Search

An insulin regimen may be necessary for about 30% of the patients with gestational diabetes mellitus (GDM). We aimed to investigate the association of free T4(fT4) levels with insulin requirement in pregnant women with GDM. We included pregnant women whose TSH levels were within the normal range and who were diagnosed with GDM, and excluded patients with thyroid dysfunction, chronic illnesses, or any previous history of antithyroid medication, levothyroxine, or antidiabetic medication use. The diagnosis and treatment of GDM were based on American Diabetes Association guidelines. Demographic features, previous history of GDM and gestational hypertension were recorded. Baseline (at diagnosis of GDM) fasting blood glucose, HbA1c, TSH, fT4, and fT3 levels were analyzed. We grouped the patients according to their baseline fT4 levels: isolated maternal hypothyroxinemia (IMH) (group A) vs. in the normal range (group B). We grouped those also based on insulin requirement in 3rd trimester. Of the patients (n=223), insulin requirement was present in 56, and IMH in 11. Insulin requirement was more frequent in group A than in group B (p=0,003). HbA1c (≥47,5 mmol/mol) and fT4 level (lower than normal range) were positive predictors for insulin requirement (OR:35,35, p=0,001; and OR:6,05, p=0,008; respectively). We showed that IMH was closely associated with insulin requirement in GDM. Pregnant women with IMH and GDM should be closely observed as regards to glycemic control. If supported by future large studies, levothyroxine treatment might be questioned as an indication for patients with GDM and IMH.

Asprosin (ASP) and subfatin are hormones that regulate glucose metabolism. The role of ASP and subfatin in serous ovarian tumors has not been investigated. We investigated the expression of subfatin and asprosin in 30 serous benign, 30 serous borderline, 30 malignant and 30 control ovarian tissues. We investigated ASP and subfatin immunoreactivity and quantification was achieved using an ELISA method. ASP and subfatin were localized in the epithelial parts of normal ovarian tissues; however, in cancer tissues, immunoreactivity was detected in the parenchymal areas. Biochemical analysis of ovarian tissues revealed significantly decreased ASP and subfatin compared to the control. We propose that ASP and subfatin are promising candidates for biomarkers to distinguish serous benign, serous borderline and malignant ovarian cancers.

Background It is well documented that patients with chronic metabolic diseases, such as diabetes and obesity, are adversely affected by the COVID-19 pandemic. However, when the subject is rare metabolic diseases, there are not enough data in the literature. Aim To investigate the course of COVID-19 among patients with Gaucher disease (GD), the most common lysosomal storage disease. Methods Based on the National Health System data, a retrospective cohort of patients with confirmed (polymerase chain reactionpositive) COVID-19 infection (n = 149 618) was investigated. The adverse outcomes between patients with GD (n = 39) and those without GD (n = 149 579) were compared with crude and propensity score-matched (PSM) groups. The outcomes were hospitalisation, the composite of intensive care unit (ICU) admission and/or mechanical ventilation and mortality. Results The patients with GD were significantly older and had a higher frequency of hypertension (HT), Type 2 diabetes mellitus (T2DM), dyslipidaemia, asthma or chronic obstructive pulmonary disease, chronic kidney disease, coronary artery disease, heart failure and cancer. Although hospitalisation rates in Gaucher patients were found to be higher in crude analyses, the PSM models (model 1, age and gender matched; model 2, matched for age, gender, HT, T2DM and cancer) revealed no difference for the outcomes between patients with GD and the general population. According to multivariate regression analyses, having a diagnosis of GD was not a significant predictor for hospitalisation (P = 0.241), ICU admission/mechanical ventilation (P = 0.403) or mortality (P = 0.231). Conclusion According to our national data, SARS-CoV-2 infection in patients with GD does not have a more severe course than the normal population.

COVID-19 is the most devastating pandemic situation we have experienced in our age, affecting all systems. Although it affects all systems, it shows its most important effect through thrombophilia. Therefore, the possible cause of sudden death due to COVID-19 may be embolism caused by thrombophilia. D-dimer amounts increase due to COVID-19. The thrombosis is associated with sudden death in COVID-19 disease in populations. Since individuals with thrombophilia will be more prone to death due to COVID-19, it may be appropriate to administer low doses of Clexane (Enoxaparin sodium) or low-weight heparin for prophylactic purposes in order to consider these individuals at high risk and to prevent deaths. Moreover, in order not to risk the lives of healthcare professionals with thrombophilia, it would be appropriate to keep them away from individuals with COVID-19 disease and to employ them in different healthcare services according to their fields of expertise. It should also not be forgotten that different symptoms related to COVID-19 appear day by day, these different symptoms probably show that the virus has undergone mutations in order to survive, but no matter what, its effect on thrombophilia has not been eliminated yet. This compilation aims to present the reasons and causes of death due to COVID-19, possible treatment options, and thrombophilia panel tests and new parameters that may have a place in the meticulous interpretation of these tests and possible etiopathology in the light of current information. Therefore, presenting this information in a rational manner and keeping the parameters of the thrombophilia panel under strict control predict that the deaths due to the virus will be partially reduced.

Hereditary spastic paraplegias (HSPs), a genetically heterogeneous group of neurodegenerative diseases, have an incidence of around 3 to 9 individuals every 100,000. Due to the broad clinical and genetic variability of HSPs, it is challenging to diagnose the disorder quickly and precisely. Hereditary spastic ataxias (HSAs) and HSPs are overlapping diseases, and their intersection has been gradually identified by next-generation sequencing. The idea of the spasticity–ataxia phenotype (SAP) spectrum is further substantiated by the similarities in phenotypes and underlying genes in ataxias and inherited spastic paraplegias and the related cellular processes and disease mechanisms these disorders exhibit. Whole-exome sequencing was performed on the 25 spastic or spastic-ataxic gait patients. Twenty-two specific HSPs–HSAs–SAP mutations, including 14 novel mutations, were found in 25 cases from 18 Turkish and 2 Syrian families. This research discovers many novel hereditary spastic paraplegia (HSP) mutations and shows a robust genotype–phenotype heterogeneity in the disease. This research helped expand the clinical and molecular scope of HSP and clarified the concept of the spasticity–ataxia phenotype, further enhancing our understanding of the complicated form of HSP and its association with ataxia. Our data broadens the spectrum of HSPs and HSAs related gene mutations and provides insights for genotype–phenotype correlations for HSPs and HSAs.

Purpose While obesity is related to more severe outcomes of coronavirus disease 2019 (COVID-19), factors leading to poor prognosis still remain unclear. The present study evaluated the outcomes of COVID-19 patients who were overweight or obese and variables associated with severe disease in a large group of consecutive cases. Methods A nationwide retrospective cohort study was performed using the Turkish National Healthcare Database. Demographic characteristics, laboratory tests, comorbidities, and medications of patients registered between March 11 and May 30, 2020, were recorded. Results A total of 14, 625 patients (median age:42, IQR:26 years; female 57.4%) with normal weight (34.7%), overweight (35.6%), and obesity (29.7%) were included. Hospitalization, ICU admission, intubation/mechanical ventilation, pulmonary involvement, and mortality were significantly higher in patients who were overweight or obese. In adjusted analyses, both overweight (OR, 95% CI: 1.82, 1.04–3.21; p=0.037) and obesity (OR, 95% CI: 2.69, 1.02–1.05; p Conclusions COVID-19 patients who were overweight or obese were more likely to have adverse outcomes but only obesity was a predictor of mortality. Such patients should receive urgent medical attention and active management, especially the elderly, men, and people with chronic kidney disease.

Purpose: Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal-recessive renal tubular disorder. FHHNC is characterized by renal wasting of magnesium (Mg) and calcium (Ca), which subsequently leads to bilateral nephrocalcinosis, renal stones, and chronic renal failure. Here, we report seven patients with FHHNC. Methods: We retrospectively analyzed pediatric cases of FHHNC between 2010-2020. Results: A total of 7 patients, 5 girls (71.4 %) and 2 boys (28.5 %) with a median age of 4 years (min:4 months, max:13 years) and a mean follow-up time of 4.4±3.5 years were included. 3 patients had been diagnosed incidentally. All of the patients had nephrocalcinosis, hypercalciuria and high PTH level. One patient had hypocalcemia and one patient had normal serum magnesium level. All patients had high urine FEMg. Five patients had CLDN 16 mutation, and two patients had CLDN19 mutation. None of them had ocular findings. Three patients had chronic renal failure at the end of the follow-up.Conclusions: We want to draw attention to the FHHNC in children with nephrocalcinosis. FHHNC should be considered in children with normal serum magnesium levels since a normal serum magnesium level does not rule out FHHNC, and high FEMg levels are more significant for the diagnosis.

To detect the frequency and possible risk factors of new-onset diabetes after liver transplantation in the patients with acute liver failure. The frequency of new-onset diabetes after transplant (NODAT) is 5–30% in liver transplant recipients. We aimed to analyze the frequency and predictors of NODAT in the patients undergoing liver transplantation due to acute liver failure. Adult patients undergoing liver transplantation due to acute liver failure were analyzed retrospectively. The patients with chronic liver failure or diabetes were excluded. We measured pretransplant random blood glucose and posttransplant fasting blood glucose. NODAT was diagnosed according to principally 1st month fasting blood glucose (group 1 125 mg/dL). The participants were subgrouped according to age, gender, body mass index, etiology, antiviral medication, thyroid function, pretransplant random blood glucose, donor type, immunosuppressive drug, common infection, and surgical complication. Mean age of total 91 patients was 33.48 (± 13.35), and 52.7% (n = 48) of them was female. The ratio of NODAT was 26.98% on the 1st month. NODAT group had a higher pretransplant random blood glucose than the others. Pretransplant hyperglycemia increased the risk of NODAT by 4.065 times (p = 0.018). We showed that pretransplant hyperglycemia increased NODAT risk by 4 times, but hypoglycemia did not affect. So, pretransplant hyperglycemia should be controlled also in the patients with acute liver failure as in the patients with chronic liver failure.

We aimed to describe the initial experience of mini-laparoscopic adrenalectomy combined with transgastric specimen extraction and to assess its safety and feasibility. We used only 5-mm trocars, three ports for left adrenalectomy and four for right. Intraoperative gastroscopy was performed for specimen extraction through the mouth via an endoscopic snare. The gastrotomy was closed intracorporeally. Demographic, perioperative and pathological data were analyzed. There were 16 patients (12 females) with the mean age of 46.5 ± 11.3 years and half of them had previous abdominal surgeries. The median operative time was 150 (45-432) min with a median blood loss of 88 (0-350) ml. The median oral intake time was 2 (1-4) days and the median length of hospital stay was 2 (2-5) days. There was no mortality and extraction-related complication. Histopathological median tumor length, width and depth were 3 cm, 2.15 cm, and 1.9 cm, respectively. The median specimen length, width and depth were 6.25 cm, 4 cm, and 2.2 cm, respectively. Mini-laparoscopic adrenalectomy combined with transgastric specimen extraction is a safe and feasible surgical technique. It provides a less invasive surgery and may also have some benefits on wound-related complications and cosmesis.

Objectives We compared the laboratory and clinical symptoms of coronavirus disease 2019 (COVID-19), other viral (beside COVID-19), and bacterial conjunctivitis patients with the values of controls. Methods Twenty COVID-19, 15 other viral, 15 bacterial patients, and 15 control group were included in the study. COVID-19 was diagnosed with the real time reverse transcription–polymerase chain reaction while the indirect immunofluorescent antibody test was used in the detection of other viral agents. Bacterial agents were determined with the detection of the agent. The ophthalmologic examination of all cases was carried out by direct penlight, and the anterior segment evaluation was performed. The laboratory findings of all cases included in the study were obtained from the hospital records. Results It was determined that 5% conjunctivitis and 5% diplopia developed in patients diagnosed with COVID-19, 20% conjunctivitis developed in patients due to other viral agents, and 66.6% conjunctivitis developed in patients due to bacterial agents. Conclusion The incidence of conjunctivitis in COVID-19 patients was lower than in other viral and bacterial groups. Neutrophil/lymphocyte ratio and C-reactive protein come to the forefront as precious parameters with high specificity and sensitivity that might be useful to distinguish these diseases.

The specialized resident-stem cells in gonads are tasked with restorating damaged ovarian cells following injury to maintain sequential reproductive events. When we talk about premature ovarian insufficiency (POI) we accept the existence of decreased stem cell and their regenerative abilities. The present study was to explain how restorating damaged ovarian cells following injury to maintain sequential reproductive events in evidence-based medicine indexed in PubMed and Web of Science. The exact mechanism is unclear stem cells transfer may improve compromised ovarian function and fertility outcome in women with POI. Soluble factors secreted by stem cell may rescue impaired mitochondrial function in oogonial stem cells, enhance metabolic capacity of resident stem cells, induce local neovascularization in the ovary, and activate gene shifting between transferred stem cells and germ cell precursors. This review may provide insight into how stem cells show some of their beneficial effects on compromised ovarian microenvironment and germ cell niche and paves the way for clinical trials for improving ovarian function of women with POI. We also had the opportunity to share our hypothesis about the design and development of induced oogonial stem cell (iOSC) and its use in POI.

Spinal muscular atrophy (SMA) is one of the common autosomal recessive disorders with global heterozygous carrier frequency of 1:50. Due to high carrier frequency, significant morbidity associated with the infantile onset disease and prohibitive cost of recently approved therapy, American College of Medical Genetics and Genomics (ACMG) recommends population based screening for SMA carrier status in eligible individuals in the reproductive age group. CODE-SEQ is a novel proprietary next generation sequencing (NGS) based assay, which is capable of detecting homozygous as well as heterozygous SMN1 exon 7 deletions. Along with the copy number estimation, this assay is capable of detecting single nucleotide polymorphisms (SNPs) associated with silent SMA carrier status or “2+0” genotype. We have validated a proprietary CODE-SEQ technology in a blinded cohort of 80 clinically well characterized samples from Turkish population for the detection of SMA carriers as well as affected cases. The results were correlated with gold standard MLPA assay. The copy numbers in exon 7 of SMN1 gene matched with MLPA results in all 80 samples giving 100% correlation. The assay accurately detected the presence/ absence of SNPs associated with “2+0” genotype in the reference samples. None of the tested clinical samples had these SNPs. The results of this study support the notion that CODE-SEQ will be extremely useful in detecting SMA genotypes in large-scale population-based screening studies.

Purpose The molecules human interleukin (IL-18), the soluble cluster of differentiation (sCD40), platelet factor 4 variant 1 (PF4V1), and neutrophil gelatinase-associated lipocalin (NGAL) are all markers of inflammation in biological systems and are linked to prognosis in several inflammatory diseases as well. Since there is no study in which the above-mentioned molecules are studied together in ocular Behçet's disease (OBD), the aim of this study is to reveal whether these molecules are activity markers in active (OABD) and inactive (OIBD) disease. Methods 30 OABD and 30 OIBD and 30 healthy individuals were included in the study. IL-18, sCD40, PF4V1, and NGAL molecules were studied in blood samples by the ELISA method. Results When OABD and OIBD were compared to healthy individuals, the levels of IL-18, sCD40, PF4V1, and NGAL molecules were found to be statistically significant. These values were even more significantly higher in patients with OABD. Conclusion When ROC values of IL-18, sCD40, PF4V1, and NGAL are evaluated, it is clear that these four molecules can be used as biomarkers to aid activity and diagnosis in OBD.

PurposeCOVID-19 disease has a worse prognosis in patients with diabetes, but the comparative data about the course of COVID-19 in patients with type 1 (T1DM) and type 2 diabetes (T2DM) are lacking. The purpose of this study was to find out the relative clinical severity and mortality of COVID-19 patients with T1DM and T2DM.MethodsA nationwide retrospective cohort of patients with confirmed (PCR positive) COVID-19 infection (n=149,671) was investigated. After exclusion of individuals with unspecified diabetes status, the adverse outcomes between patients with T1DM (n=163), T2DM (n=33,478) and the non-diabetics (n=115,108) were compared by using the propensity score matching method. The outcomes were hospitalization, the composite of intensive care unit (ICU) admission and/or mechanical ventilation and mortality.ResultsThe patients with T1DM had higher mortality than the age and gender matched patients with T2DM (n=489) and the non-diabetics (n=489) (pConclusionAccording to the results, patients with T1DM had poorer COVID-19 prognosis than those with T2DM or the non-diabetics. These patients should be cared diligently until more data will be available about the causes of increased COVID-19 mortality in T1DM.

The molecules human interleukin (IL-18), the soluble cluster of differentiation (sCD40), platelet factor 4 variant 1 (PF4V1), and neutrophil gelatinase-associated lipocalin (NGAL) are all markers of inflammation in biological systems and are linked to prognosis in several inflammatory diseases as well. Since there is no study in which the above-mentioned molecules are studied together in ocular Behçet's disease (OBD), the aim of this study is to reveal whether these molecules are activity markers in active (OABD) and inactive (OIBD) disease.30 OABD and 30 OIBD and 30 healthy individuals were included in the study. IL-18, sCD40, PF4V1, and NGAL molecules were studied in blood samples by the ELISA method.When OABD and OIBD were compared to healthy individuals, the levels of IL-18, sCD40, PF4V1, and NGAL molecules were found to be statistically significant. These values were even more significantly higher in patients with OABD.When ROC values of IL-18, sCD40, PF4V1, and NGAL are evaluated, it is clear that these four molecules can be used as biomarkers to aid activity and diagnosis in OBD.

BackgroundThe corpus callosum (CC) is the most targeted region in the cerebrum that integrates cognitive data between homologous areas in the right and left hemispheres.AimsOur study used statistical analysis to determine whether there was a correlation between shape changes in the CC in patients with schizophrenia (SZ) (deficit syndrome (DS) and non-deficit syndrome (NDS)) and healthy control (HC) subjects.MethodsThis study consisted of 27 HC subjects and 50 schizophrenic patients (20 with DS and 30 with NDS). 3 patients with DS and 4 patients with NDS were excluded. Three-dimensional, sagittal, T1-spoiled, gradient-echo imaging was used. Standard anatomical landmarks were selected and marked on each image using specific software.ResultsAs to comparing the Procrustes mean shapes of the CC, statistically significant differences were observed between HC and SZ (DS+NDS) (p=0.017, James’s Fj=73.732), HC and DS (pj=140.843), HC and NDS (p=0.006, James’s Fj=89.178) and also DS and NDS (pj=152.967). Shape variability in the form of CC was 0.131, 0.085, 0.082 and 0.086 in the HC, SZ (DS+NDS), DS and NDS groups, respectively.ConclusionsThis study reveals callosal shape variations in patients with SZ and their DS and NDS subgroups that take into account the CC’s topographic distribution.

Autonomously controlled intelligent wheelchair is an electric wheelchair system that can reach a desired position by finding paths without any need for user intervention. Pathfinding can be performed in outdoor areas with the support of global positioning system (GPS) while interior mapping is required for indoor areas. In this study, an autonomous control interface design that can work with intelligent wheelchairs has been implemented to be used on indoor areas. This interface is used building floor plans and pathfinding algorithms for planning a path to a selected destination. The autonomous control of an electrically powered wheelchair is performed using fuzzy logic on the planned path. On the hardware side, a depth camera, a single board computer, microcontrollers, speed sensors, lighting systems and a motor driver are added on the electric-powered wheelchair. All components are operated under the coordination that provided with the interface. The instantaneously detection of obstacles that may be encountered causes the path to be changed with an alternative, and this situation can be shown synchronously within a simulation software.

The new systems obtained by adding computer support to battery powered wheelchairs are called smart wheelchairs. Today, there are various map providers and navigation systems that a mobile vehicle can use to get from one location to another. However, these map providers do not support indoor spaces and satellite-aided global positioning systems cannot provide solutions in indoor environments. In this study, by using the pre-mapping of interior spaces and the use of appropriate path finding algorithms, individuals can reach their desired location in an environment that they do not know exactly, via smart wheelchairs. The designed interface software provides the path was determined with the jump point search, one of the shortest path finding algorithms, and the system was simulated with the simulation software.

Despite significant advances in medicine, mortality due to cardiovascular disease is not yet preventable. We investigated the amounts of elabela (ELA) and apelin, synthesized by cardiomyocytes, and changes of these compounds in cardiac tissue and circulation after administration of iloprost (ILO) and sildenafil (SIL) in rats with induced myocardial ischemia (MI). We also investigated a connection with circulating troponin-I, creatine kinase (CK), creatine kinase-myocardial band (CK-MB) and nitric oxide (NO), and total anti-oxidant (TAS)/total oxidant status (TOS). We established eight study groups of five rats each. Group 1, sham, was given only physiologic serum; group 2, ILO; group 3, SIL; group 4, ILO + SIL; group 5, MI; group 6, MI + ILO; group 7, MI + SIL; group 8, MI + ILO + SIL. Troponin-I, CK, CK-MB and TAS-TOS were investigated using an autoanalyzer. NO, ELA and apelin were analyzed by ELISA. Tissue apelin and ELA expressions and localizations were determined by immunohistochemistry. The MI group compared to the control (sham) group showed that ELA, apelin, troponin-I, CK, CK-MB, NO and TOS levels were elevated significantly. Concentrations of these factors increased in MI, but decreased after ILO and SIL administration. The largest decrease of TOS was identified in the ILO + SIL group. ELA and apelin may be novel indicators of MI and administration of ILO and SIL, individually or together, may be useful for treating MI.

Schizophrenia, particularly the form related to excessive dopamine (DA), is a chronic psychotic disorder affecting millions of people worldwide. Renalase metabolizes its catecholamine (CA) substrates, including DA, suggesting that there might be an association between renalase levels and schizophrenia occurrence. Therefore, the current study aimed to evaluate the renalase and CA levels in the serum of patients with schizophrenia.The study was conducted with thirty-three schizophrenia patients and an age- and gender-matched group of thirty-one controls. Renalase and CA levels were measured by using an enzyme-linked immunosorbent assay (ELISA).Renalase levels were significantly lower in the schizophrenia patients than in the control group (The high DA levels in patients with schizophrenia might be due to low renalase levels. Renalase enzyme levels may play a substantial role in the pathophysiology of schizophrenia. Thus, this enzyme might be a new future target for the treatment and diagnosis of schizophrenia after intrabrain renalase and DA dynamics have been further evaluated.Shizofrenija, posebno oblik sa povećanim dopaminom (DA) je hronični psihijatrijski poremećaj od koga boluju milioni ljudi širom sveta. Relanaza metaboliše supstrate kateholamine (CA), uključujući DA, što ukazuje da može da postoji veza između nivoa relanaze i pojave shizofrenije. Shodno ovome, ovo izučavanje je imalo za cilj da proceni nivoe relanaze i CA u serumu pacijenata sa shizofrenijom.Izučavanje je obuhvatilo trideset tri pacijenta sa shizofrenijom i trideset jednu osobu iste starosti i pola kao kontrolnu grupu. Nivoi renalaze i CA mereni su primenom ELISA metode.Nivoi renalaze bili su značajno niži kod pacijenaza sa shizofrenijom nego u kontrolnoj grupi (p0,05), dok su nivoi DA bili značajno viši (p0,05). Nivoi epinefrina (Epi) u obe grupe bili su manji (p=0,186), dok su nivoi norepinfrina u pacijenata sa shizofrenijom bili značajno niži nego u kontrolnoj grupi (p0,05). Površina ispod krive za renelaze-dopamin i renelaze-epinefrin odnose bili su 0,805, 95% konfidens interval CI: 0,594–0,859 (p=0,032); i 0,656, 95% CI: 0,520–0,791 (p=002).Visoki nivoi DA u pacijenata sa shizofrenijom mogu biti usled niskih nivoa renalaze. Nivoi renalaze enzima mogu imati značajnu ulogu u patofiziologiji shizofrenije. To znači da ovaj enzima može imati značajnu ulogu u tretmanu i dijagnostikovanju shizofrenije te ona treba dalje da bude izučavana kao i dinamika DA.

The follicle must fulfill the following criteria if it is to survive the period between early embryonic life and the luteinizing hormone (LH) peak. It should (i) be surrounded by pregranulosa cells; (ii) complete the first meiotic division and become dormant; and (iii) continue metabolism during the dormant stage. Interaction between the natriuretic peptide precursor type C (Nppc) and its receptor, natriuretic peptide receptor 2 (Npr2), affects female fertility through the production of oocytes with developmental capacity and maintain oocyte meiotic arrest. While Nppc is expressed in mural cells, cumulus cells express Npr2. Nppc/Npr2 system exerts its biological function on developing follicles by increasing the production of intracellular cyclic guanosine monophosphate (cGMP). This pathway not only contributes to the development of ovary and the uterus, but aids the formation of healthy eggs in terms of their morphological and genetic aspects. A defect in this pathway leads to asmall ovarian size, string-like uterine horns, and thin endometrium and myometrium. Disorganized chromosomes, abnormal cumulus expansion and early meiotic resumption occur in animals with defective Nppc/Npr2 signaling. The types and number of oocytes also decrease when there is incompetent Nppc/Npr2 signaling. This paper extends on most recent and relevant experimental evidence regarding Nppc/Npr2/cGMP signaling with regard to its crucial role in maintaining oocyte meiotic arrest and the production of oocytes with developmental capacity. We further discuss whether the agonist or antagonist forms of the members of this exciting pathway can be usedfor triggering final oocyte maturation.

We investigated the expression of irisin in renal cancers using immunocytochemistry. Irisin has been reported to exhibit anticancer properties. The study groups consisted of 22 cases each of control renal tissue, oncocytoma, chromophobe renal cell carcinoma (RCC), clear cell RCC (Fuhrman nuclear grades 1, 2, 3 and 4) and papillary RCC. We evaluated 10 slides for each of 176 cases. Slides were immunostained for irisin and histoscores were calculated for the prevalence and strength of immunostaining. Fuhrman nuclear grade 1, 2, 3 clear cell RCC and papillary RCC exhibited no irisin immunoreactivity. Irisin immunoreactivity was observed in some Fuhrman nuclear grade 4 RCCs. We found a significant decrease in irisin staining in chromophobe RCC compared to the control. Immunoreactivity in the oncocytoma tissue was comparable to the control group. Irisin immunoreactivity in chromophobe RCC decreased and no immunoreactivity was observed in Fuhrman nuclear grade 1, 2, 3 clear cell RCC and papillary RCC. Immunistochemical screening of irisin in renal oncocytomas and renal cancers may be useful for differential diagnosis.

Objective: The incidence of thyroid cancer has been continuously increasing. The main objective of this study was to investigate irisin expression in various thyroid pathologies and to compare these expression patterns with irisin expression in healthy thyroid tissues. Methods: The study groups consisted of 20 cases each of control thyroid tissue, Hashimoto’s thyroiditis, thyroid papillary carcinoma, oncocytic papillary carcinoma, follicular thyroid carcinoma, oncocytic follicular thyroid carcinoma, medullary thyroid carcinoma, anaplastic thyroid carcinoma. Irisin expression was evaluated using immunohistochemistry. Irisin levels in thyroid tissue supernatants were measured using ELISA. Results: Patients with HT showed increased irisin expression compared with controls (p

Background Rearrangement of the 1q21 region of chromosome 1 manifests as multiple phenotypes, including microcephaly, intellectual disability, dysmorphic facial features, eye abnormalities, cardiac defects, genitourinary anomalies, autism spectrum disorder, psychiatric conditions and seizures. Herein, we describe eight patients with 1q21 deletion and duplication syndromes, and novel deletions and findings. Methods Chromosomal microarray analysis was performed to identify the existence of copy number variation. Quantitative polymerase chain reaction was applied using specific primers for the control and 1q21 region of chromosome 1. Mutational analysis was performed in case 5 using direct genomic sequencing for exons 1-6 in RBM8A. Results Copy number variation analysis identified seven deletions and one duplication of the 1q21 region in the eight patients. In addition, four variations were de novo, and two deletions are reported here for the first time. One of the cases (case 7) presents moderate intellectual disability and dysmorphic facial findings, whereas chromosomal microarray analysis showed that case 7 had an 889-kb deletion in the 1q21 proximal region (GPR89A, PDZK1, CD160, POLR3C and NBPF12). Conclusion Although the deletion in case 5 did not include the thrombocytopenia-absent radius syndrome critical region or the RBM8A gene, he had pectoral muscle hypoplasia, radius and humerus hypoplasia and short curved ribs, which are indicative of a potential thrombocytopenia-absent radius region modifier. The findings in case 7 suggest that the proximal part of the 1q21 microdeletion syndrome region might be very important for the onset of clinical manifestations. Some novel findings were observed in the presented cases, such as radius and humerus hypoplasia and brain stem hypoplasia. The presented findings expand the spectrum of 1q21 aberrations and provide evidence of genotype-phenotype correlations for this region.

Purpose Acute myocardial infarction (AMI) is the most common cause of death in the world. Comprehensive risk assessment of patients presenting with chest pain and eliminating undesirable results should decrease morbidity and mortality rates, increase the quality of life of patients, and decrease health expenditure in many countries. In this study, the advantages and disadvantages of the enzymatic and nonenzymatic biomarkers used in the diagnosis of patients with AMI are given in historical sequence, and some candidate biomarkers - hFABP, GPBB, S100, PAPP-A, RP, TNF, IL6, IL18, CD40 ligand, MPO, MMP9, cell-adhesion molecules, oxidized LDL, glutathione, homocysteine, fibrinogen, and D-dimer procalcitonin - with a possible role in the diagnosis of AMI are discussed. Methods The present study was carried out using meta-analyses, reviews of clinical trials, evidence-based medicine, and guidelines indexed in PubMed and Web of Science. Results These numerous AMI biomarkers guide clinical applications (diagnostic methods, risk stratification, and treatment). Today, however, TnI remains the gold standard for the diagnosis of AMI. Details in the text will be given of many biomarkers for the diagnosis of AMI. Conclusion We evaluated the advantages and disadvantages of routine enzymatic and nonenzymatic biomarkers and the literature evidence of other candidate biomarkers in the diagnosis of AMI, and discuss challenges and constraints that limit translational use from bench to bedside.

Background: Molecular aberrations including MSI, RAS, RAF, and HER2 have been used to guide the management of mCRC. However, the role of PIK3CA mutations is unclear in mCRC. In this study, we aimed to determine the prognostic value of PIK3CA mutations and their predictive value of response to anti-EGFR therapy in mCRC patients (pts). Methods: Pts with mCRC and clinical next generation sequencing were identified from the Clinical Genomics Action Committee database at Moffitt Cancer Center. Clinical and molecular aberration data were retrospectively collected. Progression-free survival (PFS) was the time from treatment initiation to clinical or radiographic disease progression. Overall survival (OS) was the time from diagnosis of metastatic disease to death. Kaplan Meier method and log-rank test were used for survival analysis. A parametric exponential model was implemented for PIK3CA exon analysis to account for small sample size. Pearson correlation coefficient was determined for correlation between PIK3CA and co-mutations. An additional meta-analysis was performed including prior studies of pts with KRAS wild-type (wt) PIK3CA mutant (mut) mCRC receiving anti-EGFR therapy using random effects model. Results: Among 639 pts with mCRC, PIK3CA mutation was positively correlated with KRAS mutation (r=0.11, p=0.006) and negatively correlated with TP53 mutation (r=-0.18, p= Conclusion: PIK3CA mutation has positive correlation with KRAS mutation and negative correlation with TP53 mutation in mCRC. PIK3CA mutation confers a worse prognosis but is not predictive for response to anti-EGFR therapy in pts with KRAS wt mCRC. The latter finding was confirmed in an updated meta-analysis of 13 studies including ours. Citation Format: Elaine Tan, Wenyi Fan, Michael Schell, Ibrahim Sahin, Jason Fleming, Todd Knepper, Hao Xie. Prognostic and predictive value of PIK3CA mutations in metastatic CRC (mCRC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1239.

Objective To investigate the shape differences in the putamen of early-onset Parkinson’s patients compared with healthy controls and to assess and to assess sub-regional brain abnormalities. Methods This study was conducted using the 3-T MRI scans of 23 early-onset Parkinson’s patients and age and gender matched control subjects. Landmark coordinate data obtained and Procrustes analysis was used to compare mean shapes. The relationships between the centroid sizes of the left and right putamen, and the durations of disease examined using growth curve models. Results While there was a significant difference between the right putamen shape of control and patient groups, there was not found a significant difference in terms of left putamen. Sub-regional analyses showed that for the right putamen, the most prominent deformations were localized in the middle-posterior putamen and minimal deformations were seen in the anterior putamen. Conclusion Although they were not as pronounced as those in the right putamen, the deformations in the left putamen mimic the deformations in the right putamen which are found mainly in the middle-posterior putamen and at a lesser extend in the anterior putamen.

Objective: Our aim is to perform an analysis, using big data, of cases diagnosed with primary hypothyroidism and aged 18 and over who presented to our hospital, by evaluating the laboratory and socio-demographic data of the patients. Clustering analysis was performed in the big dataset for the purpose of structure-search study on the subject. Methods: According to ICD 10 diagnoses of hypothyroidism between 2005 to 2018 in our hospital 130159 patients aged 18 and over with E03 and E06 diagnosis codes were included in the study. Since drugs containing levothyroxine used in primary hypothyroidism treatment have an effect on the measured hormone levels, in our study, TSH, fT3 and fT4 laboratory values in the first diagnosis of cases who had not received any treatment as part of the diagnosis according to demographics were analysed. Patients with one or more missing laboratory values were excluded, and data of 2680 patients with complete data and TSH values above 4.94 mU/L were retained. Analysis was made with the k means clustering technique, with the data separated into two sets. k means clustering was performed by including age, TSH, fT3 and fT4 variables. Cliff’s Delta effect size coefficients and confidence intervals were calculated to perform size of the difference. Results: The higher prevalence of primary hypothyroidism in female and the peak in hypothyroidism at 4-5 decades in both genders were observed. In which ages were low, fT3 and fT4 values were higher, whereas TSH values were lower in male. In which ages were low, TSH values were higher, whereas fT4 values were lower in female. Conclusion: This study is the first big data analysis study carried out about primary hypothyroidism in our country. Despite the difficulties in implementation, it should not be forgotten that studies like these are important methods for enabling data to be created in our country.

Background Neoadjuvant chemoradiation with fluoropyrimidine followed by surgery and adjuvant chemotherapy has been the standard treatment of locally advanced stages II and III rectal cancer for many years. There is a high risk for disease recurrence; therefore, optimizing chemoradiation strategies remains an unmet need. Based on a few studies, there is evidence of the synergistic effect of VEGF/PDGFR blockade with radiation. Methods In this phase I, dose-escalation and dose-expansion study, we studied 3 different dose levels of lenvatinib in combination with capecitabine-based chemoradiation for locally advanced rectal cancer. Results A total of 20 patients were enrolled, and 19 were eligible for assessment of efficacy. The combination was well tolerated, with an MTD of 24 mg lenvatinib. The downstaging rate for the cohort and the pCR was 84.2% and 37.8%, respectively. Blood-based protein biomarkers TSP-2, VEGF-R3, and VEGF correlated with NAR score and were also differentially expressed between response categories. The NAR, or neoadjuvant rectal score, encompasses cT clinical tumor stage, pT pathological tumor stage, and pN pathological nodal stage and provides a continuous variable for evaluating clinical trial outcomes. Conclusion The combination of lenvatinib with capecitabine and radiation in locally advanced rectal cancer was found to be safe and tolerable, and potential blood-based biomarkers were identified. Clinical Trial Registration NCT02935309

Background:The frequency of new-onset diabetes after transplant(NODAT) is 5-30% in liver transplant recipients. Aims: We aimed to analyze the frequency and predictors of NODAT in the patients undergoing liver transplantation(LTx) due to acute liver failure(ALF), and to investigate whether pretransplant hypoglycemia had any effect on NODAT. Methods:Adult patients undergoing LTx due to ALF were analyzed retrospectively. The patients with chronic liver failure or diabetes were excluded. We measured pretransplant random blood glucose(RBG) and posttransplant fasting blood glucose(FBG). NODAT was diagnosed according to principally 1 st month FBG (group 1:125 mg/dL). The participants were subgrouped according to age, gender, BM, etiology, antiviral medication, thyroid function, pretransplant RBG, donor type, immunosuppressive drug, common infection, and surgical complication. Results:A total of 91 patients were analyzed; mean age was 33.48(±13.35), and 52.7%(n=48) of them was female. The etiology was Budd-Chiari syndrome in 3(3.29%), acute viral hepatitis in 38(41.75%), drug or toxin-related in 21(23.07%), and other/unknown causes in 29(31.86%) patients. The ratio of NODAT was 26.98% on the 1 st month. NODAT group had a higher pretransplant RBG than the others. Pretransplant hypoglycemia did not have any effect on NODAT; however, pretransplant hyperglycemia increased the risk of NODAT by 4.065 times(p=0.018). Conclusions:We showed that pretransplant hyperglycemia increased the risk of NODAT by 4 times, but hypoglycemia did not affect. The frequency of NODAT decreased progressively during follow-up. We recommend perioperative glycemic control should be maintained as early as possible to manage NODAT; however, it might be complicated in such a clinical condition.

Purpose Diabetic retinopathy (DRP) is the formation of edema and small vessels in the retina due to high blood glucose levels. Asprosin is a hormone that stimulates the release of glucose from the liver into the circulation. Considering the relationship between oxidative stress and DRP, our study aimed to determine the levels of the oxidative stress markers 4-hydroxynonenal (4-HNE) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), as well as asprosin, in the blood and aqueous humor (Aq) of patients with and without DRP. Methods Thirty patients with single-eye DRP and cataract (DRP + C), 30 patients with diabetes mellitus and cataract without DRP (DM + C), and 30 healthy control (CON) participants were enrolled into this retrospective study. Except for healthy controls, Aq and blood samples were taken from these patients during their cataract operation. Asprosin, 4-HNE, and 8-OHdG concentrations were analyzed using enzyme-linked immunosorbent assays. Results In patients with DRP, the levels of asprosin, 4-HNE, and 8-OHdG were significantly higher in both Aq and blood samples compared with the group of patients without DRP. Conclusion These findings suggest that the measurement of asprosin, 4-HNE, and 8-OHdG levels may support clinicians in determining the risk of DRP development.

Type 2 Diabetes Mellitus can affect bone metabolism by many mechanisms and increase the risk of osteoporosis. It has been reported that glucose-lowering treatments, including metformin also have an effect on bone turnover. The aim of this study is to evaluate the effect of metformin treatment on bone formation and resorption in patients with newly diagnosed type 2 Diabetes Mellitus. There were 37 patients in the study population who were newly diagnosed with type 2 Diabetes Mellitus. Fasting plasma glucose level and postprandial plasma glucose level as well as plasma Hemoglobin A1C, calcium, phosphorus, parathyroid hormone, osteocalcin and C-Telopeptide levels were measured before initiation of metformin treatment. The tests were repeated 3 months after the treatment. The levels of fasting plasma glucose and postprandial plasma glucose decreased after 3 months of metformin treatment as expected and the difference was statistically significant. However there was no significant change incalcium, phosphorus and parathyroid hormone levels. There was also a sig-nificant decrease due to Metformin treatment in osteocalcin levels, which is a bone formation mar-ker. Metformin treatment has decreased C-Telopeptide levels as well which is also a bone formation marker. Our results have shown that 3 months of metformin treatment may suppress the bone turno-ver. Another important finding of our study was the reduction in levels of bone formation markers in female patients. Controlledlong-term studies are needed to be conducted in order to manifest the clinical implications of these findings.

Thyrotropinomas (TSHoma) are rare pituitary adenomas. TSHomas can synthesize other hormones simultaneously. Co-secretion of TSH and GH is rarely reported in the literature. In these patients, signs of hyperthyroidism and acromegaly can be observed together. Its clinic is heterogeneous and in some cases, symptoms of thyrotoxicosis may mask the acromegaly symptoms. Some TSHoma patients may also be mistakenly diagnosed with Graves and experience a delay in diagnosis. We aimed to present a unique case with a diagnosis of TSHoma, who was referred to our center when Euthyroidism was not achieved and was followed up with a pre-diagnosis of Graves and also had GH co-secretion.

The purpose of this study is to test the validity and reliability of the Barriers to Insulin Treatment Questionnaire and adapt the questionnaire for Turkish society. This was a cross-sectional study. The population of this study consisted of adult patients with type 2 diabetes who were using insulin and being monitored in the Endocrine and Outpatient Clinics of Inonu University Turgut Ozal Medical Centre. The sample of the study consisted of 348 patients. The data were collected by using the Barriers to Insulin Treatment Questionnaire (BITQ) and a survey including demographic characteristics. The 14 items of the questionnaire are scored between 1 and 10. BITQ has five factors as fear of injections and self-testing, expectations regarding positive insulin-related outcomes, expected hardship from insulin treatment, stigmatization by insulin injections, and fear of hypoglycemia. In order to test the construct validity of the questionnaire, Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA) were utilized. The reliability of BITQ was evaluated by its Cronbach’s alpha internal consistency coefficient, item total correlation, and test-retest reliability. It was determined that the Cronbach’s alpha reliability coefficients of the questionnaire factors ranged between 0.70 and 0.82, the scale item factor loadings varied from 0.54 to 0.86, and the item total correlation coefficients were between 0.30 and 0.52. CFA supported the 5-factor scale structure obtained as a result of EFA. Good fit index values were obtained as a result of CFA. According to the obtained results, it may be asserted that BITQ is valid and reliable in terms of its application in Turkish society.

The goals of Type 2 diabetes treatment are to eliminate the hyperglycemia resulting from insulin insufficiency and/or insulin resistance, delay beta cell damage/depletion, and prevent other metabolic co-morbidities and complications. In the current treatment algorithms, lifestyle changes (medical nutrition therapy, physical exercise) and oral anti-diabetics are followed by insulin therapy, which is considered a replacement therapy for Type 2 diabetes. Pre-mixed insulin preparations, which are an option for patients with poor blood glucose level control under oral anti-diabetics treatment, have been developed to meet both basal and prandial insulin needs by simulating the physiological changes in insulin levels. The consensus on the necessity of individualizing insulin therapy requires physicians to have a detailed knowledge of the various uses of insulin. Therefore, this comprehensive consensus statement has been prepared by a panel of expert endocrinologists from different regions of Turkey to help physicians use biphasic insulin aspart 30 in suitable patients at the right time. In this statement, expert panel opinions on (a) Recommendations for the appropriate initiation, titration, and intensification of insulin treatment, and (b) The treatment algorithms in initiation, titration, and intensification of biphasic insulin aspart 30 treatment and special conditions specific to changing treatment regimen are presented.

OBJECTIVES AND BACKGROUND Familial Mediterranean Fever (FMF) is characterized by recurrent fever episodes as a result of inflammation of serous membranes. Changes in the number of different mtDNA copy number variations, detected in FMF patients, who developed amyloidosis, might be an important parameter in the understanding of the pathophysiology of the disease. METHODS Changes in the mtDNA copy number between 50 patients with FMF, who had M694V homozygote mutation and amyloidosis, and 50 healthy controls, who had not any MEFV mutation or FMF clinical finding, were examined. The 22 MEFV mutations were analyzed by Pyromark Q24 system. Quantitative analysis was performed on RT-PCR. The level of mtDNA was calculated using the delta Ct (ΔCt) of average Ct of mtDNA and nDNA (ΔCt = Ct mtDNA-Ct nDNA) in the same well as an exponent of 2 (2ΔCt). RESULTS A significant decrease in the amount of mtDNA was detected in FMF patients with M694V homozygous mutation carriers, who developed amyloidosis compared to the control group (p < 0.001). CONCLUSION In this study, mitochondrial dysfunction, which has been identified through changes in the mitochondrial genome in many diseases, was identified by showing that the copy number variations of mtDNA in leukocytes also decreased for FMF disease (Tab. 3, Fig. 1, Ref. 21).

Background Kidney transplantation is the best treatment method for end-stage renal disease. Technically, left kidney transplantation is easier than right kidney, and the complication rates in the right are higher than the left kidney. We performed 28 kidney transplantations from 14 deceased donors between November 2010 and May 2016. Our aim was to share our outcomes and experiences about these 28 patients. Methods We performed 182 kidney transplantations between November 2010 and May 2016. Fifty-four kidney transplantations were performed from deceased donors. Thirty-two of these were performed from 16 of the same donors. These 32 recipients' data were collected and retrospectively analyzed. We excluded the transplantations from two same-donors to their four recipients in this study. The remaining 28 recipients were included in the study. Results The left and right kidney recipients' numbers were equal (14:14). The left kidney:right kidney rate was 11:3 in the first kidney transplantation recipient group; in the second kidney transplantation recipient group, the rate was 3:11. The difference was statistically significant (P = .002). We found no statistical differences for sex, mean age, and body mass index of recipients, total ischemic time of grafts, hospitalization times, creatinine levels at discharge time, and current ratio of postoperative complications of recipients (P > .05). Conclusions There were no differences in the left or the right kidneys or in the first and the second kidney transplantations during the long follow-up period.

Linagliptin is a member of “Dipeptidyl Peptidase-4” (DPP-4) inhibitors and may be preferred for certain advantages. We present a type 2 diabetes case with developed skin findings after initiation of linagliptin. A 66-year-old type 2 diabetic woman with coronary heart disease for 10 years was admitted to our clinic with dry mouth, polydipsia and polyuria. She was on metformin, acetylsalicylic acid and nitrate treatment. The physical examination was unremarkable. On admission, blood glucose was 319 mg/dL, urine ketone was negative, serum biochemistry and arterial blood gas results were within normal limits. Linagliptin was added to treatment after glycemic regulation was achieved with intensive insulin regimen. On the second day of linagliptin treatment, palpable purpuralike lesions were seen in the lower and upper extremities. Linagliptin was considered as an etiological factor. After discontinuation of linagliptin, the lesions gradually regressed. DPP-4 inhibitors may lead to some dermatological side effects due to inhibition of other DPP enzymes. To the best of our knowledge, our case is the first case in the literature to develop palpable purpura after linagliptin treatment.

Objective: The incidence of thyroid cancer has been continuously increasing. The main objective of this study was to investigate irisin expression in various thyroid pathologies and to compare these expression patterns with irisin expression in healthy thyroid tissues. Methods: The study groups consisted of 20 cases each of control thyroid tissue, Hashimoto’s thyroiditis, thyroid papillary carcinoma, oncocytic papillary carcinoma, follicular thyroid carcinoma, oncocytic follicular thyroid carcinoma, medullary thyroid carcinoma, anaplastic thyroid carcinoma. Irisin expression was evaluated using immunohistochemistry. Irisin levels in thyroid tissue supernatants were measured using ELISA. Results: Patients with HT showed increased irisin expression compared with controls (p