Τρίτη, 23 Μαΐου 2017

Back and neck pain prevalence and their association with physical inactivity domains in adolescents

Abstract

Purpose

Back pain affects people of all ages. This may be associated with physical inactivity, and in the case of physical activity in different domains, the relationship with back pain is not clear in the literature. The aim of this study was to estimate the prevalence of low back and neck pain and investigate their association in different domains of physical inactivity.

Methods

1011 randomly selected students participated in this study. Neck and back pain were assessed using the Nordic questionnaire, whereas the Baecke Physical Activity questionnaire was used to measure physical activity domains. Separate Binary Logistic Regression models were performed to investigate the association of physical activity domains with neck or back pain.

Results

17.4% of the students reported cervical pain, while 18.0% reported low back pain. Older adolescents had a higher prevalence of cervical pain (24.4%) than younger adolescents (11.9%) (p value <0.001), as well as lumbar pain, being 25.1% in older adolescents and 12.4% in younger (p value <0.001). Adolescents physically inactive in the school environment were less likely to have pain in the cervical region [OR 0.67 (0.44–0.99)] or back pain [OR 0.60 (0.40–0.91)]. Being inactive in occupational activities was associated with cervical pain [OR 1.49 (1.06–2.10)]. Being inactive in the sports environment presented a marginal relationship with pain in the cervical region [OR 1.41 (0.99–2.02)].

Conclusions

The prevalence of neck and low back pain was higher in older adolescents and physical inactivity in the sporting context and occupational activities could be a risk factor to increase the chances of back pain.



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Determinants of the biomechanical and radiological outcome of surgical correction of adolescent idiopathic scoliosis surgery: the role of rod properties and patient characteristics

Abstract

Purpose

Aim of the study was to evaluate the role of the mechanical properties of the rod and of the characteristics of the patients (age, skeletal maturity, BMI, and Lenke type) in determining the deformity correction, its maintenance over time and the risk of mechanical failure of the instrumentation.

Methods

From March 2011 to December 2014 120 patients affected by AIS underwent posterior instrumented fusion. Two 5.5-mm CoCr rods were implanted in all patients. For every patient, age, sex, Risser grade, Lenke type curve, flexibility of the main curve, body mass index (BMI), and percentage of correction were recorded. In all patients, the Cobb angle value and rod curvature angle (RC) were evaluated. RC changes were registered and correlated to each factor to establish a possible statistically significance in a multivariate analysis. A biomechanical model was constructed to study the influence of rod diameter and material as well as the density of the anchoring implants in determining stress and deformation of rods after contouring and implantation.

Results

Radiographic and biomechanical analysis showed a different mean rod deformation for concave and convex side: 7.8° and 3.9°, respectively. RC mean value at immediate follow-up was 21.8° for the concave side and 14.6° for the convex. At 2-year minimum follow-up, RC value increases 1.5° only for the concave side. At 3.5-year mean follow-up, RC value increases 2.7°, p = 0.003, for the concave side and 1.3° for the convex, p = 0.06. The use of the stiffest material as well as of the lowest diameter resulted in higher stresses in the rods. The use of either a low or a high instrumentation density resulted only in minor differences in the loss of correction.

Conclusions

Rod diameter and material as well as patient characteristics such as BMI, age, and Risser grade play an important role in deformity correction and its maintenance over time.



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Upcoming Events in Pediatric Cardiology



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Transcatheter Retrieval of Cardiovascular Foreign Bodies in Children: A 15-Year Single Centre Experience

Abstract

There has been a rapid increase in the practice of interventional catheter treatment of congenital heart disease. Catheter retrieval of embolized cardiac devices and other foreign bodies is essential, yet no large studies have been reported in the paediatric population. Retrospective 15-year review of all children who underwent transcatheter foreign body retrieval in a tertiary cardiac centre from January 1997 to September 2012. Transcatheter retrieval of foreign bodies from the cardiovascular system was attempted in 78 patients [median age 4 (0.02–16) years and median weight 15 (1.7–74) kg] including 46 embolized devices. Transcatheter retrieval was successful in 70/78 (90%), surgical retrieval was required in 6. In two patients, small embolized coils were left in situ. Gooseneck snare was the most commonly used retrieval device. Median procedure and screening times were 90 (15–316) and 31 (2–161) min, respectively. There were no procedural deaths. Transient loss of foot pulses occurred in 5 and 2 patients required blood transfusion. Transcatheter retrieval of cardiovascular foreign bodies can be performed safely in the majority of children thus obviating the need for surgery. It is essential to have a comprehensive inventory of retrieval equipment and interventional staff conversant with its use.



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Variation in Copper Accumulation at the Tissue Level of Five Hybrid Poplars Subjected to Copper Stress

Abstract

Heavy metal contamination causes significant environmental problems around the world and poses a threat to human health. Poplar hybrids present features for potential uses in phytoremediation systems in areas with heavy metal contamination. The purpose of this study was to assess the copper (Cu) accumulation level in five poplar inter-species hybrids [(Populus trichocarpa × Populus deltoides) × P. deltoides; P. deltoides × Populus nigra; P. trichocarpa × Populus maximowiczii; P. trichocarpa × P. nigra; and (P. trichocarpa × P. deltoides) × (P. trichocarpa × P. deltoides)] grown in a hydroponic system. The treatments entailed the application of low and high doses of Cu of 8.0 and 16.0 μM, respectively. Cu accumulation was observed in roots, stems, and leaves, which was determined using flame atomic absorption spectroscopy, prior acid digestion of each sample. The methodology was validated according to certified reference material (Cypress BIMEP 432). Significant differences in Cu accumulation were found among genotypes for both roots and leaves, but not for stems. In roots, the genotype P. deltoides × P. nigra had a Cu accumulation level of 169.8% higher than the average accumulation found in the other genotypes. The (P. trichocarpa × P. deltoides) × P. deltoides hybrid showed the least Cu accumulation in leaves. The results of this study can potentially be used for proper crossovers and hybrids selection within the genus Populus for phytoremediation of Cu contaminated land.



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Airway management during induction of anaesthesia, spontaneous ventilation (SV) and controlled mechanical ventilation (CMV), using an endotracheal tube (ETT), laryngeal mask (LM), rabbit-specific supraglottic airway device (v-gel) or facemask (FM).






Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

Curcumin attenuates lipopolysaccharide/d-galactosamine-induced acute liver injury

Curcumin, a polyphenol in curry spice isolated from the rhizome of turmeric, has been reported to possess versatile biological properties including anti-inflammatory, anti-oxidant, antifibrotic, and anticancer activities. In this study, the hepatoprotective effect of curcumin was investigated in lipopolysaccharide (LPS)/d-galactosamine (d-GalN)-induced acute liver injury (ALI) in rats. Experimental ALI was induced with an intraperitoneal (ip) injection of sterile 0.9% sodium chloride (NaCl) solution containing 8μg LPS and 800mg/kg d-GalN. Curcumin was administered once daily starting three days prior to LPS/d-GalN treatment. Results indicated that curcumin could attenuate hepatic pathological damage, decrease serum ALT and AST levels, and reduce malondialdehyde (MDA) content in experimental ALI rats. Moreover, higher dosages of curcumin pretreatment inhibited NF-κB activation and reduced serum TNF-α and liver TNF-α levels induced by LPS/d-GalN ip injection. Furthermore, we found that curcumin up-regulated the expression of nuclear Nrf2 and Nrf2-dependent antioxidant defense genes including heme oxygenase-1 (HO-1), glutamate-cysteine ligase (GCLC), NAD(P)H dehydrogenase, and quinone (NQO-1) in a dose-dependent manner. Our results showed that curcumin protected experimental animals against LPS/d-GalN-induced ALI through activation of Nrf2 nuclear translocation and inhibition of NF-κB activation.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

Gout

Gout: Condition characterized by abnormally elevated levels of uric acid in the blood, recurring attacks of joint inflammation (arthritis), deposits of hard lumps of uric acid in and around the joints, and decreased kidney function and kidney stones. Uric acid is a breakdown product of purines, that are part of many foods we eat. The tendency to develop gout and elevated blood uric acid level (hyperuricemia) is often inherited and can be promoted by obesity, weight gain, alcohol intake, high blood pressure, abnormal kidney function, and drugs. The most reliable diagnostic test for gout is the identification of crystals in joints, body fluids and tissues.



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Matching phenotypes to whole genomes: Lessons learned from four iterations of the personal genome project community challenges

Abstract

The advent of next generation sequencing has dramatically decreased the cost for whole genome sequencing and increased the viability for its application in research and clinical care. The Personal Genome Project (PGP) provides unrestricted access to genomes of individuals and their associated phenotypes. This resource enabled the Critical Assessment of Genome Interpretation (CAGI) to create a community challenge to assess the bioinformatics community's ability to predict traits from whole genomes. In CAGI PGP challenge, researchers were asked to predict whether an individual had a particular trait or profile based on their whole genome. Several approaches were used to assess submissions, including ROC AUC (Area Under Receiver Operating Characteristic Curve), probability rankings, the number of correct predictions, and statistical significance simulations. Overall, we found that prediction of individual traits is difficult, relying on a strong knowledge of trait frequency within general population, while matching genomes to trait profiles relies heavily upon a small number of common traits including ancestry, blood type, and eye color. When a rare genetic disorder is present, profiles can be matched when one or more pathogenic variants are identified. Prediction accuracy has improved substantially over six years due to improved methodology and a better understanding of features.

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In vivo effect of Commiphora swynnertonii ethanolic extracts on Trypanosoma congolense and selected immunological components in mice

The search for alternative trypanocidal compounds which can be available at affordable price is of paramount importance for control of trypanosomosis in human and animals. The current study evaluates the in vi...

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A multi-target therapeutic potential of Prunus domestica gum stabilized nanoparticles exhibited prospective anticancer, antibacterial, urease-inhibition, anti-inflammatory and analgesic properties.

Phytotherapeutics exhibit diverse pharmacological effects that are based on the combined action of a mixture of phytoconstituents. In this study, Prunus domestica gum-loaded, stabilized gold and silver nanopartic...

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The progressive fragmentation of the KIT/PDGFRA wild-type (WT) gastrointestinal stromal tumors (GIST)

Recent advances in molecular biology have revolutionized the concept of KIT/PDGFRA wild type (WT) gastrointestinal stromal tumors (GIST) than the past. Indeed, from being defined as GIST without KIT or PDGFRA ...

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The spleen in liver cirrhosis: revisiting an old enemy with novel targets

The spleen is a secondary lymphoid organ which can influence the progression of multiple diseases, notably liver cirrhosis. In chronic liver diseases, splenomegaly and hypersplenism can manifest following the ...

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Blood metabolomic fingerprint is distinct in healthy coronary and in stenosing or microvascular ischemic heart disease

The endothelium is a key variable in the pathogenesis of atherosclerosis and its complications, particularly coronary artery disease (CAD). Current evidence suggests that the endothelial status can be regarded...

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Quality indicators for the acute and long-term management of anaphylaxis: a systematic review

The quality of acute and long-term anaphylaxis management is variable and this contributes to the poor outcomes experienced by many patients. Clinical practice guidelines have the potential to improve outcomes...

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Transactions of the Geological Society of London

Transactions of the Geological Society of London, published by Geological Society of London, last updated on 2017-05-23, available at http://ift.tt/2rfqWBW

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Vinasse fertirrigation alters soil resistome dynamics: an analysis based on metagenomic profiles

Every year around 300 Gl of vinasse, a by-product of ethanol distillation in sugarcane mills, are flushed into more than 9 Mha of sugarcane cropland in Brazil. This practice links fermentation waste management...

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CEROPLASTICS: Modelling the Flesh International Congress on Wax Modelling



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Corrigendum



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Recessive mutations in MSTO1 cause mitochondrial dynamics impairment, leading to myopathy and ataxia

Abstract

We report here the first families carrying recessive variants in the MSTO1 gene: compound heterozygous mutations were identified in two sisters and in an unrelated singleton case, who presented a multisystem complex phenotype mainly characterized by myopathy and cerebellar ataxia. Human MSTO1 is a poorly studied protein, suggested to have mitochondrial localization and to regulate morphology and distribution of mitochondria. As for other mutations affecting genes involved in mitochondrial dynamics, no biochemical defects typical of mitochondrial disorders were reported. Studies in patients’ fibroblasts revealed that MSTO1 protein levels were strongly reduced, the mitochondrial network was fragmented and the fusion events among mitochondria were decreased, confirming the deleterious effect of the identified variants and the role of MSTO1 in modulating mitochondrial dynamics. We also found that MSTO1 is mainly a cytosolic protein. These findings indicate recessive mutations in MSTO1 as a new cause for inherited neuromuscular disorders with multisystem features.

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Deep Hashing Based Fusing Index Method for Large-Scale Image Retrieval

Hashing has been widely deployed to perform the Approximate Nearest Neighbor (ANN) search for the large-scale image retrieval to solve the problem of storage and retrieval efficiency. Recently, deep hashing methods have been proposed to perform the simultaneous feature learning and the hash code learning with deep neural networks. Even though deep hashing has shown the better performance than traditional hashing methods with handcrafted features, the learned compact hash code from one deep hashing network may not provide the full representation of an image. In this paper, we propose a novel hashing indexing method, called the Deep Hashing based Fusing Index (DHFI), to generate a more compact hash code which has stronger expression ability and distinction capability. In our method, we train two different architecture’s deep hashing subnetworks and fuse the hash codes generated by the two subnetworks together to unify images. Experiments on two real datasets show that our method can outperform state-of-the-art image retrieval applications.

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Txndc9 Is Required for Meiotic Maturation of Mouse Oocytes

Txndc9 (thioredoxin domain containing protein 9) has been shown to be involved in mammalian mitosis; however, its function in mammalian oocyte meiosis remains unclear. In this study, we initially found that Txndc9 is expressed during meiotic maturation of mouse oocytes and higher expression of Txndc9 mRNA and protein occurred in germinal vesicle (GV) stage. By using confocal scanning, we observed that Txndc9 localized at both nucleus and cytoplasm, especially at spindle microtubules. Specific depletion of Txndc9 by siRNA in mouse oocyte resulted in decreasing the rate of first polar body extrusion and increasing abnormal spindle assemble. Moreover, knockdown of Txndc9 in germinal vesicle (GV) stage oocytes led to higher level of reactive oxygen species (ROS) and lower level of antioxidant glutathione (GSH) as compared with control oocytes, which indicated that Txndc9 may be involved in mediating the redox balance. In summary, our results demonstrated that Txndc9 is crucial for mouse oocyte maturation by regulating spindle assembly, polar body extrusion, and redox status.

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Experimental Investigation on the Material Removal of the Ultrasonic Vibration Assisted Abrasive Water Jet Machining Ceramics

The ultrasonic vibration activated in the abrasive water jet nozzle is used to enhance the capability of the abrasive water jet machinery. The experiment devices of the ultrasonic vibration assisted abrasive water jet are established; they are composed of the ultrasonic vibration producing device, the abrasive supplying device, the abrasive water jet nozzle, the water jet intensifier pump, and so on. And the effect of process parameters such as the vibration amplitude, the system working pressure, the stand-off, and the abrasive diameter on the ceramics material removal is studied. The experimental result indicates that the depth and the volume removal are increased when the ultrasonic vibration is added on abrasive water jet. With the increase of vibration amplitude, the depth and the volume of material removal are also increased. The other parameters of the ultrasonic vibration assisted abrasive water jet also have an important role in the improvement of ceramic material erosion efficiency.

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Time Optimal Control of a Thermoelastic System

This paper considers the numerical approximation for the time optimal control problem of a thermoelastic system with some control and state constraints. By the Galerkin finite element method (FEM), the original problem is projected into a semidiscrete optimal control problem governed by a system of ordinary differential equations. Then the optimal time and control parameterization method is applied to reduce the original system to an optimal parameter selection problem, in which both the optimal time and control are taken as decision variables to be optimized. This problem can be solved as a nonlinear optimization problem by a hybrid algorithm consisting of chaotic particle swarm optimization (CPSO) and sequential quadratic programming (SQP) algorithm. The numerical simulations demonstrate the effectiveness of the proposed numerical approximation method.

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Williams-Beuren Syndrome and Congenital Lobar Emphysema: Uncommon Association with Common Pathology?

Introduction. Congenital lobar emphysema (CLE) and Williams-Beuren Syndrome are two rare conditions that have only been reported together in a single case study. Case Presentation. We report another case of a male Caucasian newborn with nonspecific initial respiratory distress, with detection of CLE on repeat chest X-ray on Day 25 of life and concurrent ventricular septal defect, supravalvular aortic stenosis, and branch pulmonary stenosis, in whom a 7q11.23 deletion consistent with Williams-Beuren Syndrome was made. Conclusion. A diagnosis of congenital lobar emphysema should prompt further screening for congenital heart disease and genetic deletion, and further research is needed to investigate the role of elastin gene mutation in the development of the neonatal lung.

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Serum Metabolomics Profiling to Identify Biomarkers for Unstable Angina

Although statistical evidence is clear regarding the dangerousness of unstable angina (UA), a form of coronary heart disease (CHD) characterised by high mortality and morbidity globally, it is important to recognise that diagnostic precision for the condition is unfavourable. In the present research, to gain insight into candidate biomarkers, the author draws on 1H NMR-based serum metabolic profiling to analyze the unstable angina pectoris (UAP) metabolic signatures; this constitutes an effective way to produce medical diagnosis. 101 unstable angina pectoris patients and 132 healthy controls were enrolled and 22 serum samples from each group were analyzed. Effective separation was noted regarding the UAP and control groups, and, for the former group considered in relation to their counterpart, the serum concentrations of Lac, m-I, lipid, VLDL, 3-HB, and LDL were higher whereas the concentrations of Thr, Cr, Cho, PC/GPC, Glu, Gln, Lys, HDL, Ile, Leu, and Val were lower. The conclusion drawn in view of the results is that the plasma metabolomics examined by 1H NMR displayed promise for biomarker identification for UA. In addition to this, the analysis illuminated the metabolic processes of UA.

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Staphylococcus saprophyticus Recovered from Humans, Food, and Recreational Waters in Rio de Janeiro, Brazil

Staphylococcus saprophyticus is an important agent of urinary tract infection (UTI) in young women, but information about this pathogen in human microbiota and in common environment is lacking. The aim of this study was to characterize S. saprophyticus isolates from genitoanal microbiota of 621 pregnant women, 10 minas cheese packs, and five beaches in Rio de Janeiro city and compare PFGE profiles of these isolates with five UTI PFGE clusters described in this city. We investigated 65 S. saprophyticus isolates from microbiota, 13 from minas cheese, and 30 from beaches and 32 UTI isolates. Antimicrobial resistance was determined by disk diffusion, MIC by agar dilution, and PCR. Erythromycin-resistance genes erm(C), msr(A), msr(B), mph(C), and lin(A) were found in 93% of isolates. Trimethoprim-sulfamethoxazole resistance correlated with dfrG or dfrA genes. Three cefoxitin-resistant isolates carried the mecA gene. All isolates obtained from cheese were susceptible to all antimicrobial agents. Six of 10 pregnant women with >1 isolate had monoclonal colonization. Isolates from pregnant women shared 100% similarity with UTI PFGE cluster types A and E obtained almost 10 years previously, suggesting temporal persistence of S. saprophyticus. Antimicrobial resistance of beach isolates reflected the profiles of human isolates. Taken together, results indicate a shared source for human and environmental isolates.

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Remote Assessment of Platelet Function in Patients with Acute Stroke or Transient Ischaemic Attack

Background. The TARDIS trial assessed the safety and efficacy of intensive versus guideline antiplatelet agents given for one month in patients with acute stroke or TIA. The aim of this substudy was to assess the effect of antiplatelet agents taken at baseline on platelet function reactivity and activation. Methods. Platelet function, assessed by remotely measured surface expression of P-selectin, was assessed in patients at their time of randomisation. Data are median fluorescence values. Results. The aspirin P-selectin test demonstrated that platelet expression was lower in 494 patients taking aspirin than in 162 patients not: mean 210 (SD 188) versus 570 (435), difference 360.3 (95% CI 312.2–408.4) (). Aspirin did not suppress P-selectin levels below 500 units in 23 (4.7%) patients. The clopidogrel test showed that platelet reactivity was lower in 97 patients taking clopidogrel than in 585 patients not: 655 (296) versus 969 (315), difference 314.5 (95% CI 247.3–381.7) (). Clopidogrel did not suppress P-selectin level below 860 units in 24 (24.7%) patients. Conclusions. Aspirin and clopidogrel suppress stimulated platelet P-selectin, although one-quarter of patients on clopidogrel have high on-treatment platelet reactivity. Platelet function testing may be performed remotely in the context of a large multicentre trial. Trial registration ISRCTN47823388.

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Natural Language Processing and Fuzzy Tools for Business Processes in a Geolocation Context

In the geolocation field where high-level programs and low-level devices coexist, it is often difficult to find a friendly user interface to configure all the parameters. The challenge addressed in this paper is to propose intuitive and simple, thus natural language interfaces to interact with low-level devices. Such interfaces contain natural language processing (NLP) and fuzzy representations of words that facilitate the elicitation of business-level objectives in our context. A complete methodology is proposed, from the lexicon construction to a dialogue software agent including a fuzzy linguistic representation, based on synonymy.

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Modeling and Simulation Study of Designer’s Bidirectional Behavior of Task Selection in Open Source Design Process

Open source design (OSD) is an emerging mode of product design. In OSD process, how to select right tasks directly influences the efficiency and quality of task completion, hence impacting the whole evolution process of OSD. In this paper, designer’s bidirectional behavior of task selection integrating passive selection based on website recommendation and autonomous selection is modeled. First, the model of passive selection behavior by website recommendation is proposed with application of collaborative filtering algorithm, based on a three-dimensional matrix including information of design agents, tasks, and skills; second, the model of autonomous selection behavior is described in consideration of factors such as skill and incentive; third, the model of bidirectional selection behavior is described integrating the aforementioned two selection algorithms. At last, contrast simulation analysis of bidirectional selection, passive selection based on website recommendation, and autonomous selection is proposed with ANOVA, and results show that task selection behavior has significant effect on OSD evolution process and that bidirectional selection behavior is more effective to shorten evolution cycle according to the experiment settings. In addition, the simulation study testifies the model of bidirectional selection by describing the task selection process of OSD in microperspective.

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Analysis Bending Solutions of Clamped Rectangular Thick Plate

The bending solutions of rectangular thick plate with all edges clamped and supported were investigated in this study. The basic governing equations used for analysis are based on Mindlin’s higher-order shear deformation plate theory. Using a new function, the three coupled governing equations have been modified to independent partial differential equations that can be solved separately. These equations are coded in terms of deflection of the plate and the mentioned functions. By solving these decoupled equations, the analytic solutions of rectangular thick plate with all edges clamped and supported have been derived. The proposed method eliminates the complicated derivation for calculating coefficients and addresses the solution to problems directly. Moreover, numerical comparison shows the correctness and accuracy of the results.

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Clinical Applicability of Whole-Exome Sequencing Exemplified by a Study in Young Adults with the Advanced Cryptogenic Cholestatic Liver Diseases

Background. The proper use of new medical tests in clinical practice requires the establishment of their value and range of diagnostic usefulness. While whole-exome sequencing (WES) has already entered the medical practice, recognizing its diagnostic usefulness in multifactorial diseases has not yet been achieved. Aims. The objective of this study was to establish usability of WES in determining genetic background of chronic cholestatic liver disease (CLD) in young patients. Methods. WES was performed on six young patients (between 17 and 22 years old) with advanced fibrosis or cirrhosis due to CLD and their immediate families. Sequencing was performed on an Ion Proton sequencer. Results. On average, 19,673 variants were identified, of which from 7 to 14 variants of an individual were nonsynonymous, homozygous, recessively inherited, and considered in silico as pathogenic. Although monogenic cause of CLD has not been determined, several heterozygous rare variants and polymorphisms were uncovered in genes previously known to be associated with CLD, including ATP8B1, ABCB11, RXRA, and ABCC4, indicative of multifactorial genetic background. Conclusions. WES is a potentially useful diagnostic tool in determining genetic background of multifactorial diseases, but its main limitation results from the lack of opportunities for direct linkage between the uncovered genetic variants and molecular mechanisms of disease.

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Effect of Amplatz Sheath on Cystolithotripsy for Women with Large Bladder Stone

Objective. This study compared the effect of endourological procedures with or without the Amplatz sheath (AS) on cystolithotripsy. Methods. We retrospectively analysed 18 patients who underwent treatment for bladder stone over 30 mm. This study consisted of two groups, namely, patients who underwent cystolithotripsy with an AS (AS group) and those who underwent standard procedure without an AS (SP group). The stone-free rate, total energy used for operation, operation time, days of admission after operation, and complication of both groups were compared. Results. The number of patients in the AS and SP groups was 10 and 8, respectively. Significant differences were not found between these two groups with regard to age, stone burden, stone volume, number of stones, and history of neurogenic bladder. All patients in both groups achieved a stone-free state. Total energy was significantly increased and operation time was shorter in the AS group. No significant difference was observed in terms of days of admission after operation. Any complications were not increased by the use of AS. Struvite was the most common stone component in both groups. Conclusion. Use of an AS can shorten the operation time of cystolithotripsy without increasing perioperative complication.

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Endoplasmic Reticulum Stress-induced Degradation of DNAJB12 Stimulates BOK Accumulation and Primes Cancer Cells for Apoptosis [Cell Biology]

DNAJB12 (JB12) is an endoplasmic reticulum (ER)-associated Hsp40 family protein that recruits Hsp70 to the ER surface to coordinate the function of ER-associated and cytosolic chaperone systems in protein quality control. Hsp70 is stress inducible, but paradoxically, we report here that JB12 was degraded by the proteasome during severe ER stress. Destabilized JB12 was degraded by ER-associated degradation (ERAD) complexes that contained HERP, Sel1L, and gp78. JB12 was the only ER-associated chaperone that was destabilized by reductive stress. JB12 knockdown by siRNA led to the induction of Caspase processing, but not the unfolded protein response. ER stress-induced apoptosis is regulated by the highly labile and ER associated BCL-2 family member BOK, which is controlled at the level of protein stability by ERAD components. We found that JB12 was required in Huh-7 liver cancer cells to maintain BOK at low levels and BOK was detected in complexes with JB12 and gp78. Depletion of JB12 during reductive stress or by shRNA from Huh-7 cells was associated with accumulation of BOK, and activation of Caspase 3, 7, and 9. Absence of JB12 sensitized Huh-7 to death caused by proteotoxic agents and the proapoptotic chemotherapeutic LCL-161. In summary, JB12 is a stress sensitive Hsp40 whose degradation during severe ER stress provides a mechanism to promote BOK accumulation and induction of apoptosis.

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The ubiquitin ligase STUB1 regulates stability and activity of RUNX1 and RUNX1-RUNX1T1 [Molecular Bases of Disease]

RUNX1 is a member of RUNX transcription factors and plays important roles in hematopoiesis. Disruption of RUNX1 activity has been implicated in the development of hematopoietic neoplasms. Chromosomal translocations involving the RUNX1 gene are associated with several types of leukemia, including acute myeloid leukemia driven by a leukemogenic fusion protein RUNX1-RUNX1T1. Previous studies have shown that RUNX1 is an unstable protein and is subjected to proteolytic degradation mediated by the ubiquitin-proteasome pathway. However, the precise mechanisms of RUNX1 ubiquitination have not been fully understood. Furthermore, much less is known about the mechanisms to regulate the stability of RUNX1-RUNX1T1. In this study, we identified several RUNX1-interacting E3 ubiquitin ligases using a novel high-throughput binding assay. Among them, we found that STUB1 bound to RUNX1 and induced its ubiquitination and degradation mainly in the nucleus. Immunofluorescence analyses revealed that the STUB1-induced ubiquitination also promoted nuclear export of RUNX1, which probably contributes to the reduced transcriptional activity of RUNX1 in STUB1-overexpressing cells. STUB1 also induced ubiquitination of RUNX1-RUNX1T1 and downregulated its expression. Importantly, STUB1 overexpression showed a substantial growth-inhibitory effect in myeloid leukemia cells that harbor RUNX1-RUNX1T1, while it showed only a marginal effect in other non-RUNX1-RUNX1T1 leukemia cells and normal human cord blood cells. Taken together, these data suggest that the E3 ubiquitin ligase STUB1 is a negative regulator of both RUNX1 and RUNX1-RUNX1T1. Activation of STUB1 could be a promising therapeutic strategy for RUNX1-RUNX1T1 leukemia.

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Structural and Enzymatic Insights into Species-specific Resistance to Schistosome Parasite Drug Therapy [Enzymology]

The antischistosomal pro-drug oxamniquine is activated by a sulfotransferase (SULT) in the human parasite Schistosoma mansoni. Of the three main human blood fluke species, only S. mansoni is sensitive to oxamniquine therapy despite the presence of SULT orthologs in S. haematobium and S. japonicum. The reason for this species-specific drug action has remained a mystery for decades. Here we present the crystal structures of S. haematobium and S. japonicum SULTs, including S. haematobium SULT in complex with oxamniquine. Our finding that all three enzymes show activity toward oxamniquine in vitro reveals differences in catalytic efficiency that implicate kinetics as the determinant for species-specific toxicity. These results support the initiative for designing oxamniquine derivatives to treat infection caused by all species of blood fluke to combat emerging resistance to current therapy.

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Two Proteins for the Price of One: Structural Studies of the Dual Destiny Preproalbumin with Sunflower Trypsin Inhibitor-1 [Plant Biology]

Seed storage proteins are both an important source of nutrition for humans and essential for seedling establishment. Interestingly, unusual napin-type 2S seed storage albumin precursors in sunflower contain a sequence that is released as a macrocyclic peptide during post-translational processing. The mechanism by which such peptides emerge from linear precursors proteins has received increased attention, however the structural characterization of intact precursor proteins has been limited. Here we report the 3D NMR structure of the Helianthus annuus PreproAlbumin With Sunflower trypsin inhibitor-1 (PawS1), and provide new insights into the processing of this remarkable dual-destiny protein. In seeds PawS1 is matured by asparaginyl endopeptidases (AEP) into the cyclic peptide Sunflower Trypsin Inhibitor-1 (SFTI-1) and a heterodimeric 2S albumin. The structure of PawS1 revealed that SFTI-1 and the albumin are independently folded into well-defined domains separated by a flexible linker. PawS1 was cleaved in vitro with recombinant sunflower HaAEP1 and in situ using a sunflower seed extract in a way that resembled the expected in vivo cleavages. Recombinant HaAEP1 cleaved PawS1 at multiple positions and in situ its flexible linker was removed yielding fully mature heterodimeric albumin. Liberation and cyclization of SFTI-1, however, was inefficient suggesting specific seed conditions or components may be required for in vivo biosynthesis of SFTI-1. In summary, this study has revealed the 3D structure of a macrocyclic precursor protein and provided important mechanistic insights into the maturation of sunflower proalbumins into an albumin and a macrocyclic peptide.

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Exosomes from uninfected cells activate transcription of latent HIV-1 [Microbiology]

HIV-1 infection causes AIDS, infecting millions worldwide. The virus can persist in a state of chronic infection due to its ability to become latent. We have previously shown a link between HIV-1 infection and exosome production. Specifically, we have reported that exosomes transport viral proteins and RNA from infected cells to neighboring uninfected cells. These viral products could then elicit an innate immune response, leading to activation of the Toll-like receptor (TLR) and NF-κB pathways. In this study, we asked whether exosomes from uninfected cells could activate latent HIV-1 in infected cells. We observed that irrespective of combination antiretroviral therapy (cART), both short- and long-length viral transcripts were increased in wild-type HIV-1-infected cells exposed to purified exosomes from uninfected cells. A search for a possible mechanism for this finding revealed that the exosomes increase RNA Polymerase II loading onto the HIV-1 promoter in the infected cells. These viral transcripts, which include trans-activation response (TAR) RNA and a novel RNA we termed TAR-gag, can then be packaged into exosomes and potentially be exported to neighboring uninfected cells, leading to increased cellular activation. To better decipher the exosome release pathways involved, we used siRNA to suppress expression of endosomal sorting complex required for transport (ESCRT) proteins and found that ESCRT II and IV significantly control exosome release. Collectively, these results imply that exosomes from uninfected cells activate latent HIV-1 in infected cells and that true transcriptional latency may not be possible in vivo, especially in the presence of cART.

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In silico and cell-based analyses reveal strong divergence between prediction and observation of T cell recognized tumor antigen T cell epitopes [Methods and Resources]

Tumor exomes provide comprehensive information on mutated, over-expressed genes and aberrant splicing, which can be exploited for personalized cancer immunotherapy. Of particular interest are mutated tumor antigen T cell epitopes, because neoepitope specific T cells often are tumoricidal. However, identifying tumor-specific T cell epitopes is a major challenge. A widely used strategy relies on initial prediction of human leukocyte antigen binding peptides by in silico algorithms, but the predictive power of this approach is unclear. Here, we used the human tumor antigen NY ESO 1 (ESO) and the human leukocyte antigen variant HLA-A*0201 (A2) as a model and predicted in silico the 41 highest-affinity, A2 binding 8 to11mer peptides and assessed their binding, kinetic complex stability, and immunogenicity in A2-transgenic mice and on peripheral blood mononuclear cells from ESO-vaccinated melanoma patients. We found that nineteen of the peptides strongly bound to A2, ten of which formed stable A2-peptide complexes and induced CD8+ T cells in A2-transgenic mice. However, only five of the peptides induced cognate T cells in humans; these peptides exhibited strong binding and complex stability and contained multiple large hydrophobic and aromatic amino acids. These results were not predicted by in silico algorithms and provide new clues to improving T-cell epitope identification. In conclusion, our findings indicate that only a small fraction of in silico predicted A2-binding ESO peptides are immunogenic in humans, namely those that have high peptide-binding strength and complex stability. This observation highlights the need for improving in silico predictions of peptide immunogenicity.

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When no treatment is the best treatment: active surveillance strategies for low risk prostate cancers

Prostate cancer is the most common malignancy in men and the second most common malignancy in the Western world [1]. In the UK alone, more than 46,000 men are diagnosed and over 11,000 die from prostate cancer every year, according to Prostate Cancer UK [2].

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The inhibitor of differentiation-1 (Id-1) enables lung cancer liver colonization through activation of an EMT program in tumor cells and establishment of the pre-metastatic niche

Id1 promotes carcinogenesis and metastasis, and predicts prognosis of non-small cell lung cancer (NSCLC)-adenocarcionoma patients. We hypothesized that Id1 may play a critical role in lung cancer colonization of the liver by affecting both tumor cells and the microenvironment. Depleted levels of Id1 in LLC (Lewis lung carcinoma cells, LLC shId1) significantly reduced cell proliferation and migration in vitro. Genetic loss of Id1 in the host tissue (Id1-/- mice) impaired liver colonization and increased survival of Id1-/- animals.

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MicroRNAs in Gynecological Cancers: Small molecules with big implications

Gynecological cancers (GCs) are often diagnosed at advanced stages, limiting the efficacy of available therapeutic options. Thus, there remains an urgent and unmet need for innovative research for the efficient clinical management of GC patients. Research over past several years has revealed the enormous promise of miRNAs. These small non-coding RNAs can aid in the diagnosis, prognosis and therapy of all major GCs, viz., ovarian cancers, cervical cancers and endometrial cancers. Mechanistic details of the miRNAs-mediated regulation of multiple biological functions are under constant investigation, and a number of miRNAs are now believed to influence growth, proliferation, invasion, metastasis, chemoresistance and the relapse of different GCs.

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Distinct roles of Hes1 in normal stem cells and tumor stem-like cells of the intestine

Cancer stem cells (CSC) have attracted attention as therapeutic targets, however, CSC-targeting therapy may disrupt normal tissue homeostasis because many CSC molecules are also expressed by normal stem cells (NSC). Here we demonstrate that NSC-specific and CSC-specific roles of the stem cell transcription factor Hes1 in the intestine enable the feasibility of a specific cancer therapy. Hes1 expression was upregulated in NSC and intestinal tumors. Lineage tracing experiments in adult mouse intestine revealed that Hes1 deletion in Lgr5+ or Bmi1+ NSC resulted in loss of self-renewal but did not perturb homeostasis. Further, in Lgr5+ NSC deletion of Hes1 stabilized β-catenin, limited tumor formation and prolonged host survival. Notably, in Lgr5+ or Dclk1+ tumor stem cells derived from established intestinal tumors, Hes1 deletion triggered immediate apoptosis, reducing tumor burden. Our results show how Hes1 plays different roles in NSC and CSC, in which Hes1 disruption leads to tumor regression without perturbing normal stem cell homeostasis, preclinically validating Hes1 as a cancer therapeutic target.

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Liver metastasis is facilitated by the adherence of circulating tumor cells to vascular fibronectin deposits

The interaction between circulating tumor cells (CTC) and endothelial cells during extravasation is a critical process during metastatic colonization, but its mechanisms remain poorly characterized. Here we report that the luminal side of liver blood vessels contains fibronectin deposits that are enriched in mice bearing primary tumors and are also present in vessels from human livers affected with metastases. Cancer cells attached to endothelial fibronectin deposits via talin1, a major component of focal adhesions. Talin1 depletion impaired cancer cell adhesion to the endothelium and transendothelial migration, resulting in reduced liver metastasis formation in vivo. Talin1 expression levels in patient CTC's correlated with prognosis and therapy response. Together, our findings uncover a new mechanism for liver metastasis formation involving an active contribution of hepatic vascular fibronectin and talin1 in cancer cells.

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The damaging effect of passenger mutations on cancer progression

Genomic instability and high mutation rates cause cancer to acquire numerous mutations and chromosomal alterations during its somatic evolution, most are termed passengers because they do not confer cancer phenotypes. Evolutionary simulations and cancer genomic studies suggest that mildly deleterious passengers accumulate and can collectively slow cancer progression. Clinical data also suggest an association between passenger load and response to therapeutics, yet no causal link between the effects of passengers and cancer progression has been established. To assess this, we introduced increasing passenger loads into human cell lines and immunocompromised mouse models. We found that passengers dramatically reduced proliferative fitness (~3% per Mb), slowed tumor growth, and reduced metastatic progression. We developed new genomic measures of damaging passenger load that can accurately predicted the fitness costs of passengers in cell lines and in human breast cancers. We conclude that genomic instability and elevated load of DNA alterations in cancer is a double-edged sword: it accelerates the accumulation of adaptive drivers, but incurs a harmful passenger load that can outweigh driver benefit. The effects of passenger alterations on cancer fitness were unrelated to enhanced immunity, as our tests were performed either in cell culture or in immunocompromised animals. Our findings refute traditional paradigms of passengers as neutral events, suggesting that passenger load reduces the fitness of cancer cells and slows or prevents progression of both primary and metastatic disease. The anti-tumor effects of chemotherapies can in part be due to induction of genomic instability and increased passenger load.

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Persistent immune stimulation exacerbates genetically-driven myeloproliferative disorders via stromal remodeling

Systemic immune stimulation has been associated with increased risk of myeloid malignancies, but the pathogenic link is unknown. We demonstrate in animal models that experimental systemic immune activation alters the bone marrow stromal microenvironment, disarranging extracellular matrix (ECM) microarchitecture, with down-regulation of SPARC and collagen-I and induction of complement activation. These changes were accompanied by a decrease in Treg frequency and by an increase in activated effector T cells. Under these conditions, hematopoietic precursors harboring nucleophosmin-1 (NPM1) mutation generated myeloid cells unfit for normal hematopoiesis but prone to immunogenic death, leading to neutrophil extracellular trap (NET) formation. NET fostered the progression of the indolent NPM1-driven myeloproliferation toward an exacerbated and proliferative dysplastic phenotype. Enrichment in NET structures was found in the bone marrow of patients with autoimmune disorders and in NPM1-mutated AML patients. Genes involved in NET formation in the animal model were used to design a NET-related inflammatory gene signature for human myeloid malignancies. This signature identified two AML subsets with different genetic complexity and different enrichment in NPM1 mutation and predicted the response to immunomodulatory drugs. Our results indicate that stromal/ECM changes and priming of bone marrow NETosis by systemic inflammatory conditions can complement genetic and epigenetic events towards the development and progression of myeloid malignancy.

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Immune checkpoint blockade, immunogenic chemotherapy or IFN-{alpha} blockade boost the local and abscopal effects of oncolytic virotherapy

Athough the clinical efficacy of oncolytic viruses has been demonstrated for local treatment, the ability to induce immune-mediated regression of distant metastases is still poorly documented. We report here that the engineered oncolytic vaccinia virus VVWR-TK-RR--Fcu1 can induce immunogenic cell death and generate a systemic immune response. Effects on tumor growth and survival was largely driven by CD8+ T cells, and immune cell infiltrate in the tumor could be reprogrammed towards a higher ratio of effector T cells to regulatory CD4+ T cells. The key role of type 1-IFN pathway in oncolytic virotherapy was also highlighted, as we observed a strong abscopal response in Ifnar-/- tumors. In this model, single administration of virus directly into the tumors one one flank led to regression in the contralateral flank. Moreover, these effects were further enhanced when oncolytic treatment was combined with immunogenic chemotherapy or with immune checkpoint blockade. Taken together, our results suggest how to safely improve the efficacy of local oncolytic virotherapy in patients whose tumors are characterized by dysregulated IFN-α signaling.

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3D mathematical modeling of glioblastoma suggests that transdifferentiated vascular endothelial cells mediate resistance to current standard-of-care therapy

Glioblastoma (GBM), the most aggressive brain tumor in human patients, is decidedly heterogeneous and highly vascularized. Glioma stem/initiating cells (GSC) are found to play a crucial role by increasing cancer aggressiveness and promoting resistance to therapy. Recently, crosstalk between GSC and vascular endothelial cells has been shown to significantly promote GSC self-renewal and tumor progression. Further, GSC also transdifferentiate into bona-fide vascular endothelial cells (GEC), which inherit mutations present in GSC and are resistant to traditional anti-angiogenic therapies. Here we use 3D mathematical modeling to investigate GBM progression and response to therapy. The model predicted that GSC drive invasive fingering and that GEC spontaneously form a network within the hypoxic core, consistent with published experimental findings. Standard-of-care treatments using DNA-targeted therapy (radiation/chemo) together with anti-angiogenic therapies, reduced GBM tumor size but increased invasiveness. Anti-GEC treatments blocked the GEC support of GSC and reduced tumor size but led to increased invasiveness. Anti-GSC therapies that promote differentiation or disturb the stem cell niche effectively reduced tumor invasiveness and size, but were ultimately limited in reducing tumor size because GEC maintain GSC. Our study suggests that a combinatorial regimen targeting the vasculature, GSC, and GEC, using drugs already approved by the FDA, can reduce both tumor size and invasiveness and could lead to tumor eradication.

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SIRT3-mediated dimerization of IDH2 directs cancer cell metabolism and tumor growth

The isocitrate dehydrogenase IDH2 produces α-ketoglutarate by oxidizing isocitrate, linking glucose metabolism to oxidative phosphorylation. In this study, we report that loss of SIRT3 increases acetylation of IDH2 at lysine 413 (IDH2-K413-Ac), thereby decreasing its enzymatic activity by reducing IDH2 dimer formation. Expressing a genetic acetylation mimetic IDH2 mutant (IDH2K413Q) in cancer cells decreased IDH2 dimerization and enzymatic activity and increased cellular reactive oxygen species (ROS) and glycolysis, suggesting a shift in mitochondrial metabolism. Concurrently, overexpression of IDH2K413Q promoted cell transformation and tumorigenesis in nude mice, resulting in a tumor-permissive phenotype. Immunohistochemical staining showed that IDH2 acetylation was elevated in high-risk luminal B patients relative to low-risk luminal A patients. Overall, these results suggest a potential relationship between SIRT3 enzymatic activity, IDH2-K413 acetylation-determined dimerization, and a cancer-permissive phenotype.

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Traumatic beetle sex causes rapid evolutionary arms race

wut_6874-800x533.jpg

Male seed beetles use sharp spikes on their penises to damage females during sex, but females are evolving thicker tissue to resist them

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Traumatic beetle sex causes rapid evolutionary arms race

Male seed beetles use sharp spikes on their penises to damage females during sex, but females are evolving thicker tissue to resist them

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Correction of Sunken Upper Eyelid with Orbital Fat Transposition Flap and Dermofat Graft

A sunken upper eyelid is a commonly found deformity among Asians, mostly due to the aging process and to excessive orbital fat removal during Oriental blepharoplasty procedures. This deformity is frequently accompanied by multiple, poorly defined upper eyelid folds and blepharoptosis. To date, autologous fat graft has been the treatment of choice for this group of patients. However, accurate placement of the graft in the orbital fat is quite challenging, and it can result in contour irregularities when injected into the preseptal plane.

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Prelaminated extended temporoparietal fascia flap without tissue expansion for hemifacial reconstruction

Disfigurement of the face caused by postburn scars, resected congenital nevi and vascular malformations has both functional and psychological consequences. Ideal reconstruction of the facial components requires producing not only function but also the better appearance of the face. The skin of the neck, supraclavicular or cervicothoracic regions are the most commonly used and the most likely source of skin for facial reconstruction in those techniques which prefabrications with tissue expansion are used.

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The Foxgloves (Digitalis) Revisited

10-1055-s-0043-111240_pmb0259-1.jpg

Planta Med
DOI: 10.1055/s-0043-111240

This review provides a renewed look at the genus Digitalis. Emphasis will be put on those issues that attracted the most attention or even went through paradigmatic changes since the turn of the millennium. PubMed and Google Scholar were used (“Digitalis” and “Foxglove” were the key words) to identify research from 2000 till 2017 containing data relevant enough to be presented here. Intriguing new results emerged from studies related to the phylogeny and taxonomy of the genus as well as to the biosynthesis and potential medicinal uses of the key active compounds, the cardiac glycosides. Several Eastern and Western Foxgloves were studied with respect to their propagation in vitro. In this context, molecular biology tools were applied and phytochemical analyses were conducted. Structure elucidation and analytical methods, which have experienced less exciting progress, will not be considered here in great detail.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text



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Regulatory T Cell Populations in Children Are Affected by Age and Food Allergy Diagnosis

Young food allergic children have decreased regulatory T cell (Treg) percentages. Only Tregs from healthy controls demonstrated age-related increases in their expression of the gut-associated chemokine receptor CCR6, which may be important in maintaining oral tolerance to foods and preventing the development of allergic disease.

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Lectin array and glycogene expression analyses of ovarian cancer cell line A2780 and its cisplatin-resistant derivate cell line A2780-cp

Abstract

Background

Ovarian cancer is one of the most lethal gynecological malignancies, in which platinum resistance is a common cause of its relapse and death. Glycosylation has been reported to be involved in drug resistance, and glycomic analyses of ovarian cancer may improve our understanding of the mechanisms underlying cancer cell drug resistance and provide potential biomarkers and therapeutic targets.

Methods

The serous ovarian cancer cell line A2780 and its platinum-resistant counterpart A2780-cp were used in this study. We performed a lectin array analysis to compare the glycosylation patterns of the two cell lines, a gene expression array was employed to probe the differences in glycogenes. Furthermore, the results were verified by lectin blots.

Results

A2780-cp cell exhibited stronger intensities of Lens culinaris (LCA) Canavalia ensiformis (ConA), and Lycopersicon esculentum (LEL) and weaker intensities of Sambucus nigra (SNA) lectins. The gene expression array analysis revealed increased expression of Fut8, B3gnt4, B3gnt5, B4galt2 and decreased expression of Fut1 and ST6GalNAc 6 expression were evident in the A2780-cp cells. The lectin blot confirmed the differences in LCA, ConA, SNA and LEL between the A2780 and A2780-cp cells.

Conclusions

The combination of the lectin and gene expression analyses showed that the levels of core fucosylation and poly-LacNAc were increased in the A2780-cp cells and the levels of Fuc α1-2(gal β1-4) GlcNAc and α2-6-linked sialic structures were decreased in the A2780-cp cells. These glycans represent potential biomarkers and might be involved in the mechanism of drug resistance in ovarian cancer.



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Fluid responsiveness predicted by transcutaneous partial pressure of oxygen in patients with circulatory failure: a prospective study

Significant effort has been devoted to defining parameters for predicting fluid responsiveness. Our goal was to study the feasibility of predicting fluid responsiveness by transcutaneous partial pressure of ox...

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The Shoulder: What is New and Evidence-Based in Orthopedic Sports Medicine

Abstract

Purpose of Review

To provide an overview of common sports-related shoulder pathology and review recently published studies from 2015 to 2016, with an emphasis on imaging.

Recent Findings

Although effective at identifying complete tears of the LHBT, MRI is less effective at evaluating tendinosis and partial tears. Both CT and MRI can evaluate bone loss in glenohumeral instability, and the glenoid track concept may be superior to glenoid bone loss alone in predicting post-operative stability. MRI and MR arthrography are accurate in detecting SLAP tears; however, the ability to classify such tears is limited. Tears of the subscapularis, latissimus dorsi, and teres major muscles and stress-related injuries of the distal clavicle and acromial apophysis are uncommon, but should not be overlooked on MRI.

Summary

Imaging continues to play a critical role both in evaluating sports-related shoulder injuries and determining the optimal treatment pathway.



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PET-MRI of the Pancreas and Kidneys

Abstract

Purpose of Review

PET-MRI is a novel imaging modality which can non-invasively provide both morphological and functional information about benign and malignant lesions. In this article, recent updates in the applications of PET-MRI in pancreatic and renal cancers are reviewed.

Recent Findings

Multiparametric imaging has raised great interest in the oncology field by revealing various functional characteristics within tumors. For example, we can quantify tumor perfusion by dynamic contrast-enhanced MRI or arterial spin labeling MRI, tumor cellularity by diffusion-weighted image, tumor metabolites by MR spectroscopy, tumor metabolism by FDG-PET, and tumor heterogeneity by radiomics. Recent studies have demonstrated that these imaging biomarkers were correlated with tumor aggressiveness, treatment response, and prognosis.

Summary

Combination of these imaging biomarkers from "one-stop shop" PET-MRI has great potential to more accurately characterize and monitor tumor behavior in the clinic to deliver individualized treatment plans.



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CT and MR Imaging of the Pediatric Temporal Bone: Normal Variants and Pitfalls

Abstract

Purpose of Review

This article will discuss high-resolution CT (HRCT) and MRI of the pediatric temporal bone with a focus on variant anatomy that can mimic pathology or affect surgical planning, as well as some potential pitfalls in image interpretation.

Recent Findings

The latest research shows that with improving imaging technology, there is better visualization of temporal bone structure, both normal and abnormal, on HRCT and MRI. Examples include earlier detection of cochlear obstruction in labyrinthitis ossificans with MRI, the ability to better define ossicular chain abnormalities, and the identification of pericochlear lucency in children without hearing loss.

Summary

Advances in temporal bone imaging have contributed to a greater understanding of normal anatomy as well as temporal bone pathology and its implications for treatment and surgical planning. It is clear that correlation of imaging findings with clinical and surgical findings will be an essential part of future research.



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Gastrointestinal Imaging: Emerging Role of Dual-Energy Computed Tomography

Abstract

Purpose of Review

The clinical and research applications of dual-energy computed tomography (DECT) are evolving and exponentially growing. In this article, we focus on the different applications of DECT for gastrointestinal (GI) imaging. The basic principles of DECT are important to understand its ability to differentiate tissues via application of two energy spectra.

Recent Findings

Different DECT techniques and scanners currently used are discussed to highlight their advantages and limitations for generating dual-energy datasets. The advantage of generating virtual non-contrast, virtual monoenergetic, and iodine overlay images will be described for evaluation of bowel pathology, including inflammatory, vascular, and neoplastic conditions, as well as in the setting of acute trauma.

Summary

This review focuses on the applications of DECT across wide range of GI pathologies throughout the large and small bowel. With continuous research and further development of this technology, the use of DECT in imaging and evaluating the bowel holds a promising future.



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When no treatment is the best treatment: active surveillance strategies for low risk prostate cancers

Prostate cancer is the most common malignancy in men and the second most common malignancy in the Western world [1]. In the UK alone, more than 46,000 men are diagnosed and over 11,000 die from prostate cancer every year, according to Prostate Cancer UK [2].

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Development and validation of QRISK3 risk prediction algorithms to estimate future risk of cardiovascular disease: prospective cohort study

Objectives To develop and validate updated QRISK3 prediction algorithms to estimate the 10 year risk of cardiovascular disease in women and men accounting for potential new risk...
recent?d=yIl2AUoC8zA recent?d=dnMXMwOfBR0 recent?i=D3OXIr62OVw:Cg8il7oEql8:V_sGLiP recent?d=qj6IDK7rITs recent?i=D3OXIr62OVw:Cg8il7oEql8:gIN9vFw recent?d=l6gmwiTKsz0 recent?d=7Q72WNTAKBA recent?i=D3OXIr62OVw:Cg8il7oEql8:F7zBnMy recent?i=D3OXIr62OVw:Cg8il7oEql8:-BTjWOF


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Hypersensitivity reactions to gadolinium-based contrast agents.

Purpose of review: Gadolinium-based contrast agents (GBCAs) have been utilized since the late 1980s to enhance the diagnostic value of MRI studies. They are known to have excellent safety profile and serious adverse reactions are uncommon despite widespread global use. However, immediate hypersensitivity reactions are well described in the literature, with urticaria the most common manifestation. Anaphylaxis can occur, though fatality is extremely rare. This review explores the incidence of GBCA-related hypersensitivity reactions and highlights potential risk factors. Recent findings: Emerging evidence suggests that at least some immediate hypersensitivity reactions are IgE-mediated. Skin testing may be informative in confirmation of causality and revealing cross-reactivity patterns. Summary: GBCA hypersensitivity is infrequent but can be serious. Familiarity with management of acute hypersensitivity reactions may be lifesaving. Appropriate use of diagnostic testing can be used to guide future management of patients who have suffered from such reactions. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Alternative treatments for chronic spontaneous urticaria beyond the guideline algorithm.

Purpose of review: The international EAACI/GA2LEN/EDF/WAO guideline suggests a stepwise approach for the therapeutic management of chronic spontaneous urticaria (CSU), outlined in an algorithm. The aim of this article is to summarize and review the evidence available on alternative treatment options for CSU outside of this algorithm. Recent findings: Although CSU is a common disease, there are a limited number of high-quality studies, and only antihistamines and omalizumab are licensed for its treatment. Most studies regarding alternative therapies for CSU show methodological limitations and a high risk of bias. For many therapies, only case reports and uncontrolled studies exist. Recent publications on alternative treatments for chronic urticaria/CSU include reports on the use of adalimumab, rituximab, vitamin D, probiotics, histaglobulin, injection of autologous whole blood or serum, and phototherapy. Summary: Numerous treatments beyond the guideline algorithm have been evaluated in patients with refractory CSU. The global level of evidence to support their efficacy in CSU is low or very low. Further research is needed to assess the efficacy and safety of alternative therapies of CSU to manage adequately those patients who do not respond to the treatments included in the algorithm. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Multiparametric Assessment of Voice Quality and Quality of Life in Patients Undergoing Microlaryngeal Surgery—Correlation Between Subjective and Objective Methods

The aim of the study was to estimate voice defect and the quality of life deterioration in patients with different laryngeal pathologies qualified for microsurgery treatment. The results of videolaryngostroboscopy (VLS), perception, aerodynamics, acoustics, Dysphonia Severity Index, Voice Handicap Index (VHI), and the World Health Organization Quality of Life Scale Brief Version before microsurgery were analyzed. There were 151 patients enrolled in the study. There were 86 patients in group 1 (benign lesions), 34 in group 2 (premalignant conditions), and 31 in group 3 (malignant neoplasms).

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The brain starts to eat itself after chronic sleep deprivation

gettyimages-154953840-800x533.jpg

Sleep loss in mice sends the brain’s immune cells into overdrive. This might be helpful in the short term, but could increase the risk of dementia in the long run

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Hopefully devoted to Q: targeting glutamine addiction in cancer



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Self-sampling to improve cervical cancer screening coverage in Switzerland: a randomised controlled trial



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Extended RAS analysis and correlation with overall survival in advanced pancreatic cancer



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Long-term improvement of breast cancer survivors’ quality of life by a 2-week group physical and educational intervention: 5-year update of the ‘PACThe’ trial



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Tumour invasiveness, the local and systemic environment and the basis of staging systems in colorectal cancer



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Preoperative clinical pathway of breast cancer patients: determinants of compliance with EUSOMA quality indicators



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Cumulative risk of breast cancer screening outcomes according to the presence of previous benign breast disease and family history of breast cancer: supporting personalised screening



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The oral VEGF receptor tyrosine kinase inhibitor pazopanib in combination with the MEK inhibitor trametinib in advanced cholangiocarcinoma



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The prognostic value of dynamic contrast-enhanced MRI contrast agent transfer constant Ktrans in cervical cancer is explained by plasma flow rather than vessel permeability



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Text-message Reminders in Colorectal Cancer Screening (TRICCS): a randomised controlled trial



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Excess of a Rassf1-targeting microRNA, miR-193a-3p, perturbs cell division fidelity



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Pretreatment serum uracil concentration as a predictor of severe and fatal fluoropyrimidine-associated toxicity



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Prospective study of DNA methylation at chromosome 8q24 in peripheral blood and prostate cancer risk



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Hedgehog signalling pathway orchestrates angiogenesis in triple-negative breast cancers



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Comparison of general obesity and measures of body fat distribution in older adults in relation to cancer risk: meta-analysis of individual participant data of seven prospective cohorts in Europe



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The brain starts to eat itself after chronic sleep deprivation

Sleep loss in mice sends the brain’s immune cells into overdrive. This might be helpful in the short term, but could increase the risk of dementia in the long run

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β-Cyclodextrin induces the differentiation of resident cardiac stem cells to cardiomyocytes through autophagy

Publication date: August 2017
Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1864, Issue 8
Author(s): Xingxing Shi, Wenjing Li, Honghong Liu, Deling Yin, Jing Zhao
Cardiac stem cells (CSCs) have emerged as promising cell candidates to regenerate damaged hearts, because of the potential in differentiating to cardiomyocytes. However, the differentiation is difficult to trigger without inducers. Here we reported that β-cyclodextrin (β-CD) increased the expression of cardiac transcription factors (Nkx2.5 and GATA4), structural proteins (cardiac Troponin T, cTnt), transcriptional enhancer (Mef2c) and induced GATA4 nucleus translocation in adult resident CSCs, thus β-CD could be used to enhance myogenic transition. As the differentiation process was accompanied by autophagy, we constructed the Atg5 knockdown cell line by using the Atg5 siRNA lentivirus, and the myogenic conversion was blocked in Atg5 knockdown cells, which suggested that β-CD induces the cardiomyocytes transition of resident CSCs through autophagy. Furthermore, we found that JNK/STAT3 and GSK3β/β-catenin was the downstream pathways of β-CD-induced autophagy and differentiation using the inhibitors. Moreover, β-CD performed its functions through improving intracellular cholesterol levels and affecting cholesterol efflux. Collectively, our results reveal that β-CD as a novel tool to induce myogenic transition of CSCs, which could mobilize the resident CSCs or used together with CSCs to enhance the therapy effects of CSCs on damaged hearts. In addition, the clarified molecular mechanisms supported the new targets for inducing cardiomyocyte differentiation.

Graphical abstract

image


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Comparison of early outcomes of surgical ablation procedures for atrial fibrillation concomitant to non-mitral cardiac surgery: a Japan Adult Cardiovascular Surgery Database study

Abstract

Objective

Although the benefit of surgical ablation for atrial fibrillation (AF) performed concomitant to mitral valve surgery is established, whether that performed concomitant to non-mitral cardiac surgery is beneficial remains unclear. In non-mitral, non-left-atriotomy cardiac surgery, the optimal surgical approach for AF remains to be established. Therefore, using the Japan Adult Cardiovascular Surgery Database (JACVSD), we compared 2 surgical ablation procedures [the maze procedure and pulmonary vein isolation (PVI)] performed concomitant to non-mitral cardiac surgery.

Methods

Of 3402 JACVSD patients who had undergone elective non-mitral cardiac surgery by 2012, 1797 (53%) had undergone concomitant PVI, and 1339 (39%) had undergone the maze procedure. To compensate for patient heterogeneity, we conducted a propensity score-matched analysis of 1952 patients who had undergone PVI or the maze procedure (976 patients each).

Results

Operative procedures took significantly longer in the Maze Group. Although postoperative AF occurred in 34.3% of the PVI Group patients and in 31.9% of the Maze Group patients (p = 0.371), the incidence of first-time pacemaker implantation was significantly lower in the PVI Group (1.9 vs. 4.1%, respectively; p = 0.005). There was no significant difference in other morbidities or in operative mortality. Postoperative hospital and ICU stays tended to be longer in the Maze Group.

Conclusions

Our data indicate that surgical ablation of AF concomitant to non-mitral cardiac surgery is beneficial. Furthermore, PVI and the maze procedure appear to be of equal benefit in this context, except that the maze procedure may more frequently result in the need for pacemaker implantation.



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MEK Inhibitors in the Treatment of Metastatic Melanoma and Solid Tumors

Abstract

The mitogen-activated protein kinase (MAPK) cascade is an intracellular signaling pathway involved in the regulation of cellular proliferation and the survival of tumor cells. Several different mutations, involving BRAF or NRAS, exert an oncogenic effect by activating the MAPK pathway, resulting in an increase in cellular proliferation. These mutations have become targets for new therapeutic strategies in melanoma and other cancers. Selective MEK inhibitors have the ability to inhibit growth and induce cell death in BRAF- and NRAS-mutant melanoma cell lines. MEK inhibitor therapy in combination with a BRAF inhibitor is more effective and less toxic than treatment with a BRAF inhibitor alone, and has become the standard of care for patients with BRAF-mutated melanoma. Trametinib was the first MEK inhibitor approved for the treatment of BRAF-mutated metastatic melanoma not previously treated with BRAF inhibitors, and is also approved in combination with the BRAF inhibitor dabrafenib. Furthermore, cobimetinib is another MEK inhibitor approved for the treatment of BRAF-mutated metastatic melanoma in combination with a BRAF inhibitor, vemurafenib. The MEK inhibitor binimetinib in combination with the BRAF inhibitor encorafenib is in clinical development. The addition of an anti-PD-1/PD-L1 agent, such as pembrolizumab, durvalumab or atezolizumab, to combined BRAF and MEK inhibition has shown considerable promise, with several trials ongoing in metastatic melanoma. Binimetinib has also shown efficacy in NRAS-mutated melanoma patients. Future possibilities for MEK inhibitors in advanced melanoma, as well as other solid tumors, include their use in combination with other targeted therapies (e.g. anti-CDK4/6 inhibitors) and/or various immune-modulating antibodies.



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Microbicidal activity of N-chlorotaurine in combination with hydrogen peroxide

N-chlorotaurine (NCT) and hydrogen peroxide are powerful endogenous antiseptics. In vivo, the reaction between hydrogen peroxide and metal ions leads to the formation of free hydroxyl rad...

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Thermostabilization of the uronate dehydrogenase from Agrobacterium tumefaciens by semi-rational design

Aldaric acids represent biobased ‘top value-added chemicals’ that have the potential to substitute petroleum-derived chemicals. Until today they are mostly produced from corresponding aldoses using strong chem...

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Identification of diacetonamine from soybean curd residue as a sporulation-inducing factor toward Bacillus spp.

Under bioassay-guided investigation, a sporulation-inducing factor (SIF) toward Bacillus spp. was searched for in methanol (MeOH) extracts of soybean curd residues, and diacetonamine (1) was identified as the act...

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Biochemical markers in vascular cognitive impairment associated with subcortical small vessel disease - A consensus report

Abstract

Background

Vascular cognitive impairment (VCI) is a heterogeneous entity with multiple aetiologies, all linked to underlying vascular disease. Among these, VCI related to subcortical small vessel disease (SSVD) is emerging as a major homogeneous subtype. Its progressive course raises the need for biomarker identification and/or development for adequate therapeutic interventions to be tested. In order to shed light in the current status on biochemical markers for VCI-SSVD, experts in field reviewed the recent evidence and literature data.

Method

The group conducted a comprehensive search on Medline, PubMed and Embase databases for studies published until 15.01.2017. The proposal on current status of biochemical markers in VCI-SSVD was reviewed by all co-authors and the draft was repeatedly circulated and discussed before it was finalized.

Results

This review identifies a large number of biochemical markers derived from CSF and blood. There is a considerable overlap of VCI-SSVD clinical symptoms with those of Alzheimer's disease (AD). Although most of the published studies are small and their findings remain to be replicated in larger cohorts, several biomarkers have shown promise in separating VCI-SSVD from AD. These promising biomarkers are closely linked to underlying SSVD pathophysiology, namely disruption of blood-CSF and blood–brain barriers (BCB-BBB) and breakdown of white matter myelinated fibres and extracellular matrix, as well as blood and brain inflammation. The leading biomarker candidates are: elevated CSF/blood albumin ratio, which reflects BCB/BBB disruption; altered CSF matrix metalloproteinases, reflecting extracellular matrix breakdown; CSF neurofilment as a marker of axonal damage, and possibly blood inflammatory cytokines and adhesion molecules. The suggested SSVD biomarker deviations contrasts the characteristic CSF profile in AD, i.e. depletion of amyloid beta peptide and increased phosphorylated and total tau.

Conclusions

Combining SSVD and AD biomarkers may provide a powerful tool to identify with greater precision appropriate patients for clinical trials of more homogeneous dementia populations. Thereby, biomarkers might promote therapeutic progress not only in VCI-SSVD, but also in AD.



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05/22/17 PHD comic: 'Limits'

Piled Higher & Deeper by Jorge Cham
www.phdcomics.com
Click on the title below to read the comic
title: "Limits" - originally published 5/22/2017

For the latest news in PHD Comics, CLICK HERE!



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World Thyroid Day Recognized Globally on May 25th

American Thyroid Association

World Thyroid Day

World Thyroid Day Recognized Globally
American Thyroid Association collaborates with International Thyroid Societies

May 25, 2017

On May 25th the American Thyroid Association (ATA) (www.thyroid.org), in cooperation with the European Thyroid Association (www.eurothyroid.com), will be making an extraordinary effort to promote its year-round goals —focus attention on that small butterfly-shaped gland at the base of the neck that causes approximately 20 million Americans to experience thyroid disease.   In addition to the millions who have some form of thyroid disease, it is estimated that more than 12 percent of the U.S. population will develop a thyroid condition during their lifetime.

The important goal of the ATA and our sister thyroid organizations is to get the word out about Thyroid! Perhaps the most stunning statistics are that up to 60 percent of those with thyroid disease are unaware of their condition and that women are five to eight times more likely than men to have thyroid problems.  Almost everyone knows someone affected by thyroid disease or thyroid cancer and the ATA is proud to promote international awareness on World Thyroid Day so that symptoms, diagnosis, and treatment of conditions are available around the globe.  If you or someone you know are experiencing thyroid symptoms, make an appointment to see a thyroid specialist – you can find one in your area (in the US and internationally) by using the ATA Physician Referral Tool and you can read up on the thyroid educational materials in the ATA Thyroid Information Library.

The ATA is the leading organization devoted to thyroid biology and to the prevention and treatment of thyroid disease through excellence in research, clinical care, education, and public health.  Our mission assures that we communicate the importance of the thyroid gland, which produces hormones that influence every cell, tissue, and organ in the body. Thyroid hormones regulate the body’s metabolism—the rate at which the body produces energy from nutrients and oxygen—and affects critical body functions, such as energy level and heart rate. Through its mission, the ATA supports the clinicians and researchers who are at the frontlines of thyroid treatments and research. We also work with the public, patients, and their families to educate and increase awareness of thyroid diseases.

ATA member of 29 years, Dr. Gregory Brent – Chair, Department of Medicine from the University of California-Los Angeles says that, “The ATA has been my professional home since my fellowship and it has been a privilege to serve with my many valued colleagues and with such a committed and talented staff. I am most grateful to my mentors, who have encouraged and guided me. The professional and personal growths I have experienced from my involvement with the ATA are immeasurable.”

The ATA Patient Thyroid Information library is just a few clicks away on the ATA website – http://ift.tt/25XAFbU and we encourage you to check back regularly for updates and new materials.  We are also pleased to offer many of our brochures in Spanish – http://ift.tt/2q8V7uD and provide a translator on the website for most languages.  The ATA website provides easy-to-access, patient-friendly information on topics such as:

Hypothyroidism: One of the most common thyroid conditions that occurs when the thyroid gland does not produce enough thyroid hormone. Symptoms include fatigue, depression, forgetfulness, irregular menses and weight gain. Treatment of hypothyroidism is usually with a synthetic form of thyroid hormone called “levothyroxine.” Hashimoto’s Thyroiditis is an autoimmune disease affecting the thyroid is the most common cause of hypothyroidism in the US, affecting mostly women. Diagnosis is usually confirmed by symptoms suggesting thyroid underactivity, positive anti-thyroid antibodies, and small goiter (thyroid enlargement) on physical examination. Patients with an elevated blood level of TSH and/or goiter are treated with thyroxine (T4).

On the opposite side of the spectrum is Hyperthyroidism and this occurs when the thyroid gland produces too much thyroid hormone. Symptoms include irritability, nervousness, muscle weakness, unexplained weight loss, sleep disturbances, vision problems and eye irritation. One type of hyperthyroidism, Graves’ disease, is an autoimmune disorder that is partly genetic.

In addition to these common thyroid conditions, we also know that Thyroid Cancer is the most rapidly increasing form of cancer in the United States. The American Cancer Society estimates 58,670 new cases of thyroid cancer will be diagnosed in 2017 resulting in approximately 2,000 deaths. When thyroid cancer is identified and treated early, the majority of patients can be completely cured.

Mary Catherine Petermann whose father was diagnosed with Anaplastic Thyroid Cancer in 2006 describes how the ATA impacted her search for help, “The ATA was a valuable resource for our family when my dad was diagnosed with Anaplastic Thyroid Cancer. When you are faced with a detrimental diagnosis where even a few days can make the difference in life or death, understanding your options quickly is critical. The ATA website offers a one-stop shop for patients and caregivers to find specialists, current clinical trials, general thyroid cancer information, and links to other patient support groups and information”  Mary Catherine’s father was treated by ATA member physicians at Mayo Clinic and has clean scans as of October 2016.

For thyroid cancer, Endocrinologists can sometimes employ minimally invasive procedures to distinguish thyroid cancer from benign thyroid nodules, which are common in the population. The ATA produces management guidelines for thyroid diseases and thyroid cancer, which, are open to the public and can accessed on the ATA website here: http://ift.tt/2qTzJ9R

We invite and encourage you to take a moment on the 25th of May, World Thyroid Day, to help ATA continue to serve patients, families, and the physicians to treat them by making a donation on the ATA World Thyroid Day Donation Page:   http://ift.tt/2q8Rjt0

Your donation will help ATA continue the important work of education, research, and awareness on this most important disease.  No donation is too small and if you would like to make a recurring donation throughout the year, please visit this page: http://ift.tt/2q8GFCx and select frequency that is good for you.

Your interest and support help make a positive impact on the lives of so many who struggle with thyroid conditions and thyroid cancer every day and we thank you for joining us and helping carry-out the ATA mission!

###

The American Thyroid Association (ATA) is the leading worldwide organization dedicated to the advancement, understanding, prevention, diagnosis and treatment of thyroid disorders and thyroid cancer. ATA is an international individual membership organization for over 1,700 clinicians and researchers from 43 countries around the world, representing a broad diversity of medical disciplines. It also serves the public, patients and their family through education and awareness efforts

Celebrating its 94th anniversary, ATA delivers its mission through several key endeavors: the publication of highly regarded monthly journals, THYROID, Clinical Thyroidology, VideoEndocrinology and Clinical Thyroidology for the Public; annual scientific meetings; biennial clinical and research symposia; research grant programs for young investigators, support of online professional, public and patient educational programs; and the development of guidelines for clinical management of thyroid disease.

More information about ATA is found at www.thyroid.org.

The post World Thyroid Day Recognized Globally on May 25th appeared first on American Thyroid Association.



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Outcomes of ventriculoperitoneal shunt insertion in the management of idiopathic intracranial hypertension in children

Abstract

Purpose

The ventriculoperitoneal (VP) shunt has become the procedure of choice for treatment of idiopathic intracranial hypertension (IIH). We aimed to assess the efficacy of frameless stereotactic placement of VP shunts for the management of medically resistant IIH in children and to assess the role of gender and obesity in the aetiology of the condition.

Methods

This is a retrospective analysis of the case notes of 10 patients treated surgically at the University Hospital of Wales in Cardiff, from May 2006 to September 2012.

Results

VP shunts were successful in relieving headache, papilloedema and stabilising vision. No sex predilection was identified, and increased BMI was a feature throughout the population, regardless of age.

Conclusions

Neuronavigated VP shunt insertion is an effective mode of treatment for medically resistant IIH in children. The aetiological picture in children does not seem to be dominated by obesity, as in adults. Literature on childhood IIH is sparse, and larger scale, comparative studies would be of benefit to treating clinicians.



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