COMT rs4680 and DRD2 rs6275 variants and their association with YMRS scores in children with early-onset bipolar disorder

Background and objectives: Bipolar disorder (BD) is a clinical status with at least one manic, hypomanic or mixed attacks. Genetic factors take part significantly in early-onset BD (EOBD). Dopamine receptors (DRD) act in neurological mechanisms like motivation, learning, memory, and, control of neuroendocrine signaling. DRD2 receptor has been reported to influence the stability of DRD2 transcript. Catechol-O-Methyl transferase (COMT) inactivates catecholamines and Val158Met variation on COMT has effects on COMT activity. This study aims to explore DRD2 and COMT variants in the clinical development of EOBD.MethodsIn this case-control study, 102 EOBD patients and 168 healthy control subjects were used. DRD2 rs6275 and COMT Val158Met variations were detected by real-time polymerase chain reaction (RT-PCR). Young Mania Rating Scale (YMRS) was utilized to determine the EOBD severity.ResultsFor DRD2 rs6275 and COMT Val158Met polymorphisms, no significant relationship was observed in the genotype and allele frequencies between patient and control groups. Nevertheless, TT genotype carriers of DRD2 rs6275 polymorphism demonstrated significantly increased YMRS scores when compared with CC and CT genotype carriers (p = 0.039). Nevertheless, no significant difference was observed between COMT Val158Met genotypes and YMRS scores.ConclusionsWe suggest that the DRD2 rs6275 TT variant can be associated with symptom severity in children with EOBD and can have a clinical significance in EOBD pathogenesis. However, these results need to be confirmed with larger samples of patient and control groups. (AU)

Aborted donor hepatectomy in living donor liver transplantation: lessons learned.

BACKGROUND: Aborted donor hepatectomy (ADH) during any stage of living donor hepatectomy (LDH) is a rare event. We describe our experience and discuss the lessons from these events. METHODS: From September 2005 to January 2019, 77 of 2 031 (3.79%) LDH were aborted at various stages of surgical procedure due to donor or recipient related reasons. Demographic and clinical data of aborted donor candidates and the clinical course of their potential recipients were analysed. RESULTS: LDH of 77 donor candidates was aborted due to donor (n = 53) or recipient (n = 24) related reasons. The most common donor related reason was the quality of liver parenchyma (n = 31). The most common recipient related reason was haemodynamic instability (n = 11). Twenty-three recipients underwent either living donor liver transplantation (LDLT) (n = 21) or deceased donor liver transplantation (DDLT) (n = 2) at a median of 6 days following ADH. In one aborted due to a donor reason and two aborted for recipient reasons, LDLT was performed using the same donor candidates. Thirty-six recipients had no liver transplantation (LT) and died a median of 17.5 days following ADH. CONCLUSIONS: We believe that ADH will decrease with experience and meticulous preoperative clinical and radiological evaluations. Abandoning the donor hepatectomy is always a valid option at any stage of the surgery when the unexpected is encountered.

Comparison of two methods for the rapid radiochemical analysis of air dust samples in emergency situations.

The reliable determination of airborne radionuclides in air is a key aspect in decision-making for the protection against public exposure in the event of a nuclear or radiological emergency. Nowadays, this needs to be done in real time and at the international level. These needs require the development of fast response protocols and the harmonisation of results. This work presents two fast radiochemical methods for the simultaneous separation of alpha and beta emitters in aerosols and their performance in a series of samples.

The Alvarado Score is accurate in pregnancy: a retrospective case-control study.

BACKGROUND: Acute appendicitis is the most frequent abdominal condition that requires non-obstetric surgical intervention during pregnancy. This study aims to scan pregnant patients operated on for acute appendicitis to evaluate the efficiency of using the Alvarado Score (AS) for diagnosis. METHODS: Our study included 48 pregnant patients who were pre-diagnosed with acute appendicitis and operated on at our department of general surgery from January 2010 to July 2016 and whose files were accessed. Fifty-three non-pregnant female patients of reproductive age who were operated on for appendicitis during the same period were included in the study as the control group. The patients in both groups were divided into two groups based on their AS total score being 7 and ≥ 7. RESULTS: The mean age of the 48 pregnant patients was 28 (19-42) years, while the mean age of the 53 control patients was 31 (18-45) years. Among pregnant and non-pregnant women, about a third of patients had an AS < 7 (16 of 48 versus 18 of 53). There was no significant difference when the AS scores of both groups were compared (p = 0.947). Using pathology results as reference test, the sensitivity and specificity of the AS in pregnant women was 79 and 80%. CONCLUSIONS: As a result, when the data collected by our study are evaluated, we see that pregnancy does not have a negative effect on the efficacy of AS. Therefore, the AS system can be an easy, non-invasive auxiliary diagnostic tool with high diagnosis accuracy rates that can be used in pregnant patients suspected of having acute appendicitis.

Significance and outcome of living-donor liver transplantation in acute mushroom intoxication.

INTRODUCTION: Mushroom intoxication (MT) can lead to acute liver injury which may result in Mushroom intoxication-related liver failure (M-ALF) requiring liver transplantation (LT). In the present study, we want to share the experience of our institute regarding living-donor LT (LDLT) due to mushroom poisoning. AIM: The aim of this study is to identify the predictors of poor prognosis in patients with ALF secondary to mushroom intoxication requiring LDLT. MATERIALS AND METHODS: All patients with MT between 2008 and 2016 were evaluated. Demographics, symptoms, interval between symptoms and admission to our institute, laboratory data, model for end-stage liver disease (MELD)/pediatric end-stage liver disease (PELD) scores, clinical course, and outcomes of supportive therapy and LT were evaluated. There were two groups in the study: Group A = responsive to supportive therapy (n = 9) versus Group B = unresponsive to supportive therapy (n = 9). RESULTS: During the study, a total of 18 patients were admitted with M-ALF. Twelve (66.7%) of them were female, and the mean age was 39.9 ± 18.2 years. All of the nine patients in Group A fully recovered with supportive therapy. In Group B, one patient died during waiting period for LT and 8 patients received LDLT LDLT. Three of the eight patients who were transplanted died in the postoperative early period within postoperative 5 days. The patients in Group B had significantly higher MELD/PELD scores and encephalopathy rate than in Group A (P < 0.05). International normalized ratio (INR), bilirubin, ammonium levels, and platelet count were significantly different between groups (P < 0.05). The patients in Group B had significantly longer interval before admission to our institute (P < 0.05). CONCLUSION: The presence of encephalopathy, higher MELD/PELD, INR, bilirubin, ammonium levels, and lower platelet count was related to poor prognosis in MT. LDLT provides a good therapeutic option in patients with M-ALF. The time is a crucial factor in successful treatment of MT. Early admission to a tertiary referral center with expertise in LT results in a better prognosis and increased survival following M-ALF.

Living Donor Re-transplantation for Repeated Acute Liver Failure.

Emergency liver transplantation (LT) for acute liver failure (ALF) is a life-saving treatment. Occurrence of this situation in the same patient twice is very rare. Herein, we describe a patient who underwent two emergency LTs for ALF, both from living donors. When she was 26 years old, she underwent a right lobe living donor LT (LDLT) from her sister for ALF due to use of herbal weight loss medications. The next 3 years were uneventful but another ALF developed during a terminal stage pregnancy (37th week). Despite medical treatment, her liver functions worsened, and the baby was delivered by caesarean section. The second time, her brother was the donor and she recovered after the emergency right lobe re-LDLT. Both patient and baby were well at the 2-month follow-up. As far as we know, there is no reported similar case, and we concluded that LDLT is a paramount treatment option for both primary and secondary ALFs.

Results of an international comparison of activity measurements of 68Ge.

An international key comparison, identifier CCRI(II)-K2.Ge-68, has been performed. The National Institute of Standards and Technology (NIST) served as the pilot laboratory, distributing aliquots of a 68Ge/68Ga solution. Results for the activity concentration, CA, of 68Ge at a reference date of 12h00 UTC 14 November 2014 were submitted by 17 laboratories, encompassing many variants of coincidence methods and liquid-scintillation counting methods. The first use of 4π(Cherenkov)ß-γ coincidence and anticoincidence methods in an international comparison is reported. One participant reported results by secondary methods only. Two results, both utilizing pure liquid-scintillation methods, were identified as outliers. Evaluation using the Power-Moderated Mean method results in a proposed Comparison Reference Value (CRV) of 621.7(11)kBqg-1, based on 14 results. The degrees of equivalence and their associated uncertainties are evaluated for each participant. Several participants submitted 3.6mL ampoules to the BIPM to link the comparison to the International Reference System (SIR) which may lead to the evaluation of a Key Comparison Reference Value and associated degrees of equivalence.

Corona mortis: in vivo anatomical knowledge and the risk of injury in totally extraperitoneal inguinal hernia repair.

PURPOSE: Corona mortis (CMOR) is the arterial and/or venous vascular communication(s) between the obturator and external iliac vessels. Totally extraperitoneal (TEP) inguinal hernioplasty can be associated with vascular complications especially during the fixation of the mesh. Theoretically, CMOR is an important nominee. But, the data in literature are insufficient about CMOR injury. Additionally, most of the studies about CMOR have been usually performed on cadavers. We aimed to reveal the preperitoneal vascular anatomy of inguinal area and provide in vivo knowledge about CMOR. The risk of arterial injury was also evaluated. MATERIALS: The data of preperitoneal vascular anatomy of 321 patients who underwent TEP procedure between January 2005 and July 2014 were retrospectively evaluated. RESULTS: Mean age was 46 ± 8.9 years, 53 females vs 268 males. 391 hemipelvises were evaluated. Two types of arterial structure were identified; (1) an aberrant obturator artery forming an anastomosis with branches of ordinary obturator artery; (2) a pubic branch of inferior epigastric artery. The incidence of arterial CMOR was 28.4 % and of any arterial structure was 45.0 %. An arterial CMOR was considered as thick (≥2 mm) or thin (<2 mm). Injury of arterial CMOR during tack stapling on Cooper's ligament was seen in six cases (1.5 %). All of them were thin (<2 mm) in structure. Venous CMOR was visible only under low pressure in work space. CONCLUSION: During TEP hernia repair, CMOR and/or pubic branch of inferior epigastric artery can be damaged. To prevent this complication, tacks should be stapled to Cooper's ligament close to symphysis pubis and dissection should be careful on the posterior surface of superior pubic ramus. Small caliber (<2 mm) arterial CMOR is more prone to be injured during TEP procedure. To explore venous structures properly, pressure in workspace should be kept as low as possible.

Alterations in lipid peroxidation and T-cell function in women with hyperemesis gravidarum.

The objective of this study was to investigate serum adenosine deaminase (ADA) activity as a marker of T lymphocyte activation and parameters of oxidative stress and antioxidant defence in hyperemesis gravidarum (HG). Serum ADA activity, malondialdehyde (MDA), catalase (CAT) and glutathione peroxidase (GPx) levels were investigated in 40 pregnant women with the HG and 40 with healthy pregnancies, in a descriptive study. Although serum ADA and CAT were measured to be higher in HG group, the difference was not significant. Serum MDA and GPx levels were significantly elevated in women with HG when compared with those without HG. The significance of changes in lipid peroxidation and T-cell activation in the pathogenesis of HG and whether this is a cause or a compensatory reaction to HG requires further investigations with larger multicentre trials.

Evaluation of Potential Donors in Living Donor Liver Transplantation.

INTRODUCTION: Correct donor selection in living donor liver transplantation (LDLT) is essential not only to decrease the risks of complications for the donors but also to increase the survival of both the graft and the recipient. Knowing their most frequent reasons of donor elimination is so important for transplantation centers to gain time. In this study we evaluated the effectiveness of potential donors in LDLT and studied the reasons for nonmaturation of potential liver donors at our transplantation center. PATIENTS AND METHODS: We studied the outcomes of 342 potential living donor candidates for 161 recipient candidates for liver transplantation between January 2013 and June 2014. Donor candidates' gender, age, body mass index (BMI), relationship with recipient, and causes of exclusion were recorded. RESULTS: Among 161 recipients, 96 had a LDLT and 7 had cadaveric liver transplantation. Twelve of the 342 potential donors did not complete their evaluation; 106 of the remaining 330 donor candidates were accepted as suitable for donation (32%) but 10 of these were excluded preoperatively. The main reasons for unsuitability for liver donation were small remnant liver size (43%) and fatty changes of the liver (38.4%). Other reasons were arterial anatomic variations, ABO incompatibility, and Gilbert syndrome. Only 96 of the candidates (29% of the 330 candidates who completed the evaluation) underwent donation. Effective donors were 29% of potential and 90.5% of suitable donors. CONCLUSIONS: In our center, 106 of 330 (32%) donor candidates were suitable for donation and the main reasons for unsuitability for liver donation were small remnant liver size and fatty changes of the liver.

Pulmonary Complications After 1,150 Living Donor Hepatectomies.

AIM: Donor safety is the major concern in living-donor liver transplantation. Studies in literature related to donor hepatectomy (DH) have generally considered intra-abdominal complications. The aim of this study is to specifically evaluate pulmonary complications (PCs) after DH. MATERIALS AND METHODS: We evaluated retrospectively 1150 living donors who underwent to DH between January 2007 and July 2014. Patients with PCs, such as pneumonia, pleural effusion, pneumothorax, and respiratory insufficiency, were considered. A complication was considered only when it was clinically apparent and/or requiring interventions. Any special diagnostic tool was used to expose the clinically silent pathologies. RESULTS: A total of 986 right hepatectomies (RH) and 164 left hepatectomies (LH) (left lobectomy or left lateral segmentectomy) were performed in the study interval. There were 18 (1.6%) donors with PCs (15 males and 3 females). Mean age was 33.8 ± 9.3 years (18-51). Mean hospital stay was 23.8 ± 13.5 days (5-62). Presented PCs were pleural effusion (n = 5, 0.4%), pneumonia (n = 4, 0.3%), combinations (n = 2, 0.2%), pneumothorax (n = 2, 0.2%), and acute respiratory insufficiency (n = 5, 0.4%). Sixteen cases (1.7%) were seen after RH, whereas 2 cases (1.2%) were seen after LH (P = 1.000). CONCLUSION: The most common PCs after living donor hepatectomy were pleural effusion and acute respiratory insufficiency. There was no significant difference between RH and LH. It is possible to overcome those PCs with careful monitoring and timely and appropriate treatment.

Liver Transplantation With Livers From Octogenarians and a Nonagenarian.

INTRODUCTION: A shortage of deceased donors has compelled the use of extended-criteria donor organs in liver transplantation. The purpose of this study was to evaluate the impact of using deceased donors older than 80 years. MATERIALS AND METHODS: We retrospectively evaluated 13 patients who received a liver graft from cadaveric donors older than 80 years between December 2007 and March 2014. We analyzed the donor and their recipient characteristics together with morbidity and mortality of recipients. RESULTS: All 13 donors were older than 80 years (median age, 82.7; range, 80-93). There were 9 male and 4 female recipients with an average age of 50.7 (range, 2-65) years. All of the recipients did not have a living donor for liver transplantation. Recipients' mean model for end-stage liver disease (MELD) score was 14.2 (range, 7-20). Graft with macroscopic steatosis was not accepted. Medium follow-up was 19.5 months. The most frequent cause for liver transplantation (LT) was hepatitis B virus (HBV) cirrhosis (8/13 patients). We had 1 case of primary nonfunction, and 4 patients died in 2 weeks after surgery. Of these patients, 2 of them received a split transplant from an 80-year-old cadaver liver. Overall the survival rate after 1 year was 61.5%. CONCLUSIONS: Deceased elderly donor usage in LT could expand the donor pool. Liver grafts from donors older than 80 years can be used in necessity or emergency situations. However, care should be taken to avoid early mortality and primary nonfunction. Procedures extending cold ischemia time such as split liver transplantation may increase the risk of primary nonfunction.

Novel combination of docetaxel and thymoquinone induces synergistic cytotoxicity and apoptosis in DU-145 human prostate cancer cells by modulating PI3K–AKT pathway

Background. The treatment of castrate-resistant prostate cancer (CRPC) still remains as an important challenge of daily oncology practice. Docetaxel significantly prolongs overall survival in men with CRPC. Thymoquinone (TQ), one of the flavonoid compounds isolated from Nigealla sativa, has been shown to possess cytotoxic activity against a variety of cancer cell lines. Materials and Methods. The aim of the study was to investigate the possible synergistic cytotoxic/apoptotic effects of a novel combination, docetaxel and TQ in DU-145 hormone- and drug-refractory prostate cancer cells and their effects on PI3K and ERK signaling pathways. Results. We observed that the combination of docetaxel and TQ resulted in a significant synergistic cytotoxicy and apoptosis as compared to any single agent alone, in a dose-dependent manner. It was found that viability of the combination treated cells was not significantly changed in the presence of LY294002 as compared to inhibitor treated cells. However, in the presence of FR180204, viability of combination treated cells was significantly decreased as compared to inhibitor treated cells. In conclusion, cytotoxic effect of the docetaxel and TQ combination is correlated with the block of the PI3K/Akt signaling pathway in DU-145 cells. Conclusion. Therefore, this combination strategy may be an alternative approach for the challenging era of daily oncologic practice. Also, the combination of docetaxel and TQ might allow a reduction in docetaxel doses and diminish adverse effects of docetaxel while maintaining the therapeutic effect in patients with CRPC (AU)

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Novel combination of docetaxel and thymoquinone induces synergistic cytotoxicity and apoptosis in DU-145 human prostate cancer cells by modulating PI3K-AKT pathway.

BACKGROUND: The treatment of castrate-resistant prostate cancer (CRPC) still remains as an important challenge of daily oncology practice. Docetaxel significantly prolongs overall survival in men with CRPC. Thymoquinone (TQ), one of the flavonoid compounds isolated from Nigealla sativa, has been shown to possess cytotoxic activity against a variety of cancer cell lines. MATERIALS AND METHODS: The aim of the study was to investigate the possible synergistic cytotoxic/apoptotic effects of a novel combination, docetaxel and TQ in DU-145 hormone- and drug-refractory prostate cancer cells and their effects on PI3K and ERK signaling pathways. RESULTS: We observed that the combination of docetaxel and TQ resulted in a significant synergistic cytotoxicy and apoptosis as compared to any single agent alone, in a dose-dependent manner. It was found that viability of the combination treated cells was not significantly changed in the presence of LY294002 as compared to inhibitor treated cells. However, in the presence of FR180204, viability of combination treated cells was significantly decreased as compared to inhibitor treated cells. In conclusion, cytotoxic effect of the docetaxel and TQ combination is correlated with the block of the PI3K/Akt signaling pathway in DU-145 cells. CONCLUSION: Therefore, this combination strategy may be an alternative approach for the challenging era of daily oncologic practice. Also, the combination of docetaxel and TQ might allow a reduction in docetaxel doses and diminish adverse effects of docetaxel while maintaining the therapeutic effect in patients with CRPC.

A magnet system for the suppression of conversion electrons in alpha spectrometry.

A new magnet system has been designed and constructed to reduce coincidence effects between alpha particles and conversion electrons in high-resolution alpha-particle spectrometry. By means of a magnetic field, the conversion electrons are deflected away from the PIPS(®) detector. Compared to existing magnet systems, the new system is not restricted to point sources and can accommodate source diameters up to about 30 mm. Two yokes were built, allowing for configurations with 20 mm or 36 mm distance between the magnets. The effectiveness of both configurations is demonstrated by measuring the conversion electron spectrum of a (237)Np source. The magnet system effectively rejects 93 (7)% of electrons up to 85 keV (36 mm) and 90 (9)% of electrons up to 320 keV (20 mm). It has been successfully applied in the alpha-particle spectrometry of the long-lived nuclides (236)U and (238)U, resulting in significant improvement of the accuracy of alpha emission probabilities.

The relationship of insulin resistance and metabolic syndrome with known breast cancer prognostic factors in postmenopausal breast cancer patients.

PURPOSE: The aim of this study was to investigate the effect of metabolic syndrome and insulin resistance at the time of diagnosis on the known prognostic factors of breast cancer in postmenopausal breast cancer patients. METHODS: The study included 71 patients with a recent diagnosis of postmenopausal breast cancer, admitted at the Medical Oncology outpatient clinic of the Izmir Ataturk Training and Research Hospital between June 2010 and June 2011. We determined whether the patients had metabolic syndrome and insulin resistance at diagnosis, and recorded known prognostic factors, such as tumor size, axillary lymph node involvement, presence of distant metastasis, tumor grade, estrogen receptor (ER), progesterone receptor (PR), and CerbB-2 status. RESULTS: Among 71 patients, 25 (35%) had metabolic syndrome at the time of diagnosis, and 33 (46%) had insulin resistance with Homeostasis Model of Assessment-Insulin Resistance (HOMA-IR)>2.7. No statistically significant difference was found in the prognostic values of breast cancer, i.e. tumor size, axillary lymph node involvement, distant metastasis, tumor grade, ER, PR, and CerbB-2 status between the patients with and without metabolic syndrome. There was no statistically significant difference in the prognostic factors of breast cancer at the time of diagnosis between 33 patients with insulin resistance and 38 patients without insulin resistance. CONCLUSION: Several previous studies showed a negative relationship between metabolic syndrome and insulin resistance and prognostic factors of breast cancer in postmenopausal breast cancer patients. However, our study failed to show such a relationship. The relationship between metabolic syndrome and insulin resistance and postmenopausal breast cancer was not well demonstrated due to the small number of patients, unknown duration of the metabolic syndrome and insulin resistance, and shorter follow-up period. Further studies are required to demonstrate the effect of metabolic syndrome and insulin resistance on the prognosis of breast cancer, including larger number of patients and longer follow-up periods.

Depression and anxiety in cancer patients and their relatives.

PURPOSE: To investigate the depression and anxiety levels and the factors that affect patients receiving chemotherapy and their relatives with the Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI) scoring system. METHODS: 330 patients and 330 relatives of these patients were enrolled in this study. The study forms including the questions regarding the patient demographic characteristics, BDI, and STAI were completed during face-to-face interviews by trained interviewers for the determination of the psychological status of the patients and their relatives. BDI and STAI were validated for Turkish population by studies made before. RESULTS: According to BDI scale, 96 (29.1%) patients had mild and 60 (18.2%) had severe depression. Seventy-one (21.5%) relatives had mild and 24 (7.3%) had severe depression. Anxiety evaluation was made by STAI scale and a statistical difference emerged between patients and relatives (patients: 44.93±8.8 vs relatives: 43.27±8.5, p=0.015). The depression and anxiety levels were higher in women, in people with low socio-economic level, in people having a time period between diagnosis and participation in the study longer than 6 months, and in people having relapsing disease. CONCLUSION: Since there are many emotional and psychological disorders in patients and their relatives, much attention should be paid in order to diagnose and treat their psychiatric disorders and enough information about their disease should be given.

The association of hematologic parameters on the prognosis of patients with metastatic renal cell carcinoma.

PURPOSE: Metastatic renal cell carcinoma (mRCC) bears a poor prognosis. We investigated the prognostic significance of some hematologic parameters of patients with mRCC. METHODS: We retrospectively reviewed the records of 53 patients with mRCC . The mean follow up time was 34 months (range 5-142).We assessed the prognostic value of hematologic parameters (leukocytes ,neutrophils, lymphocytes, platelets, neutrophil to lymphocyte ratio/NLR, platelet to lymphocyte ratio/PLR), and other clinical parameters with univariate and multivariate analysis. RESULTS: Memorial Sloan-Kettering Cancer Center (MSKCC) risk group , lung metastases, sunitinib treatment, lymphocyte count, NLR, and anemia significantly correlated with median overall survival (OS) on univariate analysis. The median OS in patients with a NLR < 3.4 was 32.2 months , significantly higher than the 13.9 months in patients with a ratio ≥ 3.4 (p = 0.006). Multivariate analysis revealed that MSKCC risk group and the NLR were independent predictors of OS. CONCLUSION: Hematologic parameters may be associated with OS in mRCC. However, further studies are needed to establish their routine use.