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Genome-scale metabolic models (GEMs) are promising computational tools that contribute to elucidating host-virus interactions at the system level and developing therapeutic strategies against viral infection. In this study, the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on liver metabolism was investigated using integrated GEMs of human hepatocytes and SARS-CoV-2. They were generated for uninfected and infected hepatocytes using transcriptome data. Reporter metabolite analysis resulted in significant transcriptional changes around several metabolites involved in xenobiotics, drugs, arachidonic acid, and leukotriene metabolisms due to SARS-CoV-2 infection. Flux balance analysis and minimization of metabolic adjustment approaches unraveled possible virus-induced hepatocellular reprogramming in fatty acid, glycerophospholipid, sphingolipid cholesterol, and folate metabolisms, bile acid biosynthesis, and carnitine shuttle among others. Reaction knockout analysis provided critical reactions in glycolysis, oxidative phosphorylation, purine metabolism, and reactive oxygen species detoxification subsystems. Computational analysis also showed that administration of dopamine, glucosamine, D-xylose, cysteine, and ( R )-3-hydroxybutanoate contributes to alleviating viral infection. In essence, the reconstructed host-virus GEM helps us understand metabolic programming and develop therapeutic strategies to battle SARS-CoV-2., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Carpal tunnel syndrome (CTS) is seen in 5% of the population and 14%-30% in diabetics. Although electrophysiological tests are used as the gold standard method in the diagnosis, alternative methods are being studying. We aimed to investigate whether the measurement of median nerve cross-sectional area (CSA) by ultrasound is associated with the presence and severity of CTS. This prospective, cross-sectional observational study includes 128 randomly selected T2DM patients. Electrodiagnostic study was performed for all patients to diagnose CTS. Median nerve CSA were measured with ultrasound examination. The severity of the CTS was determined by Padua method. Among 128 diabetes mellitus (DM) patients, 54 (28%) had CTS and 53 (41%) had diabetic peripheral polyneuropathy. The mean duration of DM was 11.55 years. Median nerve CSAs of the patients were significantly higher in patients with CTS (CTS (-): 10.47 ± 2.67 vs CTS: (+) 12.37 ± 3.17; p < 0.001). Median nerve CSA cutoff value of >10 mm 2 predicts the diagnosis of CTS. However, minimal, mild, and moderate CTS groups had similar CSA according to Padua classification (p > 0.05 for all). CSA measurement with ultrasonography can be used as an effective method in diagnosing severe CTS disease. However, median nerve CSA values should not be used to reveal the severity of CTS, in order not to miss the demonstration of minimal, mild, and moderate groups, as well as being an indicator of only the severe CTS group.

Background: Preliminary data suggest that patients with comorbidities are more susceptible to severe COVID-19 infection. However, data regarding the presence of metabolic syndrome (MetS) in patients with COVID-19 are scarce., Aim: In the present study, we aim to investigate the association between MetS components and disease severity in hospitalized COVID-19 patients., Methods: We conducted a prospective observational study of 90 hospitalized patients with COVID-19 pneumonia at a tertiary hospital. The study population consisted of inpatients who tested positive by the reverse transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2. Patients with critical COVID-19 disease on admission were excluded. Adult Treatment Panel III of the National Cholesterol Education Program (NCEP-ATP III) criteria were used to define MetS. Laboratory analysis and thorax CT were performed on admission., Results: 90 patients, 60 moderate and 30 severe COVID-19 patients, included in the study. The percentage of MetS cases was higher among severe COVID-19 patients ( p =0.018). Of the MetS criteria fasting blood glucose ( p =0.004), triglycerides ( p =0.007) were significantly higher in patients with severe COVID-19 disease with no statistical significance found in waist circumference (WC) ( p =0.348), systolic blood pressure ( p =0.429), and HDL-C levels ( p =0.263) between two groups. Body mass index (BMI) values were similar in both severe and moderate cases ( p =0.854). In logistic regression analysis, serum triglycerides ( p =0.024), HDL-C ( p =0.006), and WC ( p =0.004) were found as independent prognostic factor for severe COVID-19 infection., Conclusion: Severe COVID-19 patients have higher rates of MetS. Serum triglycerides, HDL-C, and WC have an impact on disease severity in COVID-19., Competing Interests: All authors declare there are no conflicts of interest in this study., (Copyright © 2022 Hande Erman et al.)

Objective: This study aimed to investigate the QT, QTc, and QTc dispersion changes that may occur with the use of hydroxychloroquine (HCQ), favipiravir, and moxifloxacin in combination or alone in COVID 19 patients., Methods: This study was retrospectively conducted on 193 inpatients diagnosed with COVID-19. We divided the patients into four separate groups due to their medications as, group-1: favipiravir, group-2: favipiravir + HCQ, group-3: favipiravir + moxifloxacin, and group-4: favipiravir + moxifloxacin + HCQ. We recorded their pre and post-treatment QT parameters of each group and evaluated the changes of these parameters with the SPSS statistical program., Results: The mean age of the patients was 63.1±17.7. In group 1 and 2, although there were slight changes in QT parameters, these results were not statistically significant. In group 3, significant increases in QT and QTc dispersion occurred (p=0.005 and p=0.018). In the 4 th group where the triple therapy was applied, there was a significant increase only in the QTc values (p=0.027). When we compared the changes of QT parameters for each group, a significant difference was found in ΔQTc dispersion, and post hoc analysis showed that it was due to changes in the third group (p=0.047)., Conclusion: We thought that, if there is a COVID-19 infection with an additional bacterial infection, and if there is a need of using moxifloxacin alone or together with HCQ, additional risk factors that may cause QT interval prolongation should be reviewed and ECG monitoring of the patients should be performed during the treatment period., Competing Interests: No conflict of interest was declared by the authors., (© Copyright 2022 by Istanbul Provincial Directorate of Health.)

Objective: To evaluate whether normalisation of serum thyroid-stimulating hormonelevels with levothyroxine is related with metabolic parameters and psychologic wellbeing., Methods: The observational, case-control study was conducted from to May to July 2019 in the outpatient thyroid clinics of Fatih Sultan Mehmet Education and Research Hospital, Istanbul, Turkey, and comprised of hypothyroid patients in the euthyroid state with levothyroxine treatment and euthyroid controls. Psychological wellbeing was assessed using the General Health Questionnaire-12, and metabolic parameters with lipid levels and body composition were analysed for both the groups. Data was analysed using SPSS 25., Results: Of the 159 subjects, 110(69%) were cases with a mean age of 50.1±11.7 years, and 49(31%) were controls with a mean age of 47.3±15.2 years. There was no significant difference related to thyroid-stimulating hormone levels between the groups (p=0.191). Free throxine levels were significantly higher in the cases, while free triiodothyroinine levels were higher in the controls (p<0.001). Total cholesterol and triglycerides levels were significantly higher in the cases than the controls (p<0.05). The cases had lower basal metabolic rate and fat free mass than the controls, but the difference was not significant (p>0.05). The cases scored higher in terms of wellbeing than the controls, but the difference was not significant (p>0.05)., Conclusions: Thyroid hormone replacement needs to be adjusted to provide a satisfactory treatment for hypothyroid patients with normal thyroid-stimulating hormone levels who remain clinically and biochemically asymptomatic. In symptomatic patients, peripheral parameters of hypothyroidism, such as lipid levels, physiological symptoms and quality of life, might be useful in determining the levothyroxine dose and bringing the thyroid-stimulating hormone level within the normal range.

Background: While the relation of mean platelet volume (MPV) with inflammatory diseases is obvious, its role in nonalcoholic fatty liver disease (NAFLD) without cardiovascular comorbidities, obesity and diabetes mellitus is not clear., Methods: A total of 249 patients (nonobese, nondiabetic and not having cardiac diseases) who underwent an abdominal ultrasonography assessment were enrolled. They were divided according to the absence (group 1) or presence (group 2) of hepatic steatosis. The patients with steatosis were further divided according to the severity of steatosis as group 2a (grade 1), 2b (grade 2) and 2c (grade 3). The demographic and laboratory features were compared between groups., Results: Hepatic steatosis was absent in 120 patients and detected in 129 patients (grade 1, 2, 3 hepatic steatosis in 75, 49 and 5 patients, respectively). BMI, aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio and serum AST, ALT, triglyceride levels were significantly higher in group 2 than in group 1 (P < 0.001, P < 0.001, P < 0.001, P = 0.005, P < 0.001, respectively). BMI, serum AST and triglyceride levels were significant factors for NAFLD (P < 0.001, P = 0.018, P = 0.001). MPV was neither different between groups (P > 0.05) nor a predictor factor for NAFLD (P > 0.05)., Conclusion: MPV is a useless parameter to detect NAFLD without cardiovascular comorbidities, obesity and diabetes mellitus., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: We aimed to compare the effects of blood groups and Rh factor on the development of coronavirus-19 disease (COVID-19) with all aspects such as clinical course, inflammatory parameters, and organ-specific biochemical parameters with a significant number of patients., Methods: This multicenter study was carried out retrospectively on 3551 patients hospitalized with the diagnosis of COVID-19 and whose blood groups were recorded during the time of hospitalization. As control groups, 22133 individuals' medical data who were admitted to the blood bank affiliated with our hospitals during the last year was used. The differences between the blood groups and clinical characteristics were analyzed., Results: Of the 3551 patients, A Rh (+) blood group was found to be in a higher ratio in the case group than controls, with increased risk to be infected (case: 41.3% vs. control: 38.8%), (OR 1.113; 95% CI: 1.036-1.197; p=0.003). Meanwhile O Rh (+) blood group ratios were significantly lower in the case group than in the control group (case: 26% vs. control: 28.3%) (OR 0.862; 95% CI: 0.823-0.966; p=0.005). There was no significant difference between blood groups in terms of admission to the intensive care units and mortality, it was observed that patients with AB Rh (+) blood group have a greater risk for intubation than others (OR: 1.467; 95% CI: 1.040-2.071; p=0.028)., Conclusion: We demonstrated that people with blood group A Rh (+) more susceptible to COVID-19, whereas blood group 0 Rh (+) have a protective effect against the infection. Once a person has been infected with severe acute respiratory syndrome coronavirus 2, we should be mindful that patients with blood group AB Rh (+) would be prone to intubation more than other blood groups., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (Copyright: © 2021 by Istanbul Northern Anatolian Association of Public Hospitals.)

Pathogens give rise to a wide range of diseases threatening global health and hence drawing public health agencies' attention to establish preventative and curative solutions. Genome-scale metabolic modeling is ever increasingly used tool for biomedical applications including the elucidation of antibiotic resistance, virulence, single pathogen mechanisms and pathogen-host interaction systems. With this approach, the sophisticated cellular system of metabolic reactions inside the pathogens as well as between pathogen and host cells are represented in conjunction with their corresponding genes and enzymes. Along with essential metabolic reactions, alternate pathways and fluxes are predicted by performing computational flux analyses for the growth of pathogens in a very short time. The genes or enzymes responsible for the essential metabolic reactions in pathogen growth are regarded as potential drug targets, as a priori guide to researchers in the pharmaceutical field. Pathogens alter the key metabolic processes in infected host, ultimately the objective of these integrative constraint-based context-specific metabolic models is to provide novel insights toward understanding the metabolic basis of the acute and chronic processes of infection, revealing cellular mechanisms of pathogenesis, identifying strain-specific biomarkers and developing new therapeutic approaches including the combination drugs. The reaction rates predicted during different time points of pathogen development enable us to predict active pathways and those that only occur during certain stages of infection, and thus point out the putative drug targets. Among others, fatty acid and lipid syntheses reactions are recent targets of new antimicrobial drugs. Genome-scale metabolic models provide an improved understanding of how intracellular pathogens utilize the existing microenvironment of the host. Here, we reviewed the current knowledge of genome-scale metabolic modeling in pathogen cells as well as pathogen host interaction systems and the promising applications in the extension of curative strategies against pathogens for global preventative healthcare., (Copyright © 2020 Sertbas and Ulgen.)

Background: Increased mammographic breast density (MBD) is known to be associated with an increased risk of developing breast cancer. Aims: In this study, we aimed to research the possible relationship between MBD and metformin use in postmenopausal women diagnosed with type 2 diabetes mellitus (T2DM). Method: The patients were divided into two groups: women with T2DM and who were on metformin and women who were newly diagnosed with T2DM and had not yet taken metformin. MBD types are evaluated by a specialist radiologist. Results: Among the 74 women, 32 (43.2%) were in the group that did not use metformin and 42 (56.8%) were in the group of patients using metformin. The duration of breastfeeding ( p  = .0003), fasting blood glucose ( p  = .0003) and HbA1c ( p  = .0006) were statistically significantly higher in the group not using metformin. The quantitative mean ranks of the group members' MBD's were 41.81 in the metformin naïve group and 34.21 in the group using metformin ( p  = .12). Conclusions: In conclusion, metformin has no statistically significant effect on MBD in postmenopausal female patients with T2DM.

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Objective: Diabetes is one of the primary diagnoses for admission to home health care units. Although there are many studies about elderly diabetic patients, there are not many studies on home care patients with diabetes. The present study aims to analyze the current status of diabetic home care patients with their biochemical data and medications., Methods: This was a retrospective study, including 256 diabetic patients who were following up by the Home Health Unit of Istanbul Provincial Health Directorate Public Hospitals Services-2. In this study, we analyzed the current biochemical data of the patients with their medications., Results: In this study, 185 female (72.3%) and 71 male (27.7%) patients were recruited with the mean HbA1c of 8.25±1.77. Among these patients, 65% of them were using oral antidiabetic (OAD), and 58% were using insulin. There were 21 (8.2%) patients who were not receiving any treatment. While patients who were using only oral antidiabetic have better A1c levels (A1c: 7.73±1.45), patients who were insülin using had HbA1c levels as high as the patients who were not using any medication. This may be due to the progression of diabetes, fear of hypoglycemia or insufficient insülin use. While metformin was the most commonly used OAD, with a 38% usage rate. When compared to HbA1c levels, there was no difference between the types of insulin used (p=0.167)., Conclusion: As a result, it is important to plan regular visits and personalized treatment by keeping in mind the benefits to risk ratios in home-care diabetic patients., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (Copyright: © 2020 by Istanbul Northern Anatolian Association of Public Hospitals.)

INTRODUCTION Diabetes and its complications are the significant cause of morbidity and mortality. Advanced glycation end products play a major role in the pathogenesis of diabetes complications. OBJECTIVES The aim of the study was to investigate the possible use of a biomicroscope (ClearPath DS‑‑120), which shows the age‑‑adjusted lens fluorescence ratio (LFR), for the diagnosis of diabetic peripheral neuropathy (DPN). PATIENTS AND METHODS A total of 160 patients with type 2 diabetes who underwent an LFR measurement were recruited to this study. DPN was defined as the presence of neuropathic pain or feet sensory loss (or both). Neurothesiometer, monofilament test, and DN4 test results were used for the diagnosis of DPN. RESULTS The LFR of 43 patients (27%) was higher than the expected levels. According to the DN4 questionnaire, 35 of 160 patients (21%) had neuropathic pain. Thirty‑‑seven patients (23%) had higher vibration perception thresholds than expected (>25 V). The monofilament test showed that 42 patients (26%) seemed to be affected by DPN. All of the tests, when considered individually, revealed that patients with higher LFR had more problems related to DPN (P <0.05). High LFR had a sensitivity of 50% and a specificity of 81% in the diagnosis of DPN. Although there was no significant difference in fasting blood glucose levels, we observed that HbA1c levels were higher and diabetes duration was longer in patients with higher LFR (P <0.05). CONCLUSIONS The measurement of LFR may have clinical utility for a noninvasive detection of DPN.

Objective: In this study we aimed to investigate the efficacy and safety of dapagliflozin addition to diabetic patients using high dose insulin., Methods: The current study was carried out in the outpatient diabetic clinics of Fatih Sultan Mehmet Education and Research Hospital. Thirty diabetic patients who were receiving high dose (>0,5U/kg) insulin and oral antidiabetic treatment (other than SGLT 2 inhibitors) were included in this study. Primary end point was the change in HbA1c, insulin doses and serum electrolyte from the addition of dapagliflozin 10 mg to the week 12., Results: At the end of three month BMI were obviously decreased from 33.31 ±4.51 to 32.14 ±4.66 (p: 0.001). There was also an evident decrease of insulin requirement from 76 ±23.15 U/kg to 57.60 ±17.61 U/day (p<0.001). As well as the decrease in insulin doses, there was also a significant decline in HbA1c (Δ 1.6 %) and fasting blood glucose levels (Δ68.6 mg/dl) (p<0.001). Among serum electrolyte levels slight but meaningful increase of blood urea nitrogen (BUN) and sodium (Na) levels were seen (p: 0.044 and p: 0.026). There were no significant changes in serum cholesterol levels with electrolytes such as potassium, calcium, phosphorus magnesium and vitamin D (p> 0.05)., Conclusion: In diabetic patients with inadequately controlled glucose regulation despite high-dose insulin therapy, dapagliflozin may be an alternative combination choice to decrease the need of insulin dose and obtain an optimal HbA1c, fasting plasma glucose levels and weight without major side effects., Competing Interests: Conflict of Interest: None.

Aim: Early identification and treatment of infections in patients using domiciliary non-invasive mechanical ventilation (NIMV) due to chronic respiratory failure (CRF) can reduce hospital admissions. We assessed C-reactive protein (CRP), procalcitonin, and neutrophil lymphocyte ratio (NLR) as indicators of infection/inflammation. Methods: The study was designed as a retrospective, observational, cross-sectional study, and was performed in 2016 in an intensive care unit outpatient clinic in patients using NIMV. Patients who came to the outpatient clinic with dyspnea, increased sputum, increased prothrombin, and who had hemogram, procalcitonin, and serum CRP, NLR, and PLT/MPV levels assessed, were enrolled into the study. Demographic characteristics, co-morbid diseases, respiratory symptoms, hemogram, biochemistry, CRP, and procalcitonin values in stable and acute attack patients were recorded from patient files. The descriptive statistics and CRP, NLR, and procalcitonin values were assessed. Results: During the study period, 49 patients (24 female) with chronic obstructive pulmonary disease (COPD, n = 24), obesity hypoventilation syndrome (OHS, n = 15), or interstitial lung disease, n = 10), and having had three inflammatory markers assessed, were included in the study. Their mean age was 67 (SD ± 12). Stable patients vs. those who had an acute attack was 41 vs. eight, and within 7 days of outpatient admission four patients were hospitalized. CRP, NLR, and PLT/MPV values were similar in patients' who had sputum purulence, and an increase in dyspnea and sputum, but procalcitonin was significantly higher in patients who had an acute attack. Procalcitonin was not correlated with CRP, NLR, and PLT/MPV. Conclusions: Patients with CRF had similar levels of CRP and NLR during a stable and acute attack state. Procalcitonin may be a better marker for therapeutic decisions in advanced chronic inflammatory diseases.

Neurology research and clinical practice are transforming toward postgenomics integrative biology. One such example is the study of human brain metabolism that is highly sophisticated due to reactions occurring in and between the astrocytes and neurons. Because of the inherent difficulty of performing experimental studies in human brain, metabolic network modeling has grown in importance to decipher the contribution of brain metabolite kinetics to human health and disease. Multiomics system science-driven metabolic models, using genome-scale and transcriptomics Big Data, offer the promise of new insights on metabolic networks in human brain. Added to this, the availability of omics technologies in both developed and developing world, neurology research, and clinical practice ought to be repositioned with a view to systems medicine. In this expert analysis, we present a critical and in-depth overview of the basic tenets of human brain metabolism, together with the most recent metabolic modeling strategies and computational studies of brain in health and neurological diseases. Human genome-scale metabolic models developed in a both global and brain-specific manner and multiomics synthesis of knowledge are highlighted in particular. We conclude by underscoring the value of multiomics modeling for metabolic diseases and computational investigations of the brain networks, with a view to unlocking the pathophysiology of Alzheimer's disease, Parkinson's disease, migraine, stroke, epilepsy, and multiple sclerosis, among other neurological disorders of importance for global health.

Introduction: Diabetes mellitus (DM) is a metabolic disorder associated with both microvascular and macrovascular complications. Mean platelet volume (MPV) is a marker of platelet activity, which plays a major role in the development of vascular complications of DM. The aim of this study is to compare the MPV levels before and after the decrease of glycated hemoglobin (HbA 1c ) levels in a large diabetic population., Material and Methods: This was a retrospective study conducted on type 2 diabetic patients from the outpatient clinic for 1 year between 2014 and 2015 with the participation of 595 diabetic patients., Results: When we compared the basal and post-treatment values, a significant decrease of MPV and HbA 1c levels was found (HbA 1c : 9.41 ±1.98% vs. 7.43 ±1.29%, p < 0.001; MPV: 9.11 ±1.42 vs. 8.17 ±1.04, p < 0.001). There was also a positive correlation between the mean changes of MPV and HbA 1c levels after the treatment (ΔMPV: 0.93 ±0.96 vs. ΔHbA 1c : 1.96 ±1.43; p = 0.005, r = 0.115). When the participants were divided into two groups according to their basal HbA 1c levels (group A: HbA 1c ≤ 6.5% and group B: HbA 1c > 6.5%), it was clearly seen that improvement of glucose levels led to a significant decrease in MPV levels in both groups., Conclusions: The results of this study show that better glycemic control is associated with a significant decrease of MPV levels, regardless of whether the treatment modality is insulin or oral antidiabetic.

Objective: Glycemic variability (GV) is a new term with the episodes of hyper and hypoglycemia in diabetic patients. Both prolonged QT interval and QTd are potential risk factors for malignant ventricular arrhythmias affecting the mortality of different groups of patients including diabetes mellitus. In this study, we aimed to evaluate if the glucose variability increasing the QTc interval and QTc dispersion in type 2 diabetes mellitus., Methods: We included 275 consecutive patients with type 2 diabetes. We quantified the GV with standard deviation (SD) and coefficient of variation (CV) from 7 point glucose measures. We investigated the relationship of GV parameters with QT parameters., Results: The prevalence of prolonged QTc duration was 21%, no patients have prolonged QTc dispersion (> 80 ms). SD of the patients with prolonged QTc duration was significantly higher than the others (45.14 ±24.45 vs. 37.78 ±9.03 p<0.05). There was also a significant relationship between SD and QTc dispersion (r: 0.164; p: 0.007). There were no relationship between the QT parameters and microvascular diabetic complications. SD and HbA1c levels were significantly higher on the patients having peripheral neuropathy (p<0.005)., Conclusion: The result of this study demonstratess that increased glycemic variability is associated with prolonged QTc duration and QTc dispersion. It is important to focus on targeting optimal glycemic control with GV as an additional goal point along with the traditional following parameters such as fasting-postprandial blood glucose and HbA1c.

Objective: To investigate the effect of ezetimibe on platelet functions as a drug which increases mevalonate levels., Methods: This retrospective study was conducted in Istanbul, Turkey, and comprised record of normolipidaemic and hyperlipidaemic patients taken from the outpatient clinic from October 2004 to February 2015,. The results were taken from the baseline and third-month data of ezetimibe treatment. SPSS 22 was used for statistical analysis., Results: Of the total, there were 50(53%) normolipidaemic patients and 45(47%) hyperlipidaemic ones. Pre- and post-treatment values of mean platelet volume were significantly higher in the hyperlipidaemic group than controls (p<0.001). In the hyperlipidaemic group there was no significant difference between pre- and post-treatment values of mean platelet volume (8.96±0.93 vs. 8.92±0.84; p>0.05)., Conclusions: The use of ezetimibe alone should not be the first choice in hyperlipidaemia treatment.

Metformin-associated lactic acidosis (MALA) is one of the most important drug toxicities with a high morbidity and mortality rate. We report herein a case of suicide attempt with metformin presenting as MALA and acute renal failure on admission to emergency department and acute myocardial injury later on hospitalisation. An obvious improvement of metabolic parameters was seen in our patient provided by anti-ischaemic treatment together with bicarbonate infusion and haemodialysis. Although myocardial injury due to MALA is not a common disorder, we must be aware that metformin overdose with lack of tissue oxygenation, hypoperfusion, and arrhythmias may cause myocardial ischaemia.