Arterial endothelial function is acutely and chronically regulated by blood flow-associated shear stress. An acute intervention employing modest forearm cuff occlusion to simultaneously increase retrograde and decrease mean brachial artery shear rate for 30 min evokes transient impairments in flow-mediated dilation (FMD). However, the independent influence of the low mean versus the retrograde shear stress components is unclear. Healthy young adults [ n = 24 (12 women, 12 men); 22 ± 2 yr, body mass index = 25 ± 2 kg/m2 (mean ± SD)] completed three laboratory visits within 1 wk. Visits consisted of 45 min of supine rest followed by a brachial artery FMD test (duplex ultrasound) before and after a 30-min intervention: control (shear rate unchanged), cuff (mean shear rate decreased, retrograde shear rate increased), or arterial compression (mean shear rate decreased, no increase in retrograde shear rate). The mean shear rate on the compression visit was targeted to match that achieved on the cuff visit. Cuff and compression trials decreased mean shear rate to a similar extent (cuff: 43 ± 22 s−1, compression: 43 ± 21 s−1; P = 0.850) compared with control (65 ± 21 s−1; both P < 0.001), with the retrograde component elevated only in the former (cuff: −83 ± 30 s−1, compression: −7 ± 5 s−1; P < 0.001). FMD decreased by 29 ± 30% ( P < 0.001) after the cuff intervention and 32 ± 24% ( P < 0.001) after the compression trial but was unchanged on the control visit (−0.3 ± 18%; P = 0.754). This was not altered by accounting for the shear rate stimulus. An increased retrograde shear stress does not appear to be obligatory for the transient reduction in FMD achieved after a 30-min exposure to low mean shear stress. These findings provide novel mechanistic insight on the regulation of endothelial function in vivo. NEW & NOTEWORTHY Low mean and retrograde shear stress are considered atherogenic; however, their relative contribution to the acute regulation of endothelial function in humans is unclear. Matched reductions in mean shear stress (30 min), with and without increases in retrograde shear stress, elicited equivalent reductions in flow-mediated dilation in men and women. These findings afford novel insight regarding the shear stress components governing the acute (dys)regulation of conduit artery endothelial function in vivo.
Moxifloxacin diffuses through BCLs and CSs at similar rates; however, CSs have greater capacity to absorb and release moxifloxacin compared with BCLs. Vigamox-soaked CSs released 250 μg of moxifloxacin and may be a useful method to prevent endophthalmitis.
Background and Aims Glomerular diseases pose a substantial burden on the healthcare system. While the medical and economic burden of glomerular diseases is well established, the data on the health-related quality of life impact is scant. Method We used the PROMIS 29 v2.1 (Patient-Reported Outcomes Measurement Information System) tool to assess HRQOL impact of primary glomerular diseases in adult Indian patients [1], under the domains: physical function, anxiety, fatigue, depression, sleep disturbance, ability to participate in social roles and activities and pain interference in daily activities. The questionnaire was administered in English and Hindi. Patient responses were then used to calculate T-scores with a mean of 50 and an SD of 10 with the score having positive correlation with the quantum of the outcome measured. Results 141 adult patients were recruited (39 minimal change disease/ focal segmental glomerulosclerosis, 36 membranous nephropathy, 56 IgA nephropathy, 9 membrano-proliferative glomerulonephritis). Mean T-scores across domains were as follows: physical function- 48.2 (46.8-49.6), fatigue- 49.2 (47.5-51), anxiety- 52.3 (50.6-53.9), sleep impairment- 43.5 (41.9-45.1), depression- 50.7 (49-52.4), ability to participate in social roles and activities- 55 (53.3-56.7), hindrance in daily activities due to pain 51.2 (49.7-52.8). Better physical function was associated with higher eGFR (T-score of 44 at eGFR<45 ml/min/1.73m2 and 49.8 at eGFR>45 ml/min/1.73m2, p<0.001), lower BMI (42.4 in obese vs 48.6 in non-obese, p = 0.02), and male sex (50.2 vs 44.5 in females, p<0.001). Fatigue was associated with eGFR<45 ml/min/1.73m2 (52.2 vs 48.1 at eGFR>45 ml/min/1.73m2, p = 0.04), and female sex (53.2 vs 47.1 in males, p<0.001). Worse anxiety was seen in females (55.8 vs 50.4 in males, p = 0.002) and patients with eGFR<45 ml/min/1.73m2 (55.4 vs 51.1 at eGFR>45 ml/min/1.73m2, p = 0.02). Sleep impairment was seen in patients having a history of steroid usage in the last 2 months (45.8 vs 42.1, p = 0.02), females (45.8 vs 42.3, p = 0.04), and patients with eGFR<45 ml/min/1.73m2 (46.2 vs 42.5 at eGFR>45 ml/min/1.73m2, p = 0.04). Pain interference was higher in females (55.9 vs 48.8 in males, p<0.001) and patients with eGFR<45 ml/min/1.73m2 (54 vs 50.2 at eGFR>45 ml/min/1.73m2, p = 0.03). eGFR>45 ml/min/1.73m2 (56.4 vs 51.4 at eGFR<45 ml/min/1.73m2, p = 0.008) was associated with better involvement in social roles. Depression was associated with female sex (54.2 vs 48.9 in males, p = 0.003). Degree of proteinuria, serum albumin, duration of disease, immunosuppressive drug use, age, patient-reported edema, and socio-economic status were not associated with a significant decrease in HRQOL. Multivariable linear regression models were evaluated for all domains. Physical function was negatively associated with eGFR<45ml/min/1.73m2 (β = -5.46), female sex (β = -5.16), and obesity (β = -6.36). Fatigue was associated with eGFR<45ml/min/1.73m2 (β = 3.89), female sex (β = 5.76), and obesity (β = 9.62). Worse anxiety was associated with eGFR<45ml/min/1.73m2 (β = 3.82) and female sex (β = 4.97). Sleep impairment was associated with eGFR<45ml/min/1.73m2 (β = 3.46) and female sex (β = 3.24). Pain interference was associated with eGFR<45ml/min/1.73m2 (β = 3.39) and female sex (β = 7.19) Ability to participate in social roles and activities was negatively associated with eGFR<45ml/min/1.73m2 (β = -4.86) and female sex (β = −3). Depression was associated with obesity (β = 6.16) and female sex (β = 5.22). Conclusion Glomerular diseases adversely impact the quality of life. Female sex, lower renal function (eGFR), higher BMI and history of recent steroid use correlated with higher morbidity.
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