Increase in carbon dioxide accelerates the performance of endurance exercise in rats

Abstract

Endurance exercise generates CO₂ via aerobic metabolism; however, its role remains unclear. Exogenous CO₂ by transcutaneous delivery promotes muscle fibre-type switching to increase endurance power in skeletal muscles. Here we determined the performance of rats running in activity wheels with/without transcutaneous CO₂ exposure to clarify its effect on endurance exercise and recovery from muscle fatigue. Rats were randomised to control, training and CO₂ groups. Endurance exercise included activity-wheel running with/without transcutaneous CO₂ delivery. Running performance was measured after exercise initiation. We also analysed changes in muscle weight and muscle fibres in the tibialis anterior muscle. Running performance improved over the treatment period in the CO₂ group, with a concomitant switch in muscle fibres to slow-type. The mitochondrial DNA content and capillary density in the CO₂ group increased. CO₂ was beneficial for performance and muscle development during endurance exercise: it may enhance recovery from fatigue and support anabolic metabolism in skeletal muscles.

http://ift.tt/2t4Yvnc

Disease modeling in genetic kidney diseases: mice

Abstract

The mouse still represents arguably the most important mammal organism in research for modeling human genetic kidney diseases in vivo. Compared with many other mammal species, the breeding and maintenance of mice in the laboratory is relatively simple and cheap and reproduction cycles are short. In addition to classic gene knockout mouse lines, new molecular biological technologies have led to the development of a plethora of other, more sophisticated, mouse models, allowing the targeting of genes or gene function in a cell-specific, tissue-specific and time-dependent fashion. With the refinement of more recently developed genome-editing technologies, including the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system and other engineered nucleases such as zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), our "tool set" of mouse models is expected to rapidly expand. These technological advances hold great promise and should enable us to study and hence understand the biology of inherited kidney diseases in greater detail. By analogy, we may be able to answer questions regarding the impact of individual proteins on the development of human kidney disorders, the underlying mechanisms governing the evolution of the disease and the predicted responsiveness to therapeutic interventions. Moreover, knockout and transgenic mouse models can be highly informative with respect to the effects of genetic variations on renal phenotypes. This review focuses on mouse models that have been devised primarily to study monogenic human kidney diseases, which are typically caused by a single abnormal gene and passed on in a Mendelian pattern. Despite the large number of human hereditary kidney disorders and the multitude of mouse models described in the literature, we attempt to give a balanced overview of several well-known renal pathologies, a few of which are addressed in some detail.

http://ift.tt/2so70gr

Osimertinib reactivated immune-related colitis after treatment with anti-PD1 antibody for non-small cell lung cancer

Summary

We reported a case of relapsing immune-related colitis (initially caused by nivolumab) following osimertinib therapy for lung adenocarcinoma. A 45-year-old female who had never smoked was diagnosed with adenocarcinoma of the lung and underwent surgical resection. Four years after surgical resection, she was diagnosed with recurrent disease and was eventually treated with nivolumab as third-line therapy. One month after the completion of nivolumab therapy, the patient reported abdominal pain and frequent diarrhea. We diagnosed immune-related colitis and started oral prednisolone. However, the steroid therapy was ineffective, so the patient was administered infliximab and an increased dose of prednisolone. Her symptoms subsequently resolved, and her mucosal lesions improved. Six months after the last administration of nivolumab, osimertinib was initiated as fourth-line therapy, but 3 days later, the patient developed blood in the stool and frequent diarrhea. Osimertinib treatment was discontinued, given the possibility that it had reactivated the patient's immune-related colitis. We subsequently re-administered oral prednisolone (2 mg/kg/day), and the colitis resolved within a few weeks.

http://ift.tt/2rfYaN1

Bradyrhizobium sacchari sp. nov., a legume nodulating bacterium isolated from sugarcane roots

Abstract

Members of the genus Bradyrhizobium are well-known as nitrogen-fixing microsymbionts of a wide variety of leguminous species, but they have also been found in different environments, notably as endophytes in non-legumes such as sugarcane. This study presents a detailed polyphasic characterization of four Bradyrhizobium strains (type strain BR 10280^T), previously isolated from roots of sugarcane in Brazil. 16S rRNA sequence analysis, multilocus sequence analysis (MLSA) and analysis of the 16S-23S rRNA internal transcribed spacer showed that these strains form a novel clade close to, but different from B. huanghuaihaiense strain CCBAU 23303^T. Average nucleotide identity (ANI) analyses confirmed that BR 10280^T represents a novel species. Phylogenetic analysis based on nodC gene sequences also placed the strains close to CCBAU 23303^T, but different from this latter strain, the sugarcane strains did not nodulate soybean, although they effectively nodulated Vigna unguiculata, Cajanus cajan and Macroptilium atropurpureum. Physiological traits are in agreement with the placement of the strains in the genus Bradyrhizobium as a novel species for which the name Bradyrhizobium sacchari sp. nov. is proposed.

http://ift.tt/2t5bwNo

Resurrection and emendation of the Hypoxylaceae, recognised from a multigene phylogeny of the Xylariales

Abstract

A multigene phylogeny was constructed, including a significant number of representative species of the main lineages in the Xylariaceae and four DNA loci the internal transcribed spacer region (ITS), the large subunit (LSU) of the nuclear rDNA, the second largest subunit of the RNA polymerase II (RPB2), and beta-tubulin (TUB2). Specimens were selected based on more than a decade of intensive morphological and chemotaxonomic work, and cautious taxon sampling was performed to cover the major lineages of the Xylariaceae; however, with emphasis on hypoxyloid species. The comprehensive phylogenetic analysis revealed a clear-cut segregation of the Xylariaceae into several major clades, which was well in accordance with previously established morphological and chemotaxonomic concepts. One of these clades contained Annulohypoxylon, Hypoxylon, Daldinia, and other related genera that have stromatal pigments and a nodulisporium-like anamorph. They are accommodated in the family Hypoxylaceae, which is resurrected and emended. Representatives of genera with a nodulisporium-like anamorph and bipartite stromata, lacking stromatal pigments (i.e. Biscogniauxia, Camillea, and Obolarina) appeared in a clade basal to the xylarioid taxa. As they clustered with Graphostroma platystomum, they are accommodated in the Graphostromataceae. The new genus Jackrogersella with J. multiformis as type species is segregated from Annulohypoxylon. The genus Pyrenopolyporus is resurrected for Hypoxylon polyporus and allied species. The genus Daldinia and its allies Entonaema, Rhopalostroma, Ruwenzoria, and Thamnomyces appeared in two separate subclades, which may warrant further splitting of Daldinia in the future, and even Hypoxylon was divided in several clades. However, more species of these genera need to be studied before a conclusive taxonomic rearrangement can be envisaged. Epitypes were designated for several important species in which living cultures and molecular data are available, in order to stabilise the taxonomy of the Xylariales.

http://ift.tt/2sdhlft

Knockout of pprM Decreases Resistance to Desiccation and Oxidation in Deinococcus radiodurans

Abstract

Deinococcus radiodurans has attracted a great interest in the past decades due to its extraordinary resistance to ionizing radiation and highly efficient DNA repair system. Recent studies indicated that pprM is a putative pleiotropic gene in D. radiodurans and plays an important role in radioresistance and antioxidation, but its underlying mechanisms are poorly elucidated. In this study, pprM mutation was generated to investigate resistance to desiccation and oxidative stress. The result showed that the survival of pprM mutant under desiccation was markedly retarded compared to the wild strain from day 7–28. Furthermore, knockout of pprM increases the intercellular accumulation of ROS and the sensibility to H₂O₂ stress in the bacterial growth inhibition assay. The absorbance spectrum experiment for detecting the carotenoid showed that deinoxanthin, a carotenoid that peculiarly exists in Deinococcus, was reduced in the pprM mutant in the pprM mutant. Quantitative real time PCR showed decreased expression of three genes viz. CrtI (DR0861, 50%),CrtB (DR0862, 40%) and CrtO (DR0093, 50%), which are involved in deinoxanthin synthesis, and of Dps (DNA protection during starving) gene (DRB0092) relevant to ion combining and DNA protection in cells. Our results suggest that pprM may affect antioxidative ability of D. radiodurans by regulating the synthesis of deinoxanthin and the concentration of metal ions. This may provide new clues for the treatment of antioxidants.

http://ift.tt/2sMQ00R

Diagnostic and prognostic efficacy of Von Willebrand factor and Clara cell in traumatic lung injury

Abstract

Background

Chest injury is one of the most frequent causes of death and complications in different societies. The search for a marker of lung injury is desirable for diagnosis and prognosis. This study was conducted to assess the serum level of Von Willebrand factor (VWF) and Clara cell secretory protein (CC16) as biomarker in traumatic lung injuries for diagnostic and prognostic significance.

Methods

We evaluated the demographic data of all patients of chest injury presenting to the department. Mode of injury, any intervention, and outcome were evaluated. The level of the VWF and CC16 was assessed as per protocol.

Results

The duration of this study was 1 year. The total number of patients was 96. The mean age of patients was 40.84 ± 9.89 (range 14–70 years). Male to female ratio was 5.4:1. There was a statistically significant association of VWF with diagnosis of patient. Markedly elevated levels of VWF were associated with high mortality rates (p = 0.002). The level of VWF was markedly raised in patient having duration of hospital stay more than 2 weeks (p = 0.001). There was a statistically significant association of CC16 with diagnosis of patient. Markedly elevated level of CC16 was associated with high mortality rates (p = 0.001). The level of CCI6 was markedly raised in patients having duration of hospital stay more than 2 weeks (p = 0.001).

Conclusion

VWF and CC16 appear to be useful markers for thoracic trauma. They may also be helpful for the prognosis of the patient. Further studies evaluating their role may substantiate our efforts.

http://ift.tt/2t4Bocs

First successful experience of ECPR to heart transplant at a tertiary care institute

Abstract

The case of a 17-year-old boy diagnosed with dilated cardiomyopathy in end-stage heart failure is described here. The patient sustained a cardiac arrest and was resuscitated with extracorporeal membrane oxygenation during cardiopulmonary resuscitation (ECPR). He was maintained on a peripheral veno-arterial extracorporeal membrane oxygenation (ECMO) for 7 days before undergoing a heart transplant. He was discharged 1 month after his transplant. The role of ECMO in ECPR and as a bridge to transplant has been highlighted.

http://ift.tt/2s6YAt7

Application of omics in predicting anti-TNF efficacy in rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by progressive joint erosion. Tumor necrosis factor (TNF) antagonists are the most widely used biological disease-modifying anti-rheumatic drug in RA. However, there continue to be one third of RA patients who have poor or no response to TNF antagonists. Following consideration of the uncertainty of therapeutic effects and the high price of TNF antagonists, it is worthy to predict the treatment responses before anti-TNF therapy. According to the comparisons between the responders and non-responders to TNF antagonists by omic technologies, such as genomics, transcriptomics, proteomics, and metabolomics, rheumatologists are eager to find significant biomarkers to predict the effect of TNF antagonists in order to optimize the personalized treatment in RA.

http://ift.tt/2t4VjrP

Application of omics in predicting anti-TNF efficacy in rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by progressive joint erosion. Tumor necrosis factor (TNF) antagonists are the most widely used biological disease-modifying anti-rheumatic drug in RA. However, there continue to be one third of RA patients who have poor or no response to TNF antagonists. Following consideration of the uncertainty of therapeutic effects and the high price of TNF antagonists, it is worthy to predict the treatment responses before anti-TNF therapy. According to the comparisons between the responders and non-responders to TNF antagonists by omic technologies, such as genomics, transcriptomics, proteomics, and metabolomics, rheumatologists are eager to find significant biomarkers to predict the effect of TNF antagonists in order to optimize the personalized treatment in RA.

http://ift.tt/2t4VjrP

Interleukin-17A Plays the Same Role on Mice Acute Lung Injury Respectively Induced by Lipopolysaccharide and Paraquat

Abstract

Interleukin-17A (IL-17A) is involved in multiple inflammatory diseases. Our study was to investigate the role of IL-17A on acute lung injury (ALI) respectively induced by lipopolysaccharide (LPS) and paraquat (PQ) on mice. We built ALI mouse models respectively by single intraperitoneal (i.p.) injection with LPS or single gavage with PQ liquid. Two hours after the models were established, a dosage of neutralizing antibody was used to blockade IL-17A by i.p. injection. At 8, 24, and 48 h, the lung wet-to-dry ratio (W/D) was calculated and total protein in bronchoalveolar lavage fluid (BALF) was measured; hematoxylin-eosin staining was used to observe lung tissue pathological changes; inflammatory cells in BALF were recorded with a hemocytometer; cytokines were measured with enzyme-linked immunosorbent assay kits; immunohistochemistry examined the expression of IL-17A and activation of nuclear factor-κB p65 (NF-κB p65); and qPCR determined the expression of IL-17A mRNA. After being administered with LPS or PQ, all mice presented ALI pathological change; expression of IL-17A increased significantly. When blocking IL-17A with antibody, lung injury in both LPS- and PQ-administrated mice was attenuated. All the above tests decreased. Compared with those in PQ mice, IL-17A levels in LPS mice were higher. IL-17A involves the ALI induced by LPS or PQ and promotes the pathological process by activating NF-κB P65 and recruiting neutrophils, which enlarges the cascade effect of inflammation and injures lung tissues. And when blockading IL-17A with antibody, the ALI is alleviated. The reaction of IL-17A in the ALI induced by LPS is stronger than that by PQ.

http://ift.tt/2rWf852

In situ monitoring of molecular changes during cell differentiation processes in marine macroalgae through mass spectrometric imaging

Abstract

Matrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI-MSI) was employed to discriminate between cell differentiation processes in macroalgae. One of the key developmental processes in the algal life cycle is the production of germ cells (gametes and zoids). The gametogenesis of the marine green macroalga Ulva mutabilis (Chlorophyta) was monitored by metabolomic snapshots of the surface, when blade cells differentiate synchronously into gametangia and giving rise to gametes. To establish MSI for macroalgae, dimethylsulfoniopropionate (DMSP), a known algal osmolyte, was determined. MSI of the surface of U. mutabilis followed by chemometric data analysis revealed dynamic metabolomic changes during cell differentiation. DMSP and a total of 55 specific molecular biomarkers, which could be assigned to important stages of the gametogenesis, were detected. Our research contributes to the understanding of molecular mechanisms underlying macroalgal cell differentiation.

Graphical abstract

Molecular changes during cell differentiation of the marine macroalga Ulva were visualized by matrix assisted laser desorption/ionization mass spectrometric imaging (MALDI-MSI)

http://ift.tt/2sdn4lC

Simultaneous determination of pyrethroids and pyrethrins by dispersive liquid-liquid microextraction and liquid chromatography triple quadrupole mass spectrometry in environmental samples

Abstract

A simple and environmentally friendly dispersive liquid-liquid microextraction (DLLME) method coupled with electrospray ionization liquid chromatography triple quadrupole mass spectrometry (LC-QqQ-MS/MS) was developed for the simultaneous determination of 17 synthetic and natural pyrethroids. A comparison of solid-phase extraction (SPE) versus DLLME for water samples and only "dilute and shoot" versus the additional extract cleanup by DLLME for sediment samples is reported. Chloroform was the extracting solvent in the DLLME technique for both water and sediment samples. Ultrasonic energy was applied to fully extract the analytes into fine droplets, providing high recoveries in short times. Method detection limits (MDLs) ranged from 0.12 to 0.62 ng L⁻¹ and recoveries from 70 to 119% with RSD values 2–15% (n = 5) for water samples. In sediment samples, MDLs ranged from 0.50 to 2.50 ng g⁻¹ and recoveries from 71 to 112% with RSDs 2–16% (n = 5). The proposed method showed a good linearity within the range of 10–500 ng mL⁻¹, with coefficients of determination (R ²) higher than 0.99. Matrix effects were observed for most compounds in water and sediment (ME% < −10%). The proposed methodology was applied for the analysis of water and sediment samples from Albufera wetland and Turia River. Acrinathrin (48 ng g⁻¹) and etofenprox (16 ng g⁻¹) were detected in sediment samples.

Graphical abstract

Pyrethrins and pyrethroid determination in water and sediments by DLLME and LC-MS/MS.

http://ift.tt/2sd3XYL

Bilateral ocular ischemia-induced blindness as a presenting manifestation of Takayasu arteritis: a case report

Abstract

Background

Takayasu arteritis is a granulomatous panarteritis that predominantly affects the aorta and its major branches. The initial manifestations of this large-vessel vasculitis are usually nonspecific; however, as the disease progresses, typical symptoms of arterial occlusion, aneurysmal formation, and vascular pain become evident. Ischemic ocular complications of Takayasu arteritis which could lead to complete loss of vision are not uncommon and depend on the obliterated portion(s) of carotid(s), the intensity and rate of progression of ocular vascular insufficiency, and sufficiency of the collateral blood supply to the eye.

Case presentation

A 24-year-old woman of African descent with prior normal vision was referred to us with a 3-year history of gradual decline in visual acuity in both eyes and unintentional weight loss (17 kg) within the past 1 year. A physical examination revealed feeble brachial and radial arterial pulses on her left side. She had sinus tachycardia (136 beats/minute) and her blood pressure was 85/59 mmHg on her left and 134/82 mmHg on her right side. Bilateral microaneurysms, dot and blot hemorrhages, and multiple ischemic areas of retina together with neovascularization in her right eye were noted during a funduscopic examination. Computed tomography angiography of her thoracic and abdominal aorta revealed irregular narrowing with variable degrees of stenosis, tapering, and corrugated appearance.

Conclusions

Despite its rarity, Takayasu arteritis significantly impairs a patient's quality of life and has a life-threatening potential. Early initiation of appropriate therapy could delay disease progression and reduce the associated complications.

http://ift.tt/2sMvcGK

Sodium butyrate protects against oxidative stress in HepG2 cells through modulating Nrf2 pathway and mitochondrial function

Abstract

Sodium butyrate (NaBu) is a by-product of microbial fermentation of dietary fiber in the gastrointestinal tract and has been shown to increase the activity of antioxidant enzymes, such as catalase or heme oxidase-1, in vivo. However, the mechanism of this effect is still unclear. This study investigated the antioxidant effect of NaBu on HepG2 cells under H₂O₂-induced oxidative stress. NaBu (0.3 mM) attenuated cell death and accumulation of reactive oxygen species and improved multiple antioxidant parameters in H₂O₂-injured HepG2 cells. NaBu inhibited glycogen synthase kinase-3 beta (GSK-3β) by increasing the p-GSK-3β (Ser9) level and promoted nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), which increased the expression of downstream antioxidant enzymes. Together with promotion of peroxisome proliferator-activated receptor gamma coactivator 1-alpha and mitochondrial DNA copy number, NaBu modulated energy metabolism and mitochondrial function, decreasing glycolysis, increasing β-oxidation, and enhancing the tricarboxylic acid cycle and oxidative phosphorylation. NaBu increased mitochondrial manganese-superoxide dismutase and glutathione peroxidase activity. In conclusion, NaBu protected HepG2 cells against oxidative stress by modulating Nrf2 pathway activity and mitochondrial function.

http://ift.tt/2sMiPdJ

Constrained improved particle swarm optimization algorithm for optimal operation of large scale reservoir: proposing three approaches

Abstract

In this paper, the improved particle swarm optimization (IPSO) algorithm is used to solve large scale reservoir operation optimization problem proposing unconstrained and two constrained versions of this algorithm. In the two constrained versions proposed for the IPSO algorithm, named PCIPSO and FCIPSO, each particle may be forced to satisfy problem constraints during solution building. By considering water releases or storage volumes at each operation time period as decision variable of the problem, here, two formulations are proposed for each version. In the second proposed constrained version algorithm (FCIPSO), at first, the water storage volume bounds are modified in order to recognize the infeasible components of the search space and exclude from the search process before the main search starts. This mechanism leads to smaller search space size for the problem and finally better results. The simple and hydropower operation problems of "Dez" reservoir in the southern Iran over 60, 240 and 480 monthly operations time periods are solved here using both proposed formulations of theses algorithms and the results are presented and compared with other available results. The results show the capability of the proposed algorithms and especially the second constrained version of the IPSO algorithm, FCIPSO, to optimally solve the reservoir operation optimization problem. In other words, the results of both formulations of constrained IPSO and especially FCIPSO algorithm are improved significantly in comparison with unconstrained IPSO algorithm over all operations time periods of simple and hydropower operation of the reservoir.

http://ift.tt/2rfvsvS

Environmental economic dispatch using improved artificial bee colony algorithm

Abstract

Due to emissions from fossil fuel consumption in power plants, not only operational costs, but the minimization of the resulting pollution should be also considered in environmental economic dispatch problem. In this research, environmental economic dispatch problem is solved by minimization of operational cost and environmental pollution considering nonlinear constraints of generating units, forbidden regions, and ramp-rate of generating units using an improved artificial bee colony technique. With the proposed approach, data transactions among bees have been conducted using Newton's and gravitational laws, leading to a full employment of honey bees mating optimization's capability in finding the optimum solution. In order to show the effectiveness of the proposed algorithm, it is tested on IEEE 6-bus and IEEE 11-bus power systems in different load levels. Then, the obtained results are compared with those of other previously validated techniques. It is revealed that the proposed technique is superior in terms of accuracy and speed in solving power system complex problems over the other methods. In addition, it is unlikely for this approach to be trapped in local minima. Results compared to many recent competitive methods confirm the efficiency of the proposed method in term of solution quality and convergence characteristics.

http://ift.tt/2rKHT6n

Intra-operative hemorrhage due to hyperperfusion during direct revascularization surgery in an adult patient with moyamoya disease: a case report

Abstract

Hemorrhagic complication is one of the notable surgical complications of the revascularization surgery for moyamoya disease (MMD). Cerebral hyperperfusion (CHP) has been considered as the underlying cause of this complication. It mostly occurs several days after surgery, but the intra-operative hemorrhage immediately after bypass has not been reported previously. A 21-year-old woman presented right thalamic hemorrhage and was diagnosed as having MMD by cerebral angiography. In light of the location of the hemorrhage at the vascular territory of posterior circulation and the manifestation of transient ischemic attack during the follow-up period, she underwent revascularization surgery to prevent future ischemic attack and rebleeding. Superficial temporal artery (STA) was uneventfully anastomosed to the temporal M4 branch of the middle cerebral artery in an end-to-side manner. A few minutes after the completion of the anastomosis, hemorrhage occurred in the fissure adjacent to the site of anastomosis. Indocyanine green (ICG) video angiography just before hemorrhage showed focal early filling through the STA graft with early venous filling around the site of the anastomosis. The bleeding was controlled by immediate hypotensive therapy (systolic blood pressure 117 to 91 mmHg). The mean blood flows of the STA graft measured by ultrasonic flowmetry before and after hypotensive therapy were 52.8 and 24.2 ml/min, respectively. Single-photon emission computed tomography (SPECT) on the next day after surgery showed focal hyperperfusion in the surgical side. Intra-operative ultrasonic flowmetry, ICG, and postoperative SPECT would explain that CHP was the potential cause of the hemorrhagic complication. This is the first case describing intra-operative hemorrhagic complication during revascularization surgery for MMD. Surgeons need to be aware of this rare complication and its management method.

http://ift.tt/2scleRT

Wallerian demyelination: chronicle of a cellular cataclysm

Abstract

Wallerian demyelination is characteristic of peripheral nerve degeneration after traumatic injury. After axonal degeneration, the myelinated Schwann cell undergoes a stereotypical cellular program that results in the disintegration of the myelin sheath, a process termed demyelination. In this review, we chronologically describe this program starting from the late and visible features of myelin destruction and going backward to the initial molecular steps that trigger the nuclear reprogramming few hours after injury. Wallerian demyelination is a wonderful model for myelin degeneration occurring in the diverse forms of demyelinating peripheral neuropathies that plague human beings.

http://ift.tt/2smTWIh

How order and disorder within paramyxoviral nucleoproteins and phosphoproteins orchestrate the molecular interplay of transcription and replication

Abstract

In this review, we summarize computational and experimental data gathered so far showing that structural disorder is abundant within paramyxoviral nucleoproteins (N) and phosphoproteins (P). In particular, we focus on measles, Nipah, and Hendra viruses and highlight both commonalities and differences with respect to the closely related Sendai virus. The molecular mechanisms that control the disorder-to-order transition undergone by the intrinsically disordered C-terminal domain (N_TAIL) of their N proteins upon binding to the C-terminal X domain (XD) of the homologous P proteins are described in detail. By having a significant residual disorder, N_TAIL–XD complexes are illustrative examples of "fuzziness", whose possible functional significance is discussed. Finally, the relevance of N–P interactions as promising targets for innovative antiviral approaches is underscored, and the functional advantages of structural disorder for paramyxoviruses are pinpointed.

http://ift.tt/2t3y80O

Resveratrol protects against ICV collagenase-induced neurobehavioral and biochemical deficits

Abstract

Background

Indeed, intracerebral hemorrhage (ICH) account for only 15% of all strokes but it is one of the most devastating subtype of stroke associated with behavioral, cognitive and neurological deficits. The primary cause of neurological deficits in ICH is the hematoma growth, generation of free radicals, inflammatory cytokines and exhausting endogenous anti-oxidant machinery. It has been found that neuroinflammation following ICH leads to exaggeration of hallmarks of ICH. With this background, the study was aimed to evaluate the protective effect of resveratrol (RSV) in intracerebroventricular (ICV) collagenase (COL) induced neurological deficits in rats.

Methods

The present study was designed to explore the protective effects of resveratrol (5, 10, 20 mg/kg) against ICV-COL induced ICH. Animals were subjected to a battery of behavioral tests to access behavioral changes, including neurological scoring tests (cylinder test, spontaneous motility, righting reflex, horizontal bar test, forelimb flexion), actophotometer, rotarod, Randall Sellito and von Frey. Post stroke depression was estimated using forced swim test (FST). Memory deficit was monitored using Morris water maze (MWM).

Results

Chronic treatment with RSV (20 mg/kg) for 21 days restored various behavioral changes, including neurological scoring tests (cylinder test, spontaneous motility, righting reflex, horizontal bar test, forelimb flexion), actophotometer, rotarod, Randall Sellito and Von Frey. RSV also restores increase in immobility time forced swim test used to evaluate post stroke depression and impaired memory deficit in Morris water maze. RSV administration also attenuated increased nitro-oxidative stress and TNF-α level. RSV being a potent antioxidant also restores changes in endogenous anti-oxidant levels.

Conclusion

In conclusion, our research demonstrates that RSV has a protective effect against ICH by virtue of its anti-inflammatory property and antioxidant and nitrosative stress restoring property.

http://ift.tt/2smsyKi

Dramatic improvement of impulsive aggressive behaviour following shunt surgery in a patient with idiopathic normal pressure hydrocephalus

http://ift.tt/2rJlJ4e

Ascorbic Acid to Manage Psychiatric Disorders

Abstract

Ascorbate has critical roles in the central nervous system (CNS); it is a neuromodulator of glutamatergic, cholinergic, dopaminergic, and γ-aminobutyric acid (GABA)-ergic neurotransmission, provides support and structure to neurons, and participates in processes such as differentiation, maturation, and survival of neurons. Over the past decade, antioxidant properties of ascorbate have been extensively characterized and now it is known that this compound is highly concentrated in the brain and neuroendocrine tissues. All this information raised the hypothesis that ascorbate may be involved in neurological disorders. Indeed, the biological mechanisms of ascorbate in health and disease and its involvement in homeostasis of the CNS have been the subject of extensive research. In particular, evidence for an association of this vitamin with schizophrenia, major depressive disorder, and bipolar disorder has been provided. Considering that conventional pharmacotherapy for the treatment of these neuropathologies has important limitations, this review aims to explore basic and human studies that implicate ascorbic acid as a potential therapeutic strategy. Possible mechanisms involved in the beneficial effects of ascorbic acid for the management of psychiatric disorders are also discussed.

http://ift.tt/2sbF2oB

Brain-derived exosomes from dementia with Lewy bodies propagate α-synuclein pathology

Abstract

Proteins implicated in neurodegenerative conditions such as Alzheimer's disease (AD) and Dementia with Lewy Bodies (DLB) have been identified in bodily fluids encased in extracellular vesicles called exosomes. Whether exosomes found in DLB patients can transmit pathology is not clear. In this study, exosomes were successfully harvested through ultracentrifugation from brain tissue from DLB and AD patients as well as non-diseased brain tissue. Exosomes extracted from brains diagnosed with either AD or DLB contained aggregate-prone proteins. Furthermore, injection of brain-derived exosomes from DLB patients into the brains of wild type mice induced α-synuclein (α-syn) aggregation. As assessed through immunofluorescent double labeling, α-syn aggregation was observed in MAP2⁺, Rab5⁺ neurons. Using a neuronal cell line, we also identified intracellular α-syn aggregation mediated by exosomes is dependent on recipient cell endocytosis. Together, these data suggest that exosomes from DLB patients are sufficient for seeding and propagating α-syn aggregation in vivo.

http://ift.tt/2rah251

Transitional care for rheumatic conditions in Europe: current clinical practice and available resources

Abstract

Objective

To assess European pediatric rheumatology providers' current clinical practices and resources used in the transition from child-centered to adult-oriented care.

Methods

European pediatric rheumatologists were invited to complete a 17-item anonymized e-survey assessing current transition practices, transition policy awareness, and needs in advance of the publication of EULAR/PReS recommendations on transition.

Results

The response rate was 121/276 (44%), including responses from 115 centers in 22 European Union countries. Although 32/121 (26%) responded that their centers did not offer transition services, the majority (99%) agreed that a formalized process in transitioning patients to adult care is necessary. A minority (<30%) of respondents stated that they have a written transition policy although 46% have an informal transition process. Designated staff to support transitional care were available in a minority of centers: nurse (35%), physiotherapist (15%), psychologist (15%), social worker (8%), and occupational therapist (2%). The existence of a designated team member to coordinate transition was acknowledged in many centers (64% of respondents) although just 36% use a checklist for young people as part of individualized transitional care.

Conclusion

This survey of European pediatric rheumatology providers regarding transitional care practices demonstrates agreement that transitional care is important, and wide variation in current provision of transition services exists.

http://ift.tt/2rUPBJm

Hiccups in Parkinson’s disease: an analysis of cases reported in the European pharmacovigilance database and a review of the literature

Abstract

Background

Some reports have suggested an association between dopamine agonists and hiccups, involuntary contractions that merit full clinical attention because they can be very debilitating. Many drugs frequently used to treat hiccups are formally contraindicated in Parkinson's disease due to their liability to worsen motor symptoms, making the treatment of hiccups problematic in this disease. The objective of the present study was to analyze all spontaneous reports of hiccups from the European Pharmacovigilance Database in patients with Parkinson's disease and/or on dopaminergic drugs. Finally, we sought to identify evidence-based recommendations on the management of hiccups in Parkinson's disease.

Methods

We searched for all reports of hiccups in the European Pharmacovigilance Database (EudraVigilance) and calculated proportional reporting ratios for dopamine agonists and hiccups. We reviewed the literature on Parkinson's disease, dopamine agonists, and hiccups, searching for specific treatment recommendations for hiccups in this disease.

Results

Both rotigotine and pramipexole fulfilled the criteria to generate a safety signal. We found 32 and 13 cases of hiccups associated with dopamine agonists in EudraVigilance and the literature, respectively. There were no specific recommendations for the management of hiccups in Parkinson's disease in the clinical guidelines consulted.

Conclusions

We have found evidence that rotigotine and pramipexole are associated with the appearance of hiccups and that this adverse reaction occurs predominantly in males. Given the scarce information available, specific recommendations are needed in clinical guidelines for the adequate management of hiccups in Parkinson's disease.

http://ift.tt/2sLiQyF

Ameliorative Effects of Allium sativum Extract on iNOS Gene Expression and NO Production in Liver of Streptozotocin + Nicotinamide-Induced Diabetic Rats

Abstract

Diabetes mellitus (DM) is one of the most prevalent diseases in the world, which is strongly associated with liver dysfunction. Hyperglycemia, through an oxidative stress pathway, damages various tissues. Herbal medicine is a good candidate to ameliorate hyperglycemia and oxidative stress. In this study, the effects of aqueous Allium sativum (garlic) extract (AGE) on gene expression of inducible nitric oxide synthases (iNOS) and production of nitric oxide (NO) were evaluated in the liver tissue of diabetic rats. Four groups of rats contained normal control rats, garlic control rats (AGE), Streptozotocin (STZ) + nicotinamide-induced diabetic rats (DM), and diabetic rats treated with garlic (DM + AGE). Glucose levels and liver enzymes activities were determined by colorimetric assay in the serum. Gene expression of iNOS by real-time PCR, NO levels by Griess method, oxidative stress parameters by spectrophotometric method and histopathological examination by hematoxylin and eosin staining method were evaluated in the liver tissues. Glucose levels, activities of liver enzymes, oxidative stress markers, iNOS gene expression, and NO production increased significantly in diabetic rats in comparison with control rats, whereas after oral administration of garlic, these parameters decreased significantly, close to the normal levels. Hence, the beneficial effects of garlic on the liver injury of diabetes could be included in the hypoglycaemic and antioxidant properties of garlic via a decrease in gene expression of iNOS and subsequent NO production.

http://ift.tt/2rdQwmg

Schuss- und Explosionsverletzungen der Gefäße

Zusammenfassung

Festnahmen von potenziellen Attentätern in Deutschland in den letzten Monaten legen die Vermutung nahe, dass Terroranschläge wie in Paris (2015) und Brüssel (2016) unter Einsatz von Schusswaffen und Explosivstoffen zu befürchten sind. Dies sind Situationen, in denen die individualmedizinischen Behandlungsansätze den Grundsätzen der Versorgung eines Massenanfalls von Verletzten weichen. Neuere Untersuchungen der Versorgung von gefäßverletzten, polytraumatisierten Patienten zeigen jedoch auch, dass selbst unter individualmedizinischen Aspekten die Schwere des Gefäßtraumas und damit die mit gängigen Trauma-Scoring-Systemen erwartete Prognose unterschätzt wird. Die im Sommer 2016 erschienene S3-Leitlinie Polytrauma/Schwerverletzten-Behandlung der federführenden Deutschen Gesellschaft für Unfallchirurgie widmet sich durch Modifikation geltender Empfehlungen und Aufnahme von neuen Erkenntnissen in großen Teilen der Versorgung von kritischen Blutungen. Der Artikel befasst sich mit dem durch Einsatz von Schusswaffen und Explosivstoffen gefäßtraumatisierten Patienten. Neben dem Pathomechanismus von Schuss- und Explosionsverletzungen der Gefäße werden prä- und innerklinische Behandlungsoptionen auf Basis der S3-Leitlinie dem Leser vermittelt.

http://ift.tt/2t2NnHl

Do social sciences and humanities behave like life and hard sciences?

Abstract

The quantitative evaluation of Social Science and Humanities (SSH) and the investigation of the existing similarities between SSH and Life and Hard Sciences (LHS) represent the forefront of scientometrics research. We analyse the scientific production of the universe of Italian academic scholars , over a 10-year period across 2002–2012, from a national database built by the Italian National Agency for the Evaluation of Universities and Research Institutes. We demonstrate that all Italian scholars of SSH and LHS are equals, as far as their publishing habits. They share the same general law, which is a lognormal. At the same time, however, they are different, because we measured their scientific production with different indicators required by the Italian law; we eliminated the "silent" scholars and obtained different scaling values—proxy of their productivity rates. Our findings may be useful to further develop indirect quali–quantitative comparative analysis across heterogeneous disciplines and, more broadly, to investigate on the generative mechanisms behind the observed empirical regularities.

http://ift.tt/2rJjkql

Antitumor activity of interferon-β1a in hormone refractory prostate cancer with neuroendocrine differentiation

Abstract

Purpose

Type I interferons (IFN-α and IFN-β) are a class of cytokines that exert several biological activities, such as modulation of cell proliferation and differentiation and of the immune system. Although these cytokines interact with a common receptor complex, IFN-β showed a more potent antitumor activity than IFN-α in several tumor models. New recombinant human IFN-β products, such as IFN-β1a and IFN-β1b, have been produced in order to improve the stability and bioavailability of natural IFN-β. In this report, we analyzed the effects of recombinant IFN-β1a on the cell proliferation of two human androgen-resistant prostate cancer cell lines with neuroendocrine differentiation (DU-145, PC-3) and related mechanisms of action.

Methods

The effects of IFN-β1a on the cell growth proliferation, cell cycle, and apoptosis have been evaluated in DU-145 and PC-3 cells through MTT assay, DNA flow cytometry with propidium iodide, and Annexin V-FITC/propidium iodide staining, respectively. Moreover, the expression of neuron-specific enolase (NSE), cleaved caspase-3, caspase-8, and PARP was evaluated through Western blotting.

Results

IFN-β1a showed a significant anti-proliferative activity in both androgen-resistant cell lines. This effect was related to cell cycle perturbation and induction in apoptosis, as shown by flow cytometric analysis, the activation of caspase-3 and caspase-8 and PARP cleavage during incubation with IFN-β1a. Moreover, this cytokine reduced the expression of NSE in both cell lines.

Conclusions

Recombinant IFN-β1a (Rebif) showed a potent in vitro anti-proliferative activity in androgen-resistant prostate cancer cells, and it could represent a promising tool for the treatment of this tumor.

http://ift.tt/2lVO82t

Emphasis on the early diagnosis of antithyroid drug-induced agranulocytosis: retrospective analysis over 16 years at one Chinese center

Abstract

Purpose

Antithyroid drug (ATD)-induced agranulocytosis is a rare but life-threatening adverse drug reaction that occurs in patients during the treatment of Graves' disease. We aimed to comprehensively examine data for patients with this rare complication and to improve the clinical safety of ATDs.

Methods

We retrospectively reviewed the medical records of 64 hospitalized patients diagnosed with ATD-induced agranulocytosis between 2000 and 2015.

Results

Agranulocytosis occurred in 52 (81.3%) patients within the first 3 months after initiation of ATD therapy. Fever (84.4%) and sore throat (82.8%) were the most common symptoms. Although they experienced symptoms, 30 (46.9%) patients did not seek treatment immediately and delayed their diagnosis of agranulocytosis. The minimum granulocyte count was lower in the patients diagnosed after the appearance of symptoms than in those diagnosed before the appearance of symptoms (0.01 × 10⁹/L (0 × 10⁹/L − 0.06 × 10⁹/L) versus 0.26 × 10⁹/L (0.05 × 10⁹/L − 0.40 × 10⁹/L), P < 0.001). The interval days from the appearance of symptoms to the diagnosis of agranulocytosis were negatively correlated with the minimum granulocyte count (r = −0.348, P = 0.005). In addition, a lower minimum granulocyte count was associated with a longer recovery time (β = −11.899, 95% CI −15.304 to −8.496).

Conclusions

Our findings have demonstrated that delayed diagnosis of ATD-induced agranulocytosis is common in our population. Delayed diagnosis is associated with severe agranulocytosis and may prolong the recovery time from agranulocytosis. Monitoring of the white blood cell and granulocyte counts may be an effective way to establish an early diagnosis and prevent progression to severe agranulocytosis.

http://ift.tt/2kV3fMq

Resistin and NGAL are associated with inflammatory response, endothelial activation and clinical outcomes in sepsis

Abstract

Objective and design

Resistin and neutrophil gelatinase-associated lipocalin (NGAL) are upregulated in circulating leucocytes in sepsis, but the significance of this is uncertain. We evaluated associations between Resistin and NGAL with endothelial cell activation and clinical outcomes in a prospective observational study in the Emergency Department (ED).

Methods

Serum levels of Resistin, NGAL, inflammatory cytokines (IL-6, IL-10) and soluble endothelial adhesion molecules (VCAM-1, ICAM-1) were measured at defined time points up to 24 h. Patterns and relationships between markers were investigated using linear mixed regression models. Predictive values for clinical outcomes for markers at enrollment were assessed by logistic regression and receiver operator characteristic (ROC) curves.

Results

186 participants (89 septic-shock, 69 sepsis, 28 uncomplicated infection) were compared with 29 healthy controls. Median Resistin and NGAL were higher in uncomplicated infection compared to controls, and in septic shock compared to non-shock sepsis. Resistin and NGAL correlated with IL-6 and IL-10, with VCAM-1 and ICAM-1, and with organ failure. Resistin and NGAL were associated with septic shock but had limited predictive utility for mortality.

Conclusion

Resistin and NGAL correlate with expression of endothelial cell adhesion molecules in sepsis. Further evaluation of the role of Resistin and NGAL in sepsis pathogenesis is warranted.

http://ift.tt/2pBVYTj

Role of microRNAs in sepsis

Abstract

Introduction

MicroRNAs have been found to be of high significance in the regulation of various genes and processes in the body. Sepsis is a serious clinical problem which arises due to the excessive host inflammatory response to infection. The non-specific clinical features and delayed diagnosis of sepsis has been a matter of concern for long time.

Findings

MicroRNAs could enable better diagnosis of sepsis and help in the identification of the various stages of sepsis. Improved diagnosis may enable quicker and more effective treatment measures. The initial acute and transient phase of sepsis involves excessive secretion of pro-inflammatory cytokines which causes severe damage. MicroRNAs negatively regulate the toll-like receptor signaling pathway and regulate the production of inflammatory cytokines during sepsis. Likewise, microRNAs have shown to regulate the vascular barrier and endothelial function in sepsis. They are also involved in the regulation of the apoptosis, immunosuppression, and organ dysfunction in later stages of sepsis. Their importance at various levels of the pathophysiology of sepsis has been discussed along with the challenges and future perspectives.

Conclusion

MicroRNAs could be key players in the diagnosis and staging of sepsis. Their regulation at various stages of sepsis suggests that they may have an important role in altering the outcome associated with sepsis.

http://ift.tt/2moEFmZ

The immunological function of CD52 and its targeting in organ transplantation

Abstract

Introduction

CD52 (Campath-1 antigen), a glycoprotein of 12 amino acids anchored to glycosylphosphatidylinositol, is widely expressed on the cell surface of immune cells, such as mature lymphocytes, natural killer cells (NK), eosinophils, neutrophils, monocytes/macrophages, and dendritic cells (DCs). The anti-CD52 mAb, alemtuzumab, was used widely in clinics for the treatment of patients such as organ transplantation. In the present manuscript, we will briefly summarize the immunological function of CD52 and discuss the application of anti-CD52 mAb in transplantation settings.

Findings

We reviewed studies published until July 2016 to explore the role of CD52 in immune cell function and its implication in organ transplantation. We showed that ligation of cell surface CD52 molecules may offer costimulatory signals for T-cell activation and proliferation. However, soluble CD52 molecules will interact with the inhibitory sialic acid-binding immunoglobulin-like lectin 10 (Siglec10) to significantly inhibit T cell proliferation and activation. Although the physiological and pathological significances of CD52 molecules are still poorly understood, the anti-CD52 mAb, alemtuzumab, was used widely for the treatment of patients with chronic lymphocytic leukemia, autoimmune diseases as well as cell and organ transplantation in clinics.

Conclusion

Studies clearly showed that CD52 can modulate T-cell activation either by its intracellular signal pathways or by the interaction of soluble CD52 and Siglec-10 expressing on T cells. However, the regulatory functions of CD52 on other immune cell subpopulations in organ transplantation require to be studied in the near future.

http://ift.tt/2mvAkfy

Daphnetin reduces endotoxin lethality in mice and decreases LPS-induced inflammation in Raw264.7 cells via suppressing JAK/STATs activation and ROS production

Abstract

Objective

Here, we used various approaches to investigate the suppressive role of daphnetin in LPS-induced inflammatory response, with the goal to understand the underlining molecular mechanism by which daphnetin regulated these processes.

Methods

We examined the survival rate and the lung injury in the mice model of LPS-induced endotoxemia. The production of pro-inflammatory factors including tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), IL-6, nitric oxide (NO), and prostaglandin E2 (PGE2) was measured by ELISA and nitrite analysis, respectively. The expression of inducible NO synthase (iNOS), cyclooxygenase 2 (COX-2), and the activation of signaling molecules was determined by immunoblotting. The production of reactive oxygen species (ROS) was measured by the ROS assay.

Results

In vivo study showed that daphnetin enhanced the survival rate and reduced the lung injury in mice with LPS-induced endotoxemia. Both in vivo and in vitro study showed that daphnetin prevented the production of pro-inflammatory factors including TNF-α, IL-1β, IL-6, NO, and PGE2 after LPS challenge. In Raw264.7 cells, we found that daphnetin reduced LPS-induced expression of iNOS and COX-2, and suppressed LPS-induced ROS production. In addition, we found that daphnetin suppressed the activation of JAK/STATs pathway and inhibited the nucleus import of STAT1 and STAT3.

Conclusions

Here, our results indicate that daphnetin shows anti-inflammatory properties, at least in part, through suppressing LPS-induced activation of JAK/STATs cascades and ROS production.

http://ift.tt/2pagD0t

Mesenchymal stem cells cannot affect mRNA expression of toll-like receptors in different tissues during sepsis

Abstract

Objective and design

Experimental animal models and human clinical studies support a crucial role for TLRs in infectious diseases. The aim of this study was to test the ability of MSCs, which have immunomodulatory effects, of altering the mRNA expression of toll-like receptors during a experimental model of sepsis in different tissues.

Materials and methods

Three experimental groups (male C57BL/6 mice) were formed for the test: control group, untreated septic group and septic group treated with MSCs (1 × 10⁶ cells/animal). Lungs, cortex, kidney, liver and colon tissue were dissected after 12 h of sepsis induction and TLR2/3/4/9 mRNA were evaluated by RT-qPCR.

Results

We observed a decrease of TLR2 and 9 mRNA expression in the liver of the sepsis group, while TLR3 was decreased in the lung and liver. No change was found between the sepsis group and the sepsis + MSC group.

Conclusions

In this model of experimental sepsis the MSCs were unable to modify the mRNA expression of the different toll-like receptors evaluated.

http://ift.tt/2npurUY

Association of IL-1β, IL-1Ra and FABP1 gene polymorphisms with the metabolic features of polycystic ovary syndrome

Abstract

Background

Polycystic ovary syndrome (PCOS), a highly prevalent endocrinopathy is currently being designated as chronic low grade inflammatory state. IL-1β, IL-1Ra and FABP1 are critical mediators of inflammatory processes and are speculated to play a role in the pathogenesis of PCOS. The aim of this study was to study the association of IL-β, IL-1Ra and FABP1 gene polymorphisms with PCOS and related metabolic features.

Subjects

95 PCOS and 45 age matched healthy control subjects were enrolled in this study.

Methods

Polymorphism in genes IL-1β, IL-1Ra and FABP1 was studied by PCR, PCR–RFLP and sequencing methods, respectively. Hormonal and lipid profiles were evaluated for all the subjects.

Results

Hormonal and lipid profiles showed significant differences between PCOS and control subjects. Allele and genotype frequencies of IL-1β, IL-1Ra and FABP1 gene polymorphisms did not vary between the control and PCOS group. However, T allele of C[-511]T variant of IL-1β, allele II in intron 2 of IL-1Ra and A allele of A/G variant of FABP1 (rs2197076) showed significant association with many metabolic features associated with PCOS.

Conclusions

Polymorphism in genes encoding cytokines and proteins involved in lipid metabolism can provide insights into the genetics of the disease and may contribute to assess the associated risk of cardiovascular diseases (CVD), dyslipidemia and metabolic syndrome (MetS) associated with PCOS.

http://ift.tt/2ozlS9e

Probucol attenuates overt pain-like behavior and carrageenan-induced inflammatory hyperalgesia and leukocyte recruitment by inhibiting NF-кB activation and cytokine production without antioxidant effects

Abstract

Objective and design

This study aimed to evaluate the effect of probucol in inflammatory hyperalgesia and leukocyte recruitment in mice.

Treatment

Probucol at 0.3–3 mg/kg was administrated per oral 1 h before inflammatory stimulus.<?oxy_aq_start ?>Author: Kindly check and confirm the affiliation 1 have been correctly processed or not and amend if necessary.<?oxy_aq_end ?><?oxy_aqreply_start ?>Thank you. We have corrected affiliation 1. We added the information to the appropriate boxes. However the state and the postal code are in a different order when compared to the other affiliations.<?oxy_aqreply_end ?>

Methods

Overt pain-like behaviors were determined by the number of abdominal writhings induced by phenyl-p-benzoquinone and acetic acid. Mechanical and thermal hyperalgesia induced by carrageenan were determined using an electronic anesthesiometer and hot plate apparatus, respectively. Leukocyte recruitment was evaluated by direct count or by determination of myeloperoxidase and N-acetylglucosaminidase activities. Antioxidant ability was determined by measurement of GSH levels, ABTS and FRAP assays. Cytokine production and NF-кB activation were evaluated by ELISA. Data were analyzed by ANOVA followed by Tukey's post-hoc. p < 0.05 was considered significant.

Results

Probucol reduced overt pain-like behavior, and carrageenan-induced mechanical and thermal hyperalgesia. These effects were accompanied by reduced leukocyte influx in both paw skin and peritoneum exudate. Probucol did not alter carrageenan-induced tissue antioxidant capacity at anti-inflammatory/analgesic dose. On the other hand, probucol inhibited carrageenan-induced IL-1β, TNF-α and CXCL1 production as well as NF-кB activation.

Conclusion

Probucol presents analgesic and anti-inflammatory activities by employing mechanisms other than its antioxidant properties. These mechanisms involve targeting of pro-inflammatory cytokines and NF-кB activation.

http://ift.tt/2o26z6M

Paeonol protects against TNF-α-induced proliferation and cytokine release of rheumatoid arthritis fibroblast-like synoviocytes by upregulating FOXO3 through inhibition of miR-155 expression

Abstract

Background

Fibroblast-like synoviocytes (FLS) play an essential role in the pathogenesis of chronic inflammatory diseases, such as rheumatoid arthritis. Paeonol (Pae) is a phenolic compound found in many traditional Chinese medicine remedies. However, the effects of Pae on TNF-α-stimulated FLS and the underlying molecular mechanism are unknown. In this study, we aimed to investigate the anti-proliferative and anti-inflammatory effect of Pae against activated FLS.

Materials and methods

Rheumatoid arthritis FLS (RA-FLS) were pre-treated with different doses (25, 50, and 100 µM) of Pae or miR-155 inhibitor for 30 min or transfected with miR-155 mimic, and then treated with 50 ng/mL of tumor necrosis factor alpha (TNF-α) for 1 h. Cells that were untreated served as control. At 24 h after drug pretreatment, the proliferation of FLS was detected using the MTT assay. The concentrations of interleukin IL-6 and IL-1β in cell culture supernatant were examined by enzyme-linked immunosorbent assay (ELISA), and mRNA levels of Foxo3 and miR-155 expression in FLS were quantified by reverse transcription-polymerase chain reaction (RT-PCR). Protein expressions of forkhead box O3 (FOXO3), cyclin D1, and c-Myc were detected by Western Blot.

Results

TNF-α induced the proliferation of FLS, whereas Pae inhibited this proliferation in a dose-dependent manner. Pae attenuated TNF-α-induced production of IL-6 and IL-1β, and inhibited the expression of miR-155 in a dose-dependent manner. In addition, miR-155 inhibitor decreased TNF-α-induced proliferation of FLS, and attenuated TNF-α-induced production of IL-6 and IL-1β. In addition, pretreatment with different doses of Pae or miR-155 inhibitor markedly attenuated TNF-α-induced decrease in protein expression of FOXO3 in FLS. Mechanistic studies revealed FOXO3 as miR-155-5p direct target and inhibition of FOXO3 led to the abolishment of Pae protective effects.

Conclusions

Paeonol protected against TNF-α-induced proliferation and cytokine release of FLS by decreasing the expression of miR-155 and upregulating its target FOXO3.

http://ift.tt/2onFxHn

Dispersibility of carbon nanotubes in organic solvents: do we really have predictive models?

Abstract

Predicting the physico-chemical properties of carbon nanotubes (CNTs) is highly demanding owing to tedious experimental efforts involved in their determination. Dispersibility of CNTs in organic solvents is one such property; however, studies involving its quantitative prediction are quite scarce and highly questionable, particularly, when the real external predictivity is desired. This work examines the real external predictivity of the existing models as well as those developed in the present work (using quantum-chemical descriptors) for the dispersibility of single-walled CNTs (SWCNTs). The real external predictivity is assessed on the basis of state-of-the-art external validation parameters obtained by employing an external prediction set which is not exposed to the model used for the prediction. Notably, most of the present and existing models pass through the internal validation, but unfortunately, barring some exception of poly-parameter models, most of the models fail when it comes to the external validation. Their failure was attributed to the descriptors employed which are in fact based on the gas-phase single molecular structure of organic solvents as well as based on the implicit solvent methods. A future approach towards the predictive models for the dispersibility of CNTs is suggested based on the explicit solvent methods.

Graphical abstract

This quantum mechanical computational work evaluates the real external predictivity of the existing models for the dispersibility of carbon-nanotubes

http://ift.tt/2sc8BpP

The contributions of visual and central attention to visual working memory

Abstract

We investigated the role of two kinds of attention—visual and central attention—for the maintenance of visual representations in working memory (WM). In Experiment 1 we directed attention to individual items in WM by presenting cues during the retention interval of a continuous delayed-estimation task, and instructing participants to think of the cued items. Attending to items improved recall commensurate with the frequency with which items were attended (0, 1, or 2 times). Experiments 1 and 3 further tested which kind of attention—visual or central—was involved in WM maintenance. We assessed the dual-task costs of two types of distractor tasks, one tapping sustained visual attention and one tapping central attention. Only the central attention task yielded substantial dual-task costs, implying that central attention substantially contributes to maintenance of visual information in WM. Experiment 2 confirmed that the visual-attention distractor task was demanding enough to disrupt performance in a task relying on visual attention. We combined the visual-attention and the central-attention distractor tasks with a multiple object tracking (MOT) task. Distracting visual attention, but not central attention, impaired MOT performance. Jointly, the three experiments provide a double dissociation between visual and central attention, and between visual WM and visual object tracking: Whereas tracking multiple targets across the visual filed depends on visual attention, visual WM depends mostly on central attention.

http://ift.tt/2r3iG49

Ensemble coding remains accurate under object and spatial visual working memory load

Abstract

A number of studies have provided evidence that the visual system statistically summarizes large amounts of information that would exceed the limitations of attention and working memory (ensemble coding). However the necessity of working memory resources for ensemble coding has not yet been tested directly. In the current study, we used a dual task design to test the effect of object and spatial visual working memory load on size averaging accuracy. In Experiment 1, we tested participants' accuracy in comparing the mean size of two sets under various levels of object visual working memory load. Although the accuracy of average size judgments depended on the difference in mean size between the two sets, we found no effect of working memory load. In Experiment 2, we tested the same average size judgment while participants were under spatial visual working memory load, again finding no effect of load on averaging accuracy. Overall our results reveal that ensemble coding can proceed unimpeded and highly accurately under both object and spatial visual working memory load, providing further evidence that ensemble coding reflects a basic perceptual process distinct from that of individual object processing.

http://ift.tt/2slTf1W

Dopamine induces inhibitory effects on the circular muscle contractility of mouse distal colon via D1- and D2-like receptors

Abstract

Dopamine (DA) acts as gut motility modulator, via D1- and D2-like receptors, but its effective role is far from being clear. Since alterations of the dopaminergic system could lead to gastrointestinal dysfunctions, a characterization of the enteric dopaminergic system is mandatory. In this study, we investigated the role of DA and D1- and D2-like receptors in the contractility of the circular muscle of mouse distal colon by organ-bath technique. DA caused relaxation in carbachol-precontracted circular muscle strips, sensitive to domperidone, D2-like receptor antagonist, and mimicked by bromocriptine, D2-like receptor agonist. 7-Chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH-23390), D1-like receptor antagonist, neural toxins, L-NAME (nitric oxide (NO) synthase inhibitor), 2′-deoxy-N₆-methyl adenosine 3′,5′-diphosphate diammonium salt (MRS 2179), purinergic P2Y1 antagonist, or adrenergic antagonists were ineffective. DA also reduced the amplitude of neurally evoked cholinergic contractions. The effect was mimicked by (±)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrobromide (SKF-38393), D1-like receptor agonist and antagonized by SCH-23390, MRS 2179, or L-NAME. Western blotting analysis determined the expression of DA receptor proteins in mouse distal colon. Notably, SCH-23390 per se induced an increase in amplitude of spontaneous and neurally evoked cholinergic contractions, unaffected by neural blockers, L-NAME, MRS 2179, muscarinic, adrenergic, or D2-like receptor antagonists. Indeed, SCH-23390-induced effects were antagonized by an adenylyl cyclase blocker. In conclusion, DA inhibits colonic motility in mice via D2- and D1-like receptors, the latter reducing acetylcholine release from enteric neurons, involving nitrergic and purinergic systems. Whether constitutively active D1-like receptors, linked to adenylyl cyclase pathway, are involved in a tonic inhibitory control of colonic contractility is questioned.

http://ift.tt/2s4tTor

Novel tailoring algorithm for abrupt motion artifact removal in photoplethysmogram signals

Abstract

Photoplethysmogram (PPG) signals are widely used for wearable electronic devices nowadays. The PPG signal is extremely sensitive to the motion artifacts (MAs) caused by the subject's movement. The detection and removal of such MAs remains a difficult problem. Due to the complicated MA signal waveforms, none of the existing techniques can lead to satisfactory results. In this paper, a new framework to identify and tailor the abrupt MAs in PPG is proposed, which consists of feature extraction, change-point detection, and MA removal. In order to achieve the optimal performance, a data-dependent frame-size determination mechanism is employed. Experiments for the heart-beat-rate-measurement application have been conducted to demonstrate the effectiveness of our proposed method, by a correct detection rate of MAs at 98% and the average heart-beat-rate tracking accuracy above 97%. On the other hand, this new framework maintains the original signal temporal structure unlike the spectrum-based approach, and it can be further applied for the calculation of blood oxygen level (SpO₂).

http://ift.tt/2r2RYZC

The Mayo conservative hip: complication analysis and management of the first 41 cases performed at a University level 1 department

Abstract

Background

To prevent bone loss in hip arthroplasty, several short stem systems have been developed, including the Mayo conservative hip system. While there is a plethora of data confirming inherent advantages of these systems, only little is known about potential complications, especially when surgeons start to use these systems.

Methods

In this study, we present a retrospective analysis of the patients' outcome, complications and the complication management of the first 41 Mayo conservative hips performed in 37 patients. For this reason, functional scores, radiographic analyses, peri- and postoperative complications were assessed at an average follow-up of 35 months.

Results

The overall HHS improved from 61.2 pre-operatively to 85.6 post-operatively. The German Extra Short Musculoskeletal Function Assessment Questionnaire (XSFMA-D) improved from 30.3 pre-operatively to 12.2 post-operatively. The most common complication was an intraoperative non-displaced fracture of the proximal femur observed in 5 cases (12.1%). Diabetes, higher BMI and older ages were shown to be risk factors for these intra-operative periprosthetic fractures (p < 0.01). Radiographic analysis revealed a good offset reconstruction in all cases.

Conclusion

In our series, a high complication rate with 12.1% of non-displaced proximal femoral fractures was observed using the Mayo conservative hip. This may be attributed to the flat learning curve of the system or the inherent patient characteristics of the presented cohort.

http://ift.tt/2smq9zj

Influence of the Herbicide Facet® on Corticosterone Levels, Plasma Metabolites, and Antioxidant System in the Liver and Muscle of American Bullfrog Tadpoles

Abstract

This study sought to analyze the effects of the herbicide quinclorac on body condition indices; plasma levels of corticosterone, glucose, and uric acid; activity of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST); and levels of lipid peroxidation (LPO) in the liver and caudal muscle of American bullfrog (Rana catesbeiana) tadpoles. After a 7-day acclimation period, animals were exposed to four concentrations (0.05, 0.1, 0.2, and 0.4 μg/L) of herbicide for a further 7 days. Then, blood samples were obtained, animals were euthanized, and the liver and caudal muscle resected. Levels of corticosterone and uric acid were reduced in tadpoles exposed to the highest concentration of herbicide, and this reduction was preceded by an increase in glucose levels. In the liver tissue, LPO was increased after exposure to 0.1 μg/L quinclorac, followed by a return to baseline values in the remaining concentrations; this response was accompanied by an increase in SOD and GST and reduction of tissue protein levels. At the highest concentration, a reduction in activity of all enzymes was observed, with protein returning to control-like levels. In muscle, SOD and GST levels declined with exposures up to 0.1 g/L and 0.4 μg/L, respectively, whereas LPO decreased in animals exposed to 0.1 μg/L. These results suggest participation of nonenzymatic antioxidant defenses, as demonstrated by the reduction in uric acid levels. Exposure to the range of quinclorac concentrations used in this study slowed body mass and length gain, reduced corticosterone levels, and modulated antioxidant defenses.

Graphical abstract

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http://ift.tt/2sbFSRZ

The Appropriateness of an Improved Diary for the Assessment of Pre-Menstrual Mastalgia

Abstract

Current mastalgia assessment diaries are effective in reporting severity and frequency; however, literature suggests that timing and location should also be considered when assessing mastalgia alongside severity and frequency. This study aimed to assess validity, reliability, acceptability and minimal detectable change (MDC) of an improved mastalgia diary. Twenty premenopausal females who self-reported pre-menstrual mastalgia completed the diary once a day using paper, email or mobile formats, over one menstrual cycle. Predictive validity was assessed comparing pain pre- and post-menstruation. Test-retest and internal consistency established reliability. Acceptability was assessed using evaluation questions. MDC was calculated using a previously established method using the SEM to a 95% confidence interval. Results showed pre-menstrual mastalgia was significantly higher than post-menstrual, demonstrating diary validity. Reliability tests determined high test-retest reliability (ICC > 0.90) and internal consistency (α = 0.89). The diary was acceptable for >90% of participants. MDC-determined change of 1 on each question would be greater than measurement error and therefore representing 'real' change. This improved mastalgia diary is a more comprehensive, valid, reliable and acceptable tool for assessing mastalgia.

http://ift.tt/2t2Wsjn

An intravaginal ring that releases three antiviral agents and a contraceptive blocks SHIV-RT infection, reduces HSV-2 shedding, and suppresses hormonal cycling in rhesus macaques

Abstract

Women globally need access to multipurpose prevention technologies (MPTs) that prevent human immunodeficiency virus (HIV), sexually transmitted infections that increase HIV acquisition/transmission risk, and unintended pregnancy. Seeking an MPT with activity against HIV, herpes simplex virus-2 (HSV-2), and human papillomavirus (HPV), we developed a prototype intravaginal ring (IVR), the MZCL IVR, which released the antiviral agents MIV-150, zinc acetate, and carrageenan (MZC for short) and the contraceptive levonorgestrel (LNG). Previously, we showed that an MZC gel has potent activity against immunodeficiency viruses, HSV-2, and HPV and that the MZCL (MZC with LNG) IVR releases all four components in macaques in vivo at levels associated with efficacy. Vaginal fluid from treated macaques has in vitro activity against HIV, HSV-2, and HPV. Herein, we assessed the ability of the MZCL IVR to protect macaques against repeated co-challenge with HSV-2 and SHIV-RT (simian immunodeficiency virus [SIV] containing the reverse transcriptase gene from HIV) and prevent hormonal cycling. We evaluated in vivo drug release in co-challenged macaques by measuring drug levels in blood and vaginal fluid and residual drug levels in used IVRs. The MZCL IVR significantly prevented SHIV-RT infection, reduced HSV-2 vaginal shedding, and prevented cycling. No non-nucleoside HIV reverse transcriptase inhibitor (NNRTI)-resistant SHIV was detected in macaques that became infected after continuous exposure to MZC from the IVR. Macaques wearing the MZCL IVR also had carrageenan levels in vaginal fluid expected to protect from HPV (extrapolated from mice) and LNG levels in blood associated with contraceptive efficacy. The MZCL IVR is a promising MPT candidate that warrants further development.

http://ift.tt/2sL78Uq

Role of the immune system in cardiac tissue damage and repair following myocardial infarction

Abstract

Introduction

The immune system plays a crucial role in the initiation, development, and resolution of inflammation following myocardial infarction (MI). The lack of oxygen and nutrients causes the death of cardiomyocytes and leads to the exposure of danger-associated molecular patterns that are recognized by the immune system to initiate inflammation.

Results

At the initial stage of post-MI inflammation, the immune system further damages cardiac tissue to clear cell debris. The excessive production of reactive oxygen species (ROS) by immune cells and the inability of the anti-oxidant system to neutralize ROS cause oxidative stress that further aggravates inflammation. On the other hand, the cells of both innate and adaptive immune system and their secreted factors are critically instrumental in the very dynamic and complex processes of regulating inflammation and mediating cardiac repair.

Conclusions

It is important to decipher the balance between detrimental and beneficial effects of the immune system in MI. This enables us to identify better therapeutic targets for reducing the infarct size, sustaining the cardiac function, and minimizing the likelihood of heart failure. This review discusses the role of both innate and adaptive immune systems in cardiac tissue damage and repair in experimental models of MI.

http://ift.tt/2rdr8x2

Improving the Management of Psoriatic Arthritis and Axial Spondyloarthritis: Roundtable Discussions with Healthcare Professionals and Patients

Abstract

Psoriatic arthritis (PsA) and axial spondyloarthritis (AxSpA) are both chronic, inflammatory conditions that result in a substantial burden of disease and reduced quality of life for patients. Patient involvement in developing optimal disease management strategies, including defining appropriate goals, therapies, and treatment options, as well as in setting policy priorities and agendas, is key. A working group of patient organization representatives and rheumatologists explored what patients consider to be unmet needs, important treatment gaps, and future priorities in PsA and AxSpA management. Reducing pain and fatigue, and improving physical and social functioning and work productivity were identified as important treatment goals for patients. Although the major treatment target for both PsA and AxSpA is remission, with low/minimal disease activity an alternative target for patients with established or long-standing disease, the meaning of remission from the patient's perspective needs to be explored further as it may differ considerably from the physician's perspective. Key recommendations from the working group to tackle unmet needs included reducing time to diagnosis, increasing patient and physician disease awareness, focusing on patients' priorities for treatment goals, and improving patient–physician communication. By addressing these key action points moving forward, the hope is that outcomes will continue to improve for patients with PsA and AxSpA.

http://ift.tt/2r3akd5

Desflurane usage during anesthesia with and without N 2 O using FLOW-i Automatic Gas Control with three different wash-in speeds

Abstract

AGC^® (Automatic Gas Control) is the FLOW-i's automated low flow tool (Maquet, Solna, Sweden) that target controls the inspired O₂ (F_IO₂) and end-expired desflurane concentration (F_Ades) while (by design) exponentially decreasing fresh gas flow (FGF) during wash-in to a maintenance default FGF of 300 mL min⁻¹. It also offers a choice of wash-in speeds for the inhaled agents. We examined AGC performance and hypothesized that the use of lower wash-in speeds and N₂O both reduce desflurane usage (Vdes). After obtaining IRB approval and patient consent, 78 ASA I-II patients undergoing abdominal surgery were randomly assigned to 1 of 6 groups (n = 13 each), depending on carrier gas (O₂/air or O₂/N₂O) and wash-in speed (AGC speed 2, 4, or 6) of desflurane, resulting in groups air/2, air/4, air/6, N₂O/2, N₂O/4, and N₂O/6. The target for F_IO₂ was set at 35%, while the F_Ades target was selected so that the AGC displayed 1.3 MAC (corrected for the additive affect of N₂O if used). AGC was activated upon starting mechanical ventilation. Varvel's criteria were used to describe performance of achieving the targets. Patient demographics, end-expired N₂O concentration, MAC, FGF, and Vdes were compared using ANOVA. Data are presented as mean ± standard deviation, except for Varvel's criteria (median ± quartiles). Patient demographics did not differ among the groups. Median performance error was −2–0% for F_IO₂ and −3–1% for F_Ades; median absolute performance error was 1–2% for F_IO₂ and 0–3% for F_Ades. MAC increased faster in N₂O groups, but total MAC decreased 0.1–0.25 MAC below that in the O₂/air groups after 60 min. The effect of wash-in speed on Vdes faded over time. N₂O decreased Vdes by 62%. AGC performance for O₂ and desflurane targeting is excellent. After 1 h, the wash-in speeds tested are unlikely to affect desflurane usage. N₂O usage decreases Vdes proportionally with its reduction in F_Atdes.

http://ift.tt/2rUfSYs

Erratum to: What Are the Real Procedural Costs of Bariatric Surgery? A Systematic Literature Review of Published Cost Analyses

http://ift.tt/2s4JeFz

Utilization of Body Contouring Procedures Following Weight Loss Surgery: A Study of 37,806 Patients

Abstract

Background

Bariatric surgery has substantial health benefits; however, some patients desire body contouring (BC) procedures following rapid weight loss. There is a paucity of data regarding the true rate of BC following bariatric procedures. The purpose of our study is to examine the utilization of two common procedures, abdominoplasty, and panniculectomy, following bariatric surgery in New York State.

Methods

The SPARCS longitudinal administrative database was used to identify bariatric procedures by using ICD-9 and CPT codes between 2004 and 2010. Procedures included sleeve gastrectomy, Roux-en-Y gastric bypass, and laparoscopic adjustable gastric banding. Using a unique patient identifier, we tracked those patients who subsequently underwent either abdominoplasty or panniculectomy with at least a 4-year follow-up (until 2014). Multivariable Cox proportional hazard model was used to evaluate predictors of follow-up BC surgery.

Results

37,806 patients underwent bariatric surgery between 2004 and 2010. Only 5.58% (n = 2112) of these patients subsequently had a BC procedure, with 143 of them (6.8%) having ≥1 plastic surgery. The average time to plastic surgery after band, bypass, or sleeve was 1134.83 ± 671.09, 984.70 ± 570.53, and 903.02 ± 497.31 days, respectively (P < 0.0001). Following the multivariable Cox proportional hazard model, a female, SG patients, patients with Medicare or Medicaid, and patients in either <20 or >80%ile in yearly income were more likely to have plastic surgery after adjusting for age, race/ethnicity, comorbidities and complications (P values < 0.0001).

Conclusions

This study shows that plastic surgery is completed by only 6% of patients following bariatric procedures. As insurance and income are associated with pursuing surgery, improved access may increase the number of patients who are able to undergo these reconstructive procedures.

http://ift.tt/2t2ljUC

Laparoskopische Leberchirurgie

Zusammenfassung

Die laparoskopische Leberchirurgie hat einen festen Platz in der Behandlung von Lebertumoren eingenommen. Aufgrund der Vorteile für den Patienten im Kurz- und Langzeitverlauf stieg die Zahl der Zentren mit Erfahrung in laparoskopischer Leberchirurgie in den letzten Jahren stark an und die Komplexität der durchgeführten Eingriffe hat nahezu das Niveau der offenen Chirurgie erreicht. Dieser Artikel beschreibt den Stellenwert der laparoskopischen Leberchirurgie und diskutiert die Evidenzlage des Verfahrens. Zudem werden die Indikationsstellung bei den am häufigsten operierten Tumoren, Metastasen des kolorektalen Karzinoms und dem hepatozellulären Karzinom erläutert und auf Besonderheiten bei bestimmten Tumorlokalisationen hingewiesen. Des Weiteren erläutern die Autoren operationstechnische Aspekte und geben einen Überblick über neue Entwicklungen. Zur Veranschaulichung der Möglichkeiten laparoskopischer Leberchirurgie steht ein Video einer komplett laparoskopisch durchgeführten ALPPS („associating liver partition and portal vein ligation") -Prozedur als Begleitmaterial zur Verfügung.

http://ift.tt/2sL4zSf

Sekundärer Hyperparathyreoidismus nach Magenbypass

http://ift.tt/2sbDBq4

Wartezeit zwischen neoadjuvanter Radiochemotherapie und Resektion beim Rektumkarzinom

http://ift.tt/2sLkiRq

Neues aus der minimalinvasiven hepatopankreatobiliären Chirurgie

http://ift.tt/2sbz3Qj

Morphology and hydro-sensory role of superficial neuromasts in schooling behaviour of yellow-eyed mullet ( Aldrichetta forsteri )

Abstract

The lateral line system is a mechanosensory organ found in all fish species and located on the skin or in subdermal canals. The basic functional units are superficial and canal neuromasts, which are involved in hydrodynamic sensing and cohesion in schooling fish. Yellow-eyed mullet (Aldrichetta forsteri) are an obligate schooling species found commonly in shallow coastal areas of New Zealand and Australia. Schooling is a fundamental part of their behavioural repertoire, yet little is known about the structure or functionality of the lateral line in this species. We used scanning electron microscopy to characterise the morphology of trunk superficial neuromasts. We then took a multi-sensory approach and conducted behavioural experiments comparing school structure in groups of fish with and without fully functioning lateral lines, under photopic and scotopic conditions. A highly developed hydro-sensing system exists on the trunk of yellow-eyed mullet consisting of superficial neuromasts containing hundreds of hair cells aligned, with respect to their most sensitive axis, in a rostrocaudal direction. Without functioning superficial neuromasts, schooling behaviour was disrupted under both photopic and scotopic conditions and the ability to detect stationary objects decreased. Results highlight the importance of this component of the lateral line system to schooling behaviour.

http://ift.tt/2smbJPR

The nervous and visual systems of onychophorans and tardigrades: learning about arthropod evolution from their closest relatives

Abstract

Understanding the origin and evolution of arthropods requires examining their closest outgroups, the tardigrades (water bears) and onychophorans (velvet worms). Despite the rise of molecular techniques, the phylogenetic positions of tardigrades and onychophorans in the panarthropod tree (onychophorans + tardigrades + arthropods) remain unresolved. Hence, these methods alone are currently insufficient for clarifying the panarthropod topology. Therefore, the evolution of different morphological traits, such as one of the most intriguing features of panarthropods—their nervous system—becomes essential for shedding light on the origin and evolution of arthropods and their relatives within the Panarthropoda. In this review, we summarise current knowledge of the evolution of panarthropod nervous and visual systems. In particular, we focus on the evolution of segmental ganglia, the segmental identity of brain regions, and the visual system from morphological and developmental perspectives. In so doing, we address some of the many controversies surrounding these topics, such as the homology of the onychophoran eyes to those of arthropods as well as the segmentation of the tardigrade brain. Finally, we attempt to reconstruct the most likely state of these systems in the last common ancestors of arthropods and panarthropods based on what is currently known about tardigrades and onychophorans.

http://ift.tt/2r3cNnR

Improving the Management of Psoriatic Arthritis and Axial Spondyloarthritis: Roundtable Discussions with Healthcare Professionals and Patients

Abstract

Psoriatic arthritis (PsA) and axial spondyloarthritis (AxSpA) are both chronic, inflammatory conditions that result in a substantial burden of disease and reduced quality of life for patients. Patient involvement in developing optimal disease management strategies, including defining appropriate goals, therapies, and treatment options, as well as in setting policy priorities and agendas, is key. A working group of patient organization representatives and rheumatologists explored what patients consider to be unmet needs, important treatment gaps, and future priorities in PsA and AxSpA management. Reducing pain and fatigue, and improving physical and social functioning and work productivity were identified as important treatment goals for patients. Although the major treatment target for both PsA and AxSpA is remission, with low/minimal disease activity an alternative target for patients with established or long-standing disease, the meaning of remission from the patient's perspective needs to be explored further as it may differ considerably from the physician's perspective. Key recommendations from the working group to tackle unmet needs included reducing time to diagnosis, increasing patient and physician disease awareness, focusing on patients' priorities for treatment goals, and improving patient–physician communication. By addressing these key action points moving forward, the hope is that outcomes will continue to improve for patients with PsA and AxSpA.

http://ift.tt/2r3akd5

Role of the immune system in cardiac tissue damage and repair following myocardial infarction

Abstract

Introduction

The immune system plays a crucial role in the initiation, development, and resolution of inflammation following myocardial infarction (MI). The lack of oxygen and nutrients causes the death of cardiomyocytes and leads to the exposure of danger-associated molecular patterns that are recognized by the immune system to initiate inflammation.

Results

At the initial stage of post-MI inflammation, the immune system further damages cardiac tissue to clear cell debris. The excessive production of reactive oxygen species (ROS) by immune cells and the inability of the anti-oxidant system to neutralize ROS cause oxidative stress that further aggravates inflammation. On the other hand, the cells of both innate and adaptive immune system and their secreted factors are critically instrumental in the very dynamic and complex processes of regulating inflammation and mediating cardiac repair.

Conclusions

It is important to decipher the balance between detrimental and beneficial effects of the immune system in MI. This enables us to identify better therapeutic targets for reducing the infarct size, sustaining the cardiac function, and minimizing the likelihood of heart failure. This review discusses the role of both innate and adaptive immune systems in cardiac tissue damage and repair in experimental models of MI.

http://ift.tt/2rdr8x2

Solid lipid nanoparticles mediate non-viral delivery of plasmid DNA to dendritic cells

Abstract

There is an increasing demand for novel DNA vaccine delivery systems, mainly for the non-viral type as they are considered relatively safe. Therefore, solid lipid nanoparticles (SLNs) were investigated for their suitability as a non-viral DNA vaccine delivery system. SLNs were synthesised by a modified solvent-emulsification method in order to study their potential to conjugate with plasmid DNA and deliver them in vitro to dendritic cells using eGFP as the reporter plasmid. The DNA–SLN complexes were characterised by electron microscopy, gel retardation assays and dynamic light scattering. The cytotoxicity assay data supported their biocompatibility and was used to estimate safe threshold concentration resulting in high transfection rate. The transfection efficiency of these complexes in a dendritic cell line was shown to increase significantly compared to plasmid alone, and was comparable to that mediated by lipofectamine. Transmission electron microscopy studies delineated the pathway of cellular uptake. Endosomal escape was observed supporting the mechanism of transfection.

http://ift.tt/2rIIuWl

The impact of exposure to antidepressant medications during pregnancy on neonatal outcomes: a review of retrospective database cohort studies

Abstract

Introduction

Concerns with prescription antidepressant use in pregnant women have instigated the examination of potential associations between fetal exposure to antidepressant medication and outcomes including preterm delivery, congenital malformations, perinatal and post-natal adverse events, persistent pulmonary hypertension, and mortality. The retrospective cohort model is an often utilized study design. The objective of this review is to evaluate the literature on antidepressant use in pregnancy conducted as retrospective cohorts in national/regional medical, or claims databases that assess neonatal and infant outcomes for agreement between studies, ultimately providing a methodological and outcomes summary for future scientific endeavors.

Methods

PubMed was searched for literature relating to antidepressant use and infant outcomes from the earliest available date through July 15, 2016. Studies with a retrospective cohort design and conducted in national/regional medical or claims databases were included. Searched outcomes included preterm delivery, congenital malformations, low birth weight, small for gestational age, persistent pulmonary hypertension of the newborn, and other select adverse events comprising low Apgar score (5 min), convulsions/seizures, respiratory distress/problems, fetal mortality, and infant mortality.

Results

Of the 784 studies identified, 36 retrospective cohort studies met eligibility criteria. An increase in preterm delivery and respiratory distress/problems and no increase in congenital malformation or fetal and infant death were associated with prenatal use of prescription antidepressants by majority consensus (at least 2/3 [67%] of studies).

Conclusions

While consensus indicates that perinatal prescription antidepressant use has consequences for the fetus and infant, there are notable inconsistencies in the literature. More investigations that address prenatal exposure to depression and other important covariates are needed.

http://ift.tt/2t2pqjj

Clinical study of blood purification therapy in critical care in Japan: results from the survey research of the Japan Society for Blood Purification in Critical Care in 2013

Abstract

To clarify the clinical status of blood purification therapy (BPT) in critical care in Japan, we conducted a cohort study using data from a nationwide registry of the Japan Society for Blood Purification in Critical Care in 2013. We enrolled 2227 patients treated with BPT (female, 39.1%; mean age, 65.5 ± 12.1 years) in the intensive care units of 43 facilities. Patient characteristics, modes of BPT, and survival rate for each disease were investigated. In total, BPT was performed 3053 times. Continuous renal replacement therapy (CRRT) (57.9%) was the most common mode of BPT, followed by intermittent renal replacement therapy (20.2%) and direct hemoperfusion with the polymyxin B-immobilized fiber column (PMX-DHP) (11.5%). Nafamostat mesilate (84.9%) was most frequently used as the anticoagulant. The 28-day survival rate was 56.8% in all patients. The most common mode for acute kidney injury (AKI) and multiple organ failure was CRRT, while PMX-DHP and CRRT were most common for sepsis. There was no significant difference in survival rates among AKI stages 1–3. Survival rate (38.3%) was significantly lower in patients with acute lung injury (ALI) than in those with multiple organ failure (41.8%) and those with sepsis (46.6%). Multivariate regression analysis revealed that the APACHE II score and the presence of acute ALI and acute hepatic failure were significantly associated with death. This large-scale cohort study showed the clinical status of BPT in Japan. Further investigations are required to clarify the efficacy of BPT for critically ill patients.

http://ift.tt/2s4Dpbt

Occupational driving assessment for late-stage ankylosing spondylitis

http://ift.tt/2rItacb

Occupational driving assessment for late-stage ankylosing spondylitis

http://ift.tt/2rItacb

A hybrid backtracking search algorithm with wavelet mutation-based nonlinear system identification of Hammerstein models

Abstract

In this paper a novel and accurate approach is presented to identify varieties of nonlinear Hammerstein models (closed loop and open loop) with the help of an optimization algorithm that combines a recently proposed backtracking search algorithm with wavelet theory-based mutation scheme (BSA-WM). The optimum output MSE associated with each plant along with its statistical information justifies the better precision and accuracy of BSA-WM-based identification approach as compared to the other methods reported in earlier literature.

http://ift.tt/2rdbVMx

Mucosa-associated microbiota signature in colorectal cancer

Abstract

The aim of this study was to explore the gut microbiota profiles of colorectal cancer (CRC) patients and to examine the relationship between gut microbiota and other key molecular factors involved in CRC tumorigenesis. In this study, a 16S rDNA sequencing platform was used to identify possible differences in the microbiota signature between CRC and adjacent normal mucosal tissue. Differences in the microbiota composition in different anatomical colorectal tumor sites and their potential association with KRAS mutation were also explored. In this study, the number of Firmicutes and Actinobacteria decreased, while the number of Fusobacteria increased in the gut of CRC patients. In addition, at the genus level, Fusobacterium was identified as the key contributor to CRC tumorigenesis. In addition, a different distribution of gut microbiota in ascending and descending colon cancer samples was observed. Lipopolysaccharide biosynthesis-associated microbial genes were enriched in tumor tissues. Our study suggests that specific mucosa-associated microbiota signature and function are significantly changed in the gut of CRC patients, which may provide insight into the progression of CRC. These findings could also be of value in the creation of new prevention and treatment strategies for this type of cancer.

http://ift.tt/2t2fmaf

Performance and Tolerability of the Moisturizers Cetaphil ® and Excipial ® in Atopic Dermatitis: What is the Evidence Based on Randomized Trials?

Abstract

Introduction

Moisturizers play a prominent role in the management of atopic dermatitis by improving the impaired skin barrier function and enhancing skin hydration. Their efficacy was evaluated in a recently published Cochrane Review 'Emollients and moisturizers for eczema'.

Objective

In the present review, we summarize the performance and safety of Cetaphil^® and Excipial^® moisturizing products.

Methods

This review was carried out in compliance with standard Cochrane methodological procedures, which means independent study selection, data extraction, assessment of risk of bias, and analyses by two review authors. The quality of evidence for the predefined outcomes was rated with the GRADE approach. The prespecified outcomes of the review included participant assessments, satisfaction, adverse events, investigator assessments, prevention of flares, change in use of topical active treatment, skin barrier function and quality of life.

Results

Four randomized controlled studies examining these moisturizers were included in the previously published Cochrane Review. For the performance and tolerability of these moisturizers, there was very low to moderate quality evidence for the prespecified outcomes.

Conclusion

The results from these four studies are in line with those of the Cochrane Review that moisturizers themselves have beneficial effects, and that combining moisturizers with active topical treatment produced better results when compared to active topical treatment alone.

http://ift.tt/2s4i7KG

Management of blunt splenic injury in a UK major trauma centre and predicting the failure of non-operative management: a retrospective, cross-sectional study

Abstract

Purpose

To review the management of patients >16 years with blunt splenic injury in a single, UK, major trauma centre and identify whether the following are associated with success or failure of non-operative management with selective use of arterial embolization (NOM ± AE): age, Injury Severity Score (ISS), head injury, haemodynamic instability, massive transfusion, radiological hard signs [contrast extravasation or pseudoaneurysm on the initial computed tomography (CT) scan], grade, and presence of intraparenchymal haematoma or splenic laceration.

Methods

Retrospective, cross-sectional study undertaken between April 2012 and October 2015. Paediatric patients, penetrating splenic trauma, and iatrogenic injuries were excluded. Follow-up was for at least 30 days.

Results

154 patients were included. Median age was 38 years, 77.3% were male, and median ISS was 22. 14/87 (16.1%) patients re-bled following NOM in a median of 2.3 days (IQR 0.8–3.6 days). 8/28 (28.6%) patients re-bled following AE in a median of 2.0 days (IQR 1.3–3.7 days). Grade III–V injuries are a significant predictor of the failure of NOM ± AE (OR 15.6, 95% CI 3.1–78.9, p = 0.001). No grade I injuries and only 3.3% grade II injuries re-bled following NOM ± AE. Age ≥55 years, ISS, radiological hard signs, and haemodynamic instability are not significant predictors of the failure of NOM ± AE, but an intraparenchymal or subcapsular haematoma increases the likelihood of failure 11-fold (OR 10.9, 95% CI 2.2–55.1, p = 0.004).

Conclusions

Higher grade injuries (III–V) and intraparenchymal or subcapsular haematomas are associated with a higher failure rate of NOM ± AE and should be managed more aggressively. Grade I and II injuries can be discharged after 24 h with appropriate advice.

http://ift.tt/2t28rxL

Long-term carbon dioxide and hydrofluorocarbon emissions from commercial space cooling and refrigeration in India: a detailed analysis within an integrated assessment modelling framework

Abstract

Quantification of greenhouse gas emissions is a critical research gap for space cooling and refrigeration applications in Indian commercial buildings. This is especially relevant as these services are expected to grow rapidly in future driven by economic growth and urbanisation. This paper focuses on these two applications which are highly energy and emission intensive, and quantifies their carbon dioxide (CO₂) and hydrofluorocarbon (HFC) emissions through soft-linking a top-down model with a bottom-up approach. An integrated assessment modelling framework Global Change Assessment Model (GCAM)-IIM is used for modelling energy-related emissions under a business-as-usual scenario. In addition to CO₂ emissions occurring from electricity use, cooling and refrigeration in commercial buildings emit another set of highly potent greenhouse gases, emanating from application of HFCs as coolant. HFCs substitute their ozone-depleting precursors in these applications. Countries across the world have agreed to phase down HFCs under the Montreal Protocol. Before we can analyse cost-effective options to bring down these emissions, it is important to quantify and assess the amount of emissions that could be avoided in the future. Our research sets up a baseline for carbon dioxide and HFC emissions from India for the commercial air-conditioning and refrigeration sectors and finds the potential HFC emission mitigation due to the Kigali Amendment. A detailed bottom-up modelling of these emissions is undertaken and it is found that, if unabated, the HFC emissions from commercial sector will surge from mere 1.8 million tonne (Mt) CO₂e in 2015 to 211 Mt CO₂e in 2050, whereas energy-related CO₂ emissions from commercial air-conditioning and refrigeration will rise from 37 to 297 Mt CO₂e in the same period. We also highlight the role of management practices and regulation for curbing HFC emissions which is especially relevant for the commercial building sector.

http://ift.tt/2s3MfpK