Identification of EMT signaling cross-talk and gene regulatory networks by single-cell RNA sequencing.

The epithelial-to-mesenchymal transition (EMT) plays a critical role during normal development and in cancer progression. EMT is induced by various signaling pathways, including TGF-ß, BMP, Wnt-ß-catenin, NOTCH, Shh, and receptor tyrosine kinases. In this study, we performed single-cell RNA sequencing on MCF10A cells undergoing EMT by TGF-ß1 stimulation. Our comprehensive analysis revealed that cells progress through EMT at different paces. Using pseudotime clustering reconstruction of gene-expression profiles during EMT, we found sequential and parallel activation of EMT signaling pathways. We also observed various transitional cellular states during EMT. We identified regulatory signaling nodes that drive EMT with the expression of important microRNAs and transcription factors. Using a random circuit perturbation methodology, we demonstrate that the NOTCH signaling pathway acts as a key driver of TGF-ß-induced EMT. Furthermore, we demonstrate that the gene signatures of pseudotime clusters corresponding to the intermediate hybrid EMT state are associated with poor patient outcome. Overall, this study provides insight into context-specific drivers of cancer progression and highlights the complexities of the EMT process.

Chromatin state dynamics confers specific therapeutic strategies in enhancer subtypes of colorectal cancer.

OBJECTIVE: Enhancer aberrations are beginning to emerge as a key epigenetic feature of colorectal cancers (CRC), however, a comprehensive knowledge of chromatin state patterns in tumour progression, heterogeneity of these patterns and imparted therapeutic opportunities remain poorly described. DESIGN: We performed comprehensive epigenomic characterisation by mapping 222 chromatin profiles from 69 samples (33 colorectal adenocarcinomas, 4 adenomas, 21 matched normal tissues and 11 colon cancer cell lines) for six histone modification marks: H3K4me3 for Pol II-bound and CpG-rich promoters, H3K4me1 for poised enhancers, H3K27ac for enhancers and transcriptionally active promoters, H3K79me2 for transcribed regions, H3K27me3 for polycomb repressed regions and H3K9me3 for heterochromatin. RESULTS: We demonstrate that H3K27ac-marked active enhancer state could distinguish between different stages of CRC progression. By epigenomic editing, we present evidence that gains of tumour-specific enhancers for crucial oncogenes, such as ASCL2 and FZD10, was required for excessive proliferation. Consistently, combination of MEK plus bromodomain inhibition was found to have synergistic effects in CRC patient-derived xenograft models. Probing intertumour heterogeneity, we identified four distinct enhancer subtypes (EPIgenome-based Classification, EpiC), three of which correlate well with previously defined transcriptomic subtypes (consensus molecular subtypes, CMSs). Importantly, CMS2 can be divided into two EpiC subgroups with significant survival differences. Leveraging such correlation, we devised a combinatorial therapeutic strategy of enhancer-blocking bromodomain inhibitors with pathway-specific inhibitors (PARPi, EGFRi, TGFßi, mTORi and SRCi) for EpiC groups. CONCLUSION: Our data suggest that the dynamics of active enhancer underlies CRC progression and the patient-specific enhancer patterns can be leveraged for precision combination therapy.

Is thyroid autoimmunity itself associated with psychological well-being in euthyroid Hashimoto's thyroiditis?

Recent studies imply that euthyroid Hashimoto's thyroiditis (HT) might be related with impaired HRQoL, depression and anxiety. Ninety three patients with euthyroid HT and 31 age- and gender-matched euthyroid control subjects were enrolled into this study. SF-36 questionnaire, Beck Depression Inventory and Beck Anxiety Inventory tests were used for evaluating HRQoL, depression and anxiety. Beck Depression Inventory scores were higher in patients with HT compared to control subjects (7.5 (4.0-14.75) vs. 5.0 (2.25-9.0), p=0.008). Beck Anxiety Questionnaire scores were also higher in patients with HT than controls (9.50 (5.0-17.0) vs. 5.0 (2.0-11.75), p=0.021). In SF-36 questionnaire; physical functioning (26.0 (20.0-28.0) vs. 29.0 (26.0-30.0), p=0.038), general health (16.4 (13.4-20.4) vs. 19.4 (16.3-21.2), p=0.026) and mental health (20.5 (16.0-23.0) vs. 23.0 (21.0-25.0), p=0.001) scores were lower in patients with HT than control subjects. There were no significant differences between patients with HT under levothyroxine replacement therapy compared to those without therapy in terms of depression and anxiety scores and components of SF-36 questionnaire. Beck Depression Inventory scores were positively correlated with TSH (r=0.250, p=0.01). In SF-36, role physical (r=0.192, p<0.05) and vitality (r=0.181, p<0.05) were positively correlated with fT4. Role emotional was negatively correlated with TSH (r=-0.185, p<0.05) and anti-TPO (r=-0.234, p<0.05). Mental health was negatively correlated with anti-TPO (r=-0.287, p<0.01). HRQoL is impaired and depression and anxiety scores are high in patients with euthyroid HT independent of levothyroxine replacement. Therefore, our results indicate that thyroid autoimmunity itself may have an impact on psychological well-being in euthyroid patients with HT.

ASYMMETRIC DIMETHYLARGININE LEVELS AND ATHEROSCLEROSIS MARKERS IN CUSHING SYNDROME.

OBJECTIVE: As a consequence of hypercortisolism, Cushing syndrome (CS) is frequently observed with other diseases that are associated with atherosclerosis, including diabetes mellitus, dyslipidemia, hypertension, and obesity. Cardiovascular disease (CVD) is the primary cause of mortality and morbidity in CS. We investigate CVD risk markers such as asymmetric dimethylarginine (ADMA), lipoprotein-associated phospholipase A2 (Lp-PLA2), highsensitive C-reactive protein (hsCRP), homocysteine, lipid levels, ankle-brachial index (ABI), and carotid intimamedia thickness (CIMT) in CS. METHODS: Our study included 27 patients with CS and 27 age-, sex-, body mass index (BMI)-, and comorbid disease-matched control subjects. RESULTS: Plasma ADMA levels were significantly lower in the CS group than the control group (P = .013). Total cholesterol, low-density lipoprotein, triglycerides, high-density lipoprotein, and apolipoprotein A1 and apolipoprotein B levels were higher in patients with CS than the control group (P<.05). We did not find any statistically significant differences in levels of hsCRP, Lp-PLA2, or homocysteine or CIMT and ABI measurements between the CS group and comorbidity-matched control group (P>.05). CONCLUSION: We found that ADMA levels were lower in CS, the finding that should be further investigated. Levels of hsCRP, Lp-PLA2, and homocysteine levels and CIMT and ABI measurements were similar between the CS group and comorbidity-matched control group. None of these markers was prominent to show an increased risk of CVD in CS, independent of the comorbidities of CS. ABBREVIATIONS: ABI = ankle-brachial index Apo = apolipoprotein ADMA = asymmetric dimethylarginine BMI = body mass index CVD = cardiovascular disease CIMT = carotid intima-media thickness CS = Cushing syndrome DM = diabetes mellitus DDAH = dimethylarginine dimethylaminohydrolase ELISA = enzyme-linked immunosorbent assay HDL = high-density lipoprotein hsCRP = high-sensitive C-reactive protein HOMA-IR = homeostatic model assessment of insulin resistance HT = hypertension LDL = low-density lipoprotein Lp-PLA2 = lipoprotein-associated phospholipase A2 Lp-a = lipoprotein a NO = nitric oxide.

Cephalometric assessment of soft tissue morphology of patients with acromegaly.

AIM: To assess the sagittal soft tissue morphology of patients with acromegaly in comparison with a healthy control group. METHODS: Twenty-seven patients with acromegaly (11 male, 16 female; mean age 47.3 ± 11.5 years) and 30 healthy subjects (15 male, 15 female; mean age 42.2 ± 17.4 years) were included in the study. Linear and angular measurements were made on lateral cephalograms to evaluate soft tissue and skeletal characteristics. The intergroup comparisons were analysed with the Student's t-test. RESULTS: Facial convexity (p < 0.01) and the nasolabial angle (p < 0.001) were reduced in patients with acromegaly, whereas nose prominence (p < 0.01), upper lip sulcus depth (p < 0.01), upper lip thickness (p < 0.01), basic upper lip thickness (p < 0.01), lower lip protrusion (p < 0.05), mentolabial sulcus depth (p < 0.05) and soft tissue chin thickness (p < 0.001) were increased. Anterior cranial base length (p < 0.05), the supraorbital ridge (p < 0.01), the length of the maxilla and mandible (p < 0.001, p < 0.01, respectively) were significantly increased, and mandibular prognathism was an acromegalic feature (p < 0.05). CONCLUSION: Acromegalic coarsening and thickening of the craniofacial soft tissues was identified from lateral cephalograms, which may therefore contribute to early diagnosis when evaluated together with other changes caused by the disease.

Differentiated thyroid cancer: effect on quality of life, depression, and anxiety.

CONTEXT: Thyroid cancer is the most common endocrine cancer, the lifelong risk for which is approximately 1%. Despite favorable prognosis and well-tolerated treatment modalities, numerous studies have shown that thyroid cancer survivors have impaired health-related quality of life (HRQoL). Patients are also more frequently affected by depression and anxiety. OBJECTIVE: We aimed to evaluate HRQoL, depression, and anxiety status in female patients with DTC. DESIGN, SUBJECTS, AND METHODS: We compared HRQoL, depression, and anxiety status in 114 female thyroid cancer survivors with 110 healthy subjects via a cross-sectional design. For this purpose, we utilized short-form 36 (SF-36), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). RESULTS: The majority of the patients (82%) were stage I. Fifty-seven patients (51%) received radioiodine treatment. Regarding HRQoL, depression, and anxiety between groups, thyroid cancer survivors did worse on every aspect of SF-36 than the control group (p < 0.05). Thyroid cancer survivors had higher BDI and BAI scores (p < 0.05). In those receiving RAI, the dose of RAI, lymph node dissection, and tumor stage did not affect SF-36, depression, and anxiety scores. Duration since diagnosis also did not affect results. CONCLUSION: Our study further confirms the observation that survivors of DTC have impaired HRQoL. Furthermore, they are more likely to suffer from anxiety and depression.

Effect of thyroid nodule size on cytology reliability and incidence of malignancy: A large cohort of 1205 patients from a single center.

OBJECTIVE: There is controversy about whether the rates of malignancy and of false-negative malignancy are greater in large nodules. The aim of this study was to determine the reliability of cytology in ≥4cm nodules and to compare malignancy rates between ≥4cm and<4cm nodules. METHODS: The study included 1205 patients who underwent biopsy and subsequent thyroidectomy with the diagnosis of nodular thyroid disease between 2014 and 2019. The patients were separated into two groups, ≥4cm and<4cm, according to the size of the index nodule on ultrasonography. RESULTS: Two hundred and eleven index nodules (17.5%) were ≥4cm. Malignancy rate on definitive pathology was 51% in<4cm nodules and 30% in ≥4cm nodules. Malignancy risk was significantly lower in ≥4cm nodules than <4cm nodules (P<0.001). When<1cm nodules were excluded and 1-4cm and ≥4cm nodules were compared, malignancy risk was also significantly lower in ≥4cm nodules (P=0.001). On definitive pathology, there were 45 false-negative results among cytologically benign nodules. There was no difference in false-negative cytology rate between<4cm and ≥4cm nodules (P=0.209). CONCLUSION: The present study found no decrease in the reliability of cytology in ≥4cm nodules, and there may not be a linear relationship between nodule size and malignancy risk. Therefore, in asymptomatic cytologically benign ≥4cm nodules, surgery may not be recommended based on nodule size alone.

Dysregulation and Epigenetic Reprogramming of NRF2 Signaling Axis Promote Acquisition of Cisplatin Resistance and Metastasis in Head and Neck Squamous Cell Carcinoma.

PURPOSE: Cisplatin (CDDP)-based chemotherapy is a first-line treatment for patients with advanced head and neck squamous cell carcinomas (HNSCC), despite a high rate of treatment failures, acquired resistance, and subsequent aggressive behavior. The purpose of this study was to study the mechanism of CDDP resistance and metastasis in HNSCC. We investigated the role of NRF2 pathway activation as a driven event for tumor progression and metastasis of HNSCC. EXPERIMENTAL DESIGN: Human HNSCC cell lines that are highly resistant to CDDP were generated. Clonogenic survival assays and a mouse model of oral cancer were used to examine the impact of NRF2 activation in vitro and in vivo on CDDP sensitivity and development of metastasis. Western blotting, immunostaining, whole-exome sequencing, single-cell transcriptomic and epigenomic profiling platforms were performed to dissect clonal evolution and molecular mechanisms. RESULTS: Implantation of CDDP-resistant HNSCC cells into the tongues of nude mice resulted in a very high rate of distant metastases. The CDDP-resistant cells had significantly higher expression of NRF2 pathway genes in the presence of newly acquired KEAP1 mutations, or via epigenomic activation of target genes. Knockdown of NRF2 or restoration of the wild-type KEAP1 genes resensitized resistant cells to CDDP and decreased distant metastasis (DM). Finally, treatment with inhibitor of glutaminase-1, a NRF2 target gene, alleviated CDDP resistance. CONCLUSIONS: CDDP resistance and development of DM are associated with dysregulated and epigenetically reprogrammed KEAP1-NRF2 signaling pathway. A strategy targeting KEAP1/NRF2 pathway or glutamine metabolism deserves further clinical investigation in patients with CDDP-resistant head and neck tumors.

Irregularity in Plantar Fascia, Muscle Edema and Tendon Thickness in Patients with High-Risk for Diabetic Foot.

AIM: To investigate the alterations in the plantar fascia (PF), intrinsic muscles, and tendons in the feet of patients at high risk for developing diabetic foot. METHODS: The healthy feet of 22 patients with type 2 diabetes, who had developed diabetic foot ulcers on a single foot without any pathology on the contralateral extremity, and those of 22 healthy volunteers were evaluated by magnetic resonance imaging. The volume of the Achilles tendon (AT), the surface area of the PF, the thickness of AT, flexor hallucis longus, flexor digitorum longus, tibialis posterior, and peroneus longus tendons, irregularity in the PF, and edema of intrinsic foot muscles were examined. RESULTS: Nineteen patients (86%) had irregularity in the PF, whereas none of the healthy controls had any (p<0.001). Intrinsic muscle edema was more common in the group with diabetes (p=0.006). The volume of AT and the surface area of PF were decreased in patients with peripheral arterial disease (PAD) (p<0.05). Patients with diabetes mellitus but without PAD had a larger surface area of PF than that of controls (p<0.05). There were no differences in the volume of AT, the surface area of the PF, and other tendon thickness between the groups. CONCLUSION: Irregularity in the PF and muscle edema may indicate a high risk for the diabetic foot. The presence of PAD may lead to regression in the structure of AT and PF.

Machine Learning in Epigenomics: Insights into Cancer Biology and Medicine.

The recent deluge of genome-wide technologies for the mapping of the epigenome and resulting data in cancer samples has provided the opportunity for gaining insights into and understanding the roles of epigenetic processes in cancer. However, the complexity, high-dimensionality, sparsity, and noise associated with these data pose challenges for extensive integrative analyses. Machine Learning (ML) algorithms are particularly suited for epigenomic data analyses due to their flexibility and ability to learn underlying hidden structures. We will discuss four overlapping but distinct major categories under ML: dimensionality reduction, unsupervised methods, supervised methods, and deep learning (DL). We review the preferred use cases of these algorithms in analyses of cancer epigenomics data with the hope to provide an overview of how ML approaches can be used to explore fundamental questions on the roles of epigenome in cancer biology and medicine.

Reprogramming of H3K9bhb at regulatory elements is a key feature of fasting in the small intestine.

ß-hydroxybutyrate (ß-OHB) is an essential metabolic energy source during fasting and functions as a chromatin regulator by lysine ß-hydroxybutyrylation (Kbhb) modification of the core histones H3 and H4. We report that Kbhb on histone H3 (H3K9bhb) is enriched at proximal promoters of critical gene subsets associated with lipolytic and ketogenic metabolic pathways in small intestine (SI) crypts during fasting. Similar Kbhb enrichment is observed in Lgr5+ stem cell-enriched epithelial spheroids treated with ß-OHB in vitro. Combinatorial chromatin state analysis reveals that H3K9bhb is associated with active chromatin states and that fasting enriches for an H3K9bhb-H3K27ac signature at active metabolic gene promoters and distal enhancer elements. Intestinal knockout of Hmgcs2 results in marked loss of H3K9bhb-associated loci, suggesting that local production of ß-OHB is responsible for chromatin reprogramming within the SI crypt. We conclude that modulation of H3K9bhb in SI crypts is a key gene regulatory event in response to fasting.

The preventive effect of ellagic acid on brain damage in rats via regulating of Nrf-2, NF-kB and apoptotic pathway.

The aim of this study was to investigate the neuroprotective role of ellagic acid (EA) on CCl4 -induced brain injury in rats. In this study, the rats were divided into four groups. Groups: (1) Control group; (2) EA group; (3) CCl4 group; (4) EA + CCl4 group. In brain tissue, tumor necrosis factor-α (TNF-α), nuclear factor kappa b (NF-kB), cyclooxygenase-2 (COX-2), nuclear erythroid related factor 2 (Nrf-2), cysteine-aspartic acid protease (caspase-3), VEGF (vascular endothelial growth factor) and B-cell lymphoma-2 (bcl-2) protein expression levels were analyzed by western blotting. MDA (malondialdehyde), catalase enzyme activity (CAT) and glutathione (GSH) analysis were determined by spectrophotometer. In our findings, EA ameliorated Nrf-2 and caspase-3 protein expression levels, GSH and catalase activities, NF-kB, TNF-α, VEGF, Bcl-2, COX-2 protein expression levels and MDA levels in CCl4 intoxicated rats. These results suggest that EA demonstrated the neuroprotective effect on CCl4 -induced brain damage in rats. PRACTICAL APPLICATIONS: Ellagic acid has different biological activities, these are; antioxidant, anti-inflammatory, antidepressant, antifibrosis, anticancer, neuroprotective and hepatoprotective. For example it was reported that EA protects the cells against DNA injury induced by free radicals and it can prevent the traumatic brain injury. These results obtained from this study reveals that EA has a protective effect against rat brain damage and it may be used as an alternative drugs for the brain injury treatment in future.

[Reflex sympathetic dystrophy secondary to piriformis syndrome: a case report]. / Piriformis sendromuna ikincil gelisen refleks sempatik distrofi: Olgu sunumu.

Piriformis syndrome is a rare cause of hip and foot pain which may be due to sciatic nerve irritation because of anatomic abnormalities of sciatic nerve and piriformis muscle or herniated disc, facet syndrome, trochanteric bursit, sacroiliac joint dysfunction, endometriosis and other conditions where sciatic nerve is irritated. There has been no reflex sympathetic dystrophy (RSD) case presented due to piriformis syndrome before. A sixty-two-year-old female patient had right foot and hip pain (VNS: 8), redness and swelling in the foot since 15 days. Her history revealed long walks and travelling 3 weeks ago and sitting on the foot for a long time for a couple of days. Physical examination revealed painful hip movement, positive straight leg rise. Erythema and hyperalgesia was present in dorsum of the right foot. Right foot dorsiflexion was weak and hyperesthesia was found in right L4-5 dermatome. Medical treatment and ultrasound treatment to piriformis muscle was not effective. The patient was injected 40 mg triamcinolon and local anesthetic in right piriformis muscle under floroscopy by diagnosis of piriformis syndrome, neuropathic pain and RSD. Pain and hyperalgesia resolved and motor weakness was better. During follow-up right foot redness resolved and pain decreased (VNS: 1). In this case report, there was vascular, muscle and skeletal signs supporting RSD, which shows us the therapoetic effect of diagnostic piriformis injection. The patient history, physical examination and diagnostic tests were evaluated by a multidisciplinary team which contributed to the treatment.

Guided intraoperative scintigraphic tumor targeting of metastatic cervical lymph nodes in patients with differentiated thyroid cancer: a single-center report.

OBJECTIVE: Our aim was to present our experiences related to performing neck surgery using the guided intraoperative scintigraphic tumor targeting (GOSTT) procedure for patients who had locally recurrent or persistent differentiated thyroid cancer (DTC) and who had undergone previous thyroid surgery. SUBJECTS AND METHODS: We retrospectively evaluated 11 patients who had locally recurrent or persistent DTC, who had undergone previous surgery, and for whom reoperation was planned for metastatic cervical lymph nodes (LNs). We performed the neck surgery using the GOSTT procedure on all patients and at a single academic institution. RESULTS: The 11 patients had a total of 26 LNs, as marked with a radiotracer, and those LNs' mean size was 14.7 ± 8.2 mm (range: 5-34 mm). Histopathological examinations revealed DTC metastasis in all 26 of the preoperatively marked LNs. Of the 11 patients, only one needed a reoperation in the neck; she had another successful surgery (also using the GOSTT procedure). In the evaluation of the patients' final status, all were disease-free in their necks. There also were no GOSTT-associated postoperative complications. CONCLUSION: The GOSTT procedure is a useful, successful, inexpensive, and comfortable procedure for marking and mapping metastatic LNs, especially in DTC patients who have undergone previous surgery.

Evaluation of ambulatory arterial stiffness index in hyperthyroidism

Background/aim: Hyperthyroidism causes hemodynamic changes that are associated with adverse cardiovascular outcomes. Twenty-four-hour ambulatory blood pressure monitoring recordings provide us with some essential data: BP variability and ambulatory arterial stiffness index (AASI). In this study, we aimed to investigate AASI and short-term BP variability in both overt and subclinical hyperthyroidism and their relationship with thyroid hormones. Materials and methods: We enrolled 36 patients with subclinical hyperthyroidism, 23 patients with overt hyperthyroidism, and 25 healthy euthyroid controls. ABPM recording was performed for 24 h for all patients. Results: There were no statistically significant differences among the overt hyperthyroidism, subclinical hyperthyroidism, and control groups in terms of AASI (0.43 ± 0.15, 0.38 ± 0.12, 0.42 ± 0.13, respectively; P = 0.315). Variability of diastolic BP was significantly higher in patients with overt hyperthyroidism than in patients with subclinical hyperthyroidism (14.8 ± 2.6 vs. 12.8 ± 2.5%, P = 0.023). There were significant positive correlations between AASI and fT3 (r = 0.246, P = 0.02) and fT4 (r = 0.219, P = 0.04) while TSH was not correlated with AASI (r = 0.023, P = 0.838). After adjusting for confounders, age, 24-h systolic and diastolic BP, variability of systolic and diastolic BP, and fT4 were independent predictors of AASI (r2 = 0.460, P < 0.001). Conclusion: Although AASI did not differ between overt and subclinical hyperthyroidism, there was a positive relationship between AASI and free thyroid hormone levels. Furthermore, short-term BP variability was higher in overt hyperthyroidism than in subclinical hyperthyroidism.

GDF-15 and Hepcidin Levels in Nonanemic Patients with Impaired Glucose Tolerance.

Aims. Growth Differentiation Factor-15 (GDF-15) has been suggested as one of the regulators of hepcidin, an important regulatory peptide for iron deposition. Current data is conflicting about the relationship between hepcidin and disorders of glucose metabolism. We aimed to investigate serum hepcidin and GDF-15 concentrations and their associations with each other, in nonanemic subjects with impaired glucose tolerance (IGT) in comparison with the nonanemic subjects with normal glucose tolerance (NGT). Methods. Thirty-seven subjects with IGT and 32 control subjects with NGT, who were age-, gender-, and body mass index- (BMI-) matched, were included in the study. Results. Serum GDF-15 levels were significantly higher in IGT compared to NGT. There were no differences in hepcidin, interleukin-6, and high sensitive C-reactive protein levels between the groups. We found a positive correlation between GDF-15 and hepcidin levels. There were also positive correlations between GDF-15 and age, uric acid, creatinine, and area under the curve for glucose (AUC-G). Hepcidin was correlated positively with ferritin levels. In the multiple regression analysis, GDF-15 concentrations were independently associated with age, uric acid, and AUC-G. Conclusions. Impaired glucose tolerance is associated with increased GDF-15 levels even in the absence of anemia, but the levels of hepcidin are not significantly altered in prediabetic state.

Irisin and Myostatin Levels in Patients with Graves' Disease.

BACKGROUND AND AIMS: Skeletal muscle system, which is one of the primary targets for thyroid hormones, has an important role in energy metabolism. Some myokines such as irisin and myostatin have considerable effects on energy metabolism in addition to the musculoskeletal system. Our aim was to investigate circulating irisin and myostatin levels in patients with Graves' Disease (GD). METHODS: This study included 41 patients with GD who were in overt hyperthyroid status and 44 healthy subjects. RESULTS: Serum irisin levels were higher in patients with hyperthyroidism than in control group (p = 0.003). However, there was no statistical difference in myostatin levels between groups (p = 0.21). Irisin levels were positively correlated with free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin receptor antibody (TRAb) (p = 0.03, p = 0.02, p = 0.02, respectively) and negatively correlated with thyroid-stimulating hormone (TSH) (p = 0.006) in both groups. In multiple regression analysis, the presence of GD was the only significant factor associated with serum irisin levels (ß = 0.29, p = 0.01). Myostatin levels were positively correlated with age, body mass index (BMI), FT4, HOMA-IR (p = 0.001, p = 0.04, p = 0.003, p = 0.03, respectively) and negatively correlated with TSH (p = 0.01). Multiple regression analysis also revealed that age and FT4 were the significant factors associated with circulating myostatin levels (ß = 0.27, p = 0.02; ß = 0.22, p = 0.04, respectively). CONCLUSION: Our results suggest that increased irisin levels might contribute to altered energy metabolism in hyperthyroidism. Further studies to determine whether myostatin is affected due to hyperthyroidism are needed.

The effect of calpain-10 gene polymorphism on the development of type 2 diabetes mellitus in a Turkish population.

INTRODUCTION: The variations in the Calpain-10 gene have been suggested to be related to susceptibility to type 2 diabetes mellitus (T2DM) in different populations. In this study, we investigated the relationship between single nucleotide polymorphism (SNP)-19, -44 and -63 in the Calpain-10 gene and the development of T2DM in a Turkish population. MATERIAL AND METHODS: A total of 211 subjects were recruited: 118 patients with a diagnosis of T2DM and 93 unrelated healthy subjects. RESULTS: There were no significant differences in the genotype and allele distribution of SNPs studied between the patients with T2DM and controls (p > 0.05), whereas the frequencies of 121 haplotype and 122/121 haplotype combination were found to be higher in patients with T2DM than in controls (p < 0.05). No association was observed between the variations in the Calpain-10 gene and glycaemic control and lipid parameters (p > 0.05). The SNP-19 insertion/insertion was significantly related to increased body mass index (BMI) in male diabetic patients (p < 0.05). CONCLUSIONS: The present study indicates that 121 haplotype and 122/121 haplotype combination of SNP-19, -44 and -63 in the Calpain-10 gene are associated with the development of T2DM in Turkish patients.

Guided intraoperative scintigraphic tumor targeting of metastatic cervical lymph nodes in patients with differentiated thyroid cancer: a single-center report

ABSTRACT Objective: Our aim was to present our experiences related to performing neck surgery using the guided intraoperative scintigraphic tumor targeting (GOSTT) procedure for patients who had locally recurrent or persistent differentiated thyroid cancer (DTC) and who had undergone previous thyroid surgery. Subjects and methods: We retrospectively evaluated 11 patients who had locally recurrent or persistent DTC, who had undergone previous surgery, and for whom reoperation was planned for metastatic cervical lymph nodes (LNs). We performed the neck surgery using the GOSTT procedure on all patients and at a single academic institution. Results: The 11 patients had a total of 26 LNs, as marked with a radiotracer, and those LNs' mean size was 14.7 ± 8.2 mm (range: 5-34 mm). Histopathological examinations revealed DTC metastasis in all 26 of the preoperatively marked LNs. Of the 11 patients, only one needed a reoperation in the neck; she had another successful surgery (also using the GOSTT procedure). In the evaluation of the patients' final status, all were disease-free in their necks. There also were no GOSTT-associated postoperative complications. Conclusion: The GOSTT procedure is a useful, successful, inexpensive, and comfortable procedure for marking and mapping metastatic LNs, especially in DTC patients who have undergone previous surgery.

The relationship between adipocyte fatty acid binding protein-4, retinol binding protein-4 levels and early diabetic nephropathy in patients with type 2 diabetes.

Adipocyte fatty acid binding protein-4 (A-FABP4) and retinol binding protein-4 (RBP4) have recently been linked to type 2 diabetes mellitus (DM). Serum A-FABP4 and RBP4 levels and their relationships with early diabetic nephropathy were examined in 87 type 2 diabetic patients. The patients with diabetic nephropathy showed high A-FABP4 levels compared to the patients without diabetic nephropathy (p=0.0001). Log A-FABP4 correlated positively with age (p=0.02), log duration of diabetes (p=0.04), log body mass index (BMI) (p=0.0001), log creatinine (p=0.007), log C-reactive protein (CRP) (p=0.01), log albumin excretion rate (AER) (p=0.001), and negatively with MDRD-GFR (p=0.0001). Serum RBP4 levels were similar between the patients with and without diabetic nephropathy. RBP4 correlated positively with triglycerides (p=0.001), log creatinine (p=0.009), and negatively with MDRD-GFR (p=0.04). In regression analysis, log A-FABP4 was associated with age, sex, log BMI, and log AER (r(2)=0.43) and RBP4 was associated with triglycerides and log creatinine (r(2)=0.22). In conclusion, we found high serum A-FABP4 but unchanged RBP4 concentrations and their associations with renal function and early diabetic nephropathy in type 2 DM.