Common Carotid Artery Flow Measured by 3-D Ultrasonic Vector Flow Imaging and Validated with Magnetic Resonance Imaging

Publication date: Available online 12 July 2017
Source:Ultrasound in Medicine & Biology
Author(s): Simon Holbek, Kristoffer Lindskov Hansen, Hamed Bouzari, Caroline Ewertsen, Matthias Bo Stuart, Carsten Thomsen, Michael Bachmann Nielsen, Jørgen Arendt Jensen
Ultrasound (US) examination of the common carotid artery was compared with a through-plane magnetic resonance imaging (MRI) sequence to validate a recently proposed technique for 3-D US vector flow imaging. Data from the first volunteer examined were used as the training set, before volume flow and peak velocities were calculated for the remaining eight volunteers. Peak systolic velocities (PSVs) and volume flow obtained with 3-D US were, on average, 34% higher and 24% lower than those obtained with MRI, respectively. A high correlation was observed for PSV (r = 0.79), whereas a lower correlation was observed for volume flow (r = 0.43). The overall standard deviations were ±5.7% and ±5.7% for volume flow and PSV with 3-D US, compared with ±2.7% and ±3.2% for MRI. Finally, the data were re-processed with a change in the parameter settings for the echo-canceling filter to investigate its influence on overall performance. PSV was less affected by the re-processing, whereas the difference in volume flow between 3-D vector flow imaging and MRI was reduced to −9%, and with an improved overall standard deviation of ±4.7%. The results illustrate the feasibility of using 3-D US for precise and angle-independent volume flow and PSV estimation in vivo.



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Guar and Locust bean gum: Composition, total phenolic content, antioxidant and antinutritional characterisation

Publication date: Available online 12 July 2017
Source:Bioactive Carbohydrates and Dietary Fibre
Author(s): Afshan Mumtaz Hamdani, Idrees Ahmed Wani
Guar and locust bean gum are added to various food products because of their ability to modify the texture and rheology. No sufficient data is available about their bioactive roles except that these are physiologically similar to dietary fibre and may be used as low-energy fat replacers. Present study was undertaken to find out the nutraceutical and antinutritional properties of guar and locust bean gum. Antioxidant activity of gums was determined by ferrous ion chelating ability, reducing power, FRAP (ferric reducing antioxidant power) and ABTS (2, 2-azinobis (3-ethylbenzothiazolin-6-sulfonate) scavenging power. Determination of phytic acid, haemagglutinins, terpenoids, saponins and alkaloids was carried out to evaluate their antinutritional activity. Gums showed low antioxidant potential except ferrous ion chelating ability which was significant in both methanolic (65.08–66.82%) and ethanolic (36.46–55.40%) extracts. Gums also exhibited a high DPPH (1,1-diphenyl-2- picrylhydrazyl) radical scavenging activity (11.67–29.78%). Bile acid binding capacity was high i.e., 49.83% (guar gum) and 54.42% (locust bean gum). Tannin and phytic acid content varied from 1.28–3.72 TAE/g and 0.098–0.165mg/g, respectively. Haemagglutinin activity of gums was low (0.066–0.432 HU/mg protein) while the terpenoids, saponins and alkaloids were completely absent. Thus, gums may play beneficial bioactive roles in consumers in addition to conferring desirable organoleptic properties in different food products.

Graphical abstract

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Treatment of refractory and severe hypothyroidism with sublingual levothyroxine in liquid formulation

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Neoadjuvant Therapy with Weekly Nanoparticle Albumin‐Bound Paclitaxel for Luminal Early Breast Cancer Patients: Results from the NABRAX Study (GEICAM/2011‐02), a Multicenter, Non‐Randomized, Phase II Trial, with a Companion Biomarker Analysis

AbstractBackground.Nanoparticle albumin‐bound paclitaxel (nab‐Paclitaxel) is an alternative to standard taxanes for breast cancer (BC) treatment. We evaluated nab‐Paclitaxel efficacy as neoadjuvant treatment for early estrogen receptor‐positive (ER+), human epidermal growth factor receptor 2‐negative (HER2‐) disease.Materials and Methods.Women with ER+, HER2‐, stage II–III BC were treated preoperatively with four cycles of weekly nab‐Paclitaxel (150 mg/m2), 3 weeks on and 1 week off. We hypothesized that poor pathological response rate (residual cancer burden [RCB] III; Symmans criteria) would be ≤16%.Results.Eighty‐one patients with a median age of 47 years were treated; 64.2% were premenopausal, and 69% of tumors were stage II. Residual cancer burden III rate was 28.4% (95% confidence interval [CI]: 18.6%–38.2%), RCB 0+I (good response) rate was 24.7% (95% CI: 15.3%–34.1%) and RCB 0 (complete response) rate was 7.4% (95% CI: 1.7%–13.1%). Objective response rate by magnetic resonance imaging was 76.5% and rate of conversion to breast conserving surgery was 40.0%. The most frequent grade 3 and 4 toxicity was neutropenia (12.3% and 3.7% of patients, respectively), without any febrile neutropenia. Sensory neuropathy grade 2 and 3 were seen in 25.9% and 2.5% of patients, respectively. Tumor secreted protein, acidic, cysteine‐rich (SPARC) overexpression was significantly associated with RCB 0 (odds ratio: 0.079; 95% CI: 0.009–0.689; p = .0216).Conclusion.Despite failing to confirm an RCB III rate ≤16% in nab‐Paclitaxel‐treated patients, the RCB 0+I rate indicates a significant drug antitumor activity with low rates of grade 3–4 toxicity. Our exploratory biomarker analysis suggests a potential predictive role of complete response for SPARC. Confirmatory analyses are warranted, adapting dose and schedule to decrease peripheral neurotoxicity. (Trial registration: European Clinical Trials Database study number: 2011‐004476‐10; ClinicalTrials.gov: NCT01565499)Implications for Practice.The pathological response rate (residual cancer burden [RCB]; Symmans criteria) of nanoparticle albumin‐bound paclitaxel administered as neoadjuvant treatment for early estrogen receptor‐positive, human epidermal growth factor receptor 2‐negative disease was evaluated. Whereas poor response (RCB III) was 24.7%, similar to that for docetaxel, good response (RCB 0+I) reached 23.0%, far superior to the 13% for docetaxel, while keeping toxicity low. Exploratory biomarker analysis suggests secreted protein, acidic, cysteine‐rich overexpression in tumor cells as a potential predictor of complete response (RCB 0). Findings point to an encouraging single‐agent neoadjuvant treatment with low toxicity, which warrants future research and development.

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Quality Assessment of Reporting Performance for EGFR Molecular Diagnosis in Non‐Small Cell Lung Cancer

AbstractBackground.Reports serve as a bridge between laboratories and clinicians, help synthesize an overwhelming amount of raw data into evidence‐based medicine, and play a significant role in designing clinical treatments. In an effort to guarantee high‐quality epidermal growth factor receptor (EGFR) gene mutation testing and reporting performance, the National Center for Clinical Laboratories launched a proficiency testing (PT) scheme reflecting clinical practices in China since 2014. This study focuses on the quality assessment of gene mutation reports.Materials and Methods.Fifty‐three laboratories that submitted reports in both 2014 and 2016 EGFR gene mutation PT schemes were selected for report analysis and comparison according to predefined evaluation criteria.Results.The average score for reports from 2014 was 14 out of 30 points. The overall scores for reports from 2016 improved substantially, yielding an average score of 20 out of 30 points. Among the evaluation criteria, general items were well documented in the reports. However, items specific to molecular diagnosis were far from satisfactory, and some items were even missing.Conclusion.The quality assessment of clinical written reports from 2014 and 2016 demonstrates that substantial improvements have been made in overall reporting performance. However, not all statements pertaining to important elements met expectations. To continue education, repeated PT schemes need to be executed in a timely fashion to expose and address existing shortcomings in clinical reports. There remains ample room for improvement towards generating concise, comprehensive, and readable reports.Implications for Practice.This article compares the quality of clinical gene mutation reports submitted in 2014 to those submitted in 2016 epidermal growth factor receptor proficiency testing schemes, exposes the existing shortcomings, and discusses ways to communicate results more effectively in the future. The findings demonstrate that notable progress was observed in the overall reporting performance. However, key points specific to molecular diagnosis were far from expectation, and some items were even missing. Standardization needs to be emphasized to improve the report format and content. This article provides a reference that laboratories can use to write concise, comprehensive, and readily accessible clinical reports.

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Distinct Tertiary Lymphoid Structure Associations and Their Prognostic Relevance in HER2 Positive and Negative Breast Cancers

AbstractBackground.The presence of tumor infiltrating lymphocytes (TIL) is associated with favorable prognosis. Recent evidence suggested that not only their density, but also the spatial organization as tertiary lymphoid structures (TLS), play a key role in determining patient survival.Materials and Methods.In a cohort of 248 breast cancers, the clinicopathologic association and prognostic role of TLS was examined.Results.Tertiary lymphoid structures were associated with higher tumor grade, apocrine phenotype, necrosis, extensive in situ component, lymphovascular invasion (LVI), and high TIL. For biomarkers, TLS were associated with hormone receptors negativity, HER2 positivity, and c‐kit expression. Tertiary lymphoid structures were significantly related to better disease‐free survival (DFS) in HER2 positive (HER2+) breast cancers (log‐rank = 4.054), which was not dependent on high TIL status. The combined TLS and TIL status was an independent favorable factor associated with DFS in those cases. Interestingly, tumor cell infiltration into the TLS was found in 41.9% of TLS positive cases. It was associated with LVI in HER2 negative (HER2−) TLS positive (particularly estrogen receptor positive [ER+] HER2−) cases. In the ER+ HER2− cases, tumor cell infiltration into TLS was also associated with increased pathologic nodal stage (pN) stage and nodal involvement.Conclusion.Tertiary lymphoid structures showed a similar relationship with clinicopathologic features and biomarkers as TIL. The presence of TLS, irrespective of TIL level, could be an important favorable prognostic indicator in HER2+ breast cancer patients. Given the significance of TLS in promoting effective antitumor immunity, further understanding of its organization and induction may provide new opportunities to improve the current immunotherapy strategies.Implications for Practice.Despite recent interest on the clinical value of tumor infiltrating lymphocyte (TIL), little was known on the clinical significance on their spatial organization as tertiary lymphoid structures (TLS). Although TLS showed similar relationships with clinicopathologic features and biomarkers as TIL, the prognostic value of TLS, particularly in HER2 positive cancers, was independent of TIL. Moreover, tumor infiltration could be present in TLS which appears to be related to tumor invasion in HER2 negative cancers. Overall, the results demonstrated the additional value for TLS in HER2 cancer subtypes. Further investigations and its standardized evaluation will enhance its use as standard practice.

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Clinical Application of Targeted Deep Sequencing in Solid‐Cancer Patients; Utility of Targeted Deep Sequencing for Biomarker‐Selected Clinical Trial

AbstractMolecular profiling of actionable mutations in refractory cancer patients has the potential to enable "precision medicine," wherein individualized therapies are guided based on genomic profiling. The molecular‐screening program was intended to route participants to different candidate drugs in trials based on clinical‐sequencing reports. In this screening program, we used a custom target‐enrichment panel consisting of cancer‐related genes to interrogate single‐nucleotide variants, insertions and deletions, copy number variants, and a subset of gene fusions. From August 2014 through April 2015, 654 patients consented to participate in the program at Samsung Medical Center. Of these patients, 588 passed the quality control process for the 381‐gene cancer‐panel test, and 418 patients were included in the final analysis as being eligible for any anticancer treatment (127 gastric cancer, 122 colorectal cancer, 62 pancreatic/biliary tract cancer, 67 sarcoma/other cancer, and 40 genitourinary cancer patients). Of the 418 patients, 55 (12%) harbored a biomarker that guided them to a biomarker‐selected clinical trial, and 184 (44%) patients harbored at least one genomic alteration that was potentially targetable. This study demonstrated that the panel‐based sequencing program resulted in an increased rate of trial enrollment of metastatic cancer patients into biomarker‐selected clinical trials. Given the expanding list of biomarker‐selected trials, the guidance percentage to matched trials is anticipated to increase.Implications for Practice.This study demonstrated that the panel‐based sequencing program resulted in an increased rate of trial enrollment of metastatic cancer patients into biomarker‐selected clinical trials. Given the expanding list of biomarker‐selected trials, the guidance percentage to matched trials is anticipated to increase.

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Adipose‐Derived Fatty Acid‐Binding Proteins Plasma Concentrations Are Increased in Breast Cancer Patients

AbstractBackground.Adipose tissue is an endocrine organ that could play a role in tumor progression via its secreted adipokines. The role of adipose‐derived fatty acid‐binding protein (FABP) 4 and FABP5 in breast cancer is presently under study, but their circulating levels in this pathology are poorly known. We analyzed the blood concentrations of FABP4 and FABP5 in breast cancer patients to determine whether there is an association between them and breast cancer.Materials and Methods.We studied 294 women in the oncology department with a family history of breast cancer; 198 of the women had breast cancer, and 96 were healthy controls. The levels of FABP4, FABP5, lipid profile, standard biochemical parameter, and high‐sensitivity C‐reactive protein (hsCRP) were determined. We analyzed the association of FABP4 and FABP5 with breast cancer, while adjusting for demographic, anthropometric, and biochemical parameters.Results.Breast cancer patients had a 24.8% (p < .0001) and 11.4% (p < .05) higher blood concentration of FABP4 and FABP5, respectively. Fatty acid‐binding protein 4 was positively associated with age, body mass index (BMI), FABP5, very‐low‐density lipoprotein cholesterol (VLDLc), non‐high‐density lipoprote in cholesterol (non‐HDLc), Apolipoprotein B 100 (ApoB100), triglycerides, glycerol, glucose, and hsCRP (p < .05), and was negatively associated with HDLc (p < .005) in breast cancer patients. Fatty acid‐binding protein 5 was positively associated with BMI, FABP4, VLDLc, triglycerides, glycerol, and hsCRP (p < .05), and was negatively associated with HDLc and Apolipoprotein AI (ApoAI) (p < .05) in breast cancer patients. Using a logistic regression analysis and adjusting for age, BMI, hsCRP, non‐HDLc, and triglycerides, FABP4 was independently associated with breast cancer (odds ratio [OR]: 1.091 [95% CI: 1.037–1.149]). Moreover, total cholesterol, VLDLc, non‐HDLc, ApoB100, triglycerides, and hsCRP were significantly increased in breast cancer patients (p < .005). In contrast, the non‐esterified fatty acids concentrations were significantly decreased in breast cancer patients (p < .05).Conclusion.Circulating FABP4 and FABP5 levels were increased in breast cancer patients compared with controls. The positive association of FABP4 with breast cancer was maintained after adjusting for important covariates, while the association with FABP5 was lost. Our data reinforce the role of adipose tissue and their adipokines in breast cancer. Despite these data, further studies must be performed to better explain the prognosis or diagnostic value of these blood parameters and their possible role in breast cancer.Implications for Practice.We focus on the effect of adipose tissue on cancer, which is increasingly recognized. The association between adipocyte‐derived adipokines and breast cancer opens new diagnosis and therapy perspectives. In this study, we provide original data concerning FABP4 and FABP5 plasma concentrations in breast cancer patients. Compared to control group, breast cancer patients show higher FABP4 and FABP5 blood levels. Our data suggest that, particularly, circulating FABP4 levels could be considered a new independent breast cancer biomarker. Our work translates basic science data to clinic linking the relationship between adipose tissue and lipid metabolism to breast cancer.

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Feasibility and Efficacy of Microwave Ablation Combined with Iodine‐125 Seed Implantation in Local Control of Recurrent Retroperitoneal Liposarcomas: Initial Clinical Experience

AbstractIntroduction.The objective of the present study was to evaluate the feasibility, safety, and short‐term efficacy of microwave ablation (MWA) combined with iodine‐125 (125I) seed implantation in recurrent retroperitoneal liposarcomas (rRPLs).Materials and Methods.From September 2012 to March 2015, 11 patients were enrolled in this prospective study. Eleven tumors (median, 9 cm; range, 5.5–12.5 cm) were treated with computerized tomography‐guided MWA for 11 sessions and 125I seed implantation for 18 sessions. 125I seed implantation was performed 4 weeks after MWA.Results.There were no procedure‐related deaths. Post‐MWA pain (grade ≥2) was the most common complication (6 of 11 patients, 54.5%), and fever (grade ≥2) was observed in two patients. Reversible nerve injury, defined as transient limb paresthesia or leg weakness, was observed in one patient. There were fewer complications associated with the 125I seed implantation procedure compared with the MWA procedure. All 11 patients who underwent the MWA procedure achieved a partial response (PR), according to the modified Response Evaluation Criteria in Solid Tumors, 1 month post‐ablation; after 125I seed implantation was performed, a complete response was observed in three, five, and six target tumors in 3, 6, and 12 months, respectively.Conclusion.In selected patients with rRPLs, MWA combined with 125I seed implantation is feasible and safe with favorable local control efficacy.Implications for Practice.This study evaluated the feasibility, safety, and short‐term efficacy of microwave ablation (MWA) combined with iodine‐125 (125I) seed implantation in recurrent retroperitoneal liposarcomas (rRPLs). Results suggest that a single session of MWA may be not sufficient in large‐volume rRPLs and that as a supplement treatment, 125I seed implantation is safe and easy accessible. MWA combined with 125I seed has excellent local control effectiveness, and long‐term efficacy and survival benefit still need to be more comprehensively evaluated.

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Negative (18)F-FDG PET and positive CT and MRI findings in multifocal splenic hamartoma.

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Negative (18)F-FDG PET and positive CT and MRI findings in multifocal splenic hamartoma.

Hell J Nucl Med. 2017 Jul 12;:

Authors: Van de Wiele C, Verstraete K, Bourgeois S, Maes A

Abstract
We report our fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography ((18)FFDG PET/CT) findings in a 51 years old female presenting with B symptoms, respectively fever, night sweats and malaise, that underwent an (18)F-FDG PET/CT examination to exclude underlying lymphomatous disease. Whereas (18)F-FDG PET scan findings were negative, CT put to evidence the presence of multiple small lesions suggestive for multifocal hamartoma. On a subsequently performed magnetic resonance imaging (MRI) of the spleen, multiple infracentimetric foci were visualized displaying characteristic findings for hamartoma. During a follow-up period of two years no change in size or characteristics of these lesions occurred.
CONCLUSION: The normal :F-FDG PET/CT findings suggested that, at least in this patient, splenic hamartoma may display a similar :F-FDG avidity when compared to normal splenic tissue. Alternatively, due to the infra-centrimeric size of the hamartoma and spill-over from :F-FDG activity from neighbouring normal tissue, the true (18)F-FDG avidity of the hamartomas present might also be overestimated.

PMID: 28697199 [PubMed - as supplied by publisher]

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Unusual diffuse liver (18)F-FDG uptake in melanoma patient treated by ipilimumab.

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Unusual diffuse liver (18)F-FDG uptake in melanoma patient treated by ipilimumab.

Hell J Nucl Med. 2017 Jul 12;:

Authors: Raoul M, Ioannis K, Carlos A, Camilo G, Feoli F, Joseph K, Patrick F

Abstract
We present herein a case of unusual (18)F-FDG PET-CT diffuse hypermetabolic liver uptake in melanoma patient treated by ipilimumab.

PMID: 28697198 [PubMed - as supplied by publisher]

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Increased and normalized uptake of (18)F-FDG in a case of bone periprosthetic infection treated by antibiotics.

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Increased and normalized uptake of (18)F-FDG in a case of bone periprosthetic infection treated by antibiotics.

Hell J Nucl Med. 2017 Jul 12;:

Authors: Lavelli V, Ferrari C, Niccoli Asabella A, Altini C, Saverio Vella F, Rubini G

Abstract
We report the case of a 69 years old man with left hip prosthesis, who presented clinical, biochemical and imaging signs of periprosthetic infection treated with linezolid, an antibacterial agent of the oxazolidinone class. Two weeks after this treatment, a fluorine-18-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) scan showed increased uptake in the skeleton and also increased uptake in several focal areas in the spine and near the prosthesis and the surgical wound on the left gluteus medius. Bone marrow biopsy was negative; meanwhile the antibiotic therapy, after four weeks of treatment was stopped due to red blood cells and platelets toxicity. Six weeks later, the patient developed high fever again and in order to revaluate the periprosthetic inflammation, he was resubmitted to (18)F-FDG PET/CT which showed normal (18)F-FDG uptake in the whole skeleton, including the prosthesis and the subcutaneous wound. Some focal areas of increased uptake in the lumbar spine were still detected. In the next 4 weeks the patient was under a "watch and wait" follow-up in a steady state.
IN CONCLUSION: In the case we report, since we found no otnt focal areas in the lumbar spine where due to age-related bone deformities including some Schmorl's nodes. The inflammation in the bone prosthesis and the subcutaneous wound responded almost totally to the antibiotic treatment we applied.

PMID: 28697197 [PubMed - as supplied by publisher]

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Fluorine-18-fluorodeoxyglucose positron emission tomography/ computed tomography findings in a pediatric mucoepidermoid carcinoma and differential diagnosis.

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Fluorine-18-fluorodeoxyglucose positron emission tomography/ computed tomography findings in a pediatric mucoepidermoid carcinoma and differential diagnosis.

Hell J Nucl Med. 2017 Jul 12;:

Authors: Xie J, Ma C, Tang J

Abstract
An 11 years old boy was referred to our hospital. He complained for the last three months for intermittent cough and shortness of breath after exercise which worsened recently. Airways computed tomography (CT) showed an abnormal endobronchial tumor, obstructing the right main bronchus and also atelectasis in the upper lobe of the right lung. Bronchoscopy showed a wet on its surface mass obstructing the right main bronchus. Biopsy showed a mucoepidermoid carcinoma (MEC). The fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) scan showed in the same area a mass with slightly increased (18)F-FDG uptake (maximum standardized uptake value, SUVmax: 3.8), without mediastinal lymph nodes involvement. The boy had thoracoscopic resection of the right upper lobe, right main bronchus and right inferior lobe bronchial sleeve anastomosis. Histological examination confirmed the diagnosis of a low to intermediate grade malignant MEC without lymph nodes metastases. The patient has been well and free from recurrence for 2 years postoperatively.

PMID: 28697196 [PubMed - as supplied by publisher]

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Fluorine-18-FDG PET/CT in a patient with angiomyolipoma: Response to mammalian target of rapamycin inhibitor therapy.

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Fluorine-18-FDG PET/CT in a patient with angiomyolipoma: Response to mammalian target of rapamycin inhibitor therapy.

Hell J Nucl Med. 2017 Jul 12;:

Authors: Anwar H, Sachpekidis C, Schwarzbach M, Dimitrakopoulou-Strauss A

Abstract
We report on a 27 years old female patient who was referred to our department for whole-body as well as dynamic positron emission tomography/computed tomography (dPET/CT) scan of the upper and middle abdomen with fluorine-18-fluorodeoxy glucose ((18)F-FDG), for further evaluation of a mass in the left adrenal gland region. Positron emission tomography showed a suspicious, enlarged, hypermetabolic mass with an average standardized uptake value (SUV) of 4.5 and a maximum SUV of 5.9. The patient was referred for biopsy, which revealed an angiomyolipoma, a perivascular epithelioid cell tumor (PEComa) of the adrenal gland. Perivascular epithelioid cell tumors are mesenchymal tumors consisting of blood vessels, smooth muscles and fat cells. The patient received anti-proliferative treatment with Afinitor, a mammalian target of rapamycin (mTOR) inhibitor, and was referred again one month after onset of therapy for early response assessment. The follow-up (18)F-FDG PET/CT scan showed a nearly complete resolution of the previously detected adrenal mass, with very low tracer uptake and a decrease in its functional volume. Fluorine- 18-FDG PET/CT can be used for treatment response evaluation of angiomyolipoma treated with mTOR-inhibitors.

PMID: 28697195 [PubMed - as supplied by publisher]

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Enhancing contrast agents and radiotracers performance through hyaluronic acid-coating in neuroradiology and nuclear medicine.

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Enhancing contrast agents and radiotracers performance through hyaluronic acid-coating in neuroradiology and nuclear medicine.

Hell J Nucl Med. 2017 Jul 12;:

Authors: Ganau M, Syrmos NC, D'Arco F, Ganau L, Chibbaro S, Prisco L, Ligarotti GKI, Ambu R, Soddu A

Abstract
The use of hyaluronic acid nanoshells has been proposed to encapsulate prodrugs and exploit the mechanisms of interactions between living cells, like endocytes or cancer cells and hyaluronic acid, which is a natural component of the extracellular matrix. In this review we describe the potential and the limits of this promising research trend and discuss the theoretical advantages of such an engineering approach. Is it a possible scalability to increase the efficacy and biodegradability of molecules like contrast media and radiotracers especially for neuroradiology and nuclear medicine studies.

PMID: 28697194 [PubMed - as supplied by publisher]

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The value of (18)FDG PET/CT parameters, hematological parameters and tumor markers in predicting KRAS oncogene mutation in colorectal cancer.

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The value of (18)FDG PET/CT parameters, hematological parameters and tumor markers in predicting KRAS oncogene mutation in colorectal cancer.

Hell J Nucl Med. 2017 Jul 12;:

Authors: Oner AO, Budak ES, Yıldırım S, Aydın F, Sezer C

Abstract
OBJECTIVE: In this study we investigated the predictive value of maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), neutrophils/lymphocytes ratio (NLR), platelets/lymphocytes ratio (PLR), carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) in the prediction of KRAS gene mutation which plays an important role in the choice of treatment in colorectal cancer patients.
SUBJECTS AND METHODS: A total of 55 cases with untreated colorectal cancer who had undergone both PET/CT examinations for initial staging and also mutation analysis of KRAS oncogene were studied. Fluorine-18-FDG PET/CT parameters (SUVmax, MTV, TLG), hematological parameters (NLR, PLR), and tumor markers (CEA, CA 19-9) were recorded and the relationship between these parameters and KRAS oncogene mutation was evaluated using receiver operating characteristics (ROC) analysis and multiple logistic regression analysis.
RESULTS: In 20 cases mutations in the KRAS gene were detected, while in 35 cases mutations were not observed (wild-type). ROC analysis revealed that SUVmax, MTV, TLG, NLR, PLR, and CA 19-9 could not predict mutations in KRAS oncogene (P=0.600, 0.263, 0.214, 0.057, 0.104, 0.189, respectively) although CEA value showed signi..cant difference (P=0.031) but without high value of the area under the curve (0.676). Multivariate logistic regression analysis also did not show significant association between KRAS gene mutations and SUVmax, MTV, TLG, NLR, PLR, CEA, CA 19-9 values.
CONCLUSION: We observed that in patients with colorectal cancers, we cannot predict KRAS gene mutations using PET/CT parameters (SUVmax, MTV, TLG), hematological parameters (NLR, PLR) or tumor marker CA 19-9. We detected a significant but not very strong association only between CEA and KRAS mutations.

PMID: 28697193 [PubMed - as supplied by publisher]

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A prototype PET/SPECT/X-rays scanner dedicated for whole body small animal studies.

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A prototype PET/SPECT/X-rays scanner dedicated for whole body small animal studies.

Hell J Nucl Med. 2017 Jul 12;:

Authors: Rouchota M, Georgiou M, Fysikopoulos E, Fragogeorgi E, Mikropoulos K, Papadimitroulas P, Kagadis G, Loudos G

Abstract
OBJECTIVE: To present a prototype tri-modal imaging system, consisting of a single photon emission computed tomography (SPET), a positron emission tomography (PET), and a computed tomography (CT) subsystem, evaluated in planar mode.
MATERIALS AND METHODS: The subsystems are mounted on a rotating gantry, so as to be able to allow tomographic imaging in the future. The system, designed and constructed by our group, allows whole body mouse imaging of competent performance and is currently, to the best of our knowledge, unequaled in a national and regional level. The SPET camera is based on two Position Sensitive Photomultiplier Tubes (PSPMT), coupled to a pixilated Sodium Iodide activated with Thallium (NaI(Tl)) scintillator, having an active area of 5x10cm(2). The dual head PET camera is also based on two pairs of PSPMT, coupled to pixelated berillium germanium oxide (BGO) scintillators, having an active area of 5x10cm(2). The X-rays system consists of a micro focus X-rays tube and a complementary metal-oxide-semiconductor (CMOS) detector, having an active area of 12x12cm(2).
RESULTS: The scintigraphic mode has a spatial resolution of 1.88mm full width at half maximum (FWHM) and a sensitivity of 107.5cpm/0.037MBq at the collimator surface. The coincidence PET mode has an average spatial resolution of 3.5mm (FWHM) and a peak sensitivity of 29.9cpm/0.037MBq. The X-rays spatial resolution is 3.5lp/mm and the contrast discrimination function value is lower than 2%.
CONCLUSION: A compact tri-modal system was successfully built and evaluated for planar mode operation. The system has an efficient performance, allowing accurate and informative anatomical and functional imaging, as well as semi-quantitative results. Compared to other available systems, it provides a moderate but comparable performance, at a fraction of the cost and complexity. It is fully open, scalable and its main purpose is to support groups on a national and regional level and provide an open technological platform to study different detector components and acquisition strategies.

PMID: 28697192 [PubMed - as supplied by publisher]

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An innovative method for precise lymph node detection before surgical treatment.

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An innovative method for precise lymph node detection before surgical treatment.

Hell J Nucl Med. 2017 Jul 12;:

Authors: Matovic M, Nikolic D, Filipovic N, Chen D, Jeremic M, Jankovic SM, Ninkovic S, Cvetkovic A, Vlajkovic M, Rankovic A

Abstract
OBJECTIVE: To describe a new method of 3D interactive modeling which integrates images obtained by separate SPET and multi slice computed tomography (MSCT) modalities using an original software in order to better localize SNL in BC patients.
SUBJECTS AND METHODS: We used technetium-99m-colloid rhenium sulphate for identifying SNL in seven patients with BC. Markers were made of lead pearls wrapped with cotton wool soaked in (99m)Tc-pertechnetate and placed on the skin of the patients forming of a triangle. Using an original software, two separate 3D models were made after SPET and MSCT imaging and then merged into a hybrid 3D model which enabled precise visualization and localization of the SNL.
RESULTS: In all cases the position of the SNL established by our method was successfully verified using a gamma probe. Duration of SNL identification and extirpation were significantly reduced in less than 10 minutes per patient. The reproducibility of this method was confirmed by precise identification and biopsy of the SNL.
CONCLUSION: We found this integrated SPET/MSCT 3D model to be much faster and easier to use as compared with the "classic" method, which was based on a radioactivity detection probe. In addition, our method was reproducible, accurate and of low cost. In other words, the method described in this paper could be very useful for health facilities with modest budget, because it obviates the need for buying expensive integrated SPET/MSCT hybrid imaging systems while detecting SNLs more accurately and in shorter time.

PMID: 28697191 [PubMed - as supplied by publisher]

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(18)F-FDG PET/CT and histology for diagnosing recurrent/remnant tumors in head and neck cancer patients treated with radiotherapy.

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(18)F-FDG PET/CT and histology for diagnosing recurrent/remnant tumors in head and neck cancer patients treated with radiotherapy.

Hell J Nucl Med. 2017 Jul 12;:

Authors: Han EJ, O JH, Yoo IR, Kim YS, Kim MS, Kang JH, Choi WH

Abstract
OBJECTIVE: The aim of this study was to assess the diagnostic performance of fluorine-18-fluoro-2-deoxyglucose ((18)F-FDG) positron emission tomography (PET)/computed tomography (CT) for locoregional recurrent/residual tumor in patients with head and neck cancer (HNC) who underwent previous radiotherapy (RT).
SUBJECTS AND METHODS: (18)F-FDG PET/CT images from patients with HNC who previously underwent RT were retrospectively reviewed. Only cases with histological confirmation within 4 weeks of PET/CT imaging were included. Standardized uptake values were obtained for lesions and PET/CT findings were compared with histological results.
RESULTS: Of 181 cases, 114 (63%) were histologically confirmed as malignant and 67 (37%) as benign. The sensitivity, specificity, and accuracy of PET/CT were 93%, 64%, and 82%, respectively. Inflammation was the most common cause of false positives and small tumor volume and low (18)F-FDG avidity were the causes of false negatives. PET/CT had 100% sensitivity and 56% specificity for detecting recurrent or residual disease within 12 weeks after RT and 93% sensitivity and 64% specificity, more than 12 weeks after RT. The frequency of false positives in PET/CT images within 12 weeks of RT was similar to the results obtained 12 weeks after RT (15% vs. 14%). False positives were more frequent in PET/CT cases after two-dimensional or three-dimensional conformal RT than in those after intensity-modulated RT, although not statistically significant (15% vs. 9%, p>0.05).
CONCLUSION: (18)F-FDG PET/CT might aid the diagnosis of locoregional residual/recurrent tumors in patients with HNC previously treated with RT. Inflammation was the main cause of false positives regardless of the interval between RT and PET/CT, even several years after RT. Therefore, histological verification of positive PET/CT findings should be conducted during follow-up of HNC patients treated with RT.

PMID: 28697190 [PubMed - as supplied by publisher]

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Gallium-68-dotatate PET/CT is better than CT in the management of somatostatin expressing tumors: First experience in Africa.

Related Articles

Gallium-68-dotatate PET/CT is better than CT in the management of somatostatin expressing tumors: First experience in Africa.

Hell J Nucl Med. 2017 Jul 12;:

Authors: Lawal IO, Ololade KO, Lengana T, Reyneke F, Ankrah AO, Ebenhan T, Vorster M, Sathekge MM

Abstract
OBJECTIVE: In this study we aimed to present our experience on the use of Gallium-68-dotatate with positron emission tomography, computed tomography ((68) Ga-dotatate PET/CT) in the management of neuroendocrine tumors (NET) and other somatostatin expressing tumors.
SUBJECTS AND METHODS: We retrospectively reviewed patients with histologically confirmed or biochemically suspected NET and other somatostatin expressing (SSTR) tumors imaged at our department with (68)Ga-dotatate PET/CT. We determined the performance of this imaging technique as well as its impact on patients management. A total of 203 patients were studied: 103 females, 100 males median age 52years.
RESULTS: The commonest tumor type was gastroenteropancreatic NET (41% of patients) and the commonest sites of distant metastases were lymph nodes and the liver 34.0% and 30.5% respectively. Positron emission tomography detected foci of disease in 19 patients where CT was falsely negative. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of (68) Ga-dotatate PET/CT imaging of NET and other SST expressing tumors were 94.16%, 91.89%, 95.55%, 89.47% and 96.55% respectively.
CONCLUSION: Gallium-68-dotatate PET/CT was better than CT in detecting primary sites of the disease and highly sensitive and specific for diagnosis and treatment of NET and other SSTR expressing tumors.

PMID: 28697189 [PubMed - as supplied by publisher]

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Impact of tall cell variant histology on predicting relapse and changing the management of papillary thyroid carcinoma patients.

Related Articles

Impact of tall cell variant histology on predicting relapse and changing the management of papillary thyroid carcinoma patients.

Hell J Nucl Med. 2017 Jul 12;:

Authors: Gunalp B, Okuyucu K, Ince S, Ayan A, Alagoz E

Abstract
OBJECTIVE: There has been much discussion recently about the risk category of tall cell variant (TVC) histology and its effects on the management of papillary thyroid carcinoma (PTC). We, therefore, undertook a retrospective study to compare stage-matched risk factors and recurrence rates between classical PTC (cPTC) patients and patients with TCV histology.
SUBJECTS AND METHODS: A total of 3128 well-differentiated thyroid carcinoma patients who were treated and followed-up for more than 5 years in our clinic from 1995 to 2016 were included in this study. There were 2783 PTC (89%) patients, 1113 (40%) of them were cPTC and 56 (2%) of them were TCV patients.
RESULTS: In all stages, the stage-matched incidence of extrathyroidal extension (ETE), lymphovascular invasion and initial lymph node metastases were significantly higher in TCV patients than in cPTC patients (P<0.001). Recurrence was in 10 of 27 patients (37%) with TCV and in 91 of 890 (10%) patients with cPTC diagnosed in stage I (odds ratio (OR)=5.16); in 4 of 6 patients with TCV and 18 of 84 (21%) patients with cPTC in stage II (OR=7.33); in 5 of 6 patients with TCV and 11 of 46 (23%) patients with cPTC in stage III (OR=15.90); and in 13 of 17 patients with TCV and 31 of 93 (33%) patients with cPTC in stage IV (OR=6.50). Stage-matched recurrence rates were found significantly higher in all stages of TCV patients than in cPTC patients (OR=8.49, P<0.001). Recurrence with distant metastases was seen more frequently in TCV patients than in cPTC patients (P<0.001) and treatment of metastatic disease was more difficult in TCV patients.
CONCLUSION: Tall cell variant was an independent poor prognostic factor in papillary thyroid carcinoma patients even if they were diagnosed at early stages of the disease. Patients with tall cell variant histology required more aggressive therapeutic approach and closer follow-up than classical patients.

PMID: 28697188 [PubMed - as supplied by publisher]

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Can semiquantitative measurements of SUVmax and cut-off values differentiate malignant from benign colorectal cancer?

Related Articles

Can semiquantitative measurements of SUVmax and cut-off values differentiate malignant from benign colorectal cancer?

Hell J Nucl Med. 2017 Jul 12;:

Authors: Nguyen T, Hess S, Petersen H, Alavi A, Høilund-Carlsen PF

Abstract
OBJECTIVE: We investigated maximum standardized uptake value (SUVmax) and cut-off values for differentiation of malignant and benign lesions in colorectal cancer (CC) as multiple studies have questioned their validity. We also investigated more extended indices using common semi-quantification analysis in incidental colorectal findings (ICF).
SUBJECTS AND METHODS: Fluorine-18-fluoro deoxy glucose positron emission tomography/computed tomography in 25 patients with a total of 30 focal ICF was retrospectively analysed using dedicated software. Method variability was tested through application of three common threshold-based lesion delineation techniques as well as a partial-volume correction (PVC). Lesion SUVmax, SUVmean, metabolically active volume (MAV) and mean total lesion glycolysis (TLG) were thereby extracted along with PVC corrected values (cSUVmean, cTLG) and SUVpeak.
RESULTS: In all lesions, SUVmax was >5 and SUVmean≥2.7. Malignant SUVmax values (mean±SD: 16.5±6.2) were overall significantly higher than benign levels (9.8±3.6). There was a substantial overlap with values in polyps/adenomas (14.4±7.7). Both SUVpeak and SUVmean showed similar characteristics. Malignant MAV and TLG showed more distinct levels. Though different segmentation methods introduced variations, largest in MAV (-58.6%-141.5%), and PVC generally increased measures significantly by a factor of 1.2-2.7, neither changed relative levels much. SUVmax values were inadequate for aetiological differentiation of ICF, which also precludes a clinically significant cut-off value. The same applies to SUVpeak and SUVmean while TLG measures may be more indicative.
CONCLUSION: Semi-quantitative measurements of SUVmax and cut-off values proved inadequate for differentiating colorectal malignancies from benign findings. While integrated measures, e.g. cTLG, are potentially better indicators of disease severity and extent, more optimal segmentation and PVC methods are required.

PMID: 28697187 [PubMed - as supplied by publisher]

http://ift.tt/2tOSgFx

Whiplash Syndrome- a disorder of the brain?

Related Articles

Whiplash Syndrome- a disorder of the brain?

Hell J Nucl Med. 2017 Jul 12;:

Authors: Biendara J, Otte A

Abstract
In the past two decades much has been published on whiplash injury, yet both the confusion regarding the condition, and the medicolegal discussion about it have increased. In this paper, functional imaging research results are summarized using MRIcroGL 3D visualization software and assembled in an image comprising regions of cerebral activation and deactivation.

PMID: 28697186 [PubMed - as supplied by publisher]

http://ift.tt/2tOqhWM

Contents of Previous Special Issues in this Series of Perspectives

Publication date: Available online 12 July 2017
Source:DNA Repair





http://ift.tt/2tKPfHQ

Zebularine induces replication-dependent double-strand breaks which are preferentially repaired by homologous recombination

Publication date: Available online 12 July 2017
Source:DNA Repair
Author(s): Manuel Luis Orta, Nuria Pastor, Estefanía Burgos-Morón, Inmaculada Domínguez, José Manuel Calderón-Montaño, Carlos Huertas Castaño, Miguel López-Lázaro, Thomas Helleday, Santiago Mateos
Zebularine is a second-generation, highly stable hydrophilic inhibitor of DNA methylation with oral bioavailability that preferentially target cancer cells. It acts primarily as a trap for DNA methyl transferases (DNMTs) protein by forming covalent complexes between DNMT protein and zebularine-substrate DNA. It's well documented that replication-blocking DNA lesions can cause replication fork collapse and thereby to the formation of DNA double-strand breaks (DSB). DSB are dangerous lesions that can lead to potentially oncogenic genomic rearrangements or cell death. The two major pathways for repair of DSB are non-homologous end joining (NHEJ) and homologous recombination (HR). Recently, multiple functions for the HR machinery have been identified at arrested forks. Here we investigate in more detail the importance of the lesions induced by zebularine in terms of DNA damage and cytotoxicity as well as the role of HR in the repair of these lesions. When we examined the contribution of NHEJ and HR in the repair of DSB induced by zebularine we found that these breaks were preferentially repaired by HR. Also we show that the production of DSB is dependent on active replication. To test this, we determined chromosome damage by zebularine while transiently inhibiting DNA synthesis. Here we report that cells deficient in single-strand break (SSB) repair are hypersensitive to zebularine. We have observed more DSB induced by zebularine in XRCC1 deficient cells, likely to be the result of conversion of SSB into toxic DSB when encountered by a replication fork. Furthermore we demonstrate that HR is required for the repair of these breaks. Overall, our data suggest that zebularine induces replication-dependent DSB which are preferentially repaired by HR.



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Experimental investigation of performance and emissions of a VCR diesel engine fuelled with n -butanol diesel blends under varying engine parameters

Abstract

The continuous rise in the cost of fossil fuels as well as in environmental pollution has attracted research in the area of clean alternative fuels for improving the performance and emissions of internal combustion (IC) engines. In the present work, n-butanol is treated as a bio-fuel and investigations have been made to evaluate the feasibility of replacing diesel with a suitable n-butanol-diesel blend. In the current research, an experimental investigation was carried out on a variable compression ratio CI engine with n-butanol-diesel blends (10–25% by volume) to determine the optimum blending ratio and optimum operating parameters of the engine for reduced emissions. The best results of performance and emissions were observed for 20% n-butanol-diesel blend (B20) at a higher compression ratio as compared to diesel while keeping the other parameters unchanged. The observed deterioration in engine performance was within tolerable limits. The reductions in smoke, nitrogen oxides (NO_x ), and carbon monoxide (CO) were observed up to 56.52, 17.19, and 30.43%, respectively, for B20 in comparison to diesel at rated power. However, carbon dioxide (CO₂) and hydrocarbons (HC) were found to be higher by 17.58 and 15.78%, respectively, for B20. It is concluded that n-butanol-diesel blend would be a potential fuel to control emissions from diesel engines.

Graphical abstract

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Intrarater Reliability and Agreement of Linear Encoder Derived Heel-Rise Endurance Test Outcome Measures in Healthy Adults

Publication date: Available online 12 July 2017
Source:Journal of Electromyography and Kinesiology
Author(s): Christopher Byrne, David J. Keene, Sarah E. Lamb, Keith Willett
A linear encoder measuring vertical displacement during the heel-rise endurance test (HRET) enables the assessment of work and maximum height in addition to the traditional repetitions measure. We aimed to compare the test-retest reliability and agreement of these three outcome measures. Thirty-eight healthy participants (20 females, 18 males) performed the HRET on two occasions separated by a minimum of seven days. Reliability was assessed by the intraclass correlation coefficient (ICC) and agreement by a range of measures including the standard error of measurement (SEM), coefficient of variation (CV), and 95% limits of agreement (LoA). Reliability for repetitions (ICC = 0.77 (0.66, 0.85)) was equivalent to work (ICC = 0.84 (95% CI 0.76, 0.89)) and maximum height (ICC = 0.85 (0.77, 0.90)). Agreement for repetitions (SEM = 6.7 (5.8, 7.9); CV = 13.9% (11.9, 16.8%); LoA = -1.9 ± 37.2%) was equivalent to work (SEM = 419 J (361, 499 J); CV = 13.1% (11.2, 15.8%); LoA = 0.1 ± 34.8%) with maximum height superior (SEM = 0.8 cm (0.6, 1.0 cm); CV = 6.6% (5.7, 7.9%); LoA = 1.3 ± 17.1%). Work and maximum height demonstrated acceptable reliability and agreement that was at least equivalent to the traditional repetitions measure.



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Intra-operatively measured spastic semimembranosus forces of children with cerebral palsy

Publication date: Available online 12 July 2017
Source:Journal of Electromyography and Kinesiology
Author(s): Can A. Yucesoy, Yener Temelli, Filiz Ateş
The knee kept forcibly in a flexed position is typical in cerebral palsy. Using a benchmark, we investigate intra-operatively if peak spastic hamstring force is measured in flexed knee positions. This tests the assumed shift of optimal length due to adaptation of spastic muscle and a decreasing force trend towards extension. Previously we measured spastic gracilis (GRA) and semitendinosus (ST) forces. Presently, we studied spastic semimembranosus (SM) and tested the following hypotheses: spastic SM forces are (1) high in flexed and (2) low in extended positions. We compared the data to those of GRA and ST to test (3) if percentages of peak force produced in flexed positions are different. During muscle lengthening surgery of 8 CP patients (9 years, 4 months; GMFCS levels=II-IV; limbs tested=13) isometric SM forces were measured from flexion (120°) to full extension (0°). Spastic SM forces were low in flexed knee positions (only 4.2% (3.4%) and 10.7% (9.7%) of peak force at KA=120° and KA=90° respectively, indicating less force production compared to the GRA or ST) and high in extended knee positions (even 100% of peak force at KA=0°). This indicates absence of strong evidence for shift of optimal muscle length of SM towards flexion.



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Occurrence and risk assessment of antidepressants in Huangpu River of Shanghai, China

Abstract

Antidepressants are gaining public attention because of increasing reports of their occurrence in environment and their potential impact on ecosystems and human health. Continuous input of pharmaceuticals into rivers, through psychiatric hospital or wastewater treatment plant (WWTPs) effluent, may cause adverse effects on the aquatic ecosystems of the receiving water bodies. This work investigates the occurrence and sources of 8 antidepressants in main stream and tributaries of Huangpu River in Shanghai. The detected concentrations of the selected antidepressants ranged from low nanogram per liter to 42.9 ng L⁻¹ (fluoxetine) in main stream and ranged from low nanogram per liter to 33.7 ng L⁻¹ (fluoxetine) in tributaries. To study the effect of hospital or wastewater treatment plants (WWTPs) on environment, the upstream and downstream samples were analyzed. Generally, antidepressants had greater concentrations in downstream than that in upstream of the WWTPs or hospitals. It is suggesting that WWTPs and hospitals may introduce pollution into water environment. A preliminary risk assessment was conducted: none of the eight target compounds yielded risk quotient (RQ) values more than 0.1, thus indicating that no adverse effect is expected in water environment. These results will provide background data for future antidepressants pollution control and management in Shanghai, China.

http://ift.tt/2ukOqHy

Risk assessment of heavy metals in soil of Tongnan District (Southwest China): evidence from multiple indices with high-spatial-resolution sampling

Abstract

Assessment of heavy metal (HM) pollution in soil is critical for human health, ecological remediation, and soil conservation. In this study, statistical analyses and geochemical approaches such as enrichment factor (EF), the index of geoaccumulation (Igeo), and potential ecological risk index (RI) were used for characterization and risk assessment of soil HMs through a high-spatial-resolution 385 samples from Tongnan District, an important agricultural practice area in Chongqing Municipality in Southwest China. Igeo and EF indicated that Hg and Cd could be considered as low and moderate polluted, respectively, and others HMs were not a major concern. Comprehensive ecological risk information further demonstrated that the HMs have caused a moderate risk. Principal component analysis (PCA) extracted two principal components (PCs) with eigenvalue >1 explaining about 66.1% of the total variance in the HM data sets, demonstrating major source of anthropogenic activity, phosphate fertilizers, vehicle, and pesticides. These multi-index methods have the capacity of HM assessment in soil, which are useful for soil conservation and ecological remediation.

http://ift.tt/2uTjg6V

Soy molasses as a fermentation substrate for the production of biosurfactant using Pseudomonas aeruginosa ATCC 10145

Abstract

Soy molasses is a product co-generated during soybean processing that has high production and low commercial value. Its use has great potential in fermentative processes due to the high concentration of carbohydrates, lipids and proteins. This study investigated the use of Pseudomonas aeruginosa to produce biosurfactants in a soy molasses-based fermentation medium. A central composite design (CCD) was prepared with two variables and three replicates at the central point to optimize the production of biosurfactant. The concentration of soy molasses had values between 29.3 and 170.7 g/L and the initial concentration of microorganism varied between 0.2 and 5.8 g/L. All the experiments were performed in duplicate on a shaker table at 30.0 ± 1.0 °C and 120 rpm for 72 h with samples taken every 12 h. Thus, to validate the experiments, the values of 120 g/L for the initial concentration of soy molasses and 4 g/L for the initial concentration of microorganisms were used. In response, the following values were obtained at 48 h of fermentation: surface tension of 31.9 dyne/cm, emulsifying index of 97.4%, biomass concentration of 11.5 g/L, rhamnose concentration of 6.9 g/L and biosurfactant concentration of 11.70 g/L. Further analysis was carried out for critical micelle concentration (CMC) which was obtained at approximately 80 mg/L. The bands found in Fourier transform infrared spectroscopy analysis had characteristic glycolipids as reported in the literature. These values show a great potential for biosurfactant production using soy molasses as a substrate and bacteria of the species P. aeruginosa.

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Assessment of potential health risk of fluoride consumption through rice, pulses, and vegetables in addition to consumption of fluoride-contaminated drinking water of West Bengal, India

Abstract

A study was conducted in fluoride-affected Bankura and Purulia districts of West Bengal to assess the potential health risk from fluoride exposure among children, teenagers, and adults due to consumption of rice, pulses, and vegetables in addition to drinking water and incidental ingestion of soil by children. Higher mean fluoride contents (13–63 mg/kg dry weight) were observed in radish, carrot, onion bulb, brinjal, potato tuber, cauliflower, cabbage, coriander, and pigeon pea. The combined influence of rice, pulses, and vegetables to cumulative estimated daily intake (EDI) of fluoride for the studied population was found to be 9.5–16%. Results also showed that intake of ivy gourd, broad beans, rice, turnip, fenugreek leaves, mustard, spinach, and amaranth grown in the study area is safe at least for time being. The cumulative EDI values of fluoride (0.06–0.19 mg/kg-day) among different age group of people of the study area were evaluated to be ~10⁴ times higher than those living in the control area; the values for children (0.19 and 0.52 mg/kg-day for CTE and RME scenarios, respectively) were also greater than the "Tolerable Upper Intake Level" value of fluoride. The estimated hazard index (HI) for children (3.2 and 8.7 for CTE and RME scenarios, respectively) living in the two affected districts reveals that they are at high risk of developing dental fluorosis due to the consumption of fluoride-contaminated rice, pulses, and vegetables grown in the study area in addition to the consumption of contaminated drinking water.

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The necessity of intrathecal chemotherapy for the treatment of breast cancer patients with leptomeningeal metastasis: A systematic review and pooled analysis

Publication date: Available online 12 July 2017
Source:Current Problems in Cancer
Author(s): Yen-Chien Lee, Chung-Cheng Hsieh, Jen-Pin Chuang, Chung-Yi Li
BackgroundLeptomeningeal carcinomatosis is a devastating disease. Despite its numerous complications, intrathecal (IT) chemotherapy remains a longstanding treatment for leptomeningeal carcinomatosis. Using case studies with internationally reported results, we attempted to determine the necessity of IT chemotherapy in treating leptomeningeal carcinomatosis.MethodsWe conducted a systematic review and pooled analysis to compare hormone therapy, chemotherapy, and IT therapy. We excluded articles on IT trastuzumab therapy. We performed our literature search without language restriction. We retrieved articles that were published by as late as July 19, 2016. The present study was performed in accordance with the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analysis. The Cox proportional hazard regression model was performed to examine the effects of prognostic variables.ResultsA total of 34 patients from 32 studies were considered eligible. The median age of the patients in the hormone treatment, chemotherapy, and IT therapy groups was 46, 51.5, and 51 years, respectively. The median overall survival (OS) of the patients in the hormone treatment, chemotherapy, and IT therapy groups was 65, 52, and 41 weeks, respectively. One patient who received hormone therapy exhibited the longest survival of approximately 8.5 years. Only magnetic resonance imaging response was associated with overall survival (hazard ratio=0.05, 95% confidence interval 0.00–0.74; p=0.03). Hormone status, HER2 status, age, central nervous system (CNS) radiation therapy, IT therapy, metastasis sites (CNS only vs. others), and cerebrospinal fluid responses were all not associated with overall survival.ConclusionGiven its obvious side effects and lack of evidence of effectiveness from prospective randomized clinical trials, IT chemotherapy should be used with caution in the treatment of LM breast cancer patients.



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An alternative screening model for the estimation of outdoor air concentration at large contaminated sites

Publication date: September 2017
Source:Atmospheric Environment, Volume 165
Author(s): Iason Verginelli, Massimo Nocentini, Renato Baciocchi
Simplified analytical solutions of fate and transport models are often used to carry out risk assessment on contaminated sites, to evaluate the long-term air quality in relation to volatile organic compounds in either soil or groundwater. Among the different assumptions employed to develop these solutions, in this work we focus on those used in the ASTM-RBCA "box model" for the evaluation of contaminant dispersion in the atmosphere. In this simple model, it is assumed that the contaminant volatilized from the subsurface is dispersed in the atmosphere within a mixing height equal to two meters, i.e. the height of the breathing zone. In certain cases, this simplification could lead to an overestimation of the outdoor air concentration at the point of exposure. In this paper we first discuss the maximum source lengths (in the wind direction) for which the application of the "box model" can be considered acceptable. Specifically, by comparing the results of "box model" with the SCREEN3 model of U.S.EPA we found that under very stable atmospheric conditions (class F) the ASTM-RBCA approach provides acceptable results for source lengths up to 200 m while for very unstable atmospheric conditions (class A and B) the overestimation of the concentrations at the point of the exposure can be already observed for source lengths of only 10 m. In the latter case, the overestimation of the "box model" can be of more than one order of magnitude for source lengths above 500 m. To overcome this limitation, in this paper we introduce a simple analytical solution that can be used for the calculation of the concentration at the point of exposure for large contaminated sites. The method consists in the introduction of an equivalent mixing zone height that allows to account for the dispersion of the contaminants along the source length while keeping the simplistic "box model" approach that is implemented in most of risk assessment tools that are based on the ASTM-RBCA standard (e.g. RBCA toolkit). Based on our testing, we found that the developed model replicates very well the results of the more sophisticated dispersion SCREEN3 model with deviations always below 10%. The key advantage of this approach is that it can be very easily incorporated in the current risk assessment screening tools that are based on the ASTM standards while ensuring a more accurate evaluation of the concentration at the point of exposure.



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Aerosol radiative effect in UV, VIS, NIR, and SW spectra under haze and high-humidity urban conditions

Publication date: October 2017
Source:Atmospheric Environment, Volume 166
Author(s): Ming Zhang, Yingying Ma, Wei Gong, Lunche Wang, Xiangao Xia, Huizheng Che, Bo Hu, Boming Liu
Aerosol properties derived from sun-photometric observations at Wuhan during a haze period were analyzed and used as input in a radiative transfer model to calculate the aerosol radiative effect (ARE) in ultraviolet (UV), visible (VIS), near-infrared (NIR), and shortwave (SW) spectra. The results showed that the aerosol optical depth (AOD) at 440 nm increased from 0.32 under clear-air conditions to 0.85 during common haze and 1.39 during severe haze. An unusual inverse relationship was found between the Ångström exponent (AE) and AOD during the haze period at Wuhan. Under high-humidity conditions, the fine-mode median radius of aerosols increased from 0.113 μm to approximately 0.2–0.5 μm as a result of hygroscopic growth, which led to increases in the AOD and decreases in the AE simultaneously. These changes were responsible for the inverse relationship between AE and AOD at Wuhan. The surface ARE in the UV (AREUV), VIS (AREVIS), NIR (ARENIR), and SW (ARESW) spectra changed from −4.46, −25.37, −12.15, and −41.99 W/m² under clear-air conditions to −9.48, −53.96, −29.81, and −93.25 W/m² during common hazy days and −12.89, −80.16, −55.17, and −148.22 W/m² during severe hazy days, respectively, and the percentages of AREUV, AREVIS, and ARENIR in ARESW changed from 11%, 61%, and 28%–9%, 54%, and 37%, respectively. Meanwhile, the ARE efficiencies (REE) in SW varied from −206.5 W/m² under clear-air conditions to −152.94 W/m² during the common haze period and −131.47 W/m² during the severe haze period. The smallest decreasing rate of the REE in NIR was associated with the increase of ARENIR. The weakened REE values were related to the strong forward scattering and weak backward scattering of fine aerosol particles with increasing size resulting from hygroscopic growth, while the variation of the single scattering albedo showed less impact. Source region analysis by back trajectories and the concentration weighted trajectory (CWT) method showed that black carbon came from nearby regions with low trajectories, and the surrounding haze areas were major sources of fine-mode particles in the haze in Wuhan.



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Emissions from prescribed burning of agricultural fields in the Pacific Northwest

Publication date: October 2017
Source:Atmospheric Environment, Volume 166
Author(s): A.L. Holder, B.K. Gullett, S.P. Urbanski, R. Elleman, S. O'Neill, D. Tabor, W. Mitchell, K.R. Baker
Prescribed burns of winter wheat stubble and Kentucky bluegrass fields in northern Idaho and eastern Washington states (U.S.A.) were sampled using ground-, aerostat-, airplane-, and laboratory-based measurement platforms to determine emission factors, compare methods, and provide a current and comprehensive set of emissions data for air quality models, climate models, and emission inventories. Batch measurements of PM2.5, volatile organic compounds (VOCs), polycyclic aromatic hydrocarbons (PAHs), and polychlorinated dibenzodioxins/dibenzofurans (PCDDs/PCDFs), and continuous measurements of black carbon (BC), particle mass by size, CO, CO2, CH4, and aerosol characteristics were taken at ground level, on an aerostat-lofted instrument package, and from an airplane. Biomass samples gathered from the field were burned in a laboratory combustion facility for comparison with these ground and aerial field measurements. Emission factors for PM2.5, organic carbon (OC), CH4, and CO measured in the field study platforms were typically higher than those measured in the laboratory combustion facility. Field data for Kentucky bluegrass suggest that biomass residue loading is directly proportional to the PM2.5 emission factor; no such relationship was found with the limited wheat data. CO2 and BC emissions were higher in laboratory burn tests than in the field, reflecting greater carbon oxidation and flaming combustion conditions. These distinctions between field and laboratory results can be explained by measurements of the modified combustion efficiency (MCE). Higher MCEs were recorded in the laboratory burns than from the airplane platform. These MCE/emission factor trends are supported by 1–2 min grab samples from the ground and aerostat platforms. Emission factors measured here are similar to other studies measuring comparable fuels, pollutants, and combustion conditions. The size distribution of refractory BC (rBC) was single modal with a log-normal shape, which was consistent among fuel types when normalized by total rBC mass. The field and laboratory measurements of the Angstrom exponent (α) and single scattering albedo (ω) exhibit a strong decreasing trend with increasing MCEs in the range of 0.9–0.99. Field measurements of α and ω were consistently higher than laboratory burns, which is likely due to less complete combustion. When VOC emissions are compared with MCE, the results are consistent for both fuel types: emission factors increase as MCE decreases.

Graphical abstract

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Bactericidal activity of Cu-, Zn-, and Ag-containing zeolites toward Escherichia coli isolates

Abstract

Two types of zeolites—natural clinoptilolite (NZ) and synthetic zeolite A (A)—were enriched with approx. 0.25 mmol of Cu(II), Zn(II), or Ag(I) ions, and the obtained materials (M-Z) were tested against three different isolates of Escherichia coli. Two isolates were environmental isolates from waters in Serbia whereas the third one was DSM 498. Antibacterial activity was studied in different water media—nutrient-rich media (peptone water), water from Sava Lake, and commercially available spring water. The Ag-containing zeolites showed bactericidal activity in the nutrient-rich peptone water after 1 h of contact. Cu- and Zn-containing zeolites showed bactericidal activity in real water samples. Antibacterial activity of the M-Z decreases in all three examined water media in the following order: Ag-NZ ≈ Ag-A > Cu-NZ ≈ Cu-A > Zn-NZ >>> Zn-A, suggesting that mainly the metal type and not the zeolite type have a role in the antibacterial activity. Leaching experiments showed small amounts of the leached Cu(II) and Zn(II) ions, indicating that the antibacterial activity is not due to the metal ions but should be attributed to the M-Z itself. However, leached amounts of Ag(I) from Ag-NZ and Ag-A in peptone water indicate that the released Ag(I) could be mainly responsible for the bactericidal effect of the Ag(I)-containing zeolites. Since no loss of cellular material was found, the antibacterial activity is not attributed to cytoplasmic membrane damage.

http://ift.tt/2tKgrXx

Time series analysis of ambient air pollution effects on daily mortality

Abstract

Although the growths of ambient pollutants have been attracting public concern, the characteristic of the associations between air pollutants and mortality remains elusive. Time series analysis with a generalized additive model was performed to estimate the associations between ambient air pollutants and mortality outcomes in Shenzhen City for the period of 2012–2014. The results showed that nitrogen dioxide (NO₂)-induced excess risks (ER) of total non-accidental mortality and cardiovascular mortality were significantly increased (6.05% (95% CI 3.38%, 8.78%); 6.88% (95% CI 2.98%, 10.93%), respectively) in interquartile range (IQR) increase analysis. Also, these associations were strengthened after adjusting for other pollutants. Moreover, similar associations were estimated for sulfur dioxide (SO₂), particulate matter with an aerodynamic diameter of <10 μm (PM₁₀), and total non-accidental mortality. There were significant higher ERs of associations between PM₁₀ and mortality for men than women; while there were significant higher ERs of associations between PM₁₀/NO₂ and mortality for elders (65 or elder) than youngers (64 or younger). Season analyses showed that associations between NO₂ and total non-accidental mortality were more pronounced in hot seasons than in warm seasons. Taken together, NO₂ was positively associated with total non-accidental mortality and cardiovascular mortality in Shenzhen even when the concentrations were below the ambient air quality standard. Policy measures should aim at reducing residents' exposure to anthropogenic NO₂ emissions.

http://ift.tt/2tg5wkG

Response to Letter to the Editor: Safety of transcranial direct current stimulation: Evidence based update 2016

Publication date: Available online 12 July 2017
Source:Brain Stimulation
Author(s): Marom Bikson, Pnina Grossman, Adantchede Louis Zannou, Greg Kronberg, Dennis Truong, Paulo Boggio, Andre R. Brunoni, Leigh Charvet, Felipe Fregni, Brita Fritsch, Bernadette Gillick, Roy H. Hamilton, Benjamin M. Hampstead, Adam Kirton, Helena Knotkova, David Liebetanz, Anli Liu, Colleen Loo, Michael A. Nitsche, Janine Reis, Jessica D. Richardson, Alexander Rotenberg, Peter E. Turkeltaub, Adam J. Woods




http://ift.tt/2ufXxYV

Transient anger attacks associated with bifrontal transcranial direct current stimulation

Publication date: Available online 12 July 2017
Source:Brain Stimulation
Author(s): Galen Chin-Lun Hung, Ming-Chyi Huang




http://ift.tt/2vemzoJ

Bacteria Tell Us How to Protect Our Intestine

Publication date: 12 July 2017
Source:Cell Host & Microbe, Volume 22, Issue 1
Author(s): George Birchenough, Gunnar C. Hansson
The inner colon mucus layer capacity to separate bacteria from the epithelium is dependent on bacterial colonizers signaling to the host epithelium. In this issue of Cell Host & Microbe, Wlodarska et al. (2017) demonstrate that the mucin-utilizing Peptostreptococcus russellii protects the host from inflammatory disease via metabolite signals.

Teaser

The inner colon mucus layer capacity to separate bacteria from the epithelium is dependent on bacterial colonizers signaling to the host epithelium. In this issue of Cell Host & Microbe, Wlodarska et al. (2017) demonstrate that the mucin-utilizing Peptostreptococcus russellii protects the host from inflammatory disease via metabolite signals.


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Double the Trouble When Herpesviruses Join Hands

Publication date: 12 July 2017
Source:Cell Host & Microbe, Volume 22, Issue 1
Author(s): Un Yung Choi, Angela Park, Jae U. Jung
KSHV is the etiologic agent of PEL—an aggressive lymphoma. Interestingly, EBV concurrently exists in nearly 70% of PEL cases. In this issue of Cell Host & Microbe, McHugh et al. (2017) develop humanized mouse models for EBV/KSHV co-infection and identify their complementary effect on in vivo tumor formation.

Teaser

KSHV is the etiologic agent of PEL—an aggressive lymphoma. Interestingly, EBV concurrently exists in nearly 70% of PEL cases. In this issue of Cell Host & Microbe, McHugh et al. develop humanized mouse models for EBV/KSHV co-infection and identify their complementary effect on in vivo tumor formation.


http://ift.tt/2ug0mcM

War on Viruses: LC3 Recruits GTPases

Publication date: 12 July 2017
Source:Cell Host & Microbe, Volume 22, Issue 1
Author(s): Teneema Kuriakose, Thirumala-Devi Kanneganti
Interferon effector functions and autophagy are evolutionarily conserved arms of cell-autonomous immunity that restrict replication of intracellular pathogens. In this issue of Cell Host and Microbe, Biering et al., (2017) demonstrate how host cells co-opt sequential action of autophagy proteins and IFN-inducible GTPases to inhibit replication of positive-sense RNA viruses.

Teaser

Interferon effector functions and autophagy are evolutionarily conserved arms of cell-autonomous immunity that restrict replication of intracellular pathogens. In this issue of Cell Host and Microbe, Biering et al., (2017) demonstrate how host cells co-opt sequential action of autophagy proteins and IFN-inducible GTPases to inhibit replication of positive-sense RNA viruses.


http://ift.tt/2veGTGG

Dual Blades: The Role of Musashi 1 in Zika Replication and Microcephaly

Publication date: 12 July 2017
Source:Cell Host & Microbe, Volume 22, Issue 1
Author(s): Robyn S. Klein
Infection with Zika virus (ZIKV) during pregnancy may cause severe developmental defects in the human brain via unknown mechanisms. In a recent issue of Science, Chavali et al. (2017) identified a neural progenitor cell (NPC)-specific RNA binding protein that may underlie the high levels of ZIKV replication and apoptosis observed in these cells during congenital infections.

Teaser

Infection with Zika virus (ZIKV) during pregnancy may cause severe developmental defects in the human brain via unknown mechanisms. In a recent issue of Science, Chavali et al. (2017) identified a neural progenitor cell (NPC)-specific RNA binding protein that may underlie the high levels of ZIKV replication and apoptosis observed in these cells during congenital infections.


http://ift.tt/2ug0n0k

Skin Dysbiosis Goes “Off-Leish”

Publication date: 12 July 2017
Source:Cell Host & Microbe, Volume 22, Issue 1
Author(s): Tiffany C. Scharschmidt
There is increasing interest in the contribution of microbes to skin disease. In this issue of Cell Host & Microbe, Gimblet et al. (2017) demonstrate that cutaneous leishmaniasis alters the human skin microbiota. In mice, this dysbiosis is transferable to naive animals, where it augments skin inflammation and disease severity.

Teaser

There is increasing interest in the contribution of microbes to skin disease. In this issue of Cell Host & Microbe, Gimblet et al. (2017) demonstrate that cutaneous leishmaniasis alters the human skin microbiota. In mice, this dysbiosis is transferable to naive animals, where it augments skin inflammation and disease severity.


http://ift.tt/2vemqBv

Indoleacrylic Acid Produced by Commensal Peptostreptococcus Species Suppresses Inflammation

Publication date: 12 July 2017
Source:Cell Host & Microbe, Volume 22, Issue 1
Author(s): Marta Wlodarska, Chengwei Luo, Raivo Kolde, Eva d'Hennezel, John W. Annand, Cortney E. Heim, Philipp Krastel, Esther K. Schmitt, Abdifatah S. Omar, Elizabeth A. Creasey, Ashley L. Garner, Sina Mohammadi, Daniel J. O'Connell, Sahar Abubucker, Timothy D. Arthur, Eric A. Franzosa, Curtis Huttenhower, Leon O. Murphy, Henry J. Haiser, Hera Vlamakis, Jeffrey A. Porter, Ramnik J. Xavier
Host factors in the intestine help select for bacteria that promote health. Certain commensals can utilize mucins as an energy source, thus promoting their colonization. However, health conditions such as inflammatory bowel disease (IBD) are associated with a reduced mucus layer, potentially leading to dysbiosis associated with this disease. We characterize the capability of commensal species to cleave and transport mucin-associated monosaccharides and identify several Clostridiales members that utilize intestinal mucins. One such mucin utilizer, Peptostreptococcus russellii, reduces susceptibility to epithelial injury in mice. Several Peptostreptococcus species contain a gene cluster enabling production of the tryptophan metabolite indoleacrylic acid (IA), which promotes intestinal epithelial barrier function and mitigates inflammatory responses. Furthermore, metagenomic analysis of human stool samples reveals that the genetic capability of microbes to utilize mucins and metabolize tryptophan is diminished in IBD patients. Our data suggest that stimulating IA production could promote anti-inflammatory responses and have therapeutic benefits.

Graphical abstract

Teaser

Wlodarska et al. provide insight into intestinal mucin as an exemplar of a critical host-derived colonization factor that attracts bacteria that may promote intestinal health. One such mucin utilizer, Peptostreptococcus russellii, produces the tryptophan metabolite indoleacrylic acid, which has beneficial effects on intestinal epithelial barrier function and mitigates inflammatory responses.


http://ift.tt/2ufTTyq

Synergy between the Host Immune System and Bacteriophage Is Essential for Successful Phage Therapy against an Acute Respiratory Pathogen

Publication date: 12 July 2017
Source:Cell Host & Microbe, Volume 22, Issue 1
Author(s): Dwayne R. Roach, Chung Yin Leung, Marine Henry, Eric Morello, Devika Singh, James P. Di Santo, Joshua S. Weitz, Laurent Debarbieux
The rise of multi-drug-resistant (MDR) bacteria has spurred renewed interest in the use of bacteriophages in therapy. However, mechanisms contributing to phage-mediated bacterial clearance in an animal host remain unclear. We investigated the effects of host immunity on the efficacy of phage therapy for acute pneumonia caused by MDR Pseudomonas aeruginosa in a mouse model. Comparing efficacies of phage-curative and prophylactic treatments in healthy immunocompetent, MyD88-deficient, lymphocyte-deficient, and neutrophil-depleted murine hosts revealed that neutrophil-phage synergy is essential for the resolution of pneumonia. Population modeling of in vivo results further showed that neutrophils are required to control both phage-sensitive and emergent phage-resistant variants to clear infection. This "immunophage synergy" contrasts with the paradigm that phage therapy success is largely due to bacterial permissiveness to phage killing. Lastly, therapeutic phages were not cleared by pulmonary immune effector cells and were immunologically well tolerated by lung tissues.

Graphical abstract

Teaser

The mechanisms underlying phage-mediated bacterial clearance in an animal host remain unclear. By coupling animal experiments and in silico modeling, Roach et al. show that host innate immunity is essential for the efficacy of phages in treating respiratory bacterial infections, defining the concept of "immunophage synergy."


http://ift.tt/2ug0lFK

Environmental Stress Causes Lethal Neuro-Trauma during Asymptomatic Viral Infections

Publication date: 12 July 2017
Source:Cell Host & Microbe, Volume 22, Issue 1
Author(s): Jonathan Chow, Zsuzsa Márka, Imre Bartos, Szabolcs Márka, Jonathan C. Kagan
Asymptomatic infections often proceed undetected, yet can still prime the host to be sensitive to secondary environmental stress. While the mechanisms underlying disease caused by asymptomatic infections are unknown, it is believed that productive pathogen replication is required. We report that the environmental stress of carbon dioxide (CO2) anesthesia converts an asymptomatic rhabdovirus infection in Drosophila to one that is lethal. This lethality results from a pool of infectious virus in glial cells and is regulated by the antiviral RNAi pathway of the host. CO2 sensitivity is caused by the fusogenic activity of the viral glycoprotein, which results in fusion of neurons and glia. Expression of the viral glycoprotein, but not a fusion defective mutant, is sufficient to cause CO2 sensitivity, which can occur even in the absence of productive viral replication. These findings highlight how viral proteins, independent of pathogen replication, may predispose hosts to life-threatening environmental stress.

Graphical abstract

Teaser

Asymptomatic infections can severely impact host health. Chow et al. delineate a deadly outcome from asymptomatic VSV infection. CO2, a standard anesthetic in fly laboratories, induces VSV glycoprotein (G) to mediate cell-cell fusion in the nervous system. The results demonstrate that non-pathological proteins can be dangerous in the right environment.


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Persistent KSHV Infection Increases EBV-Associated Tumor Formation In Vivo via Enhanced EBV Lytic Gene Expression

Publication date: 12 July 2017
Source:Cell Host & Microbe, Volume 22, Issue 1
Author(s): Donal McHugh, Nicole Caduff, Mario Henrique M. Barros, Patrick C. Rämer, Ana Raykova, Anita Murer, Vanessa Landtwing, Isaak Quast, Christine T. Styles, Michael Spohn, Adeola Fowotade, Henri-Jacques Delecluse, Alexandra Papoudou-Bai, Yong-Moon Lee, Jin-Man Kim, Jaap Middeldorp, Thomas F. Schulz, Ethel Cesarman, Andrea Zbinden, Riccarda Capaul, Robert E. White, Martin J. Allday, Gerald Niedobitek, David J. Blackbourn, Adam Grundhoff, Christian Münz
The human tumor viruses Epstein-Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV) establish persistent infections in B cells. KSHV is linked to primary effusion lymphoma (PEL), and 90% of PELs also contain EBV. Studies on persistent KSHV infection in vivo and the role of EBV co-infection in PEL development have been hampered by the absence of small animal models. We developed mice reconstituted with human immune system components as a model for KSHV infection and find that EBV/KSHV dual infection enhanced KSHV persistence and tumorigenesis. Dual-infected cells displayed a plasma cell-like gene expression pattern similar to PELs. KSHV persisted in EBV-transformed B cells and was associated with lytic EBV gene expression, resulting in increased tumor formation. Evidence of elevated lytic EBV replication was also found in EBV/KSHV dually infected lymphoproliferative disorders in humans. Our data suggest that KSHV augments EBV-associated tumorigenesis via stimulation of lytic EBV replication.

Graphical abstract

Teaser

McHugh et al. describe a small animal model of KSHV infection and demonstrate that KSHV collaborates with another human gamma herpes virus, EBV, to establish persistent infection in B cells. The emerging transformed cells resemble primary effusion lymphomas, the malignancies that frequently harbor both viruses in humans.


http://ift.tt/2ug0LM9

Induction of INKIT by Viral Infection Negatively Regulates Antiviral Responses through Inhibiting Phosphorylation of p65 and IRF3

Publication date: 12 July 2017
Source:Cell Host & Microbe, Volume 22, Issue 1
Author(s): Bin Lu, Yujie Ren, Xueqin Sun, Cuijuan Han, Hongyan Wang, Yuxuan Chen, Qianqian Peng, Yongbo Cheng, Xiaoliang Cheng, Qiyun Zhu, Wenxin Li, Hong-Liang Li, Hai-Ning Du, Bo Zhong, Zan Huang
The transcription factors p65 and IRF3 play key roles in the induction of cellular antiviral responses. Phosphorylation of p65 and IRF3 is required for their activity and constitutes a key checkpoint. Here we report that viral infection induced upregulation of INKIT, an inhibitor for NF-κB and IRF3 that restricted innate antiviral responses by blocking phosphorylation of p65 and IRF3. INKIT overexpression inhibited virus-induced phosphorylation of p65 and IRF3 and expression of downstream genes. In contrast, knockdown or knockout of INKIT had the opposite effect: Inkit^−/− mice produced elevated levels of type I interferons and proinflammatory cytokines and were more resistant to lethal viral infection compared to wild-type. INKIT interacted with IKKα/β and TBK1/IKKɛ, impairing the recruitment and phosphorylation of p65 and IRF3. Viral infection induced IKK-mediated phosphorylation of INKIT at Ser58, resulting in its dissociation from the IKKs. Our findings thus uncover INKIT as a regulator of innate antiviral responses.

Graphical abstract

Teaser

Phosphorylation of the transcription factors IRF3 and p65 is a key checkpoint for cellular antiviral responses. Lu et al. show that INKIT inhibits the phosphorylation of IRF3 and p65 by impairing their associations with upstream kinases, thereby restricting innate antiviral signaling.


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Fusion Stage of HIV-1 Entry Depends on Virus-Induced Cell Surface Exposure of Phosphatidylserine

Publication date: 12 July 2017
Source:Cell Host & Microbe, Volume 22, Issue 1
Author(s): Elena Zaitseva, Eugene Zaitsev, Kamran Melikov, Anush Arakelyan, Mariana Marin, Rafael Villasmil, Leonid B. Margolis, Gregory B. Melikyan, Leonid V. Chernomordik
HIV-1 entry into host cells starts with interactions between the viral envelope glycoprotein (Env) and cellular CD4 receptors and coreceptors. Previous work has suggested that efficient HIV entry also depends on intracellular signaling, but this remains controversial. Here we report that formation of the pre-fusion Env-CD4-coreceptor complexes triggers non-apoptotic cell surface exposure of the membrane lipid phosphatidylserine (PS). HIV-1-induced PS redistribution depends on Ca²⁺ signaling triggered by Env-coreceptor interactions and involves the lipid scramblase TMEM16F. Externalized PS strongly promotes Env-mediated membrane fusion and HIV-1 infection. Blocking externalized PS or suppressing TMEM16F inhibited Env-mediated fusion. Exogenously added PS promoted fusion, with fusion dependence on PS being especially strong for cells with low surface density of coreceptors. These findings suggest that cell-surface PS acts as an important cofactor that promotes the fusogenic restructuring of pre-fusion complexes and likely focuses the infection on cells conducive to PS signaling.

Graphical abstract

Teaser

Zaitseva et al. show that HIV binding to target cells induces signaling that leads to exposure of phosphatidylserine on the cell surface. Interaction between the viral envelope glycoprotein and phosphatidylserine facilitates receptor-dependent merger of viral and cell membranes and infection. Phosphatidylserine dependence may focus infection on cells of certain activation status.


http://ift.tt/2ugdRsC

HIV-1-Mediated Downmodulation of HLA-C Impacts Target Cell Recognition and Antiviral Activity of NK Cells

Publication date: 12 July 2017
Source:Cell Host & Microbe, Volume 22, Issue 1
Author(s): Christian Körner, Camille R. Simoneau, Philipp Schommers, Mitchell Granoff, Maja Ziegler, Angelique Hölzemer, Sebastian Lunemann, Janet Chukwukelu, Björn Corleis, Vivek Naranbhai, Douglas S. Kwon, Eileen P. Scully, Stephanie Jost, Frank Kirchhoff, Mary Carrington, Marcus Altfeld
It was widely accepted that HIV-1 downregulates HLA-A/B to avoid CTL recognition while leaving HLA-C unaltered in order to prevent NK cell activation by engaging inhibitory NK cell receptors, but it was recently observed that most primary isolates of HIV-1 can mediate HLA-C downmodulation. Now we report that HIV-1-mediated downmodulation of HLA-C was associated with reduced binding to its respective inhibitory receptors. Despite this, HLA-C-licensed NK cells displayed reduced antiviral activity compared to their unlicensed counterparts, potentially due to residual binding to the respective inhibitory receptors. Nevertheless, NK cells were able to sense alterations of HLA-C expression demonstrated by increased antiviral activity when exposed to viral strains with differential abilities to downmodulate HLA-C. These results suggest that the capability of HLA-C-licensed NK cells to control HIV-1 replication is determined by the strength of KIR/HLA-C interactions and is thus dependent on both host genetics and the extent of virus-mediated HLA-C downregulation.

Graphical abstract

Teaser

HIV-1 modulates the expression of ligands for receptors expressed by natural killer (NK) cells on infected cells to evade NK cell recognition. Körner et al. demonstrate that NK cells are able to sense HIV-1-mediated downmodulation of HLA-C through decreased binding of inhibitory KIR receptors to HLA-C.


http://ift.tt/2ufN67M

Diabetes Enhances IL-17 Expression and Alters the Oral Microbiome to Increase Its Pathogenicity

Publication date: 12 July 2017
Source:Cell Host & Microbe, Volume 22, Issue 1
Author(s): E Xiao, Marcelo Mattos, Gustavo Henrique Apolinário Vieira, Shanshan Chen, Jôice Dias Corrêa, Yingying Wu, Mayra Laino Albiero, Kyle Bittinger, Dana T. Graves
Diabetes is a risk factor for periodontitis, an inflammatory bone disorder and the greatest cause of tooth loss in adults. Diabetes has a significant impact on the gut microbiota; however, studies in the oral cavity have been inconclusive. By 16S rRNA sequencing, we show here that diabetes causes a shift in oral bacterial composition and, by transfer to germ-free mice, that the oral microbiota of diabetic mice is more pathogenic. Furthermore, treatment with IL-17 antibody decreases the pathogenicity of the oral microbiota in diabetic mice; when transferred to recipient germ-free mice, oral microbiota from IL-17-treated donors induced reduced neutrophil recruitment, reduced IL-6 and RANKL, and less bone resorption. Thus, diabetes-enhanced IL-17 alters the oral microbiota and renders it more pathogenic. Our findings provide a mechanistic basis to better understand how diabetes can increase the risk and severity of tooth loss.

Graphical abstract

Teaser

Diabetes increases periodontal disease, a major cause of tooth loss. Xiao et al. demonstrated, by transfer to germ-free mice, that oral microbiota from diabetic mice induced more periodontal inflammation and bone loss than microbiota from normal mice. Diabetes increased the pathogenicity of the oral microbiota through an IL-17-mediated mechanism.


http://ift.tt/2ufGKFo

The sugarcane herbicide ametryn induces oxidative stress and developmental abnormalities in zebrafish embryos

Abstract

Ametryn (AMT) is one of the most widely used herbicides in tropical sugarcane crops, the main culture of São Paulo State, Brazil. It is known as a diffuse pollutant, being found in surface water and sediment of water bodies adjacent to the crop fields. In the present study, the toxicity of AMT to zebrafish (Danio rerio) embryos was evaluated using developmental and biochemical endpoints. At the biochemical level, lactate dehydrogenase responded at the lowest concentration tested (4 μg L⁻¹) indicating a high demand of energy required to cope with the stress condition. Antioxidant enzyme levels were changed at intermediate/high concentrations while oxidative damage (lipid peroxidation) was observed at the last concentration tested (10 mg L⁻¹). This suggests that, like for other herbicides from the triazine group, oxidative stress is a major pathway of toxicity for AMT. Several developmental effects such as oedemas and tail deformities were also observed. The 96 h-EC₅₀ values calculated for different developmental parameters were between 17 and 29 mg L⁻¹. AMT also affected hatching (96 h-EC₅₀ = 22.5 mg L⁻¹) and positioning in the water column (96 h-EC₅₀ = 13.2 mg L⁻¹). In a previous work of the group, lethal toxicity of AMT showed to be much higher to adults than to embryos. However, in the present work, sublethal endpoints assessed suggest that important effects are observed at lower concentrations, improving the sensitivity of the embryo test. Moreover, in this work, sublethal effects were observed for concentrations in the same range as the ones found in the environment, and thus, given that this chemical is widely used in tropical fields, a refined evaluation of risk should be performed based on the monitoring of sublethal and long-term parameters and considering mixture scenarios.

http://ift.tt/2tO1VvX

Determination of cyclic volatile methylsiloxanes in personal care products by gas chromatography

Abstract

Objective

Organosiloxanes are prevalent in personal care products (PCPs) due to the desired properties they impart in the usage and application of such products. However, the European Chemical Agency (ECHA) has recently published restriction proposals on the amount of two cyclic siloxanes, octamethylcyclotetrasiloxane (D4) and decamethylcyclotetrasiloxane (D5) allowed in wash off products such as shampoos and conditioners which are discharged down the drain during consumer use. This legislation will require that reliable analytical methods are available for manufacturers and government agencies to use in documenting compliance with the restrictions. This paper proposes a simple analytical method to enable accurate measurement of these compounds down to the circa 0.1 weight percent level in PCPs.

Methods

While gas chromatography methods are reported in the literature for quantitation of D4 and D5 in several matrices including PCPs, the potential for generation of false positives due to contamination, co-elution, and in-situ generation of cyclic volatile methylsiloxanes (cVMS) is always present and needs to be controlled. This report demonstrates the applicability of using a combination of emulsion break, liquid-liquid extraction and silylation sample preparation followed by GC-FID analysis as a suitable means of analyzing PCPs for specific cVMS.

Results

The reliability and limitations of such methodology was demonstrated through several round robin studies conducted in the laboratories of a consortium of silicone manufacturers. In addition, this report presents examples of false positives encountered during development of the method and presents a comparative analysis between this method and a published QuEChERS sample preparation procedure to illustrate the potential for generation of false positives when an inappropriate approach is applied to determination of cVMS in personal care products.

Conclusion

This report demonstrates that an approach to determine cVMS levels in personal care products is to perform an emulsion break on the sample, isolate the nonpolar phase from the emulsion break and treat with a silylation reagent to abate potential in situ formation of cyclics during the course of GC-FID analysis. Round robin studies conducted in laboratories representing multiple siloxane manufacturers demonstrated the reliability of the GC-FID method when measuring cVMS in PCPs down to circa 0.1%.

This article is protected by copyright. All rights reserved.

http://ift.tt/2uaxOS2

Conventional sunscreen application does not lead to sufficient body coverage

Abstract

Objective

This study aimed to assess sunscreen application habits and relative body coverage after single whole body application.

Methods

Fifty-two healthy volunteers were asked to use the test product once, following their usual sunscreen application routine. Standardized UV photographs (UVP), which were evaluated by Image Analysis (IA), were conducted before and immediately after product application to evaluate relative body coverage. In addition to these procedures, the volunteers completed an online self-assessment questionnaire (SAS) to assess sunscreen usage habits.

Results

After product application, the front side showed significantly less non-covered skin (4.35%) than the backside (17.27%) (p=0.0000). Females showed overall significantly less non-covered skin (8.98%) than males (13.16%) (p=0.0381). On the backside, females showed significantly less non-covered skin (13.57%) (p=0.0045) than males (21.94%) while on the front side this difference between females (4.14%) and males (4.53%) was not significant.

Conclusion

In most cases, the usual sunscreen application routine does not provide complete body coverage even though an extra light sunscreen with good absorption properties was used. On average, 11 % of the body surface was not covered by sunscreen at all. Therefore, appropriate consumer education is required to improve sunscreen application and to warrant effective sun protection.

This article is protected by copyright. All rights reserved.

http://ift.tt/2sRGp8i

Novel amino acid-based surfactant for silicone emulsification and its application in hair care products: A promising alternative to quaternary ammonium cationic surfactants

Abstract

Objective

Quaternary ammonium cationic surfactants (ACSs) and N-[3-alkyl(12,14)oxy-2-hydroxypropyl]-L-arginine hydrochloride (N-AOHPA) were used to emulsify silicone. The potential of the resulting emulsions in hair conditioning products was investigated.

Methods

The emulsions were prepared using a homogenizer and/or high-pressure homogenizer. ACSs and N-AOHPA were used as silicone emulsifiers. The stability of the emulsions were evaluated by measuring particle sizes, creaming fractions, polydispersity indexes and zeta potentials. Moreover, the N-AOHPA-stabilized emulsion was compared with the ACS-stabilized emulsion to evaluate the adsorption amount of silicone on healthy and bleached hair surfaces and the inhibitory effects on amino acid dissolution from bleached hair. The adsorption site of the N-AOHPA-stabilized emulsion was observed using a scanning electron microscope.

Results

For all surfactants, the silicone emulsions prepared using the high-pressure homogenizer were more stable than those prepared using the homogenizer. When N-AOHPA was used as the surfactant, the silicone emulsion was especially stable. Furthermore, the d50 value of the N-AOHPA-stabilized emulsion was smaller than that of the ACS-stabilized emulsion. The adsorption behavior of the silicone droplets in the different emulsions varied depending on the nature of the surfactant and the preparation method. The amount of ACS-stabilized silicone adsorbed on healthy hair was higher than that adsorbed on bleached hair, especially when the emulsion was prepared using the homogenizer. In contrast, the amount of N-AOHPA-stabilized silicone adsorbed on bleached hair was high, and no differences were observed between the N-AOHPA-stabilized emulsions prepared using the homogenizer and high-pressure homogenizer. The emulsified droplets, especially the N-AOHPA-stabilized droplets prepared using the high-pressure homogenizer, prevented amino acid dissolution from bleached hair. It was concluded that the silicone droplet adsorption site affected the dissolution process because the small N-AOHPA-stabilized droplets adsorbed at cuticle edges.

Conclusion

This study shows that N-AOHPA has good potential for use as an emulsifier in products used for improving the condition of damaged hair.

This article is protected by copyright. All rights reserved.

http://ift.tt/2uaTr4V