The Role of Lymphovascular Space Invasion and Cytology in the Prognosis of Endometrial Cancer.

BACKGROUND: Lymphovascular space invasion (LVSI) and cytology are both independent and strong prognostic factors in endometrial cancer. This study aims to highlight the impact of LVSI and cytology positivity on prognosis, in addition to molecular classification. METHODS: A retrospective review was conducted on the records of 223 patients with endometrial cancer diagnosed between January 2011 and January 2021. The inclusion criteria stipulated that the patients were diagnosed with endometrial cancer by endometrial biopsy and were operated in the clinic. The exclusion criteria included sarcoma in the postoperative pathology report results or synchronous tumor. Staging was performed according to the Fédération internationale de gynécologie et d'obstétrique (FIGO) 2009 criteria. Cytology (using 50 cc saline) was obtained upon entry into the peritoneal cavity. In 20 patients, saline was not used due to the presence of ascites in the abdomen. The Kaplan-Meier method was employed to evaluate overall survival and progression-free survival. Survival rates were compared in terms of cytology and LVSI. RESULTS: After analyzing the postoperative pathology results, it was found that the mean tumor size was 4.03 ± 2.3 cm. The most common histological type was endometrioid carcinoma, with stage IA being the most common stage. Out of 223 patients with endometrial cancer, the overall survival rate was 82.4%, and the progression-free survival rate was 88.3%. For patients negative for LVSI, the progression-free survival rate was 93%, while for LVSI-positive patients, it was 77.3% (p < 0.001). Additionally, the progression-free survival rate for patients negative for cytology was 90.4%, whereas for cytology-positive patients, it was 77.1% (p < 0.05). CONCLUSIONS: In our study, we observed that LVSI positivity and cytology positivity also reduced the overall survival rate. We aimed to highlight that, in addition to molecular classification, cytology positivity and LVSI positivity are still highly significant and independent factors in prognosis.

Acute Effect of Brace Use on Upper-Extremity Functionality in Adolescent Individuals With Idiopathic Scoliosis: A Cross-Sectional Study.

It is well known that scoliosis adversely affects the functions of the upper extremities. However, the acute effect of rigid braces, which are widely used in the conservative treatment of scoliosis, on upper-extremity functionality remains unknown. The aim of this study was to investigate the acute effect of a rigid thoracolumbosacral brace use on upper-extremity functionality in individuals with adolescent idiopathic scoliosis (AIS). Thirty-eight individuals diagnosed with AIS participated in this cross-sectional study, with a mean age of 14.55 ± 1.90 years and a range of 10-18 years. The upper-extremity functionality was assessed using the Nine-Hole Peg Test and handgrip strength, with assessments conducted under both in-brace (with their own braces) and out-of-brace conditions. Nine-Hole Peg Test durations of the AIS patients for the nondominant side were significantly lower for in-brace conditions compared with out-of-brace conditions (p = .049, effect size = 0.136). The grip strength of the nondominant side was significantly higher for in-brace conditions compared with out-of-brace conditions (p = .025, effect size = 0.365). A weak negative correlation was found between the degree of curvature and the grip strength of the dominant side for in-brace conditions (r = -.323, p = .048). It was concluded that the brace had a positive effect on upper-extremity functionality on the nondominant side by both shortening the Nine-Hole Peg Test duration and increasing grip strength. In AIS patients, the brace may positively affect daily living by improving the functionality of the nondominant extremity.

The acute effects of brace use on lower extremity performance in individuals with adolescent idiopathic scoliosis.

BACKGROUND: Braces have been a popular treatment option for scoliosis among healthcare professionals for many years. However, the effect of braces on scoliosis treatment remains a subject of ongoing debate and research. AIMS: Our study aimed to evaluate the effects of wearing a spinal brace on vertical jump, postural control, reach distance, and fall risk in patients with Adolescent Idiopathic Scoliosis (AIS). METHODS: We included 33 patients with AIS aged between 10 to 18 years old in our cross-sectional study. Patients were randomly subjected to vertical jump test, standing long jump test, timed up and go test, postural control, and forward reach test, while wearing and not wearing the scoliosis brace, respectively. RESULTS: Our findings revealed that patients wearing scoliosis braces had significantly lower vertical jumps (p = .001), standing long jumps (p < .001), and forward reach distances with their dominant (p = .002) and non-dominant limbs (p = .007) compared to those who did not wear the brace. However, there was no significant difference in postural control and timed up and go test between the two groups (p > .05). CONCLUSIONS: Our study suggests that wearing a scoliosis brace may negatively affect an individual's vertical and standing long jumps, and forward reach distances. However, wearing or not wearing the brace had no significant effect on postural control and timed stand-up test. Long-term follow-up studies are needed to evaluate the overall effectiveness of scoliosis braces in treating AIS.

Effect of Locoregional Treatments in Hepatocellular Carcinoma: What Are the Pathologic/Radiologic Milan Criteria?

OBJECTIVES: Milan criteria is the most commonly used criteria for patients with hepatocellular carcinoma awaiting liver transplant. The effects of locoregional therapy on downstaging or bridging before liver transplant on survival remain controversial. Considering that the tumor size may change with locoregional therapy and formalin fixation after explantation, we aimed to evaluate the effects of locoregional therapy on radiological and pathological Milan criteria and survival. MATERIALS AND METHODS: Demographic data, etiology, preoperative alpha-fetoprotein value, Child-Pugh and Model for End-Stage Liver Disease-Na scores, status of being inside or outside of radiological Milan criteria, status of being inside or outside of Milan criteria in explant (pathological Milan criteria), and the locoregional therapy types and combinations were evaluated for their effects on inclusion in Milan criteria and survival. RESULTS: During the study period, 396 patients underwent liver transplant at our center, with 97 because of cirrhosis and hepatocellular carcinoma. When we viewed patients according to preoperative radiologic evaluations, 67.9% were within Milan criteria and 32.1% were outside. When we viewed according to explant (pathological) evaluations, 80.7% of patients were within Milan criteria. Among 97 patients, 71 (73.2%) had locoregional therapy (22 [30.9%] for downstaging, 49 [69.0%] for bridging to transplant), and 12 patients (12.3%) were within Milan criteria on explant examination while outside of Milan criteria before LT. One-year, 3-year, and 5-year survival rates were 80.7%, 76.1%, and 71.6%, respectively. CONCLUSIONS: As a result of radiological evaluations, in patients who were outside of Milan criteria and underwent locoregional therapy, explant pathology within Milan criteria had a positive effect on survival; however, after locoregional therapy, there was no significant effect on survival in patients who were still outside of Milan criteria.

Is There Any Effect of Retrograde Intrarenal Stone Surgery on Renal Functions in Childhood?

Purpose In this study, we aimed to demonstrate whether retrograde intrarenal stone surgery (RIRS) performed due to renal stones during the childhood period has any detrimental impact on renal functions. Materials and methods We retrospectively analyzed 121 patients aged 2 to 16 years who underwent RIRS for renal stones between March 2018 and February 2023. Data were available for 41 patients. The estimated glomerular filtration rate (eGFR) was computed using the modification of diet in renal disease (MDRD) formula on the day preceding the surgery and the third month after the surgery. We employed the National Kidney Foundation's chronic kidney disease (CKD) classification to categorize the glomerular filtration rate (GFR) into five groups. Preoperative and postoperative eGFR values of pediatric patients were compared by analyzing changes in CKD groups. Results Of the patients included in the study, 21 (51.2%) were male, while 20 (48.8%) were female children. No significant difference was found between the preoperative median eGFR and the postoperative median eGFR values (p=0.958). In the 3rd month after surgery, it was observed that 5 (12.1%) patients showed an improvement in their CKD stage, while deterioration was noted in 1 (2.4%) patient. Although a negative correlation was observed between the median eGFR change and both the operation time and the stone volume in Pearson correlation analysis, it was determined that this change did not create a significant difference (p=0.213 and p=0.295, respectively). Conclusion Stone surgery conducted with RIRS appears to yield positive outcomes on kidney function in the pediatric population. Nevertheless, being particularly attentive to patients with prolonged operation times and larger stone volumes is essential.

Plasma and aqueous levels of subfatin, preptin and betatrophin in patients with diabetic retinopathy.

AIM: To examine subfatin, preptin and betatrophin levels in plasma and aqueous in patients with diabetes mellitus (DM) (with and without retinopathy). MATERIAL AND METHOD: Sixty patients, who were similar in terms of age and gender, and were scheduled for operation due to cataract, were included in the study. The patients were divided into three groups as Group C (20 weeks without diabetes and comorbidity), Group DM (20 patients with DM but no retinopathy) and Group DR (20 patients with diabetic retinopathy). The preoperative body mass index (BMI), fasting plasma glucose, HbA1c, lipid profile levels of all patients in the groups were examined. Blood samples were also taken for plasma subfatin, preptin and betatrophin levels. At the beginning of the cataract surgery, 0.1 ml of aqueous fluid was taken from the anterior chamber. Plasma and aqueous subfatin, preptin and betatrophin levels were analyzed by ELISA (enzyme-linked immunosorbent assays) method. RESULTS: In our study results, there was a significant difference in BMI, fasting plasma glucose and hemoglobin A1c levels (p < 0.05 for all parameters). Plasma and aqueous subfatin levels were higher in Group DR compared to Group C (p < 0.001, p = 0.036, respectively). Plasma and aqueous preptin levels were higher in group DR and group DM than in group C (p = 0.001, p = 0.002, p < 0.001, p = 0.001, respectively). Plasma and aqueous betatrophin levels were higher in Group DR compared to group C (p = 0.001, p = 0.010, respectively). CONCLUSION: Subfatin, preptin and betatrophin molecules may have an important role in the pathogenesis of diabetic retinopathy.

Evaluation of the Trend of Biochemical Functions in the Early Period After Cadaveric Liver Transplantation.

BACKGROUND: Monitoring biochemical parameters to detect early complications after liver transplantation (LT) is important. Thus, we aimed to investigate parameter trends indicating liver function in patients who did not develop complications after cadaveric LT. METHODS: A total of 266 cadaveric LT operations performed by a single center between 2007-2022 were included in the study. Patients with any early complications were excluded from the study. During the first 15 days, the parameters reflecting the patients' liver integrity and synthesis functions were evaluated. All parameters studied were evaluated at the same time of day and by a single laboratory. RESULTS: Regarding synthesis functions, the coagulation parameters (prothrombin time and international normalized ratio) peaked on the first day and then decreased. Regarding tissue hypoxia, there was no significant change in lactate values. Total and direct bilirubin values also decreased after peaking on the first day. No significant change was observed in albumin, another liver synthesis value. CONCLUSIONS: Although an increase in aspartate aminotransferase, alanine aminotransferase, total and direct bilirubin, prothrombin time, and international normalized ratio, which was especially seen on the first day, is considered normal, values that do not decrease after the second day or lactate values that increase gradually should be a warning in terms of possible early complications.

The long-lived reactive nitrogen species in the troposphere: DFTB model for atmospheric applications.

The longest lived reactive NO2 molecule formation in a dry and clean air environment under a high-temperature shock wave was investigated under three basic reactions (R2 for the O + NO system, R6 for the NO + NO3 system, and R7 for the NO + O3 system) in the atmospheric environment. With certain approaches, a DFTB3 model was used, which gave results close to the density functional theory. In the calculations, the related reactions up to 250 ps were examined at individual specific temperatures, and the temperature ranges that contributed to the formation of the NO2 molecule were determined. Moreover, a shock wave with both heating and cooling channels was applied only on R2 to see whether molecular concentrations were in good agreement with atmospheric information. The reaction products were examined under a shock wave of about 20 ps. At the end of the study, the applicability of the DFTB model to atmospheric systems was demonstrated by comparing it with experimental data and information. QCT approach was also used for the calculation of reaction rate constants of only O2-formation on the O + NO system. Here, all systems are focused on nitrogen species containing oxygen. In particular, the highest-population NO molecule that emerged in the lightning flash event was used as the reactant, while systems existing with the longest lived NO2 in the atmosphere after the lightning flash were focused in the product channel. As a result of the study, the hypothesis of geophysicists that almost all NO2 formed in the lightning flash event originates from the NO + O system was disproved. It has been proven that the presence of NO3 molecules that can withstand high temperatures in such systems should be evaluated.

Clinicopathological features of atypical glandular cells, not otherwise specified, on cervicovaginal pap smears.

OBJECTIVE: The Papanicolaou (Pap) smear test is a standard screening test that detects cervical lesions and cancers. In this multicentric study, we performed a retrospective analysis of cytological results associated with atypical glandular cells, not otherwise specified (AGC-NOS). METHODS: We retrospectively reviewed Pap smear tests that resulted as AGC-NOS. A total of 254 women who underwent colposcopy due to a Pap smear result of AGC-NOS were included the study between 2003 and 2021. The ages, Pap smear results, HPV results if any, colposcopic biopsy results, endocervical and endometrial pathology results, and management of these patients were analysed. RESULTS: Two hundred fifty-four patients with AGC-NOS Pap smear results were included in the study. A total of 70 (27.6%) patients had cervical and endometrial premalignant or malignant lesions. Malignancy was observed in 17 (6.7%) patients (endometrium, n = 11 [4.3%]; cervix, n = 6 [2.4%]). Isolated premalignant or malignant lesions of the cervix and endometrium were detected in 57 (22.4%) and 12 (4.7%) patients, respectively. CONCLUSIONS: Patients diagnosed with AGC-NOS should undergo a careful evaluation with all clinicopathological features. Because cancer of the cervix and endometrium is not rare in patients diagnosed with AGC-NOS, colposcopic examination with endocervical sampling should be a priority based on a cervicovaginal smear. Endometrial sampling is also required according to the patient's clinic, age, and examination characteristics.

Bis-1,2,4-triazol derivatives: Synthesis, characterization, DFT, antileishmanial activity and molecular docking study.

In this study, triazol derivatives, 4,4'-(((1E, 1E')-1,2-phenylenebis (methanylyidene)) bis (azanylidene)) bis (5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one (2), 4,4'-(((1E, 1E')-1,3-phenylenebis (methanylyidene)) bis (azanylidene)) bis (5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one (3) and 4,4'-(((1E, 1E')-1,4-phenylene bis (methanyl yidene)) bis (azanylidene)) bis (5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one (4) were synthesized from the reaction of 4-amino-5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one and phthalaldehyde/isophthalaldehyde/terephthalaldehyde, respectively. Compounds 2-4 were characterized by Fourier transform infrared (FTIR), proton and carbon-13 nuclear magnetic resonance (1H- and 13C- NMR) spectroscopic methods. Theoretical study for compounds 2-4 were carried out by DFT/B3LYP/6-311++G(d,p). Structural and spectroscopic parameters were determined theoreticaly and compared with experimental ones. Also, the molecular electrostatic potential (MEP) maps of compounds were obtained. Leishmanicidal activity of compounds 2-4 against to Leishmania infantum was determined by microdilution broth method containing alamar blue. As a result of the study, compounds 2-4 were found to be effective against the specie of Leishmania. Molecular docking analysis against Trypanothione Reductase (TRe) with compound 2 was carried out to see the necessary interactions responsible for antileishmanial activity. The docking calculations of compound 2 supported the antileishmanial activity exhibiting high inhibition constant.Communicated by Ramaswamy H. Sarma.

The Evaluation of Central Venous Catheter-related Complications in Pediatric Acute Leukemia Patients: Single Center Experience.

Central venous catheters (CVCs) are important for maintenance of childhood leukemia treatment but CVCs may develop complications. The aim of this study was to retrospectively evaluate the CVC-related complication rate, complication types, and outcome in children with acute leukemia. Complications developing in 310 CVCs (ports n=250, Hickman catheters n=60) inserted in 262 patients were evaluated. A total of 225,296 catheter days were screened. Median (range) CVC in-dwelling time was 661.5 (1 to 2636) days. In total, 157 complications developed of which 91 (58%) were infectious complications, 35 (22.3%) were vascular, 19 (12.1%) were surgical, and 12 (7.6%) were mechanical. Hickman catheters had a higher complication rate and were more prone to mechanical complications ( P <0.01) but there was no difference for other complications. A lower absolute neutrophil count at insertion was observed in children with infectious complications ( P <0.01). Seventy-eight of 136 catheters (57.3%) had to be removed prematurely. The overall complication rate was 0.65 per 1000 catheter days. In multivariate analysis, relapse leukemia, Hickman catheter and low absolute neutrophil count increased complication risk by 4.00, 1.97, and 1.92 times, respectively. Five (1.9%) deaths occurred because of catheter complications. Safe use of CVCs can be improved by early detection of complications and an experienced catheter care team.

Does Liver Transplant Improve Neurological Symptoms in Wilson Disease? Report of 24 Cases.

OBJECTIVES: Wilson disease is an inherited disorder that results in copper accumulation in the tissues with liver injury and failure. Orthotopic liver transplant is one of the treatments of choice for this disease. The aim of this study was to compare the neurological symptoms, before and after orthotopic livertransplant, of patients with liver cirrhosis due to Wilson disease, who represent a special group of patients with liver failure. MATERIALS AND METHODS: Between 2007 and 2020, there were 24 patients with Wilson disease resistant to medical treatment who underwent deceased donor orthotopic livertransplant and were followed up for 1 year, 5 years, and 10 years for evaluation with neurological scoring systems. Patients were also evaluated for postoperative complications and survival. RESULTS: Of the 24 patients evaluated, there were 13 (54.2%) female patients and 11 (45.8%) male patients, and the mean age was 34 years (range, 14-57 years). One of the patients died from early postoperative sepsis. After orthotopic livertransplant, disease scores returned to normal in 16 patients and improved in the remaining patients. Before transplant, all patients required help in their daily activities. After transplant, there were significant improvements in some symptoms, and the patients became more independent in their daily lives. CONCLUSIONS: Our study shows that orthotopic liver transplant provides significant improvement in neurological symptoms and quality of life in patients with Wilson disease.

Post-recurrence survival analysis of patients with pulmonary recurrence from gynaecologic cancers: a multi-institutional analysis of 122 patients.

In this retrospective study, patients with epithelial gynaecologic cancer with pulmonary recurrence (PR) were evaluated from five national gynaecologic oncology clinics. Patients with a diagnosis of primary endometrial, ovarian/fallopian tube/peritoneal, cervical or vaginal/vulvar tumours who developed an initial PR were included in the study A total of 122 patients were included in the study. The median follow-up time after recurrence was 7.5 (range, 1-84) months. The 2-year PRS was 48% in the main cohort. The risk of death was more than seven times higher in patients who did not receive salvage chemotherapy compared with those who did (hazard ratio: 7.6, 95% CI: 3.0-18.9; p < .001). When squamous cell carcinoma was compared with the other tumour types, the risk of death increased more than three times (hazard ratio: 3.7, 95% CI: 1.4-9.6; p = .007).IMPACT STATEMENTWhat is already known on this subject? Pulmonary recurrence (PR) from gynaecologic malignancies is rare and can cause major clinical problem. Therefore, defining the clinical and pathologic characteristics and recurrence patterns are essential.What the results of this study add? This study demonstrates non-squamous subtype and salvage chemotherapy at PR were associated with improved survival.What of these findings for clinical practice and/or further research? To the best of our knowledge, our study is the largest study to investigate the clinico-pathologic characteristics, recurrence patterns, treatment options, and post-recurrence survival (PRS) in patients with PR from epithelial gynaecologic cancers. Future research should examine the underlying causes of these findings.

Laparoscopy is a definitive diagnostic method for auto-amputated ovary in infants.

PURPOSE: Antenatal auto-amputation of the ovary is an extremely rare event, and its diagnosis is difficult. We aimed to retrospectively review the cases with antenatal auto-amputation, where the diagnosis was made based on detection of free-floating cyst during surgery. METHODS: Patients diagnosed with auto-amputated ovary during the surgery between 2012 and 2021 were included in the study. The data were reviewed retrospectively. Clinical, radiological, surgical, and histopathological findings were recorded. RESULTS: Eight patients underwent surgery for an abdominal cystic mass. The age range of patients who were operated was from 21 days to 9 months. None of the patients had symptoms, except one patient who had a large cyst and was vomiting. Prenatal ultrasound examination indicated an intra-abdominal cyst in all patients, but auto-amputated ovary diagnosis was not made. Differential postnatal diagnoses included an ovarian cyst, ovarian teratoma, tuba-ovarian torsion, mesenteric lymphatic malformation, and intestinal duplication cyst. Only one patient had an auto-amputated ovary suspicion in computed tomography. Laparoscopic exploration (n: 7) or laparotomy (n: 1) was performed. Histopathologic examination was necrosis and calcification (n: 6), necrosis (n: 1), and serous cystadenoma and necrosis (n: 1). CONCLUSION: We suggest that laparoscopy should be used for diagnosis and treatment of antenatal intra-abdominal cysts that persist postnatally because of diagnostic dilemmas. We recommend in patients diagnosed with auto-amputated ovary that the other ovary should be carefully monitored and followed up in terms of ovarian cyst, due to the possible risk of torsion.

Interleukin 18, soluble cluster of differentiation 40, platelet factor 4 variant 1, and neutrophil gelatinase-associated lipocalin can be used as biomarkers to aid activity and diagnosis in ocular Behçet's disease.

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.

Plasma and aqueous levels of alarin and adipsin in patients with and without diabetic retinopathy.

BACKROUND: Diabetic retinopathy is a disease seen with microvascular complications as a result of hyperglycemia and insulin resistance. Alarin and Adipsin are molecules with a role in energy and glucose metabolism. The aim of this study was to determine plasma and aqueous levels of Alarin and Adipsin in patients with and without diabetic retinopathy to evaluate their potential roles in diabetic retinopathy. METHODS: The study included one eye from each of 20 cataract patients without diabetes (C), 20 cataract patients with diabetes and without diabetic retinopathy (DM + C), and 20 cataract patients with diabetes and diabetic retinopathy (DR + C). Plasma and aqueous humour samples were taken from all patients during the cataract operation. Alarin and Adipsin levels were examined with the enzyme-linked immunosorbent assay (ELISA) method. RESULTS: Both plasma and aqueous Alarin levels were significantly higher in the patients with diabetic retinopathy than in the control group (p < 0.001, p = 0.006). Adipsin levels were found to be significantly higher in plasma in the control group than in the DR + C group and significantly higher in aqueous in the DR + C group than in the control group (p < 0.001, p < 0.001). CONCLUSION: These findings suggest that Alarin and Adipsin may play important role in diabetic retinopathy.

Plasma and aqueous humor levels of adiponutrin and pannexin 1 in patients with and without diabetic retinopathy.

AIM: To evaluate plasma and aqueous levels of adiponutrin and pannexin 1 in patients with and without diabetic retinopathy. METHODS: The study included three age and gender-matched groups of 20 cataract patients with no diabetes or additional disease (Group C), 20 cataract patients with diabetes and no retinopathy (Group DM+C), and 20 cataract patients with diabetic retinopathy (Group DR+C). All the patients were examined with respect to body mass index (BMI), fasting plasma glucose, hemoglobin A1c (HbA1c), and lipid profile. Phacoemulsification and intraocular lens (Phaco+IOL) implantation were performed to all patients in all the groups, and aqueous samples were taken during the operation. The plasma and aqueous adiponutrin and pannexin 1 levels were analyzed using enzyme-linked immunosorbent assays. RESULTS: A statistically significant difference was determined between the groups with respect to BMI, fasting plasma glucose, and HbA1c levels (P<0.05 for all parameters tested). The plasma adiponutrin levels of Group DR+C were statistically significantly lower than those of Group C and Group DM+C (P<0.001, P=0.004). No statistically significant difference was determined in the aqueous adiponutrin levels in three groups. The plasma pannexin 1 levels of Groups DM+C and DR+C were statistically significantly lower than those of Group C (both P=0.001). The aqueous pannexin 1 levels of Group DR+C were statistically significantly higher than those of Group C and Group DM+C (P=0.001, P<0.001). CONCLUSION: Adiponutrin and pannexin 1, which play an important role in the pathophysiology of diabetes and obesity, and have a regulatory role in hyperglycemia and insulin resistance. The measurement of adiponutrin and pannexin 1 levels may support clinicians in determining the risk of DR development.

Design of a Potent TLX Agonist by Rational Fragment Fusion.

As a master regulator of neurogenesis, the orphan nuclear receptor tailless homologue (TLX, NR2E1) maintains neuronal stem cell homeostasis by acting as a transcriptional repressor of tumor suppressor genes. It is hence considered as an appealing target for the treatment of neurodegenerative diseases, but a lack of potent TLX modulators as tools to probe pharmacological TLX control hinders further validation of its promising potential. Here, we report the development of a potent TLX agonist based on fragment screening, pharmacophore modeling, and fragment fusion. Pharmacophore similarity of a fragment screening hit and the TLX ligand ccrp2 provided a rational basis for fragment linkage, which resulted in several TLX activator scaffolds. Among them, the fused compound 10 evolved as a valuable TLX agonist tool with submicromolar potency and high selectivity over related nuclear receptors, rendering it suitable for functional studies on TLX.