Dose-response effect of elevated plasma free fatty acid on insulin signaling

The dose-response relationship between elevated plasma free fatty acid (FFA) levels and impaired insulin-mediated glucose disposal and insulin signaling was examined in 21 lean, healthy, normal glucose-tolerant subjects. Following a 4-h saline or Liposyn infusion at 30 (n = 9), 60 (n = 6), and 90 (n = 6) ml/h, subjects received a 2-h euglycemic insulin (40 mU . m(-2) . min(-1)) clamp. Basal plasma FFA concentration ( approximately 440 micromol/l) was increased to 695, 1,251, and 1,688 micromol/l after 4 h of Liposyn infusion and resulted in a dose-dependent reduction in insulin-stimulated glucose disposal (R(d)) by 22, 30, and 34%, respectively (all P < 0.05 vs. saline control). At the lowest lipid infusion rate (30 ml/h), insulin receptor and insulin receptor substrate (IRS)-1 tyrosine phosphorylation, phosphatidylinositol (PI) 3-kinase activity associated with IRS-1, and Akt serine phosphorylation were all significantly impaired (P < 0.05-0.01). The highest lipid infusion rate (90 ml/h) caused a further significant reduction in all insulin signaling events compared with the low-dose lipid infusion (P < 0.05-0.01) whereas the 60-ml/h lipid infusion caused an intermediate reduction in insulin signaling. However, about two-thirds of the maximal inhibition of insulin-stimulated glucose disposal already occurred at the rather modest increase in plasma FFA induced by the low-dose (30-ml/h) lipid infusion. Insulin-stimulated glucose disposal was inversely correlated with both the plasma FFA concentration after 4 h of lipid infusion (r = -0.50, P = 0.001) and the plasma FFA level during the last 30 min of the insulin clamp (r = -0.54, P < 0.001). PI 3-kinase activity associated with IRS-1 correlated with insulin-stimulated glucose disposal (r = 0.45, P < 0.01) and inversely with both the plasma FFA concentration after 4 h of lipid infusion (r = -0.39, P = 0.01) and during the last 30 min of the insulin clamp (r = -0.43, P < 0.01). In summary, in skeletal muscle of lean, healthy subjects, a progressive increase in plasma FFA causes a dose-dependent inhibition of insulin-stimulated glucose disposal and insulin signaling. The inhibitory effect of plasma FFA was already significant following a rather modest increase in plasma FFA and develops at concentrations that are well within the physiological range (i.e., at plasma FFA levels observed in obesity and type 2 diabetes).     

Impact of initial surgical margins and residual cancer upon re-excision on outcome of patients with localized breast cancer

Background

A significant proportion of patients undergoing breast conservation therapy require additional operations to obtain clear margins. The aim of this study was to assess the impact of initial margins and residual carcinoma found on second surgery on the outcomes of breast cancer patients.

Methods

In this retrospective study, Cox proportional-hazard regression analysis was performed to evaluate data from 437 patients with stage I to IIIA breast cancer who underwent initial breast-conserving surgery between 1994 and 2004.

Results

The distant recurrence rate was higher among patients with initial positive margins than among those with initial negative margins (15.5% vs 4.9%; hazard ratio, 3.6; 95% confidence interval 1.5-8.7; P = .003). For patients who had underwent second surgery, the finding of a residual invasive carcinoma was associated with increased risk for distant recurrence (22.8% vs 6.6%; hazard ratio, 3.5; 95% confidence interval, 1.8-7.4; P = .0001).

Conclusion

Invasive residual carcinoma found during subsequent surgery after initial compromised margins is an important prognostic marker for distant recurrence.     

Assessing seasonal trends and variability of vegetation growth from NDVI3g,MODIS NDVI and EVI over South Asia

The characterization of vegetation dynamics over South Asia (SA) has been primarily conducted using satellite time series of Advanced Very High Resolution Radiometer (AVHRR) Normalized Difference Vegetation Index (NDVI). However, various vegetation indices may show diverse trend patterns over the same area. This study analysed the consistency of the vegetation spatiotemporal trends from AVHRR version 3 NDVI (NDVI3g) with the Moderate Resolution Imaging Spectroradiometer (MODIS) NDVI and Enhanced Vegetation Index (EVI) over SA during various seasons, assuming that MODIS products are of higher quality. Results showed that the spatiotemporal vegetation trends derived from the NDVI3g were analogous to both MODIS NDVI and EVI indicating greening over semi-arid regions where croplands dominate and browning over tropical/subtropical forest areas. Correlations among them were better during winter monsoon. Discrepancies occurred in tropical/subtropical densely vegetated (humid) and complex topographic areas specifically during summer monsoon (SM). This study improved the understanding of the heterogeneous vegetation trends over the vast complicated terrain of SA. It was revealed that NDVI3g is reliable to quantify vegetation trends over SA, however, calibration errors still could introduce biases during SM season.     

Ultrasonographic estimation of fetal gestational age by fetal kidney length

Introduction: Fetal kidney length vs biparietal diameter (BPD) and femur length (FL) were comparatively evaluated and the role of fetal kidney length in estimating gestational age was determined in the second and third trimesters. Materials and methods: The study was carried out on 199 women with singleton uncomplicated pregnancies attending the outdoor patient department (OPD) for routine ultrasound fetal biometry. Fetal kidney length was measured biweekly, between 18 weeks and 38 weeks of gestation. Linear regression models for estimation of gestational age were derived from biometric indices (BPD and FL) and kidney length. Result: The earliest age at which fetal kidney could be seen sonographically was the 18th week of gestation with the mean kidney length of 12 ± 1.31 mm. The mean sonographic kidney length at the 38th week of gestation was 40.4 ± 1.71 mm, indicating that the mean fetal kidney length increases as pregnancy progresses from 18 weeks to 38 weeks of gestation. Conclusion: The best linear regression model for estimating fetal gestational age is femur length, kidney length, and biparietal diameter in that order, with standard error of ±3.85 days, ±8.04 days, and ±8.75 days, respectively.     

Acute Flaccid Quadriparesis in a Recovering COVID-19 Patient: A Clinical Dilemma

How to cite this article: Sabharwal P, Chakraborty S, Tyagi N, Kumar A. Acute Flaccid Quadriparesis in a Recovering COVID-19 Patient: A Clinical Dilemma. Indian J Crit Care Med 2021;25(2):238–239.