N-acetylcysteine reduces oxidative stress in sickle cell patients

Oxidative stress is of importance in the pathophysiology of sickle cell disease (SCD). In this open label randomized pilot study the effects of oral N-acetylcysteine (NAC) on phosphatidylserine (PS) expression as marker of cellular oxidative damage (primary end point), and markers of hemolysis, coagulation and endothelial activation and NAC tolerability (secondary end points) were studied. Eleven consecutive patients (ten homozygous [HbSS] sickle cell patients, one HbSβ0-thalassemia patient) were randomly assigned to treatment with either 1,200 or 2,400 mg NAC daily during 6 weeks. The data indicate an increment in whole blood glutathione levels and a decrease in erythrocyte outer membrane phosphatidylserine exposure, plasma levels of advanced glycation end-products (AGEs) and cell-free hemoglobin after 6 weeks of NAC treatment in both dose groups. One patient did not tolerate the 2,400 mg dose and continued with the 1,200 mg dose. During the study period, none of the patients experienced painful crises or other significant SCD or NAC related complications. These data indicate that N-acetylcysteine treatment of sickle cell patients may reduce SCD related oxidative stress

Two Concepts of Basic Equality

It has become somewhat a commonplace in recent political philosophy to remark that all plausible political theories must share at least one fundamental premise, ‘that all humans are one another's equals’. One single concept of ‘basic equality’, therefore, is cast as the common touchstone of all contemporary political thought. This paper argues that this claim is false. Virtually all do indeed say that all humans are ‘equals’ in some basic sense. However, this is not the same sense. There are not one but (at least) two concepts of basic equality, and they reflect not a grand unity within political philosophy but a deep and striking division. I call these concepts ‘Equal Worth’ and ‘Equal Authority’. The former means that each individual’s good is of equal moral worth. The latter means that no individual is under the natural authority of anyone else. Whilst these two predicates are not in themselves logically inconsistent, I demonstrate that they are inconsistent foundation stones for political theory. A theory that starts from Equal Worth will find it near impossible to justify Equal Authority. And a theory that starts from Equal Authority will find any fact about the true worth of things, including ourselves, irrelevant to justifying legitimate action. This helps us identify the origin of many of our deepest and seemingly intractable disagreements within political philosophy, and directs our attention to the need for a clear debate about the truth and/or relationship between the two concepts. In short, my call to arms can be summed up in the demand that political philosophers never again be allowed to claim ‘that all human beings are equals’ full stop. They must be clear in what dimension they claim that we are equals—Worth or Authority (or perhaps something else)

White Paper: An Integrated Perspective on the Causes of Hypometric Metabolic Scaling in Animals

Larger animals studied during ontogeny, across populations, or across species, usually have lower mass-specific metabolic rates than smaller animals (hypometric scaling). This pattern is usually observed regardless of physiological state (e.g., basal, resting, field, and maximally active). The scaling of metabolism is usually highly correlated with the scaling of many life-history traits, behaviors, physiological variables, and cellular/molecular properties, making determination of the causation of this pattern challenging. For across-species comparisons of resting and locomoting animals (but less so for across populations or during ontogeny), the mechanisms at the physiological and cellular level are becoming clear. Lower mass-specific metabolic rates of larger species at rest are due to (a) lower contents of expensive tissues (brains, liver, and kidneys), and (b) slower ion leak across membranes at least partially due to membrane composition, with lower ion pump ATPase activities. Lower mass-specific costs of larger species during locomotion are due to lower costs for lower-frequency muscle activity, with slower myosin and Ca(++) ATPase activities, and likely more elastic energy storage. The evolutionary explanation(s) for hypometric scaling remain(s) highly controversial. One subset of evolutionary hypotheses relies on constraints on larger animals due to changes in geometry with size; for example, lower surface-to-volume ratios of exchange surfaces may constrain nutrient or heat exchange, or lower cross-sectional areas of muscles and tendons relative to body mass ratios would make larger animals more fragile without compensation. Another subset of hypotheses suggests that hypometric scaling arises from biotic interactions and correlated selection, with larger animals experiencing less selection for mass-specific growth or neurolocomotor performance. An additional third type of explanation comes from population genetics. Larger animals with their lower effective population sizes and subsequent less effective selection relative to drift may have more deleterious mutations, reducing maximal performance and metabolic rates. Resolving the evolutionary explanation for the hypometric scaling of metabolism and associated variables is a major challenge for organismal and evolutionary biology. To aid progress, we identify some variation in terminology use that has impeded cross-field conversations on scaling. We also suggest that promising directions for the field to move forward include (1) studies examining the linkages between ontogenetic, population-level, and cross-species allometries; (2) studies linking scaling to ecological or phylogenetic context; (3) studies that consider multiple, possibly interacting hypotheses; and (4) obtaining better field data for metabolic rates and the life history correlates of metabolic rate such as lifespan, growth rate, and reproduction

Paediatric Cancer

This chapter describes prevalence and risk factors for fertility impairment and adequate fertility preservation in children and adolescents with cancer. As an increasing number of childhood cancer patients survive their disease, treatment-related late effects become more relevant. One-third of girls and boys diagnosed with cancer will suffer from infertility in adulthood. This number dramatically increases following intensified chemotherapy or total body irradiation, with two-thirds and more being affected by fertility disorders. Due to the type of cancers and the urgency of cancer treatment in the majority of children and adolescents with newly diagnosed cancers, fertility preservation is additionally challenging and needs to be discussed in an interdisciplinary team to best organize procedures—always taking patients and families’ needs into account