In order to present the collapse process and failure mechanism of long-span cable-stayed bridges under strong seismic excitations, a rail-cum-road steel truss cable-stayed bridge was selected as engineering background, the collapse failure numerical model of the cable-stayed bridge was established based on the explicit dynamic finite element method (FEM), and the whole collapse process of the cable-stayed bridge was analyzed and studied with three different seismic waves acted in the horizontal longitudinal direction, respectively. It can be found from the numerical simulation analysis that the whole collapse failure process and failure modes of the cable-stayed bridge under three different seismic waves are similar. Furthermore, the piers and the main pylons are critical components contributing to the collapse of the cable-stayed bridge structure. However, the cables and the main girder are damaged owing to the failure of piers and main pylons during the whole structure collapse process, so the failure of cable and main girder components is not the main reason for the collapse of cable-stayed bridge. The analysis results can provide theoretical basis for collapse resistance design and the determination of critical damage components of long-span highway and railway cable-stayed bridges in the research of seismic vulnerability analysis.
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Τετάρτη 28 Ιουνίου 2017
Research on Collapse Process of Cable-Stayed Bridges under Strong Seismic Excitations
Enhancing Health Risk Prediction with Deep Learning on Big Data and Revised Fusion Node Paradigm
With recent advances in health systems, the amount of health data is expanding rapidly in various formats. This data originates from many new sources including digital records, mobile devices, and wearable health devices. Big health data offers more opportunities for health data analysis and enhancement of health services via innovative approaches. The objective of this research is to develop a framework to enhance health prediction with the revised fusion node and deep learning paradigms. Fusion node is an information fusion model for constructing prediction systems. Deep learning involves the complex application of machine-learning algorithms, such as Bayesian fusions and neural network, for data extraction and logical inference. Deep learning, combined with information fusion paradigms, can be utilized to provide more comprehensive and reliable predictions from big health data. Based on the proposed framework, an experimental system is developed as an illustration for the framework implementation.
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Tail Nerve Electrical Stimulation and Electro-Acupuncture Can Protect Spinal Motor Neurons and Alleviate Muscle Atrophy after Spinal Cord Transection in Rats
Spinal cord injury (SCI) often results in death of spinal neurons and atrophy of muscles which they govern. Thus, following SCI, reorganizing the lumbar spinal sensorimotor pathways is crucial to alleviate muscle atrophy. Tail nerve electrical stimulation (TANES) has been shown to activate the central pattern generator (CPG) and improve the locomotion recovery of spinal contused rats. Electroacupuncture (EA) is a traditional Chinese medical practice which has been proven to have a neural protective effect. Here, we examined the effects of TANES and EA on lumbar motor neurons and hindlimb muscle in spinal transected rats, respectively. From the third day postsurgery, rats in the TANES group were treated 5 times a week and those in the EA group were treated once every other day. Four weeks later, both TANES and EA showed a significant impact in promoting survival of lumbar motor neurons and expression of choline acetyltransferase (ChAT) and ameliorating atrophy of hindlimb muscle after SCI. Meanwhile, the expression of neurotrophin-3 (NT-3) in the same spinal cord segment was significantly increased. These findings suggest that TANES and EA can augment the expression of NT-3 in the lumbar spinal cord that appears to protect the motor neurons as well as alleviate muscle atrophy.
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Online Social Network Emergency Public Event Information Propagation and Nonlinear Mathematical Modeling
Emergency public event arises everyday on social network. The information propagation of emergency public event (favorable and harmful) is researched. The dynamics of a susceptible-infected-susceptible and susceptible-infected-removed epidemic models incorporated with information propagation of emergency public event are studied. In particular, we investigate the propagation model and the infection spreading pattern using nonlinear dynamic method and results obtained through extensive numerical simulations. We further generalize the model for any arbitrary number of infective network nodes to mimic existing scenarios in online social network. The simulation results reveal that the inclusion of multiple infective node achieved stability and equilibrium in the proposed information propagation model.
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Sensitivity Evaluation of AP1000 Nuclear Power Plant Best Estimation Model
The best estimation process of AP1000 Nuclear Power Plant (NPP) requires proper selections of parameters and models so as to obtain the most accurate results compared with the actual design parameters. Therefore, it is necessary to identify and evaluate the influences of these parameters and modeling approaches quantitatively and qualitatively. Based on the best estimate thermal-hydraulic system code RELAP5/MOD3.2, sensitivity analysis has been performed on core partition methods, parameters, and model selections in AP1000 Nuclear Power Plant, like the core channel number, pressurizer node number, feedwater temperature, and so forth. The results show that core channel number, core channel node number, and the pressurizer node number have apparent influences on the coolant temperature variation and pressure drop through the reactor. The feedwater temperature is a sensitive factor to the Steam Generator (SG) outlet temperature and the Steam Generator outlet pressure. In addition, the cross-flow model nearly has no effects on the coolant temperature variation and pressure drop in the reactor, in both the steady state and the loss of power transient. Furthermore, some fittest parameters with which the most accurate results could be obtained have been put forward for the nuclear system simulation.
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The Applications of PCA in QSAR Studies: A case study on CCR5 antagonists
Abstract
Principal component analysis (PCA), as a well-known multivariate data analysis and data reduction technique, is an important and useful algebraic tool in drug design and discovery. PCA, in a typical quantitative structure activity relationship (QSAR) study, analyzes an original data matrix in which molecules are described by several inter-correlated quantitative dependent variables (molecular descriptors). Although extensively applied, there is disparity in the literature with respect to the applications of PCA in the QSAR studies. This study investigates the different applications of PCA in QSAR studies using a dataset including CCR5 inhibitors. The different types of pre-processing are used to compare the PCA performances. The use of PC plots in the exploratory investigation of matrix of descriptors is described. This work is also proved PCA analysis to be a powerful technique for exploring complex datasets in QSAR studies for identification of outliers. This study shows that PCA is able to easily applied to the pool of calculated structural descriptors, and also the extracted information can be used to help decide upon an appropriate harder model for further analysis.
This article is protected by copyright. All rights reserved.
Most important aims of PCA in QSAR studies are reviewed in this study such as to extract the important information from the molecular descriptor matrix, to represent it as a set of new orthogonal variables called principal components (PCs), and to display the pattern of similarity of the molecules in data set of interest and of the molecular descriptors as points in maps.
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Tumor angiogenesis and vascular normalization: alternative therapeutic targets
Abstract
Tumor blood vessels are a key target for cancer therapeutic management. Tumor cells secrete high levels of pro-angiogenic factors which contribute to the creation of an abnormal vascular network characterized by disorganized, immature and permeable blood vessels, resulting in poorly perfused tumors. The hypoxic microenvironment created by impaired tumor perfusion can promote the selection of more invasive and aggressive tumor cells and can also impede the tumor-killing action of immune cells. Furthermore, abnormal tumor perfusion also reduces the diffusion of chemotherapeutic drugs and radiotherapy efficiency. To fight against this defective phenotype, the normalization of the tumor vasculature has emerged as a new therapeutic strategy. Vascular normalization, by restoring proper tumor perfusion and oxygenation, could limit tumor cell invasiveness and improve the effectiveness of anticancer treatments. In this review, we investigate the mechanisms involved in tumor angiogenesis and describe strategies used to achieve vascular normalization.
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Experimental hydrodynamics of high-porosity metal foam: Effect of pore density
Commercial open-cell metal foam has very high porosity (often greater than 90%) and a large surface area density. The open flow area is copious compared to the ligament size. These properties are exploited in many applications, e.g., heat exchanger, reactors and filters. Pressure drop, flow regimes, and transition from one to another, are indispensable for any application involving flow of a fluid through the foam, and for heat transfer rates or reaction paces. These topics are not well-agreed on for foam-like porous media such as metal, graphite and polymeric foams. Pressure drop parameters such as permeability and form/inertial drag coefficients are very divergent for metal foam; the same can be said about flow regime boundaries. This paper presents experimental data for pressure drop for water flow in two commercial open-cell aluminium foams having 10 and 40 pores per inch (ppi). The two foams have similar porosities (88.5%). The wide range of flow Reynolds number covered all known flow regimes in porous media: pre-Darcy, Darcy, Forchheimer and turbulent. Flow regimes and transition between them were identified and compared. The friction factor based on the square root of permeability (measured in the Darcy regime) and the Reynolds number based on the same characteristic length were used. It is shown that the same foam exhibits different values of its permeability and Forchheimer coefficient in different flow regimes. A previously-tested foam having 20 pores per inch and a porosity of 87.6% was included in the comparisons. The basic finding of this study will inform numerical and analytical work concerning flow and heat transfer in foam-like highly-porous porous media. (C) 2016 Elsevier Ltd. All rights reserved.
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Usefulness of the European epidemic intelligence information system in the management of an outbreak of Listeriosis, Belgium, 2011
A cluster of time-linked cases and the identification of a clonal strain suggest the occurrence of an outbreak of listeriosis in Belgium in 2011, presumably due to the consumption of hard cheese made with pasteurised milk and produced by a Belgium manufacturer. The outbreak clone was identified as Listeria monocytogenes serovar 1/2a, sensitive to arsenic and cadmium and of multilocus sequence typing MLST-type 37. Food investigation of this outbreak was facilitated by the European Epidemic Intelligence Information System and data exchanged between French and Belgium listeriosis surveillance systems.
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Emulsified fuels based on fatty acid distillates and rapeseed oil : a physicochemical characterization
The emulsification of water in vegetable oils is one of the most promising techniques reported in order to reach an engine-friendly fuel with proper physicochemical properties, allowing improvements in the atomization process and exhaust emissions. For this reason, the scope of this investigation is to formulate and characterize emulsified fuels using different continuous phases, as well as to analyze the influence of the increase of the surfactant concentration on the system stability. The emulsified systems were formulated using ultrasonic equipment and consisted of continuous phase rapeseed oil and fatty acid distillates mixed with diesel fuel. Additional components such as deionized water, ethanol and octanol, as well as sorbitan monooleate and polyoxyethylene sorbitan monooleate as surfactant, were used. The formulated dispersed systems were covered under different experimental factors and summarized in ternary diagrams. Several stable dispersed systems were achieved (emulsions and microemulsions); but only with the introduction of diesel fuel to the formulations, proper viscosity values were achieved. An increase of the viscosity with increasing the amount of water was noted. The water droplets sizes of emulsified rapeseed oil were smaller than in the emulsified fatty acid distillates. Finally, an increase of surfactant percentage in the emulsification process improved the dispersed systems' stability and their optical appearance, whereas also slight differences in density, viscosity and surface tension values were noted. (C) 2016 Elsevier Ltd. All rights reserved.
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Lower seroreactivity to European than to North American H3N2 swine influenza viruses in humans, Luxembourg, 2010
Seroreactivity to H3N2 swine influenza viruses (SIVs) was evaluated in serum samples collected from 843 people aged 0 to 100 years in 2010 in Luxembourg. Sera were analysed by haemagglutination inhibition (HI) and virus neutralisation (VN) assays targeting a European H3N2 SIV, a North American H3N2 variant of swine origin (H3N2v) and human seasonal H3N2 viruses isolated in 1975, 1995 and 2005. HI antibodies (titre ≥ 10) against European H3N2 SIV were almost exclusively detected in those born before 1990, of whom 70% were seropositive. HI antibodies against H3N2v were predominantly found in those born before 2000, with 86% seropositive. Titres against the North American H3N2v were higher than against the European H3N2 SIV. VN patterns were similar, but with higher rates and titres. We also demonstrated lower seroreactivity to European H3N2 SIV than to North American H3N2v virus. Finally, we found a strong correlation between HI titres against the European H3N2 SIV and H3N2v and their respective human ancestors, A/Victoria/3/75 and A/Nanchang/933/95. This finding and the minimal contacts between humans and pigs in Luxembourg suggest that anti-SIV antibodies in human serum samples reflect serological cross-reactivity with historical human H3N2 viruses. Our findings help assess the pandemic risk of H3N2 SIV.
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Influenza at the animal-human interface: a review of the literature for virological evidence of human infection with swine or avian influenza viruses other than A(H5N1)
Factors that trigger human infection with animal influenza virus progressing into a pandemic are poorly understood. Within a project developing an evidence-based risk assessment framework for influenza viruses in animals, we conducted a review of the literature for evidence of human infection with animal influenza viruses by diagnostic methods used. The review covering Medline, Embase, SciSearch and CabAbstracts yielded 6,955 articles, of which we retained 89; for influenza A(H5N1) and A(H7N9), the official case counts of the World Health Organization were used. An additional 30 studies were included by scanning the reference lists. Here, we present the findings for confirmed infections with virological evidence. We found reports of 1,419 naturally infected human cases, of which 648 were associated with avian influenza virus (AIV) A(H5N1), 375 with other AIV subtypes, and 396 with swine influenza virus (SIV). Human cases naturally infected with AIV spanned haemagglutinin subtypes H5, H6, H7, H9 and H10. SIV cases were associated with endemic SIV of H1 and H3 subtype descending from North American and Eurasian SIV lineages and various reassortants thereof. Direct exposure to birds or swine was the most likely source of infection for the cases with available information on exposure.
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Soil survey in DR Congo : from 1935 until today
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Influenza at the animal-human interface: a review of the literature for virological evidence of human infection with swine or avian influenza viruses other than A(H5N1)
Factors that trigger human infection with animal influenza virus progressing into a pandemic are poorly understood. Within a project developing an evidence-based risk assessment framework for influenza viruses in animals, we conducted a review of the literature for evidence of human infection with animal influenza viruses by diagnostic methods used. The review covering Medline, Embase, SciSearch and CabAbstracts yielded 6,955 articles, of which we retained 89; for influenza A(H5N1) and A(H7N9), the official case counts of the World Health Organization were used. An additional 30 studies were included by scanning the reference lists. Here, we present the findings for confirmed infections with virological evidence. We found reports of 1,419 naturally infected human cases, of which 648 were associated with avian influenza virus (AIV) A(H5N1), 375 with other AIV subtypes, and 396 with swine influenza virus (SIV). Human cases naturally infected with AIV spanned haemagglutinin subtypes H5, H6, H7, H9 and H10. SIV cases were associated with endemic SIV of H1 and H3 subtype descending from North American and Eurasian SIV lineages and various reassortants thereof. Direct exposure to birds or swine was the most likely source of infection for the cases with available information on exposure.
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Lower seroreactivity to European than to North American H3N2 swine influenza viruses in humans, Luxembourg, 2010
Seroreactivity to H3N2 swine influenza viruses (SIVs) was evaluated in serum samples collected from 843 people aged 0 to 100 years in 2010 in Luxembourg. Sera were analysed by haemagglutination inhibition (HI) and virus neutralisation (VN) assays targeting a European H3N2 SIV, a North American H3N2 variant of swine origin (H3N2v) and human seasonal H3N2 viruses isolated in 1975, 1995 and 2005. HI antibodies (titre ≥ 10) against European H3N2 SIV were almost exclusively detected in those born before 1990, of whom 70% were seropositive. HI antibodies against H3N2v were predominantly found in those born before 2000, with 86% seropositive. Titres against the North American H3N2v were higher than against the European H3N2 SIV. VN patterns were similar, but with higher rates and titres. We also demonstrated lower seroreactivity to European H3N2 SIV than to North American H3N2v virus. Finally, we found a strong correlation between HI titres against the European H3N2 SIV and H3N2v and their respective human ancestors, A/Victoria/3/75 and A/Nanchang/933/95. This finding and the minimal contacts between humans and pigs in Luxembourg suggest that anti-SIV antibodies in human serum samples reflect serological cross-reactivity with historical human H3N2 viruses. Our findings help assess the pandemic risk of H3N2 SIV.
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Usefulness of the European epidemic intelligence information system in the management of an outbreak of Listeriosis, Belgium, 2011
A cluster of time-linked cases and the identification of a clonal strain suggest the occurrence of an outbreak of listeriosis in Belgium in 2011, presumably due to the consumption of hard cheese made with pasteurised milk and produced by a Belgium manufacturer. The outbreak clone was identified as Listeria monocytogenes serovar 1/2a, sensitive to arsenic and cadmium and of multilocus sequence typing MLST-type 37. Food investigation of this outbreak was facilitated by the European Epidemic Intelligence Information System and data exchanged between French and Belgium listeriosis surveillance systems.
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Emulsified fuels based on fatty acid distillates and rapeseed oil : a physicochemical characterization
The emulsification of water in vegetable oils is one of the most promising techniques reported in order to reach an engine-friendly fuel with proper physicochemical properties, allowing improvements in the atomization process and exhaust emissions. For this reason, the scope of this investigation is to formulate and characterize emulsified fuels using different continuous phases, as well as to analyze the influence of the increase of the surfactant concentration on the system stability. The emulsified systems were formulated using ultrasonic equipment and consisted of continuous phase rapeseed oil and fatty acid distillates mixed with diesel fuel. Additional components such as deionized water, ethanol and octanol, as well as sorbitan monooleate and polyoxyethylene sorbitan monooleate as surfactant, were used. The formulated dispersed systems were covered under different experimental factors and summarized in ternary diagrams. Several stable dispersed systems were achieved (emulsions and microemulsions); but only with the introduction of diesel fuel to the formulations, proper viscosity values were achieved. An increase of the viscosity with increasing the amount of water was noted. The water droplets sizes of emulsified rapeseed oil were smaller than in the emulsified fatty acid distillates. Finally, an increase of surfactant percentage in the emulsification process improved the dispersed systems' stability and their optical appearance, whereas also slight differences in density, viscosity and surface tension values were noted. (C) 2016 Elsevier Ltd. All rights reserved.
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Experimental hydrodynamics of high-porosity metal foam: Effect of pore density
Commercial open-cell metal foam has very high porosity (often greater than 90%) and a large surface area density. The open flow area is copious compared to the ligament size. These properties are exploited in many applications, e.g., heat exchanger, reactors and filters. Pressure drop, flow regimes, and transition from one to another, are indispensable for any application involving flow of a fluid through the foam, and for heat transfer rates or reaction paces. These topics are not well-agreed on for foam-like porous media such as metal, graphite and polymeric foams. Pressure drop parameters such as permeability and form/inertial drag coefficients are very divergent for metal foam; the same can be said about flow regime boundaries. This paper presents experimental data for pressure drop for water flow in two commercial open-cell aluminium foams having 10 and 40 pores per inch (ppi). The two foams have similar porosities (88.5%). The wide range of flow Reynolds number covered all known flow regimes in porous media: pre-Darcy, Darcy, Forchheimer and turbulent. Flow regimes and transition between them were identified and compared. The friction factor based on the square root of permeability (measured in the Darcy regime) and the Reynolds number based on the same characteristic length were used. It is shown that the same foam exhibits different values of its permeability and Forchheimer coefficient in different flow regimes. A previously-tested foam having 20 pores per inch and a porosity of 87.6% was included in the comparisons. The basic finding of this study will inform numerical and analytical work concerning flow and heat transfer in foam-like highly-porous porous media. (C) 2016 Elsevier Ltd. All rights reserved.
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Soil survey in DR Congo : from 1935 until today
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Notes on contributors
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Gastric Bypass and Synchronous Cholecystectomy: Not Only Numbers
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Barrett’s Oesophagus and Oesophageal Carcinogenesis Following Obesity Surgery: Helicobacter Pylori Must Be Eradicated?
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Predictive Value of C-Reactive Protein for Complications Post-Laparoscopic Roux-en-Y Gastric Bypass
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Uterine Lipoleiomyoma: A Report of Two Cases
Journal of Clinical Imaging Science 2017 7(1):26-26
We report two cases of uterine lipoleiomyoma in postmenopausal women of ages 52 and 55 years, who presented with complaints of leukorrhea and lower abdominal pain, respectively. Lipoleiomyoma is a rare benign variant of leiomyoma, having an incidence of 0.03%–0.2%. These are benign pelvic tumors which are usually asymptomatic and commonly occur in obese postmenopausal women. However, they can occasionally present with typical leiomyoma symptoms. Imaging plays a crucial role in the diagnosis of benign pelvic tumors. Ultrasonography is the first imaging modality for diagnosis of pelvic tumors in females. Computed tomography and magnetic resonance imaging are specific in demonstrating the uterine origin and fat component.
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Laparoscopic Sleeve Gastrectomy for the Management of Type 1 Diabetes Mellitus
Abstract
Background
The prevalence of obesity is on a continuous rise worldwide, with major studies clearly correlating obesity with the development of chronic metabolic disorders including type 2 diabetes. Bariatric surgery has proven to be beneficial in the management of this condition; however, a limited number of studies exist on its effect on type 1 diabetes.
Objective
The objective of this study is to evaluate the outcome of laparoscopic sleeve gastrectomy for the management of patients with type 1 diabetes (DM1).
Setting
This is a retrospective cohort study conducted in a university hospital and private practice in Kuwait.
Research Design and Methods
Analysis was conducted on 10 patients diagnosed with type 1 diabetes that underwent bariatric surgery from October 2008 until December 2016 at Amiri Hospital and Royale Hayat Hospital, Kuwait. Primary parameters included body mass index (BMI), % excess weight (%EWL) loss at follow-up, glycosylated hemoglobin (A1C), and basal insulin requirements. Total cholesterol readings and fasting blood glucose (FBS) levels were considered secondary outcomes. Statistical analysis of the data was carried out using Statistical Package for the Social Sciences (SPSS) software.
Results
Mean BMI showed a reduction from 41.9 ± 5.4 to 31.4 ± 8.4 kg/m2. Mean %EWL after the follow-up period was 74.4 ± 25.3%. A1C levels failed to show a significant difference 12 months post-op (p = 0.189). Cholesterol levels did not display a significant decrease either (p = 0.447). When it came to insulin requirements, a significant difference was perceived, with the mean number of units of insulin required dropping from 76.6 to 18.2 (p = 0.026). FBS readings also showed a drop from 15.1 ± 3.8 to 7.8 ± 2.9 mmol/L (p = 0.001).
Conclusions
Laparoscopic sleeve gastrectomy resulted in significant weight loss, comorbidity resolution as well as reduction in their insulin doses post-op. However, glycemic control does not seem to show significant improvement in these patients. Larger, more long-term studies are needed to reach a definite conclusion on this topic.
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Thorax Computed Tomography Findings in Patients with Erectile Dysfunction
Journal of Clinical Imaging Science 2017 7(1):25-25
Objective: Diabetes mellitus, smoking, dyslipidemia, and obesity play an important role in the etiology of erectile dysfunction, particularly in cases with vascular insufficiency. These risk factors also target the lungs due to their systemic effects. Materials and Methods: Patients with penile vascular insufficiency determined at Doppler ultrasonography and undergoing thoracic computerized tomography for various reasons were included in this study. A history of acute thoracic trauma, pneumonic consolidation, or pelvic surgery and trauma were regarded as exclusion criteria. Results: Thirty-seven male patients with identified vascular insufficiency (age 54.48 ± 13.62 years) were enrolled. Mass lesions with a malignant morphology were present in two patients. The most common mediastinal/vascular pathology was atherosclerosis, while the most common parenchymal lesion was emphysematous aeration. Other findings included parenchymal fibrotic bands, atelectasis, interstitial thickening, bronchiectasis, air trapping, aortic aneurysm, a dilated pulmonary artery, hiatal hernia, and pericardial effusion. Conclusion: Erectile dysfunction may be an early sign of cardiovascular diseases. Care must be taken in terms of existing or potential pulmonary pathologies in these patients due to their sharing common risk factors with systemic effects.
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User input in iterative design for prevention product development: leveraging interdisciplinary methods to optimize effectiveness
Abstract
The development of HIV-preventive topical vaginal microbicides has been challenged by a lack of sufficient adherence in later stage clinical trials to confidently evaluate effectiveness. This dilemma has highlighted the need to integrate translational research earlier in the drug development process, essentially applying behavioral science to facilitate the advances of basic science with respect to the uptake and use of biomedical prevention technologies. In the last several years, there has been an increasing recognition that the user experience, specifically the sensory experience, as well as the role of meaning-making elicited by those sensations, may play a more substantive role than previously thought. Importantly, the role of the user—their sensory perceptions, their judgements of those experiences, and their willingness to use a product—is critical in product uptake and consistent use post-marketing, ultimately realizing gains in global public health. Specifically, a successful prevention product requires an efficacious drug, an efficient drug delivery system, and an effective user. We present an integrated iterative drug development and user experience evaluation method to illustrate how user-centered formulation design can be iterated from the early stages of preclinical development to leverage the user experience. Integrating the user and their product experiences into the formulation design process may help optimize both the efficiency of drug delivery and the effectiveness of the user.
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Immunotoxicology of Metals
Publication date: 2017
Source:Reference Module in Biomedical Sciences
Author(s): M.D. Cohen
This review provides information on how our understanding of the immunotoxicology of select inorganic agents, that is, metals, has evolved over the past ≈40+ years. Specifically, it covers the literature to date dealing with arsenic, cadmium, chromium, nickel, vanadium, and zinc, in each of their various (in)organic forms with differing chemistries, sizes, and solubilities. For each metal, some background information regarding occupational/environmental levels that are readily encountered is presented. Thereafter, specific effects on humoral, cell-mediated, and innate immune functions are provided. For some metals, potential mechanisms of action are presented. Lastly, the article reports on information on immunotoxicologic mechanisms for these (and for silver and copper) that have been gleaned since the rise of proteomics, transcriptomics, genomics, etc., and even more recently, epigenomics (i.e., heritable changes). Though a large review, it is impossible to cover all metals, including some Readers may think merit more of a place here than presented. It certainly would be worthwhile to have had provided information on immunotoxicologic effects of aluminum, beryllium, lead, manganese, mercury, platinum, and/or iron. It is hoped subsequently, one or more authors will survey the literature covering those metals and provide a review of each alone—or several in compilation.
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Validation of an International Classification of Disease, Ninth Revision coding algorithm to identify decompressive craniectomy for stroke
Abstract
Background
Although International Classification of Disease, Ninth Revision, Clinical Modification (ICD9-CM) coding is the basis of administrative claims data, no study has validated an ICD9-CM algorithm to identify patients undergoing decompressive craniectomy for space-occupying supratentorial infarction.
Methods
Patients who underwent decompressive craniectomy for stroke at our institution were retrospectively identified and their associated ICD9-CM codes were extracted from billing data. An ICD9-CM algorithm was generated and its accuracy compared against physician review.
Results
A total of 10,925 neurosurgical operations were performed from December 2008 to March 2015, of which 46 (0.4%) were decompressive craniectomy for space-occupying stroke. The ICD9-CM procedure code for craniectomy (01.25) was only encoded in 67.4% of patients, while craniotomy (01.24) was used in 19.6% and lobectomy (01.39, 01.53, 01.59) in 13.1%. The ICD-9-CM algorithm included patients with a diagnosis codes for cerebral infarction (433.11, 434.01, 434.11, and 434.91) and a procedure code for craniotomy, craniectomy, or lobectomy. Patients were excluded with an ICD9-CM diagnosis code for brain tumor, intracranial abscess, subarachnoid hemorrhage, vertebrobasilar infarction, intracranial aneurysm, Moyamoya disease, intracranial venous sinus thrombosis, vertebral artery dissection, congenital cerebrovascular anomaly, head trauma or an ICD9-CM procedure code for laminectomy. This algorithm had a sensitivity of 97.8%, specificity of 99.9%, positive predictive value of 88.2%, and negative predictive value of 99.9%. The majority of false-positive results were patients who underwent evacuation of a primary intracerebral hematoma.
Conclusion
An ICD-9-CM algorithm based on diagnosis and procedure codes can effectively identify patients undergoing decompressive craniectomy for supratentorial stroke.
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False-Positive Uptake of Radioiodine in Renal Hamartoma in a Patient With Differentiated Thyroid Cancer.
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False-Positive Uptake of Radioiodine in Renal Hamartoma in a Patient With Differentiated Thyroid Cancer.
Clin Nucl Med. 2017 Jun 24;:
Authors: Shen G, Qi Z, Huang R, Liu B, Kuang A
Abstract
A 46-year-old woman with a history of papillary thyroid cancer status post total thyroidectomy underwent the second I radioiodine ablation therapy for lung metastases. Posttherapeutic whole-body I planar images showed diffuse uptake in the lungs and intense focal activity in both sides of the upper abdomen. SPECT/CT of the abdomen localized the uptake in the upper pole of the left kidney and the lower pole of the right kidney. The patient received bilateral partial nephrectomy with pathology demonstrating that these 2 renal lesions were renal hamartomas.
PMID: 28650888 [PubMed - as supplied by publisher]
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The role of monocyte subpopulations in vascular injury following partial and transient depletion
Abstract
The innate immunity system plays a critical role in vascular repair and restenosis development. Liposomes encapsulating bisphosphonates (LipBPs), but not free BPs, suppress neointima formation following vascular injury mediated in part by monocytes. The objective of this study was to elucidate the role of monocyte subpopulations on vascular healing following LipBP treatment. The potency- and dose-dependent treatment effect of clodronate (CLOD) and alendronate (ALN) liposomes on restenosis inhibition, total monocyte depletion, and monocytes subpopulation was studied. Rats subjected to carotid injury were treated by a single IV injection of LipBPs at the time of injury. Low- and high-dose LipALN treatment (3 and 10 mg/kg, respectively) resulted in a dose-dependent effect on restenosis development after 30 days. Both doses of LipALN resulted in a dose-dependent inhibition of restenosis, but only high dose of LipALN depleted monocytes (−60.1 ± 4.4%, 48 h post injury). Although LipCLOD treatment (at an equivalent potency to 3 mg/kg alendronate) significantly reduced monocyte levels (72.1 ± 6%), no restenosis inhibition was observed. The major finding of this study is the correlation found between monocyte subclasses and restenosis inhibition. Non-classical monocyte (NCM) levels were found higher in LipALN-treated rats, but lower in LipCLOD-treated rats, 24 h after injury and treatment. We suggest that the inhibition of circulating monocyte subpopulations is the predominant mechanism by which LipBPs prevent restenosis. The effect of LipBP treatment on the monocyte subpopulation correlates with the dose and potency of LipBPs.
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Current smoking is associated with extracranial carotid atherosclerotic stenosis but not with intracranial large artery disease
Abstract
Background
Accumulating evidence has shown that cigarette smoking is an important risk factor for ischemic stroke. However, it is not clear about the potential mechanisms through which cigarette smoking affects stroke risk. In the study, we aimed to investigate the relationship between cigarette smoking and the occurrence of extracranial (ECAS) and intracranial atherosclerotic stenosis (ICAS).
Methods
We analyzed patients enrolled in the Chinese intracranial atherosclerosis (CICAS), which was a prospective, multicenter, hospital-based cohort study. Smoking status was classified into never, former and current smoking. For those patients with current smoking, data on time duration (year) and extent (the number of cigarette smoked per day) was recorded and pack year of smoking was calculated. ICAS was evaluated with 3-dimentional time-of-flight MRA and ECAS was evaluated with cervical ultrasonography or contrast-enhanced MRA. Multivariable Logistic regression was performed to identify the association between smoking status and the occurrence of ECAS and ICAS.
Results
A total of 2656 patients (92.7%) of acute ischemic stroke and 208 (7.3%) of transient ischemic attack were analyzed. The mean age was 61.9 ± 11.2 and 67.8% were male. There were 141 (4.9%) patients had only ECAS, 1074 (37.5%) had only ICAS, and 261 (9.1%) had both ECAS and ICAS. Current smoking was significantly associated with the occurrence of ECAS (adjusted OR = 1.47, 95% CI = 1.09–1.99, P < 0.01). In addition, with 1 year of smoking increment, the risk of ECAS increased by 1.1% (adjusted OR = 1.011; 95% CI = 1.003–1.019; P = 0.005); with one cigarette smoked per day increment, the risk of ECAS increased by 1.0% (adjusted OR = 1.010; 95% CI = 1.001–1.020; P = 0.03); and with one pack year of smoking increment, the risk of ECAS increased by 0.7% (adjusted OR = 1.007; 95% CI = 1.002–1.012; P < 0.01). However, no significant association was found between smoking status and the occurrence of ICAS.
Conclusion
A dose–response relationship was identified between cigarette smoking and the occurrence of ECAS, but not ICAS. Further studies on molecular mechanisms were warranted.
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Occult Renal Granulomatous Inflammatory Lesions in Granulomatosis with Polyangiitis Detected by 18F-FDG PET/CT.
| Related Articles |
Occult Renal Granulomatous Inflammatory Lesions in Granulomatosis with Polyangiitis Detected by 18F-FDG PET/CT.
Clin Nucl Med. 2017 Jun 24;:
Authors: Fu Z, Liu M, Li Z, Zhang J, Li Q
Abstract
A 33-year-old woman with a 7-month history of granulomatosis with polyangiitis F-FDG PET/CT scan due to low-grade intermittent fever and elevation of serum inflammatory markers, which revealed multiple hypermetabolic lesions in bilateral kidneys. Biopsy of a lesion showed granulomatosis with polyangiitis, consistent with renal involvement of granulomatosis with polyangiitis.
PMID: 28650889 [PubMed - as supplied by publisher]
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Postmastectomy Chronic Pain in Breast Cancer Survivors: an Exploratory Study on Prevalence, Characteristics, Risk Factors, and Impact on Quality of Life
Abstract
Chronic pain following surgery for breast cancer affects over 50% of patients and is one of the important issues adversely affecting the quality of life of breast cancer survivors. However, there is little information about this problem in Indian patients. Hence, this descriptive study was planned with the objectives to explore the prevalence, pain characteristics, risk factors of postmastectomy chronic pain (PMCP), and its impact on quality of life (QOL). During the period of February 2014 to January 2017, a total of 215 breast cancer survivors, coming for follow-up visits to surgery outpatients department, were evaluated for complaint of PMCP, defined as pain over anterior chest wall, axilla, or ipsilateral arm, which was persistent for more than 3 months after breast cancer surgery. Evaluation of pain severity was done by visual analogue scale (VAS), and characteristic of pain was assessed by Neuropathic Pain Symptom Inventory (NPSI). Body charts were used to define location of pain. Assessment of QOL was done by FACT-B questionnaire. Overall prevalence of PMCP was 41.4 and 19.5% patients had clinically significant pain scores of ≥3. Character of pain was mainly described as pins and needles (59.5%) and burning sensation (30%), and the most common site of pain (52%) was around the mastectomy scar. Younger age was significantly correlated with higher pain scores. Patients with higher pain scores had poorer QOL scores. (104.0 ± 19.27 with a VAS score of <3 vs. 85.26 ± 14.00 with a VAS score of ≥3, p < 0.001). Emotional distress was an important contributor to poor QOL. PMCP is a common problem in Indian breast cancer survivors, which causes considerable emotional distress and negatively impacts QOL. Treating physicians should evaluate and appropriately address this important survivorship issue.
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Chemotherapy-induced cardiomyopathy caused by Pemetrexed
Summary
Chemotherapy-related cardiac toxicity is a rare but serious adverse event in patients with cancer. Thus far, no case of serious cardiac toxicity of pemetrexed has been reported. We describe the case of a patient with advanced lung cancer and cardiomyopathy due to pemetrexed. A 59-year-old woman visited our hospital, and we found abnormal findings on a chest radiograph. She was diagnosed as having stage IV lung adenocarcinoma. Chemotherapy with cisplatin and pemetrexed every 3 weeks was initiated. After four cycles of chemotherapy, maintenance chemotherapy with pemetrexed was administered every 3 weeks. During the seventeenth cycle of pemetrexed, she had shortness of breath in her daily life. A chest radiograph showed an enlarged cardiothoracic ratio (66%), and the transthoracic echocardiogram demonstrated expansion of the left ventricle (diastolic diameter, 67 mm), severe global hypokinesis, and reduced left ventricular ejection fraction (28%). The coronary angiogram showed no coronary constriction. There was no delayed accumulation on the contrast-enhanced cardiac magnetic resonance imaging scan. After right heart catheterization, pathological results of a myocardial biopsy from the ventricular septum indicated no cardiac muscle hypertrophy, cardiac fibrosis, inflammatory cell infiltration, or myocyte disarray. Eventually, she was diagnosed as having pemetrexed-induced cardiomyopathy. Pemetrexed was discontinued, and furosemide, enalapril, and carvedilol were started. Then her symptoms and cardiac function improved. Early detection and discontinuation of causative agents are the most important treatment strategies in similar patients. Diuretics, angiotensin-conversion enzyme inhibitors, and beta-blockers may be effective for treating heart failure.
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Pretreatment Primary Tumor SUVmax on 18F-FDG PET/CT Images Predicts Outcomes in Patients With Salivary Gland Carcinoma Treated With Definitive Intensity-Modulated Radiation Therapy.
| Related Articles |
Pretreatment Primary Tumor SUVmax on 18F-FDG PET/CT Images Predicts Outcomes in Patients With Salivary Gland Carcinoma Treated With Definitive Intensity-Modulated Radiation Therapy.
Clin Nucl Med. 2017 Jun 24;:
Authors: Hsieh CE, Ho KC, Hsieh CH, Yen TC, Liao CT, Wang HM, Lin CY
Abstract
PURPOSE: The aim of this study was to investigate the prognostic significance of F-FDG uptake in salivary gland carcinoma (SGC) patients treated with definitive intensity-modulated radiation therapy (IMRT).
METHODS: We retrospectively examined 46 SGC patients who received pretreatment F-FDG PET/CT and definitive IMRT between 2007 and 2014. Most tumors were located in the minor salivary glands (n = 35 [76%]). Forty-six percent (n = 21) of the participants had unresectable disease. The median radiation dose was 72 Gy. Treatment outcomes were examined in relation to clinicopathologic parameters and pretreatment primary tumor SUVmax on F-FDG PET/CT.
RESULTS: After a median follow-up of 54 months, the 5-year locoregional progression-free survival (LRPFS), distant metastasis-free survival, progression-free survival (PFS), and overall survival (OS) rates were 77%, 75%, 63%, and 61%, respectively. The median primary tumor SUVmax was 7.4 (range, 2.3-23.6), and the optimal cutoff value that maximized the prognostic significance for 5-year PFS was 7.4 (P = 0.006). Patients with a high SUVmax (≥7.4) had significantly lower 5-year LRPFS (P = 0.007), distant metastasis-free survival (P = 0.046), and OS (P = 0.013) rates than those with a low SUVmax (<7.4). Multivariate analyses identified SUVmax as the only independent predictor of LRPFS (P = 0.023) and PFS (P = 0.003), whereas both the performance score (P < 0.001) and SUVmax (P = 0.022) were independently associated with OS.
CONCLUSIONS: Pretreatment primary tumor SUVmax on F-FDG PET/CT predicts treatment outcomes in SGC patients. Definitive IMRT is an effective treatment strategy when organ function and cosmesis need to be preserved.
PMID: 28650891 [PubMed - as supplied by publisher]
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Occupational Immunotoxicology
Publication date: 2017
Source:Reference Module in Biomedical Sciences
Author(s): S.E. Anderson, B.J. Meade
Individuals working in a variety of occupational industries and sectors are potentially exposed to biological, chemical, and hazardous agents with dermal and respiratory being the two most common routes of exposure. These exposures can potentially result in numerous diseases and can adversely affect an individual's health and capacity to perform at work resulting in significant economic losses. Occupational immune diseases are some of the most common illnesses that affect workers including inflammation, allergy, respiratory disease, autoimmunity, or other immune modulation resulting in suppression following exposure in the work environment. Due to the complexity of the immune system, the identification of agents that induce immunotoxicity requires specific assays. Various organizations have proposed different approaches to immunotoxicity testing that include validated immune testing protocols that measure diverse immunological biomarkers and endpoints. This chapter provides descriptions of the most commonly recognized occupational immune diseases.
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Hydrazinyl arylthiazole based pyridine scaffolds: Synthesis, structural characterization, in vitro α-glucosidase inhibitory activity, and in silico studies
Publication date: Available online 26 June 2017
Source:European Journal of Medicinal Chemistry
Author(s): Farman Ali, Khalid Mohammed Khan, Uzma Salar, Muhammad Taha, Nor Hadiani Ismail, Abdul Wadood, Muhammad Riaz, Shahnaz Perveen
Acarbose, miglitol, and voglibose are the inhibitors of α-glucosidase enzyme and being clinically used for the management of type-II diabetes mellitus. However, many adverse effects are also associated with them. So, the development of new therapeutic agents is an utmost interest in medicinal chemistry research. Current study is based on the identification of new α-glucosidase inhibitors. For that purpose, hydrazinyl arylthiazole based pyridine derivatives 1–39 were synthesized via two step reaction and fully characterized by spectroscopic techniques EI-MS, HREI-MS, 1H-, and 13C-NMR. However, stereochemistry of the iminic bond was confirmed by NOESY. All compounds were subjected to in vitro α-glucosidase inhibitory activity and found many folds active (IC50 = 1.40 ± 0.01–236.10 ± 2.20 μM) as compared to the standard acarbose having IC50 value of 856.45 ± 5.60 μM. A limited structure-activity relationship was carried out in order to make a presumption about the substituent's effect on inhibitory activity which predicted that substituents of more negative inductive effect played important role in the activity as compared to the substituents of less negative inductive effect. However, in order to have a good understanding of ligand enzyme interactions, molecular docking study was also conducted. In silico study was confirmed that substituents like halogens (Cl) and nitro (NO2) which have negative inductive effect were found to make important interactions with active site residues.
Graphical abstract
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Chemical- and Drug-Induced Asthma
Publication date: 2017
Source:Reference Module in Biomedical Sciences
Author(s): B.J. Kilburg-Basnyat, M.K. Selgrade, K.M. Gowdy
Each year, approximately 300 million people worldwide are diagnosed with asthma, and more than 250,000 deaths annually are attributed to asthma. However, the sources and mechanisms behind the development of asthma are diverse. High-molecular-weight proteins, including detergent enzymes and common allergens, contribute to an immunoglobulin E (IgE)-mediated atopic asthma response. Low-molecular-weight chemicals typically are haptens that form hapten–protein complexes resulting in IgE-mediated or IgE-independent immune-mediated asthma. Hapten–protein exposures typically occur at the workplace and can include acid anhydrides, isocyanates, as well as others. Irritant-induced asthma typically results from a single, accidental exposure to a highly concentrated irritant in the workplace that induces pulmonary damage by releasing proinflammatory mediators that lead to asthma. Additionally, ingestion of certain medications including aspirin, β-blockers, or angiotensin-converting enzyme inhibitors can cause drug-induced asthma by enzymatic reactions leading to the production of proinflammatory mediators and modulation of smooth muscle function. Overall, the diversity of asthma makes this prevalent lung disease difficult to diagnose and manage. This article compares and contrasts phenotypes, mechanisms, and possible treatments for these differing types of drug- and chemical-induced asthma that are currently understudied.
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Solitary Choroidal Metastasis From Lung Adenocarcinoma on FDG PET/CT.
| Related Articles |
Solitary Choroidal Metastasis From Lung Adenocarcinoma on FDG PET/CT.
Clin Nucl Med. 2017 Jun 24;:
Authors: Li ZG
Abstract
Solitary choroidal metastasis as an initial presentation of lung cancer is rare. A 67-year-old woman who initially presented with a 3-month history of blurred vision in the right eye was suggestive of choroidal melanoma on MRI. Preoperatively, a pulmonary mass was found on x-ray. She was referred for an FDG PET/CT imaging, which revealed a choroidal lesion with minimal FDG uptake in right eye and increased FDG activity in the known lung mass. A pathological diagnosis of metastatic lung adenocarcinoma was made after enucleation of the right eyeball.
PMID: 28650890 [PubMed - as supplied by publisher]
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Sleep quality and communication aspects in children
To correlate quality of life of children in terms of sleep, with their oral language skills, auditory processing and orofacial myofunctional aspects.
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Gastric Bypass and Synchronous Cholecystectomy: Not Only Numbers
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Uterine Lipoleiomyoma: A Report of Two Cases
Journal of Clinical Imaging Science 2017 7(1):26-26
We report two cases of uterine lipoleiomyoma in postmenopausal women of ages 52 and 55 years, who presented with complaints of leukorrhea and lower abdominal pain, respectively. Lipoleiomyoma is a rare benign variant of leiomyoma, having an incidence of 0.03%–0.2%. These are benign pelvic tumors which are usually asymptomatic and commonly occur in obese postmenopausal women. However, they can occasionally present with typical leiomyoma symptoms. Imaging plays a crucial role in the diagnosis of benign pelvic tumors. Ultrasonography is the first imaging modality for diagnosis of pelvic tumors in females. Computed tomography and magnetic resonance imaging are specific in demonstrating the uterine origin and fat component.
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Transplantation of human fetal pancreatic progenitor cells ameliorates renal injury in streptozotocin-induced diabetic nephropathy
Diabetic nephropathy (DN) is a severe complication of diabetes mellitus (DM). Pancreas or islet transplantation has been reported to prevent the development of DN lesions and ameliorate or reverse existing glo...
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Thorax Computed Tomography Findings in Patients with Erectile Dysfunction
Journal of Clinical Imaging Science 2017 7(1):25-25
Objective: Diabetes mellitus, smoking, dyslipidemia, and obesity play an important role in the etiology of erectile dysfunction, particularly in cases with vascular insufficiency. These risk factors also target the lungs due to their systemic effects. Materials and Methods: Patients with penile vascular insufficiency determined at Doppler ultrasonography and undergoing thoracic computerized tomography for various reasons were included in this study. A history of acute thoracic trauma, pneumonic consolidation, or pelvic surgery and trauma were regarded as exclusion criteria. Results: Thirty-seven male patients with identified vascular insufficiency (age 54.48 ± 13.62 years) were enrolled. Mass lesions with a malignant morphology were present in two patients. The most common mediastinal/vascular pathology was atherosclerosis, while the most common parenchymal lesion was emphysematous aeration. Other findings included parenchymal fibrotic bands, atelectasis, interstitial thickening, bronchiectasis, air trapping, aortic aneurysm, a dilated pulmonary artery, hiatal hernia, and pericardial effusion. Conclusion: Erectile dysfunction may be an early sign of cardiovascular diseases. Care must be taken in terms of existing or potential pulmonary pathologies in these patients due to their sharing common risk factors with systemic effects.
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Postmastectomy Chronic Pain in Breast Cancer Survivors: an Exploratory Study on Prevalence, Characteristics, Risk Factors, and Impact on Quality of Life
Abstract
Chronic pain following surgery for breast cancer affects over 50% of patients and is one of the important issues adversely affecting the quality of life of breast cancer survivors. However, there is little information about this problem in Indian patients. Hence, this descriptive study was planned with the objectives to explore the prevalence, pain characteristics, risk factors of postmastectomy chronic pain (PMCP), and its impact on quality of life (QOL). During the period of February 2014 to January 2017, a total of 215 breast cancer survivors, coming for follow-up visits to surgery outpatients department, were evaluated for complaint of PMCP, defined as pain over anterior chest wall, axilla, or ipsilateral arm, which was persistent for more than 3 months after breast cancer surgery. Evaluation of pain severity was done by visual analogue scale (VAS), and characteristic of pain was assessed by Neuropathic Pain Symptom Inventory (NPSI). Body charts were used to define location of pain. Assessment of QOL was done by FACT-B questionnaire. Overall prevalence of PMCP was 41.4 and 19.5% patients had clinically significant pain scores of ≥3. Character of pain was mainly described as pins and needles (59.5%) and burning sensation (30%), and the most common site of pain (52%) was around the mastectomy scar. Younger age was significantly correlated with higher pain scores. Patients with higher pain scores had poorer QOL scores. (104.0 ± 19.27 with a VAS score of <3 vs. 85.26 ± 14.00 with a VAS score of ≥3, p < 0.001). Emotional distress was an important contributor to poor QOL. PMCP is a common problem in Indian breast cancer survivors, which causes considerable emotional distress and negatively impacts QOL. Treating physicians should evaluate and appropriately address this important survivorship issue.
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Pathophysiology of esophageal impairment due to button battery ingestion
The increased use of button batteries with high energy densities in devices of daily life presents a high risk of injury, especially for toddlers and young children. If an accidental ingestion of a button battery occurs, this foreign body can become caught in the constrictions of the esophagus and cause serious damage to the adjacent tissue layers. The consequences can be ulcerations, perforations with fistula formation and damage to the surrounding anatomical structures. In order to gain a better understanding of the pathophysiology after ingestion, we carried out systematic studies on fresh preparations of porcine esophagi.
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False-Positive Uptake of Radioiodine in Renal Hamartoma in a Patient With Differentiated Thyroid Cancer.
| Related Articles |
False-Positive Uptake of Radioiodine in Renal Hamartoma in a Patient With Differentiated Thyroid Cancer.
Clin Nucl Med. 2017 Jun 24;:
Authors: Shen G, Qi Z, Huang R, Liu B, Kuang A
Abstract
A 46-year-old woman with a history of papillary thyroid cancer status post total thyroidectomy underwent the second I radioiodine ablation therapy for lung metastases. Posttherapeutic whole-body I planar images showed diffuse uptake in the lungs and intense focal activity in both sides of the upper abdomen. SPECT/CT of the abdomen localized the uptake in the upper pole of the left kidney and the lower pole of the right kidney. The patient received bilateral partial nephrectomy with pathology demonstrating that these 2 renal lesions were renal hamartomas.
PMID: 28650888 [PubMed - as supplied by publisher]
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User input in iterative design for prevention product development: leveraging interdisciplinary methods to optimize effectiveness
Abstract
The development of HIV-preventive topical vaginal microbicides has been challenged by a lack of sufficient adherence in later stage clinical trials to confidently evaluate effectiveness. This dilemma has highlighted the need to integrate translational research earlier in the drug development process, essentially applying behavioral science to facilitate the advances of basic science with respect to the uptake and use of biomedical prevention technologies. In the last several years, there has been an increasing recognition that the user experience, specifically the sensory experience, as well as the role of meaning-making elicited by those sensations, may play a more substantive role than previously thought. Importantly, the role of the user—their sensory perceptions, their judgements of those experiences, and their willingness to use a product—is critical in product uptake and consistent use post-marketing, ultimately realizing gains in global public health. Specifically, a successful prevention product requires an efficacious drug, an efficient drug delivery system, and an effective user. We present an integrated iterative drug development and user experience evaluation method to illustrate how user-centered formulation design can be iterated from the early stages of preclinical development to leverage the user experience. Integrating the user and their product experiences into the formulation design process may help optimize both the efficiency of drug delivery and the effectiveness of the user.
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Eicosapentaenoic acid modulates the synergistic action of CREB1 and ID/E2A family members in the rat pup brain and mouse embryonic stem cells
Publication date: Available online 27 June 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Maurizio Rossi, Martin Spichty, Lucilla Attorri, Chiara Distante, Clara Nervi, Serafina Salvati, Luigi Vitelli
The aim of this study was to investigate the molecular mechanism by which eicosapentaenoic acid (EPA) may exert neuroprotective effects through an "EPA- cyclic AMP response element-binding protein (CREB)" signaling pathway. The current study reveals that EPA modulates the exquisite interplay of interaction of CREB1 with the inhibitor of DNA binding (ID) and E2A family members, thereby delivering mechanistic insights into specific neural differentiation program. In this scenario, our work provides evidence for the capability of CREB1 to sequester ID:E2A family members in brain tissues and neural differentiating mouse embryonic stem cells (mESCs) through formation of a [CREB1]2:ID2:E47 tetrameric complex. In essence, the molecular function of CREB1 is to dynamically regulate the location-specific assembly or disassembly of basic-helix-loop-helix (bHLH):HLH protein complexes to mediate the activation of neural/glial target genes. Together, these findings support the one-to-many binding mechanism of CREB1 and indicate that EPA treatment potentiates the integration of CREB dependent signaling with HLH/bHLH transcriptional network, adding specificity to the CREB1-mediated gene regulation during neural/glial differentiation. Our current research on the EPA-CREB axis could reveal new molecular targets for treating neurogenerative disease.
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Occult Renal Granulomatous Inflammatory Lesions in Granulomatosis with Polyangiitis Detected by 18F-FDG PET/CT.
| Related Articles |
Occult Renal Granulomatous Inflammatory Lesions in Granulomatosis with Polyangiitis Detected by 18F-FDG PET/CT.
Clin Nucl Med. 2017 Jun 24;:
Authors: Fu Z, Liu M, Li Z, Zhang J, Li Q
Abstract
A 33-year-old woman with a 7-month history of granulomatosis with polyangiitis F-FDG PET/CT scan due to low-grade intermittent fever and elevation of serum inflammatory markers, which revealed multiple hypermetabolic lesions in bilateral kidneys. Biopsy of a lesion showed granulomatosis with polyangiitis, consistent with renal involvement of granulomatosis with polyangiitis.
PMID: 28650889 [PubMed - as supplied by publisher]
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Barrett’s Oesophagus and Oesophageal Carcinogenesis Following Obesity Surgery: Helicobacter Pylori Must Be Eradicated?
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Immunotoxicology of Metals
Publication date: 2017
Source:Reference Module in Biomedical Sciences
Author(s): M.D. Cohen
This review provides information on how our understanding of the immunotoxicology of select inorganic agents, that is, metals, has evolved over the past ≈40+ years. Specifically, it covers the literature to date dealing with arsenic, cadmium, chromium, nickel, vanadium, and zinc, in each of their various (in)organic forms with differing chemistries, sizes, and solubilities. For each metal, some background information regarding occupational/environmental levels that are readily encountered is presented. Thereafter, specific effects on humoral, cell-mediated, and innate immune functions are provided. For some metals, potential mechanisms of action are presented. Lastly, the article reports on information on immunotoxicologic mechanisms for these (and for silver and copper) that have been gleaned since the rise of proteomics, transcriptomics, genomics, etc., and even more recently, epigenomics (i.e., heritable changes). Though a large review, it is impossible to cover all metals, including some Readers may think merit more of a place here than presented. It certainly would be worthwhile to have had provided information on immunotoxicologic effects of aluminum, beryllium, lead, manganese, mercury, platinum, and/or iron. It is hoped subsequently, one or more authors will survey the literature covering those metals and provide a review of each alone—or several in compilation.
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Chemical- and Drug-Induced Asthma
Publication date: 2017
Source:Reference Module in Biomedical Sciences
Author(s): B.J. Kilburg-Basnyat, M.K. Selgrade, K.M. Gowdy
Each year, approximately 300 million people worldwide are diagnosed with asthma, and more than 250,000 deaths annually are attributed to asthma. However, the sources and mechanisms behind the development of asthma are diverse. High-molecular-weight proteins, including detergent enzymes and common allergens, contribute to an immunoglobulin E (IgE)-mediated atopic asthma response. Low-molecular-weight chemicals typically are haptens that form hapten–protein complexes resulting in IgE-mediated or IgE-independent immune-mediated asthma. Hapten–protein exposures typically occur at the workplace and can include acid anhydrides, isocyanates, as well as others. Irritant-induced asthma typically results from a single, accidental exposure to a highly concentrated irritant in the workplace that induces pulmonary damage by releasing proinflammatory mediators that lead to asthma. Additionally, ingestion of certain medications including aspirin, β-blockers, or angiotensin-converting enzyme inhibitors can cause drug-induced asthma by enzymatic reactions leading to the production of proinflammatory mediators and modulation of smooth muscle function. Overall, the diversity of asthma makes this prevalent lung disease difficult to diagnose and manage. This article compares and contrasts phenotypes, mechanisms, and possible treatments for these differing types of drug- and chemical-induced asthma that are currently understudied.
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Laparoscopic Sleeve Gastrectomy for the Management of Type 1 Diabetes Mellitus
Abstract
Background
The prevalence of obesity is on a continuous rise worldwide, with major studies clearly correlating obesity with the development of chronic metabolic disorders including type 2 diabetes. Bariatric surgery has proven to be beneficial in the management of this condition; however, a limited number of studies exist on its effect on type 1 diabetes.
Objective
The objective of this study is to evaluate the outcome of laparoscopic sleeve gastrectomy for the management of patients with type 1 diabetes (DM1).
Setting
This is a retrospective cohort study conducted in a university hospital and private practice in Kuwait.
Research Design and Methods
Analysis was conducted on 10 patients diagnosed with type 1 diabetes that underwent bariatric surgery from October 2008 until December 2016 at Amiri Hospital and Royale Hayat Hospital, Kuwait. Primary parameters included body mass index (BMI), % excess weight (%EWL) loss at follow-up, glycosylated hemoglobin (A1C), and basal insulin requirements. Total cholesterol readings and fasting blood glucose (FBS) levels were considered secondary outcomes. Statistical analysis of the data was carried out using Statistical Package for the Social Sciences (SPSS) software.
Results
Mean BMI showed a reduction from 41.9 ± 5.4 to 31.4 ± 8.4 kg/m2. Mean %EWL after the follow-up period was 74.4 ± 25.3%. A1C levels failed to show a significant difference 12 months post-op (p = 0.189). Cholesterol levels did not display a significant decrease either (p = 0.447). When it came to insulin requirements, a significant difference was perceived, with the mean number of units of insulin required dropping from 76.6 to 18.2 (p = 0.026). FBS readings also showed a drop from 15.1 ± 3.8 to 7.8 ± 2.9 mmol/L (p = 0.001).
Conclusions
Laparoscopic sleeve gastrectomy resulted in significant weight loss, comorbidity resolution as well as reduction in their insulin doses post-op. However, glycemic control does not seem to show significant improvement in these patients. Larger, more long-term studies are needed to reach a definite conclusion on this topic.
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Hydrazinyl arylthiazole based pyridine scaffolds: Synthesis, structural characterization, in vitro α-glucosidase inhibitory activity, and in silico studies
Publication date: Available online 26 June 2017
Source:European Journal of Medicinal Chemistry
Author(s): Farman Ali, Khalid Mohammed Khan, Uzma Salar, Muhammad Taha, Nor Hadiani Ismail, Abdul Wadood, Muhammad Riaz, Shahnaz Perveen
Acarbose, miglitol, and voglibose are the inhibitors of α-glucosidase enzyme and being clinically used for the management of type-II diabetes mellitus. However, many adverse effects are also associated with them. So, the development of new therapeutic agents is an utmost interest in medicinal chemistry research. Current study is based on the identification of new α-glucosidase inhibitors. For that purpose, hydrazinyl arylthiazole based pyridine derivatives 1–39 were synthesized via two step reaction and fully characterized by spectroscopic techniques EI-MS, HREI-MS, 1H-, and 13C-NMR. However, stereochemistry of the iminic bond was confirmed by NOESY. All compounds were subjected to in vitro α-glucosidase inhibitory activity and found many folds active (IC50 = 1.40 ± 0.01–236.10 ± 2.20 μM) as compared to the standard acarbose having IC50 value of 856.45 ± 5.60 μM. A limited structure-activity relationship was carried out in order to make a presumption about the substituent's effect on inhibitory activity which predicted that substituents of more negative inductive effect played important role in the activity as compared to the substituents of less negative inductive effect. However, in order to have a good understanding of ligand enzyme interactions, molecular docking study was also conducted. In silico study was confirmed that substituents like halogens (Cl) and nitro (NO2) which have negative inductive effect were found to make important interactions with active site residues.
Graphical abstract
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Assessment of weight gain following adenotonsillectomy in children with Down syndrome
Adenotonsillectomy (T&A) has been associated with postoperative weight gain in children. The purpose of this study is to determine whether a similar association exists in children with Down syndrome (DS).
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Occupational Immunotoxicology
Publication date: 2017
Source:Reference Module in Biomedical Sciences
Author(s): S.E. Anderson, B.J. Meade
Individuals working in a variety of occupational industries and sectors are potentially exposed to biological, chemical, and hazardous agents with dermal and respiratory being the two most common routes of exposure. These exposures can potentially result in numerous diseases and can adversely affect an individual's health and capacity to perform at work resulting in significant economic losses. Occupational immune diseases are some of the most common illnesses that affect workers including inflammation, allergy, respiratory disease, autoimmunity, or other immune modulation resulting in suppression following exposure in the work environment. Due to the complexity of the immune system, the identification of agents that induce immunotoxicity requires specific assays. Various organizations have proposed different approaches to immunotoxicity testing that include validated immune testing protocols that measure diverse immunological biomarkers and endpoints. This chapter provides descriptions of the most commonly recognized occupational immune diseases.
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Pretreatment Primary Tumor SUVmax on 18F-FDG PET/CT Images Predicts Outcomes in Patients With Salivary Gland Carcinoma Treated With Definitive Intensity-Modulated Radiation Therapy.
| Related Articles |
Pretreatment Primary Tumor SUVmax on 18F-FDG PET/CT Images Predicts Outcomes in Patients With Salivary Gland Carcinoma Treated With Definitive Intensity-Modulated Radiation Therapy.
Clin Nucl Med. 2017 Jun 24;:
Authors: Hsieh CE, Ho KC, Hsieh CH, Yen TC, Liao CT, Wang HM, Lin CY
Abstract
PURPOSE: The aim of this study was to investigate the prognostic significance of F-FDG uptake in salivary gland carcinoma (SGC) patients treated with definitive intensity-modulated radiation therapy (IMRT).
METHODS: We retrospectively examined 46 SGC patients who received pretreatment F-FDG PET/CT and definitive IMRT between 2007 and 2014. Most tumors were located in the minor salivary glands (n = 35 [76%]). Forty-six percent (n = 21) of the participants had unresectable disease. The median radiation dose was 72 Gy. Treatment outcomes were examined in relation to clinicopathologic parameters and pretreatment primary tumor SUVmax on F-FDG PET/CT.
RESULTS: After a median follow-up of 54 months, the 5-year locoregional progression-free survival (LRPFS), distant metastasis-free survival, progression-free survival (PFS), and overall survival (OS) rates were 77%, 75%, 63%, and 61%, respectively. The median primary tumor SUVmax was 7.4 (range, 2.3-23.6), and the optimal cutoff value that maximized the prognostic significance for 5-year PFS was 7.4 (P = 0.006). Patients with a high SUVmax (≥7.4) had significantly lower 5-year LRPFS (P = 0.007), distant metastasis-free survival (P = 0.046), and OS (P = 0.013) rates than those with a low SUVmax (<7.4). Multivariate analyses identified SUVmax as the only independent predictor of LRPFS (P = 0.023) and PFS (P = 0.003), whereas both the performance score (P < 0.001) and SUVmax (P = 0.022) were independently associated with OS.
CONCLUSIONS: Pretreatment primary tumor SUVmax on F-FDG PET/CT predicts treatment outcomes in SGC patients. Definitive IMRT is an effective treatment strategy when organ function and cosmesis need to be preserved.
PMID: 28650891 [PubMed - as supplied by publisher]
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Predictive Value of C-Reactive Protein for Complications Post-Laparoscopic Roux-en-Y Gastric Bypass
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Validation of an International Classification of Disease, Ninth Revision coding algorithm to identify decompressive craniectomy for stroke
Abstract
Background
Although International Classification of Disease, Ninth Revision, Clinical Modification (ICD9-CM) coding is the basis of administrative claims data, no study has validated an ICD9-CM algorithm to identify patients undergoing decompressive craniectomy for space-occupying supratentorial infarction.
Methods
Patients who underwent decompressive craniectomy for stroke at our institution were retrospectively identified and their associated ICD9-CM codes were extracted from billing data. An ICD9-CM algorithm was generated and its accuracy compared against physician review.
Results
A total of 10,925 neurosurgical operations were performed from December 2008 to March 2015, of which 46 (0.4%) were decompressive craniectomy for space-occupying stroke. The ICD9-CM procedure code for craniectomy (01.25) was only encoded in 67.4% of patients, while craniotomy (01.24) was used in 19.6% and lobectomy (01.39, 01.53, 01.59) in 13.1%. The ICD-9-CM algorithm included patients with a diagnosis codes for cerebral infarction (433.11, 434.01, 434.11, and 434.91) and a procedure code for craniotomy, craniectomy, or lobectomy. Patients were excluded with an ICD9-CM diagnosis code for brain tumor, intracranial abscess, subarachnoid hemorrhage, vertebrobasilar infarction, intracranial aneurysm, Moyamoya disease, intracranial venous sinus thrombosis, vertebral artery dissection, congenital cerebrovascular anomaly, head trauma or an ICD9-CM procedure code for laminectomy. This algorithm had a sensitivity of 97.8%, specificity of 99.9%, positive predictive value of 88.2%, and negative predictive value of 99.9%. The majority of false-positive results were patients who underwent evacuation of a primary intracerebral hematoma.
Conclusion
An ICD-9-CM algorithm based on diagnosis and procedure codes can effectively identify patients undergoing decompressive craniectomy for supratentorial stroke.
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Assessment of complete unilateral cleft lip and palate treatment outcome using EUROCRAN index and associated factors
Assessment of treatment outcome is the only non-invasive approach to identify the effects of cleft lip and palate repair and modify management accordingly. Here the aim is to assess the outcome of complete unilateral cleft lip and palate (CUCLP) patients using EUROCRAN index and to check whether there are any factors associated with the treatment outcome.
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Current smoking is associated with extracranial carotid atherosclerotic stenosis but not with intracranial large artery disease
Abstract
Background
Accumulating evidence has shown that cigarette smoking is an important risk factor for ischemic stroke. However, it is not clear about the potential mechanisms through which cigarette smoking affects stroke risk. In the study, we aimed to investigate the relationship between cigarette smoking and the occurrence of extracranial (ECAS) and intracranial atherosclerotic stenosis (ICAS).
Methods
We analyzed patients enrolled in the Chinese intracranial atherosclerosis (CICAS), which was a prospective, multicenter, hospital-based cohort study. Smoking status was classified into never, former and current smoking. For those patients with current smoking, data on time duration (year) and extent (the number of cigarette smoked per day) was recorded and pack year of smoking was calculated. ICAS was evaluated with 3-dimentional time-of-flight MRA and ECAS was evaluated with cervical ultrasonography or contrast-enhanced MRA. Multivariable Logistic regression was performed to identify the association between smoking status and the occurrence of ECAS and ICAS.
Results
A total of 2656 patients (92.7%) of acute ischemic stroke and 208 (7.3%) of transient ischemic attack were analyzed. The mean age was 61.9 ± 11.2 and 67.8% were male. There were 141 (4.9%) patients had only ECAS, 1074 (37.5%) had only ICAS, and 261 (9.1%) had both ECAS and ICAS. Current smoking was significantly associated with the occurrence of ECAS (adjusted OR = 1.47, 95% CI = 1.09–1.99, P < 0.01). In addition, with 1 year of smoking increment, the risk of ECAS increased by 1.1% (adjusted OR = 1.011; 95% CI = 1.003–1.019; P = 0.005); with one cigarette smoked per day increment, the risk of ECAS increased by 1.0% (adjusted OR = 1.010; 95% CI = 1.001–1.020; P = 0.03); and with one pack year of smoking increment, the risk of ECAS increased by 0.7% (adjusted OR = 1.007; 95% CI = 1.002–1.012; P < 0.01). However, no significant association was found between smoking status and the occurrence of ICAS.
Conclusion
A dose–response relationship was identified between cigarette smoking and the occurrence of ECAS, but not ICAS. Further studies on molecular mechanisms were warranted.
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The role of monocyte subpopulations in vascular injury following partial and transient depletion
Abstract
The innate immunity system plays a critical role in vascular repair and restenosis development. Liposomes encapsulating bisphosphonates (LipBPs), but not free BPs, suppress neointima formation following vascular injury mediated in part by monocytes. The objective of this study was to elucidate the role of monocyte subpopulations on vascular healing following LipBP treatment. The potency- and dose-dependent treatment effect of clodronate (CLOD) and alendronate (ALN) liposomes on restenosis inhibition, total monocyte depletion, and monocytes subpopulation was studied. Rats subjected to carotid injury were treated by a single IV injection of LipBPs at the time of injury. Low- and high-dose LipALN treatment (3 and 10 mg/kg, respectively) resulted in a dose-dependent effect on restenosis development after 30 days. Both doses of LipALN resulted in a dose-dependent inhibition of restenosis, but only high dose of LipALN depleted monocytes (−60.1 ± 4.4%, 48 h post injury). Although LipCLOD treatment (at an equivalent potency to 3 mg/kg alendronate) significantly reduced monocyte levels (72.1 ± 6%), no restenosis inhibition was observed. The major finding of this study is the correlation found between monocyte subclasses and restenosis inhibition. Non-classical monocyte (NCM) levels were found higher in LipALN-treated rats, but lower in LipCLOD-treated rats, 24 h after injury and treatment. We suggest that the inhibition of circulating monocyte subpopulations is the predominant mechanism by which LipBPs prevent restenosis. The effect of LipBP treatment on the monocyte subpopulation correlates with the dose and potency of LipBPs.
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Chemotherapy-induced cardiomyopathy caused by Pemetrexed
Summary
Chemotherapy-related cardiac toxicity is a rare but serious adverse event in patients with cancer. Thus far, no case of serious cardiac toxicity of pemetrexed has been reported. We describe the case of a patient with advanced lung cancer and cardiomyopathy due to pemetrexed. A 59-year-old woman visited our hospital, and we found abnormal findings on a chest radiograph. She was diagnosed as having stage IV lung adenocarcinoma. Chemotherapy with cisplatin and pemetrexed every 3 weeks was initiated. After four cycles of chemotherapy, maintenance chemotherapy with pemetrexed was administered every 3 weeks. During the seventeenth cycle of pemetrexed, she had shortness of breath in her daily life. A chest radiograph showed an enlarged cardiothoracic ratio (66%), and the transthoracic echocardiogram demonstrated expansion of the left ventricle (diastolic diameter, 67 mm), severe global hypokinesis, and reduced left ventricular ejection fraction (28%). The coronary angiogram showed no coronary constriction. There was no delayed accumulation on the contrast-enhanced cardiac magnetic resonance imaging scan. After right heart catheterization, pathological results of a myocardial biopsy from the ventricular septum indicated no cardiac muscle hypertrophy, cardiac fibrosis, inflammatory cell infiltration, or myocyte disarray. Eventually, she was diagnosed as having pemetrexed-induced cardiomyopathy. Pemetrexed was discontinued, and furosemide, enalapril, and carvedilol were started. Then her symptoms and cardiac function improved. Early detection and discontinuation of causative agents are the most important treatment strategies in similar patients. Diuretics, angiotensin-conversion enzyme inhibitors, and beta-blockers may be effective for treating heart failure.
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Solitary Choroidal Metastasis From Lung Adenocarcinoma on FDG PET/CT.
| Related Articles |
Solitary Choroidal Metastasis From Lung Adenocarcinoma on FDG PET/CT.
Clin Nucl Med. 2017 Jun 24;:
Authors: Li ZG
Abstract
Solitary choroidal metastasis as an initial presentation of lung cancer is rare. A 67-year-old woman who initially presented with a 3-month history of blurred vision in the right eye was suggestive of choroidal melanoma on MRI. Preoperatively, a pulmonary mass was found on x-ray. She was referred for an FDG PET/CT imaging, which revealed a choroidal lesion with minimal FDG uptake in right eye and increased FDG activity in the known lung mass. A pathological diagnosis of metastatic lung adenocarcinoma was made after enucleation of the right eyeball.
PMID: 28650890 [PubMed - as supplied by publisher]
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Immunotherapeutic Approaches to Biliary Cancer
Opinion statement
Biliary tract cancers (BTCs) are rare aggressive neoplasms with a poor prognosis and a median survival of less than 1 year in the locally advanced or metastatic setting. Among the few patients who undergo curative resection the recurrence rates are high. About 90% of patients are detected at advanced stages, and systemic chemotherapy is the mainstay of their treatment. The treatment options for these patients are limited and multiple modalities of therapy from targeted therapy to immunotherapy and combination therapies (immunotherapy, targeted therapy, and chemotherapy) have been tested in this disease. Targeted therapies have failed to show a survival benefit. The deregulation of the immune system plays a significant role in the pathogenesis of BTCs. Therefore, immunotherapy, especially, immune checkpoint inhibitors hold great promise for this group of cancers. Numerous trials of immunotherapy in BTC are currently ongoing. In this review, we will discuss the available data and evidence for immunotherapy in BTC.
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Assessment of weight gain following adenotonsillectomy in children with Down syndrome
Adenotonsillectomy (T&A) has been associated with postoperative weight gain in children. The purpose of this study is to determine whether a similar association exists in children with Down syndrome (DS).
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Pathophysiology of esophageal impairment due to button battery ingestion
The increased use of button batteries with high energy densities in devices of daily life presents a high risk of injury, especially for toddlers and young children. If an accidental ingestion of a button battery occurs, this foreign body can become caught in the constrictions of the esophagus and cause serious damage to the adjacent tissue layers. The consequences can be ulcerations, perforations with fistula formation and damage to the surrounding anatomical structures. In order to gain a better understanding of the pathophysiology after ingestion, we carried out systematic studies on fresh preparations of porcine esophagi.
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Sleep quality and communication aspects in children
To correlate quality of life of children in terms of sleep, with their oral language skills, auditory processing and orofacial myofunctional aspects.
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Assessment of complete unilateral cleft lip and palate treatment outcome using EUROCRAN index and associated factors
Assessment of treatment outcome is the only non-invasive approach to identify the effects of cleft lip and palate repair and modify management accordingly. Here the aim is to assess the outcome of complete unilateral cleft lip and palate (CUCLP) patients using EUROCRAN index and to check whether there are any factors associated with the treatment outcome.
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Health, Wealth, and the U.S. Senate
New England Journal of Medicine, Ahead of Print.
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Immunotherapeutic Approaches to Biliary Cancer
Opinion statement
Biliary tract cancers (BTCs) are rare aggressive neoplasms with a poor prognosis and a median survival of less than 1 year in the locally advanced or metastatic setting. Among the few patients who undergo curative resection the recurrence rates are high. About 90% of patients are detected at advanced stages, and systemic chemotherapy is the mainstay of their treatment. The treatment options for these patients are limited and multiple modalities of therapy from targeted therapy to immunotherapy and combination therapies (immunotherapy, targeted therapy, and chemotherapy) have been tested in this disease. Targeted therapies have failed to show a survival benefit. The deregulation of the immune system plays a significant role in the pathogenesis of BTCs. Therefore, immunotherapy, especially, immune checkpoint inhibitors hold great promise for this group of cancers. Numerous trials of immunotherapy in BTC are currently ongoing. In this review, we will discuss the available data and evidence for immunotherapy in BTC.
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Recent Developments in Azaborinine Chemistry
Recent years have witnessed rapid advances in the field of BN/CC isosterism, in particular, in the case of azaborinines. Examples of each isomer have now been synthesized and characterized. This review provides a survey of the latest methods for the synthesis of new monocyclic B,N heterocycles, their reactivities and potential applications in biomedical and materials science.
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Immunotherapeutic Approaches to Biliary Cancer
Opinion statement
Biliary tract cancers (BTCs) are rare aggressive neoplasms with a poor prognosis and a median survival of less than 1 year in the locally advanced or metastatic setting. Among the few patients who undergo curative resection the recurrence rates are high. About 90% of patients are detected at advanced stages, and systemic chemotherapy is the mainstay of their treatment. The treatment options for these patients are limited and multiple modalities of therapy from targeted therapy to immunotherapy and combination therapies (immunotherapy, targeted therapy, and chemotherapy) have been tested in this disease. Targeted therapies have failed to show a survival benefit. The deregulation of the immune system plays a significant role in the pathogenesis of BTCs. Therefore, immunotherapy, especially, immune checkpoint inhibitors hold great promise for this group of cancers. Numerous trials of immunotherapy in BTC are currently ongoing. In this review, we will discuss the available data and evidence for immunotherapy in BTC.
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Immunotherapeutic Approaches to Biliary Cancer
Opinion statement
Biliary tract cancers (BTCs) are rare aggressive neoplasms with a poor prognosis and a median survival of less than 1 year in the locally advanced or metastatic setting. Among the few patients who undergo curative resection the recurrence rates are high. About 90% of patients are detected at advanced stages, and systemic chemotherapy is the mainstay of their treatment. The treatment options for these patients are limited and multiple modalities of therapy from targeted therapy to immunotherapy and combination therapies (immunotherapy, targeted therapy, and chemotherapy) have been tested in this disease. Targeted therapies have failed to show a survival benefit. The deregulation of the immune system plays a significant role in the pathogenesis of BTCs. Therefore, immunotherapy, especially, immune checkpoint inhibitors hold great promise for this group of cancers. Numerous trials of immunotherapy in BTC are currently ongoing. In this review, we will discuss the available data and evidence for immunotherapy in BTC.
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Immunotherapeutic Approaches to Biliary Cancer
Opinion statement
Biliary tract cancers (BTCs) are rare aggressive neoplasms with a poor prognosis and a median survival of less than 1 year in the locally advanced or metastatic setting. Among the few patients who undergo curative resection the recurrence rates are high. About 90% of patients are detected at advanced stages, and systemic chemotherapy is the mainstay of their treatment. The treatment options for these patients are limited and multiple modalities of therapy from targeted therapy to immunotherapy and combination therapies (immunotherapy, targeted therapy, and chemotherapy) have been tested in this disease. Targeted therapies have failed to show a survival benefit. The deregulation of the immune system plays a significant role in the pathogenesis of BTCs. Therefore, immunotherapy, especially, immune checkpoint inhibitors hold great promise for this group of cancers. Numerous trials of immunotherapy in BTC are currently ongoing. In this review, we will discuss the available data and evidence for immunotherapy in BTC.
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Summary Low-fidelity, simulation-based psychomotor skills training is a valuable first step in the educational approach to mastering com...
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Abstract Purpose Clinicians must balance the risks from hypotension with the potential adverse effects of vasopressors. Experts have rec...
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Does CBD Oil Lower Blood Pressure? This article was originally published at SundayScaries." Madeline Taylor POSTED ON January 13, 20...
