Αρχειοθήκη ιστολογίου

Αναζήτηση αυτού του ιστολογίου

Παρασκευή 26 Οκτωβρίου 2018

Window Studies in Squamous Cell Carcinoma of the Head and Neck: Values and Limits

Opinion statement

In head and neck cancer, we continue to work towards a more personalized approach to treatment of patients, where analysis of a patient's tumor guides targeting of molecular or immunologic pathways. Critically important to this pursuit is a better understanding of the direct biologic effect of a drug or combination on the tumor microenvironment in humans, as well as biomarker discovery. These goals are consistent with the primary purpose of a "window of opportunity" trial and while conduct of these trials requires a careful balance of benefits and potential risks, to date these trials have been both feasible and safe in HNSCC in the curative intent setting. In the era of immunotherapy, with countless possible combinations and ongoing clinical trials, window trials are even more important for informing clinical trial design and appropriate combination therapy, and ultimately a more personalized approach to our patients that leads to improvement in outcomes.



https://ift.tt/2PpOrUF

Current Management and Recent Advances in the Treatment of Chronic Myelomonocytic Leukemia

Opinion statement

Chronic myelomonocytic leukemia (CMML) is an aggressive myeloid neoplasm in which treatment strategies with the capacity to improve survival are currently lacking. Clinical features are heterogeneous and although the overall prognosis is poor, survival can vary significantly between individuals. This reflects the need for an individualized treatment approach which incorporates accurate risk stratification. Though numerous prognostic scores exist, newer CMML-specific models incorporating molecular data should be favored. While asymptomatic, low-risk patients should be observed until their disease progresses, the majority of patients will require treatment. Due to a deficiency in treatments with disease-modifying capacity, any patient who requires treatment should be considered for enrollment in clinical trials evaluating novel therapeutic approaches. Allogeneic stem cell transplant (allo-SCT) remains the only current therapy with the potential to cure the disease and should be considered in most patients with intermediate- to high-risk disease. However, substantial risks are involved and, in part, because of advanced age at diagnosis, a minority of patients are candidates. Hypomethylating agents (HMAs) have become a preferred treatment approach, and should be used in those with cytopenias. Patients presenting with proliferative features can be treated with hydroxyurea to manage their symptoms and control leukocytosis, though HMAs can be incorporated as well, particularly in patients with higher risk disease. HMAs should also be considered in patients with a high burden of disease prior to proceeding with allo-SCT. Induction chemotherapy should be reserved for younger, healthy patients who have transformed to acute myeloid leukemia to induce remission prior to transplant. Supportive care utilizing transfusion support, erythropoiesis-stimulating agents, and infection prevention measures should be incorporated into the care of all patients.



https://ift.tt/2JiBSVC

The Effects of High Altitude on Glucose Homeostasis, Metabolic Control, and Other Diabetes-Related Parameters: From Animal Studies to Real Life

High Altitude Medicine &Biology, Ahead of Print.


https://ift.tt/2O8HxP1

Anticipatory and compensatory postural adjustments in response to loading perturbation of unknown magnitude

Abstract

In response to sudden postural perturbations, the posture control system uses anticipatory and compensatory postural adjustments (APAs and CPAs) to maintain balance and equilibrium. APAs strengthen as the perturbation magnitude increases, while CPAs remain constant because APAs make the necessary adjustments. However, the magnitude of a postural perturbation cannot always be fully known. This research focused on postural adjustments in response to perturbations with unknown magnitude. Participants caught falling sandbags of three weights on a tray held in their hands. Participants were told about the weight used for the upcoming trial in the KNOWN condition and not told in the UNKNOWN condition. Surface electromyography (sEMG) of the lumbar muscles and displacement of the center of pressure (COP) were recorded synchronously. The results showed that APAs and CPAs were stronger in the UNKNOWN condition than in the KNOWN condition. Meanwhile, in the UNKNOWN condition, the activity of the lumbar muscles and displacements of the COP showed no difference between weight levels. The lumbar erector spinae (LES) and lumbar multifidus (LMF) activated earlier in the UNKNOWN condition than for the heaviest weight in the KNOWN condition. The outcome of this study indicates that APAs and CPAs of lumbar muscles and displacements of the COP are affected by the knowledge of postural perturbations. The central nervous system (CNS) coped with load perturbations of unknown magnitude with redundancy response strategy, based on the maximum assumption of perturbation magnitude.



https://ift.tt/2PZBTjZ

Effect of a high-fat meal on the relative bioavailability of H3B-6527, a novel FGFR4 inhibitor, in healthy volunteers

Abstract

Purpose

This Phase I study estimated the effect of a high-fat meal on the pharmacokinetics (PK) of H3B-6527, a covalent inhibitor of the fibroblast growth factor receptor (FGFR) 4 in clinical development for hepatocellular carcinoma and intrahepatic cholangiocarcinoma.

Methods

In this randomized, single center, single-dose, open-label, 2-period crossover study 12 healthy male volunteers, aged 18–55 years old, received a single 200-mg dose of H3B-6527 (capsule) following an overnight fast or a high-fat breakfast. PK samples were collected serially up to 36 h postdose. H3B-6527 concentrations were measured using a validated high-performance liquid chromatography tandem mass spectrometry method. PK data were analyzed using a noncompartmental approach based on a mixed-effects model. The safety and tolerability of H3B-6527 were also assessed.

Results

H3B-6527 plasma exposure increased after a high-fat meal with fed/fasted ratios of the geometric means (90% confidence interval) of 174% (102–298%) for Cmax and 246% (146–415%) for AUC0–t. Food delayed and prolonged absorption of H3B-6527, with a fed/fasted ratio for tmax of 200% (137–263%). PK variability was lower under the fed condition, as illustrated by the CV% for Cmax and AUC0–t of 41.9–54.5% (fed) versus 64.3–70.4% (fasted).

Conclusions

A single 200 mg dose of H3B-6527 was safe and generally well tolerated when administered to healthy adult males. A high-fat meal significantly increased exposure to H3B-6527, from 1.5- to 2.5-fold in the systemic circulation, compared to administration under fasted conditions. Food delayed and prolonged absorption of H3B-6527. In general, lower inter-subject variability was observed in the fed state in healthy volunteers.

Trial registration

ClinicalTrials.gov.: NCT03424577.



https://ift.tt/2D4LcfH

Integrating HIV care and treatment into tuberculosis clinics in Lusaka, Zambia: results from a before-after quasi-experimental study

Patients with HIV-associated tuberculosis (TB) often have their TB and HIV managed in separate vertical programs that offer care for each disease with little coordination. Such "siloed" approaches are associat...

https://ift.tt/2yFdutb

Clinical characteristics, organ failure, inflammatory markers and prediction of mortality in patients with community acquired bloodstream infection

Community acquired bloodstream infection (CABSI) in low- and middle income countries is associated with a high mortality. This study describes the clinical manifestations, laboratory findings and correlation o...

https://ift.tt/2O9sAMh

Prevalence, risk factors, and medical costs of Chlamydia trachomatis infections in Shandong Province, China: a population-based, cross-sectional study

A population-based study of Chlamydia trachomatis (CT) infections is essential in designing a specific control program; however, no large investigation of CT infections among the general population in mainland Ch...

https://ift.tt/2yAhOtI

Additional malignancies in patients with gastrointestinal stromal tumors (GIST): incidence, pathology and prognosis according to a time of occurrence-based classification

Abstract

Background

The aim of the study is to clarify if a classification based on the time of occurrence of associated malignancies in GIST patients can help in the understanding of the clinical controversies observed in these patients.

Methods

We retrospectively reviewed all the patients diagnosed with GIST tumors between January 1999 and October 2016. They were divided into GIST patients associated with other tumors (A-GIST) and those not associated (NA-GIST). A-GIST patients were also divided into four types according to the proposed classification.

Results

Of 104 GIST patients, 32 (30.7%) (A-GIST group) had at least one additional primary malignancy. The most frequent location of the associated malignancy was the GI tract (26%). Compared to NA-GIST, A-GIST were more often asymptomatic with a lower risk of recurrence. The main cause of death in NAGIST was GIST itself, being associated tumors the main cause of death in A-GIST group. No differences were found in DFS and OS between A-GIST and NA-GIST.

Conclusions

The use of the proposed classification classifies GIST patients with associated malignancies in different subtypes that differ substantially in terms of incidence, type of neoplasms associated, cause of the association and prognosis.



https://ift.tt/2O9sswh

Antigen-loaded dendritic cells triggers a specific cytotoxic T lymphocytes immune response against hepatocellular carcinoma: in vitro study

Abstract

Background

Hepatocellular carcinoma (HCC) is one of the common malignancies, characterized by poor response to conventional therapeutic options. Immunotherapy with dendritic cells (DCs)-vaccines is one of the most successful strategies used for the treatment of HCC. However, the methods applied in the preparation of antigen-loaded DCs are important factors for optimization of DCs vaccines.

Purpose

The present study was conducted to investigate the effect of HCC-whole tumor cell lysate prepared using rapid repetitive freeze–thaw cycles on the immunogenicity of DCs and evaluate the ability of whole tumor cell lysate-pulsed DCs vaccine to induce a specific cytotoxic T lymphocytes (CTLs) response against HepG2 cell line.

Methods

Immature DCs generated from peripheral blood monocytes were randomized into two groups: control DCs and whole tumor cell lysate-pulsed DCs. Phenotypic analysis of the DCs' cell maturation marker CD83 and co-stimulatory molecule CD86 was performed. HCC-specific cytotoxic activity of CD8+ CTLs was measured in vitro.

Results

Loading of DCs with necrotic whole cell lysate resulted in non-significant changes in DCs' expression of CD83, but a significant increase in expression of CD86. In addition, CD8+ CTLs stimulated with whole tumor cell lysate-pulsed DCs showed a high cytotoxic activity that specifically attack HepG2 cells.

Conclusion

Our findings indicated that pulsation of DCs with whole tumor cell lysate prepared by repetitive freeze–thaw cycles could efficiently enhance the ability of DCs to induce proliferation and clonal expansion of CD8+ CTLs. Data herein, also indicated that whole tumor cell lysate-pulsed DCs triggers a specific CD8+ CTLs against HCC tumor cells.



https://ift.tt/2yAK0fY

Inflammation-based prognostic scores in patients with extrahepatic bile duct lesions treated by percutaneous transhepatic biliary stenting combined with 125 I seeds intracavitary irradiation

Abstract

Purpose

This study aimed at investigating the efficacy of percutaneous transhepatic biliary stenting (PTBS) combined with 125I seeds intracavitary irradiation in the treatment of extrahepatic cholangiocarcinoma (EHC) and to preliminarily explore the prognostic values of inflammation-based scores in these patients.

Methods

A total of 113 clinically/pathologically diagnosed cases of EHC who received PTBS combined with 125I seeds implantation were retrospectively analyzed. The postoperative changes of clinical symptoms and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total serum bilirubin (TBIL), direct bilirubin (DBIL), and albumin (ALB) were observed. Preoperative clinical data were extracted to calculate inflammation-based scores, including systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelets-to-lymphocyte ratio (PLR). Kaplan–Meier survival curves and Cox regression analyses were used to evaluate the prognostic significance of inflammation-based scores.

Results

After operation, clinical symptoms such as jaundice and fever significantly improved in all patients. At 1 month and 3 months postoperatively, serum levels of ALT, AST, ALP, TBIL, and DBIL significantly reduced, and ALB significantly increased, compared with preoperative values. The median survival time of the patients was 12 months and the 1-year survival rate was 56.8%. Univariate analysis revealed that factors related to overall survival were CA19-9, TBIL, ALB, SII, and NLR. Multivariate analysis further identified SII and NLR as independent prognostic models.

Conclusion

The combination of PTBS and 125I seeds intracavitary irradiation is an effective palliative treatment for advanced EHC. Elevated SII and NLR can be used to predict poor survival.



https://ift.tt/2O9snIZ

ATLANTIS: a Phase III study of lurbinectedin/doxorubicin versus topotecan or cyclophosphamide/doxorubicin/vincristine in patients with small-cell lung cancer who have failed one prior platinum-containing line

Future Oncology, Ahead of Print.


https://ift.tt/2PoWeBV

Cost-Effectiveness of Herpes Zoster Vaccination: A Systematic Review

Abstract

Background

Herpes zoster (HZ) is one of the most common diseases among adults. Its reactivation is characterized by a severe and painful complication. In addition to the existing herpes zoster vaccine (ZVL), the FDA approved a new adjuvanted subunit zoster vaccine (RZV) in 2017 for use in adults aged 50 years and older. Several studies have assessed the cost-effectiveness of ZVL, many of which were conducted before the long-term vaccine  efficacy data was available in 2014.

Objective

Our objectives were to (i) summarize and compare the cost-effectiveness analyses (CEAs) of ZVL conducted before and after 2014, (ii) summarize the CEAs of RZV, and (iii) critically assess the cost-effectiveness models and identify key parameters to consider for future CEAs of RZV.

Methods

We searched PubMed and two other databases from inception to March 2018 for original cost-effectiveness, cost-utility, or cost-benefit analyses of HZ vaccines. Three investigators independently reviewed and assessed full-text articles after screening the titles and abstracts to determine eligibility. For all included studies, we assessed study quality using the Drummond and Jefferson's checklist and extracted study characteristics, model structure, vaccine characteristics, incidence of HZ and complications, incremental cost-effectiveness ratio, and sensitivity analyses. We summarized data by type of vaccine, year of publication, and funding sources.

Results

Twenty-seven studies met eligibility criteria. All studies were from high-income countries and were of moderate-to-high or high quality. Twenty studies repeatedly used four cost-effectiveness models. The assumption on long-term efficacy of ZVL was not based on clinical trial data in > 50% of studies. Fifteen out of 25 studies concluded that ZVL was cost-effective compared with no vaccine at a vaccine price ranging between US$93 and US$236 per dose (2018 US$), 40% of which were published after 2014. All industry-funded studies favored the use of ZVL. The single study assessing RZV found it to be more effective and less costly than ZVL, and cost-effective compared with no vaccination. More studies conducted after 2014 included various efficacy endpoints for ZVL, adverse reactions, and productivity loss compared with those conducted before 2014.

Conclusions

A majority of studies of ZVL found it to be cost-effective compared with no vaccine using the authors' chosen willingness-to-pay thresholds. RZV was dominant in the single study comparing the two vaccines, but the finding needs to be confirmed with further studies in different settings. Future studies should assume vaccine efficacy in line with clinical data, account for more efficacy endpoints for ZVL, and include other HZ long-term complications, vaccine adverse reactions, and productivity loss.



https://ift.tt/2SkCSwt

Does a Patient-Directed Financial Incentive Affect Patient Choices About Controller Medicines for Asthma? A Discrete Choice Experiment and Financial Impact Analysis

Abstract

Background

In Australia, many patients who are initiated on asthma controller inhalers receive combination inhaled corticosteroid/long-acting beta2-agonist (ICS/LABA) despite having asthma of sufficiently low severity that ICS-alone would be equally effective and less costly for the government.

Methods

We conducted a discrete choice experiment (DCE) in a nationally representative sample of adults (n = 792) and parents of children (n = 609) with asthma. Mixed multinomial models were estimated and calibrated to reflect the estimated market shares of ICS-alone, ICS/LABA and no controller. We then simulated the impact of varying patient co-payment on demand and the financial impact on government pharmaceutical expenditure.

Results

Preference for inhaler decreased with increasing costs to the patient or government, increasing chance of a repeat visit to the doctor, and if fewer symptoms were present. Adults preferred high-strength controllers, but parents preferred low-strength inhalers for children (general beneficiaries only). The DCE predicted a higher proportion choosing controller treatment (89%) compared to current levels (57%) at the current co-payment level, with proportionately higher uptake of ICS-alone and a lower average cost per patient [32.73 Australian dollars (AU$) c.f. AU$38.54]. Reducing the co-payment on ICS-alone by 50% would increase its market share to 50%, whilst completely removing the co-payment would only have a small marginal impact on market share, but increased average cost of treatment to the government to AU$41.04 per person.

Conclusions

Patient-directed financial incentives are unlikely to encourage much switching of medicines, and current levels of under-treatment are not explained by patient preferences. Interventions directed at prescribers are more likely to promote better use of asthma medicines.



https://ift.tt/2z5xjcw

"J BUON"[jour]; +55 new citations

55 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"J BUON"[jour]

These pubmed results were generated on 2018/10/26

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.



https://ift.tt/2ORxym5

A Multicenter Phase 2 Study of AMG 337 in Patients With MET-Amplified Gastric/Gastroesophageal Junction/Esophageal Adenocarcinoma and Other Solid Tumors

Purpose: MET gene amplification is associated with poor prognosis in gastric/gastroesophageal junction/esophageal (G/GEJ/E) cancers. We determined antitumor activity, safety, and pharmacokinetics of the small-molecule MET inhibitor AMG 337 in MET-amplified G/GEJ/E adenocarcinoma or other solid tumors. Experimental Design: In this phase 2, single-arm study, adults with MET-amplified G/GEJ/E adenocarcinoma (Cohort 1) or other MET-amplified solid tumors (Cohort 2) received AMG 337 300 mg/d orally in 28-day cycles. The primary endpoint was objective response rate (ORR; Cohort 1). Secondary endpoints included ORR (Cohort 2), progression-free survival (PFS), overall survival (OS), and safety. Results: Of 2101 patients screened for MET amplification, 132 were MET-amplified and 60 were enrolled: 45 in Cohort 1, and 15 in Cohort 2. Fifty-six patients (97%) had metastatic disease; 57 had prior lines of therapy (1 prior line, 29%; ≥ 2 prior lines, 69%). A protocol-permitted review showed efficacy that was lower-than-expected based on preliminary data from a first-in-human study, and enrollment was stopped. Fifty-eight patients received ≥1 AMG 337 dose. ORR in Cohort 1 was 18% (8 partial responses). No responses were observed in Cohort 2. Of 54 evaluable patients, median (95% CI) PFS and OS were 3.4 (2.2-5.0) and 7.9 (4.8-10.9) months, respectively. The most frequent adverse events (AEs) were headache (60%), nausea (38%), vomiting (38%), and abdominal pain, decreased appetite, and peripheral edema (33% each); 71% had grade ≥3 AEs and 59% had serious AEs. Conclusions: AMG 337 showed antitumor activity in MET-amplified G/GEJ/E adenocarcinoma but not in MET-amplified non-small-cell lung cancer.



https://ift.tt/2Ri79dZ

Identifying Recurrent Malignant Glioma after Treatment Using Amide Proton Transfer-Weighted MR Imaging: A Validation Study with Image-Guided Stereotactic Biopsy

Purpose: To quantify the accuracy of amide proton transfer-weighted (APTw) MRI for identifying active glioma post-treatment via radiographically guided stereotactic tissue validation. Experimental Design: Twenty-one patients referred for surgery for MRI features concerning for tumor progression versus treatment effect underwent pre-operative APTw imaging. Stereotactic biopsies were taken from regions of interest with varying APTw signal intensities. The relationship between final clinical pathology as well as the histopathology of each of the 64 specimens was analyzed relative to APTw results. Analysis of confirmed recurrent tumor or treatment effect tissue was used to perform receiver-operating-characteristic (ROC) analysis. Results: Eighteen of 21 patients had recurrent tumor, and 3 had treatment effect on clinical pathology. In 12 patients, there were multiple histopathologic assignments confirmed within the same tumor. Of the 64 total specimens, 20 specimens were active glioma, 27 mixed active and quiescent glioma, and 17 quiescent/no identifiable tumor. APTw signal intensity and histopathologic assignment, cellularity, and proliferation index had significant positive correlations (R = 0.651, 0.580, and 0.458, respectively; all P < 0.001). ROC analysis with a 1.79% APTw intensity cutoff differentiated active from non-active tumor (AUC of 0.881) with 85.1% sensitivity and 94.1% specificity. Analysis of clinical pathology showed the mean APTw intensity for each patient had 94.4% sensitivity and 100% positive predictive value for identifying recurrent glioma at this cutoff. Conclusions: APTw imaging hyperintensity may be a marker of active malignant glioma. It is able to distinguish between regions of heterogeneous abnormality on anatomical brain MRI with high sensitivity and specificity.



https://ift.tt/2OV9dMB

Polygenic Determinants for Subsequent Breast Cancer Risk in Survivors of Childhood Cancer: The St Jude Lifetime Cohort Study (SJLIFE)

Purpose: The risk of subsequent breast cancer among female childhood cancer survivors is markedly elevated. We aimed to determine genetic contributions to this risk, focusing on polygenic determinants implicated in breast cancer susceptibility in the general population.

Experimental Design: Whole-genome sequencing (30x) was performed on survivors in the St Jude Lifetime Cohort, and germline mutations in breast cancer predisposition genes were classified for pathogenicity. A polygenic risk score (PRS) was constructed for each survivor using 170 established common risk variants. Relative rate (RR) and 95% confidence interval (95% CI) of subsequent breast cancer incidence were estimated using multivariable piecewise exponential regression.

Results: The analysis included 1,133 female survivors of European ancestry (median age at last follow-up = 35.4 years; range, 8.4–67.4), of whom 47 were diagnosed with one or more subsequent breast cancers (median age at subsequent breast cancer = 40.3 years; range, 24.5–53.0). Adjusting for attained age, age at primary diagnosis, chest irradiation, doses of alkylating agents and anthracyclines, and genotype eigenvectors, RRs for survivors with PRS in the highest versus lowest quintiles were 2.7 (95% CI, 1.0–7.3), 3.0 (95% CI, 1.1–8.1), and 2.4 (95% CI, 0.1–81.1) for all survivors and survivors with and without chest irradiation, respectively. Similar associations were observed after excluding carriers of pathogenic/likely pathogenic mutations in breast cancer predisposition genes. Notably, the PRS was associated with the subsequent breast cancer rate under the age of 45 years (RR = 3.2; 95% CI, 1.2–8.3).

Conclusions: Genetic profiles comprised of small-effect common variants and large-effect predisposing mutations can inform personalized breast cancer risk and surveillance/intervention in female childhood cancer survivors. Clin Cancer Res; 1–6. ©2018 AACR.



https://ift.tt/2Rlo2ol

MicroRNA-210 promotes spinal cord injury recovery by inhibiting inflammation via the JAK-STAT pathway

OBJECTIVE: To investigate the effect of microRNA-210 on the spinal cord injury (SCI) and its underlying mechanism.

MATERIALS AND METHODS: The mouse SCI model was established. Mice were randomly assigned into 4 groups, namely the sham operation group (sham group), surgery group (SCI group), surgery+NC group (SCI+NC group) and surgery+microRNA-210 overexpression group (SCI+microRNA-210 mimics group). The mRNA levels of microRNA-210 and the key genes in the JAK-STAT pathway of the four groups were detected by Real-Time Polymerase Chain Reaction (RT-PCR) at different time points. Protein levels of JAK2 and STAT3 in mice of the four groups were detected by Western blot. To investigate the role of microRNA-210 in SCI recovery, changes in the motor function of mice were detected.

RESULTS: Grip strengths of right and left forelimbs in mice from the sham group were temporarily decreased at the early stage after surgery, which were gradually recovered to the preoperative levels on the 3rd postoperative day. However, mice in SCI group were unable to complete the grip strength determination at the early stage after surgery. Mice in SCI group were capable of grasping on the 7th postoperative day. Besides, grip strengths of mice in SCI group were remarkably lower than those of sham group until the end-point (on the 50th day). Furthermore, mRNA levels of microRNA-210 in mice of SCI group were decreased in a time-dependent manner (p<0.05). Higher grip strengths were observed in mice of SCI+microRNA-210 mimics group in comparison with those of SCI group and SCI+NC group (p<0.05). In addition, Western blot showed that protein levels of JAK2 and STAT3 in mice of SCI group were increased in a time-dependent manner (p<0.05). Moreover, protein levels of JAK2, STAT3, and MCP-1 in mice of SCI+NC group were remarkably higher than those in the sham group and SCI+microRNA-210 mimics group (p<0.05).

CONCLUSIONS: MicroRNA-210 is down-regulated in SCI mice. Grip strengths of SCI mice can be recovered after microRNA-210 overexpression via inhibiting inflammatory response by the JAK-STAT pathway.

L'articolo MicroRNA-210 promotes spinal cord injury recovery by inhibiting inflammation via the JAK-STAT pathway sembra essere il primo su European Review.



https://ift.tt/2O9Pfsd

GPIIb/IIIa expression changes in atrial fibrillation post radiofrequency ablation

OBJECTIVE: Atrial fibrillation (AF) is one of the most common arrhythmias affecting the patient's quality of life, and its complications of thromboembolism can lead to serious consequences. AF patients are often in hypercoagulation status that can affect the prognosis. GPIIb/IIIa is a fibrinogen receptor that can bind to the ligands of platelet and cause aggregation. Therefore, GPIIb/IIIa can be treated as a marker of hemagglutination. This work aims to analyze the changes of GPIIb/IIIa after radiofrequency ablation of atrial fibrillation, and to investigate its relationship with recurrence.

PATIENTS AND METHODS: A total of AF 80 patients in our hospital received radiofrequency ablation from January 2017 to August 2017. Peripheral blood was collected 1 week after surgery. A total of 40 healthy volunteers were enrolled as control group. GPIIb/IIIa was analyzed by enzyme-linked immunosorbent assay (ELISA). High-sensitivity troponin (hs-cTnT), fasting plasma glucose (FPG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (TC), and triglyceride levels (TG) were analyzed by using electrochemical luminescence assay. Body mass index (BMI), smoking index, and age were recorded.

RESULTS: Compared with the non-recurrence group, GPIIb/IIIa, hs-cTnT, FPG, LDL, TC, and TG levels increased, whereas HDL level declined in the recurrence group (p < 0.05). There was a positive correlation between GPIIb/IIIa and hs-cTnT, FPG, LDL, TC, TG, BMI, and smoking index, and a negative correlation with HDL (p < 0.05). GPIIb/IIIa was positively correlated with postoperative recurrence (p < 0.05).

CONCLUSIONS: Increased GPIIb/IIIa expression after radiofrequency ablation of AF is associated with myocardial injury, suggesting a risk of postoperative recurrence.

L'articolo GPIIb/IIIa expression changes in atrial fibrillation post radiofrequency ablation sembra essere il primo su European Review.



https://ift.tt/2RikrHo

Cancer Survival Higher in Teens, Young Adults Than Other Groups

FRIDAY, Oct. 26, 2018 -- Overall, cancer survival among adolescents and young adults (AYAs) has consistently exceeded that of other age groups except during the HIV/AIDS epidemic, according to a study published Oct. 15 in the Journal of the National...

https://ift.tt/2CI5udJ

ASTRO: Long-Term Benefit for Stereotactic Radn in Prostate CA

FRIDAY, Oct. 26, 2018 -- For men with low- and intermediate-risk prostate cancer (PCa), stereotactic body radiation therapy (SBRT) seems safe and effective in the long term, according to a study presented at the annual meeting of the American...

https://ift.tt/2qfQmNn

Prior-Season Vaccination Does Not Curb Flu Shot Effectiveness

FRIDAY, Oct. 26, 2018 -- Prior-season vaccination is not associated with reduced vaccine effectiveness (VE) among children aged 2 to 17 years, according to a study published online Oct. 26 in JAMA Network Open. Huong Q. McLean, Ph.D., M.P.H., from...

https://ift.tt/2CJSowN

Cardiac Implant Prices Higher in U.S. Than EU Countries

FRIDAY, Oct. 26, 2018 -- Cardiac implant prices are two to six times higher in the United States than in Germany, according to a study published in the October issue of Health Affairs. Martin Wenzl and Elias Mossialos, Ph.D., both from the London...

https://ift.tt/2qgltYV

Trump Administration Announces Plan to Cut Drug Prices

FRIDAY, Oct. 26, 2018 -- In an effort to cut high drug costs, the prices paid by Medicare for certain prescription drugs would be based on those in other advanced industrial nations, according to a proposal announced Oct. 25 by the Trump...

https://ift.tt/2CIfvHL

Intervention Strategies into Glycoprotein Hormone Receptors for Modulating (Mal–)function, with Special Emphasis on the TSH Receptor

Horm Metab Res
DOI: 10.1055/a-0749-6528

The thyrotropin receptor (TSHR), the lutropin- (LHR), and the follicotropin receptor (FSHR) belong to glycoprotein hormone receptors (GPHR), a subgroup of the class A G-protein coupled receptors. In this review, the unique features of GPHR have been taken into account for their pharmacological interventions: i) The respective hormone and stimulating or blocking antibodies are binding on the large ectodomain that is ii) via a hinge region, containing iii) an internal tethered agonist linked to the transmembrane domain. iv) Multimerization and mechanisms for negative or positive cooperativity of GPHR upon ligand binding and v) dimer- and oligomeric arrangements enabling trans-activation on GPHR signaling are considered. Available knowledge concerning the modulation of the GPHR (mal)-function and associated structural aspects by diverse entities such as antibodies, chaperones, peptides, small molecule agonists, inverse agonists, and antagonists is summarized. The TSHR is important with respect to autoimmune [Graves' disease (GD), Graves' orbitopathy (GO)] or non-autoimmune thyroid dysfunctions and cancer-development. To date there is neither an agonist nor antagonist modulator of pathogenic such as TSHR signaling in the clinics. However, several different ligands monoclonal stimulating and inhibiting antibodies and small molecule drug-like ligands have been reported in the last decade. In special focus are the most recent findings regarding the development and use of small molecule TSHR ligands. Finally, limitations of current knowledge and lack of information are discussed highlighting the need for intensified efforts towards understanding the interplay of TSHR multimers, especially their interaction with drug-like ligands. Important in this context is the biased ligand development.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text



https://ift.tt/2AubOnD

Identification of Potential miRNAs Biomarkers for High-Grade Prostate Cancer by Integrated Bioinformatics Analysis

Abstract

The increasing number of datasets available in the GEO database offers a new approach to identify new miRNAs related to PCa. The aim of our study was to suggest a miRNA signature for the detection of high-grade PCa (Gleason score ≥ 7) using bioinformatics tools. Three mRNA datasets (GSE26022, GSE30521, GSE46602) were selected to identify the differentially expressed genes (DEGs) in high-grade PCa. Furthermore, two miRNA datasets (GSE45604, GSE46738) were analyzed to select the differentially expressed miRNAs (DEMs). Functional and pathway enrichment analysis was performed using DAVID and a protein-protein interaction network (PPI) was constructed through STRING. Besides, miRNAs which regulate hub genes were predicted using microRNA.org. A total of 973 DEGs were identified after the analyses of the mRNA datasets, enriched in key mechanisms underlying PCa development. Furthermore, we identified 10 hub genes (EGFR, VEGFA, IGF1, PIK3R1, CD44, ITGB4, ANXA1, BCL2, LPAR3, LPAR1). The most significant KEGG Pathway was PI3K-Akt signaling pathway, involved in cell proliferation and survival. Moreover, we identified 30 common miRNAs between significant DEMs and the predicted hub gene regulators. Twelve of these miRNAs (miR-1, −365, −132, −195, −133a, −133b, −200c, −339, −222, −21, −221, −708) regulate two or more hub genes identified in our study. We suggested a signature including these 12 miRNAs for high-grade PCa detection. These miRNAs have been associated with aggressive PCa, poor survival and resistance to treatment in the last years.



https://ift.tt/2PXGjHT

Applications of neuromuscular ultrasound in amyotrophic lateral sclerosis

Nerve and muscle ultrasound is becoming an important ancillary investigation in the diagnosis of amyotrophic lateral sclerosis (ALS). ALS remains a clinical diagnosis without a gold standard diagnostic investigation. However, the results of supporting investigations such as electromyography (EMG) help to increase the confidence in the clinical diagnosis and eliminate potential mimicking conditions.

https://ift.tt/2CH8eIh

Concentric or Monopolar Electrode for Jitter Determination in Orbicularis Oculi

Single fiber electromyography (SFEMG), developed by Ekstedt and Stålberg in the 1960s, is the best-recognized technique for the study of motor unit microphysiology, including the neuromuscular jitter, the propagation velocity along individual muscle fibers, and muscle fiber organization within single motor units (Ekstedt, 1964; Stålberg and Ekstedt, 1968; Sanders and Stålberg, 1996). Jitter is a measure of the time variability of single muscle fibre depolarization in a motor unit, due to temporal variability at the neuromuscular junction during successive discharges.

https://ift.tt/2qbkeKy

Comparison of the EMA and FDA Guidelines on Ulcerative Colitis Drug Development

In 2016, the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) released revised (EMA) or new (FDA) draft guidelines related to the development of drugs intended for the treatment of ulcerative colitis. We sought to compare and contrast the EMA draft guideline with the FDA draft guidance in order to facilitate further discussion and perhaps harmonization between the two guidelines when they are finalized.

https://ift.tt/2D7jZci

Long-term Efficacy of Tenofovir Disoproxil Fumarate Monotherapy for Multidrug-resistant Chronic HBV infection

There are no globally agreed upon treatment guidelines for patients with chronic hepatitis B virus (HBV) with multidrug resistance (MDR). We conducted a multicenter, prospective, real-world cohort study of effects of tenofovir disoproxyl fumarate (TDF) monotherapy and TDF-based combination therapy, as rescue therapy, in patients with multidrug-resistant chronic HBV infections.

https://ift.tt/2EV4So2

Factors Associated With Efficacy of Cognitive Behavior Therapy vs Education for Patients With Irritable Bowel Syndrome

Among patients with irritable bowel syndrome (IBS), it would be helpful to identify those most likely to respond to specific treatments, yet few factors have been identified that reliably predict positive outcome. We sought to identify pretreatment baseline characteristics that associate with symptom improvement in patients who received empirically validated regimens of cognitive behavior therapy (CBT) or IBS education.

https://ift.tt/2D98tNB

Long term outcomes of autologous peripheral blood stem cell transplantation in patients with cirrhosis

Peripheral blood stem cells (PBSCs) mobilized with colony stimulating factor can promote liver regeneration and increase liver function in patients with liver diseases. However, the long-term effects of stem cell treatments on survival and risk of hepatocellular carcinoma (HCC) in patients with liver cirrhosis have not been determined. We investigated the long-term effects of autologous stem cell transplantation and risk of HCC in patients with liver cirrhosis.

https://ift.tt/2EPuanj

Prevalence of and Risk Factors for Low Bone Mineral Density in Children With Celiac Disease

Celiac disease can reduce bone mineral density. We sought to determine the prevalence and risk factors for low areal bone mineral density (aBMD) in children with celiac disease.

https://ift.tt/2D7VT0W

Infliximab Exposure-Response Relationship and Thresholds Associated with Endoscopic Healing in Patients With Ulcerative Colitis

Therapeutic drug monitoring might be used to personalize infliximab treatment of patients with ulcerative colitis (UC), although exposure thresholds associated with endoscopic healing are uncertain. We aimed to determine infliximab concentration thresholds associated with endoscopic outcomes during induction and maintenance therapy for patients with UC.

https://ift.tt/2EYS3sT

Factors Associated with Increased Risk of de Novo or Recurrent Hepatocellular Carcinoma in Patients with Cirrhosis Treated with Direct-Acting Antivirals for HCV Infection

Patients with cirrhosis and hepatitis C virus (HCV) infection treated with direct-acting antivirals (DAAs) are still at risk for developing hepatocellular carcinoma (HCC). We aimed to identify features of de novo or recurrent HCCs in these patients, and factors associated with HCC development, in a large cohort of patients with cirrhosis who received treatment with DAAs.

https://ift.tt/2D6o406

Contained aortic rupture with hematoma presenting with GI bleed



https://ift.tt/2ENY6Ae

Colorectal cancer screening: the surgery rates they are a-changing. A nationwide study on surgical resections in Italy

Growing evidence suggests that colorectal cancer (CRC) screening based on the fecal immunochemical test (FIT) reduces CRC incidence and surgical resection rates.

https://ift.tt/2Oa2WHr

Brachytherapy Training Survey of Radiation Oncology Residents

Brachytherapy utilization has declined, and ARRO performed an online survey of US residents to evaluate brachytherapy training. Comfort level with brachytherapy varies by modality and disease site. The major barrier as perceived by radiation oncology residents is case load, and an increase in performed cases is correlated with increased confidence in brachytherapy practice. Respondents appear interested in augmenting their education with dedicated training experiences that are feasible to complete during residency.

https://ift.tt/2Ji1txW

Robotic stereotactic boost in early breast cancer, a phase II trial

This phase II trial of single-dose stereotactic boost after conventional breast irradiation in early breast cancer showed excellent local control, toxicity profile and quality of life on general and breast specific items with median follow up of 38 months.

https://ift.tt/2JigOyD

Long term follow up of patients treated at a single institution using a passively scattered proton beam; observations around the occurrence of second malignancies.

To analyze the occurrence of secondary malignancies after passively scattered proton beam therapy by way of a retrospective study of patients with long term follow up treated for intracranial and cranial pathologies. The occurrences of out of field secondary malignancies were compared with the expected incidence in the general population based on national cancer statistics. No increased risk was observed for all age groups studied, and only one in field secondary malignancy was observed.

https://ift.tt/2Pkkm95

Characterizing Spatial Lung Function For Esophageal Cancer Patients Undergoing Radiotherapy

4DCT-ventilation has been studied in the lung cancer population but has yet to be extended to esophageal cancer patients. The purpose of this study was to characterize 4DCT-ventilation-based spatial lung function for esophageal cancer patients. The study used radiologist observations and developed quantitative metrics to assess pre-treatment spatial lung function profiles for esophageal cancer patients. The study presents data that can be used for 4DCT-ventilation application aimed at reducing thoracic toxicity for esophageal cancer patients.

https://ift.tt/2Pkknd9

Successful hemostasis of active lower GI bleeding using a hemostatic powder as monotherapy, combination therapy, or rescue therapy

Acute lower GI bleeding is a frequent cause of hospital admission. The objective of this study was to evaluate the safety and performance of a hemostatic powder (TC-325/Hemospray) in the treatment of nonvariceal lower GI bleeding.

https://ift.tt/2CHVuRD

Durability of radiofrequency ablation for treatment of esophageal squamous cell neoplasia: 5-year follow-up of a treated cohort in China

Radiofrequency ablation (RFA) is accepted treatment for flat Barrett's neoplasia. Less is known about RFA for esophageal squamous-cell neoplasia (ESCN). Our group has reported several prospective studies of RFA for ESCN in China with promising results through 12 months of follow-up. In this cohort study, we aimed to evaluate longer-term outcomes after RFA for ESCN.

https://ift.tt/2qkXxUF

Catfish mucus alters the Flavobacterium columnare transcriptome

Abstract
Columnaris disease, caused by Flavobacterium columnare, severely impacts the production of freshwater finfish species. Therefore, efforts to better understand the biological processes of F. columnare, including the formation of biofilms and their contribution to disease, are ongoing. In this study, we incubated F. columnare cultures with channel catfish mucus and used high-throughput RNA sequencing to evaluate global changes in gene expression. Our data show that mucus activates in vitro biofilm formation. The analysis of F. columnare transcriptomes after the addition of mucus revealed significant differentially expressed genes (DEGs) between the planktonic and biofilm states. DEGs common among all biofilms were enriched for gene ontology groups including signal transduction, ligand binding and cellular homeostasis and are likely necessary for biofilm formation. Iron acquisition systems included TonB-dependent receptor and ferroxidase genes were expressed among all biofilms, while siderophore synthesis genes were only expressed in mucus-stimulated biofilms. The current analysis of F. columnare transcriptomes adds valuable information about the basic biological processes that occur during the planktonic and biofilm states. This work serves as a basis for future studies on understanding how biofilms are established and how they contribute to disease progression.

https://ift.tt/2Sn6Uj6

Disparities in Emergency Department Visits Among Collocated Racial/Ethnic Medicare Enrollees

We estimate emergency department (ED) use differences across Medicare enrollees of different race/ethnicity who are residing in the same zip codes.

https://ift.tt/2yzikby

The Canadian Community Utilization of Stroke Prevention Study in Atrial Fibrillation in the Emergency Department (C-CUSP ED)

Lack of oral anticoagulation prescription in the emergency department (ED) has been identified as a care gap in atrial fibrillation patients. This study seeks to determine whether the use of a tool kit for emergency physicians with a follow-up community-based atrial fibrillation clinic resulted in greater oral anticoagulation prescription at ED discharge than usual care.

https://ift.tt/2O829qv

Intravenous Fluid for the Treatment of Emergency Department Patients With Migraine Headache: A Randomized Controlled Trial

The objective of this pilot study is to assess the feasibility and necessity of performing a large-scale trial to measure the effect of intravenous fluid therapy on migraine headache pain.

https://ift.tt/2yEAWXo

Can the Probiotic Lactobacillus reuteri Be Used to Treat Infant Colic?

The search identified 282 abstracts, of which 4 double-blind randomized controlled trials (345 patients, 171 placebo and 174 probiotic) met the inclusion criteria.2-5 All studies used the same probiotic, manufactured by the same company and given at the same dose, and the same placebo. All trials included breastfed infants with colic, whereas only one trial included formula-fed infants with colic. The probiotic group was approximately twice as likely as the placebo group to experience treatment success at 7, 14, and 21 days (adjusted incidence ratios were 2.08 [95% CI 1.26 to 3.42], 1.98 [95% CI 1.46 to 2.70], and 1.71 [95% CI 1.35 to 2.15], respectively) (Table).

https://ift.tt/2O5l4lO

Guardian Angel debuts Elite Series personal safety lighting devices for first responders

The new design is to increase the visibility of first responders as they attend to roadside incidents

https://ift.tt/2D7M0Ao

Single-cell RNA Sequencing of Fluorescently Labeled Mouse Neurons Using Manual Sorting and Double In Vitro Transcription with Absolute Counts Sequencing (DIVA-Seq)

This protocol describes the manual sorting procedure to isolate single fluorescently labeled neurons followed by in vitro transcription-based mRNA amplification for high-depth single-cell RNA sequencing.

https://ift.tt/2OPfGIK

Combined Genetic and Chemical Capsid Modifications of Adenovirus-Based Gene Transfer Vectors for Shielding and Targeting

The protocol described here enables researchers to specifically modify adenovirus capsids at selected sites by simple chemistry. Shielded adenovirus vectors particles and retargeted gene transfer vectors can be generated, and vector host interactions can be studied.

https://ift.tt/2RhAsxh

TBL1XR1 mutations in Pierpont syndrome are not restricted to the recurrent p.Tyr446Cys mutation

American Journal of Medical Genetics Part A, EarlyView.


https://ift.tt/2qdrxkZ

Automation of a Positron-emission Tomography (PET) Radiotracer Synthesis Protocol for Clinical Production

Positron-emission tomography (PET) imaging sites that are involved in multiple early clinical research trials need robust and versatile radiotracer manufacturing capabilities. Using the radiotracer [18F]Clofarabine as an example, we illustrate how to automate the synthesis of a radiotracer using a flexible, cassette-based radiosynthesizer and validate the synthesis for clinical use.

https://ift.tt/2PYhJ9Y

Millions of ER Visits for Asthma Due to Air Pollution

FRIDAY, Oct. 26, 2018 -- Air pollution accounts for millions of emergency room visits for asthma each year, according to a study published Oct. 24 in Environmental Health Perspectives. Susan C. Anenberg, Ph.D., from George Washington University in...

https://ift.tt/2D6R1cy

Giving Patients Treatment Choice Improves PTSD Outcomes

FRIDAY, Oct. 26, 2018 -- Giving patients with post-traumatic stress disorder (PTSD) their preferred treatment improves adherence and symptoms, according to a study published online Oct. 19 in The American Journal of Psychiatry. Lori A. Zoellner,...

https://ift.tt/2EJAWe8

ASTRO: Stereotactic Ablative RT OK for RCC in Solitary Kidneys

FRIDAY, Oct. 26, 2018 -- For patients with renal cell carcinoma (RCC), stereotactic ablative radiotherapy (SABR) seems to be as safe and effective for patients with a solitary kidney as for those with bilateral kidneys, according to a study...

https://ift.tt/2DahAxk

Procurement Bx of Deceased Donor Kidneys Poorly Reproduced

FRIDAY, Oct. 26, 2018 -- Procurement biopsies from deceased donor kidneys have poor reproducibility and do not correlate well with reperfusion biopsies, according to a study published online Oct. 25 in the Clinical Journal of the American Society of...

https://ift.tt/2EJAUD2

ASTRO: Oropharynx CA Survival Rates Worse With RT/Cetuximab

FRIDAY, Oct. 26, 2018 -- For patients with locoregionally advanced human papillomavirus (HPV)-related oropharynx cancer, radiation/cetuximab results in inferior overall and progression-free survival versus radiation/cisplatin, according to a study...

https://ift.tt/2D6zrFw

Alcohol Disorder Screening in Women Post-RYGB Inadequate

FRIDAY, Oct. 26, 2018 -- Assessing the frequency and quantity of alcohol consumption may be inadequate for identifying alcohol-related problems in women who have undergone Roux-en-Y gastric bypass (RYGB) surgery, according to a study published...

https://ift.tt/2ENI0Xe

Early Natural Menopause Linked to Shorter Life Expectancy

FRIDAY, Oct. 26, 2018 -- Compared with women who experience normal or late menopause, women who experience early natural menopause have a shorter life expectancy and spend fewer years without type 2 diabetes (T2D), according to a study published...

https://ift.tt/2D5WLTE

No Drop Seen in CT Use for Pediatric Head Trauma

FRIDAY, Oct. 26, 2018 -- Computed tomography (CT) neuroimaging did not decrease from 2007 to 2015 among pediatric patients evaluated in the emergency department for head injury, according to a study published in the October issue of...

https://ift.tt/2ENHZTa

Novel Troponin Assay, hs-cTnI Comparable in Ruling Out AMI

FRIDAY, Oct. 26, 2018 -- A single point-of-care troponin concentration measured on arrival to the emergency department (ED) with 15-minute turnaround time can accurately rule out acute myocardial infarction (AMI), according to a study published...

https://ift.tt/2D5WK22

High-Coverage Rollout of PReP Tied to Drop in HIV Diagnoses

FRIDAY, Oct. 26, 2018 -- A rapid, targeted, high-coverage rollout of HIV pre-exposure prophylaxis (PrEP) is associated with a decrease in HIV diagnoses among high-risk men who have sex with men (MSM), according to a study published online Oct. 17 in...

https://ift.tt/2EJAOeE

Definitions of response and remission for the Robarts Histopathology Index

The Robarts Histopathology Index (RHI) is a recently validated instrument that measures histological disease activity in ulcerative colitis.1 Given the increasing importance and use of histology in UC as a treatment outcome, additional evaluation and clarification of the definitions for histological remission and response using the RHI is needed.

During the development of the RHI, we demonstrated that most patients in clinical or endoscopic remission had an RHI≤6. However, an RHI≤6 should not be used to define histological remission as was recently suggested by Magro et al.2 Rather, the minimal criteria for histological remission should be the absence of neutrophils from the mucosa (both lamina propria and epithelium), as neutrophils have long been used to define histologically active disease.3 Furthermore, the presence of mucosal neutrophils in biopsies from patients in clinical remission predicts clinical relapse.4 Using the RHI, an absence of mucosal neutrophils is...



https://ift.tt/2z66wNh

Mkk4 and Mkk7 are important for retinal development and axonal injury-induced retinal ganglion cell death

Mkk4 and Mkk7 are important for retinal development and axonal injury-induced retinal ganglion cell death

<i>Mkk4</i> and <i>Mkk7</i> are important for retinal development and axonal injury-induced retinal ganglion cell death, Published online: 26 October 2018; doi:10.1038/s41419-018-1079-7

Mkk4 and Mkk7 are important for retinal development and axonal injury-induced retinal ganglion cell death

https://ift.tt/2z21ZeK

Antioxidants prevent inflammation and preserve the optic projection and visual function in experimental neurotrauma

Antioxidants prevent inflammation and preserve the optic projection and visual function in experimental neurotrauma

Antioxidants prevent inflammation and preserve the optic projection and visual function in experimental neurotrauma, Published online: 26 October 2018; doi:10.1038/s41419-018-1061-4

Antioxidants prevent inflammation and preserve the optic projection and visual function in experimental neurotrauma

https://ift.tt/2SmNlrt

Leptin in depression: a potential therapeutic target

Leptin in depression: a potential therapeutic target

Leptin in depression: a potential therapeutic target, Published online: 26 October 2018; doi:10.1038/s41419-018-1129-1

Leptin in depression: a potential therapeutic target

https://ift.tt/2z5cxJX

Manipulating Living Cells to Construct Stable 3D Cellular Assembly Without Artificial Scaffold

We demonstrate a novel method for constructing a single-cell-based 3-dimensional (3D) assembly without an artificial scaffold.

https://ift.tt/2CIHSWz

Oleic Acid-Injection in Pigs As a Model for Acute Respiratory Distress Syndrome

In this article, we present a protocol to induce acute lung injury in pigs by central-venous injection of oleic acid. This is an established animal model for studying the acute respiratory distress syndrome (ARDS).

https://ift.tt/2qbFb8r

Correction to: Role of astrocytic MeCP2 in regulation of CNS myelination by affecting oligodendrocyte and neuronal physiology and axo–glial interactions

In the typesetting of the original version of this article, the Publisher inadvertently confused the first and last names of the authors, leading to their misrepresentation in PubMed.



https://ift.tt/2EN2teU

Cell-free DNA in cancer: current insights

Abstract

Background

The field of liquid biopsies in oncology is rapidly expanding, with the application of cell-free circulating tumour DNA (ctDNA) showing promise in this era of precision medicine. Compared with traditional clinical and radiographic tumour monitoring methods, the analysis of ctDNA provides a minimally-invasive and technically feasible approach to assess temporal and spatial molecular evolutions of the tumour landscape. The constantly advancing technological platforms available for ctDNA extraction and analysis allow greater analytical sensitivities than ever before. The potential translational impact of ctDNA as a blood-based biomarker for the identification, characterization and monitoring of cancer has been demonstrated in numerous proof-of-concept studies, with ctDNA analysis beginning to be applied clinically across multiple facets of oncology.

Conclusions

In this review we discuss the biology, recent advancements, technical considerations and clinical implications of ctDNA in the context of cancer, and highlight important challenges and future directions for the integration of ctDNA into standardised patient care.



https://ift.tt/2q98WXs

Soil pH rather than elevation determines bacterial phylogenetic community assembly on Mt. Norikura, Japan

Abstract
There is considerable interest in the factors which may explain variation in microbial community assembly processes. In this study, we investigated bacterial community assembly, phylogenetic diversity and the relative role of deterministic and stochastic processes along environmental gradients on Mt. Norikura, Japan. DNA extracted from soil samples collected at a range of elevations was PCR amplified for bacterial 16S rRNA gene targeting the V3-V4 region, and sequenced using Illumina MiSeq. We hypothesized that elevation would be a strong predictor of phylogenetic community assembly, with communities being more phylogenetically clustered towards higher elevations, due to more extreme physiological conditions. We also hypothesized a greater role of stochasticity at the highest elevations, due to more frequent soil disturbance. Contrary to our hypotheses, we found that the strength of phylogenetic clustering and the role of stochasticity were strongly related to soil pH, with phylogenetic clustering and deterministic processes being strongest at lower soil pH values. Moreover, there was no trend towards stronger influence of phylogenetic clustering and stochasticity in the upper elevations of Mt. Norikura. These results reveal an overwhelming influence of soil pH on phylogenetic community assembly of soil bacteria, even when a range of other environmental gradients are present.

https://ift.tt/2qaKJ2S

Cancers, Vol. 10, Pages 403: Simultaneous Inhibition of MEK and Hh Signaling Reduces Pancreatic Cancer Metastasis

Cancers, Vol. 10, Pages 403: Simultaneous Inhibition of MEK and Hh Signaling Reduces Pancreatic Cancer Metastasis

Cancers doi: 10.3390/cancers10110403

Authors: Dongsheng Gu Hai Lin Xiaoli Zhang Qipeng Fan Shaoxiong Chen Safi Shahda Yunlong Liu Jie Sun Jingwu Xie

Pancreatic cancer, mostly pancreatic ductal adenocarcinoma (PDAC), is one of the most lethal cancer types, with an estimated 44,330 death in 2018 in the US alone. While targeted therapies and immune checkpoint inhibitors have significantly improved treatment options for patients with lung cancer and renal cell carcinomas, little progress has been made in pancreatic cancer, with a dismal 5-year survival rate currently at ~8%. Upon diagnosis, the majority of pancreatic cancer cases (~80%) are already metastatic. Thus, identifying ways to reduce pancreatic cancer metastasis is an unmet medical need. Furthermore, pancreatic cancer is notorious resistant to chemotherapy. While Kirsten RAt Sarcoma virus oncogene (K-RAS) mutation is the major driver for pancreatic cancer, specific inhibition of RAS signaling has been very challenging, and combination therapy is thought to be promising. In this study, we report that combination of hedgehog (Hh) and Mitogen-activated Protein/Extracellular Signal-regulated Kinase Kinase (MEK) signaling inhibitors reduces pancreatic cancer metastasis in mouse models. In mouse models of pancreatic cancer metastasis using human pancreatic cancer cells, we found that Hh target gene Gli1 is up-regulated during pancreatic cancer metastasis. Specific inhibition of smoothened signaling significantly altered the gene expression profile of the tumor microenvironment but had no significant effects on cancer metastasis. By combining Hh signaling inhibitor BMS833923 with RAS downstream MEK signaling inhibitor AZD6244, we observed reduced number of metastatic nodules in several mouse models for pancreatic cancer metastasis. These two inhibitors also decreased cell proliferation significantly and reduced CD45+ cells (particularly Ly6G+CD11b+ cells). We demonstrated that depleting Ly6G+ CD11b+ cells is sufficient to reduce cancer cell proliferation and the number of metastatic nodules. In vitro, Ly6G+ CD11b+ cells can stimulate cancer cell proliferation, and this effect is sensitive to MEK and Hh inhibition. Our studies may help design novel therapeutic strategies to mitigate pancreatic cancer metastasis.



https://ift.tt/2CJsPMm

Doctor, are you healthy? A cross-sectional investigation of oncologist burnout, depression, and anxiety and an investigation of their associated factors

Abstract

Purpose

Doctors who work at cancer hospitals are at high risk of developing emotional distress. This study evaluated the prevalence of burnout, anxiety, and depression in a sample of oncologists of various specialties and sought to identify how much of this distress is explained by specific pre-established characteristics.

Methods

This cross-sectional study used online surveys. Burnout was measured using the Maslach Burnout Inventory (MBI), and anxiety and depression were measured using the Hospital Anxiety and Depression Scale (HADS). The variables associated with p-values < 0.10 in the univariate analyses were included in blocks of hierarchical binary logistic regression models to identify the predictors of burnout, depression, and anxiety.

Results

Of the 227 physicians (response rate = 70.5%), 132 (58.1%) were identified as having burnout (high emotional exhaustion [EE] and depersonalization [DP]); furthermore, 28 (12.3%) had depression (HADS-D ≥ 11), and 44 (19.4%) had anxiety (HADS-A ≥ 11). The block of perceptions related to the workplace explained 22.4%, 7.7%, and 10.6% of the variances of burnout, depression, and anxiety, respectively. On the other hand, the outside-of-work characteristics block explained only 3.1%, 13.4%, and 3.4% of the variances of burnout, depression, and anxiety, respectively.

Conclusions

Work-related stressors are associated with burnout, but few are associated with anxiety and depression. Outside-of-work characteristics explained little of the distress reported by physicians. Strategies focused on perceptions of professional recognition and lower workloads that stimulate positive relationships between doctors and other health professionals are desirable in oncological context.



https://ift.tt/2O90LnA

Taxifolin, a natural flavonoid interacts with cell cycle regulators causes cell cycle arrest and causes tumor regression by activating Wnt/ β -catenin signaling pathway

Abstract

Background

New approaches for the prevention of colon cancer perseveres an essential necessity. Though, resistance to existing chemo-preventive drugs is moderately predominant in colon carcinogenesis. Taxifolin (dihydroquercetin) is a flavononol, have shown virile biological activities against few cancers. The current study was designed to investigate and equate antitumor activity of Taxifolin (TAX) in colorectal cancer cell lines and in HCT116 xenograft model in a comprehensive approach.

Methods

Two human colorectal cancer cell lines HCT116 and HT29, were used. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazoliumbromide (MMT) protocol was performed to elucidate the impact of TAX and β- catenin inhibitor (FH535) on the viability of HCT116 and HT29 cell lines. Apoptosis /cell cycle assay was performed. Data interpretation was done with a FACScan (Becton Dickinson, NJ). About 1 × 104 cells per sample were harvested. Histograms of DNA were analyzed with ModiFitLT software (verity Software House, ME, USA). Western blotting and RT-PCR were performed for protein and gene expression respectively in in vitro and in vivo.

Results

We found that TAX induced cytotoxicity in colorectal cells in a dose-dependent manner and time dependent approach. Further, our data validated that administration of TAX to human colorectal cancer HCT116 and HT29 cells resulted in cell growth arrest, variation in molecules controlling cell cycle operative in the G2 phase of the cell cycle and apoptosis in a concentration dependent approach. Further our results concluded that TAX administration decreases expression of β-catenin gene, AKT gene and Survivin gene and protein expression in in vitro and in vivo.

Conclusion

Our findings proposed that targeting β-catenin gene may encourage the alterations of cell cycle and cell cycle regulators. Wnt/β-catenin signaling pathway possibly takes part in the genesis and progression of colorectal cancer cells through regulating cell cycle and the expression of cell cycle regulators.



https://ift.tt/2yw6Ghq

Sorafenib and docosahexaenoic acid act in synergy to suppress cancer cell viability: a role of heme oxygenase 1

Abstract

Background

Docosahexaenoic acid (DHA) is a long chain n-3 polyunsaturated fatty acid that has anticancer activity. Heme oxygenase 1 (HO-1) is a potential therapeutic target due to its cytoprotective activity in cancer cells. We recently reported that DHA induces HO-1 gene transcription in human cancer cells by augmenting the degradation of Bach1 protein, which functions as a negative regulator of HO-1. Since the degradation of Bach1 protein relies on protein phosphorylation, we hypothesized that DHA-induced HO-1 gene transcription could be attenuated by kinase inhibitors, resulting in an enhanced cytotoxicity. Sorafenib, a tyrosine kinase inhibitor, was first applied to test our hypothesis.

Methods

Human cancer cell lines and a xenograft nude mouse model were applied to test our hypothesis. Gene expression was analyzed by western blot analysis and reporter gene assay. Cell viability was analyzed using a colorimetric assay. Isobologram was applied to analyze drug action.

Results

Pretreatment of cancer cells with Sorafenib significantly attenuated DHA-induced degradation of Bach1 protein. Consequently, DHA-induced HO-1 gene transcription was reversed by Sorafenib as evidenced by western blot and reporter gene analysis. Sorafenib acted synergistically with DHA to suppress cancer cell viability in various human cancer cell lines and suppressed tumor xenograft growth in mice fed a fish oil enriched diet (high n-3/DHA), as compared to mice fed a corn oil (high n-6) diet. Screening of the NCI-Oncology Drug Set IV identified a group of anticancer compounds, including Sorafenib, which enhanced DHA's cytotoxicity, as well as a set of compounds that attenuated DHA's cytotoxicity.

Conclusions

We demonstrate that sorafenib attenuates DHA-induced HO-1 expression and acts in synergy with DHA to suppress cancer cell viability and tumor growth. Considering the known health benefits of DHA and the clinical effectiveness of Sorafenib, their combination is an attractive therapeutic strategy against cancer.



https://ift.tt/2O90GjM

Clinicopathological and prognostic correlations of HER3 expression and its degradation regulators, NEDD4–1 and NRDP1, in primary breast cancer

Abstract

Background

Human epidermal growth factor receptor HER3 (ErbB3), especially in association with its relative HER2 (ErbB2), is known as a key oncogene in breast tumour biology. Nonetheless, the prognostic relevance of HER3 remains controversial. NEDD4–1 and NRDP1 are signalling molecules closely related to the degradation of HER3 via ubiquitination. NEDD4–1 and NRDP1 have been reported to contribute to HER3-mediated signalling by regulating its localization and cell membrane retention. We studied correlations between HER3, NEDD4–1, and NRDP1 protein expression and their association with tumour histopathological characteristics and clinical outcomes.

Methods

The prevalence of immunohistochemically detectable expression profiles of HER3 (n = 177), NEDD4–1 (n = 145), and NRDP1 (n = 145) proteins was studied in primary breast carcinomas on archival formalin-fixed paraffin-embedded (FFPE) samples. Clinicopathological correlations were determined statistically using Pearson's Chi-Square test. The Kaplan-Meier method, log-rank test (Mantel-Cox), and Cox regression analysis were utilized for survival analysis.

Results

HER3 protein was expressed in breast carcinomas without association with HER2 gene amplification status. Absence or low HER3 expression correlated with clinically aggressive features, such as triple-negative breast cancer (TNBC) phenotype, basal cell origin (cytokeratin 5/14 expression combined with ER negativity), large tumour size, and positive lymph node status. Low total HER3 expression was prognostic for shorter recurrence-free survival time in HER2-amplified breast cancer (p = 0.004, p = 0.020 in univariate and multivariate analyses, respectively). The majority (82.8%) of breast cancers demonstrated NEDD4–1 protein expression - while only a minor proportion (8.3%) of carcinomas expressed NRDP1. NEDD4–1 and NRDP1 expression were not associated with clinical outcomes in HER2-amplified breast cancer, irrespective of adjuvant trastuzumab therapy.

Conclusions

Low HER3 expression is suggested to be a valuable prognostic biomarker to predict recurrence in HER2-amplified breast cancer. Neither NEDD4–1 nor NRDP1 demonstrated relevance in prognostics or in the subclassification of HER2-amplified breast carcinomas.



https://ift.tt/2yEoVRT

IL-1-induced JAK/STAT signaling is antagonized by TGF-beta to shape CAF heterogeneity in pancreatic ductal adenocarcinoma [Research Articles]

Pancreatic ductal adenocarcinoma (PDAC) is poorly responsive to therapies and histologically contains a paucity of neoplastic cells embedded within a dense desmoplastic stroma. Within the stroma, cancer-associated fibroblasts (CAFs) secrete tropic factors and extracellular matrix components, and have been implicated in PDAC progression and chemotherapy resistance. We recently identified two distinct CAF subtypes characterized by either myofibroblastic or inflammatory phenotypes; however, the mechanisms underlying their diversity and their roles in PDAC remain unknown. Here, we use organoid and mouse models to identify TGF-beta and IL-1 as tumor-secreted ligands that promote CAF heterogeneity. We show that IL-1 induces LIF expression and downstream JAK/STAT activation to generate inflammatory CAFs, and demonstrate that TGF-beta antagonizes this process by downregulating IL-1R1 expression and promoting differentiation into myofibroblasts. Our results provide a mechanism through which distinct fibroblast niches are established in the PDAC microenvironment and illuminate strategies to selectively target CAFs that support tumor growth.



https://ift.tt/2qd5Bq9

LILRB4-Signaling Mediates T-cell Suppression and Leukemia Infiltration [Research Watch]

LILRB4 expression in monocytic AML cells blocks T-cell activity and promotes tumor infiltration.



https://ift.tt/2CHzCWH

Dysregulated Fermentation of Soluble Fiber May Induce Liver Cancer [Research Watch]

Increased fiber fermentation amidst microbial dysbiosis may promote tumorigenesis.



https://ift.tt/2qbofPp

A Brain-Penetrant MET Inhibitor Achieves Responses in Glioblastoma [Research Watch]

Mapping the genomic landscape of secondary glioblastoma (sGBM) identifies MET as a therapeutic target.



https://ift.tt/2CH8VkP

SABR Combats Metastatic Disease [News in Brief]

Stereotactic ablative radiotherapy improves OS, PFS, in patients with breast, colorectal, prostate, and lung cancers.



https://ift.tt/2qaIigC

Cancer Mutations Occur Frequently in Normal Esophageal Epithelium [Research Watch]

Targeted sequencing of 74 cancer genes mapped the mutational landscape of normal esophageal epithelium.



https://ift.tt/2CHzA11

Resisting CAR T-cell Therapy: A Case Study [News in Brief]

Unintentional transduction of single B cell with CAR19 gene confers resistance through CD19 epitope masking.



https://ift.tt/2qfayyV

The Super Elongation Complex May Be Targetable in MYC-Driven Tumors [Research Watch]

Identified small-molecule inhibitors of the super elongation complex (SEC) disrupt transcriptional elongation.



https://ift.tt/2CKmFv4

CAD/CAM implant crowns in a digital workflow: Five‐year follow‐up of a prospective clinical trial

Clinical Implant Dentistry and Related Research, EarlyView.


https://ift.tt/2OPrx9D

A clinical assessment of visual performance of combining the TECNIS® Symfony Extended Range of Vision IOL (ZXR00) with the +3.25 D TECNIS Multifocal 1-piece IOL (ZLB00) in subjects undergoing bilateral cataract extraction

88x31.png



https://ift.tt/2CFE6NE

Comparison of variation of intraocular pressure in noncontact tonometry in patients subjected to phacoemulsification and trabeculectomy with phacoemulsification

88x31.png



https://ift.tt/2qagBVn

Viscodilation of Schlemm’s canal for the reduction of IOP via an ab-interno approach

88x31.png



https://ift.tt/2CZVHAU

Clinical outcomes of 4-point scleral fixated 1-piece hydrophobic acrylic equiconvex intraocular lens using polytetrafluoroethylene suture

88x31.png



https://ift.tt/2qcMJYD

Neoadjuvant chemotherapy is associated with a high rate of perioperative blood transfusion at the time of interval cytoreductive surgery

Abstract

Background

The oncologic safety of allogeneic blood transfusion in ovarian cancer patients is unknow. We sought to determine the prevalence and oncologic safety of perioperative allogeneic blood transfusion during interval cytoreduction surgery among women receiving neoadjuvant chemotherapy for ovarian cancer.

Methods

We utilized retrospective chart review to identify a cohort of patients undergoing interval cytoreduction at a large academic tertiary referral center. We compared outcomes in patients who were exposed to perioperative blood transfusion compared with patients who were not exposed. Our primary endpoint was progression free survival; our secondary endpoint was overall survival. Baseline clinical characteristics were collected for patients in each group.

Results

Sixty-six women were included in the final cohort of women undergoing interval cytoreductive surgery after NACT. A total of 51 women (77%) were exposed to allogeneic perioperative pRBC transfusion. Fifteen women (23%) were not exposed to transfusion. The baseline characteristics were generally well matched. Women who were not exposed to a perioperative blood transfusion were more likely to have a normalized CA125 prior to undergoing cytoreductive surgery. Preoperative hemoglobin concentration was lower in the transfusion group (10.5 g/dLvs 11.5 g/dL, p < 0.009). Perioperative transfusion was not associated with a significant difference in progression free survival (PFS = 7.6 months for transfused, 9.4 months for not transfused; log-rank test p = 0.4617). Similarly, there was no observed difference between groups for overall survival (OS = 23.6 months for transfused, 22.5 months for not transfused; log-rank test p = 0.1723).

Conclusions

Women undergoing neoadjuvant chemotherapy for ovarian cancer are at high risk of exposure to blood transfusion at the time of interval cytoreductive surgery. Future studies will continue to evaluate the safety and impact of transfusion on ovarian cancer survival in this at risk population.



https://ift.tt/2qaxsHC

Long-term outcomes of the 2-week schedule of hypofractionated radiotherapy for recurrent hepatocellular carcinoma

Abstract

Background

The 2-week schedule of hypofractionated radiotherapy as a salvage treatment for hepatocellular carcinoma (HCC) has previously exhibited promising results; this study aimed to assess its long-term clinical outcomes in patients with recurrent HCC ineligible for curative treatments.

Methods

We retrospectively enrolled 77 patients (84 lesions) with HCC who were treated with hypofractionated radiotherapy between December 2008 and July 2013. Primary inclusion criteria were HCC unsuitable for curative treatments and HCC located within 2 cm of a critical normal organ. We administered 3.5–5 Gy/fraction for 2 weeks, resulting in a total dose of 35–50 Gy.

Results

The median follow-up period was 33.6 (range, 4.8–78.3) months. The 3- and 5-year overall survival rates were 52.3% and 40.9%, respectively, and local control rates were 79.5% and 72.6% in all treated lesions, respectively. The 5-year local control rate was better in the higher radiation dose group than in the lower radiation dose group (50 Gy: 79.7% vs. < 50 Gy: 66.1%); however, the difference was not statistically significant (P = 0.493). We observed grade ≥ 3 hepatic toxicity in 2 (2.6%) patients and grade 3 gastrointestinal bleeding in 1 (1.3%) patient. However, grade ≥ 4 toxicity was not observed after hypofractionated radiotherapy.

Conclusions

The 2-week schedule of hypofractionated radiotherapy for recurrent HCC exhibited good local control and acceptable treatment-related toxicity during the long-term follow-up period. Thus, this fractionation schedule can be a potential salvage treatment option for recurrent HCC, particularly for tumors located close to a radiosensitive gastrointestinal organ.



https://ift.tt/2CG9w6p

Compliance with Guidelines on Thromboprophylaxis for Acutely Admitted Medical Patients

Abstract

Introduction

The risk of venous thromboembolism (VTE) is increased by more than 100-fold among hospitalised medical patients compared to subjects in the community. The Danish Council for the Use of Expensive Hospital Medicines has published national guidelines on thromboprophylaxis (TP) in which the risks of VTE and bleeding are balanced. We wanted to investigate the proportion of acutely admitted medical patients for whom thromboprophylaxis was indicated and to what extent the guidelines were followed.

Methods

Data from patients hospitalised at two medical wards were screened. We registered the proportion of patients for whom mechanical or pharmacologic TP (MTP and PTP, respectively) was indicated and whether national guidelines were followed. All data extraction and analyses were performed retrospectively.

Results

After exclusion criteria were applied, 340 cases remained. PTP was indicated in 26 patients (7.6%) but only 4 patients were treated besides 12 patients who were already in anticoagulant treatment at submission. Conversely, 8/306 patients, in whom TP was not indicated, were started on PTP. MTP was indicated in 8/340 patients (2.4%) but therapy was not initiated in any of them. The majority (320/340, 94.1%) of cases was managed in accordance with existing guidelines. However, this high proportion was mainly explained by the large number of untreated patients, where TP was not indicated.

Conclusion

A large proportion of hospitalised medical patients was managed in conflict with national guidelines. A systematic approach to TP in patients with acute medical illness should be implemented.

Plain Language Summary

Plain language summary available for this article.



https://ift.tt/2OMGMQC

New Research From Psychological Science

Read about the latest research published in Psychological Science:

Dear Abby: Should I Give Advice or Receive It?
Lauren Eskreis-Winkler, Ayelet Fishbach, and Angela Duckworth

Open data, open materials, preregistration badgesTypically, individuals struggling to achieve a goal seek advice on how to accomplish their objective. In this investigation, however, Eskreis-Winkler and colleagues found that struggling goal-pursuers were more motivated by giving advice than receiving it. In a randomized, controlled, double-blind field experiment, middle-school students who gave motivational advice to younger students spent more time on homework over the following month than students who received motivational advice from expert teachers. The researchers replicated this phenomenon across other self-regulatory domains: Strugglers who gave advice, compared with those who received expert advice, were more motivated to save money, control their tempers, lose weight, and seek employment. Nevertheless, across domains, people erroneously predicted the opposite, expecting themselves and others to be less motivated by giving advice than receiving it. The evidence shows that offering advice motivated givers by raising their confidence—a reality that they did not anticipate.

Link Between Facial Identity and Expression Abilities Suggestive of Origins of Face Impairments in Autism: Support for the Social-Motivation Hypothesis
Ipek Oruc, Fakhri Shafai, and Grace Iarocci

Oruc and colleagues examined the relationship between face and expression identification in autism spectrum disorder (ASD) by testing adults with and without ASD in face identity and expression tasks. In the identification task, they rapidly presented neutral faces and participants had to identify them in sets of five faces. In the expression task, participants saw blocks of faces that morphed from a neutral expression to a target expression (angry, sad, or happy) and were asked to identify which target expression was the most represented in each block. Results indicated that adults with ASD performed worse in both tasks than adults without ASD. Moreover, the levels of identification of faces and of facial expressions were positively related for adults with ASD but not for adults without ASD. Oruc and colleagues also assessed social motivation (i.e., how much interest and enjoyment one has interacting with others) and found it to be lower for adults with ASD than for those without ASD. Plus, in adults with ASD and the lowest scores in social motivation, the lowest social motivation scores were associated with the lowest face/facial-expression identification abilities. These results suggest that impairments in face and expression processing in ASD might both derive from a lack of experience with faces, as the social-motivation hypothesis of ASD proposes.

Mind the Depth: Visual Perception of Shapes Is Better in Peripersonal Space
Elvio Blini, Clément Desoche, Romeo Salemme, Alexandre Kabil, Fadila Hadj-Bouziane, and Alessandro Farnè

Closer objects are perceived as bigger and therefore are easier to discriminate than more distant ones. Blini and colleagues examined whether the advantage for closer objects also depends on features such as depth. In a virtual 3-D environment or in a visual display that created the illusion of distance, participants rapidly saw cubes and spheres and had to identify the shapes. Those shapes appeared either within the peripersonal space (PPS; i.e., at a reachable distance) or in the extrapersonal space (EPS; i.e., out of reach), but all shapes had the same retinal size. Thus, in the EPS, the farther objects looked bigger than the ones in the PPS. Results indicated that the shapes presented in the PPS were identified more quickly than the ones presented in the EPS, despite looking smaller. This effect occurred even when shapes were placed along the same gaze line and in natural conditions in which distant objects indeed appeared smaller. Thus, across five experiments, Blini et al. obtained support for the idea that depth per se is important for the visual perception of objects, independent of their size. This indicates an advantage for processing objects within reach in the PPS.



https://ift.tt/2D6VcVB

Activity of EGFR Antibody in Non-V600 BRAF Mutant Metastatic Colorectal Cancer



https://ift.tt/2CEsUAC

Progression-free survival at 24 months (PFS24) and subsequent outcome for patients with diffuse large B-cell lymphoma (DLBCL) in the real-world setting



https://ift.tt/2qdHvvt

Disconnection: Exploring transfer from midwifery-led to consultant-led care a phenomenological study of women’s views

Publication date: Available online 25 October 2018

Source: Women and Birth

Author(s): Patricia Larkin, Deborah L. Biggerstaff

Abstract
Background

Understanding women's feelings during the transfer process can illuminate women's perspectives thus minimising the risk for postnatal psychological and emotional morbidity, and inform midwifery practice.

Aim

To explore the meaning women ascribe to their feelings when transferred from an environment emphasising a social model of pregnancy and birth in a Midwifery Led Unit, to a contrasting, more 'medicalised' setting of a Consultant Led Unit.

Methods

The study adopted an idiographic focus, by conducting semi-structured interviews with new mothers. A purposive sample of eleven women was recruited via participating midwifery led units and their 'Facebook' page. An interpretative phenomenological approach was selected to explore mothers' individual perceptions of experiences.

Findings

Participants described feeling a strong sense of community in the midwifery led unit, where they enjoyed a sense of belonging, safety, and support. The overarching theme of 'disconnection' signified feelings of muted agency when transferred to a different environment. Women used adaptive processes to reconcile themselves to a medicalised ideology. The impact of the transfer also resulted in a sense of alienation and 'not belonging'.

Conclusion

Adjustment to a different model of care meant women needed to rapidly amend their notions of normality and agency, at the same time as entering motherhood. Raising awareness about the possible psychological adjustments women have to make during at this time could provide reassurance to other women. It also highlights the need for support during and after transfer. Strengthening continuity of care could help facilitate the adjustment process.



https://ift.tt/2O4tsly

IgE Cross-Reactivity of Cashew Nut Allergens

Background: Allergic sensitisation towards cashew nut often happens without a clear history of eating cashew nut. IgE cross-reactivity between cashew and pistachio nut is well described; however, the ability of cashew nut-specific IgE to cross-react to common tree nut species and other Anacardiaceae, like mango, pink peppercorn, or sumac is largely unknown. Objectives: Cashew nut allergic individuals may cross-react to foods that are phylogenetically related to cashew. We aimed to determine IgE cross-sensitisation and cross-reactivity profiles in cashew nut-sensitised subjects, towards botanically related proteins of other Anacardiaceae family members and related tree nut species. Method: Sera from children with a suspected cashew nut allergy (n = 56) were assessed for IgE sensitisation to common tree nuts, mango, pink peppercorn, and sumac using dot blot technique. Allergen cross-reactivity patterns between Anacardiaceae species were subsequently examined by SDS-PAGE and immunoblot inhibition, and IgE-reactive allergens were identified by LC-MS/MS. Results: From the 56 subjects analysed, 36 were positive on dot blot for cashew nut (63%). Of these, 50% were mono-sensitised to cashew nuts, 19% were co-sensitised to Anacardiaceae species, and 31% were co-sensitised to tree nuts. Subjects co-sensitised to Anacardiaceae species displayed a different allergen recognition pattern than subjects sensitised to common tree nuts. In pink peppercorn, putative albumin- and legumin-type seed storage proteins were found to cross-react with serum of cashew nut-sensitised subjects in vitro. In addition, a putative luminal binding protein was identified, which, among others, may be involved in cross-reactivity between several Anacardiaceae species. Conclusions: Results demonstrate the in vitro presence of IgE cross-sensitisation in children towards multiple Anacardiaceae species. In this study, putative novel allergens were identified in cashew, pistachio, and pink peppercorn, which may pose factors that underlie the observed cross-sensitivity to these species. The clinical relevance of this widespread cross-sensitisation is unknown.
Int Arch Allergy Immunol

https://ift.tt/2Revhy8

Ara h 1 and Ara h 6 Sensitization Causes Clinical Peanut Allergy in Ara h 2-Negative Individuals

Background: Of the major peanut allergens, sensitivity to Ara h 2 has the highest prediction for clinical allergy. In this study, we evaluated sensitization to peanut components in Iceland and related Ara h 2-negative sensitization to clinical allergy. Methods: Ara h 1, Ara h 2, Ara h 3, Ara h 8, and Bet v 1 IgEs were measured (ImmunoCAP) in 220 peanut IgE (Pn-IgE)-positive serum samples. Ara h 2 IgE-negative individuals were invited to an open peanut challenge and evaluated for Ara h 6 and 9 sensitization (ISAC microarray). Results: The Ara h 2 IgE-negative group (52.3%, 115/220) was older (p = 0.04) and more likely to have a history of pollen allergy than the Ara h 2-positive group (p #x3c; 0.001). Of the Ara h 2-negative participants, 24.3% were already consuming peanuts and 38.3% were unavailable. Of the 43 who underwent an open peanut challenge, 79% were negative, 14% were positive, and 7% were inconclusive. Those who reacted to peanuts had a higher Ara h 1 IgE than that of the tolerant participants, and 3 were positive to Ara h 6 IgE, and 2 of those subjects were monosensitized. Ara h 8 may have caused a positive reaction, while Ara h 9 did not. Conclusions: Half of the peanut-sensitized individuals in Iceland were not sensitized to the major allergen Ara h 2. Ara h 1, Ara h 3, and Ara h 6 sensitizations resulted in a positive open peanut challenge and they are therefore clinically important for individuals with a peanut allergy in Iceland.
Int Arch Allergy Immunol

https://ift.tt/2OPusPQ

The ILTS Consensus Conference on NAFLD/NASH and liver transplantation

No abstract available

https://ift.tt/2z5u3hl

Perioperative complications of anterior decompression with fusion versus laminoplasty for the treatment of cervical ossification of the posterior longitudinal ligament: Propensity score matching analysis using a nation-wide inpatient database

Publication date: Available online 26 October 2018

Source: The Spine Journal

Author(s): Shingo Morishita, Toshitaka Yoshii, Atsushi Okawa, Kiyohide Fushimi, Takeo Fujiwara

Abstract
Background Context

Surgical treatment of cervical ossification of the posterior longitudinal ligament (OPLL) has a high risk of various complications. Anterior decompression with fusion (ADF) and laminoplasty (LAMP) are the most representative surgical procedures. However, few studies have compared the two procedures in terms of perioperative surgical complications.

Purpose

To compare the perioperative complications post-ADF and LAMP for cervical OPLL using a large national inpatient database.

Study design

A retrospective cohort study with propensity score matching analysis.

Patient sample

Overall, 8718 (ADF/LAMP:1333/7485) patients who underwent surgery for cervical OPLL from April 1, 2010 to March 31, 2016 in hospitals using the Diagnosis Procedure Combination (DPC) were analyzed.

Outcome measures

The occurrence of postoperative complications during hospitalization.

Methods

We compared the perioperative systemic and local complications, reoperation rates and costs between ADF and LAMP using propensity score matching analysis.

Results

One-to-one matching resulted in 1192 pairs of patients who underwent ADF and LAMP. The postoperative cardiovascular event rate was significantly higher (ADF/LAMP=1.9/0.8%, P=0.013) in the ADF group. The incidence rates of dysphagia (similarly, 2.4/0.2%, P<0.001), pneumonia (1.0/0.3%, P=0.045) and spinal fluid leakage (2.4/0.4%, P<0.001) were also higher in the ADF group, even after matching. The costs were also higher in the ADF group. However, surgical site infection (2.0/3.4%, P=0.033) was significantly lower in the ADF group. No significant difference in the reoperation rates was found between the groups.

Conclusion

The present study, using a large nationwide database, demonstrated that perioperative complications were more common in the ADF group, but that SSI was more frequently observed in the LAMP group.



https://ift.tt/2PXfV0X

The Impact of Stenosis and Translation on Spinal Cord Injuries in Traumatic Cervical Facet Dislocations

Publication date: Available online 25 October 2018

Source: The Spine Journal

Author(s): David M. Glassman, Erik Magnusson, Julie Agel, Carlo Bellabarba, Richard J. Bransford

ABSTRACT
Background Context

: Although facet dislocations account for only 6% of cervical trauma, the consequences are often devastating. Cervical facet dislocations are associated with a disproportionate amount of spinal cord injuries; however, neurologic examination of patients is often difficult, as patients commonly present with reduced levels of consciousness. There are limited studies that have investigated the impact of spinal canal diameter and translation on neurologic injury following facet dislocations.

Purpose

: Review a consecutive series of patients with facet dislocations to assess the impact of sagittal diameter and translation on SCI.

Study Design

: Retrospective review at a level I trauma center identified 97 patients with facet dislocations.

Methods

: Between 2004 and 2014, a retrospective review at a level I trauma center identified patients with traumatic facet dislocation. Demographic data, neurologic exams, and radiographic findings were reviewed. We assessed sagittal diameter at the injury level, as well as above and below, and translation. This study has no funding source and its authors have no potential conflicts of interest-associated biases.

Results

: Ninety-seven patients presented with facet dislocations. Fifty-nine (61%) presented with a SCI. Those with ASIA A averaged 8.0 mm of injury level canal diameter, and ASIA E averaged 12.6 mm (p<0.001). Additionally, those with ASIA A averaged 8.0 mm of translation, and ASIA E averaged 4.2 mm (p <0.001). Two groups were created based on their general motor function. Those with ASIA A-C averaged 8.4 mm of injury level canal diameter, and ASIA D-E averaged 12.3 mm (p<0.001). Those with ASIA A-C averaged 7.8 mm of translation, and ASIA D-E averaged 4.4 mm (p<0.001). Receiver operating characteristic (ROC) curves demonstrated that translation was a good predictor of ASIA A-C and canal diameter was an almost perfect predictor of ASIA D-E.

Conclusions

: Our data indicates that patients with greater translation and/or a smaller canal diameter at the injury level have a higher rate of SCI. Adjacent canal diameter did not correlate with neurologic injury.



https://ift.tt/2AuOqqb

Walking Speed is Correlated with the Isokinetic Muscular Strength of the Knee in Patients with Charcot-Marie-Tooth Type 1A

Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common hereditary neuropathy. Affected individuals have a distal motor deficit, initially affecting the lower limbs and impairing walking performance. Isokinetic dynamometry can be used to objectively assess muscle strength of patients with neuromuscular disorders. No studies have evaluated the effect of muscle strength deficits of knee extensors and flexors on walking parameters for patients with CMT1A. The purpose of this study was to determine correlations between the isokinetic muscular strength (IMS) of knee flexors (KFs) and knee extensors (KEs) and walk parameters for patients with CMT1A. IMS of the knee was assessed on an isokinetic dynamometer (Cybex®) and walking by instrumented walkway analysis (GaitRite®). We included 33 patients (23 females, mean age 46.7±13.3 years, mean body mass index 25.7±4.6 kg/m2). We found a correlation between walking speed and IMS of KEs for the entire population and between walking speed and IMS of KEs and KFs for patients under 50 years of age. Isokinetic dynamometry can provide objective measures of knee muscle strength, which is correlated with walking speed but not cadence or step/stride length of patients with CMT. Related author: Pr Emmanuel Coudeyre, Department of Physical Medicine and Rehabilitation, Clermont-Ferrand University Hospital, Hôpital Nord, route de Chateaugay, BP 30056, 63 118 Cébazat, France, Tel: + 33 4 73 75 09 00 Fax: + 33 4 73 75 09 01, Email: ecoudeyre@chu-clermontferrand.fr Conflict of Interest: Each individual named as an author meets the uniform Requirements for Manuscripts Submitted to biomedical Journals criteria for authorship. All the authors declare do not have any conflict of interest to declare. Funding: The authors sincerely thank Clermont-Ferrand University Hospital for funding (2012). Length of manuscript: 186 words for the abstract, 1743 for the main text, 2 tables/figures and 24 references. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2CJuTUD

A Nutritional Cause of Low Back Pain?

No abstract available

https://ift.tt/2qc1Wc8

A “BREACH” TOO FAR: EXERTIONAL RHABDOMYOLYSIS IN THE ELBOW FLEXOR MUSCLES

No abstract available

https://ift.tt/2CGV7qt

PVT1 protects diabetic peripheral neuropathy via PI3K/AKT pathway

OBJECTIVE: To investigate whether Plasmacytoma Variant Translocation 1 (PVT1) could regulate the occurrence and progression of diabetic peripheral neuropathy (DPN) via activating the PI3K/AKT pathway.

MATERIALS AND METHODS: Diabetes model in rats was constructed by streptozotocin (STZ) injection. PVT1 expression in diabetic rats and control rats was detected by quantitative real time-polymerase chain reaction (qRT-PCR). Rats were injected with PVT1 overexpression lentivirus or vector, respectively, followed by determination of mechanical withdrawal threshold (MWT), thermal withdrawal latency (TWL) and sensory nerve conduction velocity (SNCV). Cell apoptosis of dorsal root ganglia (DRG) was accessed by TUNEL. Western blot was performed to detect the expressions of neurodegeneration-related genes and neurogenesis-related genes. The regulatory effect of PVT1 on the PI3K/AKT pathway was detected by Western blot.

RESULTS: PVT1 was downregulated in diabetic rats compared with that of controls. Diabetic rats presented higher MWT, TWL and SNCV. Cell apoptosis of DRG was pronounced in diabetic rats. The amount of inflammation-related glial cells increased in diabetic rats. PVT1 overexpression remarkably decreased MWT and TWL. PVT1 downregulated expressions of neurodegeneration-related genes and upregulated neurogenesis-related genes. Western blot results suggested that PI3K/AKT pathway in diabetic rats was blocked, which was reversed by PVT1 overexpression.

CONCLUSIONS: PVT1 is lowly expressed in diabetic rats, leading to decreased mechanical withdrawal threshold, thermal withdrawal latency and sensory nerve conduction velocity. PVT1 protects diabetic peripheral neuropathy via PI3K/AKT pathway.

L'articolo PVT1 protects diabetic peripheral neuropathy via PI3K/AKT pathway sembra essere il primo su European Review.



https://ift.tt/2Sjl3hr

Nrf2-ARE signaling pathway regulates the expressions of A1R and ENT1 in the brain of epileptic rats

OBJECTIVE: To explore the behavioral changes and the expressions of the A1 receptor (A1R) and balanced nucleoside transporter-1 (ENT1) in the brain of epileptic rats after activating the NF-E2-related factor 2 (Nrf2)-ARE signaling pathway.

MATERIALS AND METHODS: Adult male Sprague-Dawley (SD) rats were randomly divided into normal control group, epilepsy group, and t-butylhydroquinone (tBHQ) group, with 10 rats in each group. Lithium-pilocarpine induced epilepsy model in rats was established. The first epileptic latency and seizure frequency within 1 hour were observed in each group using the Racine scoring system. HE (Hematoxylin and Eosin) staining was used to observe the pathological lesions in the brain tissue of each group. The expressions of A1R, ENT1, and relative genes in Nrf2-ARE pathway in rat hippocampus was detected by immunohistochemistry and Western blot.

RESULTS: Compared with rats in epileptic group, the first seizure latency was prolonged and the seizure frequency decreased in tBHQ group (p<0.05). The degree of brain lesions in tHBQ group was lighter than that of epilepsy group. ENT1 expression in rat hippocampus of epileptic group was significantly upregulated than that of normal control group and tBHQ group. Besides, the protein levels of A1R, Nrf2, HO-1, and ARE in rat hippocampus of epilepsy group markedly decreased compared with those of normal control group. However, protein expressions of A1R, Nrf2, HO-1, and ARE proteins in rat hippocampus of tBHQ group were markedly upregulated.

CONCLUSIONS: Activation of the Nrf2-ARE signaling pathway can reduce the pathological damage of rat hippocampal neurons, prolong the latency of seizures, and reduce the degree of epileptic seizure in rats.

L'articolo Nrf2-ARE signaling pathway regulates the expressions of A1R and ENT1 in the brain of epileptic rats sembra essere il primo su European Review.



https://ift.tt/2z51vo6

Montelukast enhances cytocidal effects of carfilzomib in multiple myeloma by inhibiting mTOR pathway

.


https://ift.tt/2PTQBZK

Serine/threonine kinase 32C is overexpressed in bladder cancer and contributes to tumor progression

.


https://ift.tt/2Auqzqy

Metformin inhibited colitis and colitis-associated cancer (CAC) through protecting mitochondrial structures of colorectal epithelial cells in mice

.


https://ift.tt/2PXHuqP

Identification of a novel PDGFRA point mutation at p.P6L as a potential molecular target of imatinib in an eosinophilia patient showing genetic heterogeneity

.


https://ift.tt/2AtLw59

Dynamic changes of different phenotypic and genetic circulating tumor cells as a biomarker for evaluating the prognosis of RCC

.


https://ift.tt/2PWmwZn

Ixazomib promotes CHOP-dependent DR5 induction and apoptosis in colorectal cancer cells

.


https://ift.tt/2AvAUmh

RasGRF2 promotes migration and invasion of colorectal cancer cells by modulating expression of MMP9 through Src/Akt/NF-κB pathway

.


https://ift.tt/2PWySRr

Molecular classification and subtype-specific drug sensitivity research of uterine carcinosarcoma under multi-omics framework

.


https://ift.tt/2AtKki1

Cardiac transplantation across preformed HLA-antibody barriers

No abstract available

https://ift.tt/2SlWPmv

Haploidentical Hematopoietic Stem Cell Transplant complicated by Atypical Hemolytic Uremic Syndrome and Kidney Transplant from the same donor with no Immunosuppression but C5 Inhibition

Background Atypical hemolytic uremic syndrome (aHUS) is life-threatening condition particularly when complicating allograft hematopoietic stem cell transplant (HSCT). In the past, the outcome was very poor with the majority of patients reaching end stage renal disease (ESRD) or dying with little or no chances of kidney transplant (KTx) due to the high risk of relapse. The availability of C5 inhibition has opened up significant therapeutic opportunities and has improved the outcome particularly if complement dysregulation (CD) is the underlying pathogenetic mechanism. Methods: We describe a peculiar case of a girl with aHUS complicating HSCT and her subsequent successful KTx received from the same donor thus performed without immunosuppression but anti C5 inhibition. Results Soon after HSCT performed for acute lymphoblastic leukemia, the patient developed a thrombotic microangiopathy (TA-TMA) due to CD and reached ESRD. After 2 years on dialysis the patient received a KTx from her father who was already the HSCT donor. Given the full chimerism, no immunosuppressive agent was prescribed except a short (2 days) course of steroids and eculizumab to prevent aHUS relapse. Nine months after the KTx the patient is well with normal renal function, no immunosuppression and continues eculizumab prevention of aHUS (1 infusion every 21 days). Conclusions All patients with TA-TMA should be screened for the causes of CD. C5 inhibition with eculizumab is an important therapeutic resource to manage this complication. When KTx is necessary, immunosuppression can be safely withhold in case of same donor for both grafts and documented full chimerism. Correspondence information: Ardissino Gianluigi, Center for HUS Control, Prevention and Management, Fondazione, IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Commenda, 9, 20122 Milan, Italy, e-mail: ardissino@centroseu.org Authorship page Authorship: Ardissino Gianluigi: participated in the writing of the paper Cresseri Donata: participated in the writing of the paper Giglio Fabio: participated in the writing of the paper Onida Francesco.: participated in the writing of the paper Iannuzzella Francesco: participated in the writing of the paper Tel Francesca: participated in the writing of the paper Giussani Antenore: participated in the writing of the paper Messa Piergiorgio: participated in the writing of the paper Longhi Selena: participated in the writing of the paper Vincenti Daniele: participated in the writing of the paper Tedeschi Silvana: participated in the writing of the paper Cugno Massimo: participated in the writing of the paper Ciceri Fabio: participated in the writing of the paper Disclosure: The authors declare no conflicts of interest Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2z56yF3