Ex Vivo Produced Oral Mucosa Equivalent By Using The Direct Explant Cell Culture Technique

Objective: The aim of this study is the histological and immunohistochemical evaluation of ex vivo produced oral mucosal equivalents using keratinocytes cultured by direct explant technique. Material and Methods: Oral mucosa tissue samples were obtained from the keratinized gingival tissues of 14 healthy human subjects. Human oral mucosa keratinocytes from an oral mucosa biopsy specimen were dissociated by the explant technique. Once a sufficient population of keratinocytes was reached, they were seeded onto the type IV collagen coated "AlloDerm" and taken for histological and immunohistochemical examinations at 11 days postseeding of the keratinocytes on the cadaveric human dermal matrix. Results: Histopathologically and immunohistochemically, 12 out of 14 successful ex vivo produced oral mucosa equivalents (EVPOME) that consisted of a stratified epidermis on a dermal matrix have been developed with keratinocytes cultured by the explant technique. Conclusion: The technical handling involved in the direct explant method at the beginning of the process has fewer steps than the enzymatic method and use of the direct explant technique protocol for culturing of human oral mucosa keratinocyte may be more adequate for EVPOME production.WoSScopu

A Cross-Sectional Study of Overtreatment and Deintensification of Antidiabetic and Antihypertensive Medications in Diabetes Mellitus: The TEMD Overtreatment Study

Introduction Targeting better glycated hemoglobin (HbA1c) and blood pressure (BP) goals may endanger older adults with type 2 diabetes mellitus (T2DM). Overtreatment of T2DM and hypertension is a trending issue, although undertreatment is still common. We investigated the rates and predictors of overtreatment and undertreatment of glycemia and BP in older adults with T2DM and physicians' attitudes to deintensify or intensify treatment. Methods Data from older adults (>= 65 years) enrolled in a large nationwide T2DM survey in 2017 across Turkey were analyzed. Overtreatment of glycemia was defined as HbA1c = 2 oral antihyperglycemics or insulin, and BP overtreatment was defined as systolic BP (SBP) = 2 drugs. Undertreatment of glycemia was defined as HbA1c > 9%, and BP undertreatment was defined as SBP > 150 mmHg or DBP > 90 mmHg. Deintensification or intensification rates were calculated according to treatment modification initiated by the treating physician(s). Results The rate of overtreatment in the glycemia group (n = 1264) was 9.8% (n = 124) and that in the BP group (n = 1052) was 7.3% (n = 77), whereas the rate of undertreatment was 14.2% (n = 180) and 15.2% (n = 160), respectively. In the adjusted model, use of oral secretagogues (sulfonylureas or glinides) (odds ratio [OR] 1.94, 95% confidence interval [CI] 1.2-3.1) and follow-up at a private clinic (OR 1.81, 95% CI 1.0-3.3) were predictors of glycemia overtreatment. BP overtreatment was independently associated with the use insulin-based diabetes therapies (OR 1.86, 95% CI 1.14-3.04). There was no independent association of BP undertreatment to the study confounders. The deintensification and intensification rates were 25 and 75.6%, respectively, for glycemia and 10.9 and 9.2%, respectively, for BP. Conclusions The results show that one in ten older adults with T2DM are overtreated while one in four require modification of their current antihyperglycemic and antihypertensive treatments. Physicians are eager to intensify medications while they largely ignore deintensification in diabetes management. These results warrant enforced measures to improve the care of older adults with T2DM. Plain Language Summary Plain language summary is available for this article

A Cross-Sectional Study of Overtreatment and Deintensification of Antidiabetic and Antihypertensive Medications in Diabetes Mellitus: The TEMD Overtreatment Study

Introduction Targeting better glycated hemoglobin (HbA1c) and blood pressure (BP) goals may endanger older adults with type 2 diabetes mellitus (T2DM). Overtreatment of T2DM and hypertension is a trending issue, although undertreatment is still common. We investigated the rates and predictors of overtreatment and undertreatment of glycemia and BP in older adults with T2DM and physicians' attitudes to deintensify or intensify treatment. Methods Data from older adults (>= 65 years) enrolled in a large nationwide T2DM survey in 2017 across Turkey were analyzed. Overtreatment of glycemia was defined as HbA1c = 2 oral antihyperglycemics or insulin, and BP overtreatment was defined as systolic BP (SBP) = 2 drugs. Undertreatment of glycemia was defined as HbA1c > 9%, and BP undertreatment was defined as SBP > 150 mmHg or DBP > 90 mmHg. Deintensification or intensification rates were calculated according to treatment modification initiated by the treating physician(s). Results The rate of overtreatment in the glycemia group (n = 1264) was 9.8% (n = 124) and that in the BP group (n = 1052) was 7.3% (n = 77), whereas the rate of undertreatment was 14.2% (n = 180) and 15.2% (n = 160), respectively. In the adjusted model, use of oral secretagogues (sulfonylureas or glinides) (odds ratio [OR] 1.94, 95% confidence interval [CI] 1.2-3.1) and follow-up at a private clinic (OR 1.81, 95% CI 1.0-3.3) were predictors of glycemia overtreatment. BP overtreatment was independently associated with the use insulin-based diabetes therapies (OR 1.86, 95% CI 1.14-3.04). There was no independent association of BP undertreatment to the study confounders. The deintensification and intensification rates were 25 and 75.6%, respectively, for glycemia and 10.9 and 9.2%, respectively, for BP. Conclusions The results show that one in ten older adults with T2DM are overtreated while one in four require modification of their current antihyperglycemic and antihypertensive treatments. Physicians are eager to intensify medications while they largely ignore deintensification in diabetes management. These results warrant enforced measures to improve the care of older adults with T2DM. Plain Language Summary Plain language summary is available for this article

Induction of apoptosis and autophagy via regulation of AKT and JNK mitogen-activated protein kinase pathways in breast cancer cell lines exposed to gold nanoparticles loaded with TNF-α and combined with doxorubicin

Gold nanoparticles (GNPs) tagged with peptides are pioneers in bioengineered cancer therapy. The aim of the current work was to elucidate the potential anticancer interactions between doxorubicin and GNPs loaded with tumor necrosis factor-alpha (TNF-α). To investigate whether GNPs loaded with TNF and doxorubicin could stimulate autophagy and apoptosis in breast cancer cells. Two human breast cancer cell lines, MCF-7 and AMJ-13, as well as different apoptotic and autophagy markers, were used. In both cell types, treatment with TNF-loaded GNPs in conjunction with doxorubicin increased the production of apoptotic proteins including Bad, caspase-3, caspase-7, and p53 with upregulation of the LC3-II and Beclin1 proteins. In addition, the findings showed that the mitogen-activated protein kinase signaling pathway was dramatically affected by the GNPs loaded with TNF-α and combined with doxorubicin. This had the effect of decreasing p-AKT while simultaneously increasing p-JNK1/2. The findings demonstrated that GNPs loaded with TNF-α and combined with doxorubicin can induce both autophagy and apoptosis in breast cancer cells. These results suggest that TNF- and doxorubicin-loaded GNPs provide a therapeutic option as a nanomedicine to inhibit the proliferation of breast cancer

Impact of Obesity on the Metabolic Control of Type 2 Diabetes: Results of the Turkish Nationwide Survey of Glycemic and Other Metabolic Parameters of Patients with Diabetes Mellitus (TEMD Obesity Study)

Background: Obesity is the main obstacle for metabolic control in patients with type 2 diabetes. Turkey has the highest prevalence of obesity and type 2 diabetes in Europe. The effect of obesity on the metabolic control, and the macro-and microvascular complications of patients are not apparent. Objectives: This nationwide survey aimed to investigate the prevalence of overweight and obesity among patients with type 2 diabetes and to search for the impact of obesity on the metabolic control of these patients. We also investigated the independent associates of obesity in patients with type 2 diabetes. Methods: We consecutively enrolled patients who were under follow-up for at least 1 year in 69 tertiary healthcare units in 37 cities. The demographic, anthropometric, and clinical data including medications were recorded. Patients were excluded if they were pregnant, younger than 18 years, had decompensated liver disease, psychiatric disorders interfering with cognition or compliance, had bariatric surgery, or were undergoing renal replacement therapy. Results: Only 10% of patients with type 2 diabetes (n = 4,648) had normal body mass indexes (BMI), while the others were affected by overweight (31%) or obesity (59%). Women had a significantly higher prevalence of obesity (53.4 vs. 40%) and severe obesity (16.6 vs. 3.3%). Significant associations were present between high BMI levels and lower education levels, intake of insulin, antihypertensives and statins, poor metabolic control, or the presence of microvascular complications. Age, gender, level of education, smoking, and physical inactivity were the independent associates of obesity in patients with type 2 diabetes. Conclusion: The TEMD Obesity Study shows that obesity is a major determinant of the poor metabolic control in patients with type 2 diabetes. These results underline the importance of prevention and management of obesity to improve health care in patients with type 2 diabetes. Also, the results point out the independent sociodemographic and clinical associates of obesity, which should be the prior targets to overcome, in the national fight with obesity. (c) 2019 The Author(s) Published by S. Karger AG, Base

Turkish nationwide survEy of glycemic and other Metabolic parameters of patients with Diabetes mellitus (TEMD study)

Aims: Turkey has the highest prevalence of diabetes in Europe. It is therefore essential to know the overall cardiovascular risk and reveal the predictors of metabolic control in Turkish adults with diabetes mellitus