 comprising 20 871 children (aged 4-18 years) from the International Children's Accelerometry Database. Time spent in MVPA and sedentary time were measured using accelerometry after reanalyzing raw data. The independent associations between time in MVPA and sedentary time, with outcomes, were examined using meta-analysis. Participants were stratified by tertiles of MVPA and sedentary time. MAIN OUTCOME MEASURES: Waist circumference, systolic blood pressure, fasting triglycerides, high-density lipoprotein cholesterol, and insulin. RESULTS: Times (mean [SD] min/d) accumulated by children in MVPA and being sedentary were 30 (21) and 354 (96), respectively. Time in MVPA was significantly associated with all cardiometabolic outcomes independent of sex, age, monitor wear time, time spent sedentary, and waist circumference (when not the outcome). Sedentary time was not associated with any outcome independent of time in MVPA. In the combined analyses, higher levels of MVPA were associated with better cardiometabolic risk factors across tertiles of sedentary time. The differences in outcomes between higher and lower MVPA were greater with lower sedentary time. Mean differences in waist circumference between the bottom and top tertiles of MVPA were 5.6 cm (95% CI, 4.8-6.4 cm) for high sedentary time and 3.6 cm (95% CI, 2.8-4.3 cm) for low sedentary time. Mean differences in systolic blood pressure for high and low sedentary time were 0.7 mm Hg (95% CI, -0.07 to 1.6) and 2.5 mm Hg (95% CI, 1.7-3.3), and for high-density lipoprotein cholesterol, differences were -2.6 mg/dL (95% CI, -1.4 to -3.9) and -4.5 mg/dL (95% CI, -3.3 to -5.6), respectively. Geometric mean differences for insulin and triglycerides showed similar variation. Those in the top tertile of MVPA accumulated more than 35 minutes per day in this intensity level compared with fewer than 18 minutes per day for those in the bottom tertile. In prospective analyses (N = 6413 at 2.1 years' follow-up), MVPA and sedentary time were not associated with waist circumference at follow-up, but a higher waist circumference at baseline was associated with higher amounts of sedentary time at follow-up. CONCLUSION: Higher MVPA time by children and adolescents was associated with better cardiometabolic risk factors regardless of the amount of sedentary time.

Am I my brain or my genitals? A nature-culture controversy in the hermaphrodite debate from the mid-1960s to the late 1990s.

The groundbreaking and prophetic rhetoric of neuroscience has recently highlighted the fetal brain as the most promising organ for understanding why transsexuals feel "trapped in the wrong body", and for predicting whether children born with "ambiguous" genitalia will grow up to feel like a man or a woman.This article proposes a recent history of the cerebralization of intersexuality and of transsexuality as atypical neurodevelopmental conditions. It examines the ways in which the organizational theory of brain sex differentiation developed in the late 1950s in behavioral neuroendocrinology has gained increased prominence in and through controversies over best practice issues in the case management of intersex newborns, and the etiology of transsexuality.It focuses on the American context and on the leading warrior in this battle: Milton Diamond, now a most prominent figure in professional debates about the clinical management of intersexuality, and the intersex person's best friend. Persons with an intersexed or transsexual condition consider, not their gonads, but their brains, their core sense of self, as the primary determinant of sex. (Diamond and Beh 2005, 6-7, note 1)

Deleterious mutation accumulation in asexual Timema stick insects.

Sexual reproduction is extremely widespread in spite of its presumed costs relative to asexual reproduction, indicating that it must provide significant advantages. One postulated benefit of sex and recombination is that they facilitate the purging of mildly deleterious mutations, which would accumulate in asexual lineages and contribute to their short evolutionary life span. To test this prediction, we estimated the accumulation rate of coding (nonsynonymous) mutations, which are expected to be deleterious, in parts of one mitochondrial (COI) and two nuclear (Actin and Hsp70) genes in six independently derived asexual lineages and related sexual species of Timema stick insects. We found signatures of increased coding mutation accumulation in all six asexual Timema and for each of the three analyzed genes, with 3.6- to 13.4-fold higher rates in the asexuals as compared with the sexuals. In addition, because coding mutations in the asexuals often resulted in considerable hydrophobicity changes at the concerned amino acid positions, coding mutations in the asexuals are likely associated with more strongly deleterious effects than in the sexuals. Our results demonstrate that deleterious mutation accumulation can differentially affect sexual and asexual lineages and support the idea that deleterious mutation accumulation plays an important role in limiting the long-term persistence of all-female lineages.

Female-biased mortality in experimentally parasitized Alpine Swift Apus melba nestlings

1. Sex-biased mortality in adult vertebrates is often attributed to lower immunocompetence and higher parasite susceptibility of males. Although sex-specific mortality has also been reported during growth, the importance of sex-specific immunocompetence and parasite susceptibility in explaining male-biased mortality remains ambiguous in growing individuals because of potentially confounding sources of mortality such as sexual dimorphism. 2. Here, we investigated sex-specific susceptibility to the blood-sucking louse fly Crataerina melbae and sex differences in cell-mediated immunity in a bird species that is sexually monomorphic both in size and plumage coloration at the nestling stage, the Alpine Swift, Apus melba. 3. For this purpose, we manipulated ectoparasite loads by adding or removing flies to randomly chosen nests in two years, and injected nestlings with mitogenic phytohaemagglutinin (PHA) in another year. 4. There were no significant differences between male and female offspring in immune response towards PHA, parasite load, and parasite-induced decrease in growth rate. Secondary sex ratios were however biased toward males in parasitized broods, and this was explained by a greater mortality of females in parasitized than deparasitized broods. 5. Our findings are in contrast to the widely accepted hypothesis that males suffer a greater cost of parasitism. We discuss alternative hypotheses accounting for female-specific mortality.

Bone regeneration and stem cells.

?  Introduction ?  Bone fracture healing and healing problems ?  Biomaterial scaffolds and tissue engineering in bone formation -  Bone tissue engineering -  Biomaterial scaffolds -  Synthetic scaffolds -  Micro- and nanostructural properties of scaffolds -  Conclusion ?  Mesenchymal stem cells and osteogenesis -  Bone tissue -  Origin of osteoblasts -  Isolation and characterization of bone marrow derived MSC -  In vitro differentiation of MSC into osteoblast lineage cells -  In vivo differentiation of MSC into bone -  Factors and pathways controlling osteoblast differentiation of hMSC -  Defining the relationship between osteoblast and adipocyte differentiation from MSC -  MSC and sex hormones -  Effect of aging on osteoblastogenesis -  Conclusion ?  Embryonic, foetal and adult stem cells in osteogenesis -  Cell-based therapies for bone -  Specific features of bone cells needed to be advantageous for clinical use -  Development of therapeutic biological agents -  Clinical application concerns -  Conclusion ?  Platelet-rich plasma (PRP), growth factors and osteogenesis -  PRP effects in vitro on the cells involved in bone repair -  PRP effects on osteoblasts -  PRP effects on osteoclasts -  PRP effects on endothelial cells -  PRP effects in vivo on experimental animals -  The clinical use of PRP for bone repair -  Non-union -  Distraction osteogenesis -  Spinal fusion -  Foot and ankle surgery -  Total knee arthroplasty -  Odontostomatology and maxillofacial surgery -  Conclusion ?  Molecular control of osteogenesis -  TGF-β signalling -  FGF signalling -  IGF signalling -  PDGF signalling -  MAPK signalling pathway -  Wnt signalling pathway -  Hedgehog signalling -  Notch signalling -  Ephrin signalling -  Transcription factors regulating osteoblast differentiation -  Conclusion ?  Summary This invited review covers research areas of central importance for orthopaedic and maxillofacial bone tissue repair, including normal fracture healing and healing problems, biomaterial scaffolds for tissue engineering, mesenchymal and foetal stem cells, effects of sex steroids on mesenchymal stem cells, use of platelet-rich plasma for tissue repair, osteogenesis and its molecular markers. A variety of cells in addition to stem cells, as well as advances in materials science to meet specific requirements for bone and soft tissue regeneration by addition of bioactive molecules, are discussed.