Hit evaluation of an α-helical peptide: Ala-scan, truncation and sidechain-to-sidechain macrocyclization of an RNA polymerase Inhibitor

Journal Name: Biological Chemistry
Issue: Ahead of print


from A via a.sfakia on Inoreader http://bit.ly/2S9xdgj

Presentation of Ocular Syphilis in a HIV-Positive Patient with False-Negative Serologic Screening

Purpose. The ocular sequelae of syphilis are devastating and may cause blindness. The ambiguous nature of its ocular manifestations makes syphilis difficult to detect. Though uncommon, the rise of syphilis in the United States requires a renewed understanding of its ophthalmic presentation to prevent devastating outcomes. We present this case to raise awareness for the increasing prevalence of ocular syphilis and appropriate serologic testing. Observations. We describe a 65-year-old HIV-positive male with worsening retinitis, uveitis, and rapid visual loss. Initial lab results showed a nonreactive rapid plasma reagin (RPR) for syphilis. However, subsequent Treponema pallidum antibody testing was positive 48 hours after initial false-negative serologic screening. The patient had a rapid and successful recovery following treatment with penicillin. Conclusions and Importance. The incidence of syphilis is on the rise once again, and patients living with HIV are at increased risk. Ocular syphilis should be considered in susceptible populations in the clinical setting of retinitis, uveitis, and worsening visual loss with unknown cause. In addition, retesting for syphilis will decrease the prevalence of false-negative results, especially in patients with high clinical suspicion.

from A via a.sfakia on Inoreader http://bit.ly/2TukYYi

Prognostic Value of Adjuvant Chemotherapy Following Pancreaticoduodenectomy in Elderly Patients With Pancreatic Cancer

Background/Aim: The aim of this study was to investigate the relationship between age and long-term survival among patients who underwent pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC). Patients and Methods: A total of 916 patients who underwent PD for curative resection of PDAC were included in this study. Patients were divided into younger (n=726, <70 years) and older (n=190, ≥70 years), and the overall survival (OS) between the two groups was compared. Results: Median OS was significantly longer in the younger group (p<0.001). However, the survival advantage among younger patients was not significant when analyzing only patients who received adjuvant chemotherapy (p=0.548). Among patients who did not receive adjuvant chemotherapy, OS was significantly longer in the younger group (p=0.003). Among patients who received neither adjuvant chemotherapy nor treatment for recurrence, survival was not significantly different between the groups (p=0.629). Conclusion: Adjuvant chemotherapy should be recommended, and additional treatment for recurrence is effective even among elderly who have not received adjuvant chemotherapy.

from A via a.sfakia on Inoreader http://bit.ly/2MMl0bz

Radiation Therapy for Extrapelvic Lymph Node Recurrence After Curative Treatment for Cervical Cancer

Background/Aim: To investigate outcomes of patients with cervical cancer who received radiation therapy for extrapelvic lymph node recurrence after initial pelvic radiotherapy. Patients and Methods: The treatment charts of 20 patients were retrospectively reviewed, and factors influencing patient's prognosis were statistically analyzed. Results: The three-year in-field tumor control rate was 55% and overall survival (OS) at 2, 3, and 5 years was 55%, 45%, and 37.5%, respectively. The rate of the three-year OS in patients with recurrence within and after 9 months was 20% and 70%, respectively (p=0.016). None of the 4 patients who were diagnosed with supraclavicular lymph node recurrence alone at more than 9 months after initial treatment experienced further recurrence. Five-year survival of the remaining 16 patients was only 21% (p=0.021). Conclusion: Time to recurrence significantly influenced survival in patients with cervical cancer who received radiotherapy for extra-pelvic lymph node recurrence. Supraclavicular lymph node recurrence alone had a favorable impact on patient's prognosis.

from A via a.sfakia on Inoreader http://bit.ly/2DPS0wB

The Role of KRAS in Endometrial Cancer: A Mini-Review

Endometrial cancer (EC) is the most common cancer of the female genital tract, resulting annually in 76,000 related deaths worldwide. EC originates either from oestrogen-related proliferative endometrium (type I, endometrioid), or from atrophic endometrium (type II, non-endometrioid). Each type of EC is characterized by different molecular profile alterations. The Kirsten rat sarcoma viral oncogene homolog (KRAS) gene encodes a signalling protein which moderates response to various extracellular signals via down-regulation of the mitogen-activated protein kinase (MAPK) or phosphoinositide-3-kinase/v-akt murine thymoma viral oncogene (PI3K/AKT) pathways. This article reviews the role of KRAS in predicting transition from hyperplastic endometrium to early-stage well-differentiated EC, as well as further invasive proliferation of the tumour to advanced-stage disease. KRAS seems to be directly associated with type I EC, and most studies support its early involvement in carcinogenesis. Current evidence correlates KRAS mutations with increased cell proliferation and apoptosis, as well as up-regulation of endometrial cell oestrogen receptors. Tumours positive for KRAS mutation can harbour hypermethylation-related changes in genome expression, and this can be the cause of concurrent loss of DNA repair proteins. Despite some evidence that KRAS mutation status affects cancer progression, a consensus is yet to be reached. Based on the available evidence, we suggest that screening for KRAS mutations in patients with hyperplastic endometrium or early-stage type I EC, may provide important information for prognosis stratification, and further provision of personalised treatment options.

from A via a.sfakia on Inoreader http://bit.ly/2MNXR8u

Crypts With Corrupted Shapes in Non-polypoid Adenomas

Background: Colonic crypts with normal epithelial lining exhibiting corrupted shapes (NECS) have been previously found beneath the adenomatous tissue of polypoid conventional adenomas, in both rats and humans. Aim: To assess the frequency of NECS in non-polypoid colonic flat adenomas (FAs) and lateral-spreading adenomas (LSAs). Materials and Methods: Histological hematoxylin and eosin-stained sections from 51 non-polypoid colonic adenomas were scrutinized over a 10-mm field of vision (FOV). FAs were regarded lesions encompassed within the FOV and LSAs as those surpassing that limit. The NECS/mm ratio was calculated in individual lesions as the number of NECS beneath the adenomatous tissue, divided by the length (mm) of the FA and LSA. Results: Out of the 51 non-polypoid adenomas, 27 were FAs and the remaining 24 LSAs. All 51 non-polypoid lesions were tubular adenomas. The mean number of NECS in FAs was 6.29 (range=2-10) and in LSAs was 15.29 (range=7-41) (p<0.05). On the other hand, the mean NECS/mm ratio in FAs was 0.94 (range=0.50-2.00) and in LSAs was 0.92 (range=0.40-2.93). Thus, no essential differences in the number of NECS/mm was found between FA and LSA. Conclusion: The accretion of NECS below the neoplastic canopy of FA and LSA contrasts with the rare occurrence of NECS in normal colonic mucosa. This finding emerges as a previously unaddressed major event, an event that might play an important role in the histogenesis of non-polypoid adenomas of the colon.

from A via a.sfakia on Inoreader http://bit.ly/2DRyrnU

Integrin as a Molecular Target for Anti-cancer Approaches in Lung Cancer

Integrins are cell-matrix adhesion molecules providing both mechanical engagement of cell to extracellular matrix, and generation of cellular signals that are implicated in cancer malignancies. The concept that integrins play important roles in cell survival, proliferation, motility, differentiation, and ensuring appropriate cell localization, leads to the hypothesis that inhibition of certain integrins would benefit cancer therapy. In lung cancer, integrins αv, α5, β1, β3, and β5 have been shown to augment survival and metastatic potential of cancer cells. This review presents data suggesting integrins as molecular targets for anti-cancer approaches, and the mechanisms through which integrins confer resistance of lung cancer to chemotherapeutics and metastasis. The better understanding of these key molecules may benefit the discovery of anti-cancer drugs and strategies.

from A via a.sfakia on Inoreader http://bit.ly/2MJuMuW

County Median Family Income Is an Independent Prognostic Factor for Stage IV Anaplastic Thyroid Cancer

Background/Aim: Advanced anaplastic thyroid cancer (ATC) is a rare, but highly aggressive malignancy, and its prognostic factors need to be further explored. We examined socioeconomic factors' predictive effect for survival performance in stage IV ATC patients. Materials and Methods: Using the Surveillance, Epidemiology, and End Results database, we collected 1,048 cases with stage IV anaplastic thyroid cancer (ATC) from 2004 to 2015. Demographic, clinical, and socioeconomic factors were evaluated using univariate and multivariate analyses. Results: Median family income showed a significant effect on overall survival (OS) and cancer-specific survival (CSS) in univariate analysis. Median family income level was found to be an independent prognostic factor for OS after multivariate adjustment Multivariate analysis for CSS showed similar results. Conclusion: Family income level is an independent prognostic factor for stage IV ATC.

from A via a.sfakia on Inoreader http://bit.ly/2DP76Tl

A Potent CD1d-binding Glycolipid for iNKT-Cell-based Therapy Against Human Breast Cancer

Background/Aim: Invariant natural killer T-cells (iNKT) stimulated by CD1d-binding glycolipids have been shown to exert antitumor effects by a number of studies in a mouse model. Breast cancer is a devastating disease, with different types of breast cancer recurring locally or distant as metastatic/advanced disease following initial treatment. The aim of this study was to examine the tumoricidal effect of a CD1d-binding glycolipid, called 7DW8-5, against a highly invasive human breast cancer cell line both in vitro and in vivo. Materials and Methods: Parental MDA-MB-231 cells and MDA-MB-231 cells transduced with human CD1d were labeled with carboxyfluorescein diacetate succinimidyl ester (CFSE), followed by loading with glycolipids. After co-culturing with human iNKT cells, the cells were permeabilized and stained with Alexa Flour 647-conjugated antibody to active caspase-3, and analyzed using a BD LSR II. For the in vivo tumoricidal effect, MDA-MB-231 cells transduced with human CD1d and luciferase genes were injected into the mammary fat pad of female NOD/SCID/IL2rnull (NSG) mice, followed by the injection of human iNKT cells with or without 7DW8-5, and the levels of luminescence were analyzed with whole-body imaging. Results: Human iNKT cells could kill CD1d-expressing human breast cancer cells in vitro in the presence of 7DW8-5, but not α-GalCer. As for in vivo, the adoptive transfer of human iNKT cells into tumor-challenged NSG mice significantly inhibited the growth of CD1d+ MDA-MB-231 human breast cancer cells in the presence of 7DW8-5. Conclusion: CD1d-binding, glycolipid-based iNKT-cell therapy is suggested as a potent and effective treatment against breast cancer in humans.

from A via a.sfakia on Inoreader http://bit.ly/2ML4NDy

Clinical Outcomes of 42 Renal Cell Carcinoma Patients With Metastases Solely to the Lung Who Received Sorafenib as Second-line Systemic Therapy

Background/Aim: In renal cell carcinoma (RCC), sorafenib was the first targeted agent demonstrating a definitive benefit in a large phase III clinical trial. The objective of this study was to assess the clinical outcomes of 42 consecutive RCC patients with metastases solely to the lung who received sorafenib as a second-line systemic agent. Patients and Methods: Of the 42 patients, 14 (33.3%) and 28 (66.7%) received cytokine therapy and sunitinib, respectively, prior to treatment with sorafenib. In this series, all patients initially received 400 mg of sorafenib twice daily on a continuous dosing schedule. The efficacy and safety of second-line sorafenib in these 42 patients were retrospectively evaluated. Results: As the best response to sorafenib, 2 (4.8%), 14 (33.3%), 22 (52.4%) and 4 (9.5%) patients were judged to show a complete response, partial response, stable disease and progressive disease, respectively. The median progression-free survival (PFS) and overall survival (OS) after the introduction of sorafenib was 10.6 and 30.2 months, respectively. Multivariate analyses of several parameters identified the following independent prognostic predictors: C-reactive protein (CRP) level for PFS, and International Renal Cell Carcinoma Database Consortium classification and CRP level for OS. The common adverse events associated with sorafenib were hand-foot syndrome, hypertension and diarrhea, which developed in 22 (52.4%), 17 (40.5%) and 13 (31.0%), respectively; however, any AEs corresponding to ≥grade 3 occurred in only 16 (38.1%). Conclusion: Favorable disease control with acceptable tolerability might be expected by introducing sorafenib as second-line therapy for RCC patients with metastases solely to the lung; therefore, sorafenib could be the optimal option for this category of patients.

from A via a.sfakia on Inoreader http://bit.ly/2DSe0Hv

High miR-3687 Expression Affects Migratory and Invasive Ability of Oesophageal Carcinoma

Background/Aim: Basaloid squamous cell carcinoma of the oesophagus (BSCCE) is a variant of oesophageal squamous cell carcinoma (ESCC), that has a more aggressive biological behaviour than that of typical ESCC. miR-3687 has been previously identified to be highly expressed in BSCCE. This study aimed to evaluate the prognostic impact of miR-3687 in ESCC and determine the role of miR-3687 in ESCC motility. Materials and Methods: miR-3687 expression in human ESCC cell lines and in primary tumour samples obtained from patients with ESCC who underwent esophagectomy were analyzed via real-time polymerase chain reaction (PCR). Knockdown and over-expression experiments were conducted with miR-3687 siRNA and miRNA mimic, and the effect on cell proliferation, migration, and invasion was analyzed. Results: A total of 92 samples were analyzed. High miR-3687 expression was correlated with poor prognosis. miR-3687 upregulation promoted cell migration and invasion. Conclusion: miR-3687 expression negatively impacts the prognosis of patients with ESCC.

from A via a.sfakia on Inoreader http://bit.ly/2MKIZYB

Age Adjusted Charlson Comorbidity Index Strongly Influences Survival, Irrespective of Performance Status and Age, in Patients With Advanced Prostatic Cancer Treated With Enzalutamide

Background/Aim: Enzalutamide is prescribed for advanced prostatic cancer patients, regardless of physical comorbidity. We hypothesized that comorbidity negatively affects survival regardless of age, performance status and prostate-specific antigen (PSA) response. Patients and Methods: All patients (n=106) treated at the ADRZ Medical Center with enzalutamide in the period 2015-2018 and who had undergone at least one PSA response evaluation were included in a multivariate analysis to test which variables independently affected Time to PSA progression (TPSAP) and/or overall survival (OS). Results: A poorer performance status appeared to relate to a two times increased risk of dying (HR=2.032, 95%CI=1.078-3.830). An older age did not appear to influence OS, whereas an ACCI of more than 9 points appeared to relate to a more than three times increased risk of dying (HR=3.538, 95%CI=1.466-8.538). Conclusion: Survival appeared to be strongly affected by comorbidity, irrespective of age and performance status in patients treated with enzalutamide.

from A via a.sfakia on Inoreader http://bit.ly/2DQfCBq

Association of CD31 and p53 With Survival of Ovarian Cancer Patients

Background/Aim: New markers for ovarian cancer are needed. This study aimed to examine the expression of tumour cell p53 and endothelial cell CD31 proteins and correlate them to clinicopathological factors. Patients and Methods: Expression of proteins was immunohistochemically assessed using tissue sections from 585-599 ovarian cancer patients from the Danish MALOVA study. Results: High CD31 expression was found in poorly differentiated tumours (p=0.0006), and high p53 expression was found in poorly differentiated cancers (p<0.0001), high clinical stage (p<0.0001), non-radical surgery (p<0.0001) and high serum CA-125 values (p<0.0001). CD31 expression showed no prognostic survival value, but high hazard ratios were found for patients with high p53 expression (HR=2.313, p<0.0001). An interaction was found between p53 and stage of cancer, suggesting a prognostic impact of p53 in low-stage, but not in advanced-stage cancer. Conclusion: More than 5% of p53 tissue expression may predict shorter survival of ovarian cancer patients and may be useful for predicting the risk of disease progression in low-stage patients following primary surgery. CD31 has no strong prognostic value.

from A via a.sfakia on Inoreader http://bit.ly/2MQD84c

Diagnostic Utility of Third-Look, Contrast-Enhanced Sonography Followed by Needle Biopsy for MRI, But Not Ultrasonography Breast Lesions

Background/Aim: To clarify the diagnostic utility of third-look, contrast-enhanced ultrasonography (CEUS) for MRI-detected breast lesions undetectable by unenhanced, second-look ultrasonography (MRI+/US– lesions). Patients and Methods: Clinical stage 0–IIA breast cancer patients who underwent CEUS for incidental MRI+/US– lesions (n=27; cohort 1) and patients with breast lesions detected only by MRI, to be examined by CEUS (n=15; cohort 2), were retrospectively analyzed. Results: Of the 42 MRI+/US– lesions, 23 (55%) were detected by CEUS and then examined by needle biopsy. Pathological examination showed that 10 of these 23 lesions were malignant. None of the 19 lesions undetected by CEUS were found to be histologically malignant or developed malignancy with a median follow-up of 18.5 months. The accuracy, sensitivity, and specificity of CEUS plus needle biopsy were 98%, 91%, and 100%, respectively. Conclusion: Third-look CEUS followed by needle biopsy is useful in the initial diagnosis of MRI+/US– lesions.

from A via a.sfakia on Inoreader http://bit.ly/2DSTSor

Oligodendrocytes Up-regulate the Invasive Activity of Glioblastoma Cells via the Angiopoietin-2 Signaling Pathway

Background/Aim: Glioblastoma (GBM) is one of the most lethal solid cancers due to its highly invasive nature. The malignant potential of GBM cells might be partially regulated by surrounding normal cells, such as oligodendrocytes or fibroblasts. The aim of this study was to examine the interaction between stromal cells and GBM cells. Materials and Methods: Two GBM cell lines were used. The effect of stromal cells, oligodendrocytes or fibroblasts, on the invasive ability of GBM cells was examined by wound-healing assay and invasion assay. Results: Oligodendrocytes, in contrast to fibroblasts, significantly increased the migration and invasive ability of GBM cells. Angiopoietin-2 levels were high in the conditioned medium obtained from oligodendrocytes. Angiopoietin-2 significantly increased the motility of GBM, and the motility-stimulating activity of the oligodendrocytes-derived conditioned medium was significantly decreased by anti-angiopoietin-2-neutralizing antibody. Conclusion: Glioma stromal cells, oligodendrocytes, might up-regulate the invasiveness of GBM cells via angiopoietin-2 signaling.

from A via a.sfakia on Inoreader http://bit.ly/2MNUNt9

Postoperative Pneumonia After Esophagectomy and Systemic Inflammatory Response Syndrome

Background/Aim: The aim of this study was to determine the association between post-esophagectomy pneumonia and the presence of pathogenic organisms in the sputum or pharynx and postoperative systemic inflammatory response syndrome (SIRS). Materials and Methods: This retrospective study included 98 patients diagnosed with esophageal cancer who had undergone esophagectomy. Results: Postoperative pneumonia was observed in 24 patients (24.5%). Of the total 98 patients, 45 (45.9%) were tested positive for pathogenic organisms preoperatively, and 16 of those (35.6%) developed postoperative pneumonia; postoperative pneumonia occurred at a higher rate in these patients compared to pathogenic organism-negative patients (p=0.019). Postoperative SIRS was observed in 62 patients (63.3%), and 21 of these (33.9%) developed postoperative pneumonia, a significantly higher rate compared to patients without SIRS (p=0.007). Conclusion: Postoperative pneumonia was significantly associated with the presence of pathogenic organisms in the sputum or pharynx and postoperative SIRS.

from A via a.sfakia on Inoreader http://bit.ly/2DQ3gZV

Cytoplasmic Keap1 Expression Is Associated With Poor Prognosis in Endometrial Cancer

Background/Aim: Oxidative stress is involved in several carcinogenic pathways. Nuclear factor erythroid 2-related factor (Nrf2), Kelch-like ECH-associated protein 1 (Keap1) and Park7 (DJ-1) are the main regulators of antioxidant enzymes eliminating reactive oxidative species (ROS). The roles of these proteins were studied as potential prognostic factors in endometrial cancer. Materials and Methods: Nrf2, Keap1 and DJ-1 expression in endometrial carcinomas was analyzed immunohistochemically. Correlations between staining patterns and clinical prognostic variables were evaluated. Results: Extensive cytoplasmic Keap1 staining correlated to several factors associated with poor prognosis of endometrial cancer including advanced stage, poor histological differentiation, lymphovascular invasion, pelvic lymph node metastasis and deep myometrial invasion. In multivariate analysis, cytoplasmic Keap1 was a stronger predictor of poor progression-free survival than grade. Nuclear Nrf2 staining was seen in all patients with lymph node metastasis while DJ-1 staining was associated with clinically favourable disease types. Conclusion: Cytoplasmic Keap1 expression indicates poor prognosis in endometrial cancer.

from A via a.sfakia on Inoreader http://bit.ly/2MLdVrK

Leptomeningeal Gliomatosis: A Single Institution Study of 31 Patients

Background/Aim: Secondary leptomeningeal gliomatosis (LG) is a rare and severe progression pattern of glioma. Our objective was to evaluate the characteristics and outcome of patients with LG. Patients and Methods: We retrospectively reviewed 31 patients diagnosed with secondary LG. At the time of LG diagnosis, the median age of patients was 45 years. The histological grade was IV in 20 patients and II to III in 11 patients. As a first-line of therapy for LG, 22 patients received an oncological treatment: i) BCNU-temozolomide (TMZ) (n=15), ii) other type of chemotherapy (n=7), and iii) no treatment (supportive care) (n=9). Results: Following LG diagnosis, the median progression-free survival (PFS) and overall survival (OS) were 1.8 months [95% confidence interval (CI)=0.9-2.7] and 2.1 months (95%CI=1.3-3), respectively. The univariate analyses showed an improved OS with age of less than 45 years (p<0.001), a prolonged interval from the initial glioma diagnosis (IGD) to LG diagnosis (p=0.003), BCNU–TMZ as the preferred first-line treatment for LG out of the three options (p=0.008), and Karnofsky performance status (KPS) ≥70 (p=0.012). Prolonged interval from IGD to LG diagnosis (HR=5.839) and BCNU–TMZ as the chosen first-line treatment for LG (HR=6.635) remained significant in the multivariate analyses as well. Among the 22 treated patients, the median OS was significantly higher (p=0.008) with the BCNU–TMZ treatment (5.7 months; 95%CI=4.2-7.1), compared to other types of treatment offered (2 months; 95%CI=1.1-2.9). Conclusion: The time interval from the IGD to the LG diagnosis is a potential prognostic factor for LG. BCNU–TMZ may be a therapeutic option in the present setting.

from A via a.sfakia on Inoreader http://bit.ly/2DQKbHi

Isothiocyanate-induced Cell Cycle Arrest in a Novel In Vitro Exposure Protocol of Human Malignant Melanoma (A375) Cells

Background/Aim: Several studies have documented the effects of isothiocyanates (ITCs) on cancer prevention by inducing oxidative stress, activating apoptosis, affecting cell-cycle regulation, etc. Previously, we have shown that ITCs, administered at low concentrations by the means of double-bolus are capable of potentiating cytotoxicity in human malignant melanoma (A375) cells by inducing apoptosis. The aim of the present study was to further investigate the effect of the treatment of A375 cells with ITCs on cell-cycle progression and the levels of various cell cycle regulators. Materials and Methods: Cell-cycle analysis was performed by means of flow cytometry whereas western immunoblotting was used to determine the expression levels of these protein regulators. Results: Our data showed an increase in the number of cells in the G₂/M phase accompanied by a decrease in the G₀/G₁ phase, while several cell-cycle regulators were shown to be differentially expressed upon exposure to ITCs. Conclusion: ITCs induced cell-cycle arrest in A375 cells.

from A via a.sfakia on Inoreader http://bit.ly/2MK63qz

MicroRNA-based Targeted Therapeutics in Pancreatic Cancer

The discovery during the last decade of microRNAs (miRs, miRNA) and their role in regulating normal physiological processes as well as in the pathogenesis of human tumors has been a revolutionary development in molecular oncology. miRNAs activating or inhibiting oncogenic molecular pathways that are involved in tumorigenesis, cell progression, invasion, angiogenesis and metastasis are now considered of major impact in many cancer types. miRNA-based therapeutics that inhibit the levels of oncogenic miRNAs (oncomiRs) or elevate tumor suppressor miRs have enormous potential as molecular therapeutic targets. Thus, the development of new targeted cancer therapies based on miRNAs promise to revolutionize cancer treatment due to their increased efficacy compared to conventional chemoradiation-based therapies and hopefully to lower levels of adverse effects.

from A via a.sfakia on Inoreader http://bit.ly/2DQW1ku

A genome-scale metabolic network of the aroma bacterium Leuconostoc mesenteroides subsp. cremoris

Abstract

Leuconostoc mesenteroides subsp. cremoris is an obligate heterolactic fermentative lactic acid bacterium that is mostly used in industrial dairy fermentations. The phosphoketolase pathway (PKP) is a unique feature of the obligate heterolactic fermentation, which leads to the production of lactate, ethanol, and/or acetate, and the final product profile of PKP highly depends on the energetics and redox state of the organism. Another characteristic of the L. mesenteroides subsp. cremoris is the production of aroma compounds in dairy fermentation, such as in cheese production, through the utilization of citrate. Considering its importance in dairy fermentation, a detailed metabolic characterization of the organism is necessary for its more efficient use in the industry. To this aim, a genome-scale metabolic model of dairy-origin L. mesenteroides subsp. cremoris ATCC 19254 (iLM.c559) was reconstructed to explain the energetics and redox state mechanisms of the organism in full detail. The model includes 559 genes governing 1088 reactions between 1129 metabolites, and the reactions cover citrate utilization and citrate-related flavor metabolism. The model was validated by simulating co-metabolism of glucose and citrate and comparing the in silico results to our experimental results. Model simulations further showed that, in co-metabolism of citrate and glucose, no flavor compounds were produced when citrate could stimulate the formation of biomass. Significant amounts of flavor metabolites (e.g., diacetyl and acetoin) were only produced when citrate could not enhance growth, which suggests that flavor formation only occurs under carbon and ATP excess. The effects of aerobic conditions and different carbon sources on product profiles and growth were also investigated using the reconstructed model. The analyses provided further insights for the growth stimulation and flavor formation mechanisms of the organism.

from A via a.sfakia on Inoreader http://bit.ly/2GkO88O

Recycling of crushed waste rock as backfilling material in coal mine: effects of particle size on compaction behaviours

Abstract

Crushed waste rocks can be used as materials for backfilling goafs, so as to achieve the simultaneous goals of processing solid waste and controlling surface subsidence; however, particle size distribution directly affects the compaction of crushed waste rocks. Therefore, by employing a self-designed bidirectional loading test system for granular materials, this study tested compaction characteristics of crushed waste rocks with four different particle size distributions. Moreover, this research tested the changes of parameters in lateral and axial loading of crushed waste rocks and analysed the influence of particle size distribution on lateral strain, axial strain, porosity, lateral stress, and lateral pressure coefficient during compaction. The test results show that (1) particle size distribution affects porosity, strain, and lateral pressure coefficient of crushed waste rocks under lateral and axial loading. (2) For the samples under particle size distribution ranging from 0 to 10 mm, the initial porosity is low and deformations are small under axial loading, so that particles can make contact and bear effective stress in grain-grain contact. Therefore, more stress is transferred to the lateral direction. (3) After compaction, the curves of the samples of crushed waste rocks under four particle size distributions all shift upwards in comparison with those before compaction, indicating that particles are crushed and the proportion of small particles constantly increases. (4) A reasonable particle size distribution can significantly improve stress characteristics, reduce crushing of particles in the samples, and increase the stiffness of the samples, so as to achieve better compaction effects.

from Energy Ecology Environment Ambio via Terpsi Hori on Inoreader http://bit.ly/2t3Ugu6

Evidence of non-DDD pathway in the anaerobic degradation of DDT in tropical soil

Abstract

DDT transformation to DDD in soil is the most commonly reported pathway under anaerobic conditions. A few instances of DDT conversion to products other than DDD/DDE have been reported under aerobic conditions and hardly any under anaerobic conditions. In particular, few reports exist on the anaerobic degradation of DDT in African tropical soils, despite DDT contamination arising from obsolete pesticide stockpiles in the continent as well as new contamination from DDT use for mosquito and tsetse fly control. Moreover, the development of possible remediation strategies for contaminated sites demands adequate understanding of different soil processes and their effect on DDT persistence, hence necessitating the study. The aim of this work was to study the effect of simulated anaerobic conditions and slow-release carbon sources (compost) on the dissipation of DDT in two tropical clay soils (paddy soil and field soil) amenable to periodic flooding. The results showed faster DDT dissipation in the field soil but higher metabolite formation in the paddy soil. To explain this paradox, the levels of dissolved organic carbon and carbon mineralization (CH₄ and CO₂) were correlated with p,p-DDT and p,p-DDD concentrations. It was concluded that DDT underwent reductive degradation (DDD pathway) in the paddy soil and both reductive (DDD pathway) and oxidative degradation (non-DDD pathway) in the field soil.

from Energy Ecology Environment Ambio via Terpsi Hori on Inoreader http://bit.ly/2S75Cwo

The optimal duration of adjuvant endocrine therapy in early luminal breast cancer: A concise review.

The optimal duration of adjuvant endocrine therapy in early luminal breast cancer: A concise review.

Cancer Treat Rev. 2019 Jan 25;74:29-34

Authors: Rossi L, McCartney A, De Santo I, Risi E, Moretti E, Malorni L, Biganzoli L, Di Leo A

Abstract
Patients with luminal early breast cancer are at risk of relapse, even after five years of adjuvant endocrine therapy. To date, no biomarkers have been clinically validated to identify those patients at risk of late recurrence, who might benefit from extended adjuvant endocrine therapy. In recent decades, multiple clinical trials have tested the role of extending adjuvant endocrine therapies in patients with luminal disease. However, the data currently at our disposal are conflicting. This article reviews all the major trials concerning extended adjuvant endocrine regimens, and formulates some general conclusions and hypotheses of future study.

PMID: 30708267 [PubMed - as supplied by publisher]

from A via a.sfakia on Inoreader http://bit.ly/2GjMp3h

A Multi-Institutional Experience of MR-Guided Liver Stereotactic Body Radiation Therapy.

Related Articles

A Multi-Institutional Experience of MR-Guided Liver Stereotactic Body Radiation Therapy.

Adv Radiat Oncol. 2019 Jan-Mar;4(1):142-149

Authors: Rosenberg SA, Henke LE, Shaverdian N, Mittauer K, Wojcieszynski AP, Hullett CR, Kamrava M, Lamb J, Cao M, Green OL, Kashani R, Paliwal B, Bayouth J, Harari PM, Olsen JR, Lee P, Parikh PJ, Bassetti M

Abstract
Purpose: Daily magnetic resonance (MR)-guided radiation has the potential to improve stereotactic body radiation therapy (SBRT) for tumors of the liver. Magnetic resonance imaging (MRI) introduces unique variables that are untested clinically: electron return effect, MRI geometric distortion, MRI to radiation therapy isocenter uncertainty, multileaf collimator position error, and uncertainties with voxel size and tracking. All could lead to increased toxicity and/or local recurrences with SBRT. In this multi-institutional study, we hypothesized that direct visualization provided by MR guidance could allow the use of small treatment volumes to spare normal tissues while maintaining clinical outcomes despite the aforementioned uncertainties in MR-guided treatment.
Methods and materials: Patients with primary liver tumors or metastatic lesions treated with MR-guided liver SBRT were reviewed at 3 institutions. Toxicity was assessed using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4. Freedom from local progression (FFLP) and overall survival were analyzed with the Kaplan-Meier method and χ2 test.
Results: The study population consisted of 26 patients: 6 hepatocellular carcinomas, 2 cholangiocarcinomas, and 18 metastatic liver lesions (44% colorectal metastasis). The median follow-up was 21.2 months. The median dose delivered was 50 Gy at 10 Gy/fraction. No grade 4 or greater gastrointestinal toxicities were observed after treatment. The 1-year and 2-year overall survival in this cohort is 69% and 60%, respectively. At the median follow-up, FFLP for this cohort was 80.4%. FFLP for patients with hepatocellular carcinomas, colorectal metastasis, and all other lesions were 100%, 75%, and 83%, respectively.
Conclusions: This study describes the first clinical outcomes of MR-guided liver SBRT. Treatment was well tolerated by patients with excellent local control. This study lays the foundation for future dose escalation and adaptive treatment for liver-based primary malignancies and/or metastatic disease.

PMID: 30706022 [PubMed]

from A via a.sfakia on Inoreader http://bit.ly/2SkJr58

Hepatocellular carcinoma in non-cirrhotic liver: A comprehensive review.

Related Articles

Hepatocellular carcinoma in non-cirrhotic liver: A comprehensive review.

World J Hepatol. 2019 Jan 27;11(1):1-18

Authors: Desai A, Sandhu S, Lai JP, Sandhu DS

Abstract
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, which in turns accounts for the sixth most common cancer worldwide. Despite being the 6th most common cancer it is the second leading cause of cancer related deaths. HCC typically arises in the background of cirrhosis, however, about 20% of cases can develop in a non-cirrhotic liver. This particular subgroup of HCC generally presents at an advanced stage as surveillance is not performed in a non-cirrhotic liver. HCC in non-cirrhotic patients is clinically silent in its early stages because of lack of symptoms and surveillance imaging; and higher hepatic reserve in this population. Interestingly, F3 fibrosis in non-alcoholic fatty liver disease, hepatitis B virus and hepatitis C virus infections are associated with high risk of developing HCC. Even though considerable progress has been made in the management of this entity, there is a dire need for implementation of surveillance strategies in the patient population at risk, to decrease the disease burden at presentation and improve the prognosis of these patients. This comprehensive review details the epidemiology, risk factors, clinical features, diagnosis and management of HCC in non-cirrhotic patients and provides future directions for research.

PMID: 30705715 [PubMed]

from A via a.sfakia on Inoreader http://bit.ly/2Glq45t

Studying the regression profiles of cervical tumours during radiotherapy treatment using a patient-specific multiscale model.

Related Articles

Studying the regression profiles of cervical tumours during radiotherapy treatment using a patient-specific multiscale model.

Sci Rep. 2019 Jan 31;9(1):1081

Authors: Kyroudis CA, Dionysiou DD, Kolokotroni EA, Stamatakos GS

Abstract
Apart from offering insight into the biomechanisms involved in cancer, many recent mathematical modeling efforts aspire to the ultimate goal of clinical translation, wherein models are designed to be used in the future as clinical decision support systems in the patient-individualized context. Most significant challenges are the integration of multiscale biodata and the patient-specific model parameterization. A central aim of this study was the design of a clinically-relevant parameterization methodology for a patient-specific computational model of cervical cancer response to radiotherapy treatment with concomitant cisplatin, built around a tumour features-based search of the parameter space. Additionally, a methodological framework for the predictive use of the model was designed, including a scoring method to quantitatively reflect the similarity and bilateral predictive ability of any two tumours in terms of their regression profile. The methodology was applied to the datasets of eight patients. Tumour scenarios in accordance with the available longitudinal data have been determined. Predictive investigations identified three patient cases, anyone of which can be used to predict the volumetric evolution throughout therapy of the tumours of the other two with very good results. Our observations show that the presented approach is promising in quantifiably differentiating tumours with distinct regression profiles.

PMID: 30705291 [PubMed - in process]

from A via a.sfakia on Inoreader http://bit.ly/2Slsp6N

Threats for sustainability of multidisciplinary working: Attitudes and perceptions of cancer care providers.

Related Articles

Threats for sustainability of multidisciplinary working: Attitudes and perceptions of cancer care providers.

J Cancer Res Ther. 2018 Oct-Dec;14(6):1291-1297

Authors: Ruiz-Casado A, Ortega Solano MJ, Verdugo AS, Boado HC

Abstract
Background: To develop methods for cancer teams to work effectively, it is first necessary to understand how multidisciplinary teams work together as part of an organization. Implementation and adoption of new clinical practices such as team working is a challenging task. It is known that implementation of multidisciplinary working depends on a complex, multilevel interaction of team, and organizational factors. However, little is known about the threats to the sustainability of functioning multidisciplinary teams.
Materials and Methods: A questionnaire was mailed to 125 multidisciplinary team meetings (MTMs) attendees. Five focus groups were gathered in order to discuss threats and strengths of cancer team-working. Discussions at the meetings were transcribed verbatim and analyzed for emergent themes using standard qualitative research methodology.
Results: About 31 physicians and MTMs attendees participated in the focus groups. They perceive that meetings are very useful for making a good decision over patients. Lack of dedicated time and lack of support by the institution were the most recurrent themes which could be considered as threats for sustainability of cancer conferences. Leadership and decision-making process should be refined.
Conclusions: Physicians see enormous value in MTMs but the lack of support from the organization could compromise the future effective working. This research highlights the need to explore local strengths and threats for sustainability of periodic cancer team working.

PMID: 30488846 [PubMed - indexed for MEDLINE]

from A via a.sfakia on Inoreader http://bit.ly/2GhyZVD

Immunomodulatory Effects of Current Targeted Therapies on Hepatocellular Carcinoma: Implication for the Future of Immunotherapy.

Related Articles

Immunomodulatory Effects of Current Targeted Therapies on Hepatocellular Carcinoma: Implication for the Future of Immunotherapy.

Semin Liver Dis. 2018 Nov;38(4):379-388

Authors: Lin YY, Tan CT, Chen CW, Ou DL, Cheng AL, Hsu C

Abstract
Multikinase inhibitors with antiangiogenic properties used to be standard therapy for patients with advanced hepatocellular carcinoma (HCC). Recently, several antiangiogenic agents (lenvatinib, cabozantinib, and ramucirumab) have demonstrated antitumor activity for advanced HCC in randomized controlled trials. However, the landscape of drug development for HCC may change dramatically with the advent of immune checkpoint inhibitor therapy, particularly the anti-programmed cell death-1 (anti-PD1) agents. In addition, early-phase clinical trials of combination of anti-PD-1 and antiangiogenic agents have shown very promising anti-tumor activity in patients with advanced HCC. Therefore, the critical research questions at present are whether this combination strategy will be the next generation of standard therapy and which antiangiogenic agents will be the optimal partner for the combination. All of the 4 multikinase inhibitors for HCC (sorafenib, regorafenib, lenvatinib, and cabozantinib) have been reported to have immune modulatory effects. The authors systematically reviewed the pre-clinical evidence of their immune modulatory effects to explore whether these effects were mediated by angiogenesis inhibition or by other "off-target" effects on the tumor microenvironment. Studies of sorafenib comprised the majority (58 of the 71) of the research articles reviewed. Potentially beneficial effects on anti-tumor immunity may result from increased M1 polarization of macrophages and stimulation of CD8 T cell function. On the other hand, high dosage of the kinase inhibitors in pre-clinical models and hypoxia associated with angiogenesis may contribute to immune suppression in the tumor microenvironment. Sorafenib and other multikinase inhibitors may promote anti-tumor immunity through modulation of multiple immune cell types as well as the tumor microenvironment. The optimal immune modulatory dosage should be defined to facilitate design of future combination regimens.

PMID: 30357775 [PubMed - indexed for MEDLINE]

from A via a.sfakia on Inoreader http://bit.ly/2Si5c5C

Preoperative prediction of facial nerve in patients with Vestibular Schwannomas: the role of diffusion tensor imaging. A systematic review.

Preoperative prediction of facial nerve in patients with Vestibular Schwannomas: the role of diffusion tensor imaging. A systematic review.

World Neurosurg. 2019 Jan 29;:

Authors: Baro V, Landi A, Brigadoi S, Castellaro M, Moretto M, Anglani M, Ermani M, Causin F, Denaro L, Bertoldo A, d'Avella D

Abstract
In vestibular schwannoma surgery the preservation of facial and cochlear nerves is of paramount concern with regard to their impact on the quality of life. The rate of nerve function preservation raised on account of advancement in surgical technique and neuroimaging and as well as the introduction of intraoperative neuromonitoring. Preoperative depiction of anatomical concerns between nerves and tumour could help the surgical planning; indeed many studies investigating advanced imaging for cranial nerves detection, in particular diffusion tensor imaging, have been published from the last decade. A systematic review of the literature evaluating preoperative facial nerve fiber tracking followed by intraoperative verification was conducted. Seventeen articles met our inclusion criteria, identifying 223 patients (mean age 47.5 years, range 17-77 years, male:female ratio 1:1.4). Preoperative facial nerve fiber tracking was obtained in 214 patients (96%) and the subsequent intraoperative verification revealed a correct prediction in 187 cases (85.5%). This review confirms that preoperative fiber tracking for facial nerve identification, in large vestibular schwannoma surgery, is a valuable and reliable instrument, nonetheless the studies are not comparable in terms of images, acquisitions and post-processing elaboration. Larger series and homogenous MRI parameters are required to strengthen these findings.

PMID: 30708084 [PubMed - as supplied by publisher]

from A via a.sfakia on Inoreader http://bit.ly/2GinAVr

Intracranial Administration of Nicardipine after Aneurysmal Subarachnoid Hemorrhage: A Review of the Literature.

Intracranial Administration of Nicardipine after Aneurysmal Subarachnoid Hemorrhage: A Review of the Literature.

World Neurosurg. 2019 Jan 29;:

Authors: Dodson V, Majmundar N, El-Ghanem M, Amuluru K, Gupta G, Nuoman R, Wainwright J, Kaur G, Cole C, Santarelli J, Chandy D, Bower C, Gandhi C, Al-Mufti F

Abstract
BACKGROUND: Intrathecal (IT), intraventricular (IVt), and intracisternal administration of nicardipine deliver treatment directly into the central nervous system (CNS). This route of drug delivery is being investigated as a potential treatment of vasospasm following aneurysmal subarachnoid hemorrhage (aSAH).
OBJECTIVE: The authors review the existing literature regarding the direct administration of nicardipine into the intracranial space for the treatment of vasospasm following aSAH.
METHODS: An electronic search of literature published between 1994 and 2018 was performed using PubMed in accordance with the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidelines. A variety of combinations of the search terms "intrathecal nicardipine", "intraventricular nicardipine", and "nicardipine prolonged-release" were used..
RESULTS: A total of seventeen studies are included in this systematic review, three of which were animal studies. The studies consistently demonstrated that IT nicardipine successfully reverses vasospasm, but the effect, as shown in some studies, was limited to the immediate vicinity of drug release. The data regarding long-term clinical outcomes is variable, with some studies demonstrating marked improvement while others fail to demonstrate improved outcomes when compared to patients who receive standard of care. While adverse sequalae were uncommon, IT and IVt administration and therapy were associated with adverse effects including headache, meningitis, and hydrocephalus.
CONCLUSIONS: Given the findings presented in these studies, IT, IVt, and intracisternal (pellet) nicardipine administration can be useful treatment adjuncts for vasospasm following aSAH, especially in cases refractory to conventional forms of treatment. However, larger, controlled clinical trials are warranted.

PMID: 30708083 [PubMed - as supplied by publisher]

from A via a.sfakia on Inoreader http://bit.ly/2GjmLfd

Technological and Ideological Innovations in Endoscopic Skull Base Surgery.

Technological and Ideological Innovations in Endoscopic Skull Base Surgery.

World Neurosurg. 2019 Jan 29;:

Authors: Riley CA, Soneru CP, Tabaee A, Kacker A, Anand VK, Schwartz TH

Abstract
BACKGROUND: Endoscopic skull base surgery has evolved over the last several decades due to technological advances and operative techniques. Several innovations that are not yet mainstream may have significant impact on the future of endoscopic skull base surgery.
METHODS: Current literature pertaining to innovations in endoscopic skull base surgery was retrieved using PubMed, Embase, Web of Science, and Google Scholar.
RESULTS: Several recent innovations may play an influential role in the advancement of endoscopic skull base surgery, including fluorescent dyes such as indocyanine green fluorescence, fluorescein, and 5-aminolevulinic acid, 3D endoscopes, robotic surgery, and intraoperative magnetic resonance imaging.
CONCLUSIONS: Several technologies are under current investigation with the hope to improve future outcomes in endoscopic skull base surgery. Additional research and evolution are necessary and will require intense scrutiny before becoming standard of care.

PMID: 30708082 [PubMed - as supplied by publisher]

from A via a.sfakia on Inoreader http://bit.ly/2GhrVIB

Symptomatic Idiopathic Spinal Epidural lipomatosis in nine patients: clinical, radiological and pathogenetic features.

Symptomatic Idiopathic Spinal Epidural lipomatosis in nine patients: clinical, radiological and pathogenetic features.

World Neurosurg. 2019 Jan 29;:

Authors: Kellett CG, Siva V, Norman ICF, Jung J, Grahovac G, Minhas P

Abstract
BACKGROUND: Symptomatic spinal epidural lipomatosis (SSEL) is characterised by hypertrophy of adipose tissue within the spinal canal and consequent neural compromise. The exact pathogenesis remains enigmatic. The authors describe a retrospective case series, define the full clinical spectrum and discuss possible pathogenetic mechanisms.
METHODS: The medical notes and imaging of nine patients with SSEL undergoing surgery from 2008 - 2018 were analysed. Seven patients presented secondary to lumbosacral SEL; three patients with chronic incomplete CES and three patients with acute CES (including a 25-week gravid patient and a forty-year old patient with intravenous leiomyomatosis, both patients had mild SEL). In addition, two patients presented with progressive myelopathy secondary to thoracic SEL.
RESULTS: Patients presenting with acute CES had a mean age of 37 years (range 23-49 years) and mean extradural fat:spinal canal ratio of 47% (range 41-58%), in comparison to patients with chronic CES; mean age 61 years (range 58-65 years) and EF:SC ratio 72% (range 65 - 80%). Patients underwent laminectomy and resection of epidural fat at compressive levels. All patients with CES experienced complete resolution of symptoms at follow up (range 1 - 48 months).
CONCLUSION: The clinician should be astute to the radiological features of SEL, particularly in patients presenting with CES in the absence of acute disc herniation. The outcome of patients with CES and SEL following surgery is excellent regardless of symptom duration. Venous impedance related to increased BMI and EF deposition may play a predominant role in addition to mechanical compression in the pathogenesis of SSEL.

PMID: 30708081 [PubMed - as supplied by publisher]

from A via a.sfakia on Inoreader http://bit.ly/2SpZKgY

A study of the sagittal angle of lumbar bicortical pedicle screws from the anatomical perspective of the lumbar artery.

A study of the sagittal angle of lumbar bicortical pedicle screws from the anatomical perspective of the lumbar artery.

World Neurosurg. 2019 Jan 29;:

Authors: Liu L, Wang H, Wang Q, Wang J, Liang Y, Li Y, Liang Q, Jin W, Zhou Q, Wang Z

Abstract
OBJECTIVE: Observing the anatomical relationships between lumbar bicortical pedicle screws (BPSs) at two sagittal section angles (SSAs) and the lumbar artery (LA).
METHODS: We observed two SSAs of the BPS, namely, the vertical angle and cephalic angle. Correspondingly, the positions at which the BPS breaks through the anterior vertebral cortex were defined as Point A and Point B. The distances from Point A and Point B to the LAs were measured and denoted DA-LA and DB-LA. According to these distances, the percentage of risk of injury to the LAs was calculated.
RESULTS: At the same transverse section angle (TSA) on the left and right side in L1 and L2, the DA-LA was significantly greater than the DB-LA (P < 0.001), except at a TSA of 0° on the right side in L2 (P > 0.05). At the same TSA on the left in L3 and L4, the DB-LA was significantly greater than the DA-LA (P < 0.001). The percentages of high risk of injury to the LA resulting from BPS at the vertical angle in L1 and L2 ranged from 0% to 6.2%. The percentages of high risk of injury to the LA resulting from BPS at the cephalic angle on the left side in L3 and L4 ranged from 0% to 18.5%.
CONCLUSION: Lumbar BPSs present a risk of injury to the LA. The vertical angle is the recommended SSA for the BPSs in L1 and L2, and the cephalic angle is the recommended SSA in L3 and L4.

PMID: 30708080 [PubMed - as supplied by publisher]

from A via a.sfakia on Inoreader http://bit.ly/2Glq3OX

Comparative evaluation of angioscopy and intravascular ultrasound for assessing plaque protrusion during carotid artery stenting procedures.

Comparative evaluation of angioscopy and intravascular ultrasound for assessing plaque protrusion during carotid artery stenting procedures.

World Neurosurg. 2019 Jan 29;:

Authors: Kondo H, Kiura Y, Sakamoto S, Okazaki T, Yamasaki F, Iida K, Tominaga A, Kurisu K

Abstract
OBJECTIVE: The evaluation of plaque protrusion after carotid artery stenting (CAS) is important for predicting periprocedural ischemic complications. Unlike intravascular ultrasound (IVUS), angioscopy allows direct visualization of the plaque. This study evaluated the utility and safety of angioscopy during CAS, comparing it with IVUS.
METHODS: The study included 13 carotid artery stenosis lesions in 11 consecutive patients (mean age, 70.5 years; 10 men) at a single center. During the CAS procedure, post-stenting plaque protrusion was evaluated with angioscopy and IVUS.
RESULTS: The mean level of internal carotid artery (ICA) stenosis was 79.2%. Eight lesions were symptomatic and five lesions were predicted to have vulnerable plaque by preprocedural magnetic resonance imaging (MRI). Carotid WALLSTENTs were placed in all cases. After stenting, angioscopy provided good visualization in all cases. Plaque protrusions were observed in one case by IVUS but in eight cases by angioscopy. Diffusion weighted imaging (DWI) showed positive lesions in three cases (23%). For two of these lesions, plaque protrusions were observed by angioscopy but not by IVUS. All the lesions associated with positive DWI findings were observed to have yellow plaque on angioscopy.
CONCLUSIONS: Angioscopy provided direct visualization of the stent lumens after stenting. Angioscopy detected more plaque protrusion than IVUS and allowed clearer observation of plaque characteristics; thus, it may be more useful than IVUS for the examination of plaque protrusion and plaque evaluation after CAS, especially for plaque identified as potentially vulnerable by preprocedural examination.

PMID: 30708079 [PubMed - as supplied by publisher]

from A via a.sfakia on Inoreader http://bit.ly/2SlNheg

Electrode Reconstruction Assists Post-operative Contact Selection in Deep Brain Stimulation.

Electrode Reconstruction Assists Post-operative Contact Selection in Deep Brain Stimulation.

World Neurosurg. 2019 Jan 29;:

Authors: Zhang D, Lin H, Liu J, Liu Z, Yan J, Cai X

Abstract
BACKGROUND: Post-operative contact selection of deep brain stimulation (DBS), testing one contact at a time, is a clinically time-consuming procedure being challenged by incoming applications of more complex DBS leads. The objective of this study is to guide clinicians to select the optimal contact by neuroanatomical information derived from electrode reconstruction.
METHODS: We reviewed 33 Parkinson's disease patients who underwent bilateral subthalamic nucleus (STN) DBS with pre-operative MRI and post-operative CT. All electrodes were reconstructed in standardized MNI space and the volume of tissue activated (VTA) was estimated for each contact. According to the DISTAL atlas, we calculated six neuroanatomical parameters: the distances of each contact to the STN and the motor part of STN (M-STN), the volumes of the overlapping areas of VTA and STN/M-STN, the number and ratio of fiber tracts through both VTA and motor areas (primary motor cortex and supplementary motor area).
RESULTS: All these six parameters showed significant group differences between clinical optimal and non-optimal contacts by permutation test. Moreover, the possibilities to be the optimal contacts were estimated for all contacts under the combination of these six parameters using a generalized linear model, which resulted in accuracy of 72.7% for prediction of contact selection.
CONCLUSIONS: Electrode reconstruction could assist in selecting the clinical optimal contact and improve its efficiency.

PMID: 30708078 [PubMed - as supplied by publisher]

from A via a.sfakia on Inoreader http://bit.ly/2Gh9LGQ

Robot-assisted versus fluoroscopy-guided pedicle screw placement in transforaminal lumbar interbody fusion for lumbar degenerative disease.

Robot-assisted versus fluoroscopy-guided pedicle screw placement in transforaminal lumbar interbody fusion for lumbar degenerative disease.

World Neurosurg. 2019 Jan 29;:

Authors: Qi Z, Xiao-Guang H, Yun-Feng X, Ya-Jun L, Bo L, Da H, Yu-Qing S, Wei T

Abstract
OBJECTIVE: To compare the clinical accuracy and perioperative outcomes for pedicle screw placement in transforaminal lumbar interbody fusion (TLIF) between robot-assisted (RA) technique and fluoroscopy-guided (FG) technique.
METHODS: 77 patients scheduled to undergo RA (43 patients) and FG (44 patients) TLIF surgery were included. Patient demographics, radiographic accuracy and perioperative outcomes were recorded and compared. The accuracy of pedicle screw placement was according to the Gertzbein and Robbins scale and facet joint violation. Perioperative outcome mainly included operative time, radiation exposure, and revisions.
RESULTS: Of the 176 screws in the RA group, 164 screws were grade A, and 9, 2 and 1 screws were grade B, C and D, respectively. Of the 204 screws in the FG group, 175 screws were grade A, with 16 screws scored as grade B, 8 screws grade C, 3 grade D, and 2 grade E. The rate of perfect screw position (grade A) was greater in the RA group than in FG (93.2% vs. 85.8%; P=0.020). 191 screws (93.6%) in FG group were clinically acceptable (group A + B), whereas more acceptable screw positions were achieved in RA (98.3%) (P=0.024). Less screws in the RA group violated the proximal facet joint (5 vs. 24 screws, P=0.001). The radiation dose was less in the RA group (25.9±14.2 vs. 70.5±27.3 μSv; P=0.000). 2 screws in FG required a revision, but no revision was required in RA.
CONCLUSION: RA pedicle screw placement is an accurate and safe procedure in TLIF for lumbar degenerative disease.

PMID: 30708077 [PubMed - as supplied by publisher]

from A via a.sfakia on Inoreader http://bit.ly/2GnDJsZ

Corrigendum to 'Muslin Granuloma Mimicking Parenchymal Hematoma in Patient with Seizures 30 Years After Aneurysm Wrapping' [World Neurosurgery 120 (2018) 129-130].

Related Articles

Corrigendum to 'Muslin Granuloma Mimicking Parenchymal Hematoma in Patient with Seizures 30 Years After Aneurysm Wrapping' [World Neurosurgery 120 (2018) 129-130].

World Neurosurg. 2019 Jan 28;:

Authors: Cox M, Sedora-Roman NI, Bagley LJ, Choudhri O

PMID: 30704935 [PubMed - as supplied by publisher]

from A via a.sfakia on Inoreader http://bit.ly/2Sl2bS8

Metastasis to Stomach in a Patient with Anaplastic Thyroid Carcinoma: A Clinical Challenge.

Related Articles

Metastasis to Stomach in a Patient with Anaplastic Thyroid Carcinoma: A Clinical Challenge.

Am J Case Rep. 2019 Feb 01;20:134-138

Authors: Fuladi R, Nagarkar R, Roy S

Abstract
BACKGROUND Anaplastic thyroid carcinoma (ATC) is an uncommon and aggressive form of human cancer. Despite advancement in multimodal therapy for patients with ATC, the prognosis remains poor. Most patients presenting with ATC have metastasis to the lungs and regional lymph nodes. Gastrointestinal tract metastasis is a rare entity observed among patients with ATC. We report a case of ATC with gastrointestinal metastasis. CASE REPORT A 72-year-old euthyroid female with hypertension presented to the clinic with swelling of the neck and breathlessness. Fine needle aspiration cytology revealed colloid goiter. Positron emission tomography and computed tomography revealed hypermetabolic, lobulated mass in left hemi-thyroid, displacing trachea, and hypermetabolic lymph nodes on the left side. The patient underwent total thyroidectomy along with left modified radical neck dissection. Histopathology and immunochemistry were suggestive of ATC with thyroid transcription factor 1 (TTF-1), cytokeratin, Pax8, and C53 positive while calcitonin and thyroglobulin were negative. The patient presented with persistent nausea and vomiting during adjuvant radiation therapy. After radiation therapy, the patient underwent upper gastrointestinal endoscopy that revealed large polypoidal lesions in the stomach. No active bleeding was observed. Biopsy results confirmed it to be metastasis from ATC. CONCLUSIONS ATC can spread to distant sites including the gastrointestinal tract. Patients with ATC metastasis have a poor prognosis despite multimodal therapy. This is the first case of ATC with gastrointestinal metastasis reported in India.

PMID: 30705249 [PubMed - in process]

from A via a.sfakia on Inoreader http://bit.ly/2WDXv8Z

Three-dimensional amplitude characteristics of masseter motor units and representativeness of extracted motor unit samples.

Three-dimensional amplitude characteristics of masseter motor units and representativeness of extracted motor unit samples.

Clin Neurophysiol. 2019 Jan 19;130(3):388-395

Authors: Lapatki BG, Eiglsperger U, Schindler HJ, Radeke J, Holobar A, van Dijk JP

Abstract
OBJECTIVE: This study aimed to characterize amplitude topographies for masseter motor units (MUs) three-dimensionally, and to assess whether high-density surface electromyography (HDsEMG) is able to detect MU samples that represent the masseter's entire MU pool.
METHODS: Ten healthy adult volunteers participated in the study, which combined three EMG techniques. A HDsEMG grid covering the entire masseter, and intramuscular fine-wire electrodes were used to obtain two independent MU samples for comparison. The MUs' amplitude profiles in the dimension of muscle depth were determined using scanning EMG. All data were recorded simultaneously during a low, constant contraction level controlled by 3D force feedback.
RESULTS: The median medio-lateral diameter of 4.4 mm (range: 1.2-7.9 mm) for MUs detected by HDsEMG did not differ significantly (Mann-Whitney-U test, p = 0.805) from that of 3.9 mm (0.6-8.6 mm) for MUs detected by fine-wire EMG. For individual subjects, the medio-lateral diameters of all HDsEMG-detected MUs spanned 70.5% (19.2-75.1%) of the masseter's thickness.
CONCLUSIONS: HDsEMG is able to examine small and large MUs from a great masseter proportion in one single measurement.
SIGNIFICANCE: Clinical application of HDsEMG might contribute to a better understanding of neuromuscular adaptations in patients with temporomandibular disorders (TMD) and could allow for monitoring treatment effects.

PMID: 30708279 [PubMed - as supplied by publisher]

from A via a.sfakia on Inoreader http://bit.ly/2SqtxGc

Altered lipid metabolism in post-traumatic epileptic rat model: one proposed pathway.

Related Articles

Altered lipid metabolism in post-traumatic epileptic rat model: one proposed pathway.

Mol Biol Rep. 2019 Jan 31;:

Authors: Srivastava NK, Mukherjee S, Sharma R, Das J, Sharma R, Kumar V, Sinha N, Sharma D

Abstract
Post-traumatic epilepsy (PTE) is a common long-term risk associated with traumatic brain injury (TBI). PTE rat model, proposed by Willmore et al., is a well known model that mimics human PTE. The present study explored the lipid metabolism in this PTE rat model by using in vitro, high-resolution NMR (nuclear magnetic resonance) spectroscopy and lipid staining based investigations. The level of gene expression, cytokines and enzyme activity was estimated. Level of TG (triglycerides), PL (phospholipids) and CHOL (cholesterol) was found to increase in brain tissue of PTE rats. This is an indication of the altered lipid metabolism in PTE rats. Level of lipid peroxidation and cytokines was enhanced in the brain tissue of PTE rats. A positive correlation was also observed in cytokines vs. lipid peroxidation. These results make available the evidence of the oxidative stress induced damage or destruction of the lipid components and also the cause of the inflammatory events in PTE rats. Antioxidant enzyme activity and respective gene expression were found to increase in brain tissue of PTE rats. A positive correlation was also observed in antioxidant enzyme's activity vs. respective enzyme gene expression and lipid peroxidation vs. activity of antioxidant enzymes. Such outcomes reflect the oxidative stress induced lipid damage responsible for production enhancement of antioxidant enzymes, which further responsible for enhancing the activity of antioxidant enzymes. A positive correlation was observed in lipid peroxidation vs. lipid components (TG, PL and CHOL) and provides the confirmatory verification of alteration in the level of lipid components. A negative correlation was observed in the level of cytokines and the quantity of TG. This showed that TG is consumed in the production of cytokines. MUA (Motor unit activity) is highly correlated with the level of LP and indicated that oxidative stress is responsible for the event of epileptogenesis. Positive correlation of MUA with RA (rearing activity) and MWM (Morris-water maze) showed that epileptogenesis also influences the memory of PTE rats. Overall results based analyses clearly indicate that the inflammatory activity and oxidative stress in brain tissue of PTE rats, which are responsible to establish a significant change in the lipid metabolism. This can be visualized through a well constructed possible pathway of altered lipid metabolism. This study will improve our understanding and approach in the field of epilepsy that need to be considered for the development of new drugs or therapy for patients with PTE. Representation of the proposed pathway of altered lipid metabolism in posttraumatic epileptic rats.

PMID: 30706359 [PubMed - as supplied by publisher]

from A via a.sfakia on Inoreader http://bit.ly/2GgqABQ

Adult-onset Rasmussen's Syndrome with associated cortical dysplasia.

Related Articles

Adult-onset Rasmussen's Syndrome with associated cortical dysplasia.

Epilepsy Behav Case Rep. 2019;11:54-57

Authors: Szabó CÁ, Garvin R, Hafeez S, Seifi A, Leary L, Bhavaraju-Sanka R, Henry JM, Papanastassiou AM

Abstract
We describe a 23-year-old woman with previous right temporal lobe surgeries for underlying cortical dysplasia, presenting with drug-resistant right hemispheric seizures and epilepsia partialis continua (EPC). After anti-seizure medication adjustments, she developed focal status epilepticus with progressive EEG and neuroimaging changes. Cerebrospinal fluid and serum autoimmune panels were negative except for an elevated serum acetylcholine-receptor antibody titer, but she underwent immunosuppressive therapy. Stereotactic-EEG evaluation demonstrated multifocal independent ictal patterns in the right hemisphere. Rasmussen's Syndrome was confirmed by brain biopsy, and a hemispherectomy was performed. This patient demonstrates the rare association of adult-onset EPC with cortical dysplasia, precipitously evolving into Rasmussen's Syndrome.

PMID: 30705820 [PubMed]

from A via a.sfakia on Inoreader http://bit.ly/2SklVFw

Are there mortality risks for patients with epilepsy who use cannabis treatments as monotherapy?

Related Articles

Are there mortality risks for patients with epilepsy who use cannabis treatments as monotherapy?

Epilepsy Behav Case Rep. 2019;11:52-53

Authors: Kollmyer DM, Wright KE, Warner NM, Doherty MJ

Abstract
Mortality associated with cannabis used for treatment of epilepsy is not well documented. We discuss two fatalities in the setting of epilepsy and self-determined therapy with cannabis (SDTC). One patient had probable sudden unexpected death in epilepsy, the second death was due to seizure-associated drowning. Both directed SDTC over conventional anti-seizure medications. Where recreational cannabis is legal, decisions to use cannabis are often self-directed and independent of physician advice of cannabis risks, in part because physicians may not be aware of the risk of SDTC. Further study of morbidity and mortality of SDTC in patients with epilepsy is needed.

PMID: 30705819 [PubMed]

from A via a.sfakia on Inoreader http://bit.ly/2D4k6me

Correction: Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia.

Related Articles

Correction: Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia.

Mol Psychiatry. 2019 Jan 31;:

Authors: Sønderby IE, Gústafsson Ó, Doan NT, Hibar DP, Martin-Brevet S, Abdellaoui A, Ames D, Amunts K, Andersson M, Armstrong NJ, Bernard M, Blackburn N, Blangero J, Boomsma DI, Bralten J, Brattbak HR, Brodaty H, Brouwer RM, Bülow R, Calhoun V, Caspers S, Cavalleri G, Chen CH, Cichon S, Ciufolini S, Corvin A, Crespo-Facorro B, Curran JE, Dale AM, Dalvie S, Dazzan P, de Geus EJC, de Zubicaray GI, de Zwarte SMC, Delanty N, den Braber A, Desrivières S, Donohoe G, Draganski B, Ehrlich S, Espeseth T, Fisher SE, Franke B, Frouin V, Fukunaga M, Gareau T, Glahn DC, Grabe H, Groenewold NA, Haavik J, Håberg A, Hashimoto R, Hehir-Kwa JY, Heinz A, Hillegers MHJ, Hoffmann P, Holleran L, Hottenga JJ, Hulshoff HE, Ikeda M, Jahanshad N, Jernigan T, Jockwitz C, Johansson S, Jonsdottir GA, Jönsson EG, Kahn R, Kaufmann T, Kelly S, Kikuchi M, Knowles EEM, Kolskår KK, Kwok JB, Hellard SL, Leu C, Liu J, Lundervold AJ, Lundervold A, Martin NG, Mather K, Mathias SR, McCormack M, McMahon KL, McRae A, Milaneschi Y, Moreau C, Morris D, Mothersill D, Mühleisen TW, Murray R, Nordvik JE, Nyberg L, Olde Loohuis LM, Ophoff R, Paus T, Pausova Z, Penninx B, Peralta JM, Pike B, Prieto C, Pudas S, Quinlan E, Quintana DS, Reinbold CS, Marques TR, Reymond A, Richard G, Rodriguez-Herreros B, Roiz-Santiañez R, Rokicki J, Rucker J, Sachdev P, Sanders AM, Sando SB, Schmaal L, Schofield PR, Schork AJ, Schumann G, Shin J, Shumskaya E, Sisodiya S, Steen VM, Stein DJ, Steinberg S, Strike L, Teumer A, Thalamuthu A, Tordesillas-Gutierrez D, Turner J, Ueland T, Uhlmann A, Ulfarsson MO, van 't Ent D, van der Meer D, van Haren NEM, Vaskinn A, Vassos E, Walters GB, Wang Y, Wen W, Whelan CD, Wittfeld K, Wright M, Yamamori H, Zayats T, Agartz I, Westlye LT, Jacquemont S, Djurovic S, Stefánsson H, Stefánsson K, Thompson P, Andreassen OA, 16p11.2 European Consortium, for the ENIGMA-CNV working group

Abstract
Prior to and following the publication of this article the authors noted that the complete list of authors was not included in the main article and was only present in Supplementary Table 1. The author list in the original article has now been updated to include all authors, and Supplementary Table 1 has been removed. All other supplementary files have now been updated accordingly. Furthermore, in Table 1 of this Article, the replication cohort for the row Close relative in data set, n (%) was incorrect. All values have now been corrected to 0(0%). The publishers would like to apologise for this error and the inconvenience it may have caused.

PMID: 30705424 [PubMed - as supplied by publisher]

from A via a.sfakia on Inoreader http://bit.ly/2GkDPBE

Leukocyte expression profiles reveal gene sets with prognostic value for seizure-free outcome following stereotactic laser amygdalohippocampotomy.

Related Articles

Leukocyte expression profiles reveal gene sets with prognostic value for seizure-free outcome following stereotactic laser amygdalohippocampotomy.

Sci Rep. 2019 Jan 31;9(1):1086

Authors: Sprissler R, Bina R, Kasoff W, Witte MH, Bernas M, Walter C, Labiner DM, Lau B, Hammer MF, Weinand ME

Abstract
Among patients with intractable epilepsy, the most commonly performed surgical procedure is craniotomy for amygdalohippocampectomy (AH). Stereotactic laser amygdalohippocampotomy (SLAH) has also been recently employed as a minimally invasive treatment for intractable temporal lobe epilepsy (TLE). Among patients treated with AH and SLAH approximately 65% and 54% of patients become seizure-free, respectively. Therefore, selection criteria for surgical candidates with improved prognostic value for post-operative seizure-free outcome are greatly needed. In this study, we perform RNA sequencing (RNA-Seq) on whole blood leukocyte samples taken from 16 patients with intractable TLE prior to SLAH to test the hypothesis that pre-operative leukocyte RNA expression profiles are prognostic for post-operative seizure outcome. Multidimensional scaling analysis of the RNA expression data indicated separate clustering of patients with seizure free (SF) and non-seizure-free (NSF) outcomes. Differential expression (DE) analysis performed on SF versus NSF groups revealed 24 significantly differentially expressed genes (≥2.0-fold change, p-value < 0.05, FDR <0.05). Network and pathway analyses identified differential activation of pathways involved in lipid metabolism, morphology of oligodendrocytes, inflammatory response, and development of astrocytes. These results suggest that pre-operative leukocyte expression profiles have prognostic value for seizure outcome following SLAH.

PMID: 30705324 [PubMed - in process]

from A via a.sfakia on Inoreader http://bit.ly/2SmkbeB

Seizures and Epilepsy.

Related Articles

Seizures and Epilepsy.

Med Clin North Am. 2019 Mar;103(2):309-324

Authors: Johnson EL

Abstract
Epilepsy affects 65 million people worldwide, and is a leading neurologic cause of loss of quality-adjusted life years. The diagnosis of seizures and epilepsy often depends on a careful history, and is supported with electroencephalogram and imaging. First-line treatment of epilepsy includes medical management. Antiepileptic drugs must be chosen with the patient's particular comorbidities in mind. Drug-resistant epilepsy cases should be referred to an epilepsy specialist and may be evaluated for additional medications, epilepsy surgery, neurostimulation, or dietary therapy. When caring for women, providers must take into account needs for contraception or pregnancy safety where applicable.

PMID: 30704683 [PubMed - in process]

from A via a.sfakia on Inoreader http://bit.ly/2GjCjzw

The impact of epilepsy surgery on the structural connectome and its relation to outcome.

Related Articles

The impact of epilepsy surgery on the structural connectome and its relation to outcome.

Neuroimage Clin. 2018;18:202-214

Authors: Taylor PN, Sinha N, Wang Y, Vos SB, de Tisi J, Miserocchi A, McEvoy AW, Winston GP, Duncan JS

Abstract
Background: Temporal lobe surgical resection brings seizure remission in up to 80% of patients, with long-term complete seizure freedom in 41%. However, it is unclear how surgery impacts on the structural white matter network, and how the network changes relate to seizure outcome.
Methods: We used white matter fibre tractography on preoperative diffusion MRI to generate a structural white matter network, and postoperative T1-weighted MRI to retrospectively infer the impact of surgical resection on this network. We then applied graph theory and machine learning to investigate the properties of change between the preoperative and predicted postoperative networks.
Results: Temporal lobe surgery had a modest impact on global network efficiency, despite the disruption caused. This was due to alternative shortest paths in the network leading to widespread increases in betweenness centrality post-surgery. Measurements of network change could retrospectively predict seizure outcomes with 79% accuracy and 65% specificity, which is twice as high as the empirical distribution. Fifteen connections which changed due to surgery were identified as useful for prediction of outcome, eight of which connected to the ipsilateral temporal pole.
Conclusion: Our results suggest that the use of network change metrics may have clinical value for predicting seizure outcome. This approach could be used to prospectively predict outcomes given a suggested resection mask using preoperative data only.

PMID: 29876245 [PubMed - indexed for MEDLINE]

from A via a.sfakia on Inoreader http://bit.ly/2Sifgvt

Association between HLA-B*15:02 and oxcarbazepine-induced cutaneous adverse reaction: a meta-analysis.

Related Articles

Association between HLA-B*15:02 and oxcarbazepine-induced cutaneous adverse reaction: a meta-analysis.

Pharmacogenomics. 2018 04;19(6):547-552

Authors: Liu Y, Yu Y, Nie X, Zhao L, Wang X

Abstract
AIM: HLA-B*15:02 has been demonstrated as a key risk factor for carbamazepine-induced severe cutaneous adverse reaction (sCAR), especially in Asian population. Oxcarbazepine (OXC) is a drug that has a similar structure of carbamazepine. However, the relationship between HLA-B*15:02 and induced cutaneous adverse reaction (cADR) remains unknown. This study aims to analyze this association in the published literature.
METHOD: After filtering studies, eight studies were finally included for meta-analysis, including 32 sCAR cases, 112 mild cutaneous adverse reaction (mcADR) cases, 281 OXC tolerant control and 946 population control cases.
RESULT: In the tolerant control group, an association was found between HLA-B*15:02 genotype and OXC-induced sCAR (odds ratio [OR]: 18.13; 95% CI: 6.77-48.56), but not in mcADR (OR: 1.43; 95% CI: 0.56-3.64). In population control group, an association was found between HLA-B*15:02 genotype and OXC-induced sCAR, (OR: 8.22; 95% CI: 3.03-22.34), but not in mcADR (OR: 2.06; 95% CI: 0.91-4.67).
DISCUSSION: Our study demonstrates that the genetic risk factor HLA-B*15:02 may be a factor in OXC-induced sCAR.

PMID: 29629814 [PubMed - indexed for MEDLINE]

from A via a.sfakia on Inoreader http://bit.ly/2GhwOBr

Conflict monitoring mechanism at the single-neuron level in the human ventral anterior cingulate cortex.

Related Articles

Conflict monitoring mechanism at the single-neuron level in the human ventral anterior cingulate cortex.

Neuroimage. 2018 07 15;175:45-55

Authors: Shapira-Lichter I, Strauss I, Oren N, Gazit T, Sammartino F, Giacobbe P, Kennedy S, Hutchison WD, Fried I, Hendler T, Lozano AM

Abstract
Life requires monitoring and adjusting behavior in the face of conflicts. The conflict monitoring theory implicates the anterior cingulate cortex (ACC) in these processes; its ventral aspect (vACC) specializes in emotional conflict. To elucidate the underpinning neural mechanism, we recorded vACC extracellular activity from 12 patients with mood disorders or epilepsy who performed the face-emotional Stroop task. Behaviorally, both conflict detection and adaptation to conflict were evident. The firing rate of neurons in the vACC represented current conflict, i.e., current-congruency. The late onset of the effect is compatible with a role in monitoring. Additionally, early responses of some neurons represented the immediate history of conflicts, i.e., previous-trial-congruency. Finally, in some neurons the response to the current-trial was modulated by previous-trial-congruency, laying the ground for adjusting-to-conflicts. Our results uncover a single neuron level mechanism in the vACC that encodes and integrates past and present emotional conflicts, allowing humans to accommodate their responses accordingly.

PMID: 29551460 [PubMed - indexed for MEDLINE]

from A via a.sfakia on Inoreader http://bit.ly/2Gk9WB6

The effect of a modular education program for children with epilepsy and their parents on disease management.

Related Articles

The effect of a modular education program for children with epilepsy and their parents on disease management.

Epilepsy Behav. 2018 01;78:210-218

Authors: Turan Gürhopur FD, Işler Dalgiç A

Abstract
OBJECTIVE: The objective of this study was to evaluate the efficacy of Modular Education Program for Children with Epilepsy and Their Parents on disease management. The program was prepared by researchers in an interdisciplinary team.
METHOD: Children with epilepsy and their parents were included in a randomized controlled study using a pre-posttest design. All participants of the modular education program (n=184 (92 children and their 92 parents')) answered a lot of scales immediately before the program. The researcher presented the modular education program, which included eight modules (four for the children and four for the parents), to the children and parents in the intervention group using interactive teaching methods. And all participants of the modular education program answered all scales immediately after the program and one-month, three-month follow-ups. The control group not participating in the modular education program (n=100 (50 children, 50 parents)) also answered all scales in all follow-ups. Scales used the study comprised epilepsy-specific outcome measures (e.g., knowledge, self-efficacy related to seizures, quality of life and anxiety). The statistical analyses of the study data were performed using SAS 9.3 software.
RESULTS: Children in intervention group significantly improved in knowledge (p<0.001), self-efficacy about seizures (p<0.001), and quality of life (p<0.001) compared with the control group. The parents in the intervention group also significantly improved in knowledge about epilepsy (p<0.001) compared with the control group. However, anxiety of the parents in the intervention group significantly increased (p<0.001).
CONCLUSION: The efficacy of the Modular Education Program for Children with Epilepsy and Their Parents on disease management was confirmed. The results indicate that using interactive teaching methods help children with epilepsy and their parents in improving knowledge, self-efficacy about seizures and quality of life. All health professionals who work with children with epilepsy and their parents should provide these modular education programs regularly.

PMID: 29203274 [PubMed - indexed for MEDLINE]

from A via a.sfakia on Inoreader http://bit.ly/2Snv3ZP

Seizure care in the emergency department. Identifying and bridging the gaps. A study of care and outcomes from 644 seizure presentations.

Related Articles

Seizure care in the emergency department. Identifying and bridging the gaps. A study of care and outcomes from 644 seizure presentations.

Epilepsy Behav. 2018 01;78:226-231

Authors: Williams J, Doherty J, Di Blasi C, Mabarak D, Kennedy U, Doherty CP

Abstract
Care for seizures in an emergency department setting can be variable, and there are disparities in access to onward specialist referral. The purpose of this study was to evaluate the utilization and implementation of an evidence-based seizure care pathway in a busy urban tertiary referral center. A total of 644 seizure presentations over two time points were examined. Initial pathway utilization rates were low at 26.2% but increased to 61.6% after environmental barriers had been addressed. We found that patients placed on the care pathway had higher rates of neurological examination, documentation of safety and legal guidelines as regards driving, and lower rates of seizure readmission. Twelve patients not placed on the pathway had passed away at follow-up (1.86%); the cause of death were related to significant comorbidities rather than the seizures themselves though in five, seizures could potentially have been a contributing factor. For the first time we have demonstrated that an evidence-based guideline for seizure management can be implemented in Ireland and used to standardize care for seizures in the emergency department improving documentation rates and clinical evaluation.

PMID: 29129567 [PubMed - indexed for MEDLINE]

from A via a.sfakia on Inoreader http://bit.ly/2Gikwsp

Red flags in epilepsy surgery: Identifying the patients who pay a high cognitive price for an unsuccessful surgical outcome.

Related Articles

Red flags in epilepsy surgery: Identifying the patients who pay a high cognitive price for an unsuccessful surgical outcome.

Epilepsy Behav. 2018 01;78:269-272

Authors: Baxendale S, Thompson P

Abstract
Preoperative estimates of cognitive and seizure outcome must be as accurate as possible if the candidate is to make an informed decision about epilepsy surgery. Significant declines in memory function are reported in approximately 30% of temporal lobe surgery patients. The percentage varies according to the ways in which a postoperative deterioration is defined but since the majority of outcome studies do not take into account the patient's capacity to deteriorate if they are functioning at or close to the floor of a memory test prior to surgery, the published percentages may be an underrepresentation of the true extent of memory decline following epilepsy surgery. We examined the cognitive 'cost' of epilepsy surgery in a consecutive series of 474 patients who underwent elective surgery for medically intractable epilepsy. All patients underwent a presurgical assessment prior to and 1year after the surgery. Reliable change indices were used to identify significant postoperative memory decline. Postoperative outcome was dichotomized using the ILAE 2008 classification. All patients in class one were classified as seizure-free (67.5% of the sample). Excluding patients already functioning at or below the 2nd percentile on standardized memory tests, 37.8% experienced a significant postoperative decline in memory function. Twelve percent experienced the 'double hit' of significant postoperative memory decline and ongoing seizures following surgery. Patients with pathologies other than hippocampal sclerosis and with signs of limited cognitive reserve, both in terms of memory function and overall intellectual ability were most likely to suffer a double hit. Our results indicate that caution should be exercised when operating on these patients and preoperative counseling should be tailored to reflect the likely risk/benefit ratio of a temporal lobe resection for medically intractable epilepsy in this group.

PMID: 29117924 [PubMed - indexed for MEDLINE]

from A via a.sfakia on Inoreader http://bit.ly/2SfFrTB

Development and content validation of a preliminary core set of patient- and caregiver-relevant outcomes for inclusion in a potential composite endpoint for Dravet Syndrome.

Related Articles

Development and content validation of a preliminary core set of patient- and caregiver-relevant outcomes for inclusion in a potential composite endpoint for Dravet Syndrome.

Epilepsy Behav. 2018 01;78:232-242

Authors: Nabbout R, Auvin S, Chiron C, Irwin J, Mistry A, Bonner N, Williamson N, Bennett B

Abstract
BACKGROUND: Dravet Syndrome (DS) is a rare developmental and epileptic encephalopathy characterized by multiple seizures, frequently prolonged and treatment refractory, with significant developmental disabilities and behavioral and psychiatric disorders. Patients with DS require intensive support and supervision from a caregiver, impacting significantly on both patients' and caregivers' lives. This study aimed to identify core concepts to measure the impact on both patients and caregivers in future DS clinical trials.
METHODS: Qualitative concept elicitation interviews were conducted with caregivers and healthcare professionals involved in caring for children with DS (aged 2-18years) in France to identify important concepts related to the global impact of DS. Interviews explored a range of concepts, including triggers, symptoms, impacts, and coping strategies, from which a conceptual model was developed. A Delphi consensus panel with eight international clinical experts aimed to identify important and relevant endpoints.
RESULTS: Seizure was the most commonly reported symptom with DS further impacting children's cognitive and behavioral functioning. Caregivers identified impact concepts not reported by healthcare professionals. Both groups described additional impacts on wider family members and home modifications. Clinical experts agreed on the inclusion of five patient- and caregiver-relevant concepts for measurement in future DS clinical trials in a composite endpoint. The five concepts for inclusion were; seizures, expressive communication of the child, receptive communication of the child, impact on daily activities, and social functioning of the caregiver.
CONCLUSIONS: This study showed the wider potential impact of DS to extend beyond that of seizures, demonstrating that there is a need for additional patient- and caregiver-relevant concepts to be measured in clinical trials to fully identify the value of therapeutic interventions.

PMID: 29108913 [PubMed - indexed for MEDLINE]

from A via a.sfakia on Inoreader http://bit.ly/2GjFlUh

What is changing when: Decoding visual information in movies from human intracranial recordings.

Related Articles

What is changing when: Decoding visual information in movies from human intracranial recordings.

Neuroimage. 2018 10 15;180(Pt A):147-159

Authors: Isik L, Singer J, Madsen JR, Kanwisher N, Kreiman G

Abstract
The majority of visual recognition studies have focused on the neural responses to repeated presentations of static stimuli with abrupt and well-defined onset and offset times. In contrast, natural vision involves unique renderings of visual inputs that are continuously changing without explicitly defined temporal transitions. Here we considered commercial movies as a coarse proxy to natural vision. We recorded intracranial field potential signals from 1,284 electrodes implanted in 15 patients with epilepsy while the subjects passively viewed commercial movies. We could rapidly detect large changes in the visual inputs within approximately 100 ms of their occurrence, using exclusively field potential signals from ventral visual cortical areas including the inferior temporal gyrus and inferior occipital gyrus. Furthermore, we could decode the content of those visual changes even in a single movie presentation, generalizing across the wide range of transformations present in a movie. These results present a methodological framework for studying cognition during dynamic and natural vision.

PMID: 28823828 [PubMed - indexed for MEDLINE]

from A via a.sfakia on Inoreader http://bit.ly/2St3bnn

Managing Epilepsy in Pregnancy.

Related Articles

Managing Epilepsy in Pregnancy.

Ir Med J. 2017 Feb 10;110(2):510

Authors: O'Dwyer V

PMID: 28657255 [PubMed - indexed for MEDLINE]

from A via a.sfakia on Inoreader http://bit.ly/2u1zt9T

Phosphodiesterase Type 5 (PDE5) Inhibitors Sensitize Topoisomerase II Inhibitors in Killing Prostate Cancer Through PDE5-Independent Impairment of HR and NHEJ DNA Repair Systems.

Related Articles

Phosphodiesterase Type 5 (PDE5) Inhibitors Sensitize Topoisomerase II Inhibitors in Killing Prostate Cancer Through PDE5-Independent Impairment of HR and NHEJ DNA Repair Systems.

Front Oncol. 2018;8:681

Authors: Chang JF, Hsu JL, Sheng YH, Leu WJ, Yu CC, Chan SH, Chan ML, Hsu LC, Liu SP, Guh JH

Abstract
Human castration-resistant prostate cancer (CRPC) is a significant target of clinical research. The use of DNA-damaging agents has a long history in cancer chemotherapy but is limited by their toxicities. The combination with a safer drug can be a strategy in reducing dosage and toxicity while increasing anticancer activity in CRPC treatment. Phosphodiesterase type 5 (PDE5) inhibitors are used to treat erectile dysfunction through the selective inhibition of PDE5 that is responsible for cGMP degradation in the corpus cavernosum. Several studies have reported that PDE5 inhibitors display protective effect against doxorubicin-induced cardiotoxicity. The combinatory treatment of CRPC with doxorubicin and PDE5 inhibitors has been studied accordingly. The data demonstrated that sildenafil or vardenafil (two structure-related PDE5 inhibitors) but not tadalafil (structure-unrelated to sildenafil) sensitized doxorubicin-induced apoptosis in CRPC cells with deteriorating the down-regulation of anti-apoptotic Bcl-2 family members, including Bcl-xL and Mcl-1, and amplifying caspase activation. Homologous recombination (HR) and non-homologous end joining (NHEJ) DNA repair systems were inhibited in the apoptotic sensitization through detection of nuclear foci formation of Rad51 and DNA end-binding of Ku80. PDE5 knockdown to mimic the exposure to PDE5 inhibitors did not reproduce apoptotic sensitization, suggesting a PDE5-independent mechanism. Not only doxorubicin, sildenafil combined with other inhibitors of topoisomerase II but not topoisomerase I also triggered apoptotic sensitization. In conclusion, the data suggest that sildenafil and vardenafil induce PDE5-independent apoptotic sensitization to doxorubicin (or other topoisomerase II inhibitors) through impairment of both HR and NHEJ repair systems that are evident by a decrease of nuclear Rad51 levels and their foci formation in the nucleus, and an inhibition of Ku80 DNA end-binding capability. The combinatory treatment may enable an important strategy for anti-CRPC development.

PMID: 30705876 [PubMed]

from A via a.sfakia on Inoreader http://bit.ly/2HNZOmK

Clinical Utilization Pattern of Liquid Biopsies (LB) to Detect Actionable Driver Mutations, Guide Treatment Decisions and Monitor Disease Burden During Treatment of 33 Metastatic Colorectal Cancer (mCRC) Patients (pts) at a Fox Chase Cancer Center GI Oncology Subspecialty Clinic.

Related Articles

Clinical Utilization Pattern of Liquid Biopsies (LB) to Detect Actionable Driver Mutations, Guide Treatment Decisions and Monitor Disease Burden During Treatment of 33 Metastatic Colorectal Cancer (mCRC) Patients (pts) at a Fox Chase Cancer Center GI Oncology Subspecialty Clinic.

Front Oncol. 2018;8:652

Authors: Ghatalia P, Smith CH, Winer A, Gou J, Kiedrowski LA, Slifker M, Saltzberg PD, Bubes N, Anari FM, Kasireddy V, Varshavsky A, Liu Y, Ross EA, El-Deiry WS

Abstract
Background: Liquid biopsy (LB) captures dynamic genomic alterations (alts) across metastatic colorectal cancer (mCRC) therapy and may complement tissue biopsy (TB). We sought to describe the utility of LB and better understand mCRC biology during therapy. Methods: Thirty-three patients (pts) with mCRC underwent LB. We used permutation-based t-tests to assess associations between alts, and clinical variables and used Kendall's tau to measure correlations. Results: Of 33 pts, 15 were women; 22 had colon, and the rest rectal cancer. Pts received a median of two lines of therapy before LB. Nineteen pts had limited testing on TB (RAS/RAF/TP53/APC), 11 extended NGS, and 3 no TB. Maxpct and alts correlated with CEA (p < 0.001, respectively). In 3/5 pts with serial LB, CEA correlated with maxpct trend, and CT tumor burden. In 6 pts, mutant RAS was seen in LB and not TB; 5/6 had received anti-EGFR therapy prior to LB, suggesting RAS alts developed post-therapy. In two pts RAS-mutated by TB, no RAS alts were detected on LB; these pts had low disease burden on CT at time of LB that also did not reveal APC or TP53 alts. In six patients who were KRAS wt based on TB, post anti-EGFR LB revealed subclonal KRAS mutations, likely a treatment effect. The median number of alts was higher post anti-EGFR LB (n = 12) vs. anti-EGFR naïve LB (n = 22) (9.5 vs. 5.5, p = 0.059) but not statistically significant. More alts were also noted in post anti-EGFR therapy LB vs. KRAS wt anti-EGFR-naïve LB (n = 6) (9.5 vs. 5) among patients with KRAS wild-type tumors, although the difference was not significant (p = 0.182). Conclusions: LB across mCRC therapy detects driver mutations, monitors disease burden, and identifies sub-clonal alts that reflect drug resistance, tumor evolution, and heterogeneity. Interpretation of LB results is impacted by clinical context.

PMID: 30705875 [PubMed]

from A via a.sfakia on Inoreader http://bit.ly/2D3zZtm