Association of obesity with cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease: Insights from TECOS.

BACKGROUND: Obesity is a risk factor for type 2 diabetes (T2D) and cardiovascular disease (CVD). Whether obesity affects outcomes among those with T2D and atherosclerotic CVD (ASCVD) remains uncertain. Our objective was to investigate the relationship between body mass index (BMI) and ASCVD outcomes among TECOS participants with T2D and ASCVD. METHODS: BMI categories were defined as underweight/normal weight (BMI <25 kg/m2), overweight (25-29.9 kg/m2), obese class I (30-34.9 kg/m2), obese class II (35-39.9 kg/m2), and obese class III (≥ 40 kg/m2). Asian-specific BMI categories were applied to Asian participants. Kaplan-Meier survival analysis and Cox proportional hazards models were used to examine associations between baseline BMI and a composite CV outcome (CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina). RESULTS: For 14,534 TECOS patients with available BMI, mean age was 65.5 years; 29.3% were female, 32.0% non-White, and 23.1% insulin-treated, with median 3 years' follow-up. At baseline, 11.6% (n = 1686) were underweight/normal weight, 38.1% (n = 5532) overweight, 32.2% (n = 4683) obese class I, 12.4% (n = 1806) obese class II, and 5.7% (n = 827) obese class III. The composite CV outcome occurred in 11.4% (n = 1663) of participants; the outcome risk was lower, compared with under/normal weight, in overweight (HR 0.83, 95% CI 0.71-0.98) and obese class I (HR 0.79, 95% CI 0.67-0.93) individuals. Obesity was not associated with worse glycemic control. CONCLUSIONS: The majority of TECOS participants with ASCVD and T2D were overweight or obese, yet overweight or obese class I individuals had lower CV risk than those who were under/normal weight. These results suggest the presence of an obesity paradox, but this paradox may reflect an epidemiological artifact rather than a true negative association between normal weight and clinical outcomes.

Sitagliptin does not reduce the risk of cardiovascular death or hospitalization for heart failure following myocardial infarction in patients with diabetes: observations from TECOS.

BACKGROUND: To examine the effects of the DPP-4i sitagliptin on CV outcomes during and after incident MI in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). METHODS: TECOS randomized 14,671 participants with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD) to sitagliptin or placebo, in addition to usual care. For those who had a within-trial MI, we analyzed case fatality, and for those with a nonfatal MI, we examined a composite cardiovascular (CV) outcome (CV death or hospitalization for heart failure [hHF]) by treatment group, using Cox proportional hazards models left-censored at the time of the first within-trial MI, without and with adjustment for potential confounders, in intention-to-treat analyses. RESULTS: During TECOS, 616 participants had ≥ 1 MI (sitagliptin group 300, placebo group 316, HR 0.95, 95% CI 0.81-1.11, P = 0.49), of which 25 were fatal [11 and 14, respectively]). Of the 591 patients with a nonfatal MI, 87 (15%) died subsequently, with 66 (11%) being CV deaths, and 57 (10%) experiencing hHF. The composite outcome occurred in 58 (20.1%; 13.9 per 100 person-years) sitagliptin group participants and 50 (16.6%; 11.7 per 100 person-years) placebo group participants (HR 1.21, 95% CI 0.83-1.77, P = 0.32, adjusted HR 1.23, 95% CI 0.83-1.82, P = 0.31). On-treatment sensitivity analyses also showed no significant between-group differences in post-MI outcomes. CONCLUSIONS: In patients with type 2 diabetes and ASCVD experiencing an MI, sitagliptin did not reduce subsequent risk of CV death or hHF, contrary to expectations derived from preclinical animal models. Trial registration clinicaltrials.gov no. NCT00790205.

Secondary Prevention of Cardiovascular Disease in Patients With Type 2 Diabetes Mellitus: International Insights From the TECOS Trial (Trial Evaluating Cardiovascular Outcomes With Sitagliptin).

BACKGROUND: Intensive risk factor modification significantly improves outcomes for patients with diabetes mellitus and cardiovascular disease. However, the degree to which secondary prevention treatment goals are achieved in international clinical practice is unknown. METHODS: Attainment of 5 secondary prevention parameters-aspirin use, lipid control (low-density lipoprotein cholesterol <70 mg/dL or statin therapy), blood pressure control (<140 mm Hg systolic, <90 mm Hg diastolic), angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use, and nonsmoking status-was evaluated among 13 616 patients from 38 countries with diabetes mellitus and known cardiovascular disease at entry into TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin). Logistic regression was used to evaluate the association between individual and regional factors and secondary prevention achievement at baseline. Cox proportional hazards regression analysis was used to determine the association between baseline secondary prevention achievement and cardiovascular death, myocardial infarction, or stroke. RESULTS: Overall, 29.9% of patients with diabetes mellitus and cardiovascular disease achieved all 5 secondary prevention parameters at baseline, although 71.8% achieved at least 4 parameters. North America had the highest proportion (41.2%), whereas Western Europe, Eastern Europe, and Latin America had proportions of ≈25%. Individually, blood pressure control (57.9%) had the lowest overall attainment, whereas nonsmoking status had the highest (89%). Over a median 3.0 years of follow-up, a higher baseline secondary prevention score was associated with improved outcomes in a step-wise graded relationship (adjusted hazard ratio, 0.60; 95% confidence interval, 0.47-0.77 for those patients achieving all 5 measures versus those achieving ≤2). CONCLUSIONS: In an international trial population, significant opportunities exist to improve the quality of cardiovascular secondary prevention care among patients with diabetes mellitus and cardiovascular disease, which in turn could lead to reduced risk of downstream cardiovascular events. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00790205.

Diabetic wound regeneration using heparin-mimetic peptide amphiphile gel in db/db mice.

There is an urgent need for more efficient treatment of chronic wounds in diabetic patients especially with a high risk of leg amputation. Biomaterials capable of presenting extracellular matrix-mimetic signals may assist in the recovery of diabetic wounds by creating a more conducive environment for blood vessel formation and modulating the immune system. In a previous study, we showed that glycosaminoglycan-mimetic peptide nanofibers are able to increase the rate of closure in STZ-induced diabetic rats by induction of angiogenesis. The present study investigates the effect of a heparin-mimetic peptide amphiphile (PA) nanofiber gel on full-thickness excisional wounds in a db/db diabetic mouse model, with emphasis on the ability of the PA nanofiber network to regulate angiogenesis and the expression of pro-inflammatory cytokines. Here, we showed that the heparin-mimetic PA gel can support tissue neovascularization, enhance the deposition of collagen and expression of alpha-smooth muscle actin (α-SMA), and eliminate the sustained presence of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in the diabetic wound site. As the absence of neovascularization and overexpression of pro-inflammatory markers are a hallmark of diabetes and interfere with wound recovery by preventing the healing process, the heparin-mimetic PA treatment is a promising candidate for acceleration of diabetic wound healing by modulating angiogenesis and local immune response.

Evaluation of biomechanical properties of the cornea in patients with primary hyperparathyroidism.

The purpose of this study is to compare the corneal biomechanical properties in primary hyperparathyroid patients and healthy control subjects. The study consisted of 31 patients with primary hyperparathyroidism (study group) and 31 healthy subjects (control group). Corneal biomechanical properties, including corneal hysteresis (CH), corneal resistance factor (CRF), and intraocular pressure (IOP) were measured with an ocular response analyzer (ORA). IOP was also measured using Goldmann applanation tonometry (GAT), and central corneal thickness (CCT) was measured with an ultrasonic pachymeter. The differences in ORA parameters and CCT between study and control group participants were analyzed. The mean CH in study and control groups was 8.7 ± 1.9 mmHg (5.3-13.7 mmHg) and 9.8 ± 1.5 mmHg (7.7-14.3 mmHg), respectively (p = 0.018). The mean CRF was 9.5 ± 1.8 (5.5-13.7) in the study group compared with 9.8 ± 1.5 (6.2-12.8) in the control group. The difference for CRF was not statistically significant (p = 0.41). In study and control group, corneal-compensated IOP (IOPcc) values were 18.2 ± 4.2 and 16.9 ± 2.7 mmHg, respectively (p = 0.12). Mean IOP measurement values with GAT were 16.3 ± 3.4 mmHg for study group and 16.5 ± 2.7 mmHg for control group (p = 0.71). The mean differences of IOPcc and IOPGAT in the study group eyes were higher than that of control group eyes (1.9 vs. 0.4 mmHg). CCT was 536.5 ± 25.4 µm (490-593 µm) in study group eyes compared with 534.2 ± 31.4 µm (472-602 µm) in control eyes (p = 0.75). Hyperparathyroidism could be associated with a decrease of CH. The differences between IOPcc and IOPGAT in these patients were higher than normal subjects. Underestimation of IOP readings with GAT may be a consequence of the lower CH in patients with hyperparathyroididsm.

Effect of lifestyle interventions with or without metformin therapy on serum levels of osteoprotegerin and receptor activator of nuclear factor kappa B ligand in patients with prediabetes.

Osteoprotegerin has been shown to be increased in cardiovascular disorders and type 2 diabetes mellitus. Prediabetes represents a high risk condition for diabetes and diabetic complications. Therefore, we aimed to find the relationship between prediabetes and osteoprotegerin with nuclear factor-B ligand, carotid intima media thickness, and metabolic markers. A total of 54 participants with prediabetes including impaired fasting glucose (n = 21), impaired glucose tolerance (n = 8), impaired fasting glucose and impaired glucose tolerance (n = 25), and 60 healthy individuals as a control were admitted to the study. Metabolic and anthropometric parameters, insulin resistance variables, osteoprotegerin, and nuclear factor-B ligand markers, carotid intima media thickness were examined at baseline for all participants. To evaluate the effect of therapy we determined the same parameters after the end of the study. Measurements of waist circumference, body mass index, body fat percentage and levels of fasting blood glucose, fasting insulin, homeostatic model assessment of insulin resistance, triglyceride levels and hsCRP and carotid intima media thickness were significantly higher in patients with prediabetes (p < 0.05). We also found higher osteoprotegerin and lower nuclear factor-B ligand levels in patients than in controls however, the value was non-significant (p > 0.05). Patients with prediabetes were under lifestyle interventions with (group 1, n = 33) or without metformin (group 2, n = 21) therapy. Baseline anthropometric and metabolic characteristics were not found statistically different in group 1 and group 2. Mean follow up period of the patients were 7.9 ± 2.2 month (min-max: 6-12 months). After the follow up period we evaluated the same parameters and found significant differences between waist circumference, body mass index, body fat percentage, fasting insulin, homeostatic model assessment of insulin resistance, and osteoprotegerin levels (p < 0.05). However, carotid intima media thickness, and nuclear factor-B ligand levels significantly different only in the group treated with metformin (p < 0.05). We also compared the variables after the treatment period with the control group and found significantly lower levels in terms of fasting insulin, homeostatic model assessment of insulin resistance, waist circumference, body mass index, body fat percentage, carotid intima media thickness, osteoprotegerin, and nuclear factor-B ligand values (p < 0.05). Correlation analysis revealed a negative relationship between nuclear factor-B ligand and body mass index, and body fat percentage in group 1 (p = 0.05, r = -0.646, p = 0.01, r = -0.585). Therapy of prediabetes was associated with a significant decrease in osteoprotegerin and certain metabolic variables together with an increase in nuclear factor-B ligand levels particularly in patients with under metformin therapy.

The role of BRD7 in embryo development and glucose metabolism.

Bromodomain-containing protein 7 (BRD7) is a member of bromodomain-containing protein family and its function has been implicated in several diseases. We have previously shown that BRD7 plays a role in metabolic processes. However, the effect of BRD7 deficiency in glucose metabolism and its role in in vivo have not been fully revealed. Here, we report the essential role of BRD7 during embryo development. Mice homozygous for BRD7 led to embryonic lethality at mid-gestation. Homozygous BRD7 knockout (KO) mice showed retardation in development, and eventually all BRD7 KO embryos died in utero prior to E16.5. Partial knockdown of Brd7 gene displayed mild changes in glucose metabolism.

Visceral Obesity Mediates the Association Between Metabolic Syndrome and Obstructive Sleep Apnea Syndrome.

BACKGROUND: Metabolic syndrome (MetS) and visceral obesity are more prevalent in obstructive sleep apnea syndrome (OSAS). We investigated the association of visceral fat (VF) measures with the components of MetS in OSAS patients with different severity levels, according to World Health Organization (WHO, 1999), National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III, 2001), and International Diabetes Federation (IDF, 2005) definitions. PATIENTS AND METHODS: Study population was grouped according to polysomnography results as non-OSAS [who had apnea-hypopnea index (AHI) <5, n = 51], mild OSAS (5 < AHI <15, n = 52), moderate OSAS (15 < AHI <30, n = 53), and severe OSAS (AHI >30, n = 53). VF ratio was measured by abdominal bioimpedance analysis. Waist-to-hip ratio (WHR), homeostasis model assessment of insulin resistance (HOMA-IR), and lipid profiles were assessed in all subjects. RESULTS: The prevelance of MetS in OSAS patients was 30.0%, 35.6%, and 44.4% according to WHO, NCEP-ATP III, and IDF definitions, respectively. MetS was found in 27.5% non-OSAS and 72.8% OSAS according to at least one definition (P = 0.012). Within OSAS group, 27.2% subjects had average, 38.0% had slightly excessive, and 34.8% had an excessive VF ratio. The prevelance of MetS was similar in various VF ratios (P > 0.05). However HOMA-IR increased progressively with VF ratio after adjusting for age, gender, and body mass index (BMI; P = 0.02). AHI increased progressively with BMI (P = 0.02), WHR (P = 0.03), VF ratio (P = 0.01), HOMA-IR (P = 0.02), and MetS (P = 0.016). CONCLUSION: Since severity of OSAS, in terms of AHI and insulin resistance, is both associated with VF rather than BMI, VF should be suggested to link OSAS and MetS. The IDF definition is more sensitive in OSAS patients to diagnose MetS, as central obesity and insulin resistance are obligatory components. This would allow clinicians to intervent earlier to adverse metabolic outcomes of OSAS.

Serum heart type fatty acid binding protein levels are not changed in hyperthyroidism.

BACKGROUND: Heart type fatty acid binding protein (H-FABP) is a small protein and released into the circulation when myocardial damage has occurred. Previous studies have demonstrated that H-FABP is closely associated with cardiac and some endocrinologic disorders including prediabetes, metabolic syndrome, and acromegaly. Hyperthyroism is a well-known disorder associated with cardiovascular diseases. We aimed to investigate the effect of hyperthyrodism on H-FABP levels. METHODS: Forty six patients with hyperthyroidism with no known history of coronary artery disease and 40 healthy controls are involved in the study. Serum H-FABP levels are measured using sandwich enzyme-linked immunosorbent assay. RESULTS: There was no significant difference between serum H-FABP levels of patients with hyperthyroidism and controls (871±66 pg/mL, and 816±66 pg/mL, respectively P=0.56). There was no significant correlation between H-FABP, free triiodothyronine (fT3), free thyroxine (fT4), and thyroid stimulating hormone (TSH) levels in patients and controls. CONCLUSIONS: Serum H-FABP levels are not altered in patients with hyperthyroidism.

Patient characteristics and statin discontinuation-related factors during treatment of hypercholesterolemia: an observational non-interventional study in patients with statin discontinuation (STAY study).

OBJECTIVE: The purpose of this study was to identify patient characteristics and statin discontinuation-related factors in patients with hypercholesterolemia. METHODS: A total of 532 patients (age mean±SD: 57.4±11.5 years; 52.4% women, 47.6% men) with hypercholesterolemia and statin discontinuation were included in this national cross-sectional non-interventional observational study. Data on socio-demographic characteristics of patients, cardiovascular risk factors, past treatment with and discontinuation of statin treatment were collected in one visit. RESULTS: Mean±SD duration of hypercholesterolemia was 4.9±4.2 years at time of discontinuation of statin treatment. Statin treatment was initiated by cardiologists in the majority of cases (55.8%), whereas discontinuation of statin treatment was decided by patients in the majority of cases (73.7%), with patients with higher (at least secondary education, 80.4%) more likely than those with lower (only primary education, 69.7%) to decide to discontinue treatment (p=0.022). Negative information about statin treatment disseminated by TV programs-mostly regarding coverage of hepatic (38.0%), renal (33.8%), and muscular (32.9%) side effects (32.9%)-was the most common reason for treatment discontinuation. CONCLUSION: The decision to discontinue statin treatment was made at the patient's discretion in 74% of cases, with higher likelihood of patients with higher educational status deciding to discontinue treatment and switch to non-drug lipid-lowering alternatives. Cardiologists were the physicians most frequently responsible for the initiation of the statin treatment; coverage of several non-life-threatening statin side effects by TV programs and patients' lack of information regarding high cholesterol and related risks were the leading factors predisposing to treatment discontinuation.

Role of p97/Valosin-containing protein (VCP) and Jab1/CSN5 in testicular ischaemia-reperfusion injury.

The most significant complication of testicular ischaemia is loss of the testis, which may lead to infertility. Testicular ischaemia damages protein degradation pathways which, together with the overproduction of damaged proteins and consequent upregulation of ubiquitin-conjugated protein aggregates. Despite recent advances, the factors leading to impairment of spermatogenesis owing to testicular ischaemia remain poorly understood. This study was undertaken to gain insight into the cellular and molecular mechanism underlying torsion induced germ cell apoptosis. Male rats were subjected to 2 h torsion, and testes were examined at 2, 4, 12 and 24 h after torsion repair (reperfusion). Ischaemia-reperfusion (IR) of the testes resulted in apoptosis which was revealed by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) technique. At 12 h after torsion repair germ cell loss reached peak, then decreased at 24 h repair. Western blotting showed that apoptotic proteins (active caspase 3, caspase 9 and Bax) gradually was upregulated at 12 h reperfusion, however anti-apoptotic protein (Bcl2) was downregulated in the relevant IR treatment. Furthermore, Jab1/CSN5 expression was gradually upregulated and p97/VCP expression was downregulated in IR injury according to western blotting and immunohistochemistry. To test further whether polyubiquitination was also involved in IR injury, the expression of polyubiquitinated proteins was examined, which showed that polyubiquitinated proteins were significantly increased in IR injury. These finding suggest that p97/VCP and Jab1/CSN5 provide a novel signaling pathway for testicular ischaemia and may play an important role in IR injury induced cell death in rat testis.

Serum vaspin and adiponectin levels in patients with prolactinoma.

BACKGROUND: Studies investigating serum vaspin and adiponectin levels in patients with prolactinoma are inconclusive. The aim of this study was to evaluate serum vaspin and adiponectin levels in patients with prolactinoma and healthy controls. METHODS: A total of 42 prolactinoma patients (Group 1, 21 patients; Group 2, 21 patients) and 30 healthy controls were enrolled in the study. Group 1 consisted of newly diagnosed patients who were never treated or had not received a dopamine agonist (DA) within 6 months prior to screening. Group 2 consisted of prolactinoma patients who were on DA treatment for at least 6 months at the time of screening. The control group (group 3) consisted of healthy controls. RESULTS: Patients with prolactinoma had higher homeostasis model assessment of insulin resistance and lower quantitative insulin sensitivity check index values in comparison to healthy controls (p < 0.001 for both). Serum levels of adiponectin and vaspin were also significantly lower in prolactinoma patients when compared to the control group (p < 0.01 and p < 0.001, respectively). Following adjustment for confounding factors, the respective odds ratios for prolactinoma in patients in the lower subgroup compared with those in the higher subgroup for adiponectin and vaspin were 2.733 (0.621-12.035; p > 0.05) and 5.041 (1.191-21.339; p < 0.05). CONCLUSION: This is the first study to demonstrate the presence of low vaspin levels in patients with prolactinomas. Further studies are needed to help establish the roles of vaspin and adiponectin in prolactinoma patients.

Role of an endothelin type A receptor antagonist in regulating torsion-induced testicular apoptosis in rats.

Testicular torsion is a well-known medical emergency that can lead to pathological changes in the testicular tissues and male infertility. This investigation was undertaken to gain insight into the effects of an endothelin type A receptor antagonist (BQ123) on torsion-induced germ cell loss. Twenty-eight male Wistar albino rats were divided into four groups. In group I (control group), a sham operation to the left testis was performed. In group II (I/R injury), I/R injury was created by rotating the left testis 720° in a clockwise direction for 2 h and detorsing the testis after 2 h. In group III (I/R injury+BQ123), the rats were subjected to I/R injury and BQ123 injection (1 mg/kg, intravenous). In group IV (control+BQ123), the sham operated rats were subjected to BQ123. The testes of the rats were removed in all groups. Torsion-induced apoptosis and the effects of BQ123 were examined by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end labelling (TUNEL) technique, immunohistochemistry and western blotting. In group II, the number of TUNEL-positive cells increased after testicular torsion. Immunohistochemistry and western blotting showed that apoptotic proteins (active caspase 3 and Bax) were upregulated, and the anti-apoptotic protein Bcl2 was downregulated in I/R injury. The administration of BQ123 caused a significant decrease in the number of apoptotic cells and the expression of apoptotic proteins (p<0.05) when compared with the I/R injury group. No significant effect of BQ123 was observed in the testicular cells of group IV. This animal study provides evidence of the regulatory effects of BQ123 on torsion-induced testicular apoptosis.

The effects of commonly used intravitreal steroids on proliferation index of ciliary body-derived mesenchymal stem cells: an in vitro study.

AIM: To investigate the effects of commonly used intravitreal steroids on survival and proliferation (namely, proliferation index) of ciliary body-derived mesenchymal stem cells (CB-MSC). METHODS: CB-MSCs were isolated from newborn rats' eye, and they were expanded in the medium. Commonly used intravitreal steroids such as dexamethasone (Dex) and triamcinolone acetonide (TA) were added into the medium at commonly used concentration in clinical practice (0.1 mg/mL) and at lower concentration (0.01 mg/mL). Proliferation indexes of CB-MSCs were analyzed with the xCELLigence system at nine consecutive times (at 3rd, 6th, 21th, 30th, 45th, 60th, 75th, 90th and 100th h). RESULTS: Both TA and Dex at both 0.01 mg/mL and 0.1 mg/mL concentrations had negative effect on proliferation indexes of CB-MSC. Although negative effect of TA on proliferation index of CB-MSC at both concentrations was not statistically significant, statistically significant negative effect of Dex at 0.01 mg/mL concentration started 60th h (p = 0.017) and 0.1 mg/mL concentration started 30th h (p = 0.014). DISCUSSION: Even therapeutic doses of intravitreal corticosteroid agents might have negative effects on limited numbers of stem cells. Especially, Dex caused statistically significant toxic effects on CB-MSCs even at lower concentrations of those used clinically. These novel findings deserve further in vivo investigations.

Normocalcemic hyperparathyroidism is associated with complications similar to those of hypercalcemic hyperparathyroidism.

Normocalcemic primary hyperparathyroidism (NC-PHPT) is a variant of hyperparathyroidism, characterized by normal serum calcium levels, high parathyroid hormone (PTH) and normal 25-OH vitamin D status. The present study aimed to compare complications related to hyperparathyroidism in patients with NC-PHPT and hypercalcemic PHPT (HC-PHPT). We retrospectively evaluated the records of 307 PHPT patients between January 2010 and March 2013. We excluded patients with impaired renal function and liver failure. All patients underwent a biochemical and hormonal examination including serum glucose, albumin, total calcium, phosphorus, creatinine, lipoproteins, PTH and 25-OH vitamin D. Nephrolithiasis and bone mineral density were documented based on a review of the medical records. The study population consisted of 36 (12 %) males and 271 (88 %) females with a mean age of 53.3 ± 9.5 years (29-70 years). Twenty-three of the patients were diagnosed with NC-PHPT (group 1) and 284 were diagnosed with HC-PHPT (group 2). There were no significant differences in terms of age, gender, prevalence of hypertension, low bone mineral density and kidney stones between the groups. The mean thyroid-stimulating hormone (TSH) and low-density lipoprotein (LDL) levels were significantly higher in group 1 than in group 2. Our study found that patients with NC-PHPT have similar several complications as patients with HC-PHPT. NC-PHPT patients have higher TSH levels despite being within the normal range, and higher LDL-C levels than patients with HC-PHPT. However, this relationship needs to be clarified in future studies with larger cohorts.

Angiogenic Peptide Nanofibers Improve Wound Healing in STZ-Induced Diabetic Rats.

Low expressions of angiogenic growth factors delay the healing of diabetic wounds by interfering with the process of blood vessel formation. Heparin mimetic peptide nanofibers can bind to and enhance production and activity of major angiogenic growth factors, including VEGF. In this study, we showed that heparin mimetic peptide nanofibers can serve as angiogenic scaffolds that allow slow release of growth factors and protect them from degradation, providing a new therapeutic way to accelerate healing of diabetic wounds. We treated wounds in STZ-induced diabetic rats with heparin mimetic peptide nanofibers and studied repair of full-thickness diabetic skin wounds. Wound recovery was quantified by analyses of re-epithelialization, granulation tissue formation and blood vessel density, as well as VEGF and inflammatory response measurements. Wound closure and granulation tissue formation were found to be significantly accelerated in heparin mimetic gel treated groups. In addition, blood vessel counts and the expressions of alpha smooth muscle actin and VEGF were significantly higher in bioactive gel treated animals. These results strongly suggest that angiogenic heparin mimetic nanofiber therapy can be used to support the impaired healing process in diabetic wounds.

Virus-like nanostructures for tuning immune response.

Synthetic vaccines utilize viral signatures to trigger immune responses. Although the immune responses raised against the biochemical signatures of viruses are well characterized, the mechanism of how they affect immune response in the context of physical signatures is not well studied. In this work, we investigated the ability of zero- and one-dimensional self-assembled peptide nanostructures carrying unmethylated CpG motifs (signature of viral DNA) for tuning immune response. These nanostructures represent the two most common viral shapes, spheres and rods. The nanofibrous structures were found to direct immune response towards Th1 phenotype, which is responsible for acting against intracellular pathogens such as viruses, to a greater extent than nanospheres and CpG ODN alone. In addition, nanofibers exhibited enhanced uptake into dendritic cells compared to nanospheres or the ODN itself. The chemical stability of the ODN against nuclease-mediated degradation was also observed to be enhanced when complexed with the peptide nanostructures. In vivo studies showed that nanofibers promoted antigen-specific IgG production over 10-fold better than CpG ODN alone. To the best of our knowledge, this is the first report showing the modulation of the nature of an immune response through the shape of the carrier system.

[The principles of differentiated thyroid cancer surgery and anesthesia in pregnancy: three case reports]. / Gebelikte diferansiye tiroid kanseri cerrahisi ve anestezi ilkeleri: Üç olgu sunumu.

Development of thyroid nodule during pregnancy is rare, however the cancer rate of this nodule is high. Herein, we present medical outcomes of three pregnant women who were operated with the diagnosis of differentiated thyroid carcinoma in the light of literature. As sonographic findings of three cases showed malignant characteristics, fine needle aspiration biopsy (FNAB) was performed. Cytological examination result was reported as papillary thyroid carcinoma (PTC). Surgery was performed in the second trimester in all cases. One case underwent total thyroidectomy with neck dissection at level III and VI and two cases underwent total thyroidectomy with neck dissection at level VI. Pathological examination result was also reported as PTC. Lymph node metastases in the dissected materials were detected. During the intraoperative and early postoperative period, no complications occurred and no findings of recurrence or residues were observed during one-year follow-up following surgery. In conclusion, as the first trimester has an increased risk of congenital malformations, elective surgery should be performed at the second trimester, if applicable. In pregnants with malignant sonographic features and PTC confirmed by FNAB, surgery can be applied safely by taking precautions during pre-/peri- and postoperative period. These patients should not be given premedication for anesthesia, should be properly positioned and teratogenic agents should be avoided. After surgery, mother and fetus should be monitored closely.