Effect of isoflurane anaesthetic time on ocular a-scan ultrasonography measures and their relationship to age and OCT measures in the Guinea pig.

A-scan ultrasonography enables precise measurement of internal ocular structures. Historically, its use has underpinned fundamental studies of eye development and aberrant eye growth in animal models of myopia; however, the procedure typically requires anaesthesia. Since anaesthesia affects intra-ocular pressure (IOP), we investigated changes in internal ocular structures with isoflurane exposure and compared measurements with those taken in awake animals using optical coherence tomography (OCT). Continuous A-scan ultrasonography was undertaken in tri-coloured guinea pigs aged 21 (n = 5), 90 (n = 5) or 160 (n = 5) days while anaesthetised (up to 36 min) with isoflurane (5% in 1.5L/min O2). Peaks were selected from ultrasound traces corresponding to the boundaries of the cornea, crystalline lens, retina, choroid and sclera. OCT scans (Zeiss Cirrus Photo 800) of the posterior eye layers were taken in 28-day-old animals (n = 19) and compared with ultrasound traces, with choroid and scleral thickness adjusted for the duration of anaesthesia based on the changes modelled in 21-day-old animals. Ultrasound traces recorded sequentially in left and right eyes in 14-day-old animals (n = 30) were compared, with each adjusted for anaesthesia duration. The thickness of the cornea was measured in enucleated eyes (n = 5) using OCT following the application of ultrasound gel (up to 20 min). Retinal thickness was the only ultrasound internal measure unaffected by anaesthesia. All other internal distances rapidly changed and were well fitted by exponential functions (either rise-to-max or decay). After 10 and 20 min of anaesthesia, the thickness of the cornea, crystalline lens and sclera increased by 17.1% and 23.3%, 0.4% and 0.6%, and 5.2% and 6.5% respectively, whilst the anterior chamber, vitreous chamber and choroid decreased by 4.4% and 6.1%, 0.7% and 1.1%, and 10.7% and 11.8% respectively. In enucleated eyes, prolonged contact of the cornea with ultrasound gel resulted in an increase in thickness of 9.3% after 10 min, accounting for approximately half of the expansion observed in live animals. At the back of the eye, ultrasound measurements of the thickness of the retina, choroid and sclera were highly correlated with those from posterior segment OCT images (R2 = 0.92, p = 1.2 × 10-13, R2 = 0.55, p = 4.0 × 10-4, R2 = 0.72, p = 5.0 × 10-6 respectively). Furthermore, ultrasound measures for all ocular components were highly correlated in left and right eyes measured sequentially, when each was adjusted for anaesthetic depth. This study shows that the depth of ocular components can change dramatically with anaesthesia. Researchers should therefore be wary of these concomitant effects and should employ adjustments to better render 'true' values.

Analytical methods for assessing retinal cell coupling using cut-loading.

Electrical coupling between retinal neurons contributes to the functional complexity of visual circuits. "Cut-loading" methods allow simultaneous assessment of cell-coupling between multiple retinal cell-types, but existing analysis methods impede direct comparison with gold standard direct dye injection techniques. In the current study, we both improved an existing method and developed two new approaches to address observed limitations. Each method of analysis was applied to cut-loaded dark-adapted Guinea pig retinae (n = 29) to assess coupling strength in the axonless horizontal cell type ('a-type', aHCs). Method 1 was an improved version of the standard protocol and described the distance of dye-diffusion (space constant). Method 2 adjusted for the geometric path of dye-transfer through cut-loaded cells and extracted the rate of dye-transfer across gap-junctions in terms of the coupling coefficient (kj). Method 3 measured the diffusion coefficient (De) perpendicular to the cut-axis. Dye transfer was measured after one of five diffusion times (1-20 mins), or with a coupling inhibitor, meclofenamic acid (MFA) (50-500µM after 20 mins diffusion). The standard protocol fits an exponential decay function to the fluorescence profile of a specified retina layer but includes non-specific background fluorescence. This was improved by measuring the fluorescence of individual cell soma and excluding from the fit non-horizontal cells located at the cut-edge (p<0.001) (Method 1). The space constant (Method 1) increased with diffusion time (p<0.01), whereas Methods 2 (p = 0.54) and 3 (p = 0.63) produced consistent results across all diffusion times. Adjusting distance by the mean cell-cell spacing within each tissue reduced the incidence of outliers across all three methods. Method 1 was less sensitive to detecting changes induced by MFA than Methods 2 (p<0.01) and 3 (p<0.01). Although the standard protocol was easily improved (Method 1), Methods 2 and 3 proved more sensitive and generalisable; allowing for detailed assessment of the tracer kinetics between different populations of gap-junction linked cell networks and direct comparison to dye-injection techniques.

The Effect of Long-Term Low-Dose Atropine on Refractive Progression in Myopic Australian School Children.

Myopia will affect half the global population by 2050 and is a leading cause of vision impairment. High-dose atropine slows myopia progression but with undesirable side-effects. Low-dose atropine is an alternative. We report the effects of 0.01% or 0.005% atropine eye drops on myopia progression in 13 Australian children aged between 2 and 18 years and observed for 2 years without and up to 5 years (mean 2.8 years) with treatment. Prior to treatment, myopia progression was either 'slow' (more positive than -0.5 D/year; mean -0.19 D/year) or 'fast' (more negative than -0.5 D/year; mean -1.01 D/year). Atropine reduced myopic progression rates (slow: -0.07 D/year, fast: -0.25 D/year, combined: before: -0.74, during: -0.18 D/year, p = 0.03). Rebound occurred in 3/4 eyes that ceased atropine. Atropine halved axial growth in the 'Slow' group relative to an age-matched model of untreated myopes (0.098 vs. 0.196 mm/year, p < 0.001) but was double that in emmetropes (0.051 mm/year, p < 0.01). Atropine did not slow axial growth in 'fast' progressors compared to the age-matched untreated myope model (0.265 vs. 0.245 mm/year, p = 0.754, Power = 0.8). Adverse effects (69% of patients) included dilated pupils (6/13) more common in children with blue eyes (5/7, p = 0.04). Low-dose atropine could not remove initial myopia offsets suggesting treatment should commence in at-risk children as young as possible.

'Tax-otsubo': stress cardiomyopathy following an encounter with the Inland Revenue.

An 89-year-old man developed chest pain and palpitations shortly after finishing a stressful 40 min phone call to HM Revenue and Customs. After admission to the emergency department, he had a cardiovascular collapse followed soon after by a cardiac arrest due to ventricular fibrillation (VF). The troponin T was elevated and his ECG showed extensive deep T wave inversion with prolongation of the QT interval. A portable hand-held ultrasound device (VScan; GE Healthcare) was used to demonstrate classical apical ballooning of the left ventricular apex indicating a diagnosis of takotsubo stress cardiomyopathy. Shortly following admission to the cardiac care unit, he had a further episode of VF, which was successfully defibrillated. A coronary angiogram was performed, which was normal. He was treated with a short course of benzodiazepines. He was discharged after 8 days without any neurological deficit. His echocardiogram subsequently showed complete resolution of the abnormalities of the left ventricular function.

Correction: Medical-Grade Physical Activity Monitoring for Measuring Step Count and Moderate-to-Vigorous Physical Activity: Validity and Reliability Study.

[This corrects the article DOI: 10.2196/10706.].

Medical-Grade Physical Activity Monitoring for Measuring Step Count and Moderate-to-Vigorous Physical Activity: Validity and Reliability Study.

BACKGROUND: The use of physical activity (PA) monitors is commonly associated with an increase in habitual PA level in healthy and clinical populations. The PiezoRx is a medical-grade PA monitor that uses adjustable step rate thresholds to estimate moderate-to-vigorous physical activity (MVPA) and is a valid indicator of free-living PA in adults. Laboratory validation of step count derived MVPA in adults is needed to justify the use of these monitors in clinical practice to track individuals' progress toward meeting PA guidelines that are based on MVPA, not steps. OBJECTIVE: The objective of our study was to assess the validity and interinstrument reliability of the PiezoRx to derive step count and MVPA in a laboratory setting compared with criterion measures and other frequently used PA monitors in a diverse sample of adults. METHODS: The adult participants (n=43; 39.4 years, SD 15.2) wore an Omron HJ-320 pedometer, an ActiGraph GT3X accelerometer, and four PiezoRx monitors during a progressive treadmill protocol conducted for 6 minutes at speeds of 2.4, 3.2, 4.0, 5.6, 6.4, and 7.2 km/hour, respectively. The four PiezoRx monitors were set at different MVPA step rate thresholds (MPA in steps/minute/VPA in steps/minute) 100/120, 110/130, height adjusted, and height+fitness adjusted. RESULTS: The PiezoRx was more correlated (intraclass correlation, ICC=.97; P<.001) to manual step counting than the ActiGraph (ICC=.72; P<.001) and Omron (ICC=.62; P<.001). The PiezoRxs absolute percent error in measuring steps was 2.2% (ActiGraph=15.9%; Omron=15.0%). Compared with indirect calorimetry, the height-adjusted PiezoRx and ActiGraph were accurate measures of the time spent in MVPA (both ICC=.76; P<.001). CONCLUSIONS: The PiezoRx PA monitor appears to be a valid and reliable measure of step count and MVPA in this diverse sample of adults. The device's ability to measure MVPA may be improved when anthropometric differences are considered, performing at par or better than a research grade accelerometer.

Influence of Anthropometrics on Step-Rate Thresholds for Moderate and Vigorous Physical Activity in Older Adults: Scientific Modeling Study.

BACKGROUND: Adults and older adults are recommended to engage in 150 minutes of moderate (MPA) to vigorous (VPA) aerobic physical activity (MVPA) per week, with the heuristic message of 3000 steps in 30 minutes (100 steps per minute [spm]). However, this message is based on adult populations, with a paucity of research on step-rate thresholds that correspond to absolute MVPA (moderate=3 metabolic equivalents [METs], vigorous=6 METs) and relative MVPA (moderate=40% estimated METmax, vigorous=60% estimated METmax) in older persons, who have lower stride lengths and a lower exercise capacity. Also, there is a need to consider the influence of anthropometric differences when quantifying the relationship between step rate and intensity-related physical activity. OBJECTIVE: This study assessed absolute and relative MVPA step-rate thresholds and anthropometric factors (ie, height, leg length, and body mass index [BMI]) in older adults. METHODS: Nineteen older adults (7 females; age 69 years, SD 2, BMI 26 kg/m2, SD 4) completed a staged treadmill walking protocol: six minutes at 2.4, 3.2, 4.0, 5.6, and 6.4 km/h. Steps were manually counted and volume rate of oxygen consumed (VO2) was measured via indirect calorimetry. Aerobic fitness was estimated via the submaximal single-stage treadmill protocol. RESULTS: When BMI was considered, mixed effects modeling revealed absolute and relative MPA step-rate thresholds of 108 spm and 117 spm, respectively. Absolute and relative VPA corresponded to step rates of 135 spm and 132 spm, respectively. Neither height nor leg length improved the ability of the model to predict stepping cadence from METs. CONCLUSIONS: In general, older adults need to walk faster than 100 spm (ie, approximately 110 spm) to reach MPA and in excess of approximately 130 spm to achieve VPA, depending on BMI status. Health care professionals and researchers should adjust cadence-based recommendations for differences in BMI in their older patients and consider using relative intensity to most appropriately tailor their physical activity recommendations.