Albumin concentrations are primarily determined by the body cell mass and the systemic inflammatory response in cancer patients with weight loss

The association between hypoalbuminemia and poor prognosis in patients with cancer is well recognized. However, the factors that contribute to the fall in albumin concentrations are not well understood. In the present study, we examined the relationship between circulating albumin concentrations, weight loss, the body cell mass (measured using total body potassium), and the presence of an inflammatory response (measured using C- reactive protein) in male patients (n=40) with advanced lung or gastrointestinal cancer. Albumin concentrations were significantly correlated with the percent ideal body weight (r=0.390, p lt 0.05), extent of reported weight loss (r=-0.492, p lt 0.01), percent predicted total body potassium (adjusted for age, height, and weight, r=0.686, p lt 0.001), and logo C-reactive protein concentrations (r=-0.545, p lt 0.001). On multiple regression analysis, the percent predicted total body potassium and log(10) C-reactive protein concentrations accounted for 63% of the variation in albumin concentrations (r(2) = 0.626, p lt 0.001). The interrelationship between albumin, body cell mass, and the inflammatory response is consistent with the concept that the presence of an ongoing inflammatory response contributes to the progressive loss of these vital protein components of the body and the subsequent death of patients with advanced cancer

Postcopulatory sexual selection

The female reproductive tract is where competition between the sperm of different males takes place, aided and abetted by the female herself. Intense postcopulatory sexual selection fosters inter-sexual conflict and drives rapid evolutionary change to generate a startling diversity of morphological, behavioural and physiological adaptations. We identify three main issues that should be resolved to advance our understanding of postcopulatory sexual selection. We need to determine the genetic basis of different male fertility traits and female traits that mediate sperm selection; identify the genes or genomic regions that control these traits; and establish the coevolutionary trajectory of sexes

Interrater reliability of electrodiagnosis in neonatal brachial plexopathy

Introduction: We investigated interrater reliability of overall assessment of nerve root lesions by electrodiagnostic testing (EDX) in neonatal brachial plexus palsy (NBPP). Methods: Two blinded, boardâ certified reviewers retrospectively reviewed deâ identified EDX data from 37 infants with NBPP for 2005â 2012. Only nerve conduction and electromyography needle data were included. The examiners independently assigned 1 of 4 nerve root lesion categories: (1) preâ ganglionic lesion (avulsion), (2) postâ ganglionic lesion (rupture), (3) normal, or (4) â unable to determine.â Simple percentage agreement, the Cohen kappa statistic representing interrater reliability for each nerve root (C5â T1), and overall kappa between examiners were evaluated. Results: Interrater reliabilities were substantial to almost perfect for each nerve root except C5. Considering all nerve roots, overall interrater reliability was substantial (kappa = 0.62); simple percentage agreement was 75% (138/185). Conclusions: Interrater reliability of nerve root assessment by EDX for infants with NBPP was high for C6â T1 root levels, but less reliable for C5 because of technical factors. Muscle Nerve 55: 69â 73, 2017Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135308/1/mus25193.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135308/2/mus25193_am.pd

Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders

Glucose and glutamine fuel protein O-GlcNAcylation to control T cell self-renewal and malignancy

Sustained glucose and glutamine transport are essential for activated T lymphocytes to support ATP and macromolecule biosynthesis. We now show that glutamine and glucose also fuel an indispensible dynamic regulation of intracellular protein O-GlcNAcylation at key stages of T cell development, transformation and differentiation. Glucose and glutamine are precursors of UDP-GlcNAc, a substrate for cellular glycosyltransferases. Immune activated T cells contained higher concentrations of UDP-GlcNAc and increased intracellular protein O-GlcNAcylation controlled by the enzyme O-GlcNAc glycosyltransferase as compared to naïve cells. We identified Notch, the T cell antigen receptor and c-Myc as key controllers of T cell protein O-GlcNAcylation, via regulation of glucose and glutamine transport. Loss of O-GlcNAc transferase blocked T cell progenitor renewal, malignant transformation, and peripheral T cell clonal expansion. Nutrient-dependent signaling pathways regulated by O-GlcNAc glycosyltransferase are thus fundamental for T cell biology

Biogeographic distributions of neotropical trees reflect their directly measured drought tolerances

High levels of species diversity hamper current understanding of how tropical forests may respond to environmental change. In the tropics, water availability is a leading driver of the diversity and distribution of tree species, suggesting that many tropical taxa may be physiologically incapable of tolerating dry conditions, and that their distributions along moisture gradients can be used to predict their drought tolerance. While this hypothesis has been explored at local and regional scales, large continental-scale tests are lacking. We investigate whether the relationship between drought-induced mortality and distributions holds continentally by relating experimental and observational data of drought-induced mortality across the Neotropics to the large-scale bioclimatic distributions of 115 tree genera. Across the different experiments, genera affiliated to wetter climatic regimes show higher drought-induced mortality than dry-affiliated ones, even after controlling for phylogenetic relationships. This pattern is stronger for adult trees than for saplings or seedlings, suggesting that the environmental filters exerted by drought impact adult tree survival most strongly. Overall, our analysis of experimental, observational, and bioclimatic data across neotropical forests suggests that increasing moisture-stress is indeed likely to drive significant changes in floristic composition

Aquaporins: important but elusive drug targets.

The aquaporins (AQPs) are a family of small, integral membrane proteins that facilitate water transport across the plasma membranes of cells in response to osmotic gradients. Data from knockout mice support the involvement of AQPs in epithelial fluid secretion, cell migration, brain oedema and adipocyte metabolism, which suggests that modulation of AQP function or expression could have therapeutic potential in oedema, cancer, obesity, brain injury, glaucoma and several other conditions. Moreover, loss-of-function mutations in human AQPs cause congenital cataracts (AQP0) and nephrogenic diabetes insipidus (AQP2), and autoantibodies against AQP4 cause the autoimmune demyelinating disease neuromyelitis optica. Although some potential AQP modulators have been identified, challenges associated with the development of better modulators include the druggability of the target and the suitability of the assay methods used to identify modulators

Aquaporin water channels in the nervous system.

The aquaporins (AQPs) are plasma membrane water-transporting proteins. AQP4 is the principal member of this protein family in the CNS, where it is expressed in astrocytes and is involved in water movement, cell migration and neuroexcitation. AQP1 is expressed in the choroid plexus, where it facilitates cerebrospinal fluid secretion, and in dorsal root ganglion neurons, where it tunes pain perception. The AQPs are potential drug targets for several neurological conditions. Astrocytoma cells strongly express AQP4, which may facilitate their infiltration into the brain, and the neuroinflammatory disease neuromyelitis optica is caused by AQP4-specific autoantibodies that produce complement-mediated astrocytic damage

Body size estimation in women with anorexia nervosa and healthy controls using 3D avatars

A core feature of anorexia nervosa is an over-estimation of body size. However, quantifying this over-estimation has been problematic as existing methodologies introduce a series of artefacts and inaccuracies in the stimuli used for judgements of body size. To overcome these problems, we have: (i) taken 3D scans of 15 women who have symptoms of anorexia (referred to henceforth as anorexia spectrum disorders, ANSD) and 15 healthy control women, (ii) used a 3D modelling package to build avatars from the scans, (iii) manipulated the body shapes of these avatars to reflect biometrically accurate, continuous changes in body mass index (BMI), (iv) used these personalized avatars as stimuli to allow the women to estimate their body size. The results show that women who are currently receiving treatment for ANSD show an over-estimation of body size which rapidly increases as their own BMI increases. By contrast, the women acting as healthy controls can accurately estimate their body size irrespective of their own BMI. This study demonstrates the viability of combining 3D scanning and CGI techniques to create personalised realistic avatars of individual patients to directly assess their body image perception