Ageing, hypertension and aortic valve stenosis - Understanding the series circuit using cardiac magnetic resonance and applanation tonometry.

BACKGROUND: Aortic stenosis (AS) is no longer considered to be a disease of fixed left ventricular (LV) afterload, but rather, functions as a series circuit, with important contributions from both the valve and vasculature. Patients with AS are typically elderly, with hypertension and a markedly remodelled aorta. The arterial component is sizeable, and yet, quantifying this to-date has been difficult to determine. We compared measurement of aortic pressure, flow and global LV load using a cardiac magnetic resonance (CMR)/applanation tonometry (AT) technique to uncouple ventriculo-arterial (VA) interactions. METHODS: 20 healthy elderly patients and 20 with AS underwent a CMR/AT protocol. CMR provided LV volume and aortic flow simultaneously with AT pressure acquisition. Aortic pressure was derived by transformation of the AT waveform. Systemic vascular resistance (SVR) and global LV load were determined as the relationship of pressure to flow in the frequency domain. Values from both cohorts were compared. RESULTS: AS patients were older (p â€‹< â€‹0.01) albeit with no significant difference in brachial or central aortic pressure. SVR (14228 vs 19906 â€‹dyne â€‹s.cm-3; p â€‹= â€‹0.02) and load (740 vs 946 â€‹dyne â€‹s.cm-3; p â€‹= â€‹0.02) were higher in patients with AS, whilst aortic peak flow velocity was lower (38 vs 58 â€‹cm/s; p â€‹< â€‹0.01). CONCLUSIONS: Quantification of aortic pressure, flow velocity and global LV load using a simultaneous CMR/AT technique is able to demonstrate the progressive effects of hypertension and aortic stiffening with advanced age and valvular stenosis. This technique may help to better identify future patients at risk of VA coupling mismatch after correction of AS.

Honey bee hives decrease wild bee abundance, species richness, and fruit count on farms regardless of wildflower strips.

Pollinator refuges such as wildflower strips are planted on farms with the goals of mitigating wild pollinator declines and promoting crop pollination services. It is unclear, however, whether or how these goals are impacted by managed honey bee (Apis mellifera L.) hives on farms. We examined how wildflower strips and honey bee hives and/or their interaction influence wild bee communities and the fruit count of two pollinator-dependent crops across 21 farms in the Mid-Atlantic U.S. Although wild bee species richness increased with bloom density within wildflower strips, populations did not differ significantly between farms with and without them whereas fruit counts in both crops increased on farms with wildflower strips during one of 2 years. By contrast, wild bee abundance decreased by 48%, species richness by 20%, and strawberry fruit count by 18% across all farm with honey bee hives regardless of wildflower strip presence, and winter squash fruit count was consistently lower on farms with wildflower strips with hives as well. This work demonstrates that honey bee hives could detrimentally affect fruit count and wild bee populations on farms, and that benefits conferred by wildflower strips might not offset these negative impacts. Keeping honey bee hives on farms with wildflower strips could reduce conservation and pollination services.

The pathogenic role of dendritic cells in non-infectious anterior uveitis.

BACKGROUND: Anterior uveitis (AU) is characterised by infiltration of immune cells into the anterior chamber of the eye. Dendritic cells (DC) are professional antigen presenting cells that initiate and promote inflammation. This study aims to characterise DC in AU and to examine the effects of aqueous humor (AqH) on DC maturation and function. METHODS: The frequency and phenotype of AU and healthy control (HC) circulating DC was examined. AU and HC AqH was immunostained and assessed by flow cytometry. The effect of AU and HC AqH on DC activation and maturation was examined and subsequent effects on CD4+ T cell proliferation assessed. RESULTS: AU peripheral blood demonstrated decreased circulating myeloid and plasmacytoid DC. Within AU AqH, three populations of CD45+ cells were significantly enriched compared to HC; DCs (CD11c+ HLA-DR+), neutrophils (CD15+ CD11c+) and T cells (CD4+ and CD8+). A significant increase in IFNγ, IL8 and IL6 was observed in the AU AqH, which was also significantly higher than that of paired serum. AU AqH induced expression of CD40 and CD80 on DC, which resulted in increased T cell proliferation and the production of GM-CSF, IFNγ and TNFα. CONCLUSION: DC are enriched at the site of inflammation in AU. Our data demonstrate an increase in inflammatory mediators in the AU inflamed microenvironment. AU AqH can activate DC, leading to subsequent proliferation and activation of effector T cells. Thus, the AU microenvironment contributes to immune cell responses and intraocular inflammation.

The at-risk medical student--what more can we do?

Securing a place in medical school is extremely difficult-students who are successful all have similar high levels of academic achievement. So why do some students, and not others, have difficulty with the course, and in some cases, leave the programme? Studies on medical school attrition offer valuable insight into why medical students under-perform. Identification of the 'at-risk' student can trigger additional support and early remediation, helping some students remain in their chosen profession.

Contribution of diet to aggregate arsenic exposures-an analysis across populations.

The relative contribution of dietary arsenic (As) to aggregate daily exposure has not been well-characterized, especially in relation to the current EPA maximum contaminant level (MCL) of 10 p.p.b. for As in drinking water. Our objectives were to: (1) model exposure to inorganic and total As among non-seafood eaters using subject-specific data, (2) compare the contribution of food, drinking and cooking water to estimated aggregate exposure in households with variable background tap water As levels, and (3) describe the upper distribution of potential dose at different thresholds of tap water As. Dietary As intake was modeled in regional study populations and NHANES 2003-2004 using dietary records in conjunction with published food As residue data. Water As was measured in the regional studies. Among subjects exposed to tap water As >10 p.p.b., aggregate inorganic exposure was 24.5-26.1 µg/day, with approximately 30% of intake from food. Among subjects living in homes with tap water As ≤10, 5 or 3 p.p.b., aggregate inorganic As exposure was 8.6-11.8 µg/day, with 54-85% of intake from food. Median inorganic As potential dose was 0.42-0.50 µg/kg BW/day in subjects exposed to tap water As >10 p.p.b. and less than half that among subjects exposed to tap water As ≤10 p.p.b. The majority of inorganic and total As exposure is attributable to diet in subjects with tap water As

The menopausal transition does not appear to accelerate age-related increases in arterial stiffness.

OBJECTIVE: Arterial stiffness is an independent marker of cardiovascular risk that increases with age, hypertension, diabetes and hyperlipidemia, both for men and women (although more pronounced in women). This study was designed to establish whether menopause augments the age-dependent change. METHODS: The study evaluated pulse wave analysis and pulse wave velocity using applanation tonometry in 468 women (aged 40-80 years) sampled from the general population. In multiple linear regression models, age was the predominant correlate of increasing aortic augmentation pressure (p < 0.0001), augmentation index (p < 0.0001), augmentation index adjusted to a heart rate of 75 beats/min (p < 0.0001) and carotid-femoral pulse wave velocity (p < 0.0001). RESULTS: Analysis of covariance showed no significant difference in adjusted mean of augmentation pressure, augmentation index or pulse wave velocity between menopause groups (pre-, peri-, postmenopause). Adjusted means of augmentation pressure and pulse wave velocity were comparable between women on hormone therapy (n = 130) and non-users (n = 338). CONCLUSIONS: The results of the present study challenge the assertion by some researchers that menopause accelerates age-dependent changes in arterial stiffness.

Anti-social behaviour in a large Irish teaching hospital.

BACKGROUND: Anti-social behaviour affects staff physically and psychologically and has financial implications. More information on its occurrence is required for effective risk management. AIMS: We undertook to audit the complete dataset on anti-social behaviour in an urban Irish hospital. METHODS: Data, collected from computerised incident reports between January 2005 and December 2008, were analysed with respect to date, location, incident type, person affected, type and severity of injury. RESULTS: There were 3,727 incidents over 4 years, with numbers rising annually at the approximate rate of 20%. Most involved nursing staff. Incidents occurred primarily on medical and surgical wards and were usually classified as minor. Physical or verbal assaults were most frequently reported. CONCLUSION: Anti-social behaviour appears to be increasing. Certain wards and categories of healthcare professionals are at particular risk. More research is required to explain factors leading to such behaviour and optimum strategies for its active management.

Arterial stiffness as a cause of cognitive decline and dementia: a systematic review and meta-analysis.

BACKGROUND: Although arterial stiffness has recently been confirmed as a predictor of cardiovascular disease, the association between arterial stiffness and cognitive decline is less clear. AIM: We performed a systematic review and meta-analysis to examine the evidence for large artery stiffness as a cause of cognitive decline and dementia. METHOD: Electronic databases were systematically searched until September 2011 for studies reporting on the longitudinal relationship between any validated measure of large artery stiffness and cognitive decline or dementia. Meta-analysis was performed on four studies investigating the association between aortic pulse wave velocity and a decline in Mini-Mental State Examination scores. RESULTS: Six relevant longitudinal studies were located, conducted over an average of 5 years follow up. Arterial stiffness was predictive of cognitive decline in five/six studies. In meta-analysis, higher aortic stiffness predicted lower Mini-Mental State Examination scores within the sample (ß=-0.03, 95% confidence interval (CI): -0.06 to 0.01, n= 3947), although studies were not all homogeneous, and statistical heterogeneity was present (I(2) = 71.9%, P= 0.01). Removal of one study with a relatively younger cohort and lower median aortic stiffness found higher aortic stiffness to significantly predict cognitive decline (ß=-0.04, 95% CI: -0.07 to -0.01, n= 3687) without evidence of heterogeneity (I(2) = 9.5%, P= 0.33). There was little research investigating the effects of aortic stiffness on the development of dementia. CONCLUSION: Aortic stiffness was found to predict cognitive decline in both qualitative review and quantitative analysis.

A two-system, single-analysis, fluid-structure interaction technique for modelling abdominal aortic aneurysms.

This work reports on the implementation and validation of a two-system, single-analysis, fluid-structure interaction (FSI) technique that uses the finite volume (FV) method for performing simulations on abdominal aortic aneurysm (AAA) geometries. This FSI technique, which was implemented in OpenFOAM, included fluid and solid mesh motion and incorporated a non-linear material model to represent AAA tissue. Fully implicit coupling was implemented, ensuring that both the fluid and solid domains reached convergence within each time step. The fluid and solid parts of the FSI code were validated independently through comparison with experimental data, before performing a complete FSI simulation on an idealized AAA geometry. Results from the FSI simulation showed that a vortex formed at the proximal end of the aneurysm during systolic acceleration, and moved towards the distal end of the aneurysm during diastole. Wall shear stress (WSS) values were found to peak at both the proximal and distal ends of the aneurysm and remain low along the centre of the aneurysm. The maximum von Mises stress in the aneurysm wall was found to be 408kPa, and this occurred at the proximal end of the aneurysm, while the maximum displacement of 2.31 mm occurred in the centre of the aneurysm. These results were found to be consistent with results from other FSI studies in the literature.

An investigation of the flow field within patient-specific models of an abdominal aortic aneurysm under steady inflow conditions.

The flow fields within three patient-specific models of an abdominal aortic aneurysm (AAA) were investigated under steady laminar inflow conditions over a range of Reynolds numbers. Each model extended from the renal arteries to downstream of the iliac bifurcation. The aneurysms (referred to as models A, B, and C) are mature, with D/d ratios of 1.83, 1.57, and 1.95 respectively. The mass flowrates in each of the iliac arteries were equal. Using flow visualization it was observed that the flow proximally in the aneurysm was characterized by a primary jet that separated from either the posterior wall or the lateral wall or both, producing large recirculating zones. The primary jet impinged either normally or obliquely upon the anterior or right lateral wall in the distal half of the aneurysm, the flow distally in the aneurysm having been greatly disturbed. Measurements of the turbulence intensity along the median lumen centre-line showed that in each model the onset of transition and full turbulence occurred at Reynolds numbers much lower than those previously measured in idealized models. Computational fluid dynamics showed substantial differences in the velocity and stress fields when using the shear stress transport turbulence model as opposed to a laminar viscous model. It was also observed that turbulence was largely produced along the shear layers surrounding the primary jet and, in particular, at interfaces between the jet and the recirculating zones. In conclusion, turbulence may be expected to exist at Reynolds numbers typically encountered within an AAA, and it must be taken account of in an analysis of the flow field.

Treatment of hypertension in patients 80 years of age or older.

Isolated systolic hypertension (ISH) is present in the majority of persons who reach the age of 80 years, and is caused directly or indirectly by stiffening of the aorta and large central elastic arteries. Until recently, there was no consensus on whether or not persons over 80 should be treated, according to principles established for the younger group examined in the Systolic Hypertension in the Elderly Project (SHEP). The recent Hypertension in the Very Elderly Trial (HYVET) study endorses application of SHEP to most such subjects. This review describes the background to SHEP and HYVET, including concepts of hypertension and interpretation of blood pressure values. It describes the effects of age on arterial stiffness, and effects of stiffness on the heart, large arteries and microvessels in brain and kidneys as the basis of symptomatic disease. It describes logic of therapy with newer antihypertensives which indirectly affect arterial stiffness and form the basis of therapy in older persons. It proposes how, with what and in whom antihypertensive therapy could be offered in persons over age 80.

Welcome to Serbia: feel free to smoke.

This paper reviews tobacco use and control policies in Serbia. Tobacco contributes significantly to the burden of disease in Serbia, and it has one of the highest age standardised lung cancer incidence rates in Europe. Until recently there were few restrictions on smoking or tangible tobacco control policies. Serbia has, however, now embarked on a legislative and regulatory path towards greater tobacco control, but implementation and enforcement are still lax. Increased government interventions are needed to reduce the prevalence of smoking in the population.

A comparison of the measured and predicted flowfield in a patient-specific model of an abdominal aortic aneurysm.

Numerical simulation is increasingly being used to predict the flowfield within patient-specific geometries of abdominal aortic aneurysms under physiologically realistic flow conditions. This paper reports on a comparison between the flowfield measured in vitro within a patient-specific model of a mature abdominal aortic aneurysm and that predicted using computational fluid dynamics (CFD). Visualization and traverses of axial velocity were obtained at a number of locations in the aneurysm region under both steady and physiologically realistic pulsatile flow conditions. Comparisons between the measured and predicted flowfield show good agreement throughout the aneurysm. Although turbulence was observed distal in the aneurysm during late diastole, best agreement was achieved using a simple laminar flow model.

Prolonged mechanical systole and increased arterial wave reflections in diastolic dysfunction.

OBJECTIVE: To evaluate whether left ventricular ejection time indexed for heart rate (left ventricular ejection time index (LVETI)) and arterial wave reflections (augmented pressure (AP)) are increased in patients with diastolic dysfunction (DD). DESIGN: Prospective observational study. SETTING: University teaching hospital providing primary and tertiary care. SUBJECTS: 235 consecutive patients undergoing left heart catheterisation were categorised as having definite DD, possible DD or no DD (controls) on the basis of their left ventricular end diastolic pressures and N-terminal brain natriuretic peptide concentrations. MAIN OUTCOME MEASURES: LVETI and AP were prospectively assessed non-invasively by radial applanation tonometry. In addition, all patients underwent comprehensive echocardiography, including tissue Doppler imaging of mitral annulus velocity in early diastole (E'). RESULTS: LVETI was longer in patients with definite DD than in patients with possible DD and in controls (433.6 (SD 17.2), 425.9 (17.9) and 414.3 (13.6) ms, respectively, p < 0.000001). Arterial wave reflections were higher in definite DD than in possible DD and control groups (AP was 19.4 (SD 8.9), 15.2 (8.0) and 10.7 (6.8) mm Hg, respectively, p < 0.000001). In receiver operating characteristic curve analysis, LVETI detected DD as well as echocardiography (E:E'). Area under the curve for LVETI to differentiate patients with definite DD from normal controls was 0.81 (95% CI 0.72 to 0.89, p < 0.0001). In multivariable logistic regression analysis, LVETI added significant independent power to clinical and echocardiographic variables for prediction of DD. CONCLUSIONS: Mechanical systole is prolonged and arterial wave reflections are increased in most patients with DD. Rapid non-invasive assessment of these parameters may aid in confirming or excluding DD.

Reality of out of hospital cardiac arrest.

The high mortality rates associated with out of hospital cardiac arrest, particularly those occurring in the home, stress the need for early treatment in the form of publicly accessible external defibrillators.