Purpose: There has been a long-standing interest in the investigation of interactions in science. The objective of the study is to evaluate interaction between Epidermal Growth Factor Receptor (EGFR) mutation and treatment from randomized, phase II study of chemotherapy versus chemotherapy plus erlotinib in patients with progressive Non-Small Cell Lung Cancer (NSCLC) following clinical benefit from erlotinib. <p></p> Materials and Methods: Forty-six patients with advanced stage NSCLC and progression from erlotinib were randomized to receive chemotherapy (pemetrexed or docetaxel) or chemotherapy plus erlotinib between 2008 and 2012. Patient characteristics at baseline including age, gender, tumor stage, race, smoking history and EGFR mutation status along with the clinical outcomes, namely response, Progression- Free Survival (PFS) and Overall Survival (OS) were obtained. The effects of treatment, EGFR mutation and interaction between the two on survival outcomes were evaluated using Cox proportional hazards model with first-order interaction. <p></p> Results: For PFS, there was a significant interaction between treatment (arm B) and EGFR mutation (mutant EGFR+) (p = 0.018), although the main effects of treatment (arm B vs. arm A) and EGFR mutation (mutant vs. wild-type EGFR) were statistically significant (with p = 0.03 and p = 0.088, respectively) favoring arm B and mutant EGFR+. Thus when taking the interaction between treatment and EGFR into account, the hazard ratio comparing arm B to arm A when EGFR is positive was 1.49 (95% CI: 0.72, 3.11); and the hazard ratio comparing arm B to arm A when EGFR is negative was 0.17 (95% CI: 0.04 - 0.84). Similarly, for OS, there was a significant interaction between treatment and EGFR mutation (p = 0.02), with significant main effects of treatment and EGFR favoring arm B and mutant EFGR+. Taking together, the hazard ratio comparing arm B to arm A when EGFR is positive was 1.61 (95% CI: 0.68 - 3.82); and the hazard ratio comparing arm B to arm A when EGFR is negative was 0.16 (95% CI: 0.03 - 0.9). <p></p> Conclusion: The interaction identified by Cox model shows there was an antagonistic effect between chemotherapy + erlotinib and EGFR mutation, a situation that the whole is less than the sum of the parts, despite the prolonging-survival main effect of each factor from Cox model. As a result, the continuing erlotinib beyond progression adds no benefit in survival outcomes but leads to an increase in adverse events. <p></p>
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Τρίτη 28 Μαρτίου 2017
Interaction of Treatment and Biomarker in Advanced Non-small Cell Lung Cancer
Genotype- or Phenotype-Targeting Anticancer Therapies? Lessons from Tumor Evolutionary Biology
Despite the efficacy of most cancer therapies, drug resistance remains a major problem in the clinic. The eradication of the entire tumor and the cure of the patient by chemotherapy alone are rare, in particular for advanced disease. From an evolutionary perspective, the selective pressure exerted by chemotherapy leads to the emergence of resistant clones where resistance can be associated with many different functional mechanisms at the single cell level or can involve changes in the tumor micro-environment. In the last decade, tumor genomics has contributed to the improvement of our understanding of tumorigenesis and has led to the identification of numerous cellular targets for the development of novel therapies. However, since tumors are by nature extremely heterogeneous, the drug efficacy and economical sustainability of this approach is now debatable. Importantly, tumor cell heterogeneity depends not only on genetic modifications but also on non-genetic processes involving either stochastic events or epigenetic modifications making genetic biomarkers of uncertain utility. In this review, we wish to highlight how evolutionary biology can impact our understanding of carcinogenesis and resistance to therapies. We will discuss new approaches based on applied ecology and evolution dynamics that can be used to convert the cancer into a chronic disease where the drugs would control tumor growth. Finally, we will discuss the way metabolic dysfunction or phenotypic changes can help developing new delivery systems or phenotypetargeted drugs and how exploring new sources of active compounds can conduct to the development of drugs with original mechanisms of action.
http://ift.tt/2j7JAUx
Osteophyte induced lung fibrosis prevalence and osteophyte qualities predicting disease
Publication date: July–August 2017
Source:Clinical Imaging, Volume 44
Author(s): Mary Salvatore, Claudia I. Henschke, Rowena Yip, Sukhdeep Kaur, Kunwei Li, Maria Padilla, David Yankelevitz
ObjectiveTo determine the prevalence of osteophyte induced lung fibrosis (OIF) and its relationship to osteophyte size, location, and surrounding fat.Methods94 CT scans of the chest were reviewed, size of the largest osteophyte and the presence of fibrosis were recorded.ResultsPresence of fibrosis was higher among patient with large (>10 mm) osteophytes compared to those with small (1–10mm) osteophytes. Age and presence of periosteophyte fat were significantly associated with presence of fibrosis.ConclusionsAs the size of an osteophyte increases, there is a greater likelihood of lung fibrosis. Subpleural fat protects the lung from OIF.
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Insight into anti-diabetic effect of low dose of stevioside
Publication date: June 2017
Source:Biomedicine & Pharmacotherapy, Volume 90
Author(s): Vladimirka Ilić, Saša Vukmirović, Nebojša Stilinović, Ivan Čapo, Milan Arsenović, Boris Milijašević
Diabetes mellitus is a chronic disease characterized by abnormal carbohydrate, lipid and protein metabolism due to a lack of insulin or reduced target cell sensitivity to insulin. Stevia rebaudiana is an important source of biochemically active substances with proven anti-diabetic effect. The aim of this study was to determine anti-diabetic effects of the low dose of stevioside in NMRI Haan mice. Aqueous stevioside solution (20mg/kg body weight) was administered by oral route of administration. Anti-diabetic effect of stevioside was estimated by oral glucose tolerance test, adrenaline test after a 10day stevioside treatment, and alloxan induced hyperglycaemia in mice (two experimental groups, 10day stevioside treatment before and after alloxan administration). Aqueous stevioside solution prevented significant increase in glycaemia in oral glucose tolerance test (9.22±1.13 to 9.85±1.32mmol/l, P<0.05), and not in adrenaline test. Significant difference in glycaemia was detected in mice pre-treated with saline and stevioside in alloxan induced hyperglycaemia (saline 23.32±2.14, stevioside 14.70±4.95mmol/l, P<0.05). In mice pre-treated with stevioside, smallest β cells loss was found compared to other alloxan treated groups. Preserved normal cytoarchitectonic arrangement in islets was detected. Based on the given results we presume there exist a potential therapeutic use of low dose stevioside in diabetes.
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A review of the role of orexin system in pain modulation
Publication date: June 2017
Source:Biomedicine & Pharmacotherapy, Volume 90
Author(s): Bibi Marjan Razavi, Hossein Hosseinzadeh
The roles of orexinergic system (orexin-A, orexin-B) and their receptors (orexin receptor type-1, orexin receptor type-2) in various physiological processes such as arousal, reward seeking behavior, energy homeostasis, sensory modulation, stress processing, cognition, endocrine functions, visceral functions and pain modulation have been established. This review summarizes the studies investigating orexin antinociceptive effects and their cellular mechanisms in various types of pain including neuropathic pain, migraine and cluster headache, visceral and orofacial pains. Moreover, the role of orexins in stress induced analgesia and on the development of morphine analgesic tolerance has been discussed. The antinociceptive effects of orexins have been shown in several pain models including thermal, mechanical and chemical induced nociception. Orexins modulate pain perception at both spinal and supraspinal levels. The periaqueductal gray (PAG) is one important supraspinal sites of orexin pain modulation. A possible involvement of endocannabinoids in supraspinal orexin-induced analgesia has been proposed. This review suggests a potential role of orexins in the management of pain.
http://ift.tt/2mOAK3Y
Glucocorticoid-induced leucine zipper may play an important role in icariin by suppressing osteogenesis inhibition induced by glucocorticoids in osteoblasts
Publication date: June 2017
Source:Biomedicine & Pharmacotherapy, Volume 90
Author(s): Zhong Lin, Zheng Li Jiang, Li Hua Chen, Yuan Sun, Sai Zhen Chen, Peng Zhou, Ai Xiao Xia, Hui Jin, Yan Wu Zhu, Dan Yang Chen
Background and purposeIcariin is a potent stimulator of osteogenic differentiation; however, the mechanism underlying its osteogenic effect remains unclear. The osteogenic effect of icariin is related to the upstream glucocorticoid-induced leucine zipper (GILZ) signaling pathway, and antagonism with dexamethasone-induced osteoblast inhibition was noted.MethodsMC3T3-E1 cells were cultured in induced medium treated with icariin with or without dexamethasone. After short interfering RNA (siRNA) were used to silence GILZ expression, the degree of mineralization, proliferation, and GILZ expression as well as the levels of osteogenic (OPG, RANKL, ALP, OC and RUNX2) markers were tested.ResultsDexamethasone inhibited, while icariin increased, osteogenic activity, as indicated by ALP activity and calcium nodules. Meanwhile, dexamethasone dose-dependently (10−6M–10−4M) increased GILZ and RANKL expression and reduced ALP, OPG and OC, but the pattern of mRNA expression was reversed when icariin was added. Furthermore, GILZ (dexamethasone-induced) inhibition caused by icariin or moderately silenced by GILZ siRNA abolished the osteogenesis inhibition effect of dexamethasone, as indicated by the changes in the GILZ, ALP, OPG and RANKL expression levels; ALP activity; and calcium nodule.ConclusionsThese results indicate that the GILZ-mediated osteogenic signal pathway is involved in the osteogenic effect induced by icariin.
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Gut microbiota and renal transplant outcome
Publication date: June 2017
Source:Biomedicine & Pharmacotherapy, Volume 90
Author(s): Mohammadreza Ardalan, Sepideh Zununi Vahed
Gaining long-term graft function and patient survival remain a critical challenge following kidney transplantation. Genetic and environmental factors do not completely account for the individual's graft outcome. Recently, it is reported that gut microbial community (microbiota) is associated with complications in kidney allograft recipients, as well. Commensal microbiota plays a significant role in the immunomodulation of transplant recipient responses. Different factors can disrupt the reciprocal interaction between microbiota and the host immune responses and lead to infection and rejection complications in the organ recipient. In this review, we address the relation between microbiota and immune system along with their possible roles in renal graft outcome. We next highlight the beneficial effects of probiotics on the management of kidney diseases and solid organ transplantation. Finally, we reflect on the potential impacts of probiotics on host physiology. Hopefully, a deeper understanding of the function and composition of microbiota can help clinics develop strategies to restore the normal microbiota and facilitate the clinical management of grafts in the forthcoming future.
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Hepatoprotective activity of Rhus oxyacantha root cortex extract against DDT-induced liver injury in rats
Publication date: June 2017
Source:Biomedicine & Pharmacotherapy, Volume 90
Author(s): Hanène Ben Miled, Zaineb Ben Barka, Dorsaf Hallègue, Karima Lahbib, Mohamed Ladjimi, Mounira Tlili, Mohsen Sakly, Khémais Ben Rhouma, Riadh Ksouri, Olfa Tebourbi
The present investigation aimed to study the antioxidant activity and hepatoprotective effects of ethyl acetate extract of R. oxyacantha root cortex (RE) against DDT-induced liver injury in male rats.The RE exhibited high total phenolic, flavonoid and condensed tannins contents. The antioxidant activity in vitro systems showed a significant potent free radical scavenging activity of the extract. The HPLC finger print of R. oxyacantha active extract showed the presence of five phenolic compounds with higher amounts of catechol and gallic acid. The in vivo results showed that a single intraperitoneal administration of DDT enhanced levels of hepatic markers (ALT, AST and LDH) in serum of experimental animals. It also increased the oxidative stress markers resulting in increased levels of the lipid peroxidation with a significant induction of SOD and GPx, metallothioneins (MTs) and a concomitant decrease of non protein thiols (NPSH) in liver. However, pretreatment of rats with RE at a dose of 150 and 300mg/kg body weight significantly lowered serum transaminases and LDH in treated rats. A significant reduction in hepatic thiobarbituric reactive substances and a decrease in antioxidant enzymes activities and hepatic MTs levels by treatment with plant extract against DDT, were observed. These biochemical changes were consistent with histopathological observations, suggesting marked hepatoprotective effect of RE with the two doses used. These results strongly suggest that treatment with ethyl acetate extract normalizes various biochemical parameters and protects the liver against DDT-induced oxidative damage in rats and thus help in evaluation of traditional claim on this plant.
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Emodin targets mitochondrial cyclophilin D to induce apoptosis in HepG2 cells
Publication date: June 2017
Source:Biomedicine & Pharmacotherapy, Volume 90
Author(s): Ling Zhang, Dian He, Kun Li, Hongli Liu, Baitao Wang, Lifang Zheng, Jiazhong Li
Emodin has demonstrated potent anticancer activity in human hepatocarcinoma cells and animal models, however, the cellular targets of emodin have not been fully defined. Here we report that emodin induces the dysfunction of mitochondria and the apoptosis in HepG2 cells through an enrichment in mitochondria. Specifically, A mitochondrial matrix protein (cyclophilin D, CyPD) is involved in emodin-induced apoptosis, and the inhibitor of CyPD (cyclosporin A) could almost completely suppressing the apoptosis; Moreover, as the expression of CyPD could be effectively inhibited by antioxidant N-acetyl-l-cysteine and epidermal growth factor (the activator of ERK), reactive oxygen species and ERK might be involved in the relevant role of CyPD. A further molecule-docking discloses the existence of three hydrogen-bonds in CyPD-emodin complex. Thus, target localization and CyPD in mitochondria provides an insight into the action of emodin in the treatment of liver cancer.
Graphical abstract
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Anti-coagulative and gastrointestinal motility regulative activities of Fructus Aurantii Immaturus and its effective fractions
Publication date: June 2017
Source:Biomedicine & Pharmacotherapy, Volume 90
Author(s): Wangxiao Tan, Ye Li, Yu Wang, Zhaojian Zhang, Ting Wang, Qian Zhou, Xiaoying Wang
ObjectiveFructus Aurantii Immaturus (FAI) has been used in the treatment of gastrointestinal disorders (GIDs) in traditional Chinese medicine (TCM) for thousands of years, which also has been found to have effects on cardiovascular diseases (CVDs) in recent years. The current study aimed at investigating the anti-coagulative and gastrointestinal motility regulative activities of different fractions isolated from FAI, which may have both effects on gastrointestinal and cardiovascular systems, in the manners of network pharmacology analysis and experiments in vivo and in vitro.MethodsWe obtained water decoction, volatile oils, alkaloids and flavonoids from FAI, which were identified by gas chromatography-mass spectrometry (GC–MS) and high performance liquid chromatography (HPLC). Network pharmacological analysis was used to explore the relationship between the various types of chemical constituents, gene target and biological pathways of FAI. Then, the effective fractions in terms of anti-coagulative and gastrointestinal motility regulative activities were investigated by the experiment of rabbit intestinal smooth muscles contraction, mice small intestine propulsion rate and blood-clotting time, and verified by the blood stasis model.ResultsFrom the Network pharmacological analysis, the flavonoids were predicted to be the main active ingredients on gastrointestinal and cardiovascular systems. Experimental results also showed that flavonoids could significantly increase the small intestine propulsion rate and extend the blood-clotting time of mice. The Flavonoids could alleviate the increased fractional shortening (FS), left ventricular outflow, hematocrit and fibrinogen, and ameliorate the pathological changes of myocardial tissues caused by blood stasis.ConclusionThese findings indicated that flavonoids in FAI might be the main effective fractions on gastrointestinal motility and anti-coagulation.
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Assessment of Olea europaea L. fruit extracts: Phytochemical characterization and anticancer pathway investigation
Publication date: June 2017
Source:Biomedicine & Pharmacotherapy, Volume 90
Author(s): Amina Maalej, Zouhaier Bouallagui, Fatma Hadrich, Hiroko Isoda, Sami Sayadi
Olea europaea L. has been widely used as an advantageous rich source of bioactive compounds of high economic value leading to its use in pharmaceutical, cosmetic, and agriculture industries. Ethanolic extracts of olive fruits from three different cultivars (OFE) were studied for their phytochemical contents and were investigated for antioxidant activities and anticancer potential. Major polyphenols detected in these extracts were tyrosol, hydroxytyrosol, oleuropein, rutin, quercetin and glucoside forms of luteolin and apigenin. All these compounds have shown to significantly contribute to the antioxidant activity of OFE, which was evaluated by DPPH and ABTS assays. Proliferation of hepatic and colon cancer cells, HepG2 and Caco-2, were shown to be sensitive to OFE with IC50 less than 1.6mg/ml for all tested extracts. Moreover, flow cytometry analysis showed that OFE induced cell cycle arrest in the S-phase within both HepG2 and Caco-2 cells. This has triggered a cell death mechanism as shown by DNA fragmentation, expression of p53 and phosphorylation level of Akt and Erk proteins. Interestingly, these extracts could be further used as a potential source of natural compounds with both antioxidant and anticancer effects.
Graphical abstract
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Soil Cd, Cr, Cu, Ni, Pb and Zn sorption and retention models using SVM: Variable selection and competitive model
Publication date: 1 September 2017
Source:Science of The Total Environment, Volumes 593–594
Author(s): J.J. González Costa, M.J. Reigosa, J.M. Matías, E.F. Covelo
The aim of this study was to model the sorption and retention of Cd, Cu, Ni, Pb and Zn in soils. To that extent, the sorption and retention of these metals were studied and the soil characterization was performed separately.Multiple stepwise regression was used to produce multivariate models with linear techniques and with support vector machines, all of which included 15 explanatory variables characterizing soils. When the R-squared values are represented, two different groups are noticed. Cr, Cu and Pb sorption and retention show a higher R-squared; the most explanatory variables being humified organic matter, Al oxides and, in some cases, cation-exchange capacity (CEC). The other group of metals (Cd, Ni and Zn) shows a lower R-squared, and clays are the most explanatory variables, including a percentage of vermiculite and slime. In some cases, quartz, plagioclase or hematite percentages also show some explanatory capacity.Support Vector Machine (SVM) regression shows that the different models are not as regular as in multiple regression in terms of number of variables, the regression for nickel adsorption being the one with the highest number of variables in its optimal model. On the other hand, there are cases where the most explanatory variables are the same for two metals, as it happens with Cd and Cr adsorption. A similar adsorption mechanism is thus postulated.These patterns of the introduction of variables in the model allow us to create explainability sequences. Those which are the most similar to the selectivity sequences obtained by Covelo (2005) are Mn oxides in multiple regression and change capacity in SVM. Among all the variables, the only one that is explanatory for all the metals after applying the maximum parsimony principle is the percentage of sand in the retention process.In the competitive model arising from the aforementioned sequences, the most intense competitiveness for the adsorption and retention of different metals appears between Cr and Cd, Cu and Zn in multiple regression; and between Cr and Cd in SVM regression.
Graphical abstract
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Accumulation of toxic metals and organic micro-pollutants in sediments from tropical urban rivers, Kinshasa, Democratic Republic of the Congo
Publication date: July 2017
Source:Chemosphere, Volume 179
Author(s): Pitchouna I. Kilunga, Periyasamy Sivalingam, Amandine Laffite, Dominique Grandjean, Crispin K. Mulaji, Luiz Felippe de Alencastro, Pius T. Mpiana, John Poté
The increasing contamination of fresh water resource by toxic metals and Persistence Organic Pollutants (POPs) is a major environmental concern globally. In the present investigation, surface sediments collected from three main rivers named, Makelele, Kalamu and Nsanga, draining through the city of Kinshasa, Democratic Republic of the Congo, were characterized for grain size, organic matter, toxic metals, POPs (including organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs)), and polycyclic aromatic hydrocarbons (PAHs). Furthermore, enrichment factor (EF) and geoaccumulation index (Igeo) were performed to determine metal source and pollution status. The results highlighted high concentration of toxic metals in all sediment samples, reaching the values (mg kg−1) of 325 (Cu), 549 (Zn), 165 (Pb) and 1.5 (Cd). High values of PCBs and OCPs were detected in sediment samples, e.g. in Makelele river, PCB values ranged from 0.9 to 10.9 with total PCBs (∑7 PCBs × 4.3): 169.3 μg kg−1; OCPs from 21.6 to 146.8 with ∑OCPs: 270.6 μg kg−1. The PBDEs concentrations were higher in investigated rivers comparatively with values detected in many rivers from Sub-Saharan Africa. The ΣPAHs value ranged from 22.6 to 1011.9 μg kg−1. River contamination may be explained by local intense domestic activities, urban and agricultural runoff, industrial and hospital wastewaters discharge into the rivers without prior treatment. This research provides not only a first baseline information on the extent of contamination in this tropical ecosystem but also represents useful tools incorporated to evaluate sediment quality in the river receiving systems which can be applied to similar aquatic environments.
Graphical abstract
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Scalable fabrication of size-controlled chitosan nanoparticles for oral delivery of insulin
Source:Biomaterials, Volume 130
Author(s): Zhiyu He, Jose Luis Santos, Houkuan Tian, Huahua Huang, Yizong Hu, Lixin Liu, Kam W. Leong, Yongming Chen, Hai-Quan Mao
Controlled delivery of protein would find diverse therapeutic applications. Formulation of protein nanoparticles by polyelectrolyte complexation between the protein and a natural polymer such as chitosan (CS) is a popular approach. However, the current method of batch-mode mixing faces significant challenges in scaling up while maintaining size control, high uniformity, and high encapsulation efficiency. Here we report a new method, termed flash nanocomplexation (FNC), to fabricate insulin nanoparticles by infusing aqueous solutions of CS, tripolyphosphate (TPP), and insulin under rapid mixing condition (Re > 1600) in a multi-inlet vortex mixer. In comparison with the bulk-mixing method, the optimized FNC process produces CS/TPP/insulin nanoparticles with a smaller size (down to 45 nm) and narrower size distribution, higher encapsulation efficiency (up to 90%), and pH-dependent nanoparticle dissolution and insulin release. The CS/TPP/insulin nanoparticles can be lyophilized and reconstituted without loss of activity, and produced at a throughput of 5.1 g h−1 when a flow rate of 50 mL min−1 is used. Evaluated in a Type I diabetes rat model, the smaller nanoparticles (45 nm and 115 nm) control the blood glucose level through oral administration more effectively than the larger particles (240 nm). This efficient, reproducible and continuous FNC technique is amenable to scale-up in order to address the critical barrier of manufacturing for the translation of protein nanoparticles.
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The dual-pathway model of binge eating: Is there a need for modification?
Source:Appetite, Volume 114
Author(s): Marie Sehm, Petra Warschburger
The dual-pathway model proposes that body dissatisfaction might lead to binge eating (BE) through restraint eating and negative affect. Both pathways have been confirmed longitudinally, but there is evidence that the affect-pathway might rather be found in the short-term, whereas other variables might be involved over longer periods. Research suggests that self-esteem represents a key-factor in the etiology of BE in adolescent girls and might serve as a mediator between body dissatisfaction and eating pathology. Based on these findings, the aim of this study was to investigate the original dual-pathway model across 20 months and to evaluate a modified version of the model with self-esteem instead of negative affect as a mediator in the affect-pathway.We assessed eating pathology, negative affect and self-esteem by self-report in a sample of 523 adolescent girls at two time points separated by 20 months. Data were analyzed using a cross-lagged panel design.Both, the original and the modified model provided good fit to the data, but results yielded limited support for the assumptions of the original model. Neither restraint eating nor negative affect mediated the link between body dissatisfaction and BE. The modified model fit the data slightly better and results indicated that low self-esteem mediated the relationship between body dissatisfaction and BE. Notably, our results indicated that restraint eating might even reduce the risk for BE through the enhancement of self-esteem.Results suggest that the dual-pathway model could benefit from the inclusion of a more trait-like variable such as self-esteem when evaluated across the long-term. Furthermore, our findings indicate that healthy restraint eating might have positive effects on self-esteem, thereby reducing risk for BE in adolescent girls, who are dissatisfied with their bodies.
http://ift.tt/2mNTTmF
Surface Immobilized Antibody Orientation Determined using ToF-SIMS and Multivariate Analysis
Publication date: Available online 28 March 2017
Source:Acta Biomaterialia
Author(s): Nicholas G. Welch, Robert M.T. Madiona, Thomas B. Payten, Christopher D. Easton, Luisa Pontes-Braz, Narelle Brack, Judith A. Scoble, Benjamin W. Muir, Paul J. Pigram
Antibody orientation at solid phase interfaces plays a critical role in the sensitive detection of biomolecules during immunoassays. Correctly oriented antibodies with solution-facing antigen binding regions have improved antigen capture as compared to their randomly oriented counterparts. Direct characterization of oriented proteins with surface analysis methods still remains a challenge however surface sensitive techniques such as Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) provide information-rich data that can be used to probe antibody orientation. Diethylene glycol dimethyl ether plasma polymers (DGpp) functionalized with chromium (DGpp+Cr) have improved immunoassay performance that is indicative of preferential antibody orientation. Herein, ToF-SIMS data from proteolytic fragments of anti-EGFR antibody bound to DGpp and DGpp+Cr are used to construct artificial neural network (ANN) and principal component analysis (PCA) models indicative of correctly oriented systems. Whole antibody samples (IgG) test against each of the models indicated preferential antibody orientation on DGpp+Cr. Cross-reference between ANN and PCA models yield 20 mass fragments associated with F(ab′)2 region representing correct orientation, and 23 mass fragments associated with the Fc region representing incorrect orientation. Mass fragments were then compared to amino acid fragments and amino acid composition in F(ab′)2 and Fc regions. A ratio of the sum of the ToF-SIMS ion intensities from the F(ab′)2 fragments to the Fc fragments demonstrated a 50% increase in intensity for IgG on DGpp+Cr as compared to DGpp. The systematic data analysis methodology employed herein offers a new approach for the investigation of antibody orientation applicable to a range of substrates.Statement of significanceControlled orientation of antibodies at solid phases is critical for maximizing antigen detection in biosensors and immunoassays. Surface-sensitive techniques (such as ToF-SIMS), capable of direct characterization of surface immobilized and oriented antibodies, are under-utilized in current practice. Selection of a small number of mass fragments for analysis, typically pertaining to amino acids, is commonplace in literature, leaving the majority of the information-rich spectra unanalyzed. The novelty of this work is the utilization of a comprehensive, unbiased mass fragment list and the employment of principal component analysis (PCA) and artificial neural network (ANN) models in a unique methodology to prove antibody orientation. This methodology is of significant and broad interest to the scientific community as it is applicable to a range of substrates and allows for direct, label-free characterization of surface bound proteins.
Graphical abstract
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Neural correlates of emotional inhibitory control in autism spectrum disorders
Publication date: May 2017
Source:Research in Developmental Disabilities, Volume 64
Author(s): Francisco Velasquez, Xiaoyan Angela Qin, Melissa A. Reilly, Emily Neuhaus, Annette Estes, Elizabeth Aylward, Natalia M. Kleinhans
Atypical inhibitory function is often present in individuals with autism spectrum disorder (ASD), who may have difficulty suppressing context-inappropriate behaviors. We investigated the neural correlates of inhibition in ASD in response to both emotional and non-emotional stimuli using an fMRI Go/NoGo inhibition task with human faces and letters. We also related neural activation to behavioral dysfunction in ASD. Our sample consisted of 19 individuals with ASD (mean age=25.84) and 22 typically developing (TD) control participants (mean age=29.03). As expected, no group differences in task performance (inhibition accuracy and response time) were found. However, adults with ASD exhibited greater angular gyrus activation in face response inhibition blocks, as well as greater fusiform gyrus activation than controls, in a condition comparing face inhibition to letter inhibition. In contrast, control participants yielded significantly greater anterior cingulate cortex (ACC) activation in letter inhibition blocks. A positive relationship between communication and language impairment and angular gyrus activation during face inhibition was also found. Group activation differences during inhibition tasks in the context of comparable task performance and the relationship between activation and dysfunction highlight brain regions that may be related to ASD-specific dysfunction.
http://ift.tt/2oewhEV
Culture-Bound Syndromes of a Brazilian Amazon Riverine population: Tentative correspondence between traditional and conventional medicine terms and possible ethnopharmacological implications
Publication date: 5 May 2017
Source:Journal of Ethnopharmacology, Volume 203
Author(s): E. Pagani, J. de F.L. Santos, E. Rodrigues
Ethnopharmacological relevanceIt is not always possible to correlate the "emic" terms to the "etic" ones during ethnopharmacological surveys, especially regarding those related to Culture-Bound Syndromes (CBS). Nevertheless, it is the role of ethnopharmacology to address these correlations, since they are the basis for the understanding of potential bioactives.Aim and objectivesThis study reports the clinical manifestations and therapeutic resources used for the treatment of CBS among some riverine inhabitants of Brazilian Amazonia. An effort was made to establish a correspondence between the local "emic" terms of traditional medicine and the symptoms or diseases known by conventional medicine ("etic" terms). The ultimate goal was to gain insights to suggest further pharmacological studies with the local resources.Material and methodsFieldwork was guided by methods of anthropology, botany and zoology—with the assistance of a doctor—among the traditional healing experts in Jaú National Park (during 199 days in 1995) and Unini River Extractive Reserve (210 days from 2008 to 2012).ResultsFifty-nine healers of different kinds were interviewed: a prayer-maker, medium, natural resource expert, massage therapist, midwife and snakebite healer. The clinical manifestations and healing resources of the following CBS were collected: "mau olhado" (evil eye), "quebrante" (chipping); "espante" (fright or susto); "doença do ar" (air diseases); "vento caído" (fallen wind); "derrame" (leakage); "mãe do corpo" (mother of the body) and "panema" (unlucky). The first three seem to be local variations of other CBSs already described in Latin America. "doença do ar", "vento caído", "derrame" and "mãe do corpo" seem to be folk terms for known conventional medical disorders, while "panema" is a yet undescribed Brazilian CBS that is possibly related to dysthymic disorder or depression and deserves further investigation. Treatments included prayer rituals, fumigation, baths and oral remedies using 25 plants and 10 animals.ConclusionIt was possible to establish hypothetical correlations between CBS as described by the riverine population studied and some "etic" terms. The main importance of this is to help the proposition of target-oriented pharmacological studies of the natural resources used by these communities. Accordingly, the following plants are suggested to be submitted to further studies for antidepressant and anxiolytic activities: Siparuna guianensis, Mansoa alliacea, Leucas martinicensis, Petiveria alliacea, Annona montana and Alpinia nutans; for anti-seizure activity: Protium amazonicum, Protium aracouchini and Protium heptaphyllum; finally for antispasmodic activity: Leucas martinicensis.
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Role of Health Services Research in Radiology
Source:Academic Radiology
Author(s): James V. Rawson, Paul Cronin
http://ift.tt/2mNONqN
Characteristics, Trends, and Quality of Systematic Review and Meta-Analysis in General Radiology between 2007 and 2015
Source:Academic Radiology
Author(s): Ju Yong Park, Kyung Hee Lee, You Jin Ku, Soon Gu Cho, Yeo Ju Kim, Ha Young Lee, Jun Ho Kim
Rationale and ObjectivesTo evaluate the trends, characteristics, and quality of systematic review and meta-analysis in general radiology journals.Materials and MethodsWe performed a PubMed search to identify systematic reviews and meta-analyses that had been carried out in the field of radiology between 2007 and 2015. The following data were extracted: journal, impact factor, type of research, year of publication, radiological subspecialty, imaging modalities used, number of authors, affiliated department of the first and corresponding authors, presence of a radiologist and a statistician among the authors, discordance between the first and corresponding authors, funding, country of first author, methodological quality, methods used for quality assessment, and statistics.ResultsUltimately, we included 210 articles from nine general radiology journals. The European Journal of Radiology was the most common journal represented (47 of 210; 22.4%). Meta-analyses (n = 177; 84.3%) were published about five times more than systematic reviews without meta-analysis (n = 33; 15.7%). Radiology of the gastrointestinal tract was the most commonly represented subspecialty (n = 49, 23.3%). The first authors were most frequently located in China (n = 64; 30.3%). In terms of modality, magnetic resonance imaging was used most often (n = 59; 28.1%). The number of authors tended to progressively increase over time, and the ratio of discordance between the first and corresponding authors also increased significantly, as did the proportion of research that has received funding from an external source. The mean AMSTAR assessment score improved over time (5.87/11 in 2007–2009, 7.11/11 in 2010–2012, and 7.49/11 in 2013–2015). In this regard, the journal Radiology had the highest score (7.59/11).ConclusionsThe quantity and quality of radiological meta-analyses have significantly increased over the past 9 years; however, specific weak areas remain, providing the opportunity for quality improvement.
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Evaluation of Plaque Morphology by 64-Slice Coronary Computed Tomographic Angiography Compared to Intravascular Ultrasound in Nonocclusive Segments of Coronary Arteries
Source:Academic Radiology
Author(s): Manoj Kesarwani, Rine Nakanishi, Tae-Young Choi, David M. Shavelle, Matthew J. Budoff
Rationale and ObjectivesAlthough intravascular ultrasound (IVUS) is the current gold standard for plaque characterization, noninvasive coronary computed tomographic angiography (CCTA) requires further evaluation. The ability to detect plaque morphology by CCTA remains unclear. The purpose of this study was to evaluate the diagnostic accuracy of CCTA for plaque detection and morphology.Materials and MethodsThirty-one patients underwent cardiac catheterization with IVUS and CCTA. The presence of plaque was evaluated by both modalities in nonocclusive segments (<50% stenosis) of the left anterior descending artery, left circumflex artery, and right coronary artery. Plaque morphology was classified as (1) normal, (2) soft or fibrous, (3) fibrocalcific, or (4) calcific. Results by IVUS and CCTA were compared blindly on a segment-to-segment basis with subgroup analysis based on CCTA tube voltage.ResultsAmong the 31 patients (mean age 56.2 ± 8.6 years, 27% female), 152 segments were analyzed. Of these segments, 42% were in the left anterior descending artery, 32% were in the left circumflex artery, and 26% were in the right coronary artery. Plaque morphology by IVUS identified 103 segments as fibrous (68%), 31 as fibrocalcific (20%), and 6 as calcific (4.0%); 12 segments were normal (8.0%). To evaluate for the presence of plaque, CCTA had an overall sensitivity and specificity of 99% and 75%, respectively. In patients who underwent CCTA with a tube voltage of 100 kV, both sensitivity and specificity were 100%. The sensitivity and specificity of CCTA to identify plaque as calcified (fibrocalcific or calcific) vs noncalcified (soft or fibrous) were 87% and 96%, respectively. Overall, the accuracy of CCTA to detect the presence of plaque was 97%; the accuracy to detect plaque calcification was 94%.ConclusionsCCTA offers excellent sensitivity and accuracy for plaque detection and morphology characterization in nonocclusive coronary segments. In addition, diagnostic accuracy is preserved with a reduced tube voltage protocol.
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Fluorescence Spectroscopy as a tool to in vivo discrimination of distinctive skin disorders
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Vitoria Helena Maciel, Wagner Rafael Correr, Cristina Kurachi, Vanderlei Salvador Bagnato, Cacilda da Silva Souza
BackgroundFast and non-invasive analytical methods, as fluorescence spectroscopy, have potential applications to detect modifications of biochemical and morphologic properties of malignant tissues. In this study, we propose to analyze the fluorescence spectra using k-Nearest Neighbours algorithm (k-NN) and ratio of the fluorescence intensity (FI) to differentiate skin disorders of distinctive etiologies and morphologies.Materials and methodsLaser-induced autofluorescence spectra upon excitation at 408nm were collected from basal cell carcinoma (BCC) subtypes (n=45/212 spectra), psoriasis (PS) (n=37/193 spectra) and Bowen's disease (BD) (n=04/19 spectra) lesions and respective normal skin at sun-exposed (EXP) and non-exposed (NEXP) sites of the same patient.ResultsThe mean ratios of FI values at selected wavelengths of emission (FI600nm/FI500nm) were significantly lower in BCC and PS lesions compared to EXP [P=0.0001; P=0.0002, respectively]; but there were no significant differences between abnormal conditions.The analysis of fluorescence spectra using k-NN can discriminate normal or abnormal skin conditions (EXP, BCC, BD, PS) of distinctive etiology, neoplastic or inflammatory (BCC, BD and PS) and morphologies (nodular and superficial BCC, BD and PS) as high as 88% and 93% sensitivity and specificity means, respectively; also, similar erythematous-squamous features (superficial BCC, BD and PS) with 98% and 97% sensitivity and specificity means, respectively.The k-NN computational analysis appears to be a promising approach for distinguish skin disorders.
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Expression of S100A2 and S100P in human eccrine sweat glands and their application in differentiating secretory coil-like from duct-like structures in the 3D reconstituted eccrine sweat spheroids
Abstract
Secretory coils and ducts are two components of eccrine sweat glands with different structures and functions. In our previous study, we combined keratins and α-SMA to distinguish between secretory coils and ducts. However, the key deficiency of the method was that none of the antibodies used was specific for ducts. In this study, we first examined the co-localization of K5/K7, α-SMA/K14, K7/S100P and α-SMA/S100A2 by double-immunofluorescence staining to confirm the localization of S100P and S100A2 in native human eccrine sweat glands, and second we identified secretory coil-like and duct-like structures in the 3D reconstituted eccrine sweat gland spheroids by double-immunofluorescence staining for K7/S100P and α-SMA/S100A2. In native human eccrine sweat glands, S100A2 immunoreactivity was confined to the outer layer and S100P to the inner layer of the duct. In 12-week Matrigel plugs containing eccrine sweat gland cells, double-immunofluorescence staining for K7/S100P and α-SMA/S100A2 could easily distinguish duct-like structures from secretory coil-like structures. We conclude that S100A2 and S100P can be used as specific duct markers in eccrine sweat glands, and combined use of S100P or S100A2 with keratins enables easy to distinction between secretory coils and ducts.
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Measuring Inpatient Rehabilitation Facility Quality of Care: Discharge Self-Care Functional Status Quality Measure
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Poonam Pardasaney, Anne Deutsch, Jeniffer Iriondo-Perez, Melvin Ingber, Tara McMullen
ObjectiveThis paper describes the calculation and psychometric properties of the discharge self-care functional status quality measure implemented in the Centers for Medicare & Medicaid Services' (CMS) Inpatient Rehabilitation Facility (IRF) Quality Reporting Program (QRP) on October 1, 2016.DesignMedicare fee-for-service (FFS) patients from 38 IRFs that participated in CMS' Post-Acute Care Payment Reform Demonstration were included in this cohort study. Data came from the Continuity Assessment Record and Evaluation (CARE) Item Set, IRF-Patient Assessment Instrument (IRF-PAI), and Medicare claims. For each patient, we calculated an expected discharge self-care score, risk-adjusted for demographic and baseline clinical characteristics. Each IRF's performance score equaled the percentage of patient stays where the observed discharge self-care score met or exceeded the expected score. We assessed the measure's discriminatory ability across IRFs and reliability.SettingIRF.ParticipantsMedicare FFS patients, 21 years and older.InterventionsNone.Main Outcome MeasuresFacility-level discharge self-care quality measure performance score.Results4,769 patient stays were included; 57% were female, 12.1% under 65 years. Stroke was the most common diagnosis (21.8%). The performance score mean (SD) was 55.1% (16.6%), range was 25.8% to 100%. About 54% of IRFs had scores significantly different from the percentage of stays that met or exceeded the expected discharge self-care score in the overall demonstration sample. The quality measure showed strong reliability, with intra-class correlation coefficients of 0.91.ConclusionsThe discharge self-care quality measure showed strong discriminatory ability and reliability, representing an important initial step in evaluation of IRF self-care outcomes. A wide range in performance scores suggested a gap in quality of care across IRFs. Future work should include testing the measure with nationwide data from all IRFs.
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Caregivers: Do They Make a Difference to Patient Recovery in Subacute Stroke?
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Peck-Hoon Ong, Bee-Choo Tai, Wai-Pong Wong, Liang En Wee, Cynthia Chen, Angela Cheong, Ngan Phoon Fong, Kin Ming Chan, Boon Yeow Tan, Edward Menon, Kok Keng Lee, Chye Hua Ee, Robert Petrella, Amardeep Thind, Gerald Choon-Huat Koh
ObjectiveTo evaluate the relationship between caregiver nature and availability, and rehabilitation outcomes in subacute stroke.DesignRetrospective cohort study.SettingFour community rehabilitation hospitals in Singapore.ParticipantsSubacute, first-time stroke patients (N=4,042; 48.5% men, mean age ±SD 70.12±10.4y; and 51.5% women, mean age ±SD 72.54 ±10.0y).InterventionNot applicableMain Outcome MeasuresRehabilitation effectiveness (R-effectiveness), defined as percentage of potential improvement eventually achieved with rehabilitation; and rehabilitation efficiency (R-efficiency), defined as rate of functional improvement during rehabilitation.ResultsIn our cohort, 96.7% had available caregiver(s), of which 42.0% were primarily supported by foreign domestic workers (FDWs), 25.9% by spouses, 19.3% by first-degree relatives, 7.8% by other relatives, and 5.1% by other caregivers. Using quantile regression, we found that having a caregiver was independently associated with R-efficiency (ß -3.83, 95% confidence interval (CI) -6.99 to -0.66; P=0.018). The relationship between caregiver availability and R-effectiveness was modified by patient gender in that the negative association was significantly greater in males (ß -22.81, 95%CI -32.70 to -12.94; P<0.001) than females (ß -5.64, 95%CI -14.72 to 3.44; P=0.223). Having a FDW as a caregiver compared to spousal-caregiver was negatively associated with R-effectiveness (ß -3.95, 95%CI -6.94 to -0.95; P=0.01) and R-efficiency (ß -1.83, 95%CI -3.14 to -0.53; P=0.006). The number of potential caregivers was only significantly associated with R-effectiveness at bivariate level (P=0.006).ConclusionCaregiver identity, and possibly availability, appears to negatively affect rehabilitation outcomes in subacute stroke. A better understanding of these relationships has potential implications on clinical practice and policy directions.
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Measuring Participation of Rehabilitation Patients: Test-retest Reliability and Mode of Administration Concordance of the Participation Measure--3 Domains, 4 Dimensions (PM-3D4D)
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Feng-Hang Chang
ObjectiveTo evaluate the test-retest reliability and the concordance between the interviewer-administered version and the self-administered version of a newly developed participation measure: Participation Measure--3 Domains, 4 Dimensions (PM-3D4D).DesignMulticenter observational study.SettingOutpatient rehabilitation programs.ParticipantsIn total, 262 rehabilitation outpatients participated in the study, of whom 202 participated in the test-retest study, and a separate 60 participated in the two modes of administration study.InterventionsNot applicable.Main outcome measureThe PM-3D4D includes 19 items measuring participation in productivity, social, and community domains across four dimensions: diversity, frequency, desire for change, and perceived difficulty.ResultsThe test-retest reliability was good across domains and dimensions (intraclass correlation coefficients (ICCs)=0.76∼0.96), and in neurological and non-neurological groups. The test-retest reliability was also mostly good at the item-level. Strong concordance was found between the two administration modes (ICCs=0.96∼1.00).ConclusionsStudy results lend support to the use of the PM-3D4D to reliably assess participation in rehabilitation patients. The strong concordance between the two administration modes suggests the potential use of the instrument in population-based research.
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Communication Skills Training for Practitioners to Increase Patient Adherence to Home-based Rehabilitation for Chronic Low Back Pain: Results of a Cluster Randomized Controlled Trial
Publication date: Available online 28 March 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Chris Lonsdale, Amanda M. Hall, Aileen Murray, Geoffrey C. Williams, Suzanne M. McDonough, Nikos Ntoumanis, Curtin University, Katherine Owen, Ralf Schwarzer, Phillip Parker, Gregory S. Kolt, Deirdre A. Hurley
ObjectiveTo assess the effect of an intervention designed to enhance physiotherapists' communication skills on chronic low back pain patients' adherence to home-based rehabilitation recommendations.DesignCluster randomized controlled trial.SettingPublicly funded physiotherapy clinics in Dublin, Ireland;ParticipantsPhysiotherapists (N = 53) and patients with chronic low back pain (N = 255, 54% female, M age = 45.3 years).Interventions.Patients received publicly funded individual physiotherapy care. In the control arm, care was delivered by a physiotherapist who had completed a 1-hour workshop on evidence-based chronic low back pain management. Patients in the experimental arm received care from physiotherapists who had also completed 8 hours of communications skills training.Main Outcome Measure.Patient-reported adherence to their physiotherapist's recommendations regarding home-based rehabilitation, measured at 1, 4, 12, and 24 weeks after initial treatment session. Pain and pain-related function measured at baseline, 4, 12 and 24 weeks.ResultsLinear mixed model analysis showed the experimental arm patients' ratings of adherence were greater than controls (overall mean difference = .41 [95% CI = .10 to .72, d = .28, p = .01). Moderation analyses showed that men, regardless of intervention, showed improvements in pain-related function over time. Only women in the experimental condition showed functional improvements; female controls saw little change in function over time. The CONNECT intervention did not influence patients' pain, regardless of their sex.ConclusionsCommunication skills training for physiotherapists had short-term positive effects on patient adherence. This training may provide a motivational basis for behavior change and could be a useful component in complex interventions to promote adherence. Communication skills training may also improve some clinical outcomes for women, but not men. Trial registration: ISRCTN63723433.
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Carers' experiences, needs and preferences during inpatient stroke rehabilitation: a systematic review of qualitative studies
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Julie Luker, Carolyn Murray, Elizabeth Lynch, Susanne Bernhardsson, Michelle Shannon, Julie Bernhardt
ObjectiveTo report and synthesise the experiences, needs and preferences of carers of stroke survivors undergoing inpatient rehabilitation.Data sourcesMEDLINE, CINAHL, Embase, PsycINFO and Web of Science were searched to March 2016. Reference lists of relevant publications were searched. No language restrictions were applied.Study selection, appraisal and data extractionEligible qualitative studies reported the experiences of carers of stroke survivors who underwent inpatient rehabilitation. Selection, quality appraisal, and data extraction were undertaken by two or more reviewers. The search yielded 3532 records; 93 full-text publications were assessed for eligibility and 34 documents (33 studies) were included. Comprehensiveness of reporting was assessed using the COREQ framework. All text in studies' results and discussion sections were extracted for analysis.Data synthesisExtracted texts were analysed inductively using thematic synthesis. Seven analytical themes were developed that related to the carers' experiences, needs and preferences: (1) Overwhelmed with emotions; (2) Recognition as a stakeholder in recovery; (3) Desire to be heard and informed; (4) Persisting for action and outcomes; (5) Being legitimate clients; (6) Navigating an alien culture and environment; (7) Managing the transition home.ConclusionsThis systematic review provides new insights into the experiences, needs and preferences of carers of stroke survivors undergoing inpatient rehabilitation. Carers experienced distress as they navigated a foreign culture and environment without adequate communication and processes in place for their inclusion. We recommend deliberate efforts to provide a more inclusive environment that better supports and prepares carers for their new role.
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Modification of cytokine-induced killer cells with folate receptor alpha (FRα)-specific chimeric antigen receptors enhances their antitumor immunity toward FRα-positive ovarian cancers
Source:Molecular Immunology, Volume 85
Author(s): Shuguang Zuo, Yuqing Wen, Hean Panha, Gongpeng Dai, Liping Wang, Xuequn Ren, Kanda Fu
Folate receptor alpha (FRα) is aberrantly expressed in ovarian cancers but largely absent in normal tissues, and therefore represents an attractive target for immunotherapy. In recent years, modification of T cells with chimeric antigen receptor (CAR) targeting FRα has been reported to improve antitumor immunity of T cells. However, there are limited data regarding CAR-modified cytokine-induced killer (CAR-CIK) cells. In the present study, we modified CIK cells with FRα-specific CARs and investigated their antitumor immunity against ovarian cancers. We found that both non-transduced and mock CAR-transduced CIK cells showed only low antitumor activity against either FRα-positive (FRα+) or FRα-negative (FRα−) targets. However, all three generations of CAR-modified CIK cells showed enhanced antitumor activity against FRα+ targets, but not FRα− targets. First-generation ζ-CAR-CIK cells increased production of IFN-γ, enhanced short-term cytotoxicity against FRα+ ovarian cancer cells, and showed modest and short-term suppression of established tumors; while second-generation 28ζ- and third-generation 28BBζ-CAR-CIK cells showed significant proliferation, enhanced secretion of IL-2, eliminated the FRα+ ovarian cancer cells in long-term co-culture, and showed dramatic and long-term inhibition of tumor growth and prolonged survival of xenograft-bearing mice. It is noteworthy that the 28BBζ-CAR was more potent in the modification of CIK cells than 28ζ-CAR both in vitro and in vivo. Moreover, CAR-CIK cells showed more efficient anticancer activity compared with CAR-T cells in vitro, but less efficient than CAR-T cells in vivo. According to these results, we conclude that modification of CIK cells with FRα-specific CARs enhances their antitumor immunity to FRα+ ovarian cancers. The third-generation 28BB-ζ CAR containing 4-1BB co-stimulation was more efficient in modification of CIK cells than either first-generation ζ-CAR or second-generation CD28-ζ-CAR.
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FcγRIIb expression on B cells is associated with treatment efficacy for acute rejection after kidney transplantation
Source:Molecular Immunology, Volume 85
Author(s): Juan Jin, Jianguang Gong, Bo Lin, Yiwen Li, Qiang He
BackgroundFcγ receptors (FcγR) play a role in the acute rejection (AR) of organ transplants. FcγRIIB is an inhibitory FcγR expressed on B cells. Intravenous IgG (IVIG) and CD28 monoclonal antibody (mAb) have been shown to have immunomodulatory properties against AR.AimTo examine the association between FcγRIIB expression on B cell subpopulations and AR treatment efficacy.MethodsMale F344 rats were used as kidney donors and Lewis rats as recipients to establish models of renal transplantation. Rats were divided into five groups: sham, AR-PBS, AR-IVIG, AR-PNGase F-IVIG, and AR-CD28. Serum creatinine (Scr), blood urea nitrogen (BUN), and urine protein content were determined. Inflammatory markers were measured by ELISA, FcγR by western blotting, and spleen B cell activation by flow cytometry.ResultsScr, BUN, urinary protein content, levels of CRP, IL-10, TNF-α, IL-6, IL-8, and IgG were all increased in the AR-PBS group compared with the sham group (all P<0.01); these increases were partly reversed in the AR-IVIG, AR-PNGase F IVIG, and AR-CD28 groups (all P<0.01), with IVIG showing the better efficacy than PNGase F IVIG. Furthermore, blood and spleen FcγRIA and FcγRIIIA were increased by AR, while FcγRIIB expressions in splenic activated B cells and regulatory B cells were decreased; these changes were partly alleviated by all three treatments, with IVIG having the better effect than PNGase F IVIG.ConclusionWe observed an association between B cell FcγRIIB expression and treatment efficacy for AR after kidney transplantation in rats.
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Possible effects of neonatal vitamin B12 status on TSH-screening program: a cross-sectional study from Turkey
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print
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Personalized precision medicine in extreme preterm infants with transient neonatal diabetes mellitus
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print
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Xenopus metamorphosis as a model to study thyroid hormone receptor function during vertebrate developmental transitions
Source:Molecular and Cellular Endocrinology
Author(s): Daniel R. Buchholz
A hormone-dependent developmental transition from aquatic to terrestrial existence occurs in all tetrapod vertebrates, such as birth, hatching, and metamorphosis. Thyroid hormones (TH) and their receptors (TRs) are key players in the tissue transformations comprising vertebrate developmental transitions. The African clawed frog, Xenopus, is a premier model for the role of TRs in developmental transitions because of the numerous and dramatic TH-dependent tissue transformations during metamorphosis and because of the endocrine, molecular, and genomic resources available. TRs are nuclear receptors that repress TH-response genes when plasma TH is minimal and that activate those same genes to induce tissue-specific gene regulation cascades when TH plasma levels increase. Tissue-specific TR expression levels help determine tissue sensitivity and responsivity to TH thereby regulating the initiation and rate of developmental change in TH-sensitive tissues which govern the tissue developmental asynchrony observed during metamorphosis. This review highlighting Xenopus presents the key experimental findings underpinning the roles TRs play in control of vertebrate developmental transitions.
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Paxillin and embryonic PolyAdenylation Binding Protein (ePABP) engage to regulate androgen-dependent Xenopus laevis oocyte maturation - A model of kinase-dependent regulation of protein expression
Source:Molecular and Cellular Endocrinology
Author(s): Susanne U. Miedlich, Manisha Taya, Melissa Rasar Young, Stephen R. Hammes
Steroid-triggered Xenopus laevis oocyte maturation is an elegant physiologic model of nongenomic steroid signaling, as it proceeds completely independent of transcription. We previously demonstrated that androgens are the main physiologic stimulator of oocyte maturation in Xenopus oocytes, and that the adaptor protein paxillin plays a crucial role in mediating this process through a positive feedback loop in which paxillin first enhances Mos protein translation, ensued by Erk2 activation and Erk-dependent phosphorylation of paxillin on serine residues. Phosphoserine-paxillin then further augments Mos protein translation and downstream Erk2 activation, resulting in meiotic progression. We hypothesized that paxillin enhances Mos translation by interacting with embryonic PolyAdenylation Binding Protein (ePABP) on polyadenylated Mos mRNA. Knockdown of ePABP phenocopied paxillin knockdown, with reduced Mos protein expression, Erk2 and Cdk1 activation, as well as oocyte maturation. In both Xenopus oocytes and mammalian cells (HEK-293), paxillin and ePABP constitutively interacted. Testosterone (Xenopus) or EGF (HEK-293) augmented ePABP-paxillin binding, as well as ePABP binding to Mos mRNA (Xenopus), in an Erk-dependent fashion. Thus, ePABP and paxillin work together in an Erk-dependent fashion to enhance Mos protein translation and promote oocyte maturation.
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Assessment of “YouTube” Content for Distal Radius Fracture Immobilization
Publication date: Available online 27 March 2017
Source:Journal of Surgical Education
Author(s): Abdullah Addar, Yousef Marwan, Nizar Algarni, Gregory Berry
ObjectiveDistal radius fractures (DRFs) are the most common orthopedic fractures, with >70% of cases treated by closed immobilization using a short arm cast or a sugar tong splint. However, inadequate immobilization is a risk factor for loss of reduction requiring repeat reduction or surgical treatment. Therefore, education of clinical skills for appropriate immobilization of DRFs is important. With the increasing use of web-based information by medical learners, our aim was to assess the quality and quantity of videos regarding closed immobilization of DRFs on YouTube.DesignRetrospective review of YouTube videos on distal radius fracture immobilization using specific search terms.SettingIdentified videos were analyzed for their educational value, quality of the technical skill demonstrated, and overall metrics. Educational value was scored on a 5-point scale, with "1" indicative of low quality and "5" of high quality.ParticipantsNot applicable.ResultsAmong the 68,366 videos identified, 16 met our inclusion criteria of being in English; performed by a health care professional or institution; and with casting being the major theme of the educational information provided. Of these 16 videos, 6 had an educational value score of 4 or 5, with the remaining 10 having a score ≤3. Although immobilization was demonstrated by cast technician specialized in orthopedics, skills were also performed by orthopedic attendants, urgent care physicians, orthopedic residents, and nurse practitioners. The credentials of the performer in 3 videos were not identified.ConclusionThere is a need to promote high-quality educational videos produced by established medical school faculty members on open, web-based, portals.
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Scholar : These new articles for Atmospheric and Oceanic Science Letters are available online
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Scholar : These new articles for The American Journal of Drug and Alcohol Abuse are available online
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Scholar : These new articles for The Aging Male are available online
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Influencia de la cirugía mamaria previa en la biopsia selectiva del ganglio centinela en pacientes con cáncer de mama
Publication date: Available online 27 March 2017
Source:Revista Española de Medicina Nuclear e Imagen Molecular
Author(s): V. López-Prior, R. Díaz-Expósito, I. Casáns Tormo
ObjetivoRevisar la aplicabilidad de la biopsia selectiva del ganglio centinela en pacientes con cáncer de mama y antecedente de cirugía mamaria previa, y examinar los factores que podrían influir en la detección del ganglio centinela.Material y métodosRevisamos retrospectivamente la biopsia selectiva del ganglio centinela en 91 pacientes con cáncer de mama dividiéndolas en 2 grupos según el antecedente quirúrgico de la mama: cirugía estética en 30 (grupo I) y conservadora en 61 (grupo II). Se realizó linfogammagrafía prequirúrgica tras inyección intratumoral en 21 casos y periareolar en 70. Se analizaron los patrones de drenaje linfático y la detección global del ganglio centinela según características clínicas, patológicas y quirúrgicas.ResultadosLa detección global del ganglio centinela en la linfogammagrafía fue del 92,3%, con un 7,7% de drenajes extraaxilares. La detección fue similar en el grupo I (93,3%) y grupo II (91,8%). En 2 pacientes (2,2%) detectamos ganglios centinelas en la axila contralateral, estando afectados en el estudio anatomopatológico. El porcentaje de no detección del ganglio centinela en la gammagrafía fue del 7,7%. Se encontró una proporción de no detección significativamente mayor en tumores con mayor grado histológico (28,6% grado III, 4,5% grado I y 3,6% grado II).ConclusiónSe puede realizar la biopsia selectiva del ganglio centinela en pacientes con antecedente de cirugía mamaria previa, pero serían necesarios más estudios para valorar la influencia en la detección del ganglio centinela de diferentes aspectos en este escenario clínico. Un elevado grado histológico se relaciona significativamente con una menor detección.AimThe aim of this study was to review the feasibility of selective sentinel lymph node biopsy in patients with previous surgery for breast cancer, as well as to examine the factors that may interfere with sentinel node detection.Material and methodsA retrospective review was performed on 91 patients with breast cancer and previous breast surgery, and who underwent sentinel lymph node biopsy. Patients were divided into two groups according to their previous treatment: aesthetic breast surgery in 30 patients (group I) and breast-conserving surgery in 61 (group II). Lymphoscintigraphy was performed after an intra-tumour injection in 21 cases and a peri-areolar injection in 70 cases. An analysis was made of lymphatic drainage patterns and overall sentinel node detection according to clinical, pathological and surgical variables.ResultsThe overall detection of the sentinel lymph node in the lymphoscintigraphy was 92.3%, with 7.7% of extra-axillary drainages. The identification rate was similar after aesthetic breast surgery (93.3%) and breast-conserving surgery (91.8%). Sentinel lymph nodes were found in the contralateral axilla in two patients (2.2%), and they were included in the histopathology study. The non-identification rate in the lymphoscintigraphy was 7.7%. There was a significantly higher non-detection rate in the highest histological grade tumours (28.6% grade III, 4.5% grade I and 3.6% grade II).ConclusionSentinel lymph node biopsy in patients with previous breast surgery is feasible and deserves further studies to assess the influence of different aspects in sentinel node detection in this clinical scenario. A high histological grade was significantly associated with a lower detection.
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Editorial Board/Title Page
Source:Cortex, Volume 89
http://ift.tt/2nryaht
Avoiding boredom: Caudate and insula activity reflects boredom-elicited purchase bias
Source:Cortex
Author(s): Dennis E. Dal Mas, Bianca C. Wittmann
People show a strong tendency to avoid boring situations, but the neural systems mediating this behavioural bias are yet unknown. We used fMRI to investigate how the anticipation of a boring task influences decisions to purchase entertainment. Participants accepted higher prices to avoid boredom compared to control tasks, and individual differences in boredom experience predicted the increase in price. This behavioural bias was associated with higher activity in the caudate nucleus during music purchases driven by boredom avoidance. Insula activation was increased during performance of the boring task and subsequently associated with individual differences in boredom-related decision making. These results identify a mechanism that drives decisions to avoid boring situations and potentially underlies consumer decisions.
http://ift.tt/2nrtl7M
Protective factors against disordered eating in family systems: a systematic review of research
Abstract
Objective
This systematic review aims to identify and evaluate the literature investigating protective factors and eating disorders (EDs), to establish what is known about factors in family systems that could be considered protective against the development of ED/disordered eating.
Methods
A systematic review of the literature was conducted on five databases, using search terms related to ED/disordered eating and protective factors. Studies were systematically screened and included if they made reference to a protective factor within the family system and explored associations with a quantitative measure of ED/disordered eating behaviours. All included studies were evaluated for study quality.
Results
Twenty-five studies met criteria for inclusion. Ten papers made use of longitudinal or prospective designs appropriate to identify factors potentially protecting against the development of disordered eating difficulties, while a further 15 papers report cross-sectional associations between family factors and disordered eating outcomes. Studies looked at aspects of family relationships and family practices around food or eating. There was a particular research focus on the potential protective role of regular family meals.
Conclusions and Implications
Many of the potential protective factors identified, such as family support and connectedness, may be non-specific to eating difficulties, promoting general adaptive development and a range of positive development outcomes. Factors in the family environment around food, eating and weight, such as frequent family meals and avoiding comments about weight, may be more specific to ED and disordered eating. Issues with the methodologies used severely impact on the ability to draw conclusions about whether factors are 'protective'.
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Scholar : These new articles for Addiction Research & Theory are available online
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“On-Off-On” fluorescence sensor based on g-C3N4 nanosheets for selective and sequential detection of Ag+ and S2-
Publication date: 1 June 2017
Source:Talanta, Volume 168
Author(s): Shan Wang, Qian Lu, Xu Yan, Mingming Yang, Ranfeng Ye, Dan Du, Yuehe Lin
Detection of silver (Ag+) and sulfide (S2−) ions is important because their presence in large amounts can cause many diseases. In this study, a novel, simple, "on-off-on" fluorescence sensor based on g-C3N4 nanosheets for sequential detection of Ag+ and S2- was designed. The fluorescence signal of the g-C3N4 nanosheets is quenched because Ag+ chelates with the N of the g-C3N4 nanosheets, leading to photoinduced electron transfer from the sheets to Ag+. After adding S2−, the fluorescence of the g-C3N4 nanosheets is recovered due to formation of Ag2S, which activates the fluorescence of the g-C3N4 nanosheets. The recovery efficiency was found to increase with increasing concentrations of S2-, with linear calibration ranging from 0nmol/L to 30nmol/L. Other potentially interfering species, such as SO42−, PO43−, HPO42−, H2PO4−, CO32−, NO3−, Ac−, and HCO3−, presented negligible effects on S2− detection. Moreover, the proposed sensor exhibited several advantages, including low cost, easy preparation, rapid detection, excellent biocompatibility, and a switchable fluorescence response. These attributes make this fluorescent sensor a promising tool for environmental applications.
Graphical abstract
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