Publication date: Available online 13 April 2018
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Deepa Rajagopalan, Sudhakar Jha
Cancer is characterized by inter and intra-heterogeneity and this is also observed in the context of cancers caused by pathogens. Nearly 20% of all cancers are attributable to pathogenic organisms. Pathogenic infections result in deregulation of gene expression both by genetic and epigenetic mechanisms, thereby causing malignant transformation. Another characteristic of pathogen-induced cancers is the occurrence of chronic inflammation due to activation of the innate and adaptive arms of the immune system. This review focuses on the epigenetic changes induced by oncoviruses, parasites, cancer-causing bacteria and 'endogenous pathogens' to trigger host cell proliferation indefinitely as well as the inflammation associated with pathogen-induced cancers. The opportunity of targeting components of both pathogen and host epigenetic machinery to limit tumor progression is also discussed.
https://ift.tt/2GYiJ9q
Παρασκευή 13 Απριλίου 2018
An epi(c)genetic war: Pathogens, cancer and human genome
Nervous system and primary liver cancer
Publication date: Available online 13 April 2018
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Seogsong Jeong, Bo Zheng, Hongyang Wang, Qiang Xia, Lei Chen
Recent advances have found irregular activities of the nervous system-associated factors in the development and progression of primary liver cancer. These factors contributed in the regulation of migration, proliferation, and apoptosis of cancer cells, and took a role in modulating invasion, metastasis, and recurrence after curative treatment. In clinical researches, neural-related factors were found to be significant prognostic factors, suggesting that the interactions between nervous system and primary liver cancer are indispensable in understanding underlying biological mechanisms. Herein, we reviewed up-to-date achievements in this area and the future perspectives of the interactions between the nervous system and primary liver cancer.
Graphical abstract
https://ift.tt/2HzeTor
Protein restriction and cancer
Publication date: April 2018
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Volume 1869, Issue 2
Author(s): Jie Yin, Wenkai Ren, Xingguo Huang, Tiejun Li, Yulong Yin
Protein restriction without malnutrition is currently an effective nutritional intervention known to prevent diseases and promote health span from yeast to human. Recently, low protein diets are reported to be associated with lowered cancer incidence and mortality risk of cancers in human. In murine models, protein restriction inhibits tumor growth via mTOR signaling pathway. IGF-1, amino acid metabolic programing, FGF21, and autophagy may also serve as potential mechanisms of protein restriction mediated cancer prevention. Together, dietary intervention aimed at reducing protein intake can be beneficial and has the potential to be widely adopted and effective in preventing and treating cancers.
https://ift.tt/2GYiGKM
ILT4 functions as a potential checkpoint molecule for tumor immunotherapy
Publication date: April 2018
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Volume 1869, Issue 2
Author(s): Aiqin Gao, Yuping Sun, Guangyong Peng
Immune checkpoint blockade therapy targeting CTLA4 and PD-1/PD-L1 is a promising strategy in the treatment of different types of cancers. However, the clinical success rates of these therapies are still moderate and varied among cancer types. Therefore, identification of alternative and novel checkpoint molecules or interrupting tolerogenic pathways is urgently needed for successful tumor immunotherapy. Immunoglobulin-like transcript 4 (ILT4) is as an immunosuppressive molecule predominantly expressed in myeloid cells, including monocytes, macrophages, dendritic cells and granulocytes. Recent studies revealed that ILT4 is also enriched in tumor cells and stroma cells in the tumor microenvironment of various malignancies, modulating the biological behaviors of tumor cells and promoting their immune escape. However, the underlying mechanisms responsible for ILT4-mediated tumor development and progression are still poorly understood. In this review, we explore the functional role of ILT4 as a novel checkpoint molecule in cancers. We specifically discuss the mechanisms mediated by ILT4 for controlling tumor malignant behaviors, impairing effector anti-tumor immune responses, and sustaining the tumor suppressive microenvironment. We also highlight the potential role of ILT4 as a novel immune checkpoint target for tumor immunotherapy. Improved understanding of these issues is critical for elucidation of the role of ILT4 in tumor pathogenesis and should open new avenues for cancer immunotherapy specifically targeting this novel and alternative checkpoint molecule.
https://ift.tt/2HzeN03
Hypothyroidism During Tyrosine Kinase Inhibitor Therapy Is Associated with Longer Survival in Patients with Advanced Nonthyroidal Cancers
Thyroid, Volume 28, Issue 4, Page 445-453, April 2018.
https://ift.tt/2ITAt6r
Risk Factors for New Hypothyroidism During Tyrosine Kinase Inhibitor Therapy in Advanced Nonthyroidal Cancer Patients
Thyroid, Volume 28, Issue 4, Page 437-444, April 2018.
https://ift.tt/2IRG39o
Age-related defects in short-term plasticity are reversed by acetyl-L-carnitine at the mouse calyx of Held
Source:Neurobiology of Aging, Volume 67
Author(s): Mahendra Singh, Pedro Miura, Robert Renden
Hearing acuity and sound localization are affected by aging and may contribute to cognitive dementias. Although loss of sensorineural conduction is well documented to occur with age, little is known regarding short-term synaptic plasticity in central auditory nuclei. Age-related changes in synaptic transmission properties were evaluated at the mouse calyx of Held, a sign-inverting relay synapse in the circuit for sound localization, in juvenile adults (1 month old) and late middle–aged (18–21 months old) mice. Synaptic timing and short-term plasticity were severely disrupted in older mice. Surprisingly, acetyl-l-carnitine (ALCAR), an anti-inflammatory agent that facilitates mitochondrial function, fully reversed synaptic transmission delays and defects in short-term plasticity in aged mice to reflect transmission similar to that seen in juvenile adults. These findings support ALCAR supplementation as an adjuvant to improve short-term plasticity and potentially central nervous system performance in animals compromised by age and/or neurodegenerative disease.
https://ift.tt/2HALJW7
APOE genotype modifies the association between central arterial stiffening and cognition in older adults
Source:Neurobiology of Aging, Volume 67
Author(s): Francis E. Cambronero, Dandan Liu, Jacquelyn E. Neal, Elizabeth E. Moore, Katherine A. Gifford, James G. Terry, Sangeeta Nair, Kimberly R. Pechman, Katie E. Osborn, Timothy J. Hohman, Susan P. Bell, J. David Sweatt, Thomas J. Wang, Joshua A. Beckman, John Jeffrey Carr, Angela L. Jefferson
Arterial stiffening is associated with cognitive impairment and prodromal Alzheimer's disease. This study tested the interaction between arterial stiffening and an Alzheimer's disease genetic risk factor (apolipoprotein E [APOE] genotype) on cognition among older adults. Vanderbilt Memory & Aging Project participants with normal cognition (n = 162, 72 ± 7 years, 29% APOE-ε4 carrier) and mild cognitive impairment (n = 121, 73 ± 8 years, 42% APOE-ε4 carrier) completed neuropsychological assessment and cardiac MRI to assess aortic stiffening using pulse wave velocity (PWV, m/s). Linear regression models stratified by cognitive diagnosis related aortic PWV × APOE-ε4 status to neuropsychological performances, adjusting for demographic and vascular risk factors. PWV × APOE-ε4 related to poorer performance on measures of lexical retrieval (β = −0.29, p = 0.01), executive function (β = −0.44, p = 0.02), and episodic memory (β = −3.07, p = 0.02). Among participants with higher aortic PWV, APOE-ε4 modified the association between central arterial stiffening and cognition, such that carriers had worse performances than noncarriers. Findings add to a growing body of evidence for APOE-vascular interactions on cognition in older adults and warrant further research into less heart-healthy cohorts where the association between PWV and cognition among older adults might be stronger.
https://ift.tt/2GZ982e
Muscle strength and size are associated with motor unit connectivity in aged mice
Source:Neurobiology of Aging, Volume 67
Author(s): Kajri A. Sheth, Chitra C. Iyer, Christopher G. Wier, Alexander E. Crum, Anna Bratasz, Stephen J. Kolb, Brian C. Clark, Arthur H.M. Burghes, W. David Arnold
In older adults, the loss of muscle strength (dynapenia) and the loss of muscle mass (sarcopenia) are important contributors to the loss of physical function. We sought to investigate dynapenia, sarcopenia, and the loss of motor unit function in aging mice. C57BL/6J mice were analyzed with cross-sectional (males: 3 vs. 27 months; males and females: 8 vs. 12 vs. 20 months) and longitudinal studies (males: 10–25 months) using in vivo electrophysiological measures of motor unit connectivity (triceps surae compound muscle action potential and motor unit number estimation), in vivo measures of plantar flexion torque, magnetic resonance imaging of hind limb muscle volume, and grip strength. Compound muscle action potential amplitude, motor unit number estimation, and plantar flexion torque were decreased at 20 months. In contrast, grip strength was reduced at 24 months. Motor unit number estimates correlated with muscle torque and hind limb muscle volume. Our results demonstrate that the loss of motor unit connectivity is an early finding in aging male and female mice and that muscle size and contractility are both associated with motor unit number.
https://ift.tt/2HyXtbs
Escitalopram alleviates stress-induced Alzheimer's disease-like tau pathologies and cognitive deficits by reducing hypothalamic-pituitary-adrenal axis reactivity and insulin/GSK-3β signal pathway activity
Source:Neurobiology of Aging, Volume 67
Author(s): Chao Wu, Wei-Gang Gong, Yan-Juan Wang, Jun-Jun Sun, Hong Zhou, Zhi-Jun Zhang, Qing-Guo Ren
Chronic stress, a causal factor for depression, can also cause cognitive impairments and tau pathology. However, whether and how the selective serotonin reuptake inhibitor antidepressant escitalopram ameliorates these effects are still unclear. In the present study, rats were subjected to chronic mild unpredictable stress for 8 weeks. Following the initial 4 weeks, the stressed animals were separated into susceptible (depressive) and unsusceptible (resistant) groups based on behavioral tests. Then, escitalopram (10 mg/kg i.p.) was administered for 28 days. Pathophysiological changes were assessed by performing behavioral and biochemical analyses. The results showed that both depressive and resistant rats displayed spatial memory deficits and an accumulation of tau in the hippocampus. Increased levels of corticosterone and insulin and a decreased level of glucocorticoid receptor were found in both depressive and resistant rats. We also found that activity-dependent phosphorylated insulin receptor substrate and glycogen synthase kinase-3β (Ser9 site) were significantly decreased in both depressive and resistant rats. However, other important kinases, such as cyclin-dependent kinase 5 and mitogen-activated protein kinase kinase-1/2, did not change in our study. Furthermore, we found that the mRNA expression of tau was increased in depressive and resistant rats. No significant change in LC3B expression was found. Interestingly, almost all the pathological changes in depressive and resistant rats previously mentioned could be reversed by escitalopram. Our results suggested that escitalopram ameliorates cognitive impairments and selectively attenuates phosphorylated tau accumulation in stressed rats through the regulation of hypothalamic-pituitary-adrenal axis activity and the insulin receptor substrate/glycogen synthase kinase-3β signaling pathway.
https://ift.tt/2GZdXIG
Evidence of Wnt/β-catenin alterations in brain and bone of a tauopathy mouse model of Alzheimer's disease
Source:Neurobiology of Aging, Volume 67
Author(s): Christine M. Dengler-Crish, Hope C. Ball, Li Lin, Kimberly M. Novak, Lisa Noelle Cooper
Low bone mineral density (BMD) is a significant comorbidity in Alzheimer's disease (AD) and may reflect systemic regulatory pathway dysfunction. Low BMD has been identified in several AD mouse models selective for amyloid-β or tau pathology, but these deficits were attributed to diverse mechanisms. In this study, we identified common pathophysiological mechanisms accounting for bone loss and neurodegeneration in the htau mouse, a tauopathy model with an early low BMD phenotype. We investigated the Wnt/β-catenin pathway—a cellular signaling cascade linked to both bone loss and neuropathology. We showed that low BMD persisted in male htau mice aged from 6 to 14 months, remaining significantly lower than tau-null and C57BL/6J controls. Osteogenic gene expression in female and male htau mice was markedly reduced from controls, indicating impaired bone remodeling. In both the bone and brain, htau mice showed alterations in Wnt/β-catenin signaling genes suggestive of increased inhibition of this pathway. These findings implicate dysfunctional Wnt signaling as a potential target for addressing bone loss in AD.
https://ift.tt/2HyXqMO
BmSUC1 is essential for glycometabolism modulation in the silkworm, Bombyx mori
Publication date: Available online 14 April 2018
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Quan Gan, Xinwei Zhang, Daobo Zhang, Liang Shi, Yue Zhou, Tongtong Sun, Song Jiang, Junshan Gao, Yan Meng
Sucrose is the most commonly transported sugar in plants and is easily assimilated by insects to fulfill the requirement of physiological metabolism. BmSuc1 is a novel animal β-fructofuranosidase (β-FFase, EC 3.2.1.26)-encoding gene that was firstly cloned and identified in silkworm, Bombyx mori. BmSUC1 was presumed to play an important role in the silkworm-mulberry enzymatic adaptation system by effectively hydrolyzing sucrose absorbed from mulberry leaves. However, this has not been proved with direct evidence thus far. In this study, we investigated sucrose hydrolysis activity in the larval midgut of B. mori by inhibition tests and found that sucrase activity mainly stemmed from β-FFase, not α-glucosidase. Next, we performed shRNA-mediated transgenic RNAi to analyze the growth characteristics of silkworm larvae and variations in glycometabolism in vivo in transgenic silkworms. The results showed that in the RNAi-BmSuc1 transgenic line, larval development was delayed, and their body size was markedly reduced. Finally, the activity of several disaccharidases alone in the midgut and the sugar distribution, total sugar and glycogen in the midgut, hemolymph and fat body were then determined and compared. Our results demonstrated that silencing BmSuc1 significantly reduced glucose and apparently activated maltase and trehalase in the midgut. Together with a clear decrease in both glycogen and trehalose in the fat body, we conclude that BmSUC1 acts as an essential sucrase by directly modulating the degree of sucrose hydrolysis in the silkworm larval midgut, and insufficient sugar storage in the fat body may be responsible for larval malnutrition and abnormal petite phenotypes.
Graphical abstract
https://ift.tt/2H0cD8A
An improved inventory of polychlorinated biphenyls in China: A case study on PCB-153
Publication date: June 2018
Source:Atmospheric Environment, Volume 183
Author(s): Yue Xu, Chongguo Tian, Xiaoping Wang, Jianmin Ma, Jianhui Tang, Yingjun Chen, Jun Li, Gan Zhang
Emission inventory of pollutants is essential for the environmental fate study and management of the pollutant. To construct a reasonable PCB (polychlorinated biphenyls) inventory in China, this study estimates PCB usage and emission using power generating capacity, installed capacity of power plants and transformer substations, population density and GDP as surrogates. Inventory of representative PCB (PCB-153) with a resolution of 1/4° latitude × 1/4° longitude in China from 1952 to 2005 was generated and assessed as an example. Totally, about 20.3 kt PCBs were applied in China, of which 179 t were PCB-153. By the end of 2005, most of them (56.4%) were emitted into the soil, 2.7% entered the air, and about 20.8% was sealed in storage site or still in service. Historical emissions exhibited increasing trends after 1968, 1984 and 1994, which were mainly associated with usage or disposal processes. Although primary emission has been declined since 2005, the influence of secondary emission from soils, unintentionally produced PCBs (UP-PCB), and reemission from storage sites could be a long-lasting issue in the future. This new emission inventory improves previous PCB emission inventory significantly, which underestimated PCB emission in China considerably.
Graphical abstract
https://ift.tt/2HjCewG
Relative impact of short-term emissions controls on gas and particle-phase oxidative potential during the 2015 China Victory Day Parade in Beijing, China
Publication date: June 2018
Source:Atmospheric Environment, Volume 183
Author(s): Wei Huang, Dongqing Fang, Jing Shang, Zhengqiang Li, Yang Zhang, Peng Huo, Zhaoying Liu, James J. Schauer, Yuanxun Zhang
A field observation focusing on reactive oxygen species (ROS) was conducted before, during, and after the 2015 China Victory Day Parade to understand the influence of short-term emissions controls on atmospheric oxidative activity. The hourly average concentrations of PM2.5, SO2, NO, NO2, CO, O3, as well as gas and particle-phase ROS, were measured using a series of online instruments. PM2.5 concentrations during control days were significantly lower than non-control days, which directly lead to the "Parade Blue", yet reductions of most gaseous pollutants except SO2 were not so obvious as PM. Similarly, the control measures also led to a great loss of particle-phase ROS throughout the control period, while the reduction of ROS in gas phase was not obvious until the more stringent measures implemented since September 1. Furthermore, only weak positive correlations were observed among ROS and some other measured species, indicating ROS concentrations were affected by a number of comprehensive factors that single marker could not capture. Meanwhile, meteorological condition and regional transportation were also shown to be the minor factors affecting atmospheric oxidizing capacity. The results of this observation mainly revealed the control measures were conducive to reducing particle-related ROS. However, the reduction of gas-phase ROS activity was less effective given the menu of controls employed for the 2015 China Victory Day Parade. Therefore, short-term emissions controls only aimed to PM reduction and visibility improvement will produce the blue sky but will not equivalently reduce the gas-phase ROS. Supplemental control measures will be needed to further reduce gas-phase ROS concentrations.
Graphical abstract
https://ift.tt/2ELlXuW
Characterizing the spatial variability of local and background concentration signals for air pollution at the neighbourhood scale
Publication date: June 2018
Source:Atmospheric Environment, Volume 183
Author(s): Kerolyn K. Shairsingh, Cheol-Heon Jeong, Jonathan M. Wang, Greg J. Evans
Vehicle emissions represent a major source of air pollution in urban districts, producing highly variable concentrations of some pollutants within cities. The main goal of this study was to identify a deconvolving method so as to characterize variability in local, neighbourhood and regional background concentration signals. This method was validated by examining how traffic-related and non-traffic-related sources influenced the different signals.Sampling with a mobile monitoring platform was conducted across the Greater Toronto Area over a seven-day period during summer 2015. This mobile monitoring platform was equipped with instruments for measuring a wide range of pollutants at time resolutions of 1 s (ultrafine particles, black carbon) to 20 s (nitric oxide, nitrogen oxides). The monitored neighbourhoods were selected based on their land use categories (e.g. industrial, commercial, parks and residential areas). The high time-resolution data allowed pollutant concentrations to be separated into signals representing background and local concentrations. The background signals were determined using a spline of minimums; local signals were derived by subtracting the background concentration from the total concentration.Our study showed that temporal scales of 500 s and 2400 s were associated with the neighbourhood and regional background signals respectively. The percent contribution of the pollutant concentration that was attributed to local signals was highest for nitric oxide (NO) (37–95%) and lowest for ultrafine particles (9–58%); the ultrafine particles were predominantly regional (32–87%) in origin on these days. Local concentrations showed stronger associations than total concentrations with traffic intensity in a 100 m buffer (ρ:0.21–0.44). The neighbourhood scale signal also showed stronger associations with industrial facilities than the total concentrations. Given that the signals show stronger associations with different land use suggests that resolving the ambient concentrations differentiates which emission sources drive the variability in each signal. The benefit of this deconvolution method is that it may reduce exposure misclassification when coupled with predictive models.
Graphical abstract
https://ift.tt/2qsEU1u
Isoprene emission response to drought and the impact on global atmospheric chemistry
Source:Atmospheric Environment, Volume 183
Author(s): Xiaoyan Jiang, Alex Guenther, Mark Potosnak, Chris Geron, Roger Seco, Thomas Karl, Saewung Kim, Lianhong Gu, Stephen Pallardy
Biogenic isoprene emissions play a very important role in atmospheric chemistry. These emissions are strongly dependent on various environmental conditions, such as temperature, solar radiation, plant water stress, ambient ozone and CO2 concentrations, and soil moisture. Current biogenic emission models (i.e., Model of Emissions of Gases and Aerosols from Nature, MEGAN) can simulate emission responses to some of the major driving variables, such as short-term variations in temperature and solar radiation, but the other factors are either missing or poorly represented. In this paper, we propose a new modelling approach that considers the physiological effects of drought stress on plant photosynthesis and isoprene emissions for use in the MEGAN3 biogenic emission model. We test the MEGAN3 approach by integrating the algorithm into the existing MEGAN2.1 biogenic emission model framework embedded into the global Community Land Model of the Community Earth System Model (CLM4.5/CESM1.2). Single-point simulations are compared against available field measurements at the Missouri Ozarks AmeriFlux (MOFLUX) field site. The modelling results show that the MEGAN3 approach of using of a photosynthesis parameter (Vcmax) and soil wetness factor (βt) to determine the drought activity factor leads to better simulated isoprene emissions in non-drought and drought periods. The global simulation with the MEGAN3 approach predicts a 17% reduction in global annual isoprene emissions, in comparison to the value predicted using the default CLM4.5/MEGAN2.1 without any drought effect. This reduction leads to changes in surface ozone and oxidants in the areas where the reduction of isoprene emissions is observed. Based on the results presented in this study, we conclude that it is important to simulate the drought-induced response of biogenic isoprene emission accurately in the coupled Earth System model.
https://ift.tt/2vi1aQy
The Association Between Heat Waves and Other Meteorological Parameters and Snakebites: Israel National Study
Source:The Journal of Emergency Medicine
Author(s): Sagi Shashar, Maayan Yitshak-Sade, Roman Sonkin, Victor Novack, Eli Jaffe
BackgroundPublished annual estimates report a global burden of 2.5 million snakebite cases and >100,000 deaths. In Israel, envenomations are the third most frequent cause of poisonings that are of moderate to major clinical severity. Most studies focus on the clinical descriptions of snakebites in tropical climates, and we sought to investigate the association between snakebite frequency and meteorological parameters.ObjectiveWe sought to investigate the seasonality of snakebites and evaluate the association between increasingly common heat waves and other meteorological parameters and snakebite frequency in a semiarid nontropical climate.MethodsWe obtained data for all medical evacuations (2008–2015) because of snakebites in Israel. Climate data included daily 24-hour average temperature (°C) and relative humidity (%). We used a time-stratified case crossover method, in which a conditional logistic regression was applied to estimate the association, and we also stratified our analysis by season and by region.ResultsWe identified 1234 snakebite cases over 8 years, of which most (74.2%) occurred in hot seasons and between 6 pm and 9 pm. The risk of snakebite was positively associated with temperature >23°C (odds ratio [OR] 1.24, 95% confidence interval [CI] 1.01–1.53) and inversely with humidity >40% (OR 0.74, 95% CI 0.57–0.97). We also found an association with heat waves both in cold (OR 1.62, 95% CI 1.01–2.60) and hot seasons (OR 1.50, 95% CI 1.18–1.92).ConclusionsIn a semiarid nontropical climate, we observed an association between an increase in the number of snakebite cases and higher temperatures and lower humidity. Moreover, heat waves increased the frequency of snakebites in both cold and hot seasons.
https://ift.tt/2GVMPyx
Is Transcellular Potassium Shifting With Insulin, Albuterol, or Sodium Bicarbonate in Emergency Department Patients With Hyperkalemia Associated With Recurrent Hyperkalemia After Dialysis?
Source:The Journal of Emergency Medicine
Author(s): Brian E. Driver, Lauren R. Klein, Chaitanya Chittineni, Ellen K. Cales, Nathaniel Scott
BackgroundEmergency department (ED) treatment of hyperkalemia often involves shifting potassium into the intracellular space. There is uncertainty whether transcellular shifting causes insufficient potassium removal during hemodialysis, resulting in a subsequent need for further medical therapy or multiple sessions of hemodialysis.ObjectiveWe sought to determine whether transcellular potassium shifting in ED patients with hyperkalemia who undergo hemodialysis is associated with recurrent hyperkalemia with or without repeat hemodialysis within 24 h.MethodsThis was a retrospective observational study of ED patients with a potassium value > 5.3 mmol/L and ≥1 hemodialysis run. Transcellular shifting medications were defined as albuterol, insulin, and sodium bicarbonate. Primary outcomes were recurrent hyperkalemia with and without repeat hemodialysis within 24 h of the initial dialysis run. Generalized estimating equation models were created for the outcomes using administration of a shifting medication as the primary predictor.ResultsFour hundred seventy-nine encounters were identified. In 238 (50%) encounters, a shifting medication was administered. There were 85 outcomes of recurrent hyperkalemia and 36 outcomes of recurrent hyperkalemia with repeat hemodialysis. After adjustment, administration of shifting medications was not associated with recurrent hyperkalemia (adjusted odds ratio 1.26, 95% confidence interval 0.71–2.23) or recurrent hyperkalemia with repeat dialysis (adjusted odds ratio 1.90, 95% confidence interval 0.80–4.48).ConclusionsAdministration of transcellular shifting medications for hyperkalemia in the ED was not associated with either recurrent hyperkalemia after hemodialysis or the need for a second dialysis session within 24 h. Our findings address the uncertainty regarding transcellular potassium shifting before emergent dialysis and support safe ED administration of medications that shift potassium to the intracellular space.
https://ift.tt/2qAQiYr
Nasal polyposis (or chronic olfactory rhinitis)
Publication date: Available online 13 April 2018
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): R. Jankowski, C. Rumeau, P. Gallet, D.T. Nguyen
The concept of chronic rhinosinusitis with or without polyps is founded on the structural and functional unicity of the pituitary mucosa and its united response to environmental aggression by allergens, viruses, bacteria, pollution, etc. The present review sets this concept against the evo-devo three-nose theory, in which nasal polyposis is distinguished as specific to the olfactory nose and in particular to the non-olfactory mucosa of the ethmoid, which is considered to be not a sinus but rather the skull-base bone harboring the olfactory mucosa. The evo-devo approach enables simple and precise positive diagnosis of nasal polyposis and its various clinical forms, improves differential diagnosis by distinguishing chronic diseases of the respiratory nose and those of the paranasal sinuses, hypothesizes an autoimmune origin specifically aimed at olfactory system auto-antigens, and supports the surgical concept of nasalization against that of functional sinus and ostiomeatal-complex surgery. The ventilation function of the sinuses seems minor compared to their production, storage and active release of nitric oxide (NO) serving to oxygenate arterial blood in the pulmonary alveoli. This respiratory function of the paranasal sinuses may indeed be their most important. NO trapped in the ethmoidal spaces also accounts for certain radiographic aspects associated with nasal polyposis.
https://ift.tt/2vb2wMT
Office-based endoscopic botulinum toxin injection in laryngeal movement disorders
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): A. Kaderbay, C.A. Righini, P.F. Castellanos, I. Atallah
IntroductionBotulinum toxin injection is widely used for the treatment of laryngeal movement disorders. Electromyography-guided percutaneous injection is the technique most commonly used to perform intralaryngeal botulinum toxin injection.ObjectiveWe describe an endoscopic approach for intralaryngeal botulinum toxin injection under local anaesthesia without using electromyography.TechniqueA flexible video-endoscope with an operating channel is used. After local anaesthesia of the larynx by instillation of lidocaine, a flexible needle is inserted into the operating channel in order to inject the desired dose of botulinum toxin into the vocal and/or vestibular folds.ConclusionEndoscopic botulinum toxin injection under local anaesthesia is a reliable technique for the treatment of laryngeal movement disorders. It can be performed by any laryngologist without the need for electromyography. It is easy to perform for the operator and comfortable for the patient.
https://ift.tt/2qtXRR7
Metal enhanced fluorescence (MEF) for biosensors: General approaches and a review of recent developments
Publication date: 15 July 2018
Source:Biosensors and Bioelectronics, Volume 111
Author(s): Yoon Jeong, Yun-Min Kook, Kangwon Lee, Won-Gun Koh
Fluorescence-based biosensor platforms have been intensively investigated not only to increase the sensitivity but also to improve the performance of biosensors. By exploiting metal from the macroscopic down to the nanoscopic surface, various architectures have been devised to manipulate fluorescence signals (enhancement, quenching) within near-optical fields. The interaction of a metallic surface with proximal fluorophores (in the range of 5–90 nm) has beneficial effects on optical properties such as an increased quantum yield, improved photostability and a reduced lifetime of fluorophores. This phenomenon called metal-enhanced fluorescence (MEF) has been extensively used in biosensory applications. However, their applications for biological analysis practically remain challenging in biological microenvironments. Therefore, this review primarily provides a general overview of MEF biosensor systems from the basic mechanism to state-of-the-art biological applications. The review also covers the pros and cons of MEF biosensor as well as discussions about further directions in biological perspectives.
https://ift.tt/2GXTw2S
Highly stable and regenerative graphene–diamond hybrid electrochemical biosensor for fouling target dopamine detection
Publication date: 15 July 2018
Source:Biosensors and Bioelectronics, Volume 111
Author(s): Qilong Yuan, Ying Liu, Chen Ye, Hongyan Sun, Dan Dai, Qiuping Wei, Guosong Lai, Tianzhun Wu, Aimin Yu, Li Fu, Kuan W.A. Chee, Cheng-Te Lin
Graphene is widely recognized as a promising nanomaterial for the construction of high-performance electrochemical biosensors. However, the lack of strong interfacial forces between graphene and conductive substrates is a bottleneck in the fabrication of highly stable graphene electrodes. In this work, few-layer graphene was directly formed on a high pressure high temperature (HPHT) diamond substrate via sp3-to-sp2 conversion by catalytic thermal treatment and using diamond itself as the carbon source. The hybrid electrode prototype was also highly conductive and had a linear electrochemical response to dopamine in the concentration range of 5 μM – 2 mM, with a low detection limit of 200 nM. After prolonged and repeated exposure to dopamine, electrode fouling was observed which led to sensitivity degradation. Based on the strong interfacial bonding between graphene and HPHT diamond, regeneration of the fouled electrode and full performance recovery would be easily achieved by ultrasonic cleaning. The hybrid electrode is highly robust, and shows potential in its application to the detection of biofouling molecules, food processing and wastewater treatment.
Graphical abstract
https://ift.tt/2qtMEiE
AIE-based superwettable microchips for evaporation and aggregation induced fluorescence enhancement biosensing
Publication date: 15 July 2018
Source:Biosensors and Bioelectronics, Volume 111
Author(s): Yanxia Chen, Xuehong Min, Xiqi Zhang, Feilong Zhang, Simeng Lu, Li-Ping Xu, Xiaoding Lou, Fan Xia, Xueji Zhang, Shutao Wang
Superwettable microchips with superhydrophilic microwells on superhydrophobic substrate have attracted increasing attention in fluorescence-based biological and medical diagnostics. However, traditional fluorophores often suffer from the aggregation-caused quenching (ACQ) problem at high concentration or in aggregated state. Here, we developed an AIE-based superwettable microchip by combining the evaporation-induced enrichment of superwettable microchips and the aggregation-induced emission of AIEgens together into one chip. Benefitting from the synergistic effect of the above two mechanisms, the AIE molecules (TPE-Z, a tetraphenylethene salt) were enriched from the diluted solution via evaporation and aggregated within the superhydrophilic microwell and then realized the fluorescence enhancement. Based on the dual enhancement effect of the AIE-based superwettable microchip, microRNA-141 (miR-141) can be detected with excellent reproducibility, sensitivity and specificity. A low detection limit of 1 pM can be achieved with higher signal-to-noise ratio than the traditional fluorescent probes. The proposed AIE-based superwettable microchip will provide a simple fluorescence enhancement biosensing platform for rapid, multiplexed and high-throughput analysis of specific targets in environmental monitoring, food safety, medical diagnosis and related research areas.
Graphical abstract
https://ift.tt/2GYkKXp
"Beijing Da Xue Xue Bao"[jour]; +31 new citations
31 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
"Beijing Da Xue Xue Bao"[jour]
These pubmed results were generated on 2018/04/13
PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
https://ift.tt/2EK9KqC
The Role of Semantic Representations in Verbal Working Memory.
https://ift.tt/2HldB2v
A Spacing Account of Negative Recency in Final Free Recall.
https://ift.tt/2HfTnYf
Two Sources of Information in Reconstructing Event Sequence.
https://ift.tt/2EJrQJl
Learning of Pitch and Time Structures in an Artificial Grammar Setting.
https://ift.tt/2HjwqTU
Is the Phonological Similarity Effect in Working Memory Due to Proactive Interference?.
https://ift.tt/2HiPtxx
Mechanisms Underlying Effects of Approach-Avoidance Training on Stimulus Evaluation.
https://ift.tt/2ve7pob
The Misinterpretation of Noncanonical Sentences Revisited.
https://ift.tt/2HhGfll
The Role of Preview Validity in Predictability and Frequency Effects on Eye Movements in Reading.
https://ift.tt/2vc7rND
Production of Familiar Phrases: Frequency Effects in Native Speakers and Second Language Learners.
https://ift.tt/2HldyUn
Animal models of endometriosis: Replicating the aetiology and symptoms of the human disorder
Publication date: Available online 6 April 2018
Source:Best Practice & Research Clinical Endocrinology & Metabolism
Author(s): Ioannis Simitsidellis, Douglas A. Gibson, Philippa T.K. Saunders
Endometriosis is a chronic incurable disorder that affects 1 in 10 women of reproductive age: associated symptoms include chronic pain and infertility. The aetiology of endometriosis remains poorly understood but patients, clinicians and researchers are all in agreement that new non-surgical therapies are urgently needed to reduce the severity of symptoms. Preclinical testing of drugs requires the development and validation of models that recapitulate the key features of the disorder. In this review we describe the best-validated animal models (primate, rodent, xenograft) and their contributions to our understanding of the factors underpinning the development of symptoms. We consider the evidence that these models have provided the platform for identification of new therapeutic interventions and reflect on future directions for research and drug validation.
https://ift.tt/2quyVsb
Diagnosis and management of postnatal fetal growth restriction
Publication date: Available online 5 April 2018
Source:Best Practice & Research Clinical Endocrinology & Metabolism
Author(s): Eloïse Giabicani, Aurélie Pham, Frédéric Brioude, Delphine Mitanchez, Irène Netchine
Fetal growth restriction (FGR) can result from multiple causes, such as genetic, epigenetic, environment, hormonal regulation, or vascular troubles and their potential interaction. The physiopathology of FGR is not yet fully elucidated, but the insulin-like growth factor system is known to play a central role. Specific clinical features can lead to the identification of genetic syndromes in some patients. FGR leads to multiple global health concerns, from the perinatal period, with higher morbidity/mortality, through infancy, with neurodevelopmental, growth, and metabolic issues, to the onset of puberty and later in life, with subfertility and elevated risks of cardiovascular and kidney diseases. Adequate follow-up and therapeutics should be offered to these patients. We first review the main molecular etiologies leading to FGR and their specificities. We then highlight the main issues that FGR can raise later in life before concluding with the proposed management of these children.
https://ift.tt/2GXKJ1b
Translational Studies Provide Insights for the Etiology and Treatment of Cortical Bone Osteoporosis
Publication date: Available online 3 April 2018
Source:Best Practice & Research Clinical Endocrinology & Metabolism
Author(s): Robert Brommage, Claes Ohlsson
Increasing attention is being focused on the important contributions of cortical bone to bone strength, fractures and osteoporosis therapies. Recent progress in human genome wide association studies in combination with high-throughput mouse gene knock out phenotyping efforts of multiple genes and advanced conditional gene inactivation in mouse models have successfully identified genes with crucial roles in cortical bone homeostasis. Particular attention in this review is given to genes, such as WNT16, POSTN and SFRP4, that differentially affect cortical and trabecular bone architecture. We propose that animal models of cortical bone metabolism will substantially contribute to developing anabolic osteoporosis therapies that improve cortical bone mass and reduce non-vertebral fracture risk.
https://ift.tt/2qwuuNd
Imaging endocrinology in animal models of endocrine disease
Publication date: Available online 3 April 2018
Source:Best Practice & Research Clinical Endocrinology & Metabolism
Author(s): Patrice Mollard, Marie Schaeffer
Endocrine organs secrete a variety of hormones involved in the regulation of a multitude of body functions. Although pancreatic islets were discovered at the turn of the 19th century, other endocrine glands remained commonly described as diffuse endocrine systems. Over the last two decades, development of new imaging techniques and genetically-modified animals with cell-specific fluorescent tags or specific hormone deficiencies have enabled in vivo imaging of endocrine organs and revealed intricate endocrine cell network structures and plasticity. Overall, these new tools have revolutionized our understanding of endocrine function. The overarching aim of this Review is to describe the current mechanistic understanding that has emerged from imaging studies of endocrine cell network structure/function relationships in animal models, with a particular emphasis on the pituitary gland and the endocrine pancreas.
https://ift.tt/2qwksvT
Vitamin D and calcium in the human breast milk
Source:Best Practice & Research Clinical Endocrinology & Metabolism, Volume 32, Issue 1
Author(s): Yoon Ju Bae, Juergen Kratzsch
Vitamin D and calcium in the human milk is essential for the growth and the prevention of rickets in infants. In this review, we will discuss the physiology and the functions of vitamin D and calcium and the mechanisms of vitamin D and calcium transfer into the human breast milk. This review describes the recommended intake of vitamin D and calcium for infants and lactating mothers and the factors influencing the content of vitamin D and calcium in human milk. Furthermore, the measurement of vitamin D compounds and calcium in human breast milk is described in this review.
https://ift.tt/2GXK7IV
Genetically modified mouse models to investigate thyroid development, function and growth
Publication date: Available online 3 April 2018
Source:Best Practice & Research Clinical Endocrinology & Metabolism
Author(s): C. Löf, K. Patyra, A. Kero, J. Kero
The thyroid gland produces thyroid hormones (TH), which are essential regulators for growth, development and metabolism. The thyroid is mainly controlled by the thyroid-stimulating hormone (TSH) that binds to its receptor (TSHR) on thyrocytes and mediates its action via different G protein-mediated signaling pathways. TSH primarily activates the Gs-pathway, and at higher concentrations also the Gq/11-pathway, leading to an increase of intracellular cAMP and Ca2+, respectively. To date, the physiological importance of other G protein-mediated signaling pathways in thyrocytes is unclear. Congenital hypothyroidism (CH) is defined as the lack of TH at birth. In familial cases, high-throughput sequencing methods have facilitated the identification of novel mutations. Nevertheless, the precise etiology of CH yet remains unraveled in a proportion of cases. Genetically modified mouse models can reveal new pathophysiological mechanisms of thyroid diseases. Here, we will present an overview of genetic mouse models for thyroid diseases, which have provided crucial insights into thyroid gland development, function, and growth with a special focus on TSHR and microRNA signaling.
https://ift.tt/2qxwCV1
Mouse models of peripheral metabolic disease
Publication date: Available online 31 March 2018
Source:Best Practice & Research Clinical Endocrinology & Metabolism
Author(s): Gabriela da Silva Xavier, David J. Hodson
Metabolic disease risk is driven by defects in the function of cells that regulate energy homeostasis, as well as altered communication between the different tissues or organs that these cells occupy. Thus, it is desirable to use model organisms to understand the contribution of different cells, tissues and organs to metabolism. Mice are widely used for metabolic research, since well-characterised mouse strains (in terms of their genotype and phenotype) allow comparative studies and human disease modelling. Such research involves strains containing spontaneous mutations that lead to obesity and diabetes, surgically- and chemically-induced models, those that are secondary to caloric excess, genetic mutants created by transgenesis and gene knockout technologies, and peripheral models generated by Cre-Lox or CRISPR/Cas9 approaches. Focussing on obesity and type 2 diabetes as relevant metabolic diseases, we systematically review each of these models, discussing their use, limitations, and future potential.
https://ift.tt/2GXJY8l
Mouse Models for the Analysis of Gonadotropin Secretion and Action
Publication date: Available online 31 March 2018
Source:Best Practice & Research Clinical Endocrinology & Metabolism
Author(s): Sara Babcock Gilbert, Allyson K. Roof, T. Rajendra Kumar
Gonadotropins are pituitary gonadotrope-derived glycoprotein hormones. They act by binding to G-protein coupled receptors on gonads. Gonadotropins play critical roles in reproduction by regulating both gametogenesis and steroidogenesis. Although biochemical and physiological studies provided a wealth of knowledge, gene manipulation techniques using novel mouse models gave new insights into gonadotropin synthesis, secretion and action. Both gain of function and loss of function mouse models for understanding gonadotropin action in a whole animal context have already been generated. Moreover, recent studies on gonadotropin actions in non-gonadal tissues challenged the central dogma of classical gonadotropin actions in gonads and revealed new signaling pathways in these non-gonadal tissues. In this Chapter, we have discussed our current understanding of gonadotropin synthesis, secretion and action using a variety of genetically engineered mouse models.
https://ift.tt/2qwNBaa
Evidence from animal models on the pathogenesis of PCOS
Publication date: Available online 31 March 2018
Source:Best Practice & Research Clinical Endocrinology & Metabolism
Author(s): K.A. Walters, M.J. Bertoldo, D.J. Handelsman
Polycystic ovarian syndrome (PCOS) is the most common endocrine condition in women, and is characterized by reproductive, endocrine and metabolic features. However, there is no simple unequivocal diagnostic test for PCOS, its etiology remains unknown and there is no cure. Hence, the management of PCOS is suboptimal as it relies on the ad hoc empirical management of its symptoms only. Decisive studies are required to unravel the origins of PCOS, but due to ethical and logistical reasons these are not possible in humans. Experimental animal models for PCOS have been established which have enhanced our understanding of the mechanisms underlying PCOS and propose novel mechanism-based therapies to treat the condition. This review examines the findings from various animal models to reveal the current knowledge of the mechanisms underpinning the development of PCOS, and also provides insights into the implications from these studies for improved clinical management of this disorder.
https://ift.tt/2GWNH5Z
Preface
Source:Best Practice & Research Clinical Endocrinology & Metabolism
Author(s): Anna Spada
https://ift.tt/2qybXQC
Thyrotropin receptor, still much to be learned from the patients
Source:Best Practice & Research Clinical Endocrinology & Metabolism
Author(s): Dr. Claire Briet, Valentine Suteau-Courant, Mathilde Munier, Prof. Patrice Rodien
In the absence of crystal available for the full-length thyrotropin receptor, knowledge of its structure and functioning has benefitted from the identification and characterization of mutations in patients with various thyroid dysfunctions. The characterization of activating mutations has contributed to the elaboration of a model involving the extracellular domain of the receptor as an inverse tethered agonist which, upon binding of the ligand, relieves the transmembrane domain from an inhibiting interaction and activates it. The models derived from comparisons with other receptors, enriched with the information provided by the study of mutations, have proven useful for the design of small-molecule agonists and antagonists that may be used in the future to treat thyroid dysfunctions. In this review, extrathyroidal expression of the thyrotropin receptor is described, the role of which is still poorly defined.
https://ift.tt/2GXayyf
An orphan G protein-coupled receptor causes human gigantism and/or acromegaly: Molecular biology and clinical correlations
Source:Best Practice & Research Clinical Endocrinology & Metabolism
Author(s): Giampaolo Trivellin, Laura C. Hernández-Ramírez, Jeremy Swan, Constantine A. Stratakis
X-linked acrogigantism (X-LAG) is a recently described form of familial or sporadic pituitary gigantism characterized by very early onset GH and IGF-1 excess, accelerated growth velocity, gigantism and/or acromegaloid features. Germline or somatic microduplications of the Xq26.3 chromosomal region, invariably involving the GPR101 gene, constitute the genetic defect leading to X-LAG. GPR101 encodes a class A G protein-coupled receptor that activates the 3′,5′-cyclic adenosine monophosphate signaling pathway. Highly expressed in the central nervous system, the main physiological function and ligand of GPR101 remain unknown, but it seems to play a role in the normal development of the GHRH-GH axis. Early recognition of X-LAG cases is imperative because these patients require clinical management that differs from that of other patients with acromegaly or gigantism. Medical treatment with pegvisomant seems to be the best approach, since X-LAG tumors are resistant to the treatment with somatostatin analogues and dopamine agonists; surgical cure requires near-total hypophysectomy. Currently, the efforts of our research focus on the identification of GPR101 ligands; in addition, the long-term follow-up of X-LAG patients is of extreme interest as this is expected to lead to better understanding of GPR101 effects on human pathophysiology.
https://ift.tt/2quyRZt
Adipokines in human breast milk
Source:Best Practice & Research Clinical Endocrinology & Metabolism, Volume 32, Issue 1
Author(s): Juergen Kratzsch, Yoon Ju Bae, Wieland Kiess
The review describes the molecular characteristics of so far detected breast milk adipokines and ranks their breast milk level compared to the respective levels in maternal and infant blood. Moreover, analytical knowledge for measurements of breast milk adipokines will be delineated. Next, we summarized data about two main potential influencing factors on adipokine concentration in breast milk, maternal weight and pasteurization of milk. Finally, associations between adipokines in breast milk and weight gain in infants as well as the putative mechanisms for effects of breast milk adipokines on food intake and weight gain in later life will debated. Our findings suggest that a source of adipokines in human breast milk cannot be uniformly defined. In dependence on the ratio between serum and breast milk levels the major quantity of these proteins may be derived from peripheral tissues, from the breast tissue itself or from both. Thus, leptin and in part adiponectin levels in breast milk are dependent on a plenty of influencing factors with an important relevance of maternal anthropometric characteristics There is some evidence that leptin, adiponectin and ghrelin levels in breast milk may be associated with growth gain of infants and even with increased risk for being overweight during infancy or childhood. We hypothesize that a dysregulation in adipokine homeostasis in early life could promote obesity and metabolic disturbance in later life.
https://ift.tt/2H0uHDx
G-protein coupled receptors (GPCRs) in the treatment of diabetes: Current view and future perspectives
Source:Best Practice & Research Clinical Endocrinology & Metabolism
Author(s): Guido Sebastiani, Elena Ceccarelli, Maria Grazia Castagna, Francesco Dotta
G-protein coupled receptors (GPCRs) represent the largest receptor family in the genome and are of great interest for the design of novel drugs in a wide variety of diseases including neurologic disorders, obesity and Type 2 diabetes mellitus. The latter is a chronic disease characterized by insulin resistance and impaired insulin secretion, affecting >400 million patients worldwide.Here we provide an overview on: a) The molecular basis of GPCR signalling and of its involvement in the regulation of insulin secretion and of glucose homeostasis; b) the role of GPCRs in type 2 diabetes pathophysiology and as therapeutic targets of current and future glucose-lowering drugs.
https://ift.tt/2qwouV0
Cytokines in milk and the role of TGF-beta
Source:Best Practice & Research Clinical Endocrinology & Metabolism, Volume 32, Issue 1
Author(s): Julia Brenmoehl, Daniela Ohde, Elisa Wirthgen, Andreas Hoeflich
Cytokines are required for normal growth and development of the mammary gland and TGF-β prominently represents an established effector of apoptosis, e.g., during involution of the mammary gland. By the control of intracellular signaling pathways, including JAK/STAT, MAPK, PI-3K, and NF-κB, cytokines efficiently regulate cell proliferation and inflammation in the breast. Therefore, cytokines are discussed also in a context of malignant mammary growth. As a group of tissue hormones produced by somatic cells or by cells from the immune system, cytokines are defined by their immunomodulatory potential. Over the past 40 years, multiple cytokines were identified in colostrum and milk. Importantly, cytokines derived from mammary secretions after birth are required for maturation of the immune system in the developing gastrointestinal tract from the suckling. Moreover, recent studies have further assessed the particular interactions between probiotic bacterial strains and cytokines. In light of the increasing prevalence of inflammatory diseases of the gastrointestinal system, the effects of probiotic microorganisms during milk fermentation may have immunotherapeutic potential in the future.
https://ift.tt/2H0LuGs
Novel mechanisms of GPCR functions: AT1 angiotensin receptor acts as a signaling hub and focal point of receptor cross-talk
Publication date: Available online 15 March 2018
Source:Best Practice & Research Clinical Endocrinology & Metabolism
Author(s): András D. Tóth, Gábor Turu, László Hunyady, András Balla
AT1 angiotensin receptor (AT1R), a prototypical G protein-coupled receptor (GPCR), is the main receptor, which mediates the effects of the renin-angiotensin system (RAS). AT1R plays a crucial role in the regulation of blood pressure and salt-water homeostasis, and in the development of pathological conditions, such as hypertension, heart failure, cardiovascular remodeling, renal fibrosis, inflammation, and metabolic disorders. Stimulation of AT1R leads to pleiotropic signal transduction pathways generating arrays of complex cellular responses. Growing amount of evidence shows that AT1R is a versatile GPCR, which has multiple unique faces with distinct conformations and signaling properties providing new opportunities for functionally selective pharmacological targeting of the receptor. Biased ligands of AT1R have been developed to selectively activate the β-arrestin pathway, which may have therapeutic benefits compared to the conventional angiotensin converting enzyme inhibitors and angiotensin receptor blockers. In this review, we provide a summary about the most recent findings and novel aspects of the AT1R function, signaling, regulation, dimerization or oligomerization and its cross-talk with other receptors, including epidermal growth factor (EGF) receptor, adrenergic receptors and CB1 cannabinoid receptor. Better understanding of the mechanisms and structural aspects of AT1R activation and cross-talk can lead to the development of novel type of drugs for the treatment of cardiovascular and other diseases.
https://ift.tt/2qv3gXv
Translational studies provide insights for the etiology and treatment of cortical bone osteoporosis
Source:Best Practice & Research Clinical Endocrinology & Metabolism
Author(s): Robert Brommage, Claes Ohlsson
Increasing attention is being focused on the important contributions of cortical bone to bone strength, fractures and osteoporosis therapies. Recent progress in human genome wide association studies in combination with high-throughput mouse gene knockout phenotyping efforts of multiple genes and advanced conditional gene inactivation in mouse models have successfully identified genes with crucial roles in cortical bone homeostasis. Particular attention in this review is given to genes, such as WNT16, POSTN and SFRP4, that differentially affect cortical and trabecular bone architecture. We propose that animal models of cortical bone metabolism will substantially contribute to developing anabolic osteoporosis therapies that improve cortical bone mass and reduce non-vertebral fracture risk.
https://ift.tt/2GWtn4E
The 2017 Sachs Lecture: Kindling Knowledge in Epilepsy
Source:Pediatric Neurology
Author(s): Solomon L. Moshé
https://ift.tt/2vcORVA
Health-Related Quality of Life for Genetically Determined Leukoencephalopathy Patients
Source:Pediatric Neurology
Author(s): Amytice Mirchi, Félixe Pelletier, Luan T. Tran, Stephanie Keller, Nancy Braverman, Davide Tonduti, Adeline Vanderver, Federico Roncarolo, Amy Pizzino, Marie-Emmanuelle Dilenge, Chantal Poulin, Michael Shevell, Annette Majnemer, Guillaume Sébire, Myriam Srour, Bradley Osterman, Renée-Myriam Boucher, Michel Vanasse, Elsa Rossignol, John Mitchell, Sunita Venkateswaran, Daniela Pohl, Marcelo Kauffman, Raphael Schiffmann, Cyril Goizet, Sebastien Moutton, Geneviève Bernard
AIMSTo characterize health-related quality of life (HRQOL) in patients with genetically determined leukoencephalopathies as it relates to the severity of clinical features and the presence/absence of a precise molecular diagnosis.METHODHRQOL was assessed using the Pediatric Quality of Life Inventory (PedsQL) model (Pediatric Quality of Life Inventory 4.0 Self and Proxy-reports) on 59 patients diagnosed with genetically determined leukoencephalopathies. In total, 38 male and 21 female patients aged from 1 to 32 years (mean 9 years), as well as their parents, completed the PedsQL HRQOL measures. In addition, participants underwent/filled detailed standardized clinical assessments/questionnaires. The correlation between HRQOL results and the severity of the clinical features as well as the presence/absence of a molecular diagnosis was analyzed.RESULTSPatients with more severe clinical features showed statistically significant lower total PedsQL scores. More specifically, lower HRQOL was noted in children with sialorrhea, wheelchair use, gastrostomy and dystonia.INTERPRETATIONIn this study, we have shown that patients with more severe clinical features experience a lower quality of life. Our study further highlights the importance of addressing both physical and psychosocial issues and discussing perception of quality of life with both parents and children. A future larger multicenter prospective study will be important to further define the burden of these diseases and identify modifiable factors.
https://ift.tt/2qx9iaM
Response to the Letter by Sora Yasri
Source:Pediatric Neurology, Volume 81
Author(s): Sarah B. Mulkey, Gilbert Vezina, Dorothy I. Bulas, Zarir Khademian, Anna Blask, Youssef Kousa, Caitlin Cristante, Lindsay Pesacreta, Adre J. du Plessis, Roberta L. DeBiasi
https://ift.tt/2vd3WWV
Systemic Lupus Erythematosus Presenting with Severe Optic Disc Edema
Source:Pediatric Neurology
Author(s): Shashank Shekhar, Hardik Sonani, Jagdish Desai, Riddhiben Patel
https://ift.tt/2vaOFpR
Diffusion-Weighted Imaging Changes in a Child with Posterior Ischemic Optic Neuropathy
Source:Pediatric Neurology
Author(s): Dana B. Harrar, Jessica Solomon, Ankoor S. Shah, Jennifer Vaughn, Adam D. Durbin, Michael J. Rivkin
IntroductionPosterior ischemic optic neuropathy (PION) results from ischemia of the retrobulbar aspect of the optic nerve. It presents as acute loss of vision without optic disc swelling. This is rare in children, with only seven cases reported to date. Neuroimaging is frequently used to aid in the diagnosis of acute visual complaints in children; however, none of the cases described to date delineate the neuroimaging findings of this entity in children.Case ReportWe describe the MRI findings in a 10-month-old boy with PION after intra-ophthalmic artery injection of chemotherapy for retinoblastoma.DiscussionAs targeted therapies for retinoblastoma and other diseases amenable to intravascular treatment delivery are more frequently used, the risk of grave vision-related side effects increases. PION should be considered in the differential diagnosis of any child presenting with acute loss of vision. Dedicated imaging of the orbits can elucidate specific findings that may aid in the diagnosis of this entity in children.
https://ift.tt/2qwZb5V
Impact of Prior Authorization of Anti-Epileptic Drugs in Children with Epilepsy
Source:Pediatric Neurology
Author(s): Elaine C. Wirrell, Alexander J. Vanderwiel, Lauren Nickels, Saskia L. Vanderwiel, Katherine C. Nickels
ObjectiveTo assess how commonly prior authorization (PA) results in treatment delay or missed doses in children with epilepsy.MethodsA survey was sent to parents of 462 children followed in a pediatric epilepsy clinic over a 10 month period. Epilepsy and insurance details were collected. Parents were asked if PA for AEDs was required in the prior year, and if so, whether it led to either (1) delayed initiation of a newly-prescribed AED, and/or (b) a lapse in coverage of a current AED. PA was defined as smooth if there was a <7 day delay in starting a new AED and no lapse in coverage of a current AED.Results164 families (35%) returned completed surveys. Mean age was 11.2 (SD 5.3) years and 67.4% had seizures >q3months despite trials of ≥2 AEDs. 136 (82.9%) had private primary insurance whereas 25 (15.2%) were on Medicaid.PA was required in 63 (38.4%) cases, and proceeded smoothly in only 31 (49.2%). 23 children experienced a delay of >7 days in starting a new AED, and 24 a lapse in coverage of their current AED (11-missed dose, 12-parents paid out of pocket to avoid missed dose, 1-accessed AED through patient assistance program). 7/11 who missed AED doses had increased seizures, and one required hospital admission for status epilepticus.ConclusionsPA of AEDs is common but problematic, often resulting in either delay of initiation of a new AED or lapse in coverage of a currently-used AED, with a negative impact on seizure control.
https://ift.tt/2vf7A2N
Short Takes
Source:Pediatric Neurology
Author(s): Steven G. Pavlakis
https://ift.tt/2HkX6DU
Editorial Board and Masthead
Source:Pediatric Neurology, Volume 81
https://ift.tt/2EJGT5Q
Neuroimaging Findings in Normocephalic Zika Virus Infection
Source:Pediatric Neurology, Volume 81
Author(s): Sora Yasri, Viroj Wiwanitkit
https://ift.tt/2HkWXAm
Remodeling of the Paradoxical Middle Turbinate: Preserving Function While Gaining Access.
| Related Articles |
Remodeling of the Paradoxical Middle Turbinate: Preserving Function While Gaining Access.
Am J Rhinol Allergy. 2018 Mar;32(2):98-100
Authors: Belcher RH, Ikeda AK, DelGaudio JM
Abstract
Background Endoscopic sinus surgery is performed for many reasons, most commonly for chronic rhinosinusitis refractory to medical treatment. A paradoxical middle turbinate is an anatomic variant that can hinder endoscopic access to the sinuses. No publication has addressed how to surgically treat a paradoxical middle turbinate. Method We present a basic endoscopic surgical approach to conservatively resect a paradoxical middle turbinate in order to improve access to the middle meatus and the sinuses while preserving support and function. Conclusion Conservative remodeling of the paradoxical middle turbinate can provide access to the sinuses while maintaining a significant portion of the middle turbinate.
PMID: 29644907 [PubMed - in process]
https://ift.tt/2GUwFWe
Histopathology in Chronic Rhinosinusitis Varies With Sinus Culture.
| Related Articles |
Histopathology in Chronic Rhinosinusitis Varies With Sinus Culture.
Am J Rhinol Allergy. 2018 Mar;32(2):112-118
Authors: Heilingoetter AL, Tajudeen B, Kuhar HN, Gattuso P, Ghai R, Mahdavinia M, Batra PS
Abstract
Background Structured histopathology reporting facilitates better understanding of the underlying pathophysiologic mechanisms of chronic rhinosinusitis. The microbiology of chronic rhinosinusitis has been studied extensively; however, distinct histopathologic changes associated with bacteria isolated in chronic rhinosinusitis are largely unknown. Objective The goal of this study is to better understand the relationship between culturable bacteria and histopathology in chronic rhinosinusitis. Methods A structured histopathology report was utilized to analyze sinus tissue removed during functional endoscopic sinus surgery in a group of patients with chronic rhinosinusitis refractory to medical therapy. Patients with cystic fibrosis or ciliary dysfunction were excluded. Histology variables included eosinophil count per high-power field, neutrophil infiltrate, basement membrane thickening, subepithelial edema, hyperplastic/papillary changes, mucosal ulceration, squamous metaplasia, fibrosis, fungal elements, Charcot-Leyden crystals, and eosinophil aggregates. Baseline Lund-Mackay score and Sinonasal Outcome Test 22 score were also collected. The association of culture data with the aforementioned variables was assessed. Results A total of 59 chronic rhinosinusitis patients who underwent functional endoscopic sinus surgery were included. Chronic rhinosinusitis patients with Pseudomonas aeruginosa had significantly increased neutrophil infiltrate (71.4% vs. 26.9%, p = 0.048), subepithelial edema (28.6% vs. 3.8%, p = 0.047), and a trend toward increased fungal elements (28.6% vs. 5.8%, p = 0.071). Chronic rhinosinusitis patients with Staphylococcus aureus had significantly more hyperplastic changes (20% vs. 2.3%, p = 0.050) and a trend toward increased squamous metaplasia (33.3% vs. 14.2%, p = 0.069). Conclusion Distinct histopathologic changes were noted based on sinus culture data for S. aureus and P. aeruginosa. These findings may have important implications on the extent of surgical management and prognosis after surgery.
PMID: 29644905 [PubMed - in process]
https://ift.tt/2EKcZ16
Survivin and cortactin expression in sinonasal schneiderian (inverted) papilloma and associated carcinoma.
| Related Articles |
Survivin and cortactin expression in sinonasal schneiderian (inverted) papilloma and associated carcinoma.
Am J Rhinol Allergy. 2018 Mar;32(2):78-81
Authors: Marioni G, Brescia G, Nicolè L, Marchese-Ragona R, Barion U, Giacomelli L, Marino F, Martini A, Ottaviano G
Abstract
BACKGROUND: Sinonasal inverted (schneiderian) papilloma (IP) is histologically benign but shows a propensity for malignant transformation. Survivin, a member of the inhibitor of the apoptosis family of proteins that controls cell division, apoptosis, metastasis, and, probably, also neoangiogenesis, is overexpressed in essentially all human cancers. Overexpression of the multidomain protein cortactin has also been associated with increased cell migration, invasion, and metastatic potential in several malignancies.
OBJECTIVE: The aim of the present study was to preliminarily investigate survivin and cortactin expression in a consecutive series of sinonasal IPs, and IP-associated squamous cell carcinomas (SCC).
METHODS: Immunohistochemical expression of nuclear survivin and cortactin was measured in 19 consecutive sinonasal IPs and 3 IP-associated SCCs.
RESULTS: The mean ± standard deviation nuclear survivin expression was 9.4 ± 9.2% and 31.7% ± 15.4% in sinonasal IPs and SCCs, respectively (p < 0.0001). Results of cortactin immunostaining was strongly positive in the cytoplasm of both sinonasal IPs and SCCs: no significant difference emerged between the IP and SCC epithelial components.
CONCLUSION: Nuclear survivin expression was significantly higher in SCCs than in IPs. Prospective, multi-institutional prognostic studies, preferably on an international scale (given the few cases treated at single institutions), are needed to confirm the role of survivin in IP malignant transformation.
PMID: 29644904 [PubMed - in process]
https://ift.tt/2qt05k2
Patients with chronic rhinosinusitis and obstructive sleep apnea have increased paroxysmal limb movement.
| Related Articles |
Patients with chronic rhinosinusitis and obstructive sleep apnea have increased paroxysmal limb movement.
Am J Rhinol Allergy. 2018 Mar;32(2):94-97
Authors: Mahdavinia M, Hui JW, Zitun M, Lastra A, Herdegen JJ, Codispoti CD, Khan RJ, LoSavio PS, Batra PS
Abstract
BACKGROUND: Patients with chronic rhinosinusitis (CRS) frequently experience sleep disruption and are at a higher than normal risk for obstructive sleep apnea (OSA). The purpose of this study was to determine how CRS affects polysomnography findings and sleep-related breathing in OSA.
METHODS: A cohort study was performed that included 107 adult patients with CRS and comorbid OSA (CRS+OSA group) and 137 patients with OSA and without CRS as the control group. An electronic medical records database was used to identify eligible subjects. Comorbid conditions and polysomnography data were compared between the two groups by using logistic and linear regression analyses.
RESULTS: A total of 246 patients were included: 107 patients in the CRS+OSA group and 137 patients with OSA and without CRS in the control group. After adjusting for demographic factors, the patients in the CRS+OSA group had a lower body mass index (BMI) and higher age at the time of diagnosis of OSA (p < 0.001). The patients in the CRS+OSA group had higher odds of having asthma and eczema. There was an increase in the periodic limb movement (PLM) index in the CRS+OSA group. Apnea and hypopnea indices were similar in the two groups.
CONCLUSION: Patients with CRS developed OSA at a lower BMI; patients CRS and OSA had similar sleep-related breathing patterns but higher risks for PLMs compared with patients with OSA and without CRS.
PMID: 29644903 [PubMed - in process]
https://ift.tt/2vcXoHN
Eccentric, mature osseous cap: A distinct imaging feature of sinonasal osteoblastoma.
| Related Articles |
Eccentric, mature osseous cap: A distinct imaging feature of sinonasal osteoblastoma.
Am J Rhinol Allergy. 2018 Mar;32(2):82-84
Authors: Dua SG, Locker PH, Rossi IR, Jandali D, Gattuso P, Batra PS, Tajudeen BA
Abstract
BACKGROUND: With the exception of osteomas, bone neoplasms that originate in the sinonasal cavity are seldom diagnosed on preoperative imaging due to a lack of characteristic radiographic features. Here we described the unusual occurrence of an osteoblastoma in the paranasal sinuses, and we drew focus to its salient imaging features. A highly unique imaging sign was indicated, and its pathologic basis was explained, with concurrent review of the literature.
METHODS: Case series and review of the literature.
RESULTS: Two cases of sinonasal osteoblastoma were managed by definitive surgical resection. Both tumors on preoperative computed tomography demonstrated an expansile, heterogeneous fibro-osseous lesion with an eccentric, mature osseous cap. The dense osseous cap seen on imaging corresponded to a rim of mature bone on histopathology. A review of existing literature revealed the presence of this imaging sign in all reported cases.
CONCLUSION: Sinonasal osteoblastoma is an extremely rare entity with undefined imaging characteristics to guide preoperative decision-making. Here we reported, to our knowledge, the first description of a characteristic imaging sign of an eccentric, mature osseous cap, which corresponded histologically to a single peripheral layer rim of osteoblasts, a unique trait of osteoblastoma.
PMID: 29644901 [PubMed - in process]
https://ift.tt/2IRbwsm
Discordance in Preoperative and Postoperative Histopathology of Sinonasal Tumors.
| Related Articles |
Discordance in Preoperative and Postoperative Histopathology of Sinonasal Tumors.
Am J Rhinol Allergy. 2018 Mar;32(2):101-105
Authors: Ganti A, Tajudeen BA, Plitt MA, Rossi I, Gattuso P, Batra PS
Abstract
Background Head and neck surgical pathology has been shown to be prone to histopathologic diagnostic error that can adversely impact patient care due to inappropriate management. Sinonasal tumors, in particular, present a diagnostic challenge given the relative rarity and diversity in histology and thus may have higher rates of discordant histology. Objective The purpose of this study is to determine the rate of discrepancy between preoperative and postoperative diagnoses of sinonasal tumors. Methods Retrospective chart review was performed on 52 patients treated for sinonasal tumors between January 2013 and December 2016. Initial diagnosis on preoperative biopsy was compared to postoperative diagnosis rendered at a single tertiary care referral center. A discrepant diagnosis was regarded as any change in diagnosis that resulted in further refinement of therapy or prognosis. Results Eleven (21.2%) patients had discrepancy between the preliminary pathology and postsurgical diagnosis. Of these diagnoses, four involved a change from a benign to a more aggressive benign or malignant process, three involved reclassification of a malignant tumor to a more aggressive histology, and four involved change from an aggressive process to benign histology. In all 11 cases, alteration in management strategy was rendered. The majority of discordant diagnoses were of fibro-osseous lesions and small round blue cell tumors. Conclusion Sinonasal tumors exhibit a high degree of discordance from preoperative to postoperative diagnosis. Critical decision-making should be reserved until careful review of operative specimens is performed to minimize patient morbidity and unnecessary interventions.
PMID: 29644900 [PubMed - in process]
https://ift.tt/2GZzdht
Technical notes on the endoscopic endonasal approach to the craniovertebral junction for odontoidectomy.
| Related Articles |
Technical notes on the endoscopic endonasal approach to the craniovertebral junction for odontoidectomy.
Am J Rhinol Allergy. 2018 Mar;32(2):85-86
Authors: Tang D, Roxbury C, D'Anza B, Kshettry V, Woodard T, Recinos P, Sindwani R
Abstract
INTRODUCTION: Odontoidectomy can help decompress ventral compression of the brainstem and upper cervical spinal cord in the presence of bony abnormalities of the craniovertebral junction (CVJ), e.g., an odontoid pannus. Endonasal approaches have been shown to be associated with lower morbidity compared with traditional transoral approaches. We demonstrated an entirely endonasal approach to the CVJ.
MATERIALS AND METHODS: We presented our technique for performing an endoscopic endonasal odontoidectomy.
RESULTS: The patient underwent an open posterior cervical spinal fusion to stabilize the CVJ due to destabilization that occurs with odontoidectomy either as part of a single procedure or in a staged manner, depending on the surgeon's preference. By using a two-surgeon, multihanded technique in collaboration with neurosurgery, the anterior CVJ was safely approached endoscopically through the nasopharynx. A midline incision was created and the soft tissue was lateralized widely. The first cervical vertebra (C1) arch was removed with a drill exposing the odontoid process and any associated pannus, which were then resected. Because this approach was entirely extradural, no reconstruction was necessary. Closure was accomplished by placing absorbable packing material in the defect and medializing the nasopharyngeal tissues.
CONCLUSION: Endoscopic endonasal odontoidectomy offers excellent exposure and less morbidity than traditional transoral approaches. This technique should be considered in appropriately selected patients.
PMID: 29644899 [PubMed - in process]
https://ift.tt/2Hx6vFS
A New Chapter for the American Journal of Rhinology and Allergy.
| Related Articles |
A New Chapter for the American Journal of Rhinology and Allergy.
Am J Rhinol Allergy. 2018 Mar;32(2):77
Authors: Chandra RK, Peters AT, Sindwani R
PMID: 29644898 [PubMed - in process]
https://ift.tt/2quCKOI
Effects of a Thermosensitive In Situ Gel Containing Mometasone Furoate on a Rat Allergic Rhinitis Model.
| Related Articles |
Effects of a Thermosensitive In Situ Gel Containing Mometasone Furoate on a Rat Allergic Rhinitis Model.
Am J Rhinol Allergy. 2018 Jan 01;:1945892418764951
Authors: Altuntaş E, Yener G, Doğan R, Aksoy F, Şerif Aydın M, Karataş E
Abstract
Background Mometasone furoate, one of the second generation intranasal corticosteroids, is currently used in suspension form due to its poor solubility. However, this is not favorable for nasal application because of the rapid elimination of the instilled drug from the nasal cavity by mucociliary clearance and delayed onset of action due to the slow dissolution of drug in suspension. Objective The aim of this study was to determine the antiallergic effects of mucoadhesive thermosensitive in situ gel containing mometasone furoate that we developed previously to prolong the contact between the drug and nasal mucosa and to prevent drainage of the formulation in an ovalbumin-induced rat model of allergic rhinitis. Methods An experimental allergic rhinitis model was developed in female Wistar albino rats by intraperitoneal injection of ovalbumin every 2 days for 14 days followed by its repeated intranasal instillation for 7 consecutive days. Intranasal instillation of ovalbumin was continued every other day for 14 days. Mometasone furoate in situ gel (5 μg/10 µl), mometasone furoate suspension (5 μg/10 µl), and physiological saline (10 µl) were administered into the bilateral nasal cavities from day 22 to day 35. Antiallergic effects were evaluated through histopathological evaluation, analysis of ovalbumin-specific serum immunoglobulin E, and a symptom score. Results Mometasone furoate in situ gel significantly decreased the nasal symptoms and ovalbumin-specific serum immunoglobulin E level as compared with mometasone furoate suspension and physiological saline. Additionally, inflammatory histological symptoms such as mucosal edema, vascular dilatation, eosinophil infiltration, and loss of cilia within the nasal mucosa of allergic rhinitis model rats were remarkably improved with the treatment of mometasone furoate in situ gel. Conclusion These results suggest that mometasone furoate in situ gel has a better therapeutic potential for the treatment of allergic rhinitis compared to mometasone furoate suspension.
PMID: 29644886 [PubMed - as supplied by publisher]
https://ift.tt/2EKtMRL
Diagnostic Accuracy of Symptoms, Endoscopy, and Imaging Signs of Chronic Rhinosinusitis Without Nasal Polyps Compared to Allergic Rhinitis.
| Related Articles |
Diagnostic Accuracy of Symptoms, Endoscopy, and Imaging Signs of Chronic Rhinosinusitis Without Nasal Polyps Compared to Allergic Rhinitis.
Am J Rhinol Allergy. 2018 Jan 01;:1945892418762891
Authors: Koskinen A, Numminen J, Markkola A, Karjalainen J, Karstila T, Seppälä M, Julkunen A, Lemmetyinen R, Pekkanen J, Rautiainen M, Dastidar P, Hytönen M, Toppila-Salmi S
Abstract
Objectives The diagnosis of chronic rhinosinusitis without nasal polyps (CRSsNP) and distinguishing it from allergic rhinitis is difficult. Yet, early detection of CRSsNP is important to prevent progressive and severe chronic rhinosinusitis. Our aim was to compare diagnostic accuracy of symptoms, endoscopy, and imaging signs of CRSsNP and allergic rhinitis -only phenotypes. Setting Prospective controlled follow-up study. Participants Forty-two nonsmoking patients visiting tertiary care due to CRSsNP and 19 nonsmoking volunteer controls with allergic rhinitis filled a symptoms questionnaire and underwent nasal endoscopy off-seasonally. All CRSsNP patients underwent computed tomography scans of paranasal sinuses. All the allergic rhinitis control subjects and 14 of the CRSsNP patients underwent sinus magnetic resonance imaging. Results Radiologic Lund-Mackay score, duration of symptoms, visual analogue scale scores of symptoms, and Sinonasal Outcome Test 22 were significantly higher in the CRSsNP group compared to allergic rhinitis control group. These factors also correlated in part with each other. Endoscopic score did not correlate with other factors, nor did it differ between CRSsNP and allergic rhinitis groups. The highest area under curve value was demonstrated for visual analogue scale score of facial pain/pressure (0.93) and score ≥4/10 showed 60% sensitivity and 95% specificity for detecting CRSsNP group ( P < .001). Radiologic sign of obstructed osteomeatal complex showed 100% specificity and 38% sensitivity for detecting CRSsNP group ( P < .001). Conclusions CRSsNP phenotype could be primarily distinguished from allergic rhinitis by higher facial pain/pressure score and secondarily by radiologic sings of obstructed ostiomeatal complex and higher Lund-Mackay score. Endoscopic score has limited value in distinguishing CRSsNP from allergic rhinitis.
PMID: 29644866 [PubMed - as supplied by publisher]
https://ift.tt/2Hm1KkR
HPV: Molecular Pathways and Targets
Source:Current Problems in Cancer
Author(s): Shilpi Gupta, Prabhat Kumar, Bhudev C. Das
Infection of high-risk human papillomaviruses (HR-HPVs) is a prerequisite for the development of cervical carcinoma. HPV infections are also implicated in the development of other types of carcinomas. Chronic or persistent infection of HPV is essential but HPV alone is inadequate, additional endogenous and/or exogenous cues are needed along with HPV to induce cervical carcinogenesis. The strategies that HR-HPVs have developed in differentiating epithelial cells to reach a DNA-synthesis competent state leading to tumorigenic transformation are basically due to overexpression of the E6 and E7 oncoproteins and the activation of diverse cellular regulatory/signalling pathways that are targeted by them. Moreover, the Wnt/β-catenin/Notch and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathways are deregulated in various cancers, and have also been implicated in HPV-induced cancers. These are basically related to the 'cancer hallmarks', and include sustaining proliferative signals, the evasion of growth suppression and immune destruction, replicative immortality, inflammation, invasion, metastasis and angiogenesis, as well as genome instability, resisting cell death and deregulation of cellular energetics. These information could eventually aid in identifying and/or developing new diagnostic, prognostic biomarkers, and may contribute to design more effective targeted therapeutics and treatment strategies. Although surgery, chemotherapy and radiotherapy can cure more than 90% of women with early stage cervical cancer, the recurrent and metastatic disease remains a major cause of cancer mortality. Numerous efforts have been made to design new drugs and develop gene therapies to treat cervical cancer. In recent years, research on treatment strategies has proposed several options, including the role of HPV E5, E6 and E7 oncogenes, which are retained and overexpressed in most of the cervical cancers and whose respective oncoproteins are critical to the induction and maintenance of the malignant phenotype. Other efforts have been focused on antitumor immunotherapy strategies. It is known that during the development of cervical cancer, a cascade of abnormal events is induced, including disruption of cell cycle control, perturbation of antitumor immune response, alteration of gene expression, deregulation of microRNA and cancer stem cell and stemness related markers expression could serve as novel molecular targets for reliable diagnosis and treatment of HPV positive cancers. However, the search for new proposals for disease control and prevention has brought new findings and approaches in the context of molecular biology indicating innovations and perspectives in the early detection and prevention of the disease. Thus, in this article, we discuss molecular signalling pathways activated by HPV and potential targets/biomarkers for early detection/prevention and the treatment of HPV-associated cancers.
https://ift.tt/2HAsM5J
Bifocal hepatocellular carcinoma (HCC): Magnetic resonance imaging features after trans-arterial embolization (TAE)
Publication date: Available online 28 March 2018
Source:Current Problems in Cancer
Author(s): Picchia Simona, Bali Maria Antonietta
https://ift.tt/2HzlEqb
The role of epigenetic therapies in colorectal cancer
Source:Current Problems in Cancer
Author(s): Marina Baretti, Nilofer Saba Azad
Although developments in the diagnosis and therapy of colorectal cancer (CRC) have been made in the last decade, much work remains to be done as it remains the second leading cause of cancer death. It is now well established that epigenetic events, together with genetic alterations, are key events in initiation and progression of CRC. Epigenetics refers to heritable alterations in gene expression that do not involve changes in the DNA sequence. These alterations include DNA methylation, histone alterations, chromatin remodelers, and noncoding RNAs. In CRC, aberrations in epigenome may also involve in the development of drug resistance to conventional drugs such as 5-fluorouracil, oxaliplatin, and irinotecan. Thus, it has been suggested that combined therapies with epigenetic agents may reverse drug resistance. In this regard, DNA methyltransferase inhibitors and histone deacetylase inhibitors have been extensively investigated in CRC. The aim of this review is to provide a brief overview of the preclinical data that represent a proof of principle for the employment of epigenetic agents in CRC with a focus on the advantages of combinatorial therapy over single-drug treatment. We will also critically discuss the results and limitations of initial clinical experiences of epigenetic-based therapy in CRC and summarize ongoing clinical trials. Nevertheless, since recent translational research suggest that epigenetic modulators play a key role in augmenting immunogenicity of the tumor microenvironment and in restoring immune recognition, we will also highlight the recent developments of combinations strategies of immunotherapies and epigenetic therapies in CRC, summarizing preclinical, and clinical data to signify this evolving and promising field for CRC treatment.
https://ift.tt/2GZ6lWW
A six-microRNA signature predicts survival of patients with uterine corpus endometrial carcinoma
Source:Current Problems in Cancer
Author(s): Yue Wang, Mu Xu, Qing Yang
Uterine corpus endometrial carcinoma (UCEC) is one of the most common female gynecological malignant tumors that threaten women health seriously. MicroRNAs (miRNAs) has been proved to play critical roles in tumor pathogenesis and malignant progression. In this study, we aimed to explore a novel signature of microRNA expression for predicting the overall survival (OS) of patients with UCEC. The genome-wide miRNA expression profiles and relevant clinical characteristics of 348 patients with UCEC were downloaded from the Cancer Genome Atlas (TCGA) data portal and analyzed comprehensively. A total of 144 miRNAs were confirmed to be expressed differentially in tumor tissues. Among them, 6 miRNAs (hsa-mir-15a.MIMAT0000068, hsa-mir-142.MIMAT0000433, hsa-mir-142.MIMAT0000434, hsa-mir-3170.MIMAT0015045, hsa-mir-1976.MIMAT0009451, and hsa-mir-146a.MIMAT0000449) were validated to be significantly correlated with the OS of patients with UCEC. The risk indictor established by the 6-microRNA signature was proved be an independent prognostic factor (Hazard ratio = 0.391; 95% CI: 0.195-0.783; P = 0.008). In conclusion, we identified miRNAs that were correlated with the occurrence and progression of UCEC and established a 6-microRNA expression signature as a predictor for the OS of patients with UCEC.
https://ift.tt/2GWoO6o
Risk factors for prostate cancer: A multifactorial case-control study
Source:Current Problems in Cancer
Author(s): Saima Shakil Malik, Rakshanda Batool, Nosheen Masood, Azra Yasmin
Prostate cancer is the third most commonly diagnosed cancer among Pakistani men. It is a multifactorial disease involving genetics together with environmental factors. Countries where men have greater dietary fat intake showed increased prostate cancer mortality rates. A population based case-control study was conducted to evaluate various prostate cancer risk factors. Study subjects were 896 prostate cancer cases (2010-2015) and 900 age matched controls. Odds ratio (OR) and 95% CI were used to estimate the association between different risk factors and prostate cancer. P values for different factors were computed by t-test, chi-square test, and Fisher exact test. Results showed significant association of increased age (OR = 10.6; CI: 7.92-14.31; P = 0.0001; Z = 15.7) and smoking (P = 0.05) with risk of disease. Consistent evidence suggested that fruits (P = 0.0001), vegetables (P = 0.0007), and diabetes mellitus (OR = 0.84; CI: 0.72-0.97; P = 0.02; Z = 2.28) were significantly associated with decreased prostate cancer risk. Comparison of education, marital status, occupation, intake of meat (<100 grams/week, 101-250 grams/week, >250 grams/week), number of cigarettes smoked per day, smoking duration, and family history of disease among cases and controls were not associated (P > 0.05) with risk of prostate cancer. Most of the prostate cancer patients were at stage IV with a Gleason score ranging from 7-9 and had undergone surgery. This epidemiological study illustrated that age and smoking were potential risk factors for prostate cancer in Pakistani men. Furthermore, phytonutrients can reduce its risk to a greater extent. Prospective studies with detailed analysis and greater sample size are required to explore more accurate findings.
https://ift.tt/2HyR543