Interstitial Level Research Articles

POS-071 VNN1 MEDIATES RENAL MALADAPTIVE REPAIR AFTER AKI BY INDUCING PREMATURE SENESCENCE OF RENAL TUBULAR CELLS

Renal maladaptive repair after acute kidney injury (AKI) can easily progress to chronic kidney disease. Sustained renal interstitial damage caused by accelerated senescence of renal tubular cells leads to renal fibrosis. Vanin-1 (VNN1) is an extracellular enzyme with panthenylmethylaminease activity that indirectly reduces the synthesis of glutathione, causing oxidative stress. The purpose of this study was to investigate the expression and of VNN1 in renal tissue and to study its role in senescence of renal tubular cells after ischemia reperfusion (I/R). Thirty male wild BALB/c mice were randomly divided into control group, sham group and I/R group. In the I/R group, the bilateral renal pedicle was ligatured for 35 min followed by reperfusion. The expression of VNN1 and aging markers (P16, P21, SA-b-gal) were detected. Furthermore, wild type mice and VNN1 knockout mice were used to compare the degree of renal tissue and functional damage and the senescence of renal tubular cells after I/R injury. Compared with sham group, Scr, BUN and renal injury score increased significantly in I/R group at the early stage (3d) of renal injury. Renal fibrosis was observed in the later stage (28-42d). The expression of VNN1 in renal tubular cells of I/R group increased after I/R injury. VNN1 was coexpressed with P16, suggesting that VNN1 might be related to cellular stress senescence. The SCr, BUN of VNN1 KO mice was significantly lower than that of wild type mice at 7-28 d after renal reperfusion. The renal interstitial injury score of VNN1 KO mice was significantly lower than that of wild type mice, and the renal interstitial fibrosis level was significantly higher than that of wild type mice at 42d after reperfusion. The results suggest that VNN1 KO promotes renal repair of AKI. The ratio of P16 positive tubule cells in VNN1 KO mice was significantly higher than that in wild-type mice at 7d after renal reperfusion, suggesting that VNN1 could promote the senescence of renal tubule cells during AKI repair. VNN1 mediates renal maladaptive repair after AKI by inducing premature senescence of renal tubular cells.

Assembly and Electroluminescence of Sheet-Like Zinc Oxide/Silicon Light-Emitting Diode by Radio Frequency Magnetron Sputtering Technique.

Sheet-like Zinc Oxide/Silicon ([ZnO]/[Si]) light emitting diode (LED) has been fabricated through depositing nanoscale ZnO on the p-type single crystal silicon by using a radio frequency (RF) magnetron sputtering method. The (100), (002) and (101) diffraction peaks can be observed. With the increasing sputtering time, however, the intensity of (100) and (101) diffraction peaks has gradually decreased and the intensity of (002) diffraction peak has gradually enhanced. Through low the sputtering power, the obtained ZnO shows better (002)-orientation growth. Electroluminescence (EL) from [ZnO]/[Si] LED have been decomposed into three emission bands, i.e., UV, green and orange emissions, which origin from the band gap, zinc interstitial or vacancies oxygen and shallow level, respectively. At the low sputtering power, orange emission is disappeared. It is indicated that the structures and EL properties are sensitive to the fabrication conditions. It is important to optimize and tune the fabrication condition for purposeful application in the future works.

Study on the Expansion Dynamics of MDCK Epithelium by Interstitial Flow Using a Traction Force-Measurable Microfluidic Chip.

The movement of collective cells is affected through changes in physical interactions of cells in response to external mechanical stimuli, including fluid flow. Most tissues are affected by fluid flow at the interstitial level, but few studies have investigated the physical effects in collective cells affected by a low flow rate. In this study, collective cell migration of Madin–Darby canine kidney (MDCK) epithelial cells was investigated under static or interstitial flow (0, 0.1, and 1 μL/min) using a traction microfluidic device. The optimization of calculation of cellular traction forces was first achieved by changing interrogation window size from the fluorescent bead images. Migration analysis of cell collectives patterned with a 700 μm circular shape reveals that cells under the slow flow (0.1 and 1 μL/min) showed the inhibitory migration by decreasing cell island size and cellular speed compared to that of static condition. Analysis of cellular forces shows that level of traction forces was lower in the slow flow condition (~20 Pa) compared to that of static condition (~50 Pa). Interestingly, the standard deviation of traction force of cells was dramatically decreased as the flow rate increased from 0 to 1 μL/min, which indicates that flow affects the distribution of cellular traction forces among cell collectives. Cellular tension was increased by 50% in the cells under the fluid flow rate of 1 μL/min. Treatment of calcium blocker increased the migratory speed of cells under the flow condition, whereas there is little change of cellular forces. In conclusion, it has been shown that the interstitial flow inhibited the collective movement of epithelial cells by decreasing and re-distributing cellular forces. These findings provide insights into the study of the effect of interstitial flow on cellular behavior, such as development, regeneration, and morphogenesis.

The serotonin reuptake transporter is reduced in the epithelium of active Crohn's disease and ulcerative colitis.

Serotonin is a highly conserved and ubiquitous signaling molecule involved in a vast variety of biological processes. A majority of serotonin is produced in the gastrointestinal epithelium, where it is suggested to act as a prominent regulatory molecule in the inflammatory bowel diseases (IBDs) Crohn's disease (CD) and ulcerative colitis (UC). Extracellular and circulating serotonin levels are thought to be elevated during intestinal inflammation, but the underlying mechanisms have been poorly understood. The data on human material are limited, contradictory, and in need of further investigation and substantiating. In this study, we show a potent and significant downregulation of the dominant serotonin reuptake transporter (SERT) mRNA (SLC6A4) in the epithelium from active CD ileitis, CD colitis, and UC colitis, compared with healthy controls. The mRNA of tryptophan hydroxylase 1, the rate-limiting enzyme in serotonin synthesis, was unregulated. Immunohistochemistry showed expression of the SERT protein in both the epithelium and the lamina propria and localized the downregulation to the epithelial monolayer. Laser capture microdissection followed by RNA sequencing confirmed downregulation of SLC6A4 in the epithelial monolayer during intestinal inflammation. Patient-derived colon epithelial cell lines (colonoids) incubated with the proinflammatory cytokine tumor necrosis factor alpha (TNF-α) reduced SERT expression. In summary, these results show that intestinal inflammation potently reduces the expression of SERT in both CD and UC and that TNF-α alone is sufficient to induce a similar reduction in colonoids. The reduced serotonin reuptake capacity may contribute to the increased interstitial serotonin level associated with intestinal inflammation.NEW & NOTEWORTHY The serotonin reuptake transporter is potently reduced in inflamed areas of Crohn's ileitis, Crohn's colitis, and ulcerative colitis. The changes are localized to the intestinal epithelium and can be induced by TNF-α. The serotonin synthesis through tryptophan hydroxylase 1 is unchanged. This regulation is suggested as a mechanism underlying the increased extracellular serotonin levels associated with intestinal inflammation.

The effect of a low glycaemic index diet on reducing day-long glycaemia in healthy young adults: A randomized crossover trial.

To compare the effect of a low glycaemic index (LGI) diet on reducing day-long glycaemia with a macronutrient-matched high glycaemic index (HGI) diet, using customized meal delivery to ensure compliance. We conducted a single-blinded, randomized crossover trial in 14 healthy adults (57% female) with a mean ± SD age of 21.6 ± 1.7 years. A flash glucose monitoring sensor was installed on the subjects on day 1 to capture the interstitial glucose level every 15 minutes for 14 days. Subjects were randomized to receive an LGI (dietary GI = 40) or HGI (dietary GI = 60) diet (three meals and two snacks) from day 2 for 5 consecutive days, followed by a 2-day washout, then switched to the alternative diet for another 5 days. A paired t-test was used to test the differences in the incremental area under the curve (iAUC) of glucose, postprandial glucose (PPG) concentration and maximum postprandial glucose rise (MPGR) between the LGI and HGI periods. Subjects had lower iAUC for average day-long glycaemia during the LGI intervention period compared with the HGI period (mean ± SD, 865 ± 297 vs. 1024 ± 267 mmol x min/L; P = .047). PPG for breakfast and snack 2, and MPGR for breakfast, snack 2 and dinner, were lower in the LGI period. In young healthy adults, following an LGI diet resulted in lower average day-long glycaemia compared with a macronutrient-matched HGI diet. Our results support the use of LGI diets to reduce the risk of developing glucose intolerance.

Relationship between interstitial glucose variability in ambulatory glucose profile and standardized continuous glucose monitoring metrics; a pilot study

BackgroundTreatment indexes using continuous glucose monitoring (CGM) have become standardized internationally, and the use of ambulatory glucose profile (AGP) is currently recommended. However, the relationship between AGP indexes and standardized CGM metrics has not been investigated. Using flash glucose monitoring (FGM), this retrospective study served to evaluate the association of the inter-quartile range (IQR) of AGP with standardized CGM metrics.MethodsThe study subjects were 30 patients with type 2 diabetes mellitus (T2DM) and 23 non-diabetic patients (control group). We evaluated average IQR (AIQR) and standardized CGM metrics. The primary endpoint was the relationship between AIQR and Time in range (TIR) in a 24-h period.ResultsIn the T2DM group, the AIQR was notably high and correlated negatively with TIR, and positively with Time above range, average interstitial glucose level, standard deviation of interstitial glucose, coefficient of variation of interstitial glucose, and mean of daily difference in blood glucose (MODD). For the T2DM group, the AIQR was notably lower in patients who achieved TIR > 70%, compared to those who did not. The AIQR cutoff value, as determined by ROC analysis, was 28.3 mg/dl for those who achieved TIR > 70%. No association was detected between the presence of hypoglycemia and AIQR.ConclusionsOur study is the first to provide the AIQR cutoff value for achieving the TIR target value. The range of interstitial glucose variability in AGP was associated with indexes of intra- and interday variations and hyperglycemia. Our results provide new perspectives in the yet-to-be established methods for evaluation of AGP in practical clinical settings.

P0518VNN1 MEDIATES RENAL MALADAPTIVE REPAIR AFTER AKI BY INDUCING PREMATURE SENESCENCE OF RENAL TUBUAR CELLS

Abstract Background and Aims Renal maladaptive repair after acute kidney injury (AKI) can easily progress to chronic kidney disease. Sustained renal interstitial damage caused by accelerated senescence of renal tubular cells leads to renal fibrosis. Vanin-1 (VNN1) is an extracellular enzyme with panthenylmethylaminease activity that indirectly reduces the synthesis of glutathione, causing oxidative stress. The purpose of this study was to investigate the expression and of VNN1 in renal tissue and to study its role in senescence of renal tubular cells after ischemia reperfusion (I/R). Method hirty male wild BALB/c mice were randomly divided into control group, sham group and I/R group. In the I/R group, the bilateral renal pedicle was ligatured for 35 min followed by reperfusion. The expression of VNN1 and aging markers (P16, P21, SA-b-gal) were detected. Furthermore, wild type mice and VNN1 knockout mice were used to compare the degree of renal tissue and functional damage and the senescence of renal tubular cells after I/R injury. Results Compared with sham group, Scr, BUN and renal injury score increased significantly in I/R group at the early stage (3d) of renal injury. Renal fibrosis was observed in the later stage (28-42d). The expression of VNN1 in renal tubular cells of I/R group increased after I/R injury. VNN1 was coexpressed with P16, suggesting that VNN1 might be related to cellular stress senescence. The SCr, BUN of VNN1 KO mice was significantly lower than that of wild type mice at 7-28 d after renal reperfusion. The renal interstitial injury score of VNN1 KO mice was significantly lower than that of wild type mice, and the renal interstitial fibrosis level was significantly higher than that of wild type mice at 42d after reperfusion. The results suggest that VNN1 KO promotes renal repair of AKI. The ratio of P16 positive tubule cells in VNN1 KO mice was significantly higher than that in wild-type mice at 7d after renal reperfusion, suggesting that VNN1 could promote the senescence of renal tubule cells during AKI repair. Conclusion VNN1 mediates renal maladaptive repair after AKI by inducing premature senescence of renal tubular cells.

The Physics of Fluid Dynamics Applied to Vascular Ulcers and Its Impact on Nursing Care.

The high incidence of vascular ulcers and the difficulties encountered in their healing process require the understanding of their multiple etiologies to develop effective strategies focused on providing different treatment options. This work provides a description of the principles of the physics of fluid dynamics related to vascular ulcers. The morphological characteristics of the cardiovascular system promote blood flow. The contraction force of the left ventricle is enhanced by its ability to reduce its radius of curvature and by increasing the thickness of the ventricular wall (Laplace’s Law). Arterial flow must overcome vascular resistance (Ohm’s equation). The elastic nature of the artery and the ability to reduce its diameter as flow rate progresses facilitate blood conduction at high speed up to arteriolar level, and this can be determined by the second equation of continuity. As it is a viscous fluid, we must discuss laminar flow, calculated by the Reynolds number, which favors proper conduction while aiming at the correct net filtration pressure. Any endothelial harmful process that affects the muscle wall of the vessel increases the flow speed, causing a decrease in capillary hydrostatic pressure, thus reducing the exchange of nutrients at the interstitial level. With regard to the return system, the flow direction is anti-gravity and requires endogenous aid to establish the Starling’s equilibrium. Knowledge on the physics of vascular fluid dynamics makes it easier to understand the processes of formation of these ulcers so as to choosing the optimal healing and prevention techniques for these chronic wounds.

Diabetic cardiomyopathy: How can cardiac magnetic resonance help?

Diabetes cardiomyopathy is a specific form of cardiac disease characteristic for diabetic patients. Development of echocardiography enabled diagnosis of diabetic cardiomyopathy significantly before the occurrence of heart failure. Previously was believed that left ventricular (LV) diastolic dysfunction represents the first detectable stage of diabetic cardiomyopathy. However, speckle tracking imaging and strain evaluation showed that mechanical changes occur before LV diastolic dysfunction. Nevertheless, it seems that the first detectable stage of diabetic cardiomyopathy is myocardial interstitial fibrosis, which currently could be diagnosed predominantly by cardiac magnetic resonance. T1 mapping evaluation before and after contrast injection enables assessment of extracellular volume (ECV) and provides qualitative and quantitative assessment of interstitial myocardial fibrosis in diabetic patients. Studies showed a strong correlation between ECV-parameter of interstitial fibrosis and level of glycated hemoglobin-main parameter of glucose control in diabetes. This stage of fibrosis is still not LV hypertrophy and it is reversible, which is of a great importance because of timely initiation of treatment. The necessity for early diagnose is significantly increasing due to the fact that diabetes and arterial hypertension are concomitant disorders in the large number of diabetic patients and it has been known that the risk of interstitial myocardial fibrosis is multiplied in patients with both conditions. Future follow-up investigations are essential to determine the causal relationship between interstitial fibrosis and outcome in these patients. The aim of this review was to summarize the current knowledge and clinical usefulness of CMR in diabetic patients.

Initial experiences of adolescents and young adults with type 1 diabetes and high-risk glycemic control after starting flash glucose monitoring - a qualitative study.

This study explored early experiences with a flash glucose monitoring system among adolescents and young adults with type 1 diabetes and high-risk glycemic control. Adolescents and young adults with high-risk glycemic control (HbA1c ≥ 75mmol/mol (9.0%) in the previous 6months) who had recently commenced on flash glucose monitoring as part of a trial took part in a semi-structured interview exploring their experiences with the technology. All interviews were recorded, transcribed and analyzed using an inductive approach. Fifteen interviews were conducted. Overall, participants enjoyed flash glucose monitoring and planned to continue using their system. Key findings included flash glucose monitoring reduced diabetes management burden and increased glucose monitoring. Other impacts of flash glucose monitoring use included perceived improved mood and energy, increased capacity for physical activity and less parental conflict. While participants reported healthier glycemic control, participants' mean interstitial glucose level remained above the target range of 3.9-10.0mmol/L (70-180mg/dL) over the first month of flash glucose monitoring. Common challenges included premature sensor loss and decreased scanning over the first month of use. Flash glucose monitoring may be an acceptable self-management tool to increase monitoring frequency in adolescents and young adults with type 1 diabetes and high-risk glycemic control, with the potential to improve long-term glycemic control. Initial support efforts should focus on practical strategies to prolong sensor wear and motivate frequent scanning as well as education on interpreting glucose data and making informed treatment decisions to maximize the benefits of this technology.

In vivo-mimicking microfluidic perfusion culture of pancreatic islet spheroids.

Native pancreatic islets interact with neighboring cells by establishing three-dimensional (3D) structures, and are surrounded by perfusion at an interstitial flow level. However, flow effects are generally ignored in islet culture models, although cell perfusion is known to improve the cell microenvironment and to mimic in vivo physiology better than static culture systems. Here, we have developed functional islet spheroids using a microfluidic chip that mimics interstitial flow conditions with reduced shear cell damage. Dynamic culture, compared to static culture, enhanced islet health and maintenance of islet endothelial cells, reconstituting the main component of islet extracellular matrix within spheroids. Optimized flow condition allowed localization of secreted soluble factors near spheroids, facilitating diffusion-mediated paracrine interactions within islets, and enabled long-term maintenance of islet morphology and function for a month. The proposed model can aid islet preconditioning before transplantation and has potential applications as an in vitro model for diabetic drug testing.

Therapy-driven Deep Glucose Forecasting

The automatic regulation of blood glucose for Type 1 diabetes patients is the main goal of the artificial pancreas, a closed-loop system that exploits continue glucose monitoring data to define an optimal insulin therapy. One of the most successful approaches for developing the artificial pancreas is the model predictive control, which exhibits promising results on both virtual and real patients. The performance of such controller is highly dependent on the reliability of the glucose–insulin model used for prediction purpose, which is usually implemented with classic mathematical models. The main limitation of these models consists in the difficulties of modeling the physiological nonlinear dynamics typical of this system. The availability of big amount of in silico and in vivo data moved the attention to new data-driven methods which are able to easily overcome this problem. In this paper we propose Deep Glucose Forecasting, a deep learning approach for forecasting glucose levels, based on a novel, two-headed Long-Short Term Memory implementation. It takes in input the previous values obtained through continue glucose monitoring, the carbohydrate intake, the suggested insulin therapy and forecasts the interstitial glucose level of the patient. The proposed architecture has been trained on 100 virtual adult patients of the UVA/Padova simulator, and tested on both virtual and real patients. The proposed solution is able to generalize to new unseen data, outperforms classical population models and reaches performance comparable to classical personalized models when fine-tuning is exploited on real patients.

Elucidating room-temperature optical transitions in annealed ZnO nanoparticles synthesized from an aqueous method

ZnO nanoparticles (NPs), which were grown from chemical synthesis by an aqueous method and annealed, were studied. The annealed ZnO NPs have the hexagonal phase of wurtzite and no other phase was observed. The observed grains are spheroidal except for those annealed at 800 °C. The ZnO NP grain size increases and the strain reduces as annealing temperature increases. From the photoluminescence spectra it was also observed an increase in the emission of the defect band and a decrease of the emission at the near-bandgap-edge as the annealing temperature increases. Significant emission peaks at 2.63 eV and 3.19 eV show an increase and decrease respectively, while the peak at 2.96 eV remains constant as the annealing temperature increases. The origin of the 2.63 eV peak was identified as a transition between the corresponding levels of neutral O vacancies to monovalent Zn vacancies and the origin of the 2.96 eV peak was associated to a transition from conduction band to an interstitial O level. The origin of the 3.19 eV peak was associated to a transition from an interstitial Zn energy level to the valence band. The three transitions are the main ones that take place inside the NPs. The behaviors of these PL peaks agree with the analysis of the structural results. Analysis of the FTIR spectra reveals that only at about 400 °C and higher annealing temperatures, the precursor residues are completely removed.

Analysis of variation in pre-meal exercise effect on fasting interstitial glucose level

Analysis of variation in pre-meal exercise effect on fasting interstitial glucose level

Twenty Minute Moderate-Intensity Post-Dinner Exercise Reduces the Postprandial Glucose Response in Chinese Patients with Type 2 Diabetes.

BackgroundPostprandial hyperglycemia and glycemic fluctuations are significant cardiovascular disease risk factors for patients with type 2 diabetes. We investigated the effects of a single session of post-dinner moderate-intensity exercise on the postprandial glycemic response compared with a non-exercise condition in a study population of Chinese patients with type 2 diabetes.Material/MethodsThis randomized crossover self-controlled pilot study involved 29 patients with type 2 diabetes who participated in post-dinner exercise days using non-exercise days as a control. The interstitial glucose level was monitored using a continuous glucose monitoring system, with a standardized diet and medication. For the non-exercise control days, patients pursued normal daily activities but refrained from unusual strenuous physical activity. On the exercise days, participants walked on a treadmill for 20 minutes after dinner, with a heart rate reserve of 40%.ResultsPost-dinner moderate-intensity exercise reduced the 2-hour postprandial glucose spike, mean glucose level, and peak glucose level compared to the control condition. The cumulative glucose total area under the curve during 1-hour post-exercise was lower with exercise than under the control condition. The 12-hour standard deviation of blood glucose and the coefficient variation of glucose were significantly lower in the with exercise day compared to the control day, although the 12-hour mean amplitude of glycemic fluctuations did not reach statistical significance. No nocturnal hypoglycemia subsequently occurred on the exercise day.ConclusionsA short session of moderate-intensity post-dinner exercise can improve postprandial hyperglycemia and glycemic excursions in Chinese patients with type 2 diabetes, with no potential hypoglycemia risk at a later period.

Effect of moderate exercise for 30 min at 30 min versus 60 min after dinner on glycemic control in patients with type 2 diabetes: a randomized, crossover, self-controlled study

To compare the effectiveness of moderate exercise for 30 min at 30 min and 60 min after dinner on glycemic control in patients with type 2 diabetes. This randomized, crossover, self-controlled pilot study was conducted in 15 inactive patients with type 2 diabetes without serious complications or use of exogenous insulin. The participants completed two randomly ordered exercise protocols (brisk walking for 30 min at 30 min or 60 min after dinner on the exercise day) spaced 1 week apart. All the exercise was performed while maintaining a heart rate reserve of 40%. The interstitial glucose level was monitored using a continuous glucose monitor (CGM) for all the participants, who maintained a standardized diet with routine medications. The 2-h postprandial mean glucose, peak glucose, and glucose area under the curve (AUC) were measured. The mean amplitude of glycemic excursions (MAGE) and other plasma glucose fluctuation parameters in 12 h after dinner, including the mean blood glucose (MBG) and the coefficient variation (CV) of glucose, were also calculated. The incidence of nocturnal hypoglycemia was recorded in all the participants. The participants had a mean age of 46±11 years with a mean BMI of 25.8±3.1 kg/m2 and a mean HbA1c of 7.7%. No significant differences were found between postprandial 30 min exercise group and postprandial 60 min exercise group in terms of 2-h postprandial mean glucose, peak glucose, glucose AUC, or in MBG, CV and MAGE during the 12-h period after dinner. No nocturnal hypoglycemia occurred in the participants after exercise at 30 or 60 min after dinner. However, significant reductions in the 2-h postprandial glucose levels were detected after exercise at 60 min after dinner as compared to exercise at 30 min. The timing (30 min vs 60 min after dinner) of moderate exercises for 30 min does not produce significant difference in the improvement of postprandial hyperglycemia in type 2 diabetic patients, and both exercise protocols are safe without a potential risk of hypoglycemia. Nevertheless, exercise at 60 min after dinner can be more effective to lower 2-h postprandial glucose, while exercise at 30 min after dinner might be safer for patients with a high risk of hypoglycemia.

FSCPX, a Chemical Widely Used as an Irreversible A₁ Adenosine Receptor Antagonist, Modifies the Effect of NBTI, a Nucleoside Transport Inhibitor, by Reducing the Interstitial Adenosine Level in the Guinea Pig Atrium.

Based on in silico results, recently we have assumed that FSCPX, an irreversible A1 adenosine receptor antagonist, inhibits the action of NBTI that is apparent on E/c curves of adenosine receptor agonists. As a mechanism for this unexpected effect, we hypothesized that FSCPX might modify the equilibrative and NBTI-sensitive nucleoside transporter (ENT1) in a way that allows ENT1 to transport adenosine but impedes NBTI to inhibit this transport. This assumption implies that our method developed to estimate receptor reserve for agonists with short half-life such as adenosine, in its original form, overestimates the receptor reserve. In this study, therefore, our goals were to experimentally test our assumption on this effect of FSCPX, to improve our receptor reserve-estimating method and then to compare the original and improved forms of this method. Thus, we improved our method and assessed the receptor reserve for the direct negative inotropic effect of adenosine with both forms of this method in guinea pig atria. We have found that FSCPX inhibits the effects of NBTI that are mediated by increasing the interstitial concentration of adenosine of endogenous (but not exogenous) origin. As a mechanism for this action of FSCPX, inhibition of enzymes participating in the interstitial adenosine production can be hypothesized, while modification of ENT1 can be excluded. Furthermore, we have shown that, in comparison with the improved form, the original version of our method overestimates receptor reserve but only to a small extent. Nevertheless, use of the improved form is recommended in the future.

Risk Factors of Hypoglycemia in Patients with Type 2 Diabetes Mellitus: A Study Based on Continuous Glucose Monitoring

The objective of this study was to determine the risk factors of hypoglycemia by evaluating the glycemic profile using continuous glucose monitoring (CGM) in patients with type 2 diabetes mellitus (T2DM). The participants were 294 patients with T2DM who received inpatient diabetes education. The mean blood glucose (MBG), coefficient of variation (CV), mean postprandial glucose excursion, low blood glucose index (LBGI), and percentage of time with blood glucose (BG) at <70 mg/dL were measured on admission using CGM. We predicted the risk of hypoglycemia utilizing transform to Gaussian model. The primary end point was the relationship between CGM parameters and hypoglycemia. Multivariate logistic regression analysis showed that disease duration, MBG, CV, LBGI, and Predicted% of BG correlated significantly with hypoglycemia. Receiver operating characteristic curve analysis showed that the optimal cutoff points for MBG and CV in predicting hypoglycemia were 152 mg/dL and 22%, respectively. The proportion of patients with hypoglycemia was 0% for the group with no hypoglycemia risk factors, 4.2% for the group with one risk factor, and 36.6% for the group with two risk factors, showing a linear increase across the groups (P < 0.001). LBGI was the best predictor of hypoglycemia; and Predicted% BG <70 mg/dL was very useful as an index to predict hypoglycemia. Patients with low MBG levels and large fluctuations in BG were more likely to develop hypoglycemia, suggesting that assessment of these two variables is useful for the prediction of hypoglycemia. To achieve good glycemic control free of hypoglycemia, approaches are needed that do not only lower BG level but also minimize fluctuations in blood and interstitial fluid glucose level.

Photoluminescence study of interstitial oxygen defects in ZnO nanostructures

ZnO defect luminescence is a fascinating but still highly controversial issue. Herein, the role of interstitial oxygen played on the photoluminescence (PL) property of ZnO nanostructures is investigated through oxygen plasma exposure and low temperature O2 annealing. In contrast to previous reports, no interstitial oxygen related deep level emission was observed in PL spectra from room temperature (RT) to 7 K after oxygen-rich treatments, except apparent suppression of the exciton emission due to the upward band bending effect. This work illustrates that the isolated interstitial oxygen seems not to cause the widely reported yellow/orange emission regardless of the ZnO growth method.

Surgical menopause exacerbated high-fat and high-sugar diet-induced overactive bladder in a rat model

Objective: The pathophysiology mechanism of menopause in the metabolic syndrome-associated bladder dysfunction is still not clear. The major aims of the present study were to examine the impact of high-fat-high-sugar diet and surgical menopause-induced metabolic syndrome in overactive bladder (OAB). Methods: Female Sprague Dawley rats were feed with high-fat-high-sugar diet with/without ovariectomy surgery to mimic menopause and to induce metabolic syndrome. At 6 months after high-fat-high-sugar feeding, cystometrogram, physical indicator, and urine and serum biochemistry parameters were measured. Masson's trichrome stain and Western blots were carried out to examine the expressions of interstitial fibrosis, fibrosis-associated proteins, and muscarinic or purinergic receptors. Results: Bladder hyperactivity was induced accompanied by bladder interstitial fibrosis after 6 months of high-fat-high-sugar feeding, while surgical menopause exacerbated these bladder damages and enhanced interstitial fibrosis level. In addition, surgical menopause enhanced bladder dysfunction via overexpression of muscarinic and purinergic receptors. Conclusions: High-fat-high-sugar feeding induced bladder overactivity, while ovary hormone deficiency enhanced bladder interstitial fibrosis, exacerbated OAB syndrome, and increased muscarinic and purinergic receptors expressions.