Critical analysis of cerebrovascular autoregulation during repeated head-up tilt.

BACKGROUND AND PURPOSE: Cerebrovascular autoregulation has been described with a phase lead of cerebral blood flow preceding changes in cerebral perfusion pressure (CPP), but there has been less focus on the effect of CPP on cerebral vascular resistance. We investigated these relations during spontaneous fluctuations (control) and repeated head-up tilt. METHODS: Eight healthy adults were studied in supine rest and repeated tilt with 10-second supine, 10 seconds at 45 degrees head-up tilt for a total of 12 cycles. Cerebral blood flow was estimated from mean flow velocity (MFV) by transcranial Doppler ultrasound, CPP was estimated from corrected finger pressure (CPP(F)), and cerebrovascular resistance index (CVRi) was calculated in the supine position from CPP(F)/MFV. Gain and phase relations were assessed by cross-spectral analysis. RESULTS: In the supine position, MFV preceded CPP(F), but changes in CVRi followed CPP(F). Gain and phase relations for CPP(F) as input and MFV as output were similar in supine and repeated tilt experiments. Thus, changes in cerebrovascular resistance must have had a similar pattern in the supine and tilt experiments. CONCLUSIONS: Cerebrovascular autoregulation is achieved by changes in resistance in response to modulations in perfusion pressure whether spontaneous or induced by repeated tilt. The phase lead of MFV before CPP(F) is a mathematical and physiological consequence of the relation the input variable (CPP(F)) and the manipulated variable (cerebrovascular resistance) that should not be taken as an indication of independent control of cerebral blood flow

Faster femoral artery blood velocity kinetics at the onset of exercise following short-term training.

OBJECTIVE: The hypothesis that the adaptation to endurance exercise training included a faster increase in blood flow at the onset of exercise was tested in 12 healthy young men who endurance-trained (ET) 2 h/day, for 10 days at 65% VO2 peak on a cycle ergometer, and in 11 non-training control (C) subjects. METHODS: Blood flow was estimated from changes in femoral artery mean blood velocity (MBV) by pulsed Doppler. Beat-by-beat changes in cardiac output (CO) and mean arterial pressure (MAP) were obtained by impedance cardiography and a Finapres finger cuff, respectively. MBV, MAP and CO were measured at rest and during 5 min of dynamic knee extension exercise. Both legs worked alternately with 2 s raising and lowering a weight (15% maximal voluntary contraction) followed by 2 s rest while the other leg raised and lowered the weight. RESULTS: In the ET group the time to 63% (T63%) of the approximately exponential increase in MBV following 10 days of training (8.6 +/- 1.2 s, mean +/- s.e.) was significantly faster than the Day 0 response (14.2 +/- 2.1 s, P \u3c 0.05). The T63% of femoral artery vascular conductance (VCfa) was also faster following 10 days of ET (9.4 +/- 0.9 s) versus Day 0 (16.0 +/- 2.5 s) (0.05). There was no change in the T63% of both MBV and VCfa for the C group. The kinetics of CO were not significantly affected by ET, but the amplitude of CO in the adaptive phase, and at steady state, were significantly greater (P \u3c 0.05) at Day 10 compared to Day 0 for the ET group with no change in the C group. CONCLUSIONS: These data supported the hypothesis that endurance training resulted in faster adaptation of blood flow to exercising muscle, and further showed that this response occurred early in the training program

Effect of short-term lycopene supplementation and postprandial dyslipidemia on plasma antioxidants and biomarkers of endothelial health in young, healthy individuals

The objective of this study was to test the hypothesis that the effect of a high-fat meal (HFm) on plasma lipid-soluble antioxidants and biomarkers of vascular oxidative stress and inflammation would be attenuated by short-term lycopene supplementation in young healthy subjects. Following restriction of lycopene-containing foods for 1-wk (LYr), blood was collected in a fasting state and 3 h after a HFm and a low-fat meal (LFm) in N = 18 men aged 23 ± 2 years, and after a HFm only in N = 9 women aged 23 ± 1 years. Blood was also sampled pre- and post-meals following 1-wk of 80 mg/day lycopene supplementation (LYs) under continued dietary LYr. In the fasting state, LYs compared with LYr not only evoked a >2-fold increase in plasma lycopene but also increased plasma β-carotene and α-tocopherol (p < 0.01), though LYs did not affect plasma nitrate/nitrite (biomarker of nitric oxide), malondialdehyde (biomarker of lipid oxidative stress), vascular- and intercellular-adhesion molecules or C-reactive protein (biomarkers of inflammation). Contrary to the hypothesis, the HFm-induced dyslipidemic state did not affect plasma malondialdehyde, C-reactive protein, or adhesion molecules in either LYr or LYs. Both the HFm and LFm were associated with decreases in the nitric oxide metabolites nitrate/nitrite and lipid-soluble antioxidants (p < 0.05). The data revealed that 1-wk of LYs increased plasma lycopene, β-carotene, and α-tocopherol yet despite these marked changes to the plasma lipid-soluble antioxidant pool, biomarkers of vascular oxidative stress and inflammation were unaffected in the fasted state as well as during dyslipidemia induced by a HFm in young healthy subjects

Sporadic Creutzfeldt-Jakob disease infected human cerebral organoids retain the original human brain subtype features following transmission to humanized transgenic mice

Human cerebral organoids (COs) are three-dimensional self-organizing cultures of cerebral brain tissue differentiated from induced pluripotent stem cells. We have recently shown that COs are susceptible to infection with different subtypes of Creutzfeldt-Jakob disease (CJD) prions, which in humans cause different manifestations of the disease. The ability to study live human brain tissue infected with different CJD subtypes opens a wide array of possibilities from differentiating mechanisms of cell death and identifying neuronal selective vulnerabilities to testing therapeutics. However, the question remained as to whether the prions generated in the CO model truly represent those in the infecting inoculum. Mouse models expressing human prion protein are commonly used to characterize human prion disease as they reproduce many of the molecular and clinical phenotypes associated with CJD subtypes. We therefore inoculated these mice with COs that had been infected with two CJD subtypes (MV1 and MV2) to see if the original subtype characteristics (referred to as strains once transmitted into a model organism) of the infecting prions were maintained in the COs when compared with the original human brain inocula. We found that disease characteristics caused by the molecular subtype of the disease associated prion protein were similar in mice inoculated with either CO derived material or human brain material, demonstrating that the disease associated prions generated in COs shared strain characteristics with those in humans. As the first and only in vitro model of human neurodegenerative disease that can faithfully reproduce different subtypes of prion disease, these findings support the use of the CO model for investigating human prion diseases and their subtypes

Systemic lupus erythematosus and diffuse alveolar hemorrhage, etiology and novel treatment strategies.

Diffuse alveolar hemorrhage is a severe respiratory complication of systemic lupus erythematosus. The illness develops over hours to a few days and is the systemic lupus erythematosus-associated syndrome with highest mortality. Although no specific symptoms have been identified, a number of features are associated with diffuse alveolar hemorrhage, with a drop in blood hemoglobin the most prominent. Dyspnea, blood-stained sputum, diffuse infiltrates identified by chest imaging, elevated single breath-diffusing capacity for monoxide, thrombocytopenia and C3 hypocomplementemia are other commonly reported signs of diffuse alveolar hemorrhage. The etiology is not completely understood but many patients develop diffuse alveolar hemorrhage concomitant with lupus nephritis, suggesting immune complex-driven pathology. Biopsy studies have identified both cases with capillaritis and a bland non-inflammatory phenotype. An animal model of diffuse alveolar hemorrhage has indicated requirement of B lymphocytes and complement receptor-mediated apoptotic body phagocytosis by monocytes as part of the pathogenesis. This review will discuss considerations when diagnosing the condition and available therapies. Infections and other causes of hemorrhage have to be excluded as these require different treatment strategies. Methylprednisolone and cyclophosphamide remain the most commonly used therapies. Plasmapheresis and rituximab are other beneficial treatment options. A few studies have also considered intrapulmonary Factor VII therapy, extracorporeal membrane oxygenation and mesenchymal stem cell therapy. There is an unmet need of better definition of diffuse alveolar hemorrhages etiology and pathology for development of improved treatment strategies

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

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

Survival analysis modeling with hidden censoring

There are well-established survival analysis methodologies for data sets that are complete, with accurate information on censoring. But what if they are not complete? In this article we consider how to analyze cases where “hidden censoring” occurs, where individuals have effectively left the study but the hospital is unaware of this. We develop a new Markov chain-based methodology for generating survival curves and hazard functions, and demonstrate this using a breast cancer data set from the Kurdistan region of Iraq

"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