[Investigation of the Effect of Farnesol on Biofilm Formation by Candida albicans and Candida parapsilosis Complex Isolates]. / Candida albicans ve Candida parapsilosis Kompleks Izolatlarinin Biyofilm Üretimi Üzerine Farnesol Etkisinin Arastirilmasi.

The incidence of infections caused by Candida species has significantly increased over the past three decades. Candida albicans is commonly recognized as the primary causative agent in cases of candidiasis; however, non-albicans Candida species, including Candida parapsilosis, are also frequently defined as pathogens. Treatment-resistant infections arise as a result of biofilm formation, which is one of the effective mechanisms in the pathogenesis of Candida infections. However, the mechanisms of action of farnesol, a quorum sensing (QS) system molecule, on biofilm formation by Candida species remain unclear. This study aimed to demonstrate the changes in the biofilm biomass of C.albicans and C.parapsilosis complex isolates in the presence of farnesol and reveal the expression of the EFG1 and BCR1 genes, which are believed to play a role in the production of QS molecules, using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) analysis. C.albicans (n= 91) and C.parapsilosis complex (n= 29) isolates obtained from different clinical samples were included in the study. The minimum inhibitory concentration (MIC) values of farnesol were determined using the broth microdilution method according to the M27-A3 protocol of the Clinical and Laboratory Standards Institute (CLSI). The biofilm biomass of the isolates was examined without farnesol and at the MIC-0 and MIC-2 concentrations of farnesol. Changes in the expression of the biofilm-associated EFG1 and BCR1 genes were investigated using qRT-PCR. According to the results of the study, the MIC values of farnesol were detected in the range of 1-2 mM in 82.4% (n= 75) of the C.albicans isolates and in the range of 0.5-1 mM in 72.4% (n= 21) of the C.parapsilosis complex isolates. Of the C.albicans isolates, 27 (29.7%) exhibited a strong biofilm formation and 58 (63.7%) demonstrated a weaker biofilm formation, while these rates were 34.4% (n= 10) and 62.1% (n= 18), respectively, for the C.parapsilosis complex isolates. At the MIC-0 and MIC-2 concentrations, farnesol was observed to reduce biofilm biomass among C.albicans (n= 24, 88.9%) and C.parapsilosis complex (n= 8, 80.0%) isolates that formed strong biofilms and observed to increase biofilm biomass among those that formed weak biofilms [60.3% (n= 35) and 55.6% (n= 10), respectively]. On completion of the qRT-PCR analysis supporting the results of the biofilm experiment, it was determined that the expressions of the EFG1 and BCR1 genes decreased at the MIC-0 and MIC-2 concentrations of farnesol among the strong biofilm-forming C.albicans and C.parapsilosis complex isolates, but there was an increase in gene expressions among the weak biofilm-forming isolates. In addition to the antifungal effect of farnesol on Candida species, this study provided data on the efficacy of the MIC-0 and MIC-2 concentrations of farnesol against Candida biofilm biomass. Although our results suggest that farnesol can be used as an alternative agent to reduce biofilm formation in Candida infections, they need to be supported by further studies. Moreover, this research has significance as it represents the first study to determine the EFG1 and BCR1 gene expressions among C.parapsilosis complex isolates in the presence of farnesol.

Do Histologically Aggressive Subtypes of Papillary Thyroid Microcarcinoma have Worse Clinical Outcome than Non-Aggressive Papillary Thyroid Microcarcinoma Subtypes? A Multicenter Cohort Study.

Histologically aggressive micropapillary thyroid carcinomas (PTMC) subtypes are thought to be associated with an aggressive clinical course. However, evidence for unfavorable clinical outcomes in patients with aggressive PTMC subtypes is not clear. In this study, we intended to determine the difference in clinical outcomes between patients with aggressive and non-aggressive PTMC subtypes. In this multicenter cohort study, the computer-recorded clinical and histopathological data of patients who underwent thyroid surgery between January 2000 - January 2021 in 9 referral centers and were diagnosed as PTMC were analyzed. A total of 1585 patients [female 1340 (84.5%), male 245 (15.5%), mean age 47.9±11.63 years), with a mean follow-up time of 66.55±37.16 months], were included in the study. Ninety-eight cases were diagnosed as aggressive and 1487 as non-aggressive subtypes. Persistent/recurrent disease was observed in 33 (33.7% )and 41 (2.8%) patients with aggressive and non-aggressive subtypes (p<0.001). Diseases-free survival rates were markedly lower in patients with aggressive than in those with non-aggressive PTMC subtypes (66.3 vs. 94.8%, log-rank p<0.001). Moreover, in multivariate analysis, aggressive histology was an independent predictor of persistent/recurrent disease, after controlling for other contributing factors (HR 5.78, 95% CI 3.32-10, p<0.001). Patients with aggressive PTMC subtypes had higher rates of incomplete biochemical and structural response than patients with non-aggressive subtypes as well (p<0.001). Aggressive PTMC subtypes share many characteristics with histologically identical tumors>1 cm in size. Therefore, the histopathological subtype of PTMC should be taken into consideration to tailor a personalized management plan.

Can Age at Diagnosis and Sex Improve the Performance of the American Thyroid Association Risk Stratification System for Prediction of Structural Persistent and Recurrent Disease in Patients With Differentiated Thyroid Carcinoma? A Multicenter Study.

OBJECTIVE: Although the age at diagnosis has been suggested as a major determinant of disease-specific survival in the recent TNM staging system, it is not included in the recent American Thyroid Association (ATA) guidelines to estimate the risk of recurrence. Nevertheless, the effect of sex on differentiated thyroid carcinoma (DTC) recurrence is controversial. Therefore, this multicenter study was conducted to assess whether age at diagnosis and sex can improve the performance of the ATA 3-tiered risk stratification system in patients with DTC with at least 5 years of follow-up. METHODS: In this study, the computer-recorded data of the patients diagnosed with DTC between January 1985 and January 2016 were analyzed. Only patients with proven structural persistent/recurrent disease were selected for comparisons. RESULTS: This study consisted of 1691 patients (female, 1367) with DTC. In Kaplan-Meier analysis, disease-free survival (DFS) was markedly longer in females only in the ATA low-risk category (P = .045). Nevertheless, a markedly longer DFS was observed in patients aged <45 years in the ATA low- and intermediate-risk categories (P = .004 and P = .009, respectively), whereas in patients aged <55 years, DFS was markedly longer only in the ATA low-risk category (P < .001). In the Cox proportional hazards model, ages of ≥45 and ≥55 years at diagnosis and the ATA risk stratification system were all independent predictors of persistent/recurrent disease. CONCLUSION: Applying the age cutoff of 45 years in the ATA intermediate- and low-risk categories may identify patients at a higher risk of persistence/recurrence and may improve the performance of the ATA risk stratification system, whereas sex may improve the performance of only the ATA low-risk category.

Altered immune response in organic acidemia.

BACKGROUND: Most patients with organic acidemia suffer from recurrent infections. Although neutropenia has been reported in multiple studies, other components of the immune system have not been evaluated thoroughly. This study was conducted to assess the immune status of patients with organic acidemia (OA). METHODS: Thirty-three patients with OA who were followed up in Istanbul University-Cerrahpasa, Cerrahpasa School of Medicine, Nutrition and Metabolism Department and a total of 32 age- and sex-matched healthy controls were enrolled to the study. The demographic and clinical data were recorded retrospectively from patient files. Complete blood counts, immunoglobulins, and lymphocyte immunophenotyping were recorded prospectively in a symptom- (infection-) free period. RESULTS: Of the 33 patients enrolled to the study, 21 (88%) were diagnosed with methylmalonic acidemia, 10 (33%) with propionic acidemia, and two (6.6%) with isovaleric acidemia. The mean age of the patients with OA and healthy subjects were 5.89 ± 4.11 years and 5.34 ± 4.36, respectively (P = 0.602). Twenty-nine (88%) of the patients had experienced frequent hospital admission, 13 (39%) were admitted to pediatric intensive care unit, and 18 (55%) suffered from sepsis. Naïve helper T cells and recent thymic emigrants were significantly lower in OAs (P < 0.001). Various defects in humoral immunity have also been documented including memory B cells and immunoglobulins. CONCLUSIONS: Patients with OAs may show adaptive immune defects rendering them susceptible to infections. Metabolic reprogramming based on nutritional modifications may be a promising therapeutic option in the future.

The gut microbiome in epilepsy.

The close relationship between epilepsy and autoimmune diseases and the fact that the cause of epilepsy is idiopathic in 60% of cases suggest that intestinal microbiota may play a role in the etiology of epilepsy. In this study, we analyzed and compared the intestinal microbiota composition of patients with idiopathic focal epilepsy (n = 30) and healthy volunteer group (n = 10) by 16s ribosomal DNA sequencing. Proteobacteria phylum was found to be higher in patients with epilepsy (25.4%) than in healthy volunteers group (1.5%). The genera of Campylobacter, Delftia, Haemophilus, Lautropia, Neisseria among Proteobacteria phylum were found to be statistically significantly higher in patients with epilepsy than in healthy volunteers (p < 0.05). Fusobacteria phylum was detected in 10.6% of the patients with epilepsy but not in the healthy volunteer group. The genus of the Fusobacteria phylum was found as Leptotrichia and Fusobacterium. In our study, taxonomic drift and significant differences in the intestinal microbiota of patients with epilepsy according to healthy volunteer group showed that autoimmune mechanisms and inflammation may have a role in the etiology of epilepsy. Our data should be supported by other studies as to the role of the intestinal microbiome in the prevention and treatment of epilepsy.

External Validation of the GREAT Score in Turkish Patients with Graves' Hyperthyroidism Treated with the Titration Regimen Method of Antithyroid Drugs: A Multicenter Study.

Recently, the Graves' Recurrent Events After Therapy score (GREAT) was proposed as a useful tool to predict relapse before starting antithyroid drugs (ATD) in patients with Graves' disease (GD). Therefore, we intended to assess the validity of the GREAT score in Turkish patients with GD, including patients who experienced a poorly controlled disease (multiple episodes of hyperthyroidism followed by euthyroidism or rarely hypothyroidism) during ATD dose titration. This is a retrospective multicenter study including 517 patients with the first episode of GD who were treated for at least 12 months. The patients were classified as relapse+poorly controlled disease (non-remission) and remission groups. During a median follow-up time of 35 months (12-144 months), 191 (37%) patients experienced a relapse, 136 (26.3%) a poorly controlled disease, and 190 (36.7%) remained in remission. Patients with non-remission disease tended to have significantly higher serum levels of TRAb, fT4, and fT3, and have larger goiter sizes on palpation at baseline, as compared with the remission group. Non-remission disease occurred in 12, 35, and, 53% of the patients falling into GREAT class I, II, and III, respectively (hazard ratio 2.56, 95% CI 2.02-3.51, p=0.012, and hazard ratio 3.54, 95% CI 2.12-5.91, p<0.001, for GREAT class II and III against class I, respectively). According to our study, the GREAT score is a useful tool to predict the risk of relapse as well as the occurrence of poorly controlled disease before starting treatment with ATDs.

Hypertension management: what is the role of case management?

Objective The aim of this study was to determine the effect of case management on hypertension management and on adherence to antihypertensive medication and chronic disease care of patients with hypertension. Method This study was conducted as an experimental and randomized controlled study. The sample of the study consisted of randomly selected patients with hypertension who did not have communication problems, who used antihypertensive medication treatment and whose treatment had been continuing for at least six months. The study group was given individual training (Hypertension causes, the risk factors, significance, unwanted side effects, medication treatment, changes in life style) and was applied case management model in hypertension - joint care protocol but no intervention was offered to the control group. Data was collected using the adherence to antihypertensive medication scale, the patient assessment of chronic illness care in the first and six months later interview. Results There was no significant difference between the study and control group according to adherence to antihypertensive medication and patient assessment of chronic illness care in the first interview. Otherwise, there were significant differences between the study and control group according to blood pressure, adherence to antihypertensive medication and patient assessment of chronic illness care in the six months later interview. The adherence to antihypertensive medication total score and the patient assessment of chronic illness care total score were significantly higher in the study group compared with control group in the six months later interview. Conclusion The case management plays an important role the in control of hypertension, and can improve adherence to antihypertensive medication and chronic illness care.

Protective effects of onion (Allium cepa) extract against doxorubicin-induced hepatotoxicity in rats.

BACKGROUND/AIM: Doxorubicin (DOX) is a widely used and potent chemotherapeutic agent. However, serious dose-limiting toxicity through generation of free oxygen radicals is a commonly encountered clinical problem. The aim of the current study was to assess the protective role of onion (Allium cepa) extract (ACE) against DOX-induced hepatotoxicity in rats. METHOD: A total of 24 rats were randomly divided into 3 equal experimental groups: (1) DOX; (2) ACE + DOX; and (3) control groups. ACE was given orally as 1 mL of fresh ACE juice for 14 consecutive days followed by DOX injection. DOX was injected intraperitoneally in a single dose of 30 mg/kg body weight to induce hepatotoxicity, and the rats were killed after 48 h from injection. Control group was given saline only. RESULTS: In the ACE pretreated group (ACE + DOX), serum aspartate transaminase, alanine transaminase, and tissue malondialdehyde and glutathione levels were significantly lower, while superoxide dismutase and glutathione peroxidase were higher compared with the DOX group. The histopathological examination of liver specimens revealed parenchymal necrosis, proliferation of biliary duct in DOX group; while ACE pretreatment provided marked reduction in these changes. CONCLUSION: Our study indicates that pretreatment with ACE protects against DOX-induced hepatotoxicity due to the antioxidant properties of ACE. Further studies on efficacy of antioxidant treatment by ACE in DOX-mediated toxicity and underlying mechanisms would provide a better explanation.

Neuroprotective effect of ebselen against intracerebroventricular streptozotocin-induced neuronal apoptosis and oxidative stress in rats.

The goal of this study was to examine the neuroprotective effect of ebselen against intracerebroventricular streptozotocin (ICV-STZ)-induced oxidative stress and neuronal apoptosis in rat brain. A total of 30 adult male Sprague-Dawley rats were randomly divided into 3 groups of 10 animals each: control, ICV-STZ, and ICV-STZ treated with ebselen. The ICV-STZ group rats were injected bilaterally with ICV-STZ (3 mg/kg) on days 1 and 3, and ebselen (10 mg/kg/day) was administered for 14 days starting from 1st day of ICV-STZ injection to day 14. Rats were killed at the end of the study and brain tissues were removed for biochemical and histopathological investigation. Our results demonstrated, for the first time, the neuroprotective effect of ebselen on Alzheimer's disease (AD) model in rats. Our present study, in ICV-STZ group, showed significant increase in tissue malondialdehyde levels and significant decrease in enzymatic antioxidants superoxide dismutase and glutathione peroxidase in the frontal cortex tissue. The histopathological studies in the brain of rats also supported that ebselen markedly reduced the ICV-STZ-induced histopathological changes and well preserved the normal histological architecture of the frontal cortex tissue. The number of apoptotic neurons was increased in frontal cortex tissue after ICV-STZ administration. Treatment of ebselen markedly reduced the number of degenerating apoptotic neurons. The study demonstrates the effectiveness of ebselen, as a powerful antioxidant, in preventing the oxidative damage and morphological changes caused by ICV-STZ in rats. Thus, ebselen may have a therapeutic value for the treatment of AD.

The association of vitamin D with inflammatory cytokines in diabetic peripheral neuropathy.

[Purpose] The effects of vitamin D on the circulating levels of IL-17 and IL-13 were investigated in patients with diabetic peripheral neuropathy, patients with diabetes mellitus type 2 without neuropathy, and healthy controls. [Subjects and Methods] A single-blind controlled clinical study was performed, including70 type 2 diabetic patients with or without diabetic peripheral neuropathy and 33 healthy volunteer controls. The 25(OH)D levels were evaluated using ultra-performance liquid chromatography, and IL-17 and IL-13 levels were assessed using enzyme-linked immunosorbent assays. [Results] The 25(OH) vitamin D concentration was lower in diabetic peripheral neuropathy patients than in diabetes mellitus patients without neuropathy and healthy controls. Similarly, 25(OH)D levels were lower in diabetes mellitus patients than healthy controls. IL-17 and IL-13 levels were higher in diabetes mellitus patients than in controls. Additionally, IL-13 levels were higher in diabetic peripheral neuropathy patients than in diabetes mellitus patients without neuropathy. These differences were statistically significant. There was a significant positive correlation between 25(OH)D and IL-13,and a negative correlation between 25(OH)D andIL-17 in the diabetic and diabetic neuropathy groups. [Conclusion] Vitamin D is a potential modifiable risk factor for diabetic peripheral neuropathy and may regulate inflammatory mediators, e.g., IL-17 and IL-13.

Serum YKL-40: a potential biomarker for psoriasis or endothelial dysfunction in psoriasis?

Psoriasis is a disease that can contribute to a risk of atherosclerosis. In several studies, impaired endothelial dysfunction (ED) is correlated with psoriasis. Serum YKL-40 is a new inflammatory biomarker of vascular damage, like ED and cardiovascular diseases. The aim of the study was to compare relevance of serum YKL-40 levels in psoriasis patients and healthy subjects according to ED diagnosis and identifiable cardiovascular risk factors. Sixty (31 female, 29 male) patients with plaque psoriasis, and 30 (18 female, 12 male) healthy controls were selected according to whether they had at least one or no identifiable risk factors for cardiovascular disease. All subjects were evaluated ultrasonographically for endothelial function and diagnosed as with or without ED and all groups compared for serum YKL-40 levels. YKL-40 levels of psoriatic patients with ED were higher than healthy controls with ED (P = <0.05). There were no statistical differences in between subjects without ED. YKL-40 levels of patients over age of 40 were higher than younger ones (P < 0.05). But in healthy controls, there were no differences. In comparison of cardiovascular risk-positive (RP) patients and RP healthy subjects, YKL-40 levels were higher in RP patients (P = <0.05). The elevation of plasma YKL-40 in psoriasis can be associated not only with inflammation of the disease, but also with ED. YKL-40 can be used as a marker for predicting and preventing cardiovascular diseases in RP psoriatic patients with age above 40.

The protective effects of ω-3 fatty acids on doxorubicin-induced hepatotoxicity and nephrotoxicity in rats.

This study aims to evaluate the protective effects of ω-3 fatty acids (FAs) on doxorubicin (DOX)-induced hepatotoxicity and nephrotoxicity in rats. A total of 24 adult male Sprague Dawley rats were divided into three groups. Control group was given only saline by intragastric gavage. DOX group received DOX at the dose of 30 mg/kg intraperitoneally on day 28. DOX-ω-3 FA group was given as ω-3 FAs at the dose of 400 mg/kg daily by intragastric gavage for 30 days and received DOX at the dose of 30 mg/kg intraperitoneally on day 28. At the end of the 30-day experimental period, the serum, liver and kidney tissue specimens were taken from the animals by giving a general anesthesia. Glutathione (GSH) and malondialdehyde (MDA) levels in serum and GSH and MDA levels and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in liver and kidney tissues were measured spectrophotometrically. In our study, a significant increase in MDA levels was observed in rats when given a dose of DOX and a significant decrease in the levels of GSH, SOD and GSH-Px activities in serum, liver and kidney tissues was determined when compared with control group. In addition, a significant decrease in MDA levels was observed in rats when a dose of ω-3 FAs was given with DOX and a significant increase was determined in the levels of GSH, SOD and GSH-Px activities in serum, liver and kidney tissues, when compared with DOX group. We concluded that ω-3 FA had favorable effects in rat liver and kidney tissues by preventing oxidative damage.

Reduction Mammaplasty Effect on Pulmonary Function and Arterial Blood Gas in the Overweight Female.

BACKGROUND: This study sought to prospectively determine whether reduction mammaplasty improves the results of pulmonary function tests (PFTs) and arterial blood gas (ABG) measurements among overweight or obese women with macromastia and assess whether these changes are correlated with participant weight and body mass index (BMI) changes. METHODS: Thirty women who were overweight or obese and underwent bilateral reduction mammaplasty were included in this study. PFT and ABG measurements were performed within a 4-week period before reduction mammaplasty and 3 months after reduction mammaplasty. The following selected PFT parameters were used to diagnose the restrictive patterns of ventilatory defects: forced vital capacity (FVC), forced expiratory volume at one second (FEV1), the ratio of FEV1 to FVC expressed as a percentage (FEV1/FVC%), and the average FVC flow rate of 25-75 % (FEF 25-75 %). The ABG measurements included PaO2, PaCO2, HCO3, oxygen saturation, and pH. RESULTS: A significant difference was found between certain preoperative and postoperative PFTs (i.e., predicted FVC%, predicted FEV1% and predicted FEF 25-75 %) and between all of the preoperative and postoperative ABG measurements (pH, PaO2, PaCO2, HCO3, and Sat O2). A significant positive correlation was found between specimen weight and improvements in FEF 25-75 % and Sat O2. A significant positive correlation was found between the percentage reduction in BMI and the improvements in FEF 25-75 % and FVC. CONCLUSIONS: Overweight or obese women who underwent reduction mammaplasty showed significant improvements in certain PFT and all of the ABG measurements at 3 months after surgery. The more resected breast tissue predicts greater improvements in FEF 25-75 % and Sat O2, and greater reductions in BMI predicted increased improvements in FEF 25-75 % and FVC.

Serum Neopterin, Biopterin, Tryptophan, and Kynurenine Levels in Patients with Fabry Disease

Background: Fabry disease is characterized by the accumulation of globotriaosylceramide. Substrate accumulation in lysosomes is thought to trigger an inflammatory response and is responsible for progressive organ damage through the induction of autoimmunity. The levels of pteridine and kynurenine pathway metabolites increase when immune activation is observed and are employed to monitor several diseases and determine prognosis. Aims: To elucidate the effects of immune activation on the pathophysiology of Fabry disease and to investigate the potential utility of pteridine and kynurenine metabolites. Study Design: A prospective case-control study. Methods: In this study, 33 patients with Fabry disease and 33 age-and sex-matched healthy controls were included. Blood pteridine and kynurenine metabolites were studied in both groups. Organ involvement in Fabry disease and its correlation with the pteridine and kynurenine pathways were also investigated. Results: The patients' neopterin and biopterin levels and the tryptophan/kynurenine ratio were statistically higher than those of the healthy control group (p < 0.05). A statistically significant association was found between neopterin levels and hypertrophic cardiomyopathy, cardiac arrhythmias, and GFR values (p = 0.044, p = 0.021, and p = 0.030, respectively), tryptophan and corneal verticillate, hearing loss and tinnitus (p = 0.010, p = 0.009 and p = 0.046, respectively), and kynurenine levels and valvular heart disease (p = 0.020). Conclusion: From the onset of the disease, patients with Fabry disease exhibited elevated levels of inflammation and immune activation. Furthermore, inflammation and immune activation markers can be used as early disease biomarkers.

Myxoma Virus Combination Therapy Enhances Lenalidomide and Bortezomib Treatments for Multiple Myeloma.

This study aimed to explore the effectiveness and safety of Myxoma virus (MYXV) in MM cell lines and primary myeloma cells obtained from patients with multiple myeloma. Myeloma cells were isolated from MM patients and cultured. MYXV, lenalidomide, and bortezomib were used in MM cells. The cytotoxicity assay was investigated using WST-1. Apoptosis was assessed through flow cytometry with Annexin V/PI staining and caspase-9 concentrations using ELISA. To explore MYXV entry into MM cells, monoclonal antibodies were used. Moreover, to explore the mechanisms of MYXV entry into MM cells, we examined the level of GFP-labeled MYXV within the cells after blocking with monoclonal antibodies targeting BCMA, CD20, CD28, CD33, CD38, CD56, CD86, CD117, CD138, CD200, and CD307 in MM cells. The study demonstrated the effects of treating Myxoma virus with lenalidomide and bortezomib. The treatment resulted in reduced cell viability and increased caspase-9 expression. Only low-dose CD86 blockade showed a significant difference in MYXV entry into MM cells. The virus caused an increase in the rate of apoptosis in the cells, regardless of whether it was administered alone or in combination with drugs. The groups with the presence of the virus showed higher rates of early apoptosis. The Virus, Virus + Bortezomib, and Virus + Lenalidomide groups had significantly higher rates of early apoptosis (p < 0.001). However, the measurements of late apoptosis and necrosis showed variability. The addition of MYXV resulted in a statistically significant increase in early apoptosis in both newly diagnosed and refractory MM patients. Our results highlight that patient-based therapy should also be considered for the effective management of MM.

The impact of microscopic extrathyroidal extension on the clinical outcome of classic subtype papillary thyroid microcarcinoma: a multicenter study.

OBJECTIVES: Despite the presumed overdiagnosis of papillary thyroid microcarcinoma (PTMC) which has resulted in a new trend toward less-extensive surgery and a preference for active surveillance, the impact of microscopic extrathyroidal extension (mETE) on the clinical outcomes of PTMC is still controversial. This study assessed the impact of mETE on the clinical outcomes of patients with classic subtype PTMC. METHODS: The data of consecutive patients who underwent thyroidectomy and were histopathologically diagnosed as classic subtype PTMC were analyzed. Cox's proportional hazards model was used to assess the impact of contributing variables on persistent/recurrent disease. Disease-free survival was estimated using the Kaplan-Meier method. RESULTS: This study included 1013 patients (84% females), with a mean follow-up period of 62.5 ± 35.3 months. Patients with mETE had a significantly higher rate of locoregional persistent/recurrent disease than patients without mETE (9.8% vs 2.1%, p < 0.001). The disease-free survival rate was significantly lower in patients with mETE than in those without (90.2% vs 97%, Log-Rank p < 0.001). Furthermore, mETE and neck lymph node involvement were independent predictors of persistent/recurrent disease in multivariate analysis (HR: 2.43, 95% CI:1.02-5.81, p = 0.043; HR: 4.38, 95% CI: 1.7-11.2, p = 0.002, respectively). CONCLUSIONS: In patients with the classic subtype of PTMC, mETE is an independent predictor of persistent/recurrent disease and is associated with a lower DFS rate. However, neck lymph node involvement is the strongest predictor of persistent/recurrent disease. Therefore, PTMCs with mETE and neck lymph node involvement are at a higher risk of persistent/recurrent disease than individuals lacking both characteristics.

Disease-free survival and the prognostic factors affecting disease-free survival in patients with medullary thyroid carcinoma: a multicenter cohort study.

PURPOSE: Despite several factors that may have been associated with poor disease-free survival (DFS) in patients with medullary thyroid carcinoma (MTC), only a few studies have evaluated the prognostic factors affecting DFS in MTC patients. Therefore, this study evaluated the prognostic factors affecting DFS, in a large number of patients with MTC. METHODS: Patients treated for MTC were retrospectively analyzed. Patients were stratified as having persistent/recurrent disease and no evidence of disease (NOD) at the last follow-up. The factors affecting DFS after the initial therapy and during the follow-up period were investigated. RESULTS: This study comprised 257 patients [females 160 (62.3%), hereditary disease 48 (18.7%), with a mean follow-up time of 66.8 ± 48.5 months]. Persistent/recurrent disease and NOD were observed in 131 (51%) and 126 (49%) patients, respectively. In multivariate analysis, age > 55 (HR: 1.65, p = 0.033), distant metastasis (HR: 2.41, p = 0.035), CTN doubling time (HR: 2.7, p = 0.031), and stage III vs. stage II disease (HR 3.02, p = 0.048) were independent predictors of persistent/recurrent disease. Although 9 (8%) patients with an excellent response after the initial therapy experienced a structural recurrence, the absence of an excellent response was the strongest predictor of persistent/recurrent disease (HR: 5.74, p < 0.001). CONCLUSIONS: The absence of an excellent response after initial therapy is the strongest predictor of a worse DFS. However, a significant proportion of patients who achieve an excellent response could experience a structural recurrence. Therefore, careful follow-up of patients, including those achieving an excellent response is essential.

The effects of onion (Allium cepa) extract on doxorubicin-induced apoptosis in aortic endothelial cells.

The aim of this study was to investigate the effects of onion (Allium cepa) extracts (ACE) on doxorubicin (DOX)-induced apoptosis in aortic endothelial cells. The rats in the ACE-pretreated group were given a daily dose of 1 ml ACE for 14 days. To induce aortic endothelial cell apoptosis, DOX (30 mg kg(-1) body weight) was injected intraperitoneally by a single dose and the rats were sacrificed after 48 h. To date, no such studies have been performed on antiapoptotic potential of ACE on DOX-induced apoptosis in aortic endothelial cells. Our data indicate a significant reduction in the activity of in situ identification of apoptosis using terminal dUTP nick end-labeling in aortic endothelial cells of the DOX-treated group with ACE therapy. DOX-treated with ACE groups showed a significant decrease in malondialdehyde levels and increased levels of glutathione in comparison with the DOX-treated group. Data from our study show that prevention of endothelial cell apoptosis by ACE may contribute to the restoration of aortic endothelial dysfunction that is associated with DOX treatment.

Antioxidant and anti-apoptotic effects of onion (Allium cepa) extract on doxorubicin-induced cardiotoxicity in rats.

The aim of this study was to investigate the antioxidant and anti-apoptotic effects of onion (Allium cepa) extracts (ACE) on doxorubicin (DOX)-induced cardiotoxicity. The rats in the ACE-pretreated group were given a daily dose of 1 ml ACE for 14 days. To induce cardiotoxicity, DOX (30 mg kg(-1) body weight) was injected intraperitoneally by a single dose and the rats were sacrificed after 48 h. To date, no such studies have been performed on the cardioprotective and anti-apoptotic potential of ACE on DOX-induced cardiotoxicity. Our data indicate a significant reduction in the activity of in situ identification of apoptosis using terminal dUTP nick end-labeling in cardiomyocytes of the DOX-treated group with ACE therapy. The DOX-treated with ACE groups showed a significant decrease in malondialdehyde levels, and increased activities of superoxide dismutase, glutathione and glutathione peroxidase in comparison with the DOX-treated group. Creatine kinase, creatine kinase MB, lactate dehydrogenase activities and cardiac troponin I levels were significantly decreased in the DOX + ACE group in comparison with the DOX group. These biochemical and histological disturbances were effectively attenuated on pretreatment with ACE. The present study showed that ACE may be a suitable cardioprotector against toxic effects of DOX.

[Effect of overweight on cardiac function in children]. / Çocuklarda kilo fazlaliginin kalp fonksiyonlarina etkisi.

OBJECTIVES: It is known that obesity is related to heart failure. Asymptomatic left ventricular diastolic dysfunction (LVDD) is associated with the development of heart failure. The relationship between subclinical LVDD and overweight in children is not clear. The purpose of this study was to evaluate the effect of body mass index (BMI) and waist circumference on left ventricular mass index (LVMI) and LVDD in overweight children. STUDY DESIGN: A total of 153 children were enrolled in the study. Of these, 91 were normal weight (age-adjusted BMI: 15-85 percentile), and 62 were overweight (age-adjusted BMI: 85-95 percentile). After measuring two-dimensional and M-mode echocardiographic variables, left and right ventricle diastolic functions were assessed by conventional and tissue Doppler imaging. RESULTS: Compared to controls, overweight children had increased left atrium, aortic and left ventricular diameters, left ventricular wall thickness, LVM and LVMI, and septal mitral annulus e', septal e'/a', lateral e', lateral e'/a', lateral tricuspid annulus e', and e'/a' values. There were negative correlations between tissue Doppler diastolic parameters (septal mitral annulus e', lateral mitral annulus e', lateral tricuspid annulus e', septal mitral annulus e'/a', lateral mitral annulus e'/a', and lateral tricuspid annulus e'/a') and BMI, waist circumference, insulin, HOMA index, as well as systolic and diastolic blood pressure. Positive correlations were found between LVMI and BMI and between LVMI and waist circumference. BMI was found to be the predictor of decreased mitral anulus septal e', septal e'/a', lateral e', lateral e'/a'. CONCLUSION: Compared with normal-weight children, overweight children have decreased LV diastolic function. BMI is associated with a reduction in LV diastolic function in overweight children.