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Ectopic breast tissue can develop along the mammary ridge from the axilla to the groin, and the most common site is the axillae. Primary carcinoma of ectopic breast tissue is extremely rare. We report a rare case of a 61-year-old woman with a palpable mass in her left axilla who had a history of surgical excision of accessory breast tissue in the same area. Mammography (MMG), including axillary tail view, ultrasound (US), and breast MRI were performed. We evaluated the extent and characteristics of the microcalcifications in the axillary tail view. A US-guided biopsy was done, and histopathology revealed an invasive ductal carcinoma. Enhanced abdominal CT revealed multiple hepatic masses consistent with metastases, and the patient received palliative chemotherapy. Herein, we present a rare case of breast cancer arising from accessory breast tissue in the axilla, best appreciated on the axillary tail view of the patient's MMG. [ABSTRACT FROM AUTHOR]

Primary peritoneal psammocarcinoma is a rare type of serous carcinoma that is characterized by the massive formation of psammoma bodies and the invasion of adjacent organs. A 55-year-old female who previously underwent a hysterectomy presented to the emergency room with severe abdominal pain. Contrast-enhanced CT revealed an intra-abdominal calcific mass. Initially, it was thought to be a heterotopic ossification due to the previous pelvic surgery with intact ovaries. However, this was diagnosed as a primary peritoneal psammocarcinoma. Primary peritoneal psammocarcinoma is a very rare disease entity that should be considered a differential diagnosis in patients with normal ovaries, massive ossification in the pelvic cavity, and calcific peritoneal nodules. [ABSTRACT FROM AUTHOR]

Rifampin is a potent hepatic cytochrome enzyme inducer, promoting the metabolism of many drugs. Here, we describe a case wherein rifampin-induced drug interactions affected the clinical improvement of a patient on psychiatric drugs for bipolar disorder. He was administered divalproex, risperidone, quetiapine, and clonazepam, along with anti-tuberculosis drugs HERZ, containing 600 mg rifampin. Despite taking 900 mg/day divalproex, his serum valproate levels were below 2 µg/ml, and his manic symptom persisted. Therefore, the antipsychotic risperidone (5 mg) was replaced with olanzapine (20 mg). Following this, his manic symptoms improved rapidly. Rifampin is a potent CYP3A and CYP2D6 inducer and is known to significantly reduce serum risperidone levels. Thus, even a high dose of risperidone did not induce a significant clinical effect, which was observed immediately after replacing with olanzapine. Therefore, drug interactions may have had a significant effect on clinical outcomes. Clinicians should be cognizant of drug interactions when treating psychiatric patients on rifampin therapy. The case has been sufficiently revised to protect the patient's personal information. [ABSTRACT FROM AUTHOR]

Uterine leiomyoma is the most common benign pelvic tumor in female and being symptomatic is an indication for surgical removal. As laparoscopic surgery has been developed, some cases related to parasitic leiomyomas in the port site have been reported. A 40-year-old female who a history of previous laparoscopic surgery to remove uterine myoma 2 years ago visited in outpatient clinic of general surgery with palpable mass in left lower abdomen. Contrast enhanced abdomen CT and pelvis MRI were done to evaluate the mass. It was diagnosed parasitic leiomyoma in pathologic study after surgical removal and parasitic leiomyoma should be considered when patient visited presenting abdominal mass with the history of laparoscopic myomectomy. [ABSTRACT FROM AUTHOR]

Hyperechoic lesions of the breast encompass a wide range of conditions that are occasionally encountered during breast ultrasonography. Although typical hyperechoic lesions with a distinct fat component on imaging are well known, some hyperechoic lesions are diagnosed as unexpected pathology, making the radiology-pathology correlation difficult. Therefore, understanding the pathology of these lesions and how it correlates with imaging findings can help radiologists accurately diagnose and properly manage a range of related conditions. This article presents a pictorial review of unexpected hyperechoic benign and malignant breast lesions, with a focus on the pathological conditions that give rise to the hyperechoic pattern. [ABSTRACT FROM AUTHOR]

Angioleiomyoma (vascular leiomyoma) of the uterine cervix is an extremely rare type of benign tumor composed of smooth muscle cells and thick-walled blood vessels. Only a few cases of cervical angioleiomyoma have been reported. Here, we present imaging, including ultrasonography, contrast-enhanced CT, MRI, and histopathological findings of a 38-year-old female with an angioleiomyoma of the uterine cervix. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVES: The existing prediction formulas for in-hospital mortality of very low birth weight (VLBW) infants were mostly developed in the 1990s or 2000s and thus may not reflect the recently improved levels of neonatal care. We conducted this study to build a model for predicting the in-hospital mortality using perinatal factors available soon after birth. METHODS: We gathered data on VLBW infants from the Korean Neonatal Network, a nationwide, prospective, Web-based registry that enrolled patients from 2013 to 2017. Perinatal variables that were significantly associated with mortality in univariate logistic regression or those with apparent clinical importance were included in the multivariable logistic regression model. The final formula was constructed by considering the collinearity, parsimony, goodness of fit, and clinical interpretation. RESULTS: A total of 9248 VLBW infants were analyzed, including 1105 (11.9%) who died during hospitalization. The mean gestational age was 29.0 6 2.9 weeks and the mean birth weight was 1096 6 280 g. Significant variables used in the final equation included polyhydramnios, oligohydramnios, gestational age, Apgar score at 1 minute, intubation at birth, birth weight, and base excess. In internal validation, the area under the curve (AUC) for the prediction of in-hospital mortality was 0.870 and the optimism-corrected AUC was 0.867. The prediction equation revealed good discrimination and calibration in the external validation as well (AUC: 0.876). CONCLUSIONS: The newly developed Korean Neonatal Network prediction formula for in-hospital mortality could be a useful tool in counseling by providing a reliable prediction for the in-hospital mortality of VLBW infants. [ABSTRACT FROM AUTHOR]

Purpose: Absorbable retaining thread (ART) needle localization utilizes a guiding needle with a thread; this technique was invented to reduce patient discomfort and wire migration. We investigated the feasibility of ultrasound (US)-guided ART needle localization for nonpalpable breast lesions. Methods: ART needle localization was performed for 26 nonpalpable breast lesions in 26 patients who were scheduled to undergo surgical excision the day after localization. Seventeen breast lesions were initially diagnosed as invasive ductal carcinoma, six as ductal carcinomas in situ, and one as fibrocystic change. The other two cases without an initial pathologic diagnosis had suspicious US features, and excision was planned concomitantly with contralateral breast cancer surgery. The primary outcome was the technical success rate of ART needle localization confirmed by US immediately after the procedure, and the secondary outcomes were the percentage of clear margins on pathology and the complication rate of ART needle localization. Results: The technical success rate of ART needle localization was 96.2% (25 of 26 patients), and the ART was located 1 cm away from the mass in one patient (3.8%). The lesions were successfully removed with clear margins in all 26 patients. No significant complications related to ART needle localization were observed. Conclusion: ART needle localization can be an alternative to wire needle localization for nonpalpable breast lesions. [ABSTRACT FROM AUTHOR]

Objective: Numerous studies have identified hemodynamic changes in adults with major depressive disorder (MDD) by using functional near-infrared spectroscopy (fNIRS). However, studies on adolescents with MDD are limited. As adolescence is a stage of rapid brain development, differences may occur depending on age. This study used fNIRS as an objective tool to investigate hemodynamic changes in the frontal lobe according to depression severity and age in adolescents with MDD. Methods: Thirty adolescents (12 aged 12−15 years and 18 aged 16−18 years) were retrospectively investigated. The Children’s Depression Inventory was used as a psychiatric evaluation scale, fNIRS was used as an objective brain function evaluation tool, and the Verbal Fluency Test was performed. Results: During the Verbal Fluency Test, in the younger MDD group, oxygenated-hemoglobin concentration increased in the right dorsolateral prefrontal cortex region as the severity of depression increased. In the older MDD group, the oxygenated-hemoglobin concentration decreased in the right dorsolateral prefrontal cortex region as the severity of depression increased. Conclusion: These results suggest that fNIRS may be an objective tool for identifying age differences among adolescents with MDD. To generalize the results and verify fNIRS as a potential biomarker tool, follow-up studies with a larger sample group should be conducted. [ABSTRACT FROM AUTHOR]

Objective This study aims to identify risk factors for cesarean delivery (CD) surgical site infection (SSI). Study Design Retrospective analysis of 2,739 CDs performed at the University of Pittsburgh in 2011. CD SSIs were defined using National Healthcare Safety Network (NHSN) criteria. Chi-square test and t-test were used for bivariate analyses and multivariate logistic regression was used to identify SSI risk factors. Results Of 2,739 CDs, 178 (6.5%) were complicated by SSI. Patients with a SSI were more likely to have Medicaid, have resident physicians perform the CD, an American Society of Anesthesiologists (ASA) class of ≥3, chorioamnionitis, tobacco use, and labor before CD. In multivariable analysis, labor (odds ratio [OR], 2.35; 95% confidence interval [95% CI], 1.65-3.38), chorioamnionitis (OR, 2.24; 95% CI, 1.25-3.83), resident teaching service (OR, 2.15; 95% CI, 1.54-3.00), tobacco use (OR, 1.70; 95% CI, 1.04-2.70), ASA class ≥ 3 (OR, 1.61; 95% CI, 1.06-2.39), and CDs performed for non-reassuring fetal status (OR, 0.43; 95% CI, 0.26-0.67) were significantly associated with CD SSI. Conclusion Multiple patient, provider, and procedure-specific risk factors contribute to CD SSI risk which may be targeted in infection-control efforts. [ABSTRACT FROM AUTHOR]

Liver cancer is one of the most drug-resistant cancer types, and cancer stem cells are related to drug resistance. c-Jun-N-terminal kinase (JNK) signaling is involved in drug resistance, and the side population of cells (SP cells) can be used as a model to study liver cancer stem cells. We sought to evaluate the relationship between SP cells and JNK signaling in hepatocarcinoma cells. For this purpose, we examined cell proliferation and the SP cell ratio following treatment of Huh7 cells with the anticancer drugs 5-fluorouracil (5-FU) and paclitaxel. The expression of phospho-stress-activated protein kinase (SAPK)/JNK in the treated cells was evaluated using immunoblotting. 5-FU and paclitaxel treatment increased the number of SP cells and JNK phosphorylation, and decreased cell survival. Huh7 and HepG2 cells were also treated with SP600125, a JNK inhibitor, to study the relationship between SP cells and JNK signaling. The increase in the number of SP cells and the SAPK/JNK and c-Jun phosphorylation was reverted by SP600125 treatment in these cells. We also used immunohistochemistry and showed that SAPK/JNK and c-Jun phosphorylation are increased in hepatocarcinoma tissues. In conclusion, our results demonstrate that the number of SP cells and SAPK/JNK phosphorylation are increased upon treatment with anticancer drugs, and that this increase is blocked by inhibition of JNK signaling. These findings suggest that drug resistance in liver cancer may involve an increase in the number of SP cells following JNK activation. [ABSTRACT FROM AUTHOR]

The penalized logistic regression (PLR) is a powerful statistical tool for classification. It has been commonly used in many practical problems. Despite its success, since the loss function of the PLR is unbounded, resulting classifiers can be sensitive to outliers. To build more robust classifiers, we propose the robust PLR (RPLR) which uses truncated logistic loss functions, and suggest three schemes to estimate conditional class probabilities. Connections of the RPLR with some other existing work on robust logistic regression have been discussed. Our theoretical results indicate that the RPLR is Fisher consistent and more robust to outliers. Moreover, we develop estimated generalized approximate cross validation (EGACV) for the tuning parameter selection. Through numerical examples, we demonstrate that truncating the loss function indeed yields better performance in terms of classification accuracy and class probability estimation. The Canadian Journal of Statistics 39: 300-323; 2011 © 2011 Statistical Society of Canada [ABSTRACT FROM AUTHOR]

A novel front-end structure for ultra-high-frequency RF identification reader is proposed. The proposed front-end consists of a balanced coupler and four-port feed antenna system. The proposed balanced coupler structure has high transmit/receiver isolation feature and good insensitivity to load variations. The proposed four-port feed antenna system is applied for removing the coupling among antennas, which deteriorates the isolation. The proposed system is numerically analyzed and verified experimentally as well. [ABSTRACT FROM AUTHOR]

Afferent loop syndrome (ALS) is a rare complication of gastrectomies and gastrointestinal reconstruction. This can predispose patients to fatal conditions, such as cholangitis, pancreatitis, and duodenal perforation with peritonitis. Therefore, emergency decompression is necessary to prevent these complications. Herein, we report two cases in which transcholecystic duodenal drainage, an alternative decompression treatment, was performed in ALS patients without bile duct dilatation. Two patients who underwent distal gastrectomy with Billroth II anastomosis sought consultation in an emergency department for epigastric pain and vomiting. On CT, ALS with acute pancreatitis was diagnosed. However, biliary access could not be achieved because of the absence of bile duct dilatation. To overcome this problem, a duodenal drainage catheter was placed to decompress the afferent loop after traversing the cystic duct via a transcholecystic approach. The patients were discharged without additional surgical treatment 2 weeks and 1 month after drainage. [ABSTRACT FROM AUTHOR]

Sorafenib is a systemic chemotherapeutic agent for advanced hepatocellular carcinoma (HCC). The aim of the present study was to evaluate the anticancer effect of sorafenib in cancer stem cell-like cells, such as side population (SP) cells, in HCC and to analyze the signaling pathway for drug-resistance. To evaluate the anticancer effects of sorafenib, Huh7 and Huh-BAT cells were treated with sorafenib, fluorouracil (5-FU), and sorafenib plus 5-FU. These cells were examined for growth rates, the SP fraction, sphere-forming efficacy and expression of c-Jun N-terminal kinase (JNK) signaling molecules. Sorafenib and 5-FU treatment decreased growth rates in Huh7 and Huh-BAT cells; however, the treatments exerted different effects in SP cells and on the expression levels of JNK signaling molecules. Treatment with 5-FU increased the SP cell number and upregulated the expression of JNK signaling molecules. By contrast, sorafenib decreased the SP cell number and downregulated the expression of JNK signaling molecules. No significant differences in sphere-forming efficacy were observed subsequent to 5-FU and sorafenib treatment in Huh7 and Huh-BAT cells. These results indicate that sorafenib exerted anticancer effects in HCC and SP cells by targeting JNK signaling. [ABSTRACT FROM AUTHOR]

Objective: Over 200,000 in-hospital cardiac arrests occur in the United States each year and many of these events may be preventable. Current vital sign-based risk scores for ward patients have demonstrated limited accuracy, which leads to missed opportunities to identify those patients most likely to suffer cardiac arrest and inefficient resource utilization. We derived and validated a prediction model for cardiac arrest while treating ICU transfer as a competing risk using electronic health record data. Design: A retrospective cohort study. Setting: An academic medical center in the United States with approximately 500 inpatient beds. Patients: Adult patients hospitalized from November 2008 until August 2011 who had documented ward vital signs. Interventions: None. Measurements and Main Results: Vital sign, demographic, location, and laboratory data were extracted from the electronic health record and investigated as potential predictor variables. A person-time multinomial logistic regression model was used to simultaneously predict cardiac arrest and ICU transfer. The prediction model was compared to the VitalPAC Early Warning Score using the area under the receiver operating characteristic curve and was validated using three-fold cross-validation. A total of 56,649 controls, 109 cardiac arrest patients, and 2,543 ICU transfers were included. The derived model more accurately detected cardiac arrest (area under the receiver operating characteristic curve, 0.88 vs 0.78; p < 0.001) and ICU transfer (area under the receiver operating characteristic curve, 0.77 vs 0.73; p < 0.001) than the VitalPAC Early Warning Score, and accuracy was similar with cross-validation. At a specificity of 93%, our model had a higher sensitivity than the VitalPAC Early Warning Score for cardiac arrest patients (65% vs 41%). Conclusions: We developed and validated a prediction tool for ward patients that can simultaneously predict the risk of cardiac arrest and ICU transfer. Our model was more accurate than the VitalPAC Early Warning Score and could be implemented in the electronic health record to alert caregivers with real-time information regarding patient deterioration. [ABSTRACT FROM AUTHOR]

Background: The optimal prognostic markers for neoadjuvant chemotherapy in patients with borderline resectable or locally advanced pancreatic cancer are not yet established. Method: Patients who received neoadjuvant chemotherapy prior to surgery and underwent FDG-PET/CT between July 2012 and December 2017 were included. Metabolic parameters including standardized uptake value (SUV), metabolic tumour volume (MTV), and total lesion glycolysis (TLG) on PET/CT, and response evaluations using PERCIST criteria, were investigated for its impact on survival and recurrence. Cox proportional hazards model was performed. Differences in risk were expressed as hazard ratio (HR) with 95 per cent confidence interval. Results: The patients with borderline resectable (N=106) or locally advanced pancreatic cancer (N=82) were identified. The median survival was 33.6months. Decreased metabolic parameters of PET/CT after neoadjuvant chemotherapy were associated with positive impacts on survival and recurrence such as SUVmax (HR 1.16, 95 per cent c.i. 1.01 to 1.32, P=0.025), SUVpeak (HR 1.26, 95 per cent c.i. 1.05 to 1.51, P=0.011), and MTV (HR 1.15, 95 per cent c.i. 1.04 to 1.26, P=0.005). Large delta values were related to a positive impact on recurrence such as SUVmax (HR 1.21, 95 per cent c.i. 1.06 to 1.38, P=0.005). Post-neoadjuvant chemotherapy SUVmax -3 (HR 3.46, 95 per cent c.i. 1.21 to 9.91; P=0.036) was an independent prognostic factor for negative impact on survival. Patients with postneoadjuvant chemotherapy SUVmax <3 showed more chemotherapy cycles (8.7 versus 6.2, P=0.001), more frequent complete metabolic response (25 versus 2.2 per cent, P=0.002), smaller tumour size (2.1 versus 3.1 cm, P=0.002), and less frequent lymphovascular invasion (23.7 versus 51.1 per cent, P=0.020) than patients with SUVmax -3. Conclusion: Reduction in metabolic tumour parameters of FDG-PET/CT after neoadjuvant chemotherapy indicates improved overall survival and recurrence-free survival. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The optimal duration of fasting after endoscopic hemostasis in patients with peptic ulcer bleeding has not yet been determined. We investigated the appropriate timing of feeding after endoscopic hemostasis in patients with high-risk peptic ulcer bleeding. METHODS: This study was a randomized, single center, noninferiority trial. Between February 2014 and March 2019, consecutive patients with peptic ulcer bleeding were randomized to resume feeding either 24 or 48 hours after successful endoscopic hemostasis. A total of 209 eligible patients were included in the intention-to-treat analysis and 200 in the per-protocol (PP) analysis. The primary outcome measure was recurrent bleeding within 7 days of hemostasis. Noninferiority testing was performed in the PP population, and the noninferiority margin was set at 10%. Secondary outcomes included 30-day rebleeding and mortality, transfusion requirements, and length of hospital stay. RESULTS: Recurrent bleeding rates at 7 dayswere 7.9% in the 24-hour group and 4.0% in the 48-hour group in the PP analysis; tests for noninferiority did not reach statistical significance (difference: 3.9%, 95% confidence interval [CI]:22.7 to 10.5, P value for noninferiority5 0.034). The recurrent bleeding rates within 30 days were 10.9%and4.0%inthe 24-and 48-hour groups (difference: 6.9%,95%CI:20.5 to 14.2), andthe 30- daymortality rateswere5.9%and14.1%,respectively (difference:28.2%,95%CI:216.5to0.1) inthePP analysis. The transfusion requirement and the length of hospital stay were similar between the 2 groups. DISCUSSION: Early refeeding at 24 hours after endoscopic hemostasis is not noninferior to later refeeding at 48 hours for rebleeding in patients with high-risk peptic ulcer bleeding. Our results do not allow a recommendation of refeeding at 24 hours, rather than later refeeding in this population. [ABSTRACT FROM AUTHOR]

Objective: Delaying embryo transfer (ET) enables us to select among the embryos available for transfer and is associated with positive effects on implantation and pregnancy outcomes. However, the optimal day for ET of human cleavage-stage embryos remains controversial. Methods: A retrospective study of 3,124 in vitro fertilization/intracytoplasmic sperm injection cycles (2,440 patients) was conducted. We compared the effects of day 2 and 3 ET on rates of implantation and pregnancy outcomes between young maternal age (YMA;<38 years old, n=2,295) and old maternal age (OMA; ≥38 years old, n=829) patient groups. Results: The YMA and OMA groups did not differ in terms of patient characteristics except for the proportion of unexplained factor infertility, which was significantly greater in the OMA group, and the proportion of arrested embryos, which was significantly greater in the YMA group. However, the biochemical pregnancy, clinical pregnancy, ongoing pregnancy, abortion, and implantation rates per cycle were not significantly different between day 2 and 3 ET in the YMA group or the OMA group. Conclusion: We suggest that offering patients the opportunity to decide which day would be suitable for ET could be part of a patient-friendly protocol that takes into consideration an infertile woman's circumstances and work schedule by allowing ET to be performed on day 2 instead of the traditional transfer on day 3. [ABSTRACT FROM AUTHOR]

We conducted a case-control study of 18 US transplant recipients with Rhodococcus infection and 36 matched controls. The predominant types of infection were pneumonia and bacteremia. Diabetes mellitus and recent opportunistic infection were independently associated with disease. Outcomes were generally favorable except for 1 relapse and 1 death. [ABSTRACT FROM AUTHOR]

The article discusses a study which aimed to determine the best ward vital sign predictors of cardiac arrest (CA) and when these vital signs begin to accurately detect this event prior to CA. In this study, vital signs and Modified Early Warning Scores (MEWS) were compared on admission and during the 48 hours preceding CA. Results show that maximum MEWS was the best predictor, followed by maximum respiratory rate, maximum heart rate and maximum pulse pressure.

The article discusses a research study on the association of job satisfaction, staff morale and burnout with the characteristics of patient-centered medical home (PCMH). Surveyed were 382 clinical staff and 391 providers of 65 safety net clinics in 2010 and perceptions of respondents measured on a scale of 0 to 100. Results showed the association of higher morale, freedom from burnout and job satisfaction with a 10% increase in PCMH quality improvement.

The article presents a study which examines the association between the use of metformin diabetes drug by ovarian cancer patients with type II diabetes and the improvement of patient survival. It shows that the five-year survival rate of diabetic patients treated with metformin was 51% compared to 23% for nondiabetic patients and 8% for diabetic patients who did not use metformin. It notes that patients under metformin medication had improved survival in ovarian cancer treatment.

TopBP1 plays important roles in chromosome replication, DNA damage response, and other cellular regulatory functions in vertebrates. Although the roles of TopBP1 have been studied mostly in cancer cell lines, its physiological function remains unclear in mice and untransformed cells. We generated conditional knock-out mice in which exons 5 and 6 of the TopBP1 gene are flanked by loxP sequences. Although TopBP1-deficient embryos developed to the blastocyst stage, no homozygous mutant embryos were recovered at E8.5 or beyond, and completely resorbed embryos were frequent at E7.5, indicating that mutant embryos tend to die at the peri-implantation stage. This finding indicated that TopBP1 is essential for cell proliferation during early embryogenesis. Ablation of TopBP1 in TopBP1flox/flox mouse embryonic fibroblasts and 3T3 cells using Cre recombinase-expressing retrovirus arrests cell cycle progression at the G1, S, and G2/M phases. The TopBP1-ablated mouse cells exhibit phosphorylation of H2AX and Chk2, indicating that the cells contain DNA breaks. The TopBP1-ablated mouse cells enter cellular senescence. Although RNA interference-mediated knockdown of TopBP1 induced cellular senescence in human primary cells, it induced apoptosis in cancer cells. Therefore, TopBP1 deficiency in untransformed mouse and human primary cells induces cellular senescence rather than apoptosis. These results indicate that TopBP1 is essential for cell proliferation and maintenance of chromosomal integrity. [ABSTRACT FROM AUTHOR]

This study was performed to investigate the association between FSH receptor (FSHR) gene polymorphism at position 680 and the outcomes of controlled ovarian hyperstimulation (COH) for in vitro fertilization and embryo transfer (IVF-ET) in Korean women. Two hundred and sixty-three patients under 40 years of age who underwent IVF-ET procedures were included in this study. Patients with polycystic ovary syndrome, endometriosis, or a previous history of ovarian surgery were excluded. Following extraction of genomic DNA, the FSHR polymorphism at position 680 was determined by polymerase chain reaction and restriction fragment length polymorphism analysis. The FSHR genotype distribution was 41.8% for Asn/Asn, 45.6% for Asn/Ser, and 12.5% for Ser/Ser FSHR genotype groups. Although there was no difference among the three genotype groups in terms of the age and infertility diagnosis of study subjects, the basal levels of FSH (day 3) were significantly different [5.7 ± 0.3 IU/l (mean±SEM), 6.0 ± 0.3 IU/l, and 8.2 ± 0.9 IU/l for Asn/Asn, Asn/Ser, and Ser/Ser groups, respectively. The Ser/Ser group tended to require a higher dose of gonadotropins for COH, and tended to show lower serum estradiol levels at the time of hCG administration than the other two groups, though these differences did not reach statistical significance. The numbers of oocytes retrieved tended to be different for the three groups (9.6 ± 0.6, 10.2 ± 0.6, and 7.9 ± 0.8 for Asn/Asn, Asn/Ser, and Ser/Ser groups, respectively). Clinical pregnancy rate was significantly higher in Asn/Asn, compared to the others (45.7 vs. 30.5%, P=0.013). The homozygous Ser/Ser genotype of FSHR polymorphism at position 680 may be associated with a reduced ovarian response to COH for IVF-ET, while Asn/Asn genotypes showed a higher pregnancy rate. [ABSTRACT FROM AUTHOR]

Objective: Cerebral edema in TBI is the consequence of multiple underlying mechanisms, and is associated with unfavorable outcomes. Genetic variability in these pathways likely explains some of the clinical heterogeneity observed in edema development. A role for Sulfonylurea-receptor-1 (Sur1) in edema generation is supported. However, there are no prior studies examining the effect of genetic variability in the Sur1 gene (Abcc8) on the development of cerebral edema. We hypothesize that single nucleotide polymorphisms (SNP) in Abcc8 are predictive of cerebral edema. Methods: DNA was extracted from 385 consecutively enrolled patients of primarily North American ancestry (CEU). Exomic and non-exomic SNPs in Abcc8 were genotyped using multiplex. SNPs with a minor allele frequency (MAF) ζ 0.2 were excluded. Measurements of cerebral edema included acute CT edema, mean and peak intracranial pressure (ICP) measurements, and need for decompressive craniotomy. Results: 14 SNPs with MAF > 0.2 were identified. 4 SNPS rs2283261, rs3819521, rs2283258 and rs1799857 were associated with edema measures in univariate and multivariate analyses. In the multivariate model, recessive genotypes in rs2283261, rs3819521, and rs2283258 increased the odds of CT edema (OR = 2.45, p = 0.007; OR = 2.95, p = 0.025; OR = 3.00, p = 0.013 respectively) and had higher mean (b = 3.13, p = 0.000; b = 2.95, p = 0.005; b = 3.20, p = 0.008 respectively) and peak (b = 8.00, p = 0.001; b = 7.64, p = 0.007; b = 6.89, p = 0.034) ICP. The dominant genotype of rs1799857 had decreased odds of decompressive craniotomy (OR = 0.47, p = 0.004). Conclusions: This is the first report assessing the impact of Abcc8 genetic variability on cerebral edema development in severe TBI. The minor Abcc8 SNP genotypes appeared to confer increased risk of cerebral edema, while dominant SNP alleles were protective-potentially suggesting an evolutionary advantage. These findings could guide risk stratification, treatment responder classification, and the development of novel targeted or gene-based therapies against cerebral edema in TBI and other neurological disorders. [ABSTRACT FROM AUTHOR]