Mode Analysis of NMR Relaxation in a Polymer Melt
Αυτή η ειδοποίηση αποστέλλεται από τον Μελετητή Google. Ο Μελετητής Google είναι μια υπηρεσία που παρέχεται από την Google.
Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,
Αυτή η ειδοποίηση αποστέλλεται από τον Μελετητή Google. Ο Μελετητής Google είναι μια υπηρεσία που παρέχεται από την Google.
Publication date: Available online 1 August 2018
Source: Journal of Autoimmunity
Author(s): Pavanish Kumar, Leong Jing Yao, Suzan Saidin, Bhairav Paleja, Jorg van Loosdregt, Camillus Chua, Thaschawee Arkachaisri, Alessandro Consolaro, Marco Gattorno, Alberto Martini, Ken D. Pischel, Gary W. Williams, Martin Lotz, Salvatore Albani
T-cell resilience is critical to the immune pathogenesis of human autoimmune arthritis. Autophagy is essential for memory T cell generation and associated with pathogenesis in rheumatoid arthritis (RA). Our aim here was to delineate the role and molecular mechanism of autophagy in resilience and persistence of pathogenic T cells from autoimmune arthritis.
We demonstrated "Autophagic memory" as elevated autophagy levels in CD4+ memory T cells compared to CD4+ naive T cells and in Jurkat Human T cell line trained with starvation stress. We then showed increased levels of autophagy in pathogenic CD4+ T cells subsets from autoimmune arthritis patients. Using RNA-sequencing, transcription factor gene regulatory network and methylation analyses we identified MYC as a key regulator of autophagic memory. We validated MYC levels using qPCR and further demonstrated that inhibiting MYC increased autophagy. The present study proposes the novel concept of autophagic memory and suggests that autophagic memory confers metabolic advantage to pathogenic T cells from arthritis and supports its resilience and long term survival. Particularly, suppression of MYC imparted the heightened autophagy levels in pathogenic T cells. These studies have a direct translational valency as they identify autophagy and its metabolic controllers as a novel therapeutic target.
Publication date: Available online 2 August 2018
Source: Magnetic Resonance Imaging
Author(s): Bihong T. Chen, Kiarash Ghassaban, Taihao Jin, Sunita K. Patel, Ningrong Ye, Can-Lan Sun, Heeyoung Kim, Russell C. Rockne, E. Mark Haacke, James C. Root, Andrew J. Saykin, Tim A. Ahles, Andrei I. Holodny, Neal Prakash, Joanne Mortimer, James Waisman, Yuan Yuan, George Somlo, Daneng Li, Richard Yang
As the number of older adults in the U.S. increases, so too will the incidence of cancer and cancer-related cognitive impairment (CRCI). However, the exact underlying biological mechanism for CRCI is not yet well understood. We utilized susceptibility-weighted imaging with quantitative susceptibility mapping, a non-invasive MRI-based technique, to assess longitudinal iron deposition in subcortical gray matter structures and evaluate its association with cognitive performance in women age 60+ with breast cancer receiving adjuvant chemotherapy and age-matched women without breast cancer as controls. Brain MRI scans and neurocognitive scores from the NIH Toolbox for Cognition were obtained before chemotherapy (time point 1) and within one month after the last infusion of chemotherapy for the patients and at matched intervals for the controls (time point 2). There were 14 patients age 60+ with breast cancer (mean age 66.3 ± 5.3 years) and 13 controls (mean age 68.2 ± 6.1 years) included in this study. Brain iron increased as age increased. There were no significant between- or within- group differences in neurocognitive scores or iron deposition at time point 1 or between time points 1 and 2 (p > 0.01). However, there was a negative correlation between iron in the globus pallidus and the fluid cognition composite scores in the control group at time point 1 (r = −0.71; p < 0.01), but not in the chemotherapy group. Baseline iron in the putamen was negatively associated with changes in the oral reading recognition scores in the control group (r = 0.74, p < 0.01), but not in the chemotherapy group. Brain iron assessment did not indicate cancer or chemotherapy related short-term differences, yet some associations with cognition were observed. Studies with larger samples and longer follow-up intervals are warranted.
Magnetic nanoparticles (MNPs), based on iron oxide (magnetite) and ferrogel of gelatin and MNPs, were employed as efficient tools for the removal of heavy metals and nutrients from water samples from Bahia Blanca estuarine (BBE). An exhaustive adsorption performance of Cu, NO3−, and NO2− was conducted in batch using model solutions aiming to adjust the adsorption conditions. Adsorption studies using water simulating the real samples were also performed. Both kinds of nanomaterials demonstrated an efficiency between 60 and 80%, and 85% for the removal of heavy metals and NO3− and NO2−, respectively. Similar adsorption assays were performed using BBE water samples, employing the experimental conditions explored with model and simulated water. The reached efficiency was 30 and 45% for heavy metal and nutrient removal, respectively, using nanoparticles; meanwhile, ferrogels displayed a removal capacity around 50–60%. The nanoparticles showed structural instability by the leaching of iron to the medium after the adsorption processes. Ferrogels remained almost inalterable in terms of their integrity during the adsorption time. These materials showed satisfactory perspectives regarding their reuse possibilities. They were used for almost five repeated cycles of adsorption without losing efficiency on the adsorption. The results of this study suggest that MNPs and FGs appear as versatile and promising materials that may be considered as valid alternatives to the actual tools for the remediation of real water samples.
The fate and transport of antibiotics in the aquatic environment are usually influenced by the combined effects of environmental factors. In this study, batch-type experiments were conducted to investigate the combined effects of phosphate and salinity on oxytetracycline (OTC) adsorption on, and desorption from, two marine sediments. Pseudo-second-order kinetic model fitted the kinetic data better than pseudo-first-order model. The pseudo-second-order kinetic rate (k2) of OTC increased significantly with increasing phosphate concentrations. Sorption isotherms of OTC can be well described by both the Langmuir and Freundlich models. Compared with the control experiments (without phosphate addition), Freundlich distribution coefficients (KF) after addition of 50 mg L−1 phosphate decreased from 24.9 to 17.9 L kg−1 on sediments collected from Laizhou Bay, and from 52.2 to 31.3 L kg−1 on sediments collected from Bohai Bay, which indicated that phosphate could inhibit adsorption of OTC on marine sediments. Furthermore, phosphate had a stronger inhibitory effect on OTC adsorption at low salinity level than at high salinity level. The effects of phosphate on OTC adsorption can be explained by ion exchange, change of sediment surface charge, and electrostatic repulsion mechanisms. Desorption experiments showed that phosphate can enhance the total desorption percentage of OTC from marine sediments. Overall, the presence of phosphate in marine system may enhance OTC's long-term transport.
This article presents an example of the application of simulation tools to estimate the post-closure evolution of leachate in a non-hazardous waste landfill. The objective of this work is to predict the behavior of leachate after the closure of the landfill for use as basic information with which to design the leachate management strategy in the following years. The MODUELO 4.0 mathematical landfill simulation software package was used for this purpose. The results of the simulation show that the concentrations in the leachate increase during the post-closure period, from values close to 2200 mg/L of COD and 1500 mg/L of NH4+ at the time of landfill closure to 3200 mg/L of COD and 5300 mg/L of NH4+ 20 years later. This increase is mainly due to the reduction in the flows, from 105 to 17 m3/day on average, since the surface lining was installed. Consequently, pollutant fluxes decrease to values below 100 kg/day in both COD and NH4+ 3 months after closure. This evolution indicates that the management of this leachate will be simpler in the future, especially if it is co-treated with urban wastewater, as its contribution decreases. On the other hand, external water connections to the leachate collectors may cause a relevant increase in the volume of the global landfill effluent. Controlling runoff management and underground infiltrations could lead to important savings in leachate treatment during the aftercare phase.
AbstractBackground.Clinical trial completion is critical for new cancer therapies. Premature trial termination or withdrawal is common and impairs progress. We assessed factors of early terminated/withdrawn oncology trials focusing on trials with immune checkpoint inhibitors (ICI), hypothesizing that the latter may be associated with lower rates of premature discontinuation.Materials and Methods.We reviewed all adult, intervention, oncology trials registered in ClinicalTrials.gov (November 16, 2011, to April 16, 2015) to identify all terminated/withdrawn trials and reasons for termination. Logistics regression model was used to identify factors associated with early termination/withdrawal. Discontinuation rate was compared in trials with and without ICI.Results.We identified 12,875 trials (35% industry funded, 12% federal funded), of which 8.5% were prematurely terminated (5%) or withdrawn (3.5%); the main reasons were poor accrual (33%) and logistical (24%). ICI trials (n = 350) had a nonsignificant lower rate of termination or withdrawal compared with all other oncology trials (5.4% vs. 8.5%; p = .9) and were less likely to discontinue due to poor accrual (nonsignificant difference: 21% vs. 33%; p = .4). ICI trials were also less likely to discontinue compared with all other oncology drug trials (e.g., chemotherapy, targeted inhibitors, antiangiogenesis, biologics; 5.4% vs. 7.9%, respectively, nonsignificant difference). The 4‐year cumulative incidence of failing to complete for reasons unrelated to toxicity or efficacy was 18% (95% confidence interval 16%–20%). There was no association between annual incidence across different tumor types or accrual goal and rate of trial termination.Conclusion.Poor accrual represents the main cause of early cancer trial termination. Premature termination/withdrawal rate was not significantly lower in ICI compared with other trials. Clinical trial completion remains a high priority and can be influenced by provider and patient factors.Implications for Practice.Clinical trial completion is critical for new cancer therapies. Premature trial termination or withdrawal is common and impairs progress. This study assessed factors of early terminated/withdrawn oncology trials, focusing on trials with immune checkpoint inhibitors (ICI), and found that poor accrual represents the main cause of early cancer trial termination. Premature termination/withdrawal rate was not significantly lower in immune checkpoint inhibitor trials compared to other trials. The discussion herein is focused on measures taken by the National Cancer Institute and other institutions to improve clinical trial accrual and prevent premature clinical trial discontinuation.
https://ift.tt/2v8sZba
|
Surgery for congenital blephaloptosis is often performed at about 4-5 years of age. Long-term follow-up is important during facial growth. We performed frontal suspension using a single rhomboid-shaped autogenous fascial strip. We conducted a long-term evaluation of severe congenital unilateral blephaloptosis patients.
https://ift.tt/2vtot6y
To assess the importance of shortening of the urethral plate occurred with complete penile disassembly technique in epispadias repair and its impact on cosmetic and functional results (on urinary incontinency).
https://ift.tt/2LL15g0
The success of endodontic treatment depends on the thorough removal of microorganisms from the root canal system. The search for new ways to eliminate the microorganisms is therefore justified. Nd:YAP is a laser that uses yttrium aluminum perovskite, doped with neodymium crystal, as active laser medium. We used the Nd:YAP laser in an in vitro experiment to evaluate the bactericidal effect of three parameters of Nd:YAP laser-activated irrigation on biofilms of Enterococcus faecalis in root canals. The canals of 45 extracted human single-root teeth were prepared on a #35 Mtwo instrument and contaminated with E. faecalis for 14 days. Forty infected single-root teeth were then randomly divided into four groups according to the irrigation agitation protocols as follows: 5.25% sodium hypochlorite (NaOCl), Nd:YAP laser (180 mJ) + NaOCl, Nd:YAP laser (280 mJ) + NaOCl, and Nd:YAP laser (360 mJ) + NaOCl. The remaining bacteria were counted immediately using the cell count method. Teeth were firstly spilt and one half examined by scanning electron microscopy (SEM). The other half involved examination of bacterial colonization in dentinal tubules using confocal laser scanning microscopy (CLSM). Nd:YAP laser (280 mJ) + NaOCl and Nd:YAP laser (360 mJ) + NaOCl completely removed the E. faecalis biofilms from the root canal walls and made it the cleanest among the treatment groups. Bacterial reductions in the treatment groups for dentinal tubules are presented in a descending order as follows: Nd:YAP laser (360 mJ) (53.7%), Nd:YAP laser (280 mJ) (51.5%) > Nd:YAP laser (180 mJ) (45.3%) > 5.25% NaOCl (31.9%) > control (19.3%) (p < 0.05). Nd:YAP laser of 280 mJ and 360 mJ showed effective bactericidal effect in removing E. faecalis biofilm from the root canal walls and dentinal tubules.
Clinical Endocrinology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2v9WJ7F
|
Recent studies from national registries have described changing patterns in epidemiology of acromegaly. Our retrospective study used administrative databases to estimate prevalence and incidence of acromegaly in the Piedmont Region, Italy.
This study was conducted in Piedmont between 2012 and 2016 on administrative health databases for inpatients and outpatients of any age. Enrollees were included if claims suggestive of acromegaly were identified in at least two of the following databases: Drug Claims Registry, Hospital Information System, Co-payment Exemption Registry and Outpatient Specialist Service Information System.
369 individuals (M = 146, F = 223) met our criteria. Overall incidence was 5.3 per million person years (95% CI 4.2–6.7), and prevalence was 83 cases per million inhabitants (95% CI 75–92). Mean age was 50.9 years. Both incidence and prevalence were slightly higher among women (rate ratio 1.08, prevalence ratio 1.43). Age-specific incidence was similar between sexes up to 39 years and diverged thereafter, with an increasing trend recorded among men. Prevalence was higher in women aged 40–79 years, and increased continuously up to 79 years in both sexes.
This is the first population-based study conducted in Italy to estimate incidence and prevalence of acromegaly and results show a higher prevalence than previously reported. Although our algorithm requires proper validation, it constitutes a promising tool to describe the epidemiology of acromegaly.
Publication date: Available online 1 August 2018
Source: Journal of Autoimmunity
Author(s): Roberto Giacomelli, Piero Ruscitti, Yehuda Shoenfeld
Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown etiology usually affecting young adults; spiking fever, arthritis and evanescent rash are commonly observed during the disease. Other frequently observed clinical features include sore throat, hepatomegaly, splenomegaly, lymphadenopathy and serositis. Furthermore, AOSD patients may experience different life-threating complications. Macrophage activation syndrome (MAS) has been reported up to 15% of AOSD patients and it is considered to be the most severe complication of the disease being characterised by high mortality rate. During AOSD, laboratory tests reflect the systemic inflammatory process showing high levels of erythrocyte sedimentation rate and C-reactive protein. In addition, the ferritin levels are typically higher than those observed in other autoimmune, inflammatory, infectious, or neoplastic diseases. Analysing AOSD disease course, 3 different clinical patterns of AOSD have been identified: i. monocyclic pattern, characterised by a systemic single episode; ii. polycyclic pattern, characterised by multiple, ≤ 1 year lasting, flares, alternating with remissions; iii. chronic pattern, related to a persistently active disease with associated polyarthritis. At present, AOSD therapeutic strategy is aimed at targeting pro-inflammatory signs and symptoms, preventing organ damage and life-threating complications and minimising adverse effects of treatment. However, the treatment of AOSD remains largely empirical, lacking controlled clinical trials. High dosages of corticosteroids are usually the first line therapy when the systemic symptoms predominate. Despite this treatment, a large percentage of patients experiences several flares with an evolution toward the chronic disease course and up to 16% of patients die during the follow up, due to AOSD-related complications. On these bases, in the last years, biological agents have been successfully used in refractory cases. Finally, multiple recent lines of evidence have suggested new insights in AOSD pathogenesis unmasking further therapeutic targets. In fact, small molecules, used in experimental MAS models, might represent new therapeutic options.
|
Publication date: Available online 1 August 2018
Source: Magnetic Resonance Imaging
Author(s): Amrit Bansod, Ravindra Kumar Garg, Imran Rizvi, Hardeep Singh Malhotra, Neeraj Kumar, Amita Jain, Rajesh Verma, Neera Kohli, Praveen Kumar Sharma, Ravi Uniyal, Shweta Pandey
This study evaluated the prevalence and predictors of venographic abnormalities in tuberculous meningitis.
Consecutive patients of tuberculous meningitis were included in the study. Clinical evaluation, cerebrospinal fluid examination and contrast-enhanced MRI of brain were done. Every subject was subjected to time of flight magnetic resonance venography (MRV). Presence of filling defects at superior sagittal sinus, dominant transverse or sigmoid sinus, and non-visualization of deep venous system was suggestive of thrombosis. The presence of filling defects at non-dominant transverse or sigmoid sinus was considered suggestive of thrombosis only in the presence of corresponding changes in T1, T2, and GRE sequences, parenchymal changes or presence of collaterals. The patients were followed up for 6 months. A modified Barthel index ≤12 at 6 months was taken as poor outcome.
Out of 107 patients, MRV was found to be abnormal in 12 patients (11.2%). The superior sagittal sinus was the most commonly involved sinus. On univariate analysis, the presence of vomiting (P = 0.004), altered sensorium (P = 0.004), seizures (P < 0.001), vision impairment (P = 0.038), papilledema (P < 0.001), diplopia, oculomotor palsies at baseline, and basal exudates (P = 0.004) were significantly associated with an abnormal MRV. On multivariate analysis, none of the above factors were found to be significant. No association was found between poor outcome and abnormal MRV.
MRV abnormalities suggestive of venous sinus thrombosis can occur in about 11% patients. Superior sagittal sinus is the most commonly involved sinus. An abnormal MRV is not associated with a poor outcome.
To evaluate the ability of CT and PET radiomics features to classify lung lesions as primary or metastatic, and secondly to differentiate histological subtypes of primary lung cancers.
A cohort of 534 patients with lung lesions were retrospectively studied. Radiomics texture features were extracted using the LIFEx package from semiautomatically segmented PET and CT images. Histology data were recorded in all patients. The patient cohort was divided into a training and a validation group and linear discriminant analysis (LDA) was performed to classify the lesions using both direct and backward stepwise methods. The robustness of the procedure was tested by repeating the entire process 100 times with different assignments to the training and validation groups. Scoring metrics included analysis of the receiver operating characteristic curves in terms of area under the curve (AUC), sensitivity, specificity and accuracy.
Radiomics features extracted from CT and PET datasets were able to differentiate primary tumours from metastases in both the training and the validation group (AUCs 0.79 ± 0.03 and 0.70 ± 0.04, respectively, from the CT dataset; AUCs 0.92 ± 0.01 and 0.91 ± 0.03, respectively, from the PET dataset). The AUC cut-off thresholds identified by LDA using direct and backward elimination strategies were −0.79 ± 0.06 and −0.81 ± 0.08, respectively (CT dataset) and −0.69 ± 0.05 and −0.68 ± 0.04, respectively (PET dataset). For differentiation between primary subgroups based on CT features, the AUCs in the training and validation groups were 0.81 ± 0.02 and 0.69 ± 0.04 for adenocarcinoma (Adc) vs. squamous cell carcinoma (Sqc) or "Other", 0.85 ± 0.02 and 0.70 ± 0.05 for Sqc vs. Adc or Other, and 0.77 ± 0.03 and 0.57 ± 0.05 for Other vs. Adc or Sqc. The same analyses for the PET data revealed AUCs of 0.90 ± 0.10 and 0.80 ± 0.04, 0.80 ± 0.02 and 0.61 ± 0.06, and 0.97 ± 0.01 and 0.88 ± 0.04, respectively.
PET radiomics features were able to differentiate between primary and metastatic lung lesions and showed the potential to identify primary lung cancer subtypes.
During neoadjuvant chemoradiotherapy for oesophageal cancer, or in the interval prior to surgery, some patients develop systemic metastasis. This study aimed to evaluate the diagnostic performance of 18F-FDG PET/CT for the detection of interval metastasis and to identify predictors of interval metastases in a large cohort of oesophageal cancer patients.
In total, 783 consecutive patients with potentially resectable oesophageal cancer who underwent chemoradiotherapy and pre- and post-treatment 18F-FDG PET/CT between 2006 and 2015 were analyzed from a prospectively maintained database. Diagnostic accuracy measures were calculated on a per-patient basis using histological verification or clinical follow-up as a reference standard. Multivariable logistic regression analysis was performed to determine pre-treatment predictors of interval metastasis. A prediction score was developed to predict the probability of interval metastasis.
Of 783 patients that underwent 18F-FDG PET/CT restaging, 65 (8.3%) were found to have interval metastasis and 44 (5.6%) were deemed to have false positive lesions. The resulting sensitivity and specificity was 74.7% (95% CI: 64.3–83.4%) and 93.7% (95% CI: 91.6–95.4%), respectively. Multivariable analysis revealed that tumor length, cN status, squamous cell tumor histology, and baseline SUVmax were associated with interval metastasis. Based on these criteria, a prediction score was developed with an optimism adjusted C-index of 0.67 that demonstrated accurate calibration.
18F-FDG PET/CT restaging detects distant interval metastases in 8.3% of patients after chemoradiotherapy for oesophageal cancer. The provided prediction score may stratify risk of developing interval metastasis, and could be used to prioritize additional restaging modalities for patients most likely to benefit.
The aim of this study was to determine if functional parameters extracted from the hybrid positron emission tomography/magnetic resonance imaging (PET/MRI) correlate with the immunohistochemical markers of breast cancer (BC) lesions, to assess their ability to predict BC subtype.
This prospective study was approved by the institution's Ethics Committee, and all patients provided written informed consent. A total of 50 BC patients at diagnosis underwent PET/MRI before pharmacological and surgical treatment. For each primary lesion, the following data were extracted: morphological data including tumour-node-metastasis stage and lesion size; apparent diffusion coefficient (ADC); perfusion data including forward volume transfer constant (Ktrans), reverse efflux volume transfer constant (Kep) and extravascular extracellular space volume (Ve); and metabolic data including standardized uptake value (SUV), lean body mass (SUL), metabolic tumour volume and total lesion glycolysis. Immunohistochemical reports were used to determine receptor status (oestrogen, progesterone, and human epidermal growth factor receptor 2), cellular differentiation status (grade), and proliferation index (Ki67) of the tumour lesions. Correlation studies (Mann–Whitney U test and Spearman's test), receiver operating characteristic (ROC) curve analysis, and multivariate analysis were performed.
Association studies were performed to assess the correlations between imaging and histological prognostic markers of BC. Imaging biomarkers, which significantly correlated with biological markers, were selected to perform ROC curve analysis to determine their ability to discriminate among BC subtypes. SUVmax, SUVmean and SUL were able to discriminate between luminal A and luminal B subtypes (AUCSUVmean = 0.799; AUCSUVmax = 0.833; AUCSUL = 0.813) and between luminal A and nonluminal subtypes (AUCSUVmean = 0.926; AUCSUVmax = 0.917; AUCSUL = 0.945), and the lowest SUV and SUL values were associated with the luminal A subtype. Kepmax was able to discriminate between luminal A and luminal B subtypes (AUC = 0.779), and its highest values were associated with the luminal B subtype. Ktransmax (AUC = 0.881) was able to discriminate between luminal A and nonluminal subtypes, and the highest perfusion values were associated with the nonluminal subtype. In addition, ADC (AUC = 0.877) was able to discriminate between luminal B and nonluminal subtypes, and the lowest ADCmean values were associated with the luminal B subtype. Multivariate analysis was performed to develop a prognostic model, and the best predictive model included Ktransmax and SUVmax parameters.
Using multivariate analysis of both PET and MRI parameters, a prognostic model including Ktransmax and SUVmax was able to predict the tumour subtype in 38 of 49 patients (77.6%, p < 0.001), with higher accuracy for the luminal B subtype (86.2%).
To evaluate the added value of 18F-Fluorocholine (18F-FCH) PET/CT in presurgical imaging of patients with primary hyperparathyroidism (HPT) and challenging localization of the hyper-functioning parathyroid glands.
We included 27 consecutive patients with primary HPT (19 F; median age: 58 years), with either (i) non-conclusive pre-surgical localization with 99mTc-sestaMIBI scintigraphy and neck ultrasonography (US), (ii) recurrence of previously operated HPT, or (iii) familiar HPT with a suspicion of multiple gland disease. Histological findings and resolution of HPT were considered as the gold standard.
18F-FCH PET/CT was positive in 24/27 patients. Twenty-one patients underwent surgery with 27 resected lesions (14 adenomas, 11 hyperplastic glands, two hyper-functioning histologically normal glands), with resolution of HPT in 19/21 patients (90%). 18F-FCH PET/CT localized 22 lesions in 17/21 patients (per patient: sensitivity 81%, positive predictive value (PPV) 94%; per gland: sensitivity 76%, PPV 85%, specificity 91%, negative predictive value (NPV) 86%). 18F-FCH PET/CT found eight lesions which were undetectable on both 99mTc-sestaMIBI scintigraphy and US. In patients with a familial HPT and/or a multiple gland disease, sensitivity was 100 and 79% on a per-patient and a per-gland analysis respectively, while NPV was 63%. In six patients with a persistence or recurrence of previously treated HPT, 18F-FCH PET/CT localized all lesions, both in sporadic and familiar disease.
18F-FCH PET/CT is a promising modality in challenging pre-surgical localization of hyper-functioning parathyroid glands, such as inconclusive standard imaging, recurrence after surgery, or suspected multiple gland disease.
Oncogenic osteomalacia is an endocrine disorder induced by small benign tumours (TIO) producing excessive fibroblast growth factor-23 (FGF23). The only way of curing oncogenic osteomalacia is surgical resection of the culprit TIO, which is extremely difficult to detect using conventional imaging modalities due to its small size and variable location in the body. Since TIO frequently overexpress somatostatin receptors, a clinical utility of SPECT or PET with radiolabelled somatostatin analogues has been reported. Among them, 68Ga-DOTA-TOC has recently been granted a marketing authorization, facilitating its routine application. We report here the results of the first series evaluating the diagnostic performance of 68Ga-DOTA-TOC PET/CT in detecting TIO and its impact on patient management.
68Ga-DOTA-TOC PET/CT and clinical and imaging data from 15 patients with clinical and biochemical signs of oncogenic osteomalacia were retrospectively reviewed. The 68Ga-DOTA-TOC PET/CT findings were compared with the results of post-surgical pathology and clinical and biochemical follow-up.
68Ga-DOTA-TOC PET/CT resulted in the detection of one focus suspicious for TIO in nine of 15 patients (60%), and a tumour was surgically removed in eight. Post-operative pathology confirmed a TIO in those eight patients whose symptoms diminished promptly and biochemical anomalies resolved. 68Ga-DOTA-TOC PET/CT sensitivity, specificity and accuracy were 73%, 67% and 71%, respectively. 68Ga-DOTA-TOC PET/CT findings affected patient management in 67% of cases. In particular, 68Ga-DOTA-TOC PET/CT was able to detect the TIO with a negative or a false-positive result of a previous 111In-pentetreotide SPECT/CT in 5/8 patients (63%) or a previous FDG PET/CT in 7/11 patients (64%). No close relationship was found between the positivity of 68Ga-DOTA-TOC PET/CT and the serum level of a biochemical marker. However, a true-positive result of 68Ga-DOTA-TOC PET/CT was obtained in only one patient with a non-elevated serum level of FGF23.
68Ga-DOTA-TOC PET/CT is an accurate imaging modality in the detection of TIO; in particular, it is worthwhile after failure of somatostatin receptor SPECT(/CT) or FDG PET/CT.
Plasmablastic lymphoma (PBL) is a rare variant of diffuse large B cell lymphomas (DLBCL) clinically characterized by a poorer prognostic. Few clinical and imaging data are available and derived from pooled case reports and small series. The aim of the study was to evaluate the FDG avidity at baseline and the utility of 18-Fluorodeoxyglucose (FDG) positron-emission-tomography/computed-tomography (PET/CT) for staging and response assessment.
Patients with newly diagnosed PBL seen at Lymphoma Study Association centers during the period 2005–2015 were included if they underwent a PET/CT at staging and at the end of treatment (eotPET) and had received an anthracycline-based first line therapy. EotPET scans were analyzed using the 5-point-scale visual analysis in accordance with Lugano criteria. Patients were classified in complete metabolic response (CMR) or no-CMR including partial metabolic response (PMR), stable disease (SD) and progression disease (PD). EotPET results were assessed for the ability to predict event free survival (EFS) and overall survival (OS).
Thirty-five PBL patients fulfilled the inclusion criteria. The median follow-up was 34 months (2.8–120 months). FDG avidity was found in all patients at diagnosis. Most patients (80%) achieved CMR, and 20% were no-CMR including 9% PMR, 6% SD, and 6% PD. A CMR after first line chemotherapy predicted higher EFS (p < 0.0001) and OS (p = 0.0006).
This study confirmed the FDG avidity of PBL subtype and the usefulness of PET/CT scanning in restaging an aggressive lymphoma at the completion of chemotherapy. EotPET can predict outcomes following treatment in patients with PBL.
The purpose of this study was to evaluate therapeutic response to neoadjuvant chemotherapy (NAC) and predict breast cancer recurrence using Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST).
Fifty-nine breast cancer patients underwent fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) before and after NAC prior to planned surgical resection. Pathological complete response (pCR) of the primary tumor was evaluated using PERCIST, while effects of clinicopathological factors on progression-free survival (PFS) were examined using log-rank and Cox methods.
Fifty-six patients and 54 primary tumors were evaluated. Complete metabolic response (CMR), partial metabolic response, stable metabolic disease, and progressive metabolic disease were seen in 45, 7, 3, and 1 patients, respectively, and 43, 7, 3, and 1 primary tumors, respectively. Eighteen (33.3%) of the 54 primary tumors showed pCR. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PERCIST to predict pCR were 100% (18/18), 30.6% (11/36), 41.9% (18/43), 100% (11/11), and 53.7% (29/54), respectively. An optimal percent decrease in peak standardized uptake value for a primary tumor corrected for lean body mass (SULpeak) of 84.3% was found to have a sensitivity of 77.8% (14/18), specificity of 77.8% (28/36), PPV of 63.6% (14/22), NPV of 87.5% (28/32), and accuracy of 77.8% (42/54). Seven (12.5%) of the 56 patients developed recurrent disease (median follow-up 28.1 months, range 11.4–96.4 months). CMR (p = 0.031), pCR (p = 0.024), and early TNM stage (p = 0.033) were significantly associated with longer PFS.
PERCIST is useful for predicting pathological response and prognosis following NAC in breast cancer patients. However, FDG-PET/CT showed a tendency toward underestimation of the residual tumor, and relatively low specificity and PPV of PERCIST showed that a combination of other imaging modalities would still be needed to predict pCR.
A unit error concerning the tumor volume surface ratio (TVSR) is present throughout the article. The unit reported is "cm" but is actually "mm".
18F-FDG uptake in irradiated non-tumour-affected oesophagus (NTO) on restaging PET is a potential surrogate for the measurement of radiation-induced inflammation. Radiation-induced inflammation itself has been shown to be of high prognostic relevance in patients undergoing preoperative radiochemotherapy (RCT) for locally advanced oesophageal cancer. We assessed the prognostic relevance of FDG uptake in the NTO in an independent cohort of patients treated with definitive RCT.
This retrospective evaluation included 72 patients with oesophageal squamous cell carcinoma treated with definitive RCT with curative intent. All patients underwent pretreatment and restaging FDG PET after receiving a radiation dose of 40–50 Gy. Standardized uptake values (SUVmax/SUVmean), metabolic tumour volume (MTV) and relative changes from pretreatment to restaging PET (∆SUVmax/∆SUVmean) were determined within the tumour and NTO. Univariate Cox regression with respect to overall survival (OS), local control (LC), distant metastases (DM) and treatment failure (TF) was performed. Independence of parameters was tested by multivariate Cox regression.
∆SUVmax NTO and MTV were prognostic factors for all investigated clinical endpoints (OS, LC, DM, TF). Inclusion of clinical and PET tumour parameters in multivariate analysis showed that ∆SUVmax NTO was an independent prognostic factor. Furthermore, multivariate analysis of ∆SUVmax NTO using previously published cut-off values from preoperatively treated patients revealed that ∆SUVmax NTO was independent prognostic factor for OS (HR = 1.88, p = 0.038), TF (HR = 2.11, p = 0.048) and DM (HR = 3.02, p = 0.047).
NTO-related tracer uptake during the course of treatment in patients with oesophageal carcinoma was shown to be of high prognostic relevance. Thus, metabolically activity of NTO measured in terms of ∆SUVmax NTO is a potential candidate for future treatment individualization (i.e. organ preservation).
Radioembolisation is part of the multimodal treatment of hepatocellular carcinoma (HCC) at specialist liver centres. This study analysed the impact of prior treatment on tolerability and survival following radioembolisation.
This was a retrospective analysis of 325 consecutive patients with a confirmed diagnosis of HCC, who received radioembolisation with yttrium-90 resin microspheres at eight European centres between September 2003 and December 2009. The decision to treat was based on the clinical judgement of multidisciplinary teams. Patients were followed from the date of radioembolisation to last contact or death and the nature and severity of all adverse events (AEs) recorded from medical records.
Most radioembolisation candidates were Child-Pugh class A (82.5%) with multinodular HCC (75.9%) invading both lobes (53.1%); 56.3% were advanced stage. Radioembolisation was used first-line in 57.5% of patients and second-line in 34.2%. Common prior procedures were transarterial (chemo)embolisation therapies (27.1%), surgical resection/transplantation (17.2%) and ablation (8.6%). There was no difference in AE incidence and severity between prior treatment subgroups. Median (95% confidence interval [CI]) survival following radioembolisation was similar between procedure-naive and prior treatment groups for Barcelona Clinic Liver Cancer (BCLC) stage A: 22.1 months (15.1–45.9) versus 30.9 months (19.6–46.8); p = 0.243); stage B: 18.4 months (11.2–19.4) versus 22.8 months (10.9–34.2); p = 0.815; and stage C: 8.8 months (7.1–10.8) versus 10.8 months (7.7–12.6); p = 0.976.
Radioembolisation is a valuable treatment option for patients who relapse following surgical, ablative or vascular procedures and remain suitable candidates for this treatment.
Our aim was to study the prognostic value of two new 18F-FDG PET biomarkers in diffuse large B-cell lymphoma (DLBCL). We examined the total tumor surface (TTS), describing the tumor–host interface, and the tumor volume surface ratio (TVSR), corresponding to the ratio between the total metabolic tumor volume (TMTV) and TTS, describing the tumor fragmentation.
We retrospectively included 215 patients with DLBCL. Patients underwent initial 18F-FDG PET/CT before R-CHOP (73%) or intensified R-CHOP (R-ACVBP) regimens (27%). The TMTV was measured using a fixed threshold value of 41% of SUVmax. To calculate TTS and TVSR, the surface was measured using an in-house software based on the marching cube algorithm. Spearman's rank correlation coefficient (ρ) was computed between TMTV, TTS, and TVSR, and ROC analysis was performed. Survival functions at 5 years were studied using a Kaplan-Meier method and uni/multivariate Cox analysis.
TVSR was poorly correlated with TMTV (ρ = 0.5) and TTS (ρ = 0.26), while TTS was highly correlated with TMTV (ρ = 0.94) and was, therefore, excluded from the analysis. TMTV had the highest area under the ROC curve (0.711) and the best sensitivity (0.797), while TVSR had the best specificity (0.745). The optimal cut-off values to predict 5-year OS were 222 cm3 for TMTV and 6.0 cm for TVSR. Patients with high TMTV and TVSR had significantly worse prognosis in Kaplan-Meier and Cox univariate analysis. In a multivariate Cox analysis combining the International Prognostic Index (IPI), the type of chemotherapy, TMTV, and TVSR, all parameters were independent and significant prognostic factors (HR [95%CI]: IPI 1.4 [1.1-1.8], type of chemotherapy 4.5 [2.0-10.5], TMTV 2.8 [1.4-5.5], TVSR 2.1 [1.3-3.4]). A synergistic effect between TMTV and TVSR was observed in a Kaplan-Meier analysis combining the two parameters.
TVSR measured on the initial 18F-FDG PET is an independent prognostic factor in DLBCL and has an additional prognostic value when combined with TMTV, IPI score and chemotherapy.
Radiolabelled autologous white blood cells (WBC) scintigraphy is being standardized all over the world to ensure high quality, specificity and reproducibility. Similarly, in many European countries radiolabelled anti-granulocyte antibodies (anti-G-mAb) are used instead of WBC with high diagnostic accuracy. The EANM Inflammation & Infection Committee is deeply involved in this process of standardization as a primary goal of the group.
The main aim of this guideline is to support and promote good clinical practice despite the complex environment of a national health care system with its ethical, economic and legal aspects that must also be taken into consideration.
After the standardization of the WBC labelling procedure (already published), a group of experts from the EANM Infection & Inflammation Committee developed and validated these guidelines based on published evidences.
Here we describe image acquisition protocols, image display procedures and image analyses as well as image interpretation criteria for the use of radiolabelled WBC and monoclonal antigranulocyte antibodies. Clinical application for WBC and anti-G-mAb scintigraphy is also described.
These guidelines should be applied by all nuclear medicine centers in favor of a highly reproducible standardized practice.
Selective internal radiation therapy (SIRT) appears to be an interesting treatment possibility for locally-advanced intrahepatic cholangiocarcinoma (ICC), yet the appropriate dosimetry has never been evaluated in this context.
We retrospectively studied data from 40 patients treated at our institution with 90Y-loaded glass microsphere SIRT combined with chemotherapy for inoperable ICC as first-line treatment. Macroaggregated albumin (MAA)-based single-photon emission computed tomography (SPECT)/computed tomography (CT) quantitative analysis was used to calculate the tumor dose (TD), healthy-injected liver dose (HILD), and injected liver dose (ILD). Response was evaluated at 3 months using the European Association for the Study of the Liver criteria. Factors associated with response and toxicity were analyzed using univariate analysis.
We assessed a total of 35 patients (five excluded) receiving 55 injections. Mean TD was 322 ± 165Gy and mean HILD was 74 ± 24Gy for a mean ILD of 128 ± 28Gy. All but two lesions responded, with a minimal TD for responding lesions of 158Gy. Six Grade 3–4 permanent liver toxicities were observed. Mean HILD was not associated with liver toxicity (73.2 ± 25.8Gy for patients with liver toxicity and 77.8 ± 16.9Gy for patients without, ns). Only underlying Child-Pugh status (p = 0.0014) and underlying cirrhosis (p = 0.0021) were associated with liver toxicity. Median progression-free survival was 12.7 months and median overall survival (OS) was 28.6 months. Median OS was 52.7 months for patients with Child-Pugh A5 status.
When combined with chemotherapy, SIRT is highly effective, with a TD > 158Gy. Tolerance was good except for the few patients with cirrhosis or Child-Pugh status ≥A6, who exhibited some liver toxicity. Prospective studies are warranted to confirm.
Despite improved treatment options, multiple myeloma (MM) remains an incurable disease. The aim of this study was to investigate the prognostic value of positron emission tomography/computed tomography (PET/CT) using 18F-2'-deoxy-2'-fluorodeoxyglucose ([18F]FDG) in MM patients shortly before and ~100 days after allogeneic hematopoietic cell transplantation (allo-HCT).
In this retrospective analysis, we evaluated [18F]FDG-PET/CT-scans of 45 heavily pre-treated MM patients before and 27 patients after scheduled allo-HCT. All scans were qualitatively and semi-quantitatively assessed for the presence of active disease. Serological response was recorded according to International Myeloma Working Group (IMWG) criteria. Progression-free (PFS) and overall survival (OS) were correlated with different PET/CT-derived parameters, such as presence, number and maximum standardized uptake value (SUVmax) of focal myeloma lesions. The impact of extramedullary disease on patient outcome was also assessed.
PET/CT negativity -prior to or following allo-HCT- was a favorable prognostic factor for progression-free and overall survival (both, PFS and OS: pre-HSCT p < 0.001, post-HCT p < 0.005). High FDG-uptake (SUVmax > 6.5) revealed a significantly shortened survival compared to patients with a lower SUVmax (<6.5) (OS, 5.0 ± 1.1 m vs. not reached - longest 122.0 m; p < 0.001). Moreover, our data prove that a higher number (>3) of focal lesions (pre-HCT: both PFS and OS: p < 0.001; post-HCT PFS: p < 0.001, OS: p = 0.139) as well as the presence of extramedullary disease serve as adverse prognostic factors prior to and after allo-HCT. At response assessment after allo-HCT, [18F]FDG-PET/CT had a complementary value in prognostication in addition to IMWG criteria alone.
[18F]FDG-PET/CT before and shortly after allogeneic HCT is a powerful predictor for progression-free and overall survival in MM patients.
The 30th Annual Congress of the European Association of Nuclear Medicine (EANM) was held in Vienna, Austria, from 21 to 25 October 2017 under the chairmanship of Professor Francesco Giammarile. As always, the Congress was a great success: more than 6,379 participants came from 90 countries from all continents. Participants were presented with an excellent programme consisting of symposia, and scientific and featured sessions, CME sessions, and plenary lectures. These lectures were devoted to nuclear medicine imaging and therapy, including hybrid imaging and molecular life sciences. Additionally, the latest technology and innovations in the field were presented, and added to the success of the Congress. This review summarizes the major scientific contributions which were selected from more than 1,900 submitted abstracts, and presented in the closing highlights session. They cover the diverse areas of nuclear medicine, with particular focus on oncology, cardiovascular science, neurology, technological innovation and novel tracers, and also other clinical sciences. A particular focus of the Congress was on targeted radionuclide-based therapies, which all show promising and great innovations. The Congress was a unique opportunity to be thoroughly updated on this research. This Highlights Lecture could only be a brief summary of the large amount of data presented and discussed during the meeting, which can be found in much greater detail in the Congress proceedings book, published as volume 44, supplement 2 of the European Journal of Nuclear Medicine and Molecular Imaging in October 2017.
In this prospective study we compared the accuracy of 18F-fluorocholine PET/CT with that of 99mTc-MIBI or99mTc-tetrofosmin SPECT/CT in the preoperative detection of parathyroid adenoma in patients with primary hyperparathyroidism. We also assessed the value of semiquantitative parameters in differentiating between parathyroid hyperplasia and adenoma.
Both 18F-fluorocholine PET/CT and 99mTc-MIBI/tetrofosmin SPECT/CT were performed in 100 consecutive patients with biochemical evidence of primary hyperparathyroidism. At least one abnormal focus on either 18F-fluorocholine or 99mTc-MIBI/tetrofosmin corresponding to a parathyroid gland or ectopic parathyroid tissue was considered as a positive finding. In 76 patients with positive findings on at least one imaging modality, surgical exploration was performed within 6 months, and the results were related to histopathological findings and clinical and laboratory findings at 3–6 months as the standard of truth. In 24 patients, no surgery was performed: in 18 patients with positive imaging findings surgery was refused or considered risky, and in 6 patients imaging was negative. Therefore, data from 82 patients (76 undergoing surgery, 6 without surgery) in whom the standard of truth criteria were met, were used in the final analysis.
All patients showed biochemical evidence of primary hyperparathyroidism with a mean serum calcium level of 2.78 ± 0.34 mmol/l and parathormone (PTH) level of 196.5 ± 236.4 pg/ml. The study results in 76 patients with verified histopathology and 3 patients with negative imaging findings were analysed. Three of six patients with negative imaging showed normalized serum PTH and calcium levels on laboratory follow-up at 3 and 6 months, and the results were considered true negative. In a patient-based analysis, the detection rate with 18F-fluorocholine PET/CT was 93% (76/82), but was only 61% (50/82) with 99mTc-MIBI/tetrofosmin SPECT/CT. In a lesion-based analysis, the sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy of 18F-fluorocholine PET/CT in the detection of parathyroid adenoma were 93.7%, 96.0%, 90.2%, 97.4% and 95.3%, respectively, and of 99mTc-MIBI/tetrofosmin SPECT/CT were 60.8%, 98.5%, 94.1%, 86.3% and 87.7%, respectively. Although 18F-fluorocholine PET-positive adenomatous lesions showed higher SUVmax values than the hyperplastic glands (6.80 ± 3.78 vs. 4.53 ± 0.40) in the semiquantitative analysis, the difference was not significant (p = 0.236). The mean size (measured as the length of the greatest dimension) and weight of adenomas were 15.9 ± 7.6 mm (median 15 mm, range 1–40 mm) and 1.71 ± 1.86 g (median 1 g, range: 0.25–9 g), respectively. Among the analysed parameters including serum calcium and PTH and the size and weight of parathyroid adenomas, size was significantly different between patients with negative 99mTc-MIBI/tetrofosmin SPECT/CT and those with positive 99mTc-MIBI/tetrofosmin SPECT/CT (mean size 13.4 ± 7.6 mm vs. 16.9 ± 7.4 mm, respectively; p = 0.042).
In this prospective study, 18F-fluorocholine PET/CT showed promise as a functional imaging modality, being clearly superior to 99mTc-MIBI/tetrofosmin SPECT/CT, especially in the detection and localization of small parathyroid adenomas in patients with primary hyperparathyroidism. SUVmax was higher in parathyroid adenomas than in hyperplasia. However, further evaluation of this modality is needed.
An adsorption-enhanced soil aquifer treatment (SAT) system was designed to reduce the level of estrogens below the threshold stipulated by the standards. The 17β-E2 adsorption by graphene and MARs (H103) was investigated and an optimum amount of graphene and MARs in the mixture was determined using the linear programming. The kinetics and isotherm characteristics of both adsorbents were well described by the Lagergren pseudo-second order and the Freundlich model, respectively. The 17β-E2 adsorption on graphene and H103 was 88% and 70.37%, and the high temperature was beneficial to the 17β-E2 adsorption on graphene while the thermodynamic behaviors of H103 were in direct contrast to that of graphene. The study found that the maximum economic benefits could be achieved when the mass of graphene and H103 in the mixture is 2.79 g and 13.20 kg, respectively.
To assess the impact of postmastectomy radiotherapy (PMRT) on overall survival and relapse-free survival among breast cancer patients with T1–T2 N1 disease who received standard adjuvant systemic therapy.
This is an individual patient data pooled analysis of 1053 breast cancer patients referred for adjuvant therapy in three clinical trials (BIG 02/98, BCIRG001, and BCIRG005). Overall survival was assessed according to whether or not patients received adjuvant radiotherapy through Kaplan–Meier analysis. Univariate and multivariate analyses of predictors of overall and relapse-free survival were conducted through Cox regression analysis.
Locoregional relapse rates (after a median follow up of 116 months) were 5.6% among patients who received adjuvant radiotherapy vs. 6.6% among patients who did not receive adjuvant radiotherapy. Actuarial 5‑ and 10-year locoregional relapse-free survival rates were 94 and 93%, respectively, among patients who did not receive adjuvant radiotherapy versus 95 and 92% among patients who received adjuvant radiotherapy. The following factors were associated with worse overall survival in multivariate Cox regression analysis: age < 40 years (P < 0.0001), T2 stage (P = 0.004), higher lymph node ratio (P < 0.0001), and negative hormone receptor status (P < 0.0001). Likewise, the following factors were predictive of shorter locoregional relapse-free survival: age ≤ 40 (P < 0.0001), no PMRT (P = 0.034), fluorouracil/adriamycin/cyclophosphamide (FAC) chemotherapy (P = 0.001), and higher T stage (P = 0.002).
The current analysis does not show a beneficial impact of PMRT on overall or relapse-free survival among patients with T1–T2 N1 disease who received standard adjuvant systemic therapy. There is, however, evidence of improvement in locoregional relapse-free survival with PMRT. These findings need to be prospectively validated.
This study was conducted to investigate the potential predictive value of tumor budding for neoadjuvant chemoradiotherapy response in locally advanced rectal cancer.
Surgical specimens of 128 ypUICC (Union for International Cancer Control) stage 0–III mid-to-low rectal cancer patients were identified from a prospectively maintained colorectal cancer database and classified into two groups using the 10 high-power field average method: none/mild tumor budding (BD-0) and moderate/severe tumor budding (BD-1). Overall survival, relapse-free survival (RFS), and recurrence estimates were calculated using the Kaplan–Meier method and compared with the log-rank test. For RFS, a multivariable Cox's proportional hazards regression analysis was performed.
No (n = 20) or mild (n = 27) tumor budding (BD-0) was identified in 47 (37%) and moderate (n = 52) or severe (n = 29) tumor budding (BD-1) in 81 (63%) surgical specimens. Positive tumor budding (BD-1) was associated with significantly reduced T‑level downstaging (P < 0.001) and tumor regression (P < 0.001). After a median follow-up time of 7 years (range 2.9–146.7 months), BD-0 patients had more favorable 5‑year RFS (90 vs. 71%, P = 0.02) and distant recurrence (2 vs. 12%, P = 0.03) estimates. Multivariable analyses confirmed BD-1 as a negative predictive parameter for RFS (hazard ratio = 3.44, 95% confidence interval 1.23–9.63, P = 0.018).
Our data confirm tumor budding as a strong prognostic factor and its potential predictive value for neoadjuvant chemoradiotherapy response in locally advanced rectal cancer patients. This provides the opportunity to modify and individualize neoadjuvant therapy regimens for non-responders.
|
Cosmetics, Vol. 5, Pages 48: Cosmetic Formulation Based on an Açai Extract
Cosmetics doi: 10.3390/cosmetics5030048
Authors: Roberta Censi Dolores Vargas Peregrina Giovanna Lacava Dimitrios Agas Giulio Lupidi Maria Giovanna Sabbieti Piera Di Martino
(1) Background: Açai berry extract is known for its high content in polyphenols and thus is a promising ingredient for cosmetic antiaging formulations; (2) Methods: In this study, the açai extract was firstly evaluated for its total phenol content (Folin Ciocalteau essay) and antioxidant activity (radical scavenging activity—DPPH; radical cation scavenging capacity—ABTS; ferric reducing antioxidant capacity—FRAP). Next, the açai extract was included in an O/W formulation and again was evaluated for its polyphenol content and antioxidant capacity. The formulation was tested for general characteristics, physicochemical properties and microbial stability. The proliferative effect on human immortalized fibroblasts was evaluated by the MTT essay, while TAC assay served to confirm that fibroblasts are protected from UV irradiation. The irritant potential was verified on 20 volunteers. The study concluded with the assessment of the sensorial characteristics of the cosmetic formulation; (3) Results: The pure açai extract exhibited high polyphenol content and antioxidant activity, and these characteristics were preserved in the O/W formulation as well. The O/W cosmetic formulation proved to be stable under accelerated and normal conditions, and the preservatives were successful in challenging the resistance against microbial contamination. The mean irritant potential was zero in all volunteers, and the cosmetic formulation showed a good sensorial profile; (4) Conclusions: Açai extract is an interesting ingredient for cosmetic antiaging formulations.
Epidermal growth factor receptor (EGFR) is a theranostic biomarker for a variety of cancer types. The aim of the present study was to develop an 18F radiolabeled EGFR targeting RNA aptamer, and to investigate its ability to visualize and quantify EGFR in xenograft models.
Biolayer interferometry binding assay was used to detect the binding affinity of the alkyne-modified EGFR aptamer MinE07 (denoted as ME07) with recombinant human wild-type EGFR protein and the mutant EGFRvIII protein. Cy5-conjugated ME07 was used for flow cytometry and immunofluorescence staining, and an Alexa Fluor 488-labeled EGFR antibody (ab193244) was used as a control. 18F-Fluorobenzoyl (FB) azide was employed as a synthon to produce 18F-FB-ME07 via click chemistry, and the cellular uptake and internalization characteristics of 18F-FB-ME07 were investigated. Static PET scans, 60-min dynamic scans, and biodistribution study of 18F-FB-ME07 were performed in three types of tumor models.
The Kd values of ME07 to wtEGFR and EGFRvIII proteins were 0.3 nM and 271 nM respectively. The A431, U87MG, and HCT-116 cells showed strong, weak, and negative binding with Cy5-ME07, which is consistent with EGFR expression level in these cells. Peak cell uptake values of 18F-FB-ME07 in A431, U87MG and HCT-116 cells were 2.86%, 2.19% and 0.88% of the added dose respectively. The mean internalization of 18F-FB-ME07 in these cells were 60.02%, 53.1%, and 52.8% of the total accumulated radioactivity. In static PET imaging, despite high uptake in the liver and kidneys, 18F-FB-ME07 showed reasonable accumulation in A431 tumors (1.02 ± 0.13 %ID/g at 30 min after injection). Of note, the uptake of 18F-FB-ME07 in A431 xenografts was significantly higher than that in U87MG and HCT-116 xenografts. In A431 xenografted mice, the tumor/blood ratio was 3.89 and the tumor/muscle ratio reached 8.65.
We for the first time generated an aptamer-derived EGFR targeting PET tracer 18F-FB-ME07, which showed highly selective targeting ability in mouse tumor models expressing different levels of EGFR. Our results suggest that 18F-FB-ME07 is a potential EGFR targeting molecular imaging probe for future clinical translation.
Publication date: Available online 1 August 2018
Source: Journal of the American Academy of Dermatology
Author(s): K.T. Ashique, Feroze Kaliyadan
Publication date: Available online 1 August 2018
Source: Magnetic Resonance Imaging
Author(s): Yunyun Yang, Dongcai Tian, Boying Wu
In recent years, with the rapid development of modern medical image technology, the medical image processing technology is becoming more important. In particular, the accurate segmentation of medical images is significant for doctors to diagnose and analyze the etiology. However, the false contours appearing in medical images due to fuzzy image boundary, intensity inhomogeneity and random noise, may lead to the inaccurate segmentation results. In this paper, an improved active contour model based on global image information is proposed, which can accurately segment images disturbed by intensity inhomogeneities and serious noise. We give the two-phase energy functional and multi-phase energy functional of our model, and apply it to segment magnetic resonance (MR) images, ultrasound (US) images and synthetic images. Experimental results and comparisons with other models have shown that our model has the advantages of higher accuracy, higher efficiency and robustness in dealing with the intensity inhomogeneity and serious noise in image segmentation.
The effects of diatomaceous earth (DE) on the penetrating behavior, tunneling behavior, mortality, and body surface characteristics of the subterranean termite Reticulitermes chinensis were investigated in this study. Our results show that the workers of R. chinensis were able to penetrate 1- and 2-mm layers of dry DE but not 3-mm layers. After treatment with dry DE for 6 h, the mortality of termites reached 100%, which was significantly higher than in the treatment with DE with a 10 and 25% moisture content and treatment with sand of three different moisture contents. The tunneling distances of workers in DE with 10, 25, and 50% moisture contents were all significantly shorter than those in sand with the same moisture contents (10, 25, and 50%), indicating that DE has a good suppressing effect on the tunneling behavior of workers. After treatment with dry DE for different times (1, 3, and 6 h), many DE particles adhered to the bodies of workers, whereas no particles adhered to the body of workers in the case of treatment with dry sand. The treatment with dry DE for 6 h resulted in the death of all workers, which presented conspicuous abdominal shrinkage, whereas workers treated with sand had no significant mortality and no obvious abdominal shrinkage. In summary, we suggest that dry DE has ideal insecticidal activity against the subterranean termite R. chinensis and can be further exploited for controlling termites inside houses.