APOL1 risk alleles are associated with exaggerated age-related changes in glomerular number and volume in African-American adults: an autopsy study

APOL1 genetic variants contribute to kidney disease in African Americans. We assessed correlations between APOL1 profiles and renal histological features in subjects without renal disease. Glomerular number (N-glom,) and mean glomerular volume (V-glom,) were measured by the dissector/fractionator method in kidneys of African-American and non-African-American adults without renal disease, undergoing autopsies in Jackson, Mississippi. APOL1 risk alleles were genotyped and the kidney findings were evaluated in the context of those profiles. The proportions of African Americans with none, one, and two APOL1 risk alleles were 38%, 43%, and 19%, respectively; 38% of African Americans had G1 allele variants and 31% of African Americans had G2 allele variants. Only APOL1-positive African Americans had significant reductions in N-glom and increases in V-glom with increasing age. Regression analysis predicted an annual average loss of 8834 (P=0.03, sex adjusted) glomeruli per single kidney over the first 38 years of adult life in African Americans with two risk alleles. Body mass index above the group medians, but below the obesity definition of >= 30 kg/m(2), enhanced the expression of age-related changes in N-glom in African Americans with either one or two APOL1 risk alleles. These findings indicate that APOL1 risk alleles are associated with exaggerated age-related nephron loss, probably decaying from a larger pool of smaller glomeruli in early adult life, along with enlargement of the remaining glomeruli. These phenomena might mark mechanisms of accentuated susceptibility to kidney disease in APOL1-positive African Americans

Foraging Alters Resilience/Vulnerability to Sleep Disruption and Starvation in Drosophila

Recent human studies suggest that genetic polymorphisms allow an individual to maintain optimal cognitive functioning during sleep deprivation. If such polymorphisms were not associated with additional costs, selective pressures would allow these alleles to spread through the population such that an evolutionary alternative to sleep would emerge. To determine whether there are indeed costs associated with resiliency to sleep loss, we challenged natural allelic variants of the foraging gene (for) with either sleep deprivation or starvation. Flies with high levels of Protein Kinase G (PKG) (forR) do not display deficits in short-term memory following 12 h of sleep deprivation. However, short-term memory is significantly disrupted when forR flies are starved overnight. In contrast, flies with low levels of PKG (fors, fors2) show substantial deficits in short-term memory following sleep deprivation but retain their ability to learn after 12 h of starvation. We found that forR phenotypes could be largely recapitulated in fors flies by selectively increasing the level of PKG in the α/ß lobes of the mushroom bodies, a structure known to regulate both sleep and memory. Together, these data indicate that whereas the expression of for may appear to provide resilience in one environmental context, it may confer an unexpected vulnerability in other situations. Understanding how these tradeoffs confer resilience or vulnerability to specific environmental challenges may provide additional clues as to why an evolutionary alternative to sleep has not emerged

Rapid and sensitive RT-QuIC detection of human Creutzfeldt-Jakob disease using cerebrospinal fluid.

Fast, definitive diagnosis of Creutzfeldt-Jakob disease (CJD) is important in assessing patient care options and transmission risks. Real-time quaking-induced conversion (RT-QuIC) assays of cerebrospinal fluid (CSF) and nasal-brushing specimens are valuable in distinguishing CJD from non-CJD conditions but have required 2.5 to 5 days. Here, an improved RT-QuIC assay is described which identified positive CSF samples within 4 to 14 h with better analytical sensitivity. Moreover, analysis of 11 CJD patients demonstrated that while 7 were RT-QuIC positive using the previous conditions, 10 were positive using the new assay. In these and further analyses, a total of 46 of 48 CSF samples from sporadic CJD patients were positive, while all 39 non-CJD patients were negative, giving 95.8% diagnostic sensitivity and 100% specificity. This second-generation RT-QuIC assay markedly improved the speed and sensitivity of detecting prion seeds in CSF specimens from CJD patients. This should enhance prospects for rapid and accurate ante mortem CJD diagnosis. IMPORTANCE\u2002: A long-standing problem in dealing with various neurodegenerative protein misfolding diseases is early and accurate diagnosis. This issue is particularly important with human prion diseases, such as CJD, because prions are deadly, transmissible, and unusually resistant to decontamination. The recently developed RT-QuIC test allows for highly sensitive and specific detection of CJD in human cerebrospinal fluid and is being broadly implemented as a key diagnostic tool. However, as currently applied, RT-QuIC takes 2.5 to 5 days and misses 11 to 23% of CJD cases. Now, we have markedly improved RT-QuIC analysis of human CSF such that CJD and non-CJD patients can be discriminated in a matter of hours rather than days with enhanced sensitivity. These improvements should allow for much faster, more accurate, and practical testing for CJD. In broader terms, our study provides a prototype for tests for misfolded protein aggregates that cause many important amyloid diseases, such as Alzheimer's, Parkinson's, and tauopathies

"Aye, but it were wasted on thee": Cricket, British Asians, ethnic identities, and the 'magical recovery of community'

People in sport tend to possess rather jaded perceptions of its colour-blindness and thus, they are reluctant to confront the fact that, quite often racism is endemic. Yorkshire cricket in particular, has faced frequent accusations from minority ethnic communities of inveterate and institutionalised racism and territorial defensiveness. Drawing upon semi-structured interviews conducted with amateur white and British Asian cricketers, this paper examines the construction of regional identities in Yorkshire at a time when traditional myths and invented traditions of Yorkshire and 'Yorkshireness' are being deconstructed. This is conceptualised through a reading of John Clarke's 'magical recovery of community'. Although cricket has been multiracial for decades, I argue that some people's position as insiders is more straightforward than others. I present evidence to suggest that, regardless of being committed to Yorkshire and their 'Yorkshireness', white Yorkshire people may never fully accept British Asians as 'one of us'. Ideologically and practically, white Yorkshire people are engaged in constructing British Asians as anathema to Yorkshire culture. The paper concludes by advocating that, for sports cultures to be truly egalitarian, the ideology of sport itself has to change. True equality will only ever be achieved within a deracialised discourse that not only accepts difference, but embraces it

The Artification of Football: A Sociological Reconsideration of the ‘Beautiful Game'

Football is widely referred to as the ‘beautiful game’. This gives the impression that the sport can be aesthetically appreciated by its human observers. However, while many people might acknowledge that some of the physical movements made by top level football players exhibit grace, even beauty, this does not equate to football being accepted as a form of culture comparable to other areas of human activity described collectively as ‘the arts’. While this article takes an interest in philosophical inquiry into the aesthetic possibilities of football, it is primarily concerned with a sociological explanation as to how football has become ‘artified’. In doing so, the article draws upon the concept ‘artification’ as developed by Roberta Shapiro and Nathalie Heinich. The approach is not concerned with definitions of art according to aesthetic criteria or notions of appreciation, but with ‘how and under what circumstances art comes about’. This requires examining football in relation to discernible ‘constituent processes’ of artification. For reasons explained in the article, the contextual focus is on the artification of football in England. Artification is not a closed and finished matter. In that it can be said to have occurred, artification must be balanced against ‘de-artification’ in the form of potentially countervailing tendencies. Such consideration is taken up in the conclusion, via reflection upon the damaging impact of the excesses of commercial organisational control. Overall, artification is advocated as a sociological model that offers insight into the cultural significance of football in contemporary life

Renal biopsy findings among Indigenous Australians: a nationwide review

Australia's Indigenous people have high rates of chronic kidney disease and kidney failure. To define renal disease among these people, we reviewed 643 renal biopsies on Indigenous people across Australia, and compared them with 249 biopsies of non-Indigenous patients. The intent was to reach a consensus on pathological findings and terminology, quantify glomerular size, and establish and compare regional biopsy profiles. The relative population-adjusted biopsy frequencies were 16.9, 6.6, and 1, respectively, for Aboriginal people living remotely/very remotely, for Torres Strait Islander people, and for non-remote-living Aboriginal people. Indigenous people more often had heavy proteinuria and renal failure at biopsy. No single condition defined the Indigenous biopsies and, where biopsy rates were high, all common conditions were in absolute excess. Indigenous people were more often diabetic than non-Indigenous people, but diabetic changes were still present in fewer than half their biopsies. Their biopsies also had higher rates of segmental sclerosis, post-infectious glomerulonephritis, and mixed morphologies. Among the great excess of biopsies in remote/very remote Aborigines, females predominated, with younger age at biopsy and larger mean glomerular volumes. Glomerulomegaly characterized biopsies with mesangiopathic changes only, with IgA deposition, or with diabetic change, and with focal segmental glomerulosclerosis (FSGS). This review reveals great variations in biopsy rates and findings among Indigenous Australians, and findings refute the prevailing dogma that most indigenous renal disease is due to diabetes. Glomerulomegaly in remote/very remote Aboriginal people is probably due to nephron deficiency, in part related to low birth weight, and probably contributes to the increased susceptibility to kidney disease and the predisposition to FSGS

Feminist phenomenology and the woman in the running body

Modern phenomenology, with its roots in Husserlian philosophy, has been taken up and utilised in a myriad of ways within different disciplines, but until recently has remained relatively under-used within sports studies. A corpus of sociological-phenomenological work is now beginning to develop in this domain, alongside a longer standing literature in feminist phenomenology. These specific social-phenomenological forms explore the situatedness of lived-body experience within a particular social structure. After providing a brief overview of key strands of phenomenology, this article considers some of the ways in which sociological, and particularly feminist phenomenology, might be used to analyse female sporting embodiment. For illustrative purposes, data from an autophenomenographic project on female distance running are also included, in order briefly to demonstrate the application of phenomenology within sociology, as both theoretical framework and methodological approach

Dispersing the Mists: An Experimental History of Medicine Study into the Quality of Volatile Inhalations

This document is the Accepted Manuscript version. The final publication is available from Mary Ann Liebert, Inc. Publishers at https://doi.org/10.1089/jamp.2016.1357.Background: Dr. Nelson's Improved Inhaler was first marketed with an advertisement in The Lancet in 1865. Revolutionary at the time for its ease of use and patient-friendliness, the inhaler is still in use for self-treatment by many all over the world. On the occasion of its 150th anniversary, this study reports an experimental historical medicine approach to identify evidence for the quality of vapor inhalers. Methods: Through accessing reviews of the device's use by the contemporary medical establishment, it was established that Dr. Nelson's Inhaler enjoyed a reputation of quality and efficacy among reputable physicians generating empirical evidence of clinical performance. There was a general absence of product performance tests during this period. Therefore, modern inhalation performance testing was applied to test the aerosol delivery performance for Friars' Balsam, and its key chemical constituent, benzoic acid (BA). Results: A respirable dose of 59.9 ± 9.0 μg of BA was aerosolized in a 10 minutes period from a dose of 3.3 mL Friars' Balsam (equivalent to 35.1 ± 0.2 mg of BA) in 375 mL of steaming water using the glass twin stage impinger at a flow rate of 60 L·min−1. The respirable dose from a standardized aqueous BA inhalation formulation increased from 115.9 ± 10.6 to 200.2 ± 19.9 μg by increasing the simulated inhalation period from 5 to 10 minutes. When tested with a simulated inhalation maneuver (500 mL tidal volume, 13 minutes−1 respiration rate, 1:2 inspiratory:expiratory ratio) a respirable dose of 112.8 ± 40.3 μg was produced. Conclusions: This work has highlighted the potential for aerosol drug delivery using steam inhalers that are popular with patients. Physicians should therefore be aware of the potential for lung dosing with irritants when patients self-medicate using the Nelson Inhaler with vaporizing formulations such as Friars' Balsam.Peer reviewedFinal Accepted Versio

The effect of hypoxia and work intensity on insulin resistance in type 2 diabetes

Context:Hypoxia and muscle contraction stimulate glucose transport in vitro. We have previously demonstrated that exercise and hypoxia have an additive effect on insulin sensitivity in type 2 diabetics.Objectives:Our objective was to examine the effects of three different hypoxic/exercise (Hy Ex) trials on glucose metabolism and insulin resistance in the 48 h after acute hypoxia in type 2 diabetics.Design, Participants, and Interventions:Eight male type 2 diabetics completed 60 min of hypoxic [mean (sem) O(2) = ∼14.7 (0.2)%] exercise at 90% of lactate threshold [Hy Ex(60); 49 (1) W]. Patients completed an additional two hypoxic trials of equal work, lasting 40 min [Hy Ex(40); 70 (1) W] and 20 min [Hy Ex(20); 140 (12) W].Main Outcome Measures:Glucose rate of appearance and rate of disappearance were determined using the one-compartment minimal model. Homeostasis models of insulin resistance (HOMA(IR)), fasting insulin resistance index and β-cell function (HOMA(β-cell)) were calculated at 24 and 48 h after trials.Results:Peak glucose rate of appearance was highest during Hy Ex(20) [8.89 (0.56) mg/kg · min, P < 0.05]. HOMA(IR) and fasting insulin resistance index were improved in the 24 and 48 h after Hy Ex(60) and Hy Ex(40) (P < 0.05). HOMA(IR) decreased 24 h after Hy Ex(20) (P < 0.05) and returned to baseline values at 48 h.Conclusions:Moderate-intensity exercise in hypoxia (Hy Ex(60) and Hy Ex(40)) stimulates acute- and moderate-term improvements in insulin sensitivity that were less apparent in Hy Ex(20). Results suggest that exercise duration and not total work completed has a greater influence on acute and moderate-term glucose control in type 2 diabetics