The potential association between thiamin, hyperglycemia and chronic diseases

Chronic diseases, such as cardiovascular disease and diabetes, are the leading causes of morbidity and mortality worldwide. Recent studies have shown that in addition to diabetes mellitus, non-diabetic degrees of fasting and postprandial hyperglycemia are also directly linked to accelerated risks of cardiovascular diseases. Thiamin is a water soluble vitamin playing a key regulatory role as a co-enzyme in metabolic pathways implicated in the glucose metabolism. There is some evidence that diabetic patients are prone to thiamin deficiency possibly because of an increased excretion of thiamin in the urine. However, there has been no published study to investigate thiamin status in individuals with pre-diabetic range of hyperglycemia. Given this gap, we undertook a cross-sectional study, evaluating blood thiamin concentration of subjects with impaired glucose regulation compared with healthy people.To examine the main objective of this study, data of 64 subjects (29 men and 35 women) were analysed. These subjects consisted of 39 normal healthy volunteers and 25 hyperglycemics with plasma glucose levels at pre-diabetic ranges (16 IGT, 9 IFG). The mean intake of thiamin in both groups as assessed by a validated semiquantitative food frequency questionnaire was 1.37±0.72 mg/day for normal subjects and 1.46±0.51 mg/day for those with hyperglycemia. These values exceeded the Australian RDI for thiamin. There was no significant difference in the levels of RBC thiamin in hyperglycemic subjects relative to those in the normoglycemic group (0.95±0.17 vs. 0.88±0.24 nmol/g Hb, p=0.22).The two groups were also evaluated for a range of risk factors for CVD, including arterial stiffness. Hyperglycemic subjects had higher levels of fasting DVP parameters (SI & RI), accompanied with tendencies toward blunted response to ingested glucose load relative to normoglycemic group. These results suggest that screening of individuals with hyperglycemia by using a Pulse Trace machine may be a means of recognising cardiovascular complications at early stages. Further research with a larger sample size is recommended to extend these interesting results.Hyperglycemia is known to induce a variety of biochemical alterations at the cellular level, resulting in a range of vascular and tissue damages. The mechanism of action of supplemental thiamin seems to involve the diversion of "excess" metabolic load (glycolytic intermediates) away from glycolysis and toward the reductive pentose pathway, a secondary pathway for glucose catabolism. Thiamin supplementation was also shown to improve cardiovascular risk factors in diabetic rats, suggesting the potential effects of thiamin in prevention of diabetic complications.To date there has been no published study to investigate these effects in individuals with pre-diabetic range of hyperglycemia (IGT). Therefore, our objective in the second study was to assess the chronic effect of high dose thiamin supplement (300 mg/d) on glucose tolerance and some cardiovascular risk factors in individuals with hyperglycemia at an early stage. In this intervention study with a double blind cross - over design, the hyperglycemic subjects (n=12) were randomly allocated into two groups to receive either placebo for 6 weeks followed by a 14-week washout period and then thiamin for 6 weeks; or thiamin for 6 weeks, a 14-week washout period and placebo for 6 weeks.The results of our intervention study showed that after 6 weeks of supplementation, RBC thiamin increased from 0.93 (±0.17) nmol/g Hb to 1.56 (±0.31) nmol/g Hb. In subjects receiving placebo, fasting plasma glucose increased significantly from baseline after six weeks (6.11±0.70 vs. 5.87±0.63 mmol/L, p=0.003). This significant change was accompanied with concomitant increases in fasting plasma insulin (7.67± 4.39 vs. 6.64± 3.45 μIU/mL, p=0.04), and HOMA score (2.10±1.32 vs. 1.75±1.01, p= 0.02). However in the supplement arm, there was no significant change in fasting plasma glucose (6.01±0.79 vs. 6.02±0.68 mmol/L, p=0.83), fasting insulin (7.46 ±4.67 vs. 7.36± 4.40 μIU/mL, p> 0.05) or HOMA score (2.05±1.51 vs. 2.00±1.32, p=0.75) determined at week 6 compared to baseline (week 0), indicating that supplementation with high dose thiamin may have prevented the natural progression of hyperglycemia toward diabetes mellitus in individuals with impaired glucose metabolism at early stages. We also found that high dose thiamin therapy can improve glucose tolerance (week 0: 9.89±2.50 vs. week 6: 8.78±2.20 mmol/L, p=0.004), and attenuate diastolic blood pressure (week 0: 71.42 ±7.41 vs. week 6: 79.2± 5.84 mm Hg, p=0.005) in patients with impaired glucose metabolism. The findings of the present study suggest that thiamin therapy may be effective in patients with hyperglycemia at early stages.Previous studies examining the potential effects of thiamin under hyperglycemic condition have mainly been limited to animals. The current clinical study suggests that thiamin supplementation may be beneficial in humans with pre-diabetic ranges of hyperglycemia. Further studies are required to confirm these results and investigate the impact of thiamin supplementation on insulin secretion.The findings of this research have the potential to inform food formulations and dietary recommendations for people who are at risk of developing diabetes mellitus, and may have a role in the prevention of hyperglycemic complications. The findings of this study serve as a base for further research investigating the effectiveness of different doses of thiamin on cardiovascular risk factors

Assessment of vascular function in individuals with hyperglycemia: A cross-sectional study of glucose-induced changes in digital volume pulse

Background: Arterial stiffness is an independent risk factor for cardiovascular disease and its progression may be accelerated in the presence of hyperglycemia, either fasting or postprandial. The current study assessed vascular function in subjects with pre-diabetes hyperglycemia, using digital volume pulse analysis technique.Methods: We conducted a cross-sectional study examining vascular function in the fasting and postprandial (glucose-induced) state in 44 adults, consisting of 17 subjects with pre-diabetic hyperglycemia and 27 normoglycemic volunteers. Photoplethysmography of the digital volume pulse (DVP) was used to determine stiffness index (SI) and reflective index (RI), as main measures of larger artery stiffness and vascular tone, respectively.Results: Our results showed a significantly higher (Ln) fasting SI in the hyperglycemic group compared with the control group (2.19 ± 0.32 vs. 1.96 ± 0.22, P = 0.005). However, this pattern reversed after adjustment for potential confounders. In multiple linear regression analysis, (Ln) SI was related to age (ß = 0.01, 95% CI: 0.01-0.02, P < 0.001) and systolic blood pressure (SBP) (ß = 0.01, 95% CI: 0.00-0.01, P < 0.05), but not with W/H, diastolic blood pressure (DBP), fasting plasma glucose (FPG) or serum lipids. Furthermore, age (ß = 0.02, 95% CI: 0.01-0.03, P < 0.001) and mean arterial pressure (MAP) (ß = 0.01, 95% CI: 0.00-0.02, P < 0.05) were found as the strong predictors of fasting SI in hyperglycemic group. Neither FPG nor 2-h plasma glucose was a significant predictor for SI in hyperglycemic group, after accounting for age and MAP. Subjects with hyperglycemia had a 15% blunted change in postprandial AUCs for RI, adjusted for the respective baseline measurements (-9.40 ± 3.59 vs. -11.00 ± 2.84%) but these did not attain statistical significance.Conclusion: Increased arterial stiffness in pre-diabetic subjects is strongly associated with age and MAP. The increased DVP-derived SI reported in patients with pre-diabetic hyperglycemia may result from different frequently accompanied risk factors not just glycemic changes in this range

Characterisation and Modification of the Optical Properties of Zirconia-Based Ceramics for Aesthetic Dental Restorations

The use of 3Y-TZP for monolithic dental restorations is well established in the dentistry field. However, the challenges of colour matching generally necessitates the application of layering, although this introduces a second layer of uncertainty. The present work aimed to examine the relevant factors of sintering temperature (1h, 2 h, 4h at 1400°C, 1500°C, 1600°C) and post-sintering annealing conditions (1 min at 750°C) commensurate with the processes of layering, which are done in two atmospheric conditions (vacuum, air). The analytical techniques applied to the detailed examination of these materials were extensive and included ultraviolet-visible (UV-Vis) spectrophotometry, the data of which were used to determine the CIE colour parameters in reflection, transmission, and calculated absorption modes; translucency and opalescence also were examined. The UV-Vis data also were used to determine the optical direct and indirect band gaps. The microstructural analyses involved grain size determination by the line-intercept method using scanning electron microscopy (SEM), image analysis, and electron backscattered diffraction (EBSD). High-magnification microstructural and chemical analyses were done using ex-situ transmission electron microscopy (TEM) and in situ high-resolution transmission electron microscopy (HRTEM). The roughnesses were determined by atomic force microscopy (AFM). The mineralogical and crystallographic characteristics were based on X-ray diffraction (XRD), the data from which were processed through the Williamson-Hall and Rietveld refinement methods. The defect chemistry was examined in detail, including the application of four major approaches. First, time-of-flight secondary ion mass spectroscopy (ToF-SIMS) was used to probe surface and bulk chemistries. Second, UV-Vis was used generally to assess the defect types. Third, X-ray photoelectron spectroscopy was used to determine ionic valences, particularly in terms of valence shifts resulting from redox reactions, intervalence charge transfer (IVCT), and multivalence charge transfer (MVCT). Fourth, electron paramagnetic resonance (EPR) spectroscopy was used to confirm the feasibility of formation of different defect types. The experimental outcomes of the experimental work were extensive, involving presentation and analysis of the data obtained using the preceding techniques. However, the key findings that challenge conventional assumptions about the nature of solid solutions of Y in ZrO2 are as follows: Five separate sets of data (XPS, XRD, UVvis, EPR, and ToFSIMS) are consistent in that they indicate that the solid solubility mechanism of Y in ZrO2 is not the universally held substitutional solid solubility but interstitial solid solubility. This outcome has significant ramifications for the potential defect equilibria because interstitial solid solubility would cause Y to be a donor dopant rather than an acceptor dopant, so Y would not be capable of creating oxygen vacancies for charge compensation. The XPS peak assignment data indicate that the charge-compensation mechanism is not ionic or electronic but redox, where Zr4+ is reduced to Zr2+ and Zr3+, both of which represent defects. The valence shifts indicated in the XPS data also indicate that IVCT results in the formation of another type of defect that results from the indicative reaction Zr4+ + Y3+ → Zr5+ + Y2+. Essentially all of the data present a consistent picture that the principal causes of colour derive from (A) the formation of the Zr2+ and Zr3+ from charge compensation from Y interstitial solid solubility; (B) oxygen Schottky pair formation from interaction of the surface and lattice with photons and phonons, resulting in the formation of the colour centre F0 (V_O^(••)); (C) charge exchange by oxidation of adjacent Zr3+ and Zr2+ and reduction of V_O^(••) to form the colour centres F+ (V_O^•) and F++ (V_O^x), respectively. The reflected colour of the surface, which results from the effects of highly mobile defects at the surface (redox and IVCT/MVCT), is dominated by the yellow F++ colour centre (with the blue F+ (V_O^•) colour centres as minority). In contrast, the absorbed colour, which results from the less mobile defects in the bulk (elastic photon and phonon interactions with the lattice), is dominated by blue F+ (V_O^•) colour centre (with the violet F0 (V_O^(••)) colour centre. More broadly, the microstructures were highly dense (>99.5% of theoretical) as a function of sintering temperature are described as follows: 1400°C: Formation of a grain boundary Y silicate glass; the rhombohedral ZrO2 superlattice was detected by XRD; the rhombohedral ZrO2 transformed to tetragonal by annealing at 750°C. 1500°C: Establishment of an ordered and homogeneous microstructure in which the Y silicate glass had redissolved. 1600°C: Y segregation on the grain boundaries; monoclinic ZrO2 was detected by XRD; Zr clustering occurred upon annealing. This work has ramifications for dental laboratories fabricating ZrO2-based materials. Perhaps the most important observation is that sintering at 1500°C results in the most homogenous and colour-stable microstructure, although this observation is limited to post-sintering processing by annealing under vacuum at 750°C. However, if higher sintering temperatures are used in order to increase light transmission, then annealing should be avoided and post-annealing optimises the outcome colour. Although sintering at 1400°C results in the lowest colour-causing defect concentration, annealing and post-annealing significantly increased the concentration. Consequently, dental restorations sintered at this temperature should be mechanically polished only

High-Dose Thiamine Supplementation Improves Glucose Tolerance in Hyperglycemic Individuals: a Randomized, Double-Blind Cross-Over Trial

Purpose: To assess the effect of high-dose oral thiamine supplements on glucose tolerance in patients with impaired glucose metabolism. Methods: Twelve hyperglycemic subjects (10 cases of impaired glucose tolerance and 2 new cases of type 2 diabetes) completed this randomized, double-blind trial, where all participants received both placebo and thiamine capsules (3 × 100 mg/day) for 6 weeks in a cross-over manner. The main endpoint was changes in 2-h plasma glucose. Fasting plasma glucose and insulin, 2-h plasma insulin, the hemostatic model assessment of insulin resistance (HOMA-IR), renal function measurement and thiamin status were also evaluated at the commencement and completion of each treatment period. Results: Thiamine supplementation resulted in significant decrease in 2-h plasma glucose relative to baseline (8.78 ± 2.20 vs. 9.89 ± 2.50 mmol/l, p = 0.004), with no significant change in the placebo arm. Fasting plasma glucose and insulin, and HOMA-IR increased significantly from baseline after 6 weeks in the placebo arm (p = 0.003, p = 0.04 and p = 0.02, respectively). These variables did not change with thiamine supplementation. There were no significant changes in 2-h plasma insulin or renal function marker, within or between arms. Conclusion/interpretation: Supplementation with high-dose thiamine may prevent deterioration in fasting glucose and insulin, and improve glucose tolerance in patients with hyperglycemia. High-dose thiamine supplementation may prevent or slow the progression of hyperglycemia toward diabetes mellitus in individuals with impaired glucose regulation

Communication-Efficient Laplace Mechanism for Differential Privacy via Random Quantization

We propose the first method that realizes the Laplace mechanism exactly (i.e., a Laplace noise is added to the data) that requires only a finite amount of communication (whereas the original Laplace mechanism requires the transmission of a real number) while guaranteeing privacy against the server and database. Our mechanism can serve as a drop-in replacement for local or centralized differential privacy applications where the Laplace mechanism is used. Our mechanism is constructed using a random quantization technique. Unlike the simple and prevalent Laplace-mechanism-then-quantize approach, the quantization in our mechanism does not result in any distortion or degradation of utility. Unlike existing dithered quantization and channel simulation schemes for simulating additive Laplacian noise, our mechanism guarantees privacy not only against the database and downstream, but also against the honest but curious server which attempts to decode the data using the dither signals.Comment: 11 pages, 3 figures, short version to be submitted at 2024 IEEE International Conference on Acoustics, Speech and Signal Processin

A symmetric method for weakly imposing Dirichlet boundary conditions in embedded finite element meshes

In this paper, we propose a way to weakly prescribe Dirichlet boundary conditions in embedded finite element meshes. The key feature of the method is that the algorithmic parameter of the formulation which allows to ensure stability is independent of the numerical approximation, relatively small, and can be fixed&nbsp;a priori. Moreover, the formulation is symmetric for symmetric problems. An additional element‐discontinuous stress field is used to enforce the boundary conditions in the Poisson problem. Additional terms are required in order to guarantee stability in the convection&ndash;diffusion equation and the Stokes problem. The proposed method is then easily extended to the transient Navier&ndash;Stokes equations

Do Patients with Penetrating Abdominal Stab Wounds Require Laparotomy?

Background: The optimal management of hemodynamically stable asymptomatic patients with anterior abdominal stab wounds (AASWs) remains controversial. The goal is to identify and treat injuries in a safe cost-effective manner. Common evaluation strategies are local wound exploration (LWE), diagnostic peritoneal lavage (DPL), serial clinical assessment (SCAs) and computed tomography (CT) imaging. Making a decision about the right time to operate on a patient with a penetrating abdominal stab wound, especially those who have visceral evisceration, is a continuing challenge. Objectives: Until the year 2010, our strategy was emergency laparotomy in patients with penetrating anterior fascia and those with visceral evisceration. This survey was conducted towards evaluating the results of emergency laparotomy. So, better management can be done in patients with penetrating abdominal stab wounds. Patients and Methods: This retrospective cross-sectional study was performed on patients with abdominal penetrating trauma who referred to Al- Zahra hospital in Isfahan, Iran from October 2000 to October 2010. It should be noted that patients with abdominal blunt trauma, patients under 14 years old, those with lateral abdomen penetrating trauma and patients who had unstable hemodynamic status were excluded from the study. Medical records of patients were reviewed and demographic and clinical data were collected for all patients including: age, sex, mechanism of trauma and the results of LWE and laparotomy. Data were analyzed with PASW v.20 software. All data were expressed as mean ± SD. The distribution of nominal variables was compared using the Chi-squared test. Also diagnostic index for LWE were calculated. A two-sided P value less than 0.05 was considered to be statistically significant. Results: During the 10 year period of the study, 1100 consecutive patients with stab wounds were admitted to Al-Zahra hospital Isfahan, Iran. In total, about 150 cases had penetrating traumas in the anterior abdomen area. Sixty-three (42%) patients were operated immediately due to shock, visceral evisceration or aspiration of blood via a nasogastric tube on admission. Organ injury was seen in 78% of patients with visceral evisceration. Among these 87 cases, 29 patients’ (33.3%) anterior fascia was not penetrated in LWE. So, they were observed for several hours and discharged from the hospital without surgery. While for the remaining 58 patients (66.6%), whose LWE detected penetration of anterior abdominal fascia, laparotomy was performed which showed visceral injuries in 11 (18%) cases. Conclusions: All in all, 82 percent of laparotomies in patients with penetrated anterior abdominal fascia without visceral evisceration, who had no signs of peritoneal irritation, were negative. So, we recommended further evaluation in these patients. However, visceral evisceration is an indication for exploratory laparotomy, since in our study; the majority of patients had organ damages

Analyzing and Interpreting the Effects of the of Borrowed Size Concept on the Development of Small Towns (Case Study of Bahnamir)

In recent years, some researchers have used the concept of "Borrowed size" as a justification for the efficiency of small and medium-sized cities in Poly-centric urban regions. They believe that smaller cities located near or within an integrated functional urban area can take advantage of the population, facilities, and amenities of larger cities while avoiding the agglomeration costs of larger cities such as traffic, high housing prices, and congestion. In this regard, the present article tries to use this concept, in addition to explaining the growth of the furniture industry in the city of Bahnamir, to open the way for its application in urban and regional policies. For this purpose, the applicability of this concept in Bahnamir was measured in four phases: first, specialization and concentration using locational coefficient and firm density, second, a geographical overlap of demand market by connectivity field index, third measurement polycentricity using Green indicator and entropy of daily travel flow data, and finally, the balance between agglomeration economies and diseconomies using Correspondence analysis. Findings show that the city has been able to access the market demand of larger and coastal cities, lower production costs due to cheap land prices, land ownership and cheaper labor, and increasing returns become into a specialized furniture market that achieves better performance than larger cities by increasing competition, lowering prices, diversity and competition. In this regard, it is suggested that this concept could be used as support to reconsider the development role of small and medium-sized cities