Purpose
Insulin resistance and compensatory hyperinsulinism are the predominant metabolic defects in polycystic ovary syndrome (PCOS). However, hyperinsulinism, as well as being compensatory, can ...also express a condition of reduced insulin clearance. Our aim was to evaluate the differences in insulin action and metabolism between women with PCOS (with normal glucose tolerance) and age- and BMI-matched women with prediabetes (without hyperandrogenism and ovulatory disorders).
Methods
22 women with PCOS and 21 age/BMI-matched women with prediabetes were subjected to a Hyperinsulinemic-euglycemic clamp and an Oral Glucose tolerance Test (OGTT). Insulin sensitivity was assessed by the glucose infusion rate during clamp (
M
value); insulin secretion by Insulinogenic index, Oral Disposition Index (DIo) and AUC
2h-insulin
during OGTT; and insulin clearance by the metabolic clearance rate of insulin (MCRI) during clamp.
Results
Women with PCOS showed significantly higher levels of AUC
2h-insulin
(
p
< 0.011), Insulinogenic Index (
p
< 0.001), DIo (
p
= 0.002) and significantly lower levels of AUC
2h-glucose
(
p
= 0.001). No difference was found between the two groups regarding insulin sensitivity (
M
value). Lower levels of MCRI were found in women with PCOS 420 (IQR 227–588) vs. 743 (IQR 597–888) ml m
−2
min
−1
:
p
< 0.001. Furthermore, in the PCOS group, a strong independent inverse correlation was only observed between MCRI and AUC
2h-insulin
(PCOS: β:−0.878;
p
< 0.001; Prediabetes: β:−0.501;
p
= 0.019).
Conclusions
Our study suggests that in normoglycemic women with PCOS there is peripheral insulin sensitivity similar to that of women with prediabetes. What sets PCOS apart is the hyperinsulinism, today still simplistically defined “compensatory”; actually this is mainly related to decreased insulin clearance whose specific causes and dynamics have yet to be clarified.
We report plasma-enhanced atomic layer deposition (ALD) to prepare conformal nickel thin films and nanotubes using nickelocene as a precursor, water as the oxidant agent, and an in-cycle ...plasma-enhanced reduction step with hydrogen. The optimized ALD pulse sequence, combined with a post-processing annealing treatment, allowed us to prepare 30 nm-thick metallic Ni layers with a resistivity of 8 μΩ cm at room temperature and good conformality both on the planar substrates and nanotemplates. Thus, we fabricated several micrometers-long nickel nanotubes with diameters ranging from 120 to 330 nm. We report the correlation between ALD growth and functional properties of individual Ni nanotubes characterized in terms of magnetotransport and the confinement of spin-wave modes. The findings offer novel perspectives for Ni-based spintronics and magnonic devices operated in the GHz frequency regime with 3D device architectures.
Context:
The visceral adiposity index (VAI) has proved to be a marker of visceral adipose dysfunction, strongly associated with insulin sensitivity in both the general and specific populations of ...patients at metabolic risk.
Objective:
The objective of the study was to test VAI as a useful tool to assess early metabolic risk in acromegaly.
Patients:
Twenty-four newly diagnosed acromegalic patients (11 women and 13 men, aged 54.9 ± 13.6 yr) were grouped into those with normal (group A, n = 13, 54.2%) and those with high VAI (group B, n = 11, 45.8%).
Outcome Measures:
Glucose, hemoglobin A1c, nadir and area under the curve (AUC) of GH (AUCGH) during the oral glucose tolerance test, AUCCpeptide during a mixed-meal tolerance test, M value during euglycemic-hyperinsulinemic clamp, oral dispositional index (DIo), each component of the metabolic syndrome, leptin, adiponectin, TNF-α, and IL-6.
Results:
The VAI value was positively correlated with the age of patients (ρ = 0.408; P = 0.048), tumor volume (ρ = 0.638; P = 0.001), basal GH (ρ = 0.622; P = 0.001), nadir GH (ρ = 0.534; P = 0.007), AUCGH (ρ = 0.603; P = 0.002), IGF-I (ρ = 0.618; P = 0.001), TNF-α (ρ = 0.512; P = 0.010), and AUCCpeptide (ρ = 0.715; p<0.001) and negatively with adiponectin (ρ = −0.766; P < 0.001), M value (ρ = −0.818; P < 0.001), and DIo (ρ = −0.512; P = 0.011). Patients with high VAI showed significantly higher basal GH levels (P = 0.018), AUCGH (P = 0.047), IGF-I (P = 0.047), AUCCpeptide (P = 0.018), lower M value (P < 0.001), DIo (P = 0.006), and adiponectin levels (P < 0.001), despite the absence of a significantly higher prevalence in the overt metabolic syndrome and glucose tolerance abnormalities. AUCGH proved to be the main independent factor influencing VAI.
Conclusions:
In acromegaly, VAI appears to be associated with disease activity, adiponectin levels, and insulin sensitivity and secretion and is influenced independently by GH levels. VAI could therefore be used as an easy and useful new tool in daily clinical practice for the assessment of early metabolic risk associated with active acromegaly.
Obesity is associated with a major prevalence of cardiovascular risk factors and high risk of cardiovascular events and contributes to the increase in cardiovascular morbidity and mortality ...worldwide. Beyond the fat mass
per se
, the pattern of fat distribution has a profound influence on cardiometabolic risk. The increase in abdominal adipose tissue confers an independent risk, while the amount of gluteofemoral body fat is thought to be protective. Changes in the capacity of different depots to store and release fatty acids and to produce adipocytokines are important determinants of fat distribution and its metabolic consequences. Because of the complexity of the assessment of body fat with imaging techniques, great attention has been paid to other measures of adiposity, such as waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR), which provide information on body fat distribution, although body mass index (BMI) is the established clinical measure to estimate the cardiovascular risk disease associated with excessive body weight. Abdominal obesity is a main predictive factor of the metabolic syndrome, so it is certain that it represents a better marker of cardiovascular risk than BMI. Visceral adiposity index (VAI) has recently proven to be a marker of visceral adipose distribution and function, associated with insulin sensitivity in patients at metabolic risk; however, the evidence needs to be further confirmed. In summary, BMI, WC, WHR, WHtR, and VAI are all useful tools for assessing adiposity/obesity in clinical practice, and should be evaluated along with other cardiometabolic risk factors to define cardiovascular risk stratification.
Purpose
Radiation dermatitis (RD) represents one of the most frequent side effects in radiotherapy (RT). Despite technical progress, mild and moderate RD still affects major subsets of patients and ...identification and management of patients with a high risk of severe RD is essential. We sought to characterize surveillance and nonpharmaceutical preventive management of RD in German-speaking hospitals and private centers.
Methods
We conducted a survey on RD among German-speaking radiation oncologists inquiring for their evaluation of risk factors, assessment methods, and nonpharmaceutical preventive management of RD.
Results
A total of 244 health professionals from public and private institutions in Germany, Austria, and Switzerland participated in the survey. RT-dependent factors were deemed most relevant for RD onset followed by lifestyle factors, emphasizing the impact of treatment conceptualization and patient education. While a broad majority of 92.8% assess RD at least once during RT, 59.0% of participants report RD at least partially arbitrarily and 17.4% stated to classify RD severity solely arbitrarily. 83.7% of all participants were unaware of patient-reported outcomes (PROs). Consensus exists on some lifestyle recommendations like avoidance of sun exposure (98.7%), hot baths (95.1%), and mechanical irritation (91.8%) under RT, while deodorant use (63.4% not at all, 22.1% with restrictions) or application of skin lotion (15.1% disapproval) remain controversial and are not recommended by guidelines or evidence-based practices.
Conclusion
Identification of patients at an increased risk of RD and subsequent implementation of adequate preventive measures remain relevant and challenging aspects of clinical routines. Consensus exists on several risk factors and nonpharmaceutical prevention recommendations, while RT-dependent risk factors, e.g., the fractionation scheme, or hygienic measures like deodorant use remain controversial. Surveillance is widely lacking methodology and objectivity. Intensifying outreach in the radiation oncology community is needed to improve practice patterns.
Sorafenib has shown survival benefits in patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh (CP) class A liver function. There are few prospective data on sorafenib in patients with ...HCC and CP class B.
A consecutive prospective series of 300 patients with CP class A or B HCC were enrolled in a dual-phase trial to determine survival and safety data according to liver function (class A or B) in patients receiving oral sorafenib 800 mg daily. Results of this study were presented in part at the ASCO 2012 Gastrointestinal Cancers Symposium, 19–21 January 2012. J Clin Oncol 2012; 30 (Suppl 4): abstract 306.
Overall progression-free survival (PFS), time to progression (TTP) and overall survival (OS) were 3.9, 4.1 and 9.1 months, respectively. For patients with CP class A versus B status, PFS was 4.3 versus 2.1 months, TTP was 4.2 versus 3.8 months and OS was 10.0 versus 3. 8 months. Extrahepatic spread was associated with worse outcomes but taken together with CP class, liver function played a greater role in reducing survival. Adverse events for the two CP groups were similar.
Although patients with HCC and CP class B liver function have poorer outcomes than those with CP class A function, data suggest that patients with CP class B liver function can tolerate treatment and may still benefit from sorafenib.
A microchip solid-phase extraction method for purification of DNA from biological samples, such as blood, is demonstrated. Silica beads were packed into glass microchips and the beads immobilized ...with sol−gel to provide a stable and reproducible solid phase onto which DNA could be adsorbed. Optimization of the DNA loading conditions established a higher DNA recovery at pH 6.1 than 7.6. This lower pH also allowed for the flow rate to be increased, resulting in a decrease in extraction time from 25 min to less than 15 min. Using this procedure, template genomic DNA from human whole blood was purified on the microchip platform with the only sample preparation being mixing of the blood with load buffer prior to loading on the microchip device. Comparison between the microchip SPE (μchipSPE) procedure and a commercial microcentrifuge method showed comparable amounts of PCR-amplifiable DNA could be isolated from cultures of Salmonella typhimurium. The greatest potential of the μchipSPE device was illustrated by purifying DNA from spores from the vaccine strain of Bacillus anthracis, where eventual integration of SPE, PCR, and separation on a single microdevice could potentially enable complete detection of the infectious agent in less than 30 min.
The effects of cadmium and lead were investigated in Cynara cardunculus L. Plant uptake by root and shoot, changes in cell ultrastructure and photosynthetic efficiency, photosynthetic key protein ...levels, as well as regulation of stress-induced Hsp70 were examined. Cynara cardunculus accumulated Cd and Pb in their tissue, with a different trend for the two metals. The prompt translocation of Cd to the shoot may justify the ultrastructural injuries, especially observed in chloroplasts. However, Cd- treated plants did not show any decline in photochemistry; it is likely that Cd in shoot tissue triggers defense mechanisms, increasing the level of proteins involved in photosynthesis (i.e., Rubisco and D1 increased 7 and 4.5 fold respectively) as a compensatory response to neutralize chloroplast damage. The accumulation of Pb mainly in root, can explain the increase in Hsp70 level (23 folds) in this tissue. Pb reached the shoots, even at low amounts, causing an overall significant change in some photochemical parameters (QY and NPQ decreases and increases of 25%, respectively). The results suggest a higher sensitivity of C. cardunculus to Pb than Cd, although maximal photochemical efficiency suggests that this species seems to tolerate Pb and Cd and hence, it is a suitable candidate for phytoremediation.
•Effects of Cd and Pb on uptake and photochemistry were studied in C. cardunculus.•Cd-treated plants showed ultrastructural injuries, but no decline in photochemistry.•Pb induced an increase of Hsp70 in root and a decrease of photochemistry.•The overall results suggest a higher sensitivity of C. cardunculus to Pb than Cd.
Somatic copy number alterations (SCNAs) are pervasive in advanced human cancers, but their prevalence and spatial distribution in early-stage, localized tumors and their surrounding normal tissues ...are poorly characterized. Here, we perform multi-region, single-cell DNA sequencing to characterize the SCNA landscape across tumor-rich and normal tissue in two male patients with localized prostate cancer. We identify two distinct karyotypes: 'pseudo-diploid' cells harboring few SCNAs and highly aneuploid cells. Pseudo-diploid cells form numerous small-sized subclones ranging from highly spatially localized to broadly spread subclones. In contrast, aneuploid cells do not form subclones and are detected throughout the prostate, including normal tissue regions. Highly localized pseudo-diploid subclones are confined within tumor-rich regions and carry deletions in multiple tumor-suppressor genes. Our study reveals that SCNAs are widespread in normal and tumor regions across the prostate in localized prostate cancer patients and suggests that a subset of pseudo-diploid cells drive tumorigenesis in the aging prostate.
Metal–metal oxide (MMO), graphite and laboratory-made Ag/AgCl electrodes were electrochemically characterized to be used as reference electrodes embedded in concrete structures. Electrodes were ...studied in both, aqueous solutions of pH ranging from 7 to 13.5 and embedded into cement mortars; and the electrochemical studies were carried out in the absence and presence of chloride ions. Potential evolution, polarization behaviour, galvanostatic pulse response and impedance characteristics of the electrodes were carried out in aqueous solutions. Besides, the electrochemical stability of the electrodes embedded in mortar was studied for an exposure period of 2 years. It was found that the MMO pseudo-reference electrode is pH-sensitive, the graphite pseudo-reference electrode is oxygen sensitive and the Ag/AgCl pseudo-reference electrode is chloride sensitive. In spite of the fact that any of them can be used to determine the corrosion rates of rebars because they do not depend on the absolute potential and/or the long-term stability of the reference electrode when using traditional electrochemical techniques, long-term drifts in the electrode potentials may lead to misinterpretations of the rebar state. In this context graphite electrodes are recommended because they provide conservative results regarding the active/passive state of the rebars.
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