The role of metformin response in lipid metabolism in patients with recent-onset type 2 diabetes: HbA1c level as a criterion for designating patients as responders or nonresponders to metformin

Background: In this study, we investigated whether response to metformin, the most frequently drug for diabetes treatment, influences the therapeutic effects of antilipidemic medication in newly diagnosed patients with type 2 diabetes mellitus (T2DM). Methods: A total of 150 patients with T2DM were classified into two groups following 3 months of metformin therapy (1000mg twice daily): responders (patients showing >1% reduction in HbA1c from baseline) and nonresponders (patients showing <1% reduction in HbA1c from baseline). The patients received atorvastatin 20 mg, gemfibrozil 300 mg, or atorvastatin 20 mg and gemfibrozil 300 mg daily. Principal Findings: HbA1c and fasting glucose levels were significantly different between baseline and 3 months among responders receiving atorvastatin; however, these differences were not statistically significant in nonresponders. Atherogenic ratios of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LDL-C/HDL-C; p = 0.002), total cholesterol to HDL-C (TC/HDL-C; p<0.001) and AIP (the atherogenic index of plasma; p = 0.004) decreased significantly in responders receiving atorvastatin than in nonresponders. Moreover, responders receiving atorvastatin showed a significant increase in HDL-C levels but nonresponders receiving atorvastatin did not (p = 0.007). The multivariate model identified a significant association between metformin response (as the independent variable) and TG, TC, HDL-C and LDL-C (dependent variables; Wilk's λ = 0.927, p = 0.036). Conclusions: Metformin response affects therapeutic outcomes of atorvastatin on atherogenic lipid markers in patients newly diagnosed with T2DM. Metformin has a greater impact on BMI in responders of metformin compared to nonresponders. Adoption of better therapeutic strategies for reducing atherogenic lipid markers may be necessary for metformin nonresponders. © 2016 Kashi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

The Rapid and Sensitive Quantitative Determination of Galactose by Combined Enzymatic and Colorimetric Method: Application in Neonatal Screening

The quantitative measurement of galactose in blood is essential for the early diagnosis, treatment, and dietary monitoring of galactosemia patients. In this communication, we aimed to develop a rapid, sensitive, and cost-effective combined method for galactose determination in dry blood spots. This procedure was based on the combination of enzymatic reactions of galactose dehydrogenase (GalDH), dihydrolipoyl dehydrogenase (DLD), and alkaline phosphates with a colorimetric system. The incubation time and the concentration of enzymes used in new method were also optimized. The analytical performance was studied by the precision, recovery, linearity, and sensitivity parameters. Statistical analysis was applied to method comparison experiment. The regression equation and correlation coefficient (R2) were Y = 0.0085x + 0.032 and R2 = 0.998, respectively. This assay exhibited a recovery in the range of 91.7–114.3 % and had the limit detection of 0.5 mg/dl for galactose. The between-run coefficient of variation (CV) was between 2.6 and 11.1 . The within-run CV was between 4.9 and 9.2 . Our results indicated that the new and reference methods were in agreement because no significant biases exist between them. Briefly, a quick and reliable combined enzymatic and colorimetric assay was presented for application in newborn mass screening and monitoring of galactosemia patients. © 2016 Springer Science+Business Media New Yor

The complex combination of COVID-19 and diabetes: pleiotropic changes in glucose metabolism

Purpose: Angiotensin converting enzyme 2 (ACE2) is the door for SARS-CoV-2, expressed in critical metabolic tissues. So, it is rational that the new virus causes pleiotropic alterations in glucose metabolism, resulting in the complication of pre-existing diabetes’s pathophysiology or creating new disease mechanisms. However, it seems that less attention has been paid to this issue. This review aimed to highlight the importance of long-term consequences and pleiotropic alterations in glucose metabolism following COVID-19 and emphasize the need for basic and clinical research in metabolism and endocrinology. Results: SARS-CoV-2 shifts cellular metabolism from oxidative phosphorylation to glycolysis, which leads to a decrease in ATP generation. Together with metabolic imbalance, the impaired immune system elevates the susceptibility of patients with diabetes to this deadly virus. SARS-CoV-2-induced metabolic alterations in immune cells can result in hyper inflammation and a cytokine storm. Metabolic dysfunction may affect therapies against SARS-CoV-2 infection. The effective control of metabolic complications could prove useful therapeutic targets for combating COVID-19. It is also necessary to understand the long-term consequences that will affect patients with diabetes who survived COVID-19. Conclusions: Since the pathophysiology of COVID-19 is still mostly unknown, identifying the metabolic mechanisms contributing to its progression is essential to provide specific ways to prevent and improve this dangerous virus’s detrimental effects. The findings show that the new virus may induce new-onset diabetes with uncertain metabolic and clinical features, supporting a potential role of COVID-19 in the development of diabetes

The complex combination of COVID-19 and diabetes: pleiotropic changes in glucose metabolism

PURPOSE: Angiotensin converting enzyme 2 (ACE2) is the door for SARS-CoV-2, expressed in critical metabolic tissues. So, it is rational that the new virus causes pleiotropic alterations in glucose metabolism, resulting in the complication of pre-existing diabetes's pathophysiology or creating new disease mechanisms. However, it seems that less attention has been paid to this issue. This review aimed to highlight the importance of long-term consequences and pleiotropic alterations in glucose metabolism following COVID-19 and emphasize the need for basic and clinical research in metabolism and endocrinology.RESULTS: SARS-CoV-2 shifts cellular metabolism from oxidative phosphorylation to glycolysis, which leads to a decrease in ATP generation. Together with metabolic imbalance, the impaired immune system elevates the susceptibility of patients with diabetes to this deadly virus. SARS-CoV-2-induced metabolic alterations in immune cells can result in hyper inflammation and a cytokine storm. Metabolic dysfunction may affect therapies against SARS-CoV-2 infection. The effective control of metabolic complications could prove useful therapeutic targets for combating COVID-19. It is also necessary to understand the long-term consequences that will affect patients with diabetes who survived COVID-19.CONCLUSIONS: Since the pathophysiology of COVID-19 is still mostly unknown, identifying the metabolic mechanisms contributing to its progression is essential to provide specific ways to prevent and improve this dangerous virus's detrimental effects. The findings show that the new virus may induce new-onset diabetes with uncertain metabolic and clinical features, supporting a potential role of COVID-19 in the development of diabetes

Purification and Characterization of Recombinant Darbepoetin Alfa from Leishmania tarentolae

Darbepoetin alfa is a biopharmaceutical glycoprotein that stimulates erythropoiesis and is used to treat anemia, which associated with renal failure and cancer chemotherapy. We herein describe the structural characterization of recombinant darbepoetin alfa produced by Leishmania tarentolae T7-TR host. The DNA expression cassette was integrated into the L. tarentolae genome through homologous recombination. Transformed clones were selected by antibiotic resistance, diagnostic PCRs, and protein expression analysis. The structure of recombinant darbepoetin alfa was analyzed by isoelectric focusing, ultraviolet–visible spectrum, and circular dichroism (CD) spectroscopy. Expression analysis showed the presence of a protein band at 40 kDa, and its expression level was 51.2 mg/ml of culture medium. Darbepoetin alfa have 5 isoforms with varying degree of sialylation. The UV absorption and CD spectra were analogous to original drug (Aranesp), which confirmed that the produced protein was darbepoetin alfa. Potency test results revealed that the purified protein was biologically active. In brief, the structural and biological characteristics of expressed darbepoetin alfa were very similar to Aranesp which has been normally expressed in CHO. Our data also suggest that produced protein has potential to be developed for clinical use. © 2016, Springer Science+Business Media New York

Cloning and expression of codon-optimized recombinant darbepoetin alfa in Leishmania tarentolae T7-TR

Darbepoetin alfa is an engineered and hyperglycosylated analog of recombinant human erythropoietin (EPO) which is used as a drug in treating anemia in patients with chronic kidney failure and cancer. This study desribes the secretory expression of a codon-optimized recombinant form of darbepoetin alfa in Leishmania tarentolae T7-TR. Synthetic codon-optimized gene was amplified by PCR and cloned into the pLEXSY-I-blecherry3 vector. The resultant expression vector, pLEXSYDarbo, was purified, digested, and electroporated into the L. tarentolae. Expression of recombinant darbepoetin alfa was evaluated by ELISA, reverse-transcription PCR (RT-PCR), Western blotting, and biological activity. After codon optimization, codon adaptation index (CAI) of the gene raised from 0.50 to 0.99 and its GC content changed from 56 to 58. Expression analysis confirmed the presence of a protein band at 40 kDa. Furthermore, reticulocyte experiment results revealed that the activity of expressed darbepoetin alfa was similar to that of its equivalent expressed in Chinese hamster ovary (CHO) cells. These data suggested that the codon optimization and expression in L. tarentolae host provided an efficient approach for high level expression of darbepoetin alfa. © 2015 Elsevier Ltd. All rights reserved

The effect of the mother's heartbeat sound on physiological parameters and pain intensity after blood sampling in neonates in the intensive care unit : A randomized controlled clinical trial

Author's accepted version (postprint).This is an Accepted Manuscript of an article published by Elsevier in Journal of Neonatal Nursing on 30/07/2020.Available online: https://reader.elsevier.com/reader/sd/pii/S1355184120301071?token=9849B201D2679C1FB92FE2628EF5652235C327C76AF943D7D29CDB3822DE6B5428F4184CE7B38F9BD0D507B9DB549CFDacceptedVersio

Neurocognitive Manifestations of SARSCoV2: A Narrative Review of Mechanisms

Since the outbreak of COVID-19 that is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) in 2020 throughout the world, a lot of aspects of people’s lives are affected includingtheir psychological status. Follow-up assessment of survivors of this infection showed that theyhad multiple psychological disorders including depression, panic attacks, obsessive compulsivedisorder, and post-traumatic stress disorder. It is estimated that more than one-third of patients withCOVID-19 experience neuropsychiatric symptoms, including headache, paresthesia, and disturbedconsciousness. Among patients affected by COVID-19, there are different mechanisms that cancause cognitive dysfunction. COVID-19 can affect the central nervous system (CNS) directly byinvasion and indirectly by inducing hypoxia, inflammation, and delirium. The pandemic and fearof infection can also cause anxiety which impairs the cognition as well. By assessing the patients’cognition and knowing the higher probable cause of cognitive impairment, we can form a betterstrategy to better treat the impairment. Cognitive behavioral therapy can be effective in reducing theanxiety and cognitive rehabilitation therapy (CRT) can be used to lower the detrimental effects ofcognitive impairment caused by COVID-19

Executive Function Assessment in Patients With Idiopathic Generalized Epilepsy: Applyingthe Frontal Assessment Battery

&nbsp; &nbsp;Background: Executive dysfunction is seen in idiopathic generalized epilepsy (IGE). The Frontal Assessment Battery (FAB) is a short neuropsychological instrument designed in clinical settings to evaluate frontal lobe activity. We aimed to assess the clinical use of FAB in patients with IGE for to detect executive impairment. Method: In this study, 30 patients with IGE and 30 age- and sex-matched healthy controls were included. The presence and severity of executive dysfunction was investigated with FAB. Cognitive flexibility, decision making, working memory, and general intelligence level were examined using Wisconsin Card Sorting Task (WCST), Iowa Gambling Task (IGT), N-back, and Wechsler Adult Intelligence Scale, respectively. In patients with IGE, FAB results were related to their neuropsychological task performance. Results: The FAB score in patients with IGE was significantly lower compared to healthy participants. In motor programming tasks, patients with IGE performed substantially worse. However, no correlation was found between FAB and neuropsychological task and clinical characteristics. Conclusion: Executive dysfunction was present in patients with IGE and FAB may be used in these patients as an effective tool for evaluating frontal lobe function

Microplastic appraisal of soil, water, ditch sediment and airborne dust: the case of agricultural systems

Although microplastic pollution jeopardizes both terrestrial and aquatic ecosystems, the movement of plastic particles through terrestrial environments is still poorly understood. Agricultural soils exposed to different managements are important sites of storage and dispersal of microplastics. This study aimed to identify the abundance, distribution, and type of microplastics present in agricultural soils, water, airborne dust, and ditch sediments. Soil health was also assessed using soil macroinvertebrate abundance and diversity. Sixteen fields were evaluated, 6 of which had been exposed to more than 5 years of compost application, 5 were exposed to at least 5 years of plastic mulch use, and 5 were not exposed to any specific management (controls) within the last 5 years. We also evaluated the spread of microplastics from the farms into nearby water bodies and airborne dust. We found 11 types of microplastics in soil, among which Light Density Polyethylene (LDPE) and Light Density Polyethylene covered with pro-oxidant additives (PAC) were the most abundant. The highest concentrations of plastics were found in soils exposed to plastic mulch management (128.7 ± 320 MPs.g-1 soil and 224.84 ± 488 MPs.g-1 soil, respectively) and the particles measured from 50 to 150 μm. Nine types of microplastics were found in water, with the highest concentrations observed in systems exposed to compost. Farms applying compost had higher LDPE and PAC concentrations in ditch sediments as compared to control and mulch systems; a significant correlation between soil polypropylene (PP) microplastics with ditch sediment microplastics (r2 0.7 p < 0.05) was found. LDPE, PAC, PE (Polyethylene), and PP were the most abundant microplastics in airborne dust. Soil invertebrates were scarce in the systems using plastic mulch. A cocktail of microplastics was found in all assessed matrices