Fish burger enriched by olive oil industrial by-product

Abstract

Oil industry produces large volume of waste, which represents a disposal and a potential environmental pollution problem. Nevertheless, they are also promising sources of compounds that can be recovered and used as valuable substances. The aim of this work is to exploit solid olive by-products, in particular dry olive paste flour (DOPF) coming from Coratina cultivar, to enrich fish burger and enhance the quality characteristics. In particular, the addition of olive by-products leads to an increase of the phenolic content and the antioxidant activity; however, it also provokes a deterioration of sensory quality. Therefore, to balance quality and sensory characteristics of fish burgers, three subsequent phases have been carried out: first, the quality of DOPF in terms of phenolic compounds content and antioxidant activity has been assessed; afterward, DOPF has been properly added to fish burgers and, finally, the formulation of the enriched fish burgers has been optimized in order to improve the sensory quality. Results suggested that the enriched burgers with 10% DOPF showed considerable amounts of polyphenols and antioxidant activity, even though they are not very acceptable from the sensory point of view. Pre-treating DOPF by hydration/extraction with milk, significantly improved the burger sensory quality by reducing the concentration of bitter components.

The aim of this study is to develop fish burgers enriched with olive by-products, in particular dry olive paste flour (DOPF) coming from Coratina cultivar. Burgers with 10% of DOPF were developed. Both nutritional and sensory quality were optimized.

http://ift.tt/2ru6m0G

Cost-Effectiveness of Drug Treatments for Advanced Melanoma: A Systematic Literature Review

Abstract

Background

Until recently, advanced melanoma (unresectable and metastatic) has had a poor prognosis and has been treated with chemotherapy. The introduction of new treatments (BRAF and MEK inhibitors and immunotherapy) has improved overall survival and progression-free survival of some patients.

Objective

The objective of this study was to review the published evidence on the cost-effectiveness of pharmacological treatments for advanced melanoma.

Methods

A systematic literature search was conducted, without date or language restrictions, in PubMed, EMBASE, Scopus, the Cochrane Library, the UK National Institute for Health and Care Excellence databases and the Health Technology Assessment journal. Internet searches were also made to identify possible grey literature. Main study characteristics, methods and outcomes were extracted and critically assessed. The quality of health economic studies was assessed by the Quality Assessment of Economic Evaluation in Health Care checklist.

Results

The search identified nine full-text pharmacoeconomic analyses of advanced melanoma treatments. According to the economic analyses published in the articles, the new treatments have been shown to be more effective (with more life-years and quality-adjusted life-years) than chemotherapy, although generally the cost per quality-adjusted life-year gained was above the commonly accepted threshold. Because of the variability of the available analyses comparing the new treatments, we cannot determine which treatment is the most cost-effective.

Conclusions

From the available data, it cannot be concluded that the new drugs (BRAF and MEK inhibitors and immunotherapy) are cost effective compared with chemotherapy or which is the most cost-effective new treatment.

http://ift.tt/2s9p5uV

Care Bundles in Emergency Medicine

Abstract

The ability to make sound clinical decisions in a high stress and often chaotic atmosphere lies at the heart of emergency medicine. This can be a daunting task when one considers the sheer volume of pathology covered under the umbrella of emergency medicine.

This article is protected by copyright. All rights reserved.

http://ift.tt/2s2SSGq

Automated Image Analysis of HER2 Fluorescence In Situ Hybridization to Refine Definitions of Genetic Heterogeneity in Breast Cancer Tissue

Human epidermal growth factor receptor 2 gene- (HER2-) targeted therapy for breast cancer relies primarily on HER2 overexpression established by immunohistochemistry (IHC) with borderline cases being further tested for amplification by fluorescence in situ hybridization (FISH). Manual interpretation of HER2 FISH is based on a limited number of cells and rather complex definitions of equivocal, polysomic, and genetically heterogeneous (GH) cases. Image analysis (IA) can extract high-capacity data and potentially improve HER2 testing in borderline cases. We investigated statistically derived indicators of HER2 heterogeneity in HER2 FISH data obtained by automated IA of 50 IHC borderline (2+) cases of invasive ductal breast carcinoma. Overall, IA significantly underestimated the conventional HER2, CEP17 counts, and HER2/CEP17 ratio; however, it collected more amplified cells in some cases below the lower limit of GH definition by manual procedure. Indicators for amplification, polysomy, and bimodality were extracted by factor analysis and allowed clustering of the tumors into amplified, nonamplified, and equivocal/polysomy categories. The bimodality indicator provided independent cell diversity characteristics for all clusters. Tumors classified as bimodal only partially coincided with the conventional GH heterogeneity category. We conclude that automated high-capacity nonselective tumor cell assay can generate evidence-based HER2 intratumor heterogeneity indicators to refine GH definitions.

http://ift.tt/2rt4oO4

Targeting Tumor Microenvironment: Effects of Chinese Herbal Formulae on Macrophage-Mediated Lung Cancer in Mice

Our previous studies have shown that Qing-Re-Huo-Xue (QRHX) formulae had significant anti-inflammatory effects in chronic airway diseases such as asthma and chronic obstructive lung disease. Here, we examined the effects of QRHX on lung cancer cell invasion and the potential associated mechanism(s), mainly polarization of macrophages in the tumor microenvironment. In vivo, QRHX both inhibited tumor growth and decreased the number of tumor-associated macrophages (TAMs) in mice with lung cancer. Further study indicated that QRHX inhibited cancer-related inflammation in tumor by decreasing infiltration of TAMs and IL-6 and TNF-α production and meanwhile decreased arginase 1 (Arg-1) expression and increased inducible NO synthase (iNOS) expression. QRHX could markedly inhibit CD31 and VEGF protein expression. Additionally, CXCL12/CXCR4 expression and JAK2/STAT3 phosphorylation were reduced in QRHX treatment group. Thus, we draw that QRHX played a more important role in inhibiting tumor growth by regulating TAMs in mice, which was found to be associated with the inhibition of inflammation and the CXCL12/CXCR4/JAK2/STAT3 signaling pathway.

http://ift.tt/2s2F92j

Moxibustion Alleviates Injury in a Rat Focal Segmental Glomerulosclerosis Model

Objectives. To evaluate the therapeutic effects of moxibustion at Shenshu (BL-23) and Geshu (BL-17) acupoints in a focal segmental glomerulosclerosis (FSGS) model in rats. Methods. A FSGS rat model was established by single nephrectomy and repeated injection of doxorubicin. The FSGS rats were randomly divided into the model group, losartan (positive control) group, Shenshu moxibustion group, and Geshu moxibustion group. Molecular indicators of kidney function and renal pathological changes were monitored. Results. Urinary protein, serum creatinine, urea nitrogen, and serum uric acid were significantly reduced after 12-week intervention with losartan, Shenshu, or Geshu moxibustion. Renal α-SMA, FN, and TGF-β were also decreased, while podocin and nephrin protein and mRNA were increased. The pathological damage in renal tissue was obviously alleviated by all three treatments, which suggests that moxibustion may have similar efficacy to losartan in the treatment of FSGS. Conclusion. Moxibustion alleviates podocyte injury and inhibits renal interstitial fibrosis in the FSGS rat model, thereby minimizing the progression of glomerular sclerosis and improving renal function.

http://ift.tt/2rtk3gC

Plesiomonas shigelloides: An Unusual Cause of Septic Abortion

Plesiomonas shigelloides, the only oxidase-positive Enterobacteriaceae, is an inhabitant of freshwater and estuary ecosystems. We report the first possible case of Plesiomonas shigelloides-induced septic abortion. This 24-year-old female was successfully treated by dilatation and curettage as well as antimicrobial therapy.

http://ift.tt/2rttE6V

Refusal of Emergency Medical Treatment: Case Studies and Ethical Foundations

Informed consent is an important component of emergency medical treatment. Most emergency department patients can provide informed consent for treatment upon arrival. Informed consent should also be obtained for emergency medical interventions that may entail significant risk. A related concept to informed consent is informed refusal of treatment. Patients may refuse emergency medical treatment during their evaluation and treatment. This article addresses important considerations for patients who refuse treatment, including case studies and discussion of definitions, epidemiology, assessment of decisional capacity, information delivery, medicolegal considerations, and alternative care plans.

http://ift.tt/2r8evF1

Nonphysician Out-of-Hospital Rapid Sequence Intubation Success and Adverse Events: A Systematic Review and Meta-Analysis

Rapid sequence intubation performed by nonphysicians such as paramedics or nurses has become increasingly common in many countries; however, concerns have been stated in regard to the safe use and appropriateness of rapid sequence intubation when performed by these health care providers. The aim of our study is to compare rapid sequence intubation success and adverse events between nonphysician and physician in the out-of-hospital setting.

http://ift.tt/2qo76Vf

Rib Fracture Diagnosis in the Panscan Era

With increased use of chest computed tomography (CT) in trauma evaluation, traditional teachings in regard to rib fracture morbidity and mortality may no longer be accurate. We seek to determine rates of rib fracture observed on chest CT only; admission and mortality of patients with isolated rib fractures, rib fractures observed on CT only, and first or second rib fractures; and first or second rib fracture–associated great vessel injury.

http://ift.tt/2r8G29C

Association of Out-of-Hospital Hypotension Depth and Duration With Traumatic Brain Injury Mortality

Out-of-hospital hypotension has been associated with increased mortality in traumatic brain injury (TBI). The association of TBI mortality with the depth or duration of out-of-hospital hypotension is unknown. We evaluated the relationship between the depth and duration of out-of-hospital hypotension and mortality in major traumatic brain injury.

http://ift.tt/2qnLgkC

Repeated Emergency Medical Services Use by Older Adults: Analysis of a Comprehensive Statewide Database

The objective of this study is to characterize repeated emergency medical services (EMS) transports among older adults across a large and socioeconomically diverse region.

http://ift.tt/2r8rF5c

Geographic Variation in Use of Ambulance Transport to the Emergency Department

Evidence on variability in emergency medical services use is limited. We obtain national evidence on geographic variation in the use of ambulance transport to the emergency department (ED) among Medicare enrollees and assess the role of health status, socioeconomic status, and provider availability.

http://ift.tt/2qnCl2p

The Effect of Utilization Review on Emergency Department Operations

Increasingly, hospitals are using utilization review software to reduce hospital admissions in an effort to contain costs. Such practices have the potential to increase the number of unsafe discharges, particularly in public safety-net hospitals. Utilization review software tools are not well studied with regard to their effect on emergency department (ED) operations. We study the effect of prospectively used admission decision support on ED operations.

http://ift.tt/2r8mAK5

External Defibrillator Damage Associated With Attempted Synchronized Dual-Dose Cardioversion

The simultaneous use of 2 external defibrillators to administer either dual or sequential cardioversion or defibrillation for refractory cardiac arrhythmias is increasing in both the out-of-hospital and inhospital settings. Using 2 defibrillators to administer higher energy levels than can be achieved with a single defibrillator is considered off-label and is currently not part of published advanced cardiac life support guidelines. We report the first case in which the use of dual-dose cardioversion was associated with external defibrillator damage.

http://ift.tt/2qnwoTs

Shared Decisionmaking in the Emergency Department: A Guiding Framework for Clinicians

Shared decisionmaking has been proposed as a method to promote active engagement of patients in emergency care decisions. Despite the recent attention shared decisionmaking has received in the emergency medicine community, including being the topic of the 2016 Academic Emergency Medicine Consensus Conference, misconceptions remain in regard to the precise meaning of the term, the process, and the conditions under which it is most likely to be valuable. With the help of a patient representative and an interaction designer, we developed a simple framework to illustrate how shared decisionmaking should be approached in clinical practice.

http://ift.tt/2r8h7Tn

Are α-Blockers Beneficial for Outpatient Management of Uncomplicated Ureteric Stones?

The initial search strategy identified 443 unique studies; screening against inclusion or exclusion criteria yielded 55 randomized controlled trials comparing α-blocker medical expulsive therapy for passage of uncomplicated ureteric stones less than 10 mm versus either a placebo (14 studies) or expectant management (41 studies) control. Tamsulosin was the primary α-blocker used (40 of 55 studies), at various dosages (0.2 to 0.4 mg) and for various durations (7 to 30 days); however, the results did not differ among α-blockers.

http://ift.tt/2qnGymU

Coming Fast out of the Gate: Pacing and Productivity From a Resident Perspective

SEE RELATED ARTICLE, P. ■■■.

http://ift.tt/2r8jAgG

A Qualitative Analysis of Adolescent and Caregiver Acceptability of Universally Offered Gonorrhea and Chlamydia Screening in the Pediatric Emergency Department

We qualitatively explore adolescent and parent or guardian attitudes about benefits and barriers to universally offered gonorrhea and chlamydia screening and modalities for assessing interest in screening in the pediatric emergency department (ED).

http://ift.tt/2qnRnpd

In this issue

http://ift.tt/2rav2u7

Colorectal cancer molecular profiling: from IHC to NGS in search of optimal algorithm

Abstract

Advances in defining the mutational landscape of colorectal cancer (CRC) over the past decades have revolutionized the molecular understanding and clinical testing algorithms for this disease. Mutation testing is standard of care for the work-up of CRCs. This review focuses on the current indications and strategies for molecular testing in CRC and discusses the potential changes in CRC testing approach associated with the emerging clinical application of genomic-based technologies.

http://ift.tt/2s8Q4Xo

Loss of gait control assessed by cognitive-motor dual-tasks: pros and cons in detecting people at risk of developing Alzheimer’s and Parkinson’s diseases

Abstract

Alzheimer's and Parkinson's diseases are age-related progressive neurodegenerative diseases of increasing prevalence worldwide. In the absence of curative therapy, current research is interested in prevention, by identifying subtle signs of early-stage neurodegeneration. Today, the field of behavioral neuroscience has emerged as one of the most promising areas of research on this topic. Recently, it has been shown that the exacerbation of gait disorders under dual-task conditions (i.e., simultaneous performance of cognitive and motor tasks) could be a characteristic feature of Alzheimer's and Parkinson's diseases. The cognitive-motor dual-task paradigm during walking allows to assess whether (i) executive attention is abnormally impaired in prodromal Alzheimer's disease or (ii) compensation strategies are used in order to preserve gait function when the basal ganglia system is altered in prodromal Parkinson's disease. This review aims at (i) identifying patterns of dual-task-related gait changes that are specific to Alzheimer's and Parkinson's diseases, respectively, (ii) demonstrating that these changes could potentially be used as prediagnostic markers for disease onset, (iii) reviewing pros and cons of existing dual-task studies, and (iv) proposing future directions for clinical research.

http://ift.tt/2s8CO51

Protective effects of royal jelly on the histomorphologic, oxidative stress and sperm parameters in Ofloxacin treated rat

Abstract

Royal jelly is produced by worker bees as nutrition for bee larvae and adult queens and has also been shown to have protective effects against antibiotics. The aim of this investigation was to determine protective effect of royal jelly on the reproductive functions of male rats treated with ofloxacin. In this experiment, 32 mature male albino rats were randomly allocated into four groups (n = 8): control, ofloxacin only, royal jelly only, and ofloxacin with royal jelly. The results revealed that ofloxacin alone caused significant decreases (P < 0.05) in follicle-stimulating hormone, luteinizing hormone, testosterone, sperm count, sperm viability, total thiol molecules, and total antioxidant capacity compared to the control group. However, levels of immature sperm, DNA impaired sperm, malondialdehyde and nitric oxide were significantly increased (P < 0.05) in the ofloxacin group compared to the control. In the ofloxacin with royal jelly group, no significant increases or decreases were observed. Royal jelly has protective effects on reproductive function of male rat treated with ofloxacin.

http://ift.tt/2rsZaCh

A rare case of sarcoidosis in accessory spleen

http://ift.tt/2qv9wfD

Concurrent Focal Fat Sparing and Peritumoral Fat Sparing in Diffuse Fatty Liver Identified on 18F-FDG PETCT and Multiparametric Magnetic Resonance Imaging

http://ift.tt/2rKeE4o

MiR-1271 Inhibits Cell Growth in Prostate Cancer by Targeting ERG

Abstract

ETS-related gene (ERG) is an oncogene that is commonly found in prostate cancer (PCa). Several miRNAs have been reported to be associated with PCa. This study was undertaken to identify miRNAs that act as a tumor suppressor by targeting ERG. We collected 70 PCa and paired adjacent non-tumor (Adjacent-N) tissues and analyzed ERG expression by immunohistochemistry(IHC). Expression of 6 miRNAs (miR-21,-34a,-96,-125b,-150 and miR-1271) was analyzed by qRT-PCR. Luciferase reporter assay was performed to examine miRNA binding to the 3′-UTR of target genes. The effects of ectopic expression of miRNA on cell growth and MAPK signaling pathway were investigated in in PC-3 and LNCaP cell lines. Among 70 PCa cases, 13 (18.6%) were ERG positive. No significant difference of miR-34a, 96, 125b, and 150 expression was found between PCa and Adjacent-N tissues. Significantly higher level of miR-21 and lower level of miR-1271 expression were found in cancer tissues. Furthermore, miR-1271 was down-regulated in ERG-positive PCa cases (p < 0.05). Based on luciferase reporter assay, we identified ERG gene as a direct target gene for miR-1271. Transfection of a miR-1271 mimics into PC-3 and LNCaP cells repressed the ERG expression and significantly suppressed cell growth. Lastly, ectopic expression of miR-1271 inhibits AKT1, p38gama and CREB kinase activity. Our results suggested that reduced expression of miR-1271 may be involved in the ERG expression and that miR-1271 could be a therapeutic target for ERG-positive prostate cancer patients.

http://ift.tt/2s2gAm9

The Effects of Gender Neuroessentialism on Transprejudice: An Experimental Study

Abstract

This experimental study examined the impacts of gender neuroessentialism on stereotyping and prejudice against transgender people. We randomly assigned 132 Chinese, mostly heterosexual college students to read one of three fictitious articles in which the first article explained sex differences in personality and social behavior by neurological factors (biological determinist), a second article questioned this deterministic claim (interactionist), and a third article was unrelated to gender (neutral baseline). The biological determinist condition aimed to foster essentialist beliefs by priming the deterministic ways that the brain relates to personality and behavior, whereas the interactionist condition highlighted the interactive roles of the brain and environments on people's personality and behavior. We found that participants in the biological determinist condition showed more negative stereotypes and stronger prejudicial attitudes toward transgender people compared with participants in the interactionist condition and those in the control condition. There were no significant differences in transprejudice between the interactionist and control conditions. The present study represents one of the few studies that examined the connection between gender essentialism and transprejudice. The findings suggest that essentialist claims that ground the male/female binary in biology may lead to more transprejudice.

http://ift.tt/2s1VFzH

Macrophage-derived interleukin-1beta promotes human breast cancer cell migration and lymphatic adhesion in vitro

Abstract

Lymphovascular invasion (LVI), encompassing blood and lymphatic vessel invasion, is an important event in tumourigenesis. Macrophages within the tumour microenvironment are linked to the presence of LVI and angiogenesis. This study investigates the role of macrophage-derived, caspase-1-dependent interleukin-1beta (IL-1β) in an in vitro model of LVI. IL-1β significantly augmented the adhesion and transmigration of breast cancer cell lines MCF7 and MDA-MB-231 across endothelial cell barriers. MDA-MB-231 and MCF7 showed a higher percentage of adhesion to lymphatic endothelial cells than blood endothelial cells following endothelial cell IL-1β stimulation (P < 0.001 and P < 0.0001, respectively). Supernatants from activated macrophages increased the adhesion of tumour cells to lymphatic and blood endothelium. Secretion of IL-1β was caspase-1 dependent, and treatment with caspase-1 inhibitor reduced IL-1β production by 73% and concomitantly reduced tumour cell adhesion to levels obtained with resting macrophages. Transmigration of MDA-MB-231 cells across blood and lymphatic endothelial monolayers was significantly increased following IL-1β stimulation. Furthermore, supernatants from activated macrophages increased transmigration of MDA-MB-231 cells across endothelial monolayers, which was abolished by caspase-1 inhibition. IL-1β stimulation of tumour cells significantly increased their migratory ability and a significant increase in migration was observed when MDA-MB-231 cells were stimulated with macrophage conditioned media (two of three donors). Results demonstrate that macrophage production of IL-1β plays an important role in the migration of breast cancer cells and their adhesion to, and transmigration across, blood and lymphatic endothelial cells. Results suggest that IL-1β may play a role in the adhesion to lymphatic endothelial cells in particular.

http://ift.tt/2s7DDep

CD45RA − Foxp3 high regulatory T cells have a negative impact on the clinical outcome of head and neck squamous cell carcinoma

Abstract

Background

Although regulatory T cells (Tregs) are thought to play an important role in immune suppression, their clinical significance in head and neck squamous cell carcinoma (HNSCC) is unclear. A recent study reported Tregs could be divided into functional subsets based on the expression of CD45RA and Foxp3.

Method

The frequency of circulating Treg subsets was analyzed in patients with HNSCC and compared with the frequency in patients with benign tumors. The association of Treg subsets with the frequency of lymphocyte subsets, status of progression, clinical course, and prognosis were also examined.

Results

The frequency of CD4⁺Foxp3⁺ Tregs was comparable between HNSCC patients and age-matched benign tumor patients; however, CD45RA⁻Foxp3^high Tregs were significantly increased in HNSCC patients, in particular those with advanced stage tumors. The high frequency of CD45RA⁻Foxp3^high Tregs correlated with a poor prognosis and the low frequency of CD45RA⁻Foxp3^high Tregs before treatment showed a better clinical outcome, even in patients with advanced stage tumors. CD45RA⁻Foxp3^high Treg numbers were decreased after intensive treatments; however, Treg numbers recovered in the early stages of recurrent cases, even before the clinical manifestation.

Conclusion

CD45RA⁻Foxp3^high Tregs are associated with the clinical course of HNSCC and might be a new target for treatment and an early marker of tumor recurrence in HNSCC patients.

http://ift.tt/2r9mx2P

iSepsis – Introduction to the iSepsis Website

Introduction to ISepsis

EMCrit by Paul Marik.

http://ift.tt/2r7oKcK

Extramedullary plasmacytoma of the ureter in an HIV-positive patient

Abstract

A 45-year-old Japanese man, who was undergoing HIV infection treatment, was aware that he had gross hematuria, and he was diagnosed as having a ureteral tumor by radiographic examination. Therefore, he was referred to our department for further examination and treatment. We considered that the ureteral tumor was a urothelial carcinoma (cT2N0M0) because of the left ureteral tumor and urine cytology results, and thus, laparoscopic ureteronephrectomy was performed. The pathological diagnosis was a solitary extramedullary plasmacytoma (EMP) of the ureter. Currently, he is alive and free of disease at 7 months postoperatively. EMP develops in the nasal cavity, paranasal cavity, gastrointestinal tract, lung, thyroid, eye socket, lymph node, and various organs, but the ureter is an extremely rare site of EMP. In addition, the patient had an HIV infection. To the best of our knowledge, this is the first case of EMP of the ureter in an HIV-positive patient.

http://ift.tt/2rrc0Rg

Fluorescent CXCR4 targeting peptide as alternative for antibody staining in Ewing sarcoma

Abstract

Background

Ewing sarcoma is an aggressive, highly metastatic primary bone and soft tissue tumor most frequently occurring in the bone of young adolescents. Patients, especially those diagnosed with a metastatic disease, have a poor overall survival. Chemokine receptor CXCR4 has a key pro-tumorigenic role in the tumor microenvironment of Ewing sarcoma and has been suggested to be involved in the increased metastatic propensity. Earlier studies on CXCR4 protein expression in Ewing sarcoma yielded contradictory results when compared to CXCR4 RNA expression studies. Previously, we demonstrated that CXCR4 expression could be detected in vivo using the fluorescently tagged CXCR4-specific peptide MSAP-Ac-TZ14011. Therefore, we studied the membranous CXCR4 expression in Ewing sarcoma cell lines using MSAP-Ac-TZ14011.

Methods

The CXCR4 membrane expression levels were studied in EWS cell lines by flow cytometry using the hybrid peptide MSAP-Ac-TZ14011 and were correlated to CXCR4 RNA expression levels. The measurements were compared to levels detected using the CXCR4 antibody ab2074 under various cell preparation conditions. In addition, the staining patterns were analyzed by confocal fluorescence microscopy over time.

Results

The hybrid peptide MSAP-Ac-TZ14011 levels showed a strong and better correlation of CXCR4 membrane expression with the CXCR4 RNA expression levels than observed with the anti-CXCR4 antibody ab2074. With the hybrid peptide MSAP-Ac-TZ14011 using live cell confocal microscopy CXCR4 membrane staining and internalization was detected and the signal intensity correlated well with CXCR4 mRNA expression levels.

Conclusions

The fluorescently labeled CXCR4 targeting peptide-based method provides a reliable alternative to antibody staining to study the CXCR4 membrane expression in live cells using either flow cytometry or live cell fluorescence microscopy. The fluorescently tagged CXCR4 targeting peptide could enable in vivo detection of CXCR4 expression in Ewing sarcoma which may help to stratify cases for anti-CXCR4 therapy.

http://ift.tt/2qqt31F

Glyoxalase 1 expression is associated with an unfavorable prognosis of oropharyngeal squamous cell carcinoma

Abstract

Background

Glyoxalase 1 is a key enzyme in the detoxification of reactive metabolites such as methylglyoxal and induced Glyoxalase 1 expression has been demonstrated for several human malignancies. However, the regulation and clinical relevance of Glyoxalase 1 in the context of head and neck squamous cell carcinoma has not been addressed so far.

Methods

Argpyrimidine modification as a surrogate for methylglyoxal accumulation and Glyoxalase 1 expression in tumor cells was assessed by immunohistochemical staining of tissue microarrays with specimens from oropharyngeal squamous cell carcinoma patients (n = 154). Prognostic values of distinct Glyoxalase 1 staining patterns were demonstrated by Kaplan-Meier, univariate and multivariate Cox proportional hazard model analysis. The impact of exogenous methylglyoxal or a Glyoxalase 1 inhibitor on the viability of two established tumor cell lines was monitored by a colony-forming assay in vitro.

Results

Glyoxalase 1 expression in tumor cells of oropharyngeal squamous cell carcinoma patients was positively correlated with the presence of Argpyrimidine modification and administration of exogenous methylglyoxal induced Glyoxalase 1 protein levels in FaDu and Cal27 cells in vitro. Cal27 cells with lower basal and methylglyoxal-induced Glyoxalase 1 expression were more sensitive to the cytotoxic effect at high methylgyoxal concentrations and both cell lines showed a decrease in colony formation with increasing amounts of a Glyoxalase 1 inhibitor. A high and nuclear Glyoxalase 1 staining was significantly correlated with shorter progression-free and disease-specific survival, and served as an independent risk factor for an unfavorable prognosis of oropharyngeal squamous cell carcinoma patients.

Conclusions

Induced Glyoxalase 1 expression is a common feature in the pathogenesis of oropharyngeal squamous cell carcinoma and most likely represents an adaptive response to the accumulation of cytotoxic metabolites. Oropharyngeal squamous cell carcinoma patients with a high and nuclear Glyoxalase 1 staining pattern have a high risk for treatment failure, but might benefit from pharmacological targeting Glyoxalase 1 activity.

http://ift.tt/2rJQuXA

Macrophage-derived interleukin-1beta promotes human breast cancer cell migration and lymphatic adhesion in vitro

Abstract

Lymphovascular invasion (LVI), encompassing blood and lymphatic vessel invasion, is an important event in tumourigenesis. Macrophages within the tumour microenvironment are linked to the presence of LVI and angiogenesis. This study investigates the role of macrophage-derived, caspase-1-dependent interleukin-1beta (IL-1β) in an in vitro model of LVI. IL-1β significantly augmented the adhesion and transmigration of breast cancer cell lines MCF7 and MDA-MB-231 across endothelial cell barriers. MDA-MB-231 and MCF7 showed a higher percentage of adhesion to lymphatic endothelial cells than blood endothelial cells following endothelial cell IL-1β stimulation (P < 0.001 and P < 0.0001, respectively). Supernatants from activated macrophages increased the adhesion of tumour cells to lymphatic and blood endothelium. Secretion of IL-1β was caspase-1 dependent, and treatment with caspase-1 inhibitor reduced IL-1β production by 73% and concomitantly reduced tumour cell adhesion to levels obtained with resting macrophages. Transmigration of MDA-MB-231 cells across blood and lymphatic endothelial monolayers was significantly increased following IL-1β stimulation. Furthermore, supernatants from activated macrophages increased transmigration of MDA-MB-231 cells across endothelial monolayers, which was abolished by caspase-1 inhibition. IL-1β stimulation of tumour cells significantly increased their migratory ability and a significant increase in migration was observed when MDA-MB-231 cells were stimulated with macrophage conditioned media (two of three donors). Results demonstrate that macrophage production of IL-1β plays an important role in the migration of breast cancer cells and their adhesion to, and transmigration across, blood and lymphatic endothelial cells. Results suggest that IL-1β may play a role in the adhesion to lymphatic endothelial cells in particular.

http://ift.tt/2s7DDep

CD45RA − Foxp3 high regulatory T cells have a negative impact on the clinical outcome of head and neck squamous cell carcinoma

Abstract

Background

Although regulatory T cells (Tregs) are thought to play an important role in immune suppression, their clinical significance in head and neck squamous cell carcinoma (HNSCC) is unclear. A recent study reported Tregs could be divided into functional subsets based on the expression of CD45RA and Foxp3.

Method

The frequency of circulating Treg subsets was analyzed in patients with HNSCC and compared with the frequency in patients with benign tumors. The association of Treg subsets with the frequency of lymphocyte subsets, status of progression, clinical course, and prognosis were also examined.

Results

The frequency of CD4⁺Foxp3⁺ Tregs was comparable between HNSCC patients and age-matched benign tumor patients; however, CD45RA⁻Foxp3^high Tregs were significantly increased in HNSCC patients, in particular those with advanced stage tumors. The high frequency of CD45RA⁻Foxp3^high Tregs correlated with a poor prognosis and the low frequency of CD45RA⁻Foxp3^high Tregs before treatment showed a better clinical outcome, even in patients with advanced stage tumors. CD45RA⁻Foxp3^high Treg numbers were decreased after intensive treatments; however, Treg numbers recovered in the early stages of recurrent cases, even before the clinical manifestation.

Conclusion

CD45RA⁻Foxp3^high Tregs are associated with the clinical course of HNSCC and might be a new target for treatment and an early marker of tumor recurrence in HNSCC patients.

http://ift.tt/2r9mx2P

Voltage-clamp Fluorometry in Xenopus Oocytes Using Fluorescent Unnatural Amino Acids

This article describes an enhancement of conventional Voltage-Clamp Fluorometry (VCF) where Fluorescent Unnatural Amino Acids (fUAA) are used instead of maleimide dyes, to probe structural rearrangements in ion channels. The procedure includes Xenopus oocyte DNA injection, RNA/fUAA coinjection, and simultaneous current and fluorescence measurements.

http://ift.tt/2r9yAgm

Orofacial Pain Biomarkers 2017

Jean-Paul Goulet Description This book provides up-to-date information on all aspects of orofacial pain biomarkers. It opens by presenting background information on clinical phenotypes and the neurobiological substrates underlying chronic... Read more »

http://ift.tt/2r7UIG0

Atlas of Implant Dentistry and Tooth-Preserving Surgery : Prevention and Management of Complications

Zoran Stajcic Description This atlas is unique in comparing the two disciplines of dental implant surgery and tooth-preserving surgery with respect to common procedures, problems, and failures and in providing... Read more »

http://ift.tt/2qmTlpE

Screen-detected gallstone disease and cardiovascular disease

Abstract

Knowledge about temporal associations for screen-detected gallstone disease and cardiovascular disease is limited. The objective of this study was to determine if screen-detected gallstones or cholecystectomy was associated with development of cardiovascular disease. A cohort study of three randomly selected groups from the general population of Copenhagen was performed. Participants (n = 5928) were examined 1982–1992 and underwent abdominal ultrasound examination to detect gallstone disease and were not informed of their gallstone status. Participants were followed up for occurrence of cardiovascular disease through nationwide registers until December 2014. Multivariable Cox regression analyses were performed including traditional cardiovascular disease risk factors and apolipoprotein E genotype. Gallstone disease was identified in 10% (591/5928) of participants at baseline of whom 6.8% had gallstones and 3.2% had cholecystectomy. The study population was followed for a period of 32 years with only 1% lost to follow-up. Gallstone disease was associated with all cardiovascular disease (hazard ratio (HR) 1.36, 95% confidence interval (CI) [1.17;1.59]) and to the subgroups coronary artery (HR 1.34, 95% CI [1.10;1.64]), cerebrovascular (HR 1.22, 95% CI [0.97;1.52]), and peripheral artery disease (HR 1.57, 95% CI [1.15;2.13]). No differences in estimates were identified for gallstones detected at ultrasound or cholecystectomy. Adjustment did not change estimates substantially. Gallstone disease seems to be independently associated to cardiovascular disease. Associations cannot be explained through traditional cardiovascular disease risk factors, apolipoprotein E4 allele, or detection bias. Future studies should explore the link between gallstone and cardiovascular disease further and gut microbiota may be a candidate mechanism.

http://ift.tt/2r9dY7P

Treatment of moderate-to-high hyperopia with the WaveLight Allegretto 400 and EX500 excimer laser systems

http://ift.tt/2r6F6CI

Primary mucosa-associated lymphoid tissue (MALT) lymphoma of the gallbladder and review of the literature

Mucosa-associated lymphoid tissue (MALT) lymphoma is rarely observed in the gallbladder, and its diagnosis before surgery is difficult. This report describes a case of primary MALT lymphoma of the gallbladder in an 80-year-old man. Imaging studies revealed a protruding lesion on the inside of the gallbladder, which led us to diagnose gallbladder carcinoma prior to the patient undergoing extended cholecystectomy. Microscopic examination of the resected specimen of the gallbladder demonstrated lymphoid follicles with atypical lymphocytes and the formation of lymphoepithelial lesions. These findings led to a final pathological diagnosis of primary MALT lymphoma of the gallbladder. The patient has been free of recurrence for 39 months after the surgery. Although precise diagnosis before the surgery was difficult in this case, preoperative examinations revealed a submucosal tumour-like lesion. MALT lymphomas should be considered when imaging findings are atypical for gallbladder carcinoma.

http://ift.tt/2r8My1S

Sequential episodes of ethylene glycol poisoning in the same person

Ethylene glycol is a common alcohol found in many household products such as household hard surface cleaner, paints, varnish, auto glass cleaner and antifreeze. While extremely toxic and often fatal on ingestion, few cases with early presentation by the patient have resulted in death; thus, rapid diagnosis is paramount to effectively treating ethylene glycol poisoning. In this study, we compare two sequential cases of ethylene glycol poisoning in a single individual, which resulted in strikingly different outcomes.

http://ift.tt/2s72JKt

Exstrophy variant in a female child

Description

Bladder exstrophy–epispadias complex is a spectrum of rare congenital malformations involving the urinary, genital and musculoskeletal systems. The condition can be subdivided into classic/typical forms, comprising epispadias, classical bladder and cloacal exstrophy, and variant/atypical forms, including duplicated, covered and pseudoexstrophy. Diagnosis can be made clinically. Incidence varies. However, the occurrence is higher in males. Genetic and environmental components likely contribute to the aetiopathogenesis, which remains unknown.1 2 There is a hypothesis that cloacal exstrophy variant could result from an ischiopagus conjoined twinning with blighting of one twin.3

We present a 9-year-old girl with urinary incontinence. She was initially referred at 2-1/2 years for ambiguous genitalia but did not continue follow-up. The mother denied receiving prenatal care or completing postnatal studies. On examination, she has a bifid clitoris, symphysis pubis widely separated and low-placed umbilicus with midline muscle defect where the bladder seemed to herniate...

http://ift.tt/2r8tpNO

A rare cause of acute dysphagia: acute calcific tendonitis of the longus colli muscle

We are presenting a case of a 78-year-old female with multiple comorbidities and history of neck surgery, who presented with acute dysphagia, odynophagia and neck pain that has been progressively getting worse over the course of 2 days, with no recent injury or infection. The patient was afebrile. There were no visible signs of infection on routine oropharyngeal examination. Initial workup was unremarkable except for elevated erythrocyte sedimentation rate, C-reactive protein and creatinine. CT of the cervical spine ruled out any fracture or cervical spine injury but showed an area of calcification, prevertebral oedema and fluid collection inferior to the anterior arch of C1. MRI of the cervical spine also showed prevertebral oedema and fluid collection in the retropharyngeal space from the skull base to the C3 level without abnormal surrounding enhancement that supported the diagnosis of acute calcific tendonitis of the longus colli muscle rather than an infectious process. There was significant improvement of symptoms 48 hours after initiating treatment with systemic steroids. The patient remains asymptomatic 6 months after treatment.

http://ift.tt/2s72Q8X

Mycoplasma pneumoniae-induced rash and mucositis (MIRM): an unusual mild skin rash associated with severe mucosal involvement

Description

A 10-year-old boy was referred to the paediatric department because of ulcerative and haemorrhagic mucosal lesions involving lips and oral cavity (figure 1). These caused significant pain and discomfort to the patient, needing intravenous hydration and nutritional support for some days. The child showed minimal skin involvement, consisting of a mild serpiginous eruption (figure 2), and some lesions were located in the genital and anal areas, too. No pre-existing diseases were reported and, importantly, no drugs were administered during the previous days; interestingly, he reported a self-limiting episode of cough and fever in the previous week. HIV, herpes viruses, cytomegalovirus, Epstein-Barr virus and parvovirus B19 infections were ruled out and no immunological abnormalities emerged. Interestingly, the child presented a serology indicating a recent infection with Mycoplasma pneumoniae, as an elevated specific IgM titre (>27 UA/mL; nv<10 UA/mL) was recovered, whereas the corresponding IgG titre was negative....

http://ift.tt/2r8Pyvr

Novel variant of common variable immunodeficiency

A 57-year-old woman with frequent respiratory infections was initially diagnosed with IgG subclass deficiency based on low levels of IgG subclasses 2 and 3. Three years later, she progressed to having IgA deficiency as well. With a normal total IgG level, she does not meet criteria for common variable immunodeficiency (CVID). This may represent a variant of CVID. This also highlights the importance of immunoglobulin subclass estimation in patients where immunodeficiency is suspected clinically. She is being treated with rotational antibiotics the first 10 days of every month, monthly intravenous immunoglobulin (IVIG) infusion and osteopathic manipulation one to two times per month. On this regimen, although she has had several viral respiratory infections, she has avoided further hospitalisation for more than 1 year.

http://ift.tt/2s72qPL

Cranial neuropathies in uncontrolled diabetes: May not always be due to diabetic microangiopathy

Description

A 22-year-old man, detected to have type 1 diabetes at the age of 9 years, presented with left-sided frontotemporal headache for 1 week followed by left-sided ptosis and binocular diplopia for 4 days. The headache was deep seated and his ocular complaints were of insidious onset and progressive in nature. On admission, he was afebrile with normal vitals except for elevated blood pressure (160/110 mm Hg). He had left-sided complete ophthalmoplegia (palsies of III, IV and VI cranial nerves) along with loss of sensations along the distribution of the ophthalmic division of the left trigeminal nerve (figures 1 and  2). The pupils were equal and reacting to light and the plantar responses were down going. Anterior and posterior rhinoscopy did not reveal any bloody discharge or black eschars. Baseline biochemistry on admission revealed uncontrolled blood sugars (fasting plasma glucose: 198 mg/dL; postprandial plasma glucose: 324 mg/dL; haemoglobin A1c: 9.5%) and deranged renal...

http://ift.tt/2r8Exdh

Papillary renal cell carcinoma with synchronous ovarian metastasis: a rare entity

Description

A 45-year-old woman presented with left-lower abdominal lump for the last 3 months. On examination, she had a palpable lump in the left iliac region, 10 cm in size, firm, non-tender and mobile. Incidentally, another lump was palpable in her left flank which was ballotable. Ultrasonography revealed the presence of a large adnexal mass and showed a concomitant left renal mass. Contrast-enhanced computed tomography abdomen revealed the presence of heterogeneously enhancing space occupying lesion in the mid and lower pole of the left kidney (10.6x8.8x9.0 cm) and a large heterogeneously enhancing lesion was seen in the left adnexal region (11.7x8.7x12.2 cm) (figure 1). Para-aortic lymph nodes were enlarged. Cancer antigen (CA) 125 levels were 170 U/mL.

Figure 1

Contrast-enhanced computed tomography abdomen showing concomitant renal and ovarian mass (renal mass marked by yellow arrow, ovarian tumour marked by red arrow).

Patient underwent open left radical nephrectomy and excision of the...

http://ift.tt/2s6GpR9

Vibrio vulnificus septic shock due to a contaminated tattoo

We present a case of Vibrio vulnificus septic shock and cellulitis in a patient with chronic liver disease that occurred after obtaining a leg tattoo with subsequent seawater exposure in the Gulf of Mexico. Initial suspicion for V. vulnificus was high and he was started on empiric doxycycline and ceftriaxone at admission. Blood and wound cultures grew oxidase positive and comma-shaped Gram-negative rods ultimately confirmed to be V. vulnificus. Despite aggressive initial treatment, the patient developed septic shock and died. This case highlights the association of chronic liver disease and high mortality associated with infections of V. vulnificus. Health providers should remain vigilant for V. vulnificus infections in patients with chronic liver disease and raw oyster ingestion or seawater exposure.

http://ift.tt/2r8GIxO

Abdominoscrotal hydrocele in an infant boy

Abdominoscrotal hydrocele (ASH) is the rarest type of hydrocele. This condition is characterised by a large abdominal and scrotal component connected by an isthmus within the inguinal canal. The incidence among the paediatric population is reported to be less than 3%, although it might be underdiagnosed. Several theories have been proposed in the literature but the aetiology of ASH remains unknown. Diagnosis can be made clinically and confirmed by ultrasound. Spontaneous resolution is rare and long-standing ASH may lead to complications, thus early surgical intervention is recommended. Different techniques have been described, but dissection remains challenging due to the tunica vaginalis adherence to the testis and the distal cord. We present a male infant with ASH who underwent inguinal repair. The procedure was facilitated by needle decompression of the mass. Identification and preservation of the vessels and vas deferens was done successfully without compromising the testis.

http://ift.tt/2s6RjX1

Persistent ST-segment elevation due to cardiac metastasis

Description

A man aged 68 years with a known history of squamous cell carcinoma of the lung presented to the emergency room complaining of an acute episode of dyspnoea. His symptoms had resolved on presentation to the hospital. An EKG was obtained, which showed marked ST-segment elevation (STE) in the anteroseptal leads (figure 1A). No prior EKG was available for comparison. The patient denied any chest pain or pressure, and had no evidence of myocardial necrosis by cardiac biomarkers. Nevertheless, he was taken emergently to the cardiac catheterisation laboratory for a presumed diagnosis of STE myocardial infarction (STEMI). He was found to have severe two-vessel coronary artery disease with possible plaque rupture in the mid-left anterior descending artery (LAD) (figure 2). Overlapping bare metal stents were deployed to the LAD. Concerningly, the patient's right ventricle was noted to be in a fixed motion suggestive of...

http://ift.tt/2r8MvTK

Grey-Turners sign following iatrogenic duodenal perforation

Description

A 45-year-old man presented with a 6-hour history of acute epigastric pain radiating to the back, following endoscopic retrograde cholangiopancreatography (ERCP), sphincterotomy and biliary stenting for obstructive jaundice secondary to choledocholithiasis.

The patient was markedly tender in the epigastrium and right flank, with the pain becoming progressively worse over the following 48 hours. A CT scan of the abdomen and pelvis was performed, revealing a normally enhancing pancreas with pockets of free air and fluid adjacent to the second part of the duodenum and in the retroperitoneum, extending to the right flank, an associated perinephric collection and extensive peritoneal fat stranding. Inflammatory markers were raised alongside a moderately elevated amylase, with a clotting screen within normal limits and stable serial haemoglobin levels. These findings were in keeping with a posterior duodenal perforation (figure 1A,B).

Figure 1

Axial (A) and coronal (B) CT images demonstrating the retroperitoneal collection containing...

http://ift.tt/2s6URsi

Clozapine re-exposure after dilated cardiomyopathy

A 63-year-old woman with diabetes type II and a history of breast cancer was treated with clozapine for her refractory schizophrenia. She developed a dilated cardiomyopathy with an ejection fraction of 25%, a life-threatening event. The cause of heart failure could be multifactorial, with clozapine, family history, chemotherapy, diabetes type II and/or lithium as possible contributing risk factors. Clozapine was discontinued and the patient was referred to a hospice. Two weeks later, her heart failure slowly improved. Subsequently, she became extremely psychotic with a severe decline in quality of life. Therefore, it was decided to restart clozapine under cardiac monitoring. The patient's psychotic symptoms improved and her heart failure status remained stable for more than a year. Thereafter, a small deterioration was seen in cardiac function. In this case, re-exposure to clozapine was successful for at least 2 years.

http://ift.tt/2r8Mu2v

Pure posterior communicating artery occlusion treated with mechanical thrombectomy

There has been no report of mechanical thrombectomy for a pure posterior communicating artery (PComA) occlusion. Here, we report the case of an 87-year-old woman with a disturbance of consciousness and left hemiparesis diagnosed with a right PComA occlusion. The patient was successfully treated using mechanical thrombectomy in combination with a stent retriever and the Penumbra system. A CT perfusion image showed cerebral blood flow reduction in the ipsilateral occipital lobe and thalamus. A CT angiography supported the diagnosis of an occlusion of fetal type PComA. The PComA could not be detected by internal carotidangiogram, but after deployment of stent retriever, the PComA was recanalised and distal embolus at the right posterior cerebral artery was visualised. The thrombus was then removed using the Penumbra system. Although the treatment for a PComA occlusion requires further investigation, the present case supports a thrombectomy as an effective rescue strategy for PComA occlusions.

http://ift.tt/2s6UPka

Successful hybrid coronary artery revascularisation in a patient with severe cerebrovascular disease: a new treatment option to minimise the risk of stroke

Here we present a case involving a patient with severe distal left main coronary artery stenosis with extensive coexisting extracranial cerebrovascular disease where hybrid coronary artery revascularisation was successfully performed. This illustrates the potential for hybrid revascularisation in those patients with an inherit risk of stroke.

http://ift.tt/2r8njwL

Awake caudal anaesthesia in neonates/young infants for improved patient safety

Caudal epidural block in a conscious infant is a recognised technique that allows the avoidance of general anaesthesia and risks associated with it. It is also technically easier to perform reliably compared with an awake subarachnoid block in skilled hands.¹ While local anaesthetic systemic toxicity is a rare complication of caudal anaesthesia, this case illustrates the potential for caudal anaesthesia done awake in enhancing patient safety through early recognition of local anaesthetic systemic toxicity.

http://ift.tt/2s6UOwC

The efficacy of surgical treatment of recurrent or persistent cervical cancer that develops in a previously irradiated field: a monoinstitutional experience

Abstract

Background

There are no guidelines about the selection of recurrent cervical cancer patients for salvage surgery.

Methods

Patients who developed recurrent or persistent cervical cancer in a previously irradiated field and were subsequently treated with salvage surgery (the surgery group) or palliative care alone (the palliative group) were identified. Patient characteristics, treatment-related complications, and survival were retrospectively compared between the two groups.

Results

A total of 79 patients (surgery group, n = 51; palliative group, n = 28) were identified. In the surgery group, no intraoperative complications or treatment-related deaths occurred. Eleven patients (21.6%) experienced severe postoperative complications. After a median follow-up period of 41.5 months, 23 patients (45.1%) had developed recurrent disease, predominantly at distant sites, and 19 patients (37.3%) had died of disease progression. The estimated 3-year progression-free survival (PFS) and overall survival rates of the surgery group were 50.4 and 56.5%, respectively. In the palliative group, all of the patients died of disease progression. Positive surgical margins and lymph node metastasis were found to be independent prognostic factors for PFS in the surgery group. Among the patients with no or one poor prognostic factor, the patients in the surgery group survived significantly longer than those in the palliative group. However, among the patients with 2 poor prognostic factors, the surgery group and palliative group displayed similar survival periods.

Conclusions

Salvage surgery is a curative treatment in recurrent or persistent cervical cancer patients. However, considering its high surgical complication rate, salvage surgery should only be offered to carefully selected patients.

http://ift.tt/2rJ1uVa

High expression of GRP78/BiP as a novel predictor of favorable outcomes in patients with advanced thymic carcinoma

Abstract

Background

Glucose-regulated protein (GRP) 78/immunoglobulin heavy chain binding protein (BiP) is a member of the endoplasmic reticulum chaperone family, and its role in various types of human malignancies has recently been investigated. However, the clinicopathological characteristics of GRP78/BiP in advanced thymic carcinoma (ATC) remain unknown. We aimed to examine the relationship between GRP78/BiP expression and the clinical outcomes of ATC patients.

Methods

Thirty-four patients with ATC receiving combination chemotherapy at three institutions between April 1998 and April 2014 were enrolled in this study. We retrospectively collected patient characteristics such as therapeutic efficacy, pathological findings, and survival data from their medical records. We performed immunohistochemical analysis to evaluate the expression of GRP78/BiP in tumor specimens obtained from surgical resection or biopsy.

Results

This study included 21 men (68%) and 13 women (32%) with a median age of 62 years (range 36–75 years). GRP78/BiP overexpression was observed in 65% of the patients (22 of 34 patients). There was no correlation between GRP78/BiP expression and any patient characteristic. Patients with a high level of GRP78/BiP expression had significantly longer overall survival (OS) compared to those with a low level (46.2 vs. 16.8 months, p = 0.04). Multivariate analysis demonstrated that a high level of GRP78/BiP expression was an independent prognostic factor for prolonged OS.

Conclusions

Our findings indicate that the overexpression of GRP78/BiP is a novel predictor of favorable outcomes in patients with ATC who receive combination chemotherapy.

http://ift.tt/2qpRrRh

Comparison of visual acuity, refractive outcomes, and satisfaction between LASIK performed with a microkeratome and a femto laser

http://ift.tt/2qpnuR1

Comprehensive review of visual defects reported with topiramate

http://ift.tt/2rIPovt

Refractive predictability in eyes with intraocular gas tamponade – results of a prospective controlled clinical trial

http://ift.tt/2qpCzCj

Automated retinal imaging and trend analysis – a tool for health monitoring

http://ift.tt/2rJ8wte

Two Pa. ambulance companies merge

The merger means the two companies will be sharing staff and riding together on calls

http://ift.tt/2s0OBmI

Quinazolinone derivatives as inhibitors of homologous recombinase RAD51.

Related Articles

Quinazolinone derivatives as inhibitors of homologous recombinase RAD51.

Bioorg Med Chem Lett. 2017 May 15;:

Authors: Ward A, Dong L, Harris JM, Khanna KK, Al-Ejeh F, Fairlie DP, Wiegmans AP, Liu L

Abstract
RAD51 is a vital component of the homologous recombination DNA repair pathway and is overexpressed in drug-resistant cancers, including aggressive triple negative breast cancer (TNBC). A proposed strategy for improving therapeutic outcomes for patients is through small molecule inhibition of RAD51, thereby sensitizing tumor cells to DNA damaging irradiation and/or chemotherapy. Here we report structure-activity relationships for a library of quinazolinone derivatives. A novel RAD51 inhibitor (17) displays up to 15-fold enhanced inhibition of cell growth in a panel of TNBC cell lines compared to compound B02, and approximately 2-fold increased inhibition of irradiation-induced RAD51 foci formation. Additionally, compound 17 significantly inhibits TNBC cell sensitivity to DNA damage, implying a potentially targeted therapy for cancer treatment.

PMID: 28545975 [PubMed - as supplied by publisher]

http://ift.tt/2r6bGV9

Histopathologic Features are more Important Prognostic Factors than Primary Tumour Location in Gastro-oesophageal Adenocarcinoma Treated with Preoperative Chemoradiation and Surgery

Abstract

The aim of present study was to evaluate the impact of primary tumour location and other factors on the outcome of preoperative chemoradiation followed by surgery in adenocarcinomas of distal oesophagus, gastro-oesophageal junction and stomach. We retrospectively reviewed the institutional patient database. The therapeutic response was re-evaluated as a percentage of residual tumor cells in surgical resection specimens. Overall survival (OS) and disease-free survival (DFS) were assessed. The effect primary tumour location, clinical and pathological TNM stage, and histopathological factors (histological type, grade, angioinvasion, perineural invasion, tumour response) on treatment outcome were evaluated. A total of 108 patients underwent preoperative chemoradiation for adenocarcinoma of distal oesophagus, gastro-oesophageal junction or stomach. The median prescribed dose of radiation was 45 Gy. The concurrent chemotherapy consisted of 5-fluorouracil +/− cisplatin +/− taxanes. R0 resection was achieved in 80 patients (74%). The complete response was observed in 19%. The median follow-up was 50.8 months. Three-year and 5-year OS and DFS were 36.2% and 25.3%; and 28.1% and 23.7%, respectively. Pretreatment T-stage, pathological N-stage, radicality of resection, histological subtype, grade, angioinvasion and perineural invasion, were identified as statistical significant OS predictors in univariate analysis; pathological N-stage, radicality of resection and angioinvasion, in multivariate analysis. The primary tumor location did not influence the prognosis. The pathologic response to chemoradiation had borderline significance. In conclusion, no prognostic impact of primary tumour location, in contrast to other investigated factors, was evident in the present study. The most important predictors of prognosis were angioinvasion status and pN–stage.

http://ift.tt/2r7Yrp7

Biochemical evaluation of amniotic and allantoic fluids of the Red Sokoto goat in the second term of pregnancy—a preliminary study

Abstract

The amnion and allantois contain fluids and serve as cushion to protect the foetus against mechanical shock. Biochemical studies of the amniotic and allantoic fluids are important in understanding foetal metabolism and possible pathologic condition which may occur during gestation. This study evaluated the biochemical profile of the allantoic and amniotic fluids of pregnant Red Sokoto goats in their second term of pregnancy. Aliquots of each of the allantoic and amniotic fluids were aspirated and placed into separate clean sample bottles. These foetal membrane fluids samples were preserved at −20° and used for the biochemical evaluations. The foetuses were exteriorized, and the sexes of the foetuses were noted, while their crown-rump lengths (CRL) were measured. The CRL was used for gestational age determination. Allantoic and amniotic fluids from does of gestational age between 50 and 100 days were selected for the study. Gestational age between days 50 and 75 was considered early stage of the second term of pregnancy, while gestational age between days 76 and 100 was considered late stage. Standard procedures were followed in the determination of foetal fluid alanine aminotransferase (ALT), aspartate aminotransferase (AST) activities, and urea nitrogen, creatinine, calcium, sodium, and chloride ion levels. No significant (p > 0.05) variation was recorded in the mean allantoic and amniotic fluids values of AST, ALT, and sodium and chloride ions. Mean allantoic fluid values of urea nitrogen, creatinine, calcium, and potassium ions were significantly (p < 0.05) higher than those of amniotic fluid. In the early stage of the second term of pregnancy, mean allantoic fluid values of urea nitrogen, creatinine, calcium, chloride, and potassium ions were significantly lower (p < 0.05) when compared to the values obtained at the late stage. In the late stage of the second term of pregnancy, mean ALT, urea nitrogen, creatinine, and calcium amniotic fluid values were higher than the values obtained at the early stage. As the gestational age increases, allantoic and amniotic fluid levels of urea nitrogen, creatinine, and calcium ion increases.

http://ift.tt/2r8iuUn

Inhibitory effects of lactic acid bacteria isolated from traditional fermented foods against aflatoxigenic Aspergillus spp.

Abstract

In the present study, after molecular identification of dominant lactic acid bacteria (LAB) isolated from traditional fermented foods, antifungal activity of the isolates was investigated against aflatoxigenic Aspergillus spp. Based on screening results, among the isolated LAB, Pediococus lolii had the highest inhibitory effect against Aspergillus flavus (70.32%) and Aspergillus niger (98.8%). Furthermore, antifungal activity of P. lolii stationary phase cell-free supernatant (CFS) was significantly (P < 0.05) higher than the effect of the logarithmic phase CFS. MIC values of P. lolii CFSs from logarithmic and stationary phases against A. flavus were 2 and 1%, and against A. niger were 4 and 1% (v/v), respectively. The media containing ≥4% of CFSs from logarithmic and stationary phases (v/v) had also totally inhibited from germination of A. flavus and A. niger spores. Safety assessment during 28-day oral administration of P. lolii revealed that there was no noticeable difference in specific growth rate, activity, behavior, hair luster, clinical chemistry, and hematological indices in treated rats in comparison to control group.

http://ift.tt/2s6nlTe

Eosinophilic granulomatosis with polyangiitis and mononeuritis multiplex responded to induction cyclophosphamide

We report a case of 28-year-old Malay woman who initially presented with multiple joints pain with underlying poorly controlled asthma since her childhood. She was treated as seronegative arthritis. However, the involvement of joints, asthma and high-eosinophil counts raised suspicion of Churg-Strauss syndrome. This disease is undoubtedly rare in Malaysians or even in Asian populations. After appropriate therapy was delivered for the correct diagnosis her clinical condition improved. She is currently receiving maintenance treatment.

http://ift.tt/2s6ia5B

Pregnancy outcome in more than 5000 births to women with viral hepatitis: a population-based cohort study in Sweden

Abstract

Previous studies have shown inconsistent results with respect to hepatitis B (HBV), hepatitis C (HCV) and pregnancy outcome. The aim of this study was to investigate pregnancy outcome in women with HBV or HCV. In a nationwide cohort of births between 2001 and 2011 we investigated the risks of adverse pregnancy outcomes in 2990 births to women with HBV and 2056 births to women with HCV using data from Swedish healthcare registries. Births to women without HBV (n = 1090 979), and births without HCV (n = 1091 913) served as population controls. Crude and adjusted relative risks (aRR) were calculated using Poisson regression analysis. Women with HCV were more likely to smoke (46.7 vs. 8.0%) and to have alcohol dependence (18.9 vs. 1.3%) compared with population controls. Most women with HBV were born in non-Nordic countries (91.9%). Maternal HCV was associated with a decreased risk of preeclampsia (aRR: 0.39, 95% CI: 0.24–0.64), but an increased risk of preterm birth (aRR: 1.32, 95% CI: 1.08–1.60) and late neonatal death (7–27 days: aRR: 3.79, 95% CI: 1.07–13.39) Preterm birth were also more common in mothers with HBV, aRR: 1.21 (95% CI: 1.02–1.45). Both HBV and HCV are risk factors for preterm birth, while HCV seems to be associated with a decreased risk for preeclampsia. Future studies should corroborate these findings.

http://ift.tt/2r88NVT

Correlation of c-MET Expression with PD-L1 Expression in Metastatic Clear Cell Renal Cell Carcinoma Treated by Sunitinib First-Line Therapy

Abstract

Background

Clear cell renal cell carcinoma (ccRCC) is highly metastatic. Cabozantinib, an anti-angiogenic tyrosine kinase inhibitor that targets c-MET, provided interesting results in metastatic ccRCC treatment.

Objective

To understand better the role of c-MET in ccRCC, we assessed its status in a population of patients with metastatic ccRCC.

Patients and Methods

For this purpose, tumor samples were analyzed for c-MET expression by immunohistochemistry (IHC), for c-MET copy number alterations by fluorescence in situ hybridization (FISH), and for c-MET mutations by next generation sequencing (NGS) in a retrospective cohort of 90 primary ccRCC of patients with metastases treated by first-line sunitinib. The expression of c-MET was correlated with pathological, immunohistochemical (VEGFA, CAIX, PD-L1), clinical, and molecular criteria (VHL status) by univariate and multivariate analyses and to clinical outcome using Kaplan-Meier curves compared by log-rank test.

Results

Of ccRCC, 31.1% had low c-MET expression (absent to weak intensity by IHC) versus 68.9% with high expression (moderate to strong intensity). High expression of c-MET was associated with a gain in FISH analysis (p=0.0284) without amplification. No mutations were detected in NGS. Moreover, high c-MET expression was associated with lymph node metastases (p=0.004), sarcomatoid component (p=0.029), VEGFA (p=0.037), and PD-L1 (p=0.001) overexpression, the only factor that remained independently associated (p<0.001) after logistic regression. No difference was observed in clinical outcomes.

Conclusion

This study is the first to analyse c-MET status in metastatic ccRCC. The high expression of c-MET in the majority of ccRCC and its independent association with PD-L1 expression, may suggest a potential benefit from combining c-MET inhibitors and targeted immunotherapy.

http://ift.tt/2s0G57l

Traumatic globe rupture after deep anterior lamellar keratoplasty – a novel management technique

Abstract

Background: A traumatic wound dehiscence can occur many years after surgery in 2-6% of all keratoplasties. Intraocular tissue prolapse can lead to severe visual loss. Deep anterior lamellar keratoplasty (DALK) leads to higher wound stability because of the intact Descemet membrane. We report a case of a novel management of wound dehiscence following DALK.

Methods: A 59-year-old patient underwent uncomplicated DALK for advanced keratoconus. Eighteen months later he experienced a traumatic wound dehiscence (globe rupture) after a fall. Visual acuity decreased to light perception on the affected eye, the iris and prolapsed vitreous were incarcerated, and no retinal details were recognizable. The corneal graft was dehiscent over eight clock hours, the Descemet membrane was ruptured, and the stroma dissolved over 30% of its surface in a bell shape.

Results: Primary wound closure was performed with nylon 10-0 single interrupted corneal sutures. One day after emergency treatment, a 23 gauge pars-plana-vitrectomy for vitreous hemorrhage was conducted and a retinal tear was treated with laser photocoagulation. The Descemet membrane was repositioned using a 23 g vitrectomy probe under air and the globe was filled with SF₆ gas. Postoperatively, visual acuity increased to 6/15 and the cornea cleared up.

Conclusion: Corneal graft and Descemet membrane repositioning after trauma can avoid a further keratoplasty and the risk of immunological rejection of donor endothelial cells. This article is protected by copyright. All rights reserved.

http://ift.tt/2r6j2YP

Confocal microscopy in acanthamoeba keratitis as an early relapse-marker

Abstract

Acanthameoba keratitis is a serious ophthalmological condition with a potentially vision-threatening prognosis. Early diagnosis and recognition of relapse, and the detection of persistent acanthamoeba cysts, are essential for informing the prognosis and managing the condition. We suggest the use of in-vivo confocal microscopy not only to identify the early signs of relapse after keratoplasty in patients with acanthamoeba keratitis, but also as an additional follow-up tool after antimicrobial crosslinking. This study shows that in-vivo confocal microscopy is, in experienced hands, a quick and reliable diagnostic tool. This article is protected by copyright. All rights reserved.

http://ift.tt/2qm0Z3u

Microsurgical anatomy of the maxillary artery for extracranial-intracranial bypass in the pterygopalatine segment of the maxillary artery

Abstract

The extracranial-intracranial (EC-IC) bypass using the maxillary artery (MA) has been successfully completed using a radial artery graft but the complicated anatomy and narrow exposure make it difficult. The purpose of this article is to define the microsurgical exposure of the MA through the middle fossa and describe the branches, diameter, and length of the MA available for the EC-IC bypass in the sphenopalatine fossa and anterior part of the infratemporal fossa. 5 cadaveric specimens were dissected bilaterally (10 MA dissections) to define the microsurgical anatomy of the MA through an intracranial approach. The exposable branches of the MA at the level of the infratemporal and sphenopalatine fossae were the anterior deep temporal, posterior superior alveolar, and infraorbital arteries. The origin of each branch could be exposed. The available section of the MA for use as a donor vessel is between the origin of the anterior deep temporal artery and the infraorbital artery. The mean exposable length of the MA was 19.4 mm. The mean outer diameter of the donor MA was 3.2 mm. Tension-free EC-IC bypass was possible using a radial artery graft between the MA and the middle cerebral artery, the MA and the supraclinoid internal carotid artery, or the MA and the petrous internal carotid artery. Exposure of the MA at the infratemporal and sphenopalatine fossae is complicated but provides length and diameter suitable as a donor artery for the EC-IC bypass. This article is protected by copyright. All rights reserved.

http://ift.tt/2r6vgAF

Anatomical study of the internal nasal branch of the infraorbital nerve: application to minimizing nerve damage with surgery in and around the nose

Abstract

INTRODUCTION The internal nasal branch of the infraorbital nerve runs down the nose and around the ala to be distributed to the nasal septum and vestibule. The aim of this study was to measure the internal nasal branch around the ala of the nose and discuss its possible relevance in clinical/surgical practice. MATERIALS AND METHODS Twelve sides from seven specimens derived from fresh frozen and embalmed Caucasian cadaveric heads were dissected. The specimens included three males and four females. The ages of the cadavers at death ranged from 65 to 84 years. The diameter of the internal nasal branch, horizontal distance from the lateral contour of the ala (Point A) to the branch (distance H) and vertical distance from the bottom part of the ala (Point B) to the branch (distance V) were recorded. RESULTS Distance H ranged from -1.6 to 1.5mm on right sides and -1.0 to 1.5mm on left sides. The diameter of the nerves at Point A ranged from 1.3 to 1.8mm on right sides and 1.3 to 1.6mm on left sides. Distance V ranged from -1.5 to 1.0mm on right sides and -2.3 to 1.1mm on left sides. The diameter of the nerves at Point B ranged from 0.7 to 1.3mm on right sides and 0.8 to 1.2mm on left sides. CONCLUSIONS The results of this study are the first to detail the topography of the internal nasal branch of the infraorbital nerve. This article is protected by copyright. All rights reserved.

http://ift.tt/2qlLGI1

Pro-angiogenic TIE-2-expressing monocytes/TEMs as a biomarker of the effect of sorafenib in patients with advanced hepatocellular carcinoma

Abstract

Sorafenib, a multi-kinase inhibitor, inhibits tumor angiogenesis and is the first-line systemic therapy for patients with advanced hepatocellular carcinoma (HCC). However, due to its limited effects and frequent occurrence of side effects, biomarkers are needed to predict the effects of sorafenib. We considered the possibility of using TIE-2-expressing monocytes (TEMs) to predict the response in sorafenib-treated patients with advanced HCC. TEMs serve as a diagnostic marker of HCC and are related to angiogenesis. We analyzed 25 advanced HCC patients and prospectively evaluated TEMs before (Pre TEMs) and at 1 month after initial therapy (T1m TEMs). The radiologic response was evaluated by modified Response Evaluation Criteria in Solid Tumors (mRECIST). Median survival time (MST) was significantly longer in the partial response/stable disease (PR/SD) group (21.8 months) than in the PD group (8.7 months). ΔTEMs (changes of T1m TEMs compared to Pre TEMs) were significantly lower in the PR/SD group than in the PD group. MST of the ΔTEMs low group (14.2 months) was significantly longer than that of the high group (8.7 months). Univariate and multivariate Cox regression analyses showed that ΔTEMs (hazard ratio [HR] = 8.53, 95% confidence interval [CI] = 1.51 – 48.16, P = 0.015) and Child-Pugh class (HR = 5.59, 95% CI = 1.06 – 29.63, P = 0.043) were independently associated with overall survival. Our results suggest that ΔTEMs could serve as a biomarker for predicting radiologic response and overall survival in sorafenib-treated patients with advanced HCC. This article is protected by copyright. All rights reserved.

http://ift.tt/2qpeCLt