Evaluation of the Effect of Favipiravir on QT Intervals in COVID-19 Patients with and without Diabetes Mellitus.

OBJECTIVE: To evaluate the effect of favipiravir administered to diabetic and non-diabetic COVID-19 patients on the QT/QTc interval. STUDY DESIGN: Analytical study. Place and Duration of the Study: Republic of Turkey, Ministry of Health, State Hospital, Corlu, Tekirdag, Turkiye, from March to September 2021. METHODOLOGY: Electrocardiogram (ECG) analysis was performed on all participants (n=180) divided into four groups. Group 1 included only healthy volunteers. Group 2 included only cases diagnosed with T2DM. Group 3 included only severe acute respiratory syndrome coronavirus-2 (SARS-Cov-2) cases. Group 4 included cases diagnosed with both SARS and T2DM. Favipiravir was administered only to the cases in Group 3 and Group 4. In the cases that were administered favipiravir, the QT/QTc interval was calculated and recorded at different time intervals on the first and fifth days of the therapy. The difference between groups was determined by Tukeye's test after ANOVA. Pearson's correlation test was used to determine whether there was a linear relationship between two numericals. The alpha significance value was determined to be <0.05 in all statistical analyses. RESULTS: When all groups were compared, it was seen that both QT and QTc values ​​increased in Groups 3 and 4, which were administered favipiravir (p <0.05). Favipiravir may cause an increased risk of ventricular and atrial arrhythmias. CONCLUSION: Favipiravir may cause QT interval prolongation, particularly in SARS-Cov-2 patients diagnosed with T2DM. KEY WORDS: COVID-19, Drug-induced long QT syndrome, Intra-infarct haemorrhage; Favipiravir, Type 2 diabetes mellitus.

Effectiveness of Peripheral Nerve Block in Terms of Search for a Standardized Treatment Protocol in Diabetic Foot Patients Using Anticoagulants: A Double-Center Study.

BACKGROUND: Lower-extremity amputation for a diabetic foot is mainly performed under general or central neuraxial anesthesia. Ultrasound-guided peripheral nerve block (PNB) can be a good alternative, especially for patients who require continuous anticoagulation treatment and patients with additional comorbidities. We evaluated bleeding due to PNB application in patients with diabetic foot receiving antiplatelet or anticoagulant therapy. Perioperative morbidity and mortality and the need for intensive care hospitalization were analyzed. METHODS: This study included 105 patients with diabetic foot or debridement who underwent distal foot amputation or debridement between February and October 2020. Popliteal nerve block (17 mL of 5% bupivacaine and 3 mL of saline) and saphenous nerve block (5 mL of 2% lidocaine) were applied to the patients. Postoperative pain scores (at 4, 8, 12, and 24 hours) and complications due to PNB were evaluated. Intensive care admission and 1-month mortality were recorded. RESULTS: The most common diseases accompanying diabetes were hypertension and peripheral artery disease. No complications due to PNB were observed. Mean ± SD postoperative first analgesic need was determined to be 14.1 ± 4.1 hours. Except for one patient, this group was followed up without the need for postoperative intensive care. In 16 patients, bleeding occurred as leakage from the surgical area, and it was stopped with repeated pressure dressing. Mean ± SD patient satisfaction score was 8.36 ± 1.59. Perioperative mortality was not observed. CONCLUSIONS: Ultrasound-guided PNB can be an effective and safe anesthetic technique for diabetic patients undergoing distal foot amputation, especially those receiving antiplatelet or anticoagulant therapy and considered high risk.

The Performance of Chatbots and the AAPOS Website as a Tool for Amblyopia Education.

PURPOSE: To evaluate the understandability, actionability, and readability of responses provided by the website of the American Association for Pediatric Ophthalmology and Strabismus (AAPOS), ChatGPT-3.5, Bard, and Bing Chat about amblyopia and the appropriateness of the responses generated by the chatbots. METHOD: Twenty-five questions provided by the AAPOS website were directed three times to fresh ChatGPT-3.5, Bard, and Bing Chat interfaces. Two experienced pediatric ophthalmologists categorized the responses of the chatbots in terms of their appropriateness. Flesch Reading Ease (FRE), Flesch Kincaid Grade Level (FKGL), and Coleman-Liau Index (CLI) were used to evaluate the readability of the responses of the AAPOS website and chatbots. Furthermore, the understandability scores were evaluated using the Patient Education Materials Assessment Tool (PEMAT). RESULTS: The appropriateness of the chatbots' responses was 84.0% for ChatGPT-3.5 and Bard and 80% for Bing Chat (P > .05). For understandability (mean PEMAT-U score AAPOS website: 81.5%, Bard: 77.6%, ChatGPT-3.5: 76.1%, and Bing Chat: 71.5%, P < .05) and actionability (mean PEMAT-A score AAPOS website: 74.6%, Bard: 69.2%, ChatGPT-3.5: 67.8%, and Bing Chat: 64.8%, P < .05), the AAPOs website scored better than the chat-bots. Three readability analyses showed that Bard had the highest mean score, followed by the AAPOS website, Bing Chat, and ChatGPT-3.5, and these scores were more challenging than the recommended level. CONCLUSIONS: Chatbots have the potential to provide detailed and appropriate responses at acceptable levels. The AAPOS website has the advantage of providing information that is more understandable and actionable. The AAPOS website and chatbots, especially Chat-GPT, provided difficult-to-read data for patient education regarding amblyopia. [J Pediatr Ophthalmol Strabismus. 20XX;X(X):XXX-XXX.].

Artificial Intelligence Advances in Transplant Pathology.

Transplant pathology plays a critical role in ensuring that transplanted organs function properly and the immune systems of the recipients do not reject them. To improve outcomes for transplant recipients, accurate diagnosis and timely treatment are essential. Recent advances in artificial intelligence (AI)-empowered digital pathology could help monitor allograft rejection and weaning of immunosuppressive drugs. To explore the role of AI in transplant pathology, we conducted a systematic search of electronic databases from January 2010 to April 2023. The PRISMA checklist was used as a guide for screening article titles, abstracts, and full texts, and we selected articles that met our inclusion criteria. Through this search, we identified 68 articles from multiple databases. After careful screening, only 14 articles were included based on title and abstract. Our review focuses on the AI approaches applied to four transplant organs: heart, lungs, liver, and kidneys. Specifically, we found that several deep learning-based AI models have been developed to analyze digital pathology slides of biopsy specimens from transplant organs. The use of AI models could improve clinicians' decision-making capabilities and reduce diagnostic variability. In conclusion, our review highlights the advancements and limitations of AI in transplant pathology. We believe that these AI technologies have the potential to significantly improve transplant outcomes and pave the way for future advancements in this field.

Quaternary Knot Technique: Suture Knot Burial without Scleral Flap or Incision for Trans-scleral Fixation.

Despite the introduction of novel sutureless posterior chamber intraocular lens (IOL) fixation techniques, some conditions still require suture-assisted scleral fixation. If the scleral fixation suture knot is left directly under the conjunctiva, it may become exposed, resulting in an increased risk of endophthalmitis. To avoid this problem, we offer a new alternative, simple, and safe way for burying the end of the suture using knots in this report.

A cyanobiphenyl-based fluorescent ''lighting-up'' sensor for highly selective and sensitive recognition of Al3+: Theoretical, practical and bioimaging studies.

The recognition of toxic Al3+ in foods and biosystems has of great interest to researchers. Herein, a novel cyanobiphenyl-based chemosensor CATH (E)-N'-((4'-cyano-4-hydroxy-[1,1'-biphenyl]-3-yl)methylene)thiophene-2-carbohydrazide was fabricated and shown to recognize Al3+ in HEPES buffer:EtOH (90:10, v:v, pH = 7.4) by ''lighting-up'' fluorescence sensing. The CATH evidenced high sensitivity (LOD = 13.1 nM) and excellent selectivity to Al3+ over competing cations. The Job's plot, TOF-MS and theoretical computation studies were performed to probe the binding mechanism of Al3+ to CATH. Additionally; CATH was successfully utilized to practical applications and employed to recover of Al3+ from different food samples. More importantly, it was employed to intracellular Al3+ detection in living cells including THLE2 and HepG2.

Anti-inflammatory activity of bupropion through immunomodulation of the macrophages.

Depression might manifest itself with a chronic inflammation in different tissues and organs independent of the central nervous system. Psoriasis, Crohn's disease, and fibromyalgia are among these disorders accompanying the depression. The treatment options for these conditions are a combination of the anti-depressants and anti-inflammatory agents. Bupropion has been widely utilized as an anti-depressant. It has been preferred among the patients with Crohn's disease and psoriasis due to its anti-inflammatory role, as well. In this study, we aimed to decipher its target in the immune system. Macrophages were activated in the presence of LPS and increasing concentrations of the bupropion. TNF-α, IL-6, GM-CSF, and IL-12p40 cytokines' production levels were measured by ELISA to compare it to the control groups. These cytokines have been associated with the aggressive inflammation in different tissues. Moreover, p38 and PI3K proteins' phosphorylated levels were measured to examine whether bupropion acts through these pathways or not. Our results suggest that bupropion had anti-inflammatory action on the activated macrophages and its mechanism of action was partially dependent on p38 but independent of PI3K pathways.

Effects of antidiabetics and exercise therapy on suppressors of cytokine signaling-1, suppressors of cytokine signaling-3, and insulin receptor substrate-1 molecules in diabetes and obesity.

OBJECTIVE: Pathological destruction of insulin signaling molecules such as insulin receptor substrate, especially due to the increase in suppressors of cytokine signaling molecules, has been demonstrated in experimental diabetes. The contribution of suppressors of cytokine signaling proteins to the development of insulin resistance and the effects of antidiabetic drugs and exercise on suppressors of cytokine signaling proteins are not clearly known. METHODS: A total of 48 Wistar albino adult male rats were divided into six groups: control group, obese group with diabetes, obese diabetic rats treated with metformin, obese diabetic rats treated with pioglitazone, obese diabetic rats treated with exenatide, and obese diabetic rats with applied exercise program. Immunohistochemical staining was performed in both the liver and adipose tissue. RESULTS: There was a statistically significant decrease in suppressors of cytokine signaling-1, a decrease in suppressors of cytokine signaling-3, an increase in insulin receptor substrate-1, and a decrease in immunohistochemical staining in the obese group treated with metformin and exenatide compared to the obese group without treatment in the liver tissue (p<0.05). A statistically significant decrease in immunohistochemical staining of suppressors of cytokine signaling-1 and suppressors of cytokine signaling-3 was found in the obese group receiving exercise therapy compared to the obese group without treatment in visceral adipose tissue (p<0.05). Likewise, no significant immunohistochemistry staining was seen in diabetic obese groups. CONCLUSION: Metformin or exenatide treatment could prevent the degradation of insulin receptor substrate-1 protein by reducing the effect of suppressors of cytokine signaling-1 and suppressors of cytokine signaling-3 proteins, especially in the liver tissue. In addition, exercise can play a role as a complementary therapy by reducing suppressors of cytokine signaling-1 and suppressors of cytokine signaling-3 proteins in visceral adipose tissue.

Fetal pancreas size and maternal serum biomarkers glycated albumin and insulin-regulated aminopeptidase provide no potential for early prediction of gestational diabetes mellitus.

PURPOSE: We aimed to determine the predictive values of fetal pancreas size and maternal serum biomarkers glycated albumin (GA) and insulin-regulated aminopeptidase (IRAP) for gestational diabetes mellitus (GDM). MATERIALS AND METHODS: In this prospective observational study including 109 pregnant women, the fetal pancreas size and maternal serum biomarkers GA and IRAP were measured at the gestational age of 20-22 weeks and later at the gestational age of 24-28 weeks, in 19 participants of them, GDM was confirmed with the 75-g oral glucose tolerance test (OGTT) and the fetal pancreas size was measured in all the participants again. RESULTS: The median fetal pancreas sizes were significantly higher in women with or without GDM when measured at the 24-28 weeks of pregnancy compared to those at the 20-22 weeks of pregnancy (p < 0.05). At both of the 20-22 and 24-28 weeks of pregnancy, the median values of fetal pancreas sizes in the women with or without GDM were found comparable (p > 0.05). There were no significant differences between pregnant women with or without GDM regarding maternal serum biomarkers GA and IRAP (p > 0.05). Multivariate logistic regression analysis revealed no meaningful association of study parameters with the development of GDM. CONCLUSION: The fetal pancreas size and maternal serum biomarkers GA and IRAP provide no potential for early prediction of GDM at the 20-22 weeks of gestation. Further studies, including serial measurement of these parameters during the second and third trimesters of GDM pregnancies, may clarify their role in the antenatal care of women with GDM. CLINICAL TRIALS: NCT05392231.

Assessment of safety and feasibility of non-invasive vagus nerve stimulation for treatment of acute stroke.

BACKGROUND: Non-invasive vagus nerve stimulation (nVNS) using a hand-held stimulator placed on the neck is an FDA-approved treatment for primary headache disorders. The safety of nVNS is unknown in stroke patients. OBJECTIVE: To assess the safety and feasibility of nVNS for the acute treatment of stroke. METHODS: TR-VENUS (clinicaltrials.gov identifier NCT03733431) was a randomized, sham-controlled, open-label, multicenter trial conducted in patients with acute ischemic stroke (IS) or intracerebral hemorrhage (ICH). Patients were randomly assigned to standard-dose nVNS, high-dose nVNS, or sham stimulation. The primary endpoint was a composite safety outcome defined as bradycardia or reduction in mean arterial blood pressure during treatment or progression of neurological or death within 24 h of treatment. The feasibility endpoints were the proportion of eligible subjects receiving nVNS within 6 h of symptom onset and the proportion completing all pre-specified treatment doses. Efficacy assessments included infarct growth from baseline to 24 h after treatment. RESULTS: Sixty-nine patients (61 IS, 8 ICH) completed the study. The composite safety outcome was achieved in 32.0% in sham and 47.7% in nVNS group (p = 0.203). Treatment was initiated in all but two randomized patients. All dosed subjects received 100% of prespecified stimulations. A non-significant reduction in infarct growth was observed in the high-dose nVNS group (184.2% in sham vs. 63.3% in high-dose nVNS; p = 0.109). CONCLUSIONS: The results of this study suggest that nVNS may be safe and feasible in the setting of acute stroke. These findings support further development of nVNS as a potential treatment for acute ischemic stroke.

Evaluation of Calciferol, Cobalamin, and Stromelysin-1 in Patients with Diabetic Peripheral Neuropathy due to Type-2 Diabetes Mellitus.

OBJECTIVE: To evaluate the relationship between calciferol (vitamin D), cobalamin (vitamin-B12), and Stromelysin-1 (MMP-3) circulating levels in patients with diabetic peripheral neuropathy (DPN), patients with DM type 2 (T2DM) without neuropathy, and healthy control groups. STUDY DESIGN: Cross-sectional descriptive study. PLACE AND DURATION OF STUDY: Department of Internal Medicine, Namik Kemal University of Medicine, Tekirdag, Turkey, between November 2020 and February 2022. METHODOLOGY: Healthy, age, and gender matched volunteers who were admitted to the hospital for a check-up with no health problem constituted the control group (n=30). Cases diagnosed with T2DM (n=30) and those with DPN (n=30) comprised the experimental group. Stromelysin-1, calciferol, and cobalamin levels were analysed from blood samples from all groups using enzyme-linked immunosorbent assay (ELISA) with a commercial kit. Tukey's Honest Significant Difference (HSD) test was performed after one-way analysis of variance (ANOVA) for intergroup comparisons. Alpha significance level was accepted as.

Coexistence of SARS-CoV-2 and cerebrovascular diseases: does COVID-19 positivity trigger cerebrovascular pathologies?

The objectives of this study were to determine the prevalence of cerebrovascular diseases caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, and to assess the pharmacological agents used in such cases as reported in the literature. Patient files were retrospectively scanned to determine the prevalence of neurological symptoms of the central nervous system (headache, dizziness, lack of smell and taste, numbness in arms and legs, change in consciousness, muscle weakness, loss of urine and stool control) and cerebrovascular diseases (ischemic cerebrovascular diseases, cerebral venous sinus thrombosis, intracerebral hemorrhage, subarachnoid/subdural hemorrhage) in 2019 novel coronavirus (2019-nCoV) disease (COVID-19) cases (n = 20,099). The diagnostic laboratory, radiology examinations and treatments applied to these cases were recorded. The data from studies presenting cerebrovascular diseases associated with SARS-Cov-2, which constituted 0.035% of all cases, were systematically evaluated from electronic databases. During the treatment of cerebrovascular diseases, it was discovered that high doses of enoxaparin sodium anti-Xa are combined with apixaban or acetylsalicylic acid or clopidogrel or piracetam, and mannitol, in addition to SARS-CoV-2 treatment modalities. While neurological symptoms of the central nervous system are uncommon in cases of SARS-CoV-2 infection, cerebrovascular diseases are far less common, according to the findings of this study. Acute cerebral ischemia was discovered to be the most common cerebrovascular disease associated with SARS-CoV-2. The mortality rate increases with the association between SARS-CoV-2 and cerebrovascular disease.

Study of Transesophageal Echocardiography in Young Patients with Cryptogenic Stroke: Prevalence of Patent Foramen Ovale and Interpretation of the RoPE Score.

OBJECTIVE: Cryptogenic stroke (CS) is considered to be the most common stroke subtype in young patients. The Risk of Paradoxical Embolism (RoPE) score is a tool that stratifies patients with CS according to the probability of patent foramen ovale (PFO). The aim of this retrospective study is to determine the prevalence of PFO in young patients with transesophageal echocardi- ography (TEE) and to evaluate the role of RoPE score in PFO-related strokes. METHODS: The medical records of patients with acute arterial ischemic stroke, who underwent TEE between 2016 and 2020, were reviewed. Patients aged 18-55 years were included in the study. Presence of PFO, PFO characteristics, presence of atrial septal aneurysm (ASA) were detected by examining the image records of the patients from the archive system. RoPE score was calculated for all patients as determined in the literature. RESULTS: Totally, 50 CS patients were included in the study (mean age: 39.6±9.4 years). PFO was detected in 19 (38%) patients and it was the most common cardiac abnormality in CS patients. ASA was detected in 7 (14%) patients. The mean RoPE score in patients with PFO was higher than patients without PFO, although it did not reach statistical significance (7.68±1.1 versus 6.77±1.9 P = .07). Eighteen of 19 patients with PFO had a RoPE score ≥7. CONCLUSION: In our study, PFO prevalence in the CS patients was higher than normal popula- tion. In patients with cryptogenic stroke, the RoPE score can help determine the probability of PFO related stroke and which patients should undergo TEE.

The effects of rivaroxaban, an oral anticoagulant, on human IVD primary cultures.

Introduction: The present study aimed to investigate the potential effects of rivaroxaban, an oral anticoagulant that inhibits the effects of factor Xa, on intact intervertebral disc tissue cells and the extracellular matrix (ECM). Material and methods: Rivaroxaban was applied to primary human cell cultures prepared from tissues of the intervertebral disc. Comparative molecular analyses were performed on non-drug-treated control group samples. Descriptive statistics were presented as the mean ± standard deviation. An analysis of variance test was performed to determine whether there were significant differences in the mean across the groups. When differences across groups were observed, Tukey's honestly significant difference post-hoc test was used for multiple pairwise comparisons. The significance of the obtained data was determined statistically. The α significance value was < 0.05. Results: The cells in the control group and in the rivaroxaban-treated group were viable, healthy, and proliferated (p < 0.05). However, the expression levels of the chondroadherin gene (CHAD), cartilage oligo matrix protein (COMP), matrix metalloproteinase (MMP)-13, and MMP-19 genes were changed (p < 0.05). Conclusions: Although rivaroxaban does not suppress cell proliferation due to morphological, biological, and biochemical changes in the intervertebral disc tissue, it may change the expression of genes that are related to ECM maintenance.

Is Favipiravir a Potential Therapeutic Agent in the Treatment of Intervertebral Disc Degeneration by Suppressing Autophagy and Apoptosis?

AIM: To evaluate the effects of favipiravir (FVP) on cell viability and cytotoxicity in human degenerated primary intervertebral disc (IVD) tissue cell cultures. Furthermore, the protein expressions of hypoxia-inducible factor 1 alpha (HIF-1α), nuclear factor-kappa-b (NF-kB), and interleukin-1 beta (IL-1ß) were also examined. MATERIAL AND METHODS: Untreated cell cultures served as the control group, named group 1. Cell cultures treated with FVP served as the study group, named group 2. Pharmacomolecular analyses were performed in all groups at 0, 24, 48, and 72 hours (h). Obtained data were evaluated statistically. RESULTS: Cell proliferation was suppressed in the FVP-treated samples compared to the control group samples at 24 and 72 h, and this was statistically significant (p < 0.05). Decreased or increased protein expression levels of HIF-1α, NF-κB, and IL-1ß in FVPtreated samples may be an indication of suppression in anabolic events as well as proliferation in IVD cultures. FVP administration showed that AF/NP cells in a culture medium may induce a strong inflammatory response to FVP. This strong inflammatory response is likely to cause slowed proliferation. It may also be a trigger for many catabolic events. NF-κB expression increased within the first 24 h and then decreased rapidly. Based on the data obtained, it may be suggested that the rapidly increasing NF-kB may have stimulated the expression of many antiproliferative genes. CONCLUSION: The suppression of IL-1ß and NF-kB protein expressions in IVD cells treated with FVP is important in the treatment of IVD degeneration (IDD). If the protein expression of HIF-1α could be increased along with the suppression of IL-1ß and NF-kB, FVP would perhaps be a promising pharmacological agent in the treatment of IDD.

The use of autologous epidermal grafts for diabetic foot ulcer emergencies: A clinical study.

BACKGROUND: There are various surgical and invasive treatment systems such as conservative skin grafts and autologous epider-mal grafting (AEG) for diabetic foot ulcers. This study aims to evaluate the feasibility of using a novel epidermal graft harvesting system in diabetic foot ulcer emergencies. METHODS: A retrospective clinical study was conducted with 15 diabetic foot ulcer patients, and after written and signed consent forms were taken, AEG system was applied to all patients. All of the clinical data of the patients such as their American Society of Anesthesiologists (ASA) Physical Status Classification System scores, size of pre-application wound area (cm2), time to complete re-epithelization of the wound, pain scores using the visual analog scale (VAS) for both donor and recipient sites, changes in size of wound, complete dermal response time, and patients' demographics, comorbidities were recorded. The age, gender, pre-post appli-cation wound area (cm2), time of healing, ASA, and VAS variables were compared each other and analyzed statistically. P<0.05 was considered as statistically significant. RESULTS: The mean of time for complete wound healing was 5.9 (range 4-8) weeks. There was no statistically difference between recipient wound size and patient's age; size of both types of wounds (cm2) and time (weeks) for complete reduction for both types of wounds; and time to complete both types of wound healing and gender (p=0.509, 0.788, and 0.233, respectively). ASA scores did not impact the time required for complete healing of the wound (p=0.749). CONCLUSION: The current study has tried to evaluate the efficacy of the AEG system in a homogenous population with diabetic foot ulcers. An epidermal harvesting system may be used effectively and safely in patients with diabetic foot ulcer emergencies.

Challenges in pediatric cataract surgery: comparison of intraocular lens power calculation formulas using optical biometry.

PURPOSE: Comparison of the accuracy of intraocular lens (IOL) power calculation formulas (SRK II, SRK/T, Holladay 1, Hoffer Q and Barrett II Universal, Haigis) in pediatric cataract surgery using optical biometry. METHOD: This prospective study included seventy eyes of 70 patients between ages of 3-15 who had undergone cataract surgery with IOL implantation. Anterior segment parameters and axial length (AL) were measured with an optical biometer. Barrett II Universal formula results were used to determine the diopter of implanted IOL. Postoperative refraction was taken at first month, and differences from the estimated refractive value [mean absolute predictive error (APE)] were compared between formulas. Formulas were also compared according to AL. RESULTS: The lowest APE was achieved with Barrett II formula (0.64 ± 0.73D) and the highest with Haigis formula (1.06 ± 0.84D) in the whole study population (p < 0.01). APE values were lowest with Holladay 1 (0.79 ± 0.71D) and highest with Haigis (1.44 ± 0.92D) in patients with an AL ≤ 22 mm; lowest APE was achieved with Barrett II (0.47 ± 0.54D) and highest with Haigis (0.84 ± 0.72D) in patients with an AL > 22 mm. CONCLUSION: Barrett II formula had the best results in eyes with average AL, and SRK/T and Holladay 1 formulas were better in eyes with shorter AL. Haigis formula statistically had the highest predictive error in all formulas.

Propylimidazole Functionalized Coumarin Derivative as Dual Responsive Fluorescent Chemoprobe for Picric Acid and Fe3+ Recognition: DFT and Natural Spring Water Applications.

A propylimidazole functionalized coumarin derivative (IPC) was fabricated for the first time and applied as a dual responsive fluorescent chemoprobe for sensitive and selective recognition of picric acid (PA) and Fe3+. Strong fluorescence quenching phenomena of the IPC were observed in H2O/ACN (5/95, v/v) medium (λem=408 nm) upon the additions of Fe3+or PA. The fabricated dual responsive IPC offered good selectivity and sensitivity with the low limit of detection values (0.92 µM for PA and 0.22 µM for Fe3+) lower than the acceptable amounts of Fe3+ and PA by the international official authorities. The validation study for the chemoprobe IPC for PA and Fe3+ was also performed. The interaction phenomena of IPC with PA and Fe3+ based on the findings of a range of experiments were considered and DFT computations were done to verify their recognition mechanisms. The sensing phenomena of IPC towards PA (1:1) and Fe3+ (3:1) were confirmed by the MALDI TOF-MS, FT-IR, 1H-NMR titration and Job's methods. Furthermore, the compound IPC was effectively applied as a fluorescent sensor for Fe3+ and PA detection in real natural spring water samples.

Crystal structure and Hirshfeld surface analysis of (Z)-4-{[4-(3-methyl-3-phenyl-cyclo-but-yl)thia-zol-2-yl]amino}-4-oxobut-2-enoic acid.

The title cyclo-butyl compound, C18H18N2O3S, was synthesized by the inter-action of 4-(3-methyl-3-phenyl-cyclo-but-yl)thia-zol-2-amine and maleic anhydride, and crystallizes in the ortho-rhom-bic space group P212121 with Z' = 1. The mol-ecular geometry is partially stabilized by an intra-molecular N-H⋯O hydrogen bond forming an S 1 1(7) ring motif. The mol-ecule is non-planar with a dihedral angle of 88.29 (11)° between the thia-zole and benzene rings. In the crystal, the mol-ecules are linked by O-H⋯N hydrogen bonds, forming supra-molecular ribbons with C 1 1(9) chain motifs. To further analyze the inter-molecular inter-actions, a Hirshfeld surface analysis was performed. The results indicate that the most important contributions to the overall surface are from H⋯H (43%), C⋯H (18%), O⋯H (17%) and N⋯H (6%), inter-actions.

The effects of metformin, pioglitazone, exenatide and exercise on fatty liver in obese diabetic rats: the role of IRS-1 and SOCS-3 molecules.

BACKGROUND: Obesity-induced inflammation mechanism is seen as a mechanism that may be the cause of insulin resistance and non-alcoholic fatty liver disease (NAFLD). Pathological destruction of insulin signaling molecules such as insulin receptor substrate proteins (IRS), especially due to the increase of cytokine signal suppressors (SOCS), has been demonstrated in experimental diabetes. The aim of this study was to determine the effects of metformin, pioglitazone, exenatide and exercise treatments used in type 2 diabetes on fatty liver and the role of Irs-1 and Socs3 molecules in this process in obese diabetic rats. METHODS: The study was conducted on 48 Wistar albino adult male rats weighing 180-220 g and randomly divided into 6 groups. The obese rat model with fatty liver was formed with a 60% fat diet for 4 weeks. Afterwards, drug treatment with metformin (Ob + D + M), pioglitazone (Ob + D + P), exenatide (Ob + D + ExA)) or exercise (Ob + D + ExE) was applied for 4 weeks to these obese groups, in which diabetes was induced by streptozocin (STZ). At the end of the experimental protocol, liver tissue samples were taken from all rat groups and histopathological and genetic analyses were performed. RESULTS: The mean steatosis degrees of the Ob + D + ExA and Ob + D + ExE groups were statistically significantly decreased compared to the obese diabetic group (p < 0.001). The group with the lowest mean steatosis grade was the Ob + D + ExE. Decrease in SOCS-3 expression was significant in Ob + D + M and Ob + D + P groups than other groups (p < 0.05). Mean staining intensities of Ob + D + Ex group, Ob + D + ExE group and Ob + D + P group according to IRS-1 expression statistically significantly increased compared to obese diabetic group (p < 0.05). Average staining intensity of Ob + D + ExE group according to IRS-1 expression was significant than other groups. CONCLUSION: Exercise and exenatide treatments seemed to be the prominent treatment methods by showing a statistically significant effect in decreasing the degree of steatosis, decreasing the Socs3 expression level and increasing the Irs-1 expression level.