IN VITRO EFFECT OF EPHEDRINE, ADRENALINE, NORADRENALINE AND ISOPRENALINE ON HALOTHANE-INDUCED CONTRACTURES IN SKELETAL MUSCLE FROM PATIENTS POTENTIALLY SUSCEPTIBLE TO MALIGNANT HYPERTHERMIA

SUMMARY We have measured the effects of ephedrine, adrenaline, noradrenaline and isoprenaline on halothaneinduced contractures in muscle biopsies from patients potentially susceptible to malignant hyperthermia (MH). At concentrations of 4-24 mmol litre−1, ephedrine induced in vitro contractures in halothane 0.44 mmol litre−1-prechallenged muscle, whilst adrenaline, noradrenaline and isoprenaline had no effect. There was a shift of the ephedrine concentration-response curve to theleft and an increased maximum muscle contracturein the MH susceptible group compared with the MH negative group (P < 0.001). We conclude that ephedrine increased halothane-induced muscle contractures in vitro either by an unknown pharmacological mechanism or by an adrenergic stimulation which was different from those of the other investigatedadrenoceptoragonists. (Br. J. Anaesth. 1993; 70:76-79

Media events, spectacles and risky globalization: a critical review and possible avenues for future research

We review the research conducted to date on media events and media spectacles. We posit that the main phenomena challenging the current conceptualizations of media event and media spectacle are (1) the understanding of risk, (2) the context of disasters and (3) globalization and the mediation of news in the context of transnational and transitional societies. We suggest that more research on disruptive events is needed. In the context of the new media landscape in particular, the ritual researcher may need to take into account the concepts of temporality and unpredictability as inherent features of media events and rituals – the traumatic events researcher may benefit from the concept of global risk society. Finally, we argue that more research needs to be carried out on transitional societies, as we need to learn more about the role of mediation, events and spectacles in democratization processes and in contemporary revolutions. Overall, our findings indicate that in the context of global risk society, constant disruptions and unplanned events, together with the changes in news transmission, need to be taken as a starting point also in the research frames used to understand the mediation of events in contemporary society

Diagnosis and management of pseudohypoparathyroidism and related disorders: first international Consensus Statement

This Consensus Statement covers recommendations for the diagnosis and management of patients with pseudohypoparathyroidism (PHP) and related disorders, which comprise metabolic disorders characterized by physical findings that variably include short bones, short stature, a stocky build, early-onset obesity and ectopic ossifications, as well as endocrine defects that often include resistance to parathyroid hormone (PTH) and TSH. The presentation and severity of PHP and its related disorders vary between affected individuals with considerable clinical and molecular overlap between the different types. A specific diagnosis is often delayed owing to lack of recognition of the syndrome and associated features. The participants in this Consensus Statement agreed that the diagnosis of PHP should be based on major criteria, including resistance to PTH, ectopic ossifications, brachydactyly and early-onset obesity. The clinical and laboratory diagnosis should be confirmed by a molecular genetic analysis. Patients should be screened at diagnosis and during follow-up for specific features, such as PTH resistance, TSH resistance, growth hormone deficiency, hypogonadism, skeletal deformities, oral health, weight gain, glucose intolerance or type 2 diabetes mellitus, and hypertension, as well as subcutaneous and/or deeper ectopic ossifications and neurocognitive impairment. Overall, a coordinated and multidisciplinary approach from infancy through adulthood, including a transition programme, should help us to improve the care of patients affected by these disorders

Recommendations for Diagnosis and Treatment of Pseudohypoparathyroidism and Related Disorders : An Updated Practical Tool for Physicians and Patients

Patients affected by pseudohypoparathyroidism (PHP) or related disorders are characterized by physical findings that may include brachydactyly, a short stature, a stocky build, early-onset obesity, ectopic ossifications, and neurodevelopmental deficits, as well as hormonal resistance most prominently to parathyroid hormone (PTH). In addition to these alterations, patients may develop other hormonal resistances, leading to overt or subclinical hypothyroidism, hypogonadism and growth hormone (GH) deficiency, impaired growth without measurable evidence for hormonal abnormalities, type 2 diabetes, and skeletal issues with potentially severe limitation of mobility. PHP and related disorders are primarily clinical diagnoses. Given the variability of the clinical, radiological, and biochemical presentation, establishment of the molecular diagnosis is of critical importance for patients. It facilitates management, including prevention of complications, screening and treatment of endocrine deficits, supportive measures, and appropriate genetic counselling. Based on the first international consensus statement for these disorders, this article provides an updated and ready-to-use tool to help physicians and patients outlining relevant interventions and their timing. A life-long coordinated and multidisciplinary approach is recommended, starting as far as possible in early infancy and continuing throughout adulthood with an appropriate and timely transition from pediatric to adult care.Peer reviewe

Diagnosis and management of pseudohypoparathyroidism and related disorders : first international Consensus Statement

This Consensus Statement covers recommendations for the diagnosis and management of patients with pseudohypoparathyroidism (PHP) and related disorders, which comprise metabolic disorders characterized by physical findings that variably include short bones, short stature, a stocky build, early-onset obesity and ectopic ossifications, as well as endocrine defects that often include resistance to parathyroid hormone (PTH) and TSH. The presentation and severity of PHP and its related disorders vary between affected individuals with considerable clinical and molecular overlap between the different types. A specific diagnosis is often delayed owing to lack of recognition of the syndrome and associated features. The participants in this Consensus Statement agreed that the diagnosis of PHP should be based on major criteria, including resistance to PTH, ectopic ossifications, brachydactyly and early-onset obesity. The clinical and laboratory diagnosis should be confirmed by a molecular genetic analysis. Patients should be screened at diagnosis and during follow-up for specific features, such as PTH resistance, TSH resistance, growth hormone deficiency, hypogonadism, skeletal deformities, oral health, weight gain, glucose intolerance or type 2 diabetes mellitus, and hypertension, as well as subcutaneous and/or deeper ectopic ossifications and neurocognitive impairment. Overall, a coordinated and multidisciplinary approach from infancy through adulthood, including a transition programme, should help us to improve the care of patients affected by these disorders.Peer reviewe

Mixing of Honeybees with Different Genotypes Affects Individual Worker Behavior and Transcription of Genes in the Neuronal Substrate

Division of labor in social insects has made the evolution of collective traits possible that cannot be achieved by individuals alone. Differences in behavioral responses produce variation in engagement in behavioral tasks, which as a consequence, generates a division of labor. We still have little understanding of the genetic components influencing these behaviors, although several candidate genomic regions and genes influencing individual behavior have been identified. Here, we report that mixing of worker honeybees with different genotypes influences the expression of individual worker behaviors and the transcription of genes in the neuronal substrate. These indirect genetic effects arise in a colony because numerous interactions between workers produce interacting phenotypes and genotypes across organisms. We studied hygienic behavior of honeybee workers, which involves the cleaning of diseased brood cells in the colony. We mixed ∼500 newly emerged honeybee workers with genotypes of preferred Low (L) and High (H) hygienic behaviors. The L/H genotypic mixing affected the behavioral engagement of L worker bees in a hygienic task, the cooperation among workers in uncapping single brood cells, and switching between hygienic tasks. We found no evidence that recruiting and task-related stimuli are the primary source of the indirect genetic effects on behavior. We suggested that behavioral responsiveness of L bees was affected by genotypic mixing and found evidence for changes in the brain in terms of 943 differently expressed genes. The functional categories of cell adhesion, cellular component organization, anatomical structure development, protein localization, developmental growth and cell morphogenesis were overrepresented in this set of 943 genes, suggesting that indirect genetic effects can play a role in modulating and modifying the neuronal substrate. Our results suggest that genotypes of social partners affect the behavioral responsiveness and the neuronal substrate of individual workers, indicating a complex genetic architecture underlying the expression of behavior

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Different standards: engineers’ expectations and listener adoption of digital and FM radio broadcasting

As digital radio broadcasting enters its third decade of operation, few would argue that it has met all expectations expressed at the time of its launch in the mid-1990s. Observers are now more circumspect, with views divided on the pace of transition to an all-digital future. In exploring this mismatch between expectation and actuality, this article considers the introduction of FM radio from the 1950s. It too was expected to replace its forebear (AM) but, like digital radio, its adoption by listeners was slower than anticipated. An examination of published literature, in particular engineering and technical documents, reveals a number of similarities in the development of digital radio and FM. Assumptions about listeners’ needs and preferences appear to have been based on little actual audience research and, with continual reference in the literature to the supposed deficiencies of the predecessor technology, suggest an emphasis in decision making on the technical qualities of radio broadcasting over an appreciation of actual audience preferences