Prevalence and risk factors for subclinical hypothyroidism in older patients with major depressive disorder.

BACKGROUND: Subclinical hypothyroidism (SCH) is highly correlated with major depressive disorder (MDD). However, the prevalence and risk factors for SCH in older patients with MDD have rarely been reported in China. METHODS: This cross-sectional study included 266 older MDD patients with SCH was performed. Clinical and anthropometric, biochemical, and thyroid function data were collected. Depression, anxiety, and psychotic symptoms were assessed using the Hamilton Depression Scale, the Hamilton Anxiety Scale, and the Positive and Negative Syndrome Scale positive subscale, respectively. RESULTS: Among older patients with MDD, the prevalence of SCH was 64.7% (172/266). Compared to patients without SCH, older MDD patients with SCH had a longer disease course and higher TSH, A-TG, A-TPO, HDL-C, LDL-C, TC, FPG, and systolic pressure levels (all P ≤ 0.002). Furthermore, disease progression (OR 1.082, 95% CI 1.020-1.147, P = 0.009), A-TG (OR 1.005, 95% CI 1.001-1.009, P = 0.017), TC (OR 2.024, 95% CI 1.213-3.377, P = 0.007), FPG (OR 2.916, 95% CI 1.637-5.194, P < 0.001), systolic pressure (OR 1.053, 95% CI 1.008-1.100, P = 0.022) were independently associated with SCH, in older patients with MDD. CONCLUSIONS: Our findings suggest a high prevalence of SCH in older patients with MDD. Several demographic and clinical variables were independently associated with SCH in older patients with MDD.

A 96-week, double-blind, randomized controlled trial comparing bexagliflozin to glimepiride as an adjunct to metformin for the treatment of type 2 diabetes in adults.

AIM: To compare the effects of bexagliflozin tablets 20 mg, with those of optimally titrated glimepiride when used to treat adults with type 2 diabetes mellitus (T2DM) inadequately controlled by metformin. METHODS: Adults with type 2 diabetes (n = 426) taking metformin, and with a glycated haemoglobin (HbA1c) level between 53 and 91 mmol/mol [7.0% and 10.5%], were randomized to receive bexagliflozin tablets 20 mg or titrated glimepiride. The primary endpoint was the intergroup difference in the change from baseline to Week 60 in percent HbA1c. Secondary endpoints included changes from baseline in body mass and systolic blood pressure (SBP), and proportion of subjects experiencing severe or documented symptomatic hypoglycaemia. RESULTS: The intergroup difference in percent HbA1c (bexagliflozin minus glimepiride) from baseline to Week 60 was -0.55 mmol/mol (95% confidence interval [CI] -2.30, 1.20)-[-0.05% (-0.21, 0.11)], establishing noninferiority of bexagliflozin to glimepiride by the prespecified margin of 3.83 mmol/mol [0.35%]. Prespecified tests gave, in order, a difference in body mass of -4.31 kg (95% CI -5.10, -3.52; P < 0.0001), a difference in SBP of -6.53 mm Hg (95% CI -10.56, -2.51; P = 0.0008), and an odds ratio of 0.12 (95% CI 0.05, 0.28; P < 0.0001) for severe or documented symptomatic hypoglycaemia. At the follow-up visit the mean difference in estimated glomerular filtration rate (eGFR) between arms was 6.05 mL min-1 per 1.73 m2 (95% CI, 3.24, 8.87; P < 0.0001). CONCLUSIONS: Bexagliflozin was noninferior to glimepiride in lowering HbA1c, was superior to glimepiride for decreases in body mass and SBP, and was associated with significantly fewer hypoglycaemic events than glimepiride. A favourable effect on eGFR was observed.

Bexagliflozin as an adjunct to metformin for the treatment of type 2 diabetes in adults: A 24-week, randomized, double-blind, placebo-controlled trial.

AIM: To evaluate the relative safety and effectiveness of bexagliflozin as an adjunct to metformin for the treatment of type 2 diabetes mellitus. METHODS: In total, 317 participants were randomized to receive bexagliflozin or placebo plus metformin. The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline to week 24, with secondary endpoints for systolic blood pressure (SBP), fasting plasma glucose and weight loss. An open label arm enrolled participants with HbA1c >10.5% and was analysed separately. RESULTS: The mean change in HbA1c was -1.09% (95% CI -1.24%, -0.94%) in the bexagliflozin arm and -0.56% (-0.71%, -0.41%) in the placebo arm, a difference of -0.53% (-0.74%, -0.32%; p < .0001). Excluding observations after rescue medication, the intergroup difference was -0.70% (-0.92, -0.48; p < .0001). The open label group change in HbA1c was -2.82% (-3.23%, -2.41%). Placebo-adjusted changes from baseline SBP, fasting plasma glucose and body mass were -7.07 mmHg (-9.83, -4.32; p < .0001), -1.35 mmol/L (-1.83, -0.86; p < .0001) and -2.51 kg (-3.45, -1.57; p < .0001). Adverse events affected 42.4% and 47.2% of subjects in the bexagliflozin and placebo arms, respectively; fewer subjects in the bexagliflozin arm experienced serious adverse events. CONCLUSIONS: Bexagliflozin produced clinically meaningful improvement in glycaemic control, estimated glomerular filtration rate and SBP when added to metformin in a population of adults with diabetes.

Assay conditions for estimating differences in base excision repair activity with Fpg-modified comet assay.

DNA repair is an essential agent in cancer development, progression, prognosis, and response to therapy. We have adapted a cellular repair assay based on the formamidopyrimidine DNA glycosylase (Fpg)-modified comet assay to assess DNA repair kinetics. The removal of oxidized nucleobases over time (0-480 min) was analyzed in peripheral blood mononuclear cells (PBMCs) and 8 cell lines. DNA damage was induced by exposure to either Ro19-8022 plus visible light or potassium bromate (KBrO3). The initial amount of damage induced by Ro 19-8022 plus light varied between cell lines, and this was apparently associated with the rate of repair. However, the amount of DNA damage induced by KBrO3 varied less between cell types, so we used this agent to study the kinetics of DNA repair. We found an early phase of ca. 60 min with fast removal of Fpg-sensitive sites, followed by slower removal over the following 7 h. In conclusion, adjusting the initial damage at T0 to an equal level can be achieved by the use of KBrO3, which allows for accurate analysis of subsequent cellular DNA repair kinetics in the first hour after exposure.

Unexpected finding of a rare pathogenic germline BRCA1 variant in an intrahepatic cholangiocarcinoma using the Oncomine Focus DNA assay: clinical and diagnostic implications.

BACKGROUND: Cholangiocarcinoma (CCA) is a malignant tumor arising from the epithelial cells of the bile ducts and is the second most common liver cancer after hepatocellular carcinoma. Recently, our Institution launched a Comprehensive Genomic Profiling (CGP) program (named FPG500 program), set up to provide a complete molecular characterization through the TruSight Oncology 500 High Throughput (TSO500HT) solution and samples that do not reach pre-set sample quantity and/or quality thresholds required for TSO500HT, are addressed to Oncomine Focus DNA Assay (OFA) and the Archer's FusionPlex Lung Panel (AFL). METHODS AND RESULTS: Here we report the case of a patient with iCCA enrolled in the FPG500 program and screened by the orthogonal workflow (OFA/AFL). Although BRCA1 is not among the genes declared in the OFA panel, we unexpectedly detected a pathogenic variant in this gene (c.5278-2del, rs878853285). CONCLUSIONS: This case highlights the diagnostic capabilities of CGP, now widely used in both clinical practice and academic setting. The incidental involvement of BRCA1 focuses attention on the role of BRCA genes in biliary tract cancers. Finally, as an orthogonal test confirmed the germline origin of BRCA1 c.5278-2del variant, the germline implications of CGP need to be considered.

Toxicological evaluation of polycrystalline wools in human lung cells.

Aim: Polycrystalline wools (PCW) are included with Refractory ceramic fibers (RCF) in the alumino-silicates family of High Temperature Insulation Wools (HTIW). IARC includes PCW in the ceramic fibers group and considers them as possible human carcinogens (GROUP 2B). Since PCW toxicity is not yet clear, our aim was to evaluate their toxic and inflammatory effects and to compare them with the known RCF effects.Method: We exposed human bronchial (BEAS-2B) and alveolar (A549) cells to 2-100 µg/mL (2.4 × 103-1.2 × 105 fibers/mL; 2.51 × 103-1.26 × 105 fibers/cm2 of PCW and 7.4 × 103-3.7 × 105 fibers/mL; 7.75 × 103-3.87 × 105 fibers/cm2 of RCF) of the tested fibers to evaluate potential viability reduction, apoptosis, membrane damage, direct/oxidative DNA-damage, cytokine release.Results: In A549, PCW did not induce cytotoxicity and apoptosis but they induced significant dose-dependent DNA-damage, although lower than RCF; only RCF induced oxidative effects. PCW also induced an increase in IL-6 release at 100 µg/mL (1.2 × 105 fibers/mL; 1.26 × 105 fibers/cm2). In BEAS-2B, PCW did not induce cell-viability reduction RCF induced a dose-dependent cell-viability decrease. Both fibers show a dose-dependent increase of apoptosis. In BEAS-2B, PCW also induced dose-dependent DNA-damage, although lower than RCF, and slight oxidative effects similar to RCF. PCW also induced an increase of IL-6 release; RCF induced a decrease of IL-8. Summarizing, PCW induce direct-oxidative DNA-damage although to a lower extent than RCF observed by both mass-based and fiber number-based analysis.Conclusion: For the first time, the study shows the potential toxicity of PCW, usually considered safe, and suggests to perform further in vitro studies, also on other cell types, to confirm these findings.

Aluminium(III) Oxide-The Silent Killer of Bacteria.

In this article, we describe the antimicrobial properties of pristine anodised aluminium oxide matrices-the material many consider biologically inert. During a typical anodisation process, chromium and chlorine compounds are used for electropolishing and the removal of the first-step aluminium oxide. Matrices without the use of those harmful compounds were also fabricated and tested for comparison. The antibacterial tests were conducted on four strains of Escherichia coli: K12, R2, R3 and R4. The properties of the matrices were also compared to the three types of antibiotics: ciprofloxacin, bleomycin and cloxacillin using the Minimal Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) tests. Moreover, DNA was isolated from the analysed bacteria which was additionally digested with formamidopyrimidine-DNA glycosylase (Fpg) protein from the group of repair glycosases. These enzymes are markers of modified oxidised bases in nucleic acids produced during oxidative stress in cells. Preliminary cellular studies, MIC and MBC tests and digestion with Fpg protein after modification of bacterial DNA suggest that these compounds may have greater potential as antibacterial agents than the aforementioned antibiotics. The described composites are highly specific for the analysed model Escherichia coli strains and may be used in the future as new substitutes for commonly used antibiotics in clinical and nosocomial infections in the progressing pandemic era. The results show much stronger antibacterial properties of the functionalised membranes on the action of bacterial membranes in comparison to the antibiotics in the Fpg digestion experiment. This is most likely due to the strong induction of oxidative stress in the cell through the breakdown of the analysed bacterial DNA.

The dangerous link between coal dust exposure and DNA damage: unraveling the role of some of the chemical agents and oxidative stress.

Exposure to coal mining dust poses a substantial health hazard to individuals due to the complex mixture of components released during the extraction process. This study aimed to assess the oxidative potential of residual coal mining dust on human lymphocyte DNA and telomeres and to perform a chemical characterization of coal dust and urine samples. The study included 150 individuals exposed to coal dust for over ten years, along with 120 control individuals. The results revealed significantly higher levels of DNA damage in the exposed group, as indicated by the standard comet assay, and oxidative damage, as determined by the FPG-modified comet assay. Moreover, the exposed individuals exhibited significantly shorter telomeres compared to the control group, and a significant correlation was found between telomere length and oxidative DNA damage. Using the PIXE method on urine samples, significantly higher concentrations of sodium (Na), phosphorus (P), sulfur (S), chlorine (Cl), potassium (K), iron (Fe), zinc (Zn), and bromine (Br) were observed in the exposed group compared to the control group. Furthermore, men showed shorter telomeres, greater DNA damage, and higher concentrations of nickel (Ni), calcium (Ca), and chromium (Cr) compared to exposed women. Additionally, the study characterized the particles released into the environment through GC-MS analysis, identifying several compounds, including polycyclic aromatic hydrocarbons (PAHs) such as fluoranthene, naphthalene, anthracene, 7H-benzo[c]fluorene, phenanthrene, pyrene, benz[a]anthracene, chrysene, and some alkyl derivatives. These findings underscore the significant health risks associated with exposure to coal mining dust, emphasizing the importance of further research and the implementation of regulatory measures to safeguard the health of individuals in affected populations.

Aberrant Repair of 8-Oxoguanine in Short DNA Bulges.

The presence of DNA damage can increase the likelihood of DNA replication errors and promote mutations. In particular, pauses of DNA polymerase at the site of damage can lead to polymerase slippage and the formation of 1-2-nucleotide bulges. Repair of such structures using an undamaged DNA template leads to small deletions. One of the most abundant oxidative DNA lesions, 8-oxoguanine (oxoG), was shown to induce small deletions, but the mechanism of this phenomenon is currently unknown. We studied the aberrant repair of oxoG located in one- and two-nucleotide bulges by the Escherichia coli and human base excision repair systems. Our results indicate that the repair in such substrates can serve as a mechanism for fixing small deletions in bacteria but not in humans.

Accumulation of DNA damage alters microRNA gene transcription in Arabidopsis thaliana.

BACKGROUND: MicroRNAs (miRNAs) and other epigenetic modifications play fundamental roles in all eukaryotic biological processes. DNA damage repair is a key process for maintaining the genomic integrity of different organisms exposed to diverse stresses. However, the reaction of miRNAs in the DNA damage repair process is unclear. RESULTS: In this study, we found that the simultaneous mutation of zinc finger DNA 3'-phosphoesterase (ZDP) and AP endonuclease 2 (APE2), two genes that play overlapping roles in active DNA demethylation and base excision repair (BER), led to genome-wide alteration of miRNAs. The transcripts of newly transcribed miRNA-encoding genes (MIRs) decreased significantly in zdp/ape2, indicating that the mutation of ZDP and APE2 affected the accumulation of miRNAs at the transcriptional level. In addition, the introduction of base damage with the DNA-alkylating reagent methyl methanesulfonate (MMS) accelerated the reduction of miRNAs in zdp/ape2. Further mutation of FORMAMIDOPYRIMIDINE DNA GLYCOSYLASE (FPG), a bifunctional DNA glycosylase/lyase, rescued the accumulation of miRNAs in zdp/ape2, suggesting that the accumulation of DNA damage repair intermediates induced the transcriptional repression of miRNAs. CONCLUSIONS: Our investigation indicates that the accumulation of DNA damage repair intermediates inhibit miRNAs accumulation by inhibiting MIR transcriptions.

Association between the cut-off value of the first trimester fasting plasma glucose level and gestational diabetes mellitus: a retrospective study from southern China.

PURPOSE: Our previous studies have suggested that the first trimester fasting plasma glucose (FPG) level is associated with gestational diabetes mellitus (GDM) and is a predictor of GDM. The aim of the present study was to provide valuable insights into the accuracy of the first trimester FPG level in the screening and diagnosis of GDM in southern China. METHODS: This retrospective study included pregnant women who had their first trimester FPG level recorded at 9-13+6 weeks and underwent screening for GDM using the 2-h 75 g oral glucose tolerance test (OGTT) between the 24th and 28th gestational weeks. Differences between the GDM and non-GDM groups were assessed by Student's t test and the chi-squared test according to the nature of the variables. A restricted cubic spine was used to explore the relationship between the first trimester FPG level and the odds ratio (OR) of GDM in pregnant women. Cut-off values of first trimester FPG were determined using receiver operating characteristic (ROC) curves and the area under the curve (AUC), and 95% confidence intervals (CIs), the positive predictive value (PPV) and the negative predictive value (NPV) were calculated. RESULTS: The medical records of 28,030 pregnant women were analysed, and 4,669 (16.66%) of them were diagnosed with GDM. The average first trimester FPG level was 4.62 ± 0.37 mmol/L. The OR of GDM increased with increasing first trimester FPG levels and with a value of first trimester FPG of approximately 4.6 mmol/L, which was equal to 1 (Chi-Square = 665.79, P < 0.001), and then started to increase rapidly afterwards. The ROC curve for fasting plasma glucose in the first trimester (4.735 mmol/L) for predicting gestational diabetes mellitus in pregnant women was 0.608 (95% CI: 0.598-0.617), with a sensitivity of 0.490 and a specificity of 0.676. CONCLUSION: Based on the research, we recommend that all pregnant women undergo FPG testing in the first trimester, particularly at the first antenatal visit. Furthermore, we suggest that the risks of GDM should be given increased attention and management as soon as the first trimester FPG value is more than 4.7 mmol/L. First trimester FPG levels should be considered a screening marker when diagnosing GDM in pregnant women but this needs to be confirmed by more prospective studies. These factors may have a significant impact on the clinical treatment of pregnant women.

Functionalised Anodised Aluminium Oxide as a Biocidal Agent.

In this article, we describe the antimicrobial properties of a new composite based on anodic aluminium oxide (AAO) membranes containing propyl-copper-phosphonate units arranged at a predetermined density inside the AAO channels. The samples were prepared with four concentrations of copper ions and tested as antimicrobial drug on four different strains of Escherichia coli (K12, R2, R3 and R4). For comparison, the same strains were tested with three types of antibiotics using the minimal inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) tests. Moreover, DNA was isolated from the analysed bacteria which was additionally digested with formamidopyrimidine-DNA glycosylase (Fpg) protein from the group of repair glycosases. These enzymes are markers of modified oxidised bases in nucleic acids produced during oxidative stress in cells. Preliminary cellular studies, MIC and MBC tests and digestion with Fpg protein after modification of bacterial DNA suggest that these compounds may have greater potential as antibacterial agents than antibiotics such as ciprofloxacin, bleomycin and cloxacillin. The described composites are highly specific for the analysed model Escherichia coli strains and may be used in the future as new substitutes for commonly used antibiotics in clinical and nosocomial infections in the progressing pandemic era. The results show much stronger antibacterial properties of the functionalised membranes on the action of bacterial membranes in comparison to the antibiotics in the Fpg digestion experiment. This is most likely due to the strong induction of oxidative stress in the cell through the breakdown of the analysed bacterial DNA. We have also observed that the intermolecular distances between the functional units play an important role for the antimicrobial properties of the used material. Hence, we utilised the idea of the 2D solvent to tailor them.

A Novel Biocidal Nanocomposite: Spherical Silica with Silver Ions Anchored at the Surface.

This article is devoted to a novel class of antimicrobial agents: nanocomposites composed of spherical silica and silver ions located at the silica's surface with the assumed distribution. Such materials are in high demand due to the increasing threat from bacterial strains that are becoming resistant to currently known antibiotics. In particular, we focus on materials that make it possible to limit the growth of bacterial colonies on a variety of tactile surfaces. In this paper, we present a method for preparing a silica-based nanocomposite containing silver ions and the analysis of their antimicrobial properties. Our research revealed that the presence of tested nanocomposite induces very high oxidative stress in the bacteria cell, damaging and modifying bacterial DNA, creating oxidized guanines, cytosines, or adenines, which causes its very rapid destruction, leading to cell death.

The Synthesis and Evaluation of Diethyl Benzylphosphonates as Potential Antimicrobial Agents.

The impact of substituent at phenyl ring of diethyl benzylphosphonate derivatives on cytotoxic activity was studied. The organophosphonates were obtained based on developed palladium-catalyzed α, ß-homodiarylation of vinyl esters protocol. The new synthetic pathway toward 1,2-bis(4-((diethoxyphosphoryl)methyl)phenyl)ethyl acetate was proposed which significantly improves the overall yield of the final product (from 1% to 38%). Several newly synthesized organophosphonates were tested as new potential antimicrobial drugs on model Escherichia coli bacterial strains (K12 and R2-R3). All tested compounds show the highest selectivity and activity against K12 and R2 strains. Preliminary cellular studies using MIC and MBC tests and digestion of Fpg after modification of bacterial DNA suggest that selected benzylphosphonate derivatives may have greater potential as antibacterial agents than typically used antibiotics such as ciprofloxacin, bleomycin and cloxacillin. These compounds are highly specific for pathogenic E. coli strains based on the model strains used and may be engaged in the future as new substitutes for commonly used antibiotics, which is especially important due to the increasing resistance of bacteria to various drugs and antibiotics.

Efficacy and safety of hydroxychloroquine as add-on therapy in uncontrolled type 2 diabetes patients who were using two oral antidiabetic drugs.

OBJECTIVE: To evaluate the Safety and Efficacy of Hydroxychloroquine as add-on therapy in uncontrolled type 2 diabetes patients who were using two oral antidiabetic drugs. MATERIALS AND METHODS: This was a double blind, placebo controlled, parallel group study in 304 inadequately controlled type 2 diabetes (T2DM) subjects with two oral antidiabetic drugs (glimepiride 4 mg and metformin 500 mg) were randomised to hydroxychloroquine (HCQ) 200 mg, 300 mg, 400 mg once daily (OD) or placebo. Dose of hydroxychloroquine was selected as per body weight of the subject. Primary end point was glycated haemoglobin (HbA1c) change at week 12 from baseline. Secondary endpoint was change in fasting plasma glucose (FPG), post prandial plasma glucose (PPG), body weight and any adverse reaction including no of hypoglycemic events, as well as a change in the percentage of subjects with A1C < 7.0% and > 6.5% after 12 weeks of treatment.. In follow-up of 400 mg once daily was once again divided to 200 mg twice daily (BD) to study the effect on tolerability profile for further 12 weeks. RESULTS: Hydroxychloroquine was associated with significant reduction in HbA1c from baseline (7-8.5%) in 12 weeks -0.78%, -0.91% and 1.2% for hydroxychloroquine 200 mg, 300 mg and 400 mg OD, respectively, versus 0.13% with placebo (P < 0.005). FPG and PPG were reduced by -25 to -38 mg/dl and 34-53 mg/dl, respectively. Body weight also reduced in each group of HCQ. Hypoglycemia was reported only with 300 mg (1.2%) and 400 mg (2.1%) group of HCQ. It was observed that patients who complains with mild GI disturbance with HCQ 400 mg glycemic efficacy was maintained with 200 mg BD with significant relief of the symptoms. CONCLUSION: Hydroxychloroquine added to sulphonylurea and metformin, improves glycemic control significantly in T2DM patients. Glycemic effect of different dose of hydroxychloroquine is dose dependent. The safety/tolerability profile of hydroxychloroquine was favourable except GI disturbance which is more frequent with 400 mg. This can be avoided with 200 mg BD without compromise on efficacy.

Study on release suppression of cinnamaldehyde from κ-carrageenan gel by HR-MASNMR and pulsed field gradient NMR (PFG-NMR).

Aiming toward the production and characterization of delicious and functional gel foods, this communication studies the flavor release from cinnamon-containing κ-carrageenan gel. Cinnamaldehyde, which provides the flavor of cinnamon, was released in a trace amount from the gel and detected by flame ionization detector gas chromatography. The retention of cinnamaldehyde in κ-carrageenan gel and the interaction between flavor and polysaccharide were investigated by high-resolution magic-angle spinning nuclear magnetic resonance (HR-MAS NMR) and pulsed-field gradient NMR (PFG NMR). The intact cinnamaldehyde in the gel was also observed by HR-MAS NMR. The relative mobility difference of the flavor and polysaccharide molecules was observed from the diffusion-ordered NMR spectrum of PFG NMR.

Visit-to-visit fasting plasma glucose variability is associated with left ventricular adverse remodeling in diabetic patients with STEMI.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are predisposed to poor cardiovascular outcomes after ST-segment elevation myocardial infarction (STEMI). Left ventricular adverse remodeling (LVAR) triggered upon myocardial infarction is recognized as the predominant pathological process in the development of heart failure. In the present study, we sought to investigate whether visit-to-visit fasting plasma glucose (FPG) variability is a potential predictor of LVAR in T2DM patients after STEMI. METHODS: From January 2014 to December 2018 in Ruijin Hospital, T2DM patients with STEMI who underwent primary percutaneous coronary intervention were consecutively enrolled and followed up for ~ 12 months. The changes in left ventricular geometric and functional parameters between baseline and 12-month follow-up were assessed by echocardiography. The incidence of LVAR, defined as 20% increase in indexed left ventricular end-diastolic volume (LVEDV), and its relationship with visit-to-visit FPG variability were analyzed. Multivariate regression models were constructed to test the predictive value of FPG variability for post-infarction LVAR. RESULTS: A total of 437 patients with type 2 diabetes and STEMI were included in the final analysis. During a mean follow-up of 12.4 ± 1.1 months, the incidence of LVAR was 20.6% and mean enlargement of indexed LVEDV was 3.31 ± 14.4 mL/m2, which was significantly increased in patients with higher coefficient variance (CV) of FPG (P = 0.002) irrespective of baseline glycemic levels. In multivariate analysis, FPG variability was independently associated with incidence of post-infarction LVAR after adjustment for traditional risk factors, baseline HbA1c as well as mean FPG during follow-up (OR: 3.021 [95% CI 1.081-8.764] for highest vs. lowest tertile of CV of FPG). Assessing FPG variability by other two measures, including standard deviation (SD) and variability independent of the mean (VIM), yielded similar findings. CONCLUSIONS: This study suggests that visit-to-visit FPG variability is an independent predictor of incidence of LVAR in T2DM patients with STEMI. Trial registration Trials number, NCT02089360; registered on March 17,2014.

Thiopurine Derivative-Induced Fpg/Nei DNA Glycosylase Inhibition: Structural, Dynamic and Functional Insights.

DNA glycosylases are emerging as relevant pharmacological targets in inflammation, cancer and neurodegenerative diseases. Consequently, the search for inhibitors of these enzymes has become a very active research field. As a continuation of previous work that showed that 2-thioxanthine (2TX) is an irreversible inhibitor of zinc finger (ZnF)-containing Fpg/Nei DNA glycosylases, we designed and synthesized a mini-library of 2TX-derivatives (TXn) and evaluated their ability to inhibit Fpg/Nei enzymes. Among forty compounds, four TXn were better inhibitors than 2TX for Fpg. Unexpectedly, but very interestingly, two dithiolated derivatives more selectively and efficiently inhibit the zincless finger (ZnLF)-containing enzymes (human and mimivirus Neil1 DNA glycosylases hNeil1 and MvNei1, respectively). By combining chemistry, biochemistry, mass spectrometry, blind and flexible docking and X-ray structure analysis, we localized new TXn binding sites on Fpg/Nei enzymes. This endeavor allowed us to decipher at the atomic level the mode of action for the best TXn inhibitors on the ZnF-containing enzymes. We discovered an original inhibition mechanism for the ZnLF-containing Fpg/Nei DNA glycosylases by disulfide cyclic trimeric forms of dithiopurines. This work paves the way for the design and synthesis of a new structural class of inhibitors for selective pharmacological targeting of hNeil1 in cancer and neurodegenerative diseases.

Effects of magnesium supplementation on carotid intima-media thickness and metabolic profiles in diabetic haemodialysis patients: a randomised, double-blind, placebo-controlled trial.

This study evaluated the effects of Mg administration on carotid intima-media thickness (CIMT), glycaemic control and markers of cardio-metabolic risk in diabetic haemodialysis (HD) patients. This randomised, double-blind, placebo-controlled clinical trial was conducted in fifty-four diabetic HD patients. Participants were randomly divided into two groups to take either 250 mg/d Mg as magnesium oxide (n 27) or placebo (n 27) for 24 weeks. Mg supplementation resulted in a significant reduction in mean (P<0·001) and maximum levels of left CIMT (P=0·02) and mean levels of right CIMT (P=0·004) compared with the placebo. In addition, taking Mg supplements significantly reduced serum insulin levels (ß=-9·42 pmol/l; 95% CI -14·94, -3·90; P=0·001), homoeostasis model of assessment-insulin resistance (ß=-0·56; 95 % CI -0·89, -0·24; P=0·001) and HbA1c (ß=-0·74 %; 95 % CI -1·10, -0·39; P<0·001) and significantly increased the quantitative insulin sensitivity check index (ß=0·008; 95 % CI 0·002, 0·01; P=0·002) compared with the placebo. In addition, Mg administration led to a significant reduction in serum total cholesterol (ß=-0·30 mmol/l; 95% CI -0·56, -0·04; P=0·02), LDL-cholesterol (ß=-0·29 mmol/l; 95% CI -0·52, -0·05; P=0·01), high-sensitivity C-reactive protein (hs-CRP) (P<0·001) and plasma malondialdehyde (MDA) (P=0·04) and a significant rise in plasma total antioxidant capacity (TAC) levels (P<0·001) compared with the placebo. Overall, we found that taking Mg for 24 weeks by diabetic HD patients significantly improved mean and maximum levels of left and mean levels of right CIMT, insulin metabolism, HbA1c, total cholesterol and LDL-cholesterol, hs-CRP, TAC and MDA levels.

The efficacy of omega-3 fatty acid for gestational diabetes: a meta-analysis of randomized controlled trials.

INTRODUCTION: The efficacy of omega-3 fatty acid to treat gestational diabetes remains controversial. We conduct a systematic review and meta-analysis to explore the influence of omega-3 fatty acid versus placebo on gestational diabetes. METHODS: We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through March 2018 for randomized controlled trials (RCTs) assessing the effect of omega-3 fatty acid versus placebo on gestational diabetes. This meta-analysis is performed using the random-effect model. RESULTS: Five RCTs are included in the meta-analysis. Overall, compared with control group for gestational diabetes, omega-3 fatty acid can significantly reduce fasting plasma glucose (FPG) (mean difference (MD) = -4.91; 95% confidence interval (CI) = -8.16 to -1.66; p = .003), homeostatic model of assessment for insulin resistance (HOMA-IR, MD = -0.99; 95% CI = -1.61 to -0.37; p = .002), high sensitivity C-reactive protein (hs-CRP, MD = -1.43; 95% CI = -2.54 to -0.31; p = .01), but has no remarkable influence on preterm delivery (RR = 1.61; 95% CI = 0.36-7.16; p = .53), gestational age (MD = 0.09; 95% CI = -0.01 to 0.20; p = .08), macrosomia (RR = 0.64; 95% CI = 0.26-1.62; p = .3), newborn weight (MD = 3.37; 95% CI = -15.75 to 22.50; p = .73), and 5-min Apgar score (MD = 0; 95% CI = -0.02 to 0.02; p = .92). CONCLUSIONS: Omega-3 fatty acids is associated with significantly reduced FPG, HOMA-IR, and hs-CRP in patients with gestational diabetes.