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Σάββατο 17 Δεκεμβρίου 2016

DRα1-MOG-35-55 Reduces Permanent Ischemic Brain Injury

Abstract

Stroke induces a catastrophic immune response that involves the global activation of peripheral leukocytes, especially T cells. The human leukocyte antigen-DRα1 domain linked to MOG-35-55 peptide (DRα1-MOG-35-55) is a partial major histocompatibility complex (MHC) class II construct which can inhibit neuroantigen-specific T cells and block binding of the cytokine/chemokine macrophage migration inhibitory factor (MIF) to its CD74 receptor on monocytes and macrophages. Here, we evaluated the therapeutic effect of DRα1-MOG-35-55 in a mouse model of permanent distal middle cerebral artery occlusion (dMCAO). DRα1-MOG-35-55 was administered to WT C57BL/6 mice by subcutaneous injection starting 4 h after the onset of ischemia followed by three daily injections. We demonstrated that DRα1-MOG-35-55 post treatment significantly reduced brain infarct volume, improved functional outcomes, and inhibited the accumulation of CD4+ and CD8+ T cells and expression of pro-inflammatory cytokines in the ischemic brain 96 h after dMCAO. In addition, DRα1-MOG-35-55 treatment shifted microglia/macrophages in the ischemic brain to a beneficial M2 phenotype without changing their total numbers in the brain or blood. This study demonstrates for the first time the therapeutic efficacy of the DRα1-MOG-35-55 construct in dMCAO across MHC class II barriers in C57BL/6 mice. This MHC-independent effect obviates the need for tissue typing and will thus greatly expedite treatment with DRα1-MOG-35-55 in human stroke subjects. Taken together, our findings suggest that DRα1-MOG-35-55 treatment may reduce ischemic brain injury by regulating post-stroke immune responses in the brain and the periphery.



http://ift.tt/2hM69y3

Jim Crow and estrogen-receptor-negative breast cancer: US-born black and white non-Hispanic women, 1992–2012

Abstract

Purpose

It is unknown whether Jim Crow—i.e., legal racial discrimination practiced by 21 US states and the District of Columbia and outlawed by the US Civil Rights Act in 1964—affects US cancer outcomes. We hypothesized that Jim Crow birthplace would be associated with higher risk of estrogen-receptor-negative (ER−) breast tumors among US black, but not white, women and also a higher black versus white risk for ER− tumors.

Methods

We analyzed data from the SEER 13 registry group (excluding Alaska) for 47,157 US-born black non-Hispanic and 348,514 US-born white non-Hispanic women, aged 25–84 inclusive, diagnosed with primary invasive breast cancer between 1 January 1992 and 31 December 2012.

Results

Jim Crow birthplace was associated with increased odds of ER− breast cancer only among the black, not white women, with the effect strongest for women born before 1965. Among black women, the odds ratio (OR) for an ER− tumor, comparing women born in a Jim Crow versus not Jim Crow state, equaled 1.09 (95% confidence interval [CI] 1.06, 1.13), on par with the OR comparing women in the worst versus best census tract socioeconomic quintiles (1.15; 95% CI 1.07, 1.23). The black versus white OR for ER− was higher among women born in Jim Crow versus non-Jim Crow states (1.41 [95% CI 1.13, 1.46] vs. 1.27 [95% CI 1.24, 1.31]).

Conclusions

The unique Jim Crow effect for US black women for breast cancer ER status underscores why analysis of racial/ethnic inequities must be historically contextualized.



http://ift.tt/2husXEx

Application of Green Manure and Pig Manure to Cd-Contaminated Paddy Soil Increases the Risk of Cd Uptake by Rice and Cd Downward Migration into Groundwater: Field Micro-Plot Trials

Abstract

Land application of organic manure, crop residue, and biosolid, an important means for the disposal and recycling of wastes, has been shown to significantly increase the amount of dissolved organic matter (DOM) in soil. However, limited information is available on the dynamics of DOM, the concentration is usually expressed by dissolved organic carbon (DOC), and its influence on Cd behaviors in paddy soil amended with and without organic materials during rice (kinmaze) growing season. In this study, in situ field experiments were conducted to investigate the dynamics of DOC in paddy soil amended with green manure (GM), pig manure (PM), and chemical fertilizer (F) and its effect on Cd mobility and bioavailability. The results showed that DOC concentrations in soil solutions extracted from different depths were higher in GM and PM plots than those in F plot, and DOC concentrations all declined with time and rice growth. DOC concentrations in the root zone soil for all treatments were higher than those in the non-root zone due to root exudation and the higher pH value. The temporal dynamics of DOC in the root zone were found to be correlated to rice growth stage, as DOC concentrations decreased in the initial stage (week 1 to 6) of rice seedling and then gradually increased and reached the highest levels with 30.42 mg DOC L−1 for GM, 28.88 mg DOC L−1 for PM, and 19.19 mg DOC L−1 for F at rice heading and flowering stage (week 10), hereafter decreased again until when the rice was harvested. However, soil DOC in the non-root zone exhibited a continuous decrease trend and remained at a relatively low level after week 10 with 15.36 mg DOC L−1 for GM, 15.31 mg DOC L−1 for PM, and 8.43 mg DOC L−1 for F. The dynamics of water soluble Cd displayed statistically significant positive relationship with DOC (r 0.01 = 0.765, n = 9) regardless of soil depth and root presence/absence, suggesting that DOC enhanced the mobility and transport of through the formation of Cd-DOC complexes. As a result, DOC could increase the potential uptake of Cd by rice as well as the downward Cd migration to deeper soil. In these experiments, the uptake of Cd by rice grown in the GM and PM plots reached 5.55 and 3.71 mg plot−1, respectively, which were much higher than that in the F plot with 1.88 mg plot−1. The amounts of Cd downward migration were 17.0 mg plot−1 for GM plot, 14.74 mg plot−1 for PM plot, and 4.13 mg plot−1 for F plot, respectively. It could be concluded that the application of green manure and pig manure to Cd-contaminated paddy soil will increase the risk of Cd uptake by rice and Cd downward migration into groundwater. For this reason, care should be taken when organic manures was applied to contaminated soil to remediate or alleviate soil pollution and maintain soil fertility as well as provide nutrients for plant growth.



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Ozone and Nitrogen Effects on Juvenile Subalpine Plants: Complex Interactions with Species and Colonization by Arbuscular Mycorrhizal Fungi (AMF)

Abstract

Increasing concentrations of tropospheric ozone and reactive nitrogen threaten the composition and function of semi-natural plant communities. Using a free-air fumigation system, we investigated the effects of elevated ozone (1.73 × ambient concentration; +O3) and nitrogen (+50 k g N ha year−1; +N) deposition on growth of juveniles of three subalpine grassland species and their colonization by arbuscular mycorrhizal fungi (AMF) in situ. In a subsample, the extra-radical mycelium was regularly disrupted to determine the effect of AMF on the plants' pollutant sensitivity. The plants reacted sensitively to the pollutants: +N increased shoot growth in Festuca rubra, while +O3 decreased root growth in Trifolium alpinum and F. rubra. Colonization with AMF was stimulated by N in Leontodon helveticus and was strongly reduced by O3 in F. rubra and L. helveticus, probably due to lower carbon allocation belowground. Conversely, AMF did not protect plants from O3 neither did they increase the species' responsiveness to N. Our results indicate that irrespective of AMF colonization, juvenile plants are highly sensitive to O3 stress, probably since their growth is primarily limited by carbon assimilation.



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Novel insights into biosynthesis and uptake of rhamnolipids and their precursors

Abstract

The human pathogenic bacterium Pseudomonas aeruginosa produces rhamnolipids, glycolipids with functions for bacterial motility, biofilm formation, and uptake of hydrophobic substrates. Rhamnolipids represent a chemically heterogeneous group of secondary metabolites composed of one or two rhamnose molecules linked to one or mostly two 3-hydroxyfatty acids of various chain lengths. The biosynthetic pathway involves rhamnosyltransferase I encoded by the rhlAB operon, which synthesizes 3-(3-hydroxyalkanoyloxy)alkanoic acids (HAAs) followed by their coupling to one rhamnose moiety. The resulting mono-rhamnolipids are converted to di-rhamnolipids in a third reaction catalyzed by the rhamnosyltransferase II RhlC. However, the mechanism behind the biosynthesis of rhamnolipids containing only a single fatty acid is still unknown. To understand the role of proteins involved in rhamnolipid biosynthesis the heterologous expression of rhl-genes in non-pathogenic Pseudomonas putida KT2440 strains was used in this study to circumvent the complex quorum sensing regulation in P. aeruginosa. Our results reveal that RhlA and RhlB are independently involved in rhamnolipid biosynthesis and not in the form of a RhlAB heterodimer complex as it has been previously postulated. Furthermore, we demonstrate that mono-rhamnolipids provided extracellularly as well as HAAs as their precursors are generally taken up into the cell and are subsequently converted to di-rhamnolipids by P. putida and the native host P. aeruginosa. Finally, our results throw light on the biosynthesis of rhamnolipids containing one fatty acid, which occurs by hydrolyzation of typical rhamnolipids containing two fatty acids, valuable for the production of designer rhamnolipids with desired physicochemical properties.



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Cost-Effectiveness Analysis of Apixaban, Dabigatran, Rivaroxaban, and Warfarin for Stroke Prevention in Atrial Fibrillation in Taiwan

Abstract

Background and Objectives

The aim of this study was to evaluate the cost effectiveness of novel oral anticoagulants (NOACs) for stroke prevention among atrial fibrillation (AF) patients by incorporating Taiwanese demographic information derived from a population-based database, the National Health Insurance Research Database (NHIRD), into cost-effectiveness analysis.

Methods

From 1 January to 31 December 2012, 98,213 AF patients were selected from the NHIRD database. A Markov model was constructed that combined published secondary data with the Taiwan NHIRD to compare the cost and incremental cost effectiveness of apixaban 5 mg twice daily, dabigatran 110 or 150 mg twice daily, rivaroxaban 20 mg once daily, and warfarin.

Results

The lifetime costs of warfarin, dabigatran 110 mg, dabigatran 150 mg, rivaroxaban 20 mg, and apixaban 5 mg were US$10,660, US$13,693, US$13,426, US$13,455, US$15,965, respectively. Apixaban resulted in an incremental cost effectiveness of US$39,351, US$27,039, US$41,298, and US$48,896 per quality-adjusted life-year (QALY) compared with warfarin, dabigatran 110 mg, dabigatran 150 mg, and rivaroxaban 20 mg, respectively. In Monte-Carlo analyses, apixaban 5 mg, rivaroxaban 20 mg, warfarin, and dabigatran 110 mg were cost effective in 83, 10.4, 7, and 0.8%, respectively, of the simulations using a willingness-to-pay (WTP) threshold of US$50,000 per QALY.

Conclusions

Apixaban was more cost effective than warfarin, dabigatran, and rivaroxaban for stroke prevention in patients with AF. Among the anticoagulant therapies, the WTP threshold of apixaban was about US$50,000 per QALY gained. These cost-effectiveness estimations provide useful information to aid clinical decision making in stroke prevention for AF patients.



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Video analysis of epileptic-like motor patterns in REM behaviour disorder: a case series



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A novel anti-viral role for STAT3 in IFN-α signalling responses

Abstract

The cytokine, Interferon (IFN)-α, induces a wide spectrum of anti-viral mediators, via the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. STAT1 and STAT2 are well characterised to upregulate IFN-stimulated gene (ISG) expression; but even though STAT3 is also activated by IFN-α, its role in anti-viral ISG induction is unclear. Several viruses, including Hepatitis C and Mumps, reduce cellular STAT3 protein levels, via the promotion of ubiquitin-mediated proteasomal degradation. This viral immune evasion mechanism suggests an undiscovered anti-viral role for STAT3 in IFN-α signalling. To investigate STAT3's functional involvement in this Type I IFN pathway, we first analysed its effect upon the replication of two viruses, Influenza and Vaccinia. Viral plaque assays, using Wild Type (WT) and STAT3-/- Murine Embryonic Fibroblasts (MEFs), revealed that STAT3 is required for the inhibition of Influenza and Vaccinia replication. Furthermore, STAT3 shRNA knockdown also enhanced Influenza replication and hindered induction of several, well characterised, anti-viral ISGs: PKR, OAS2, MxB and ISG15; while STAT3 expression had no effect upon induction of a separate ISG group: Viperin, IFI27, CXCL10 and CCL5. These discoveries reveal, for the first time, an anti-viral role for STAT3 in the IFN-α pathway and characterise a requirement for STAT3 in the expression of specific ISGs. These findings also identify STAT3 as a therapeutic target against viral infection and highlight it as an essential pathway component for endogenous and therapeutic IFN-α responsiveness.



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Endovascular treatment of giant-dissecting posterior cerebral artery aneurysm in an infant



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Edaravone reduces astrogliosis and apoptosis in young rats with kaolin-induced hydrocephalus

Abstract

Purpose

We investigated the possible neuroprotective effects of the free radical scavenger edaravone in experimental hydrocephalus.

Methods

Seven-day-old Wistar rats were divided into three groups: control group (C), untreated hydrocephalic (H), and hydrocephalic treated with edaravone (EH). The H and EH groups were subjected to hydrocephalus induction by 20% kaolin intracisternal injection. The edaravone (20 mg/kg) was administered daily for 14 days from the induction of hydrocephalus. All animals were daily weighed and submitted to behavioral test and assessment by magnetic resonance imaging. After 14 days, the animals were sacrificed and the brain was removed for histological, immunohistochemical, and biochemical studies.

Results

The gain weight was similar between groups from the ninth post-induction day. The open field test performance of EH group was better (p < 0.05) as compared to untreated hydrocephalic animals. Hydrocephalic animals (H and EH) showed ventricular ratio values were higher (p < 0.05), whereas magnetization transfer values were lower (p < 0.05), as compared to control animals. Astrocyte activity (glial fibrillary acidic protein) and apoptotic cells (caspase-3) of EH group were decreased on the corpus callosum (p > 0.01), germinal matrix (p > 0.05), and cerebral cortex (p > 0.05), as compared to H group.

Conclusions

We have demonstrated that administration of edaravone for 14 consecutive days after induction of hydrocephalus reduced astrocyte activity and that it has some beneficial effects over apoptotic cell death.



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Persistent shunt dependency and very late shunt failure in a 3-year-old boy with idiopathic intracranial hypertension (IIH)



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Therapeutic hypothermia for neonatal hypoxic ischemic encephalopathy is associated with short-term reduction of seizures after discharge from the neonatal intensive care unit

Abstract

Introduction

Therapeutic hypothermia for the treatment of moderate to severe neonatal hypoxic ischemic encephalopathy has been shown to reduce death and disability, but the effects on seizures after discharge from the Neonatal ICU are not known.

Methods

A retrospective cohort study was conducted involving 56 neonates admitted to the Neonatal ICU at Children's Hospital of Orange County, CA from January 1, 2007 to September 1, 2013 with hypoxic ischemic encephalopathy who met criteria for selective brain cooling. Fifteen patients received supportive care. Forty-one patients received cooling, of whom 25 were included for analysis. Sixteen patients from the hypothermia group and 12 from the no hypothermia group developed clinical seizures while inpatient. Up to 6 months, four patients (16%) had continued seizures in the therapeutic hypothermia group compared to eight (53%) patients who did not receive hypothermia.

Discussion

Our study shows an association between therapeutic hypothermia and reduced seizures after discharge from the neonatal intensive care unit. The short duration of follow-up, 6 months, is a limitation of this study. Another limitation is its observational nature, where reasons for treatment selection and exclusions are unmeasurable confounding factors. Further studies are needed to determine long-term effects.



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Posterior hemivertebrectomy and short segment fixation—long term results

Abstract

Objectives

The objectives of this study were to study the long-term results of one-stage single and multiple level posterior hemivertebrectomies and to find out the safety and efficacy of the procedure.

Method

Twenty patients (9 male and 11 female) with mean age of 9.2 years (2 years 4 months–14 years 10 months) with congenital scoliosis (hemivertebrae) were treated with posterior hemivertebrectomy with intraoperative neuromonitoring. Posterior exposure and transpedicular fixation of the adjoining vertebrae was done. The hemivertebra was approached from the convex side, and transpedicular decancellation followed by complete excision was done. Controlled compression at the convexity was done after a cantilever manoeuvre was done for rod capturing on the convexity to achieve the reduction.

Results

Average number of hemivertebra removed was 1.46 (1–3). Mean pre-op and post-op coronal Cobb angle was 48.8° (range 22 to 80) and 24.2° (range 7 to 41), respectively (p < 0.001). Mean pre-op and post-op sagittal Cobb angle was 32.1° (range 7 to 76) and 13.6° (range 0 to 23) respectively, (p < 0.005). Mean coronal and sagittal Cobb correction percentage achieved was 50.2 and 51.8%, respectively. Mean follow-up was 62.4 months (range 24–73 months). Mean loss of coronal and sagittal correction at final follow-up was 2.26° (0–8) and 1.55° (0–5), respectively. Maximum correction in both coronal (p = 0.167) and sagittal (p = 0.095) planes was achieved in thoracolumbar vertebrae. Maximum correction was achieved in 3 level hemivertebrae in sagittal (p = 0.9) and 2 level hemivertebrae in coronal plane (p = 0.740).

Conclusions

Posterior hemivertebrectomy is a safe and effective procedure for congenital scoliosis. Not only single but up to 3 level hemivertebrae can be safely removed with good correction of deformity. Long-term follow-up reveals good maintenance of correction.



http://ift.tt/2i117Nr

Systematic review of rheumatic disease phenotypes and outcomes in the Indigenous populations of Canada, the USA, Australia and New Zealand

Abstract

We performed a systematic review designed to characterize clinical phenotypes and outcomes in Indigenous populations with rheumatic disease to enhance the understanding of how rheumatic disease presents in Indigenous populations and allow for better projection of the healthcare needs of the communities affected. A systematic search was performed in medical (Medline, EMBASE, CINAHL), Indigenous and conference abstract databases (to June 2015). Search terms for Indigenous populations were combined with terms for inflammatory arthritis conditions, connective tissue disorders, crystal arthritis and osteoarthritis. Studies were included if they reported on disease features, disease activity measures, or patient-reported outcomes in Canadian, American, Australian or New Zealand Indigenous populations. Data were extracted in duplicate, and a narrative summary was prepared. A total of 5269 titles and abstracts were reviewed, of which 504 underwent full-text review and 85 met inclusion criteria. Nearly all the studies described outcomes in the North American populations (n = 77), with only four studies from Australia and four studies from New Zealand. The majority of studies were in rheumatoid arthritis (n = 31) and systemic lupus erythematosus (n = 19). Indigenous patients with rheumatoid arthritis had higher disease activity and reported more significant impact on patient-reported outcomes and quality of life than non-Indigenous patients. Spondyloarthropathy features were described in North American populations, with most patients having advanced manifestations. In systemic lupus erythematosus, nephritis was more frequent in Indigenous populations. Gout and osteoarthritis were more severe in New Zealand Maori populations. The existing literature supports differences in disease phenotype and severity in Indigenous populations of Canada, America, Australia and New Zealand. We encourage investigators in this area of research to undertake contemporary studies that disentangle differences between phenotype and severity that are biologic in etiology or merely reflecting differences in access to care and that provide a longitudinal assessment of outcomes in more diverse populations.



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Comparative Pharmacology and Guide to the Use of the Serotonin 5-HT 3 Receptor Antagonists for Postoperative Nausea and Vomiting

Abstract

Since the introduction of the serotonin 5-hydroxy tryptamine 3 (5-HT3) receptor antagonists in the early 1990s, the incidence of postoperative nausea and vomiting (PONV) and post-discharge nausea and vomiting (PDNV) has decreased, yet continues to be a problem for the surgical patient. The clinical application of the 5-HT3 receptor antagonists has helped define the approach and role of these antiemetics in the prevention and treatment of PONV and PDNV. Pharmacological and clinical differences exist among these medications resulting in corresponding differences in effectiveness, safety, optimal dosage, time of administration, and use as combination and rescue antiemetic therapy. The clinical application of the 5-HT3 receptor antagonist antiemetics has improved the prevention and treatment of PONV and PDNV. The most recent consensus guidelines for PONV published in 2014 outline the use of these antiemetics. The 5-HT3 receptor antagonists play an important role to help prevent PONV and PDNV in perioperative care pathways such as Enhanced Recovery After Surgery (ERAS). Comparisons and guidelines for use of the 5-HT3 receptor antagonists in relation to the risk for PONV and PDNV are reviewed.



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Coagulation Factor IX (Recombinant), Albumin Fusion Protein (Albutrepenonacog Alfa; Idelvion ® ): A Review of Its Use in Haemophilia B

Abstract

Albutrepenonacog alfa (Idelvion®), a fusion protein that genetically fuses recombinant factor IX (rFIX) with recombinant human albumin (rAlbumin), is indicated in the treatment of haemophilia B. This narrative review discusses the pharmacological properties and clinical data related to the use of this novel fusion protein, hereafter referred to as rIX-FP. The fusion of rFIX to rAlbumin prolongs the elimination half-life of rIX-FP in the circulation, allowing routine prophylaxis to be administered once every 7–14 days. In the pivotal phase 3 clinical trials in previously treated patients with moderately severe to severe haemophilia B, routine rIX-FP prophylaxis (administered once every 7 days in children, and once every 7–14 days in adolescents and adults) was associated with low annualized spontaneous, total and joint bleeding rates, and was associated with significantly fewer bleeding episodes than on-demand treatment. rIX-FP was also effective in controlling bleeding episodes when used as on-demand treatment and in maintaining haemostasis in the perioperative setting. rIX-FP was well tolerated in the clinical trials, with no reports of inhibitor development. In conclusion, rIX-FP provides an effective, well-tolerated option for the treatment and management of haemophilia B that, by virtue of its extended half-life, is less burdensome than conventional FIX products.



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Insulin Resistance and Neurodegeneration: Progress Towards the Development of New Therapeutics for Alzheimer’s Disease

Abstract

Alzheimer's disease (AD) should be regarded as a degenerative metabolic disease caused by brain insulin resistance and deficiency, and overlapping with the molecular, biochemical, pathophysiological, and metabolic dysfunctions in diabetes mellitus, non-alcoholic fatty liver disease, and metabolic syndrome. Although most of the diagnostic and therapeutic approaches over the past several decades have focused on amyloid-beta (Aβ42) and aberrantly phosphorylated tau, which could be caused by consequences of brain insulin resistance, the broader array of pathologies including white matter atrophy with loss of myelinated fibrils and leukoaraiosis, non-Aβ42 microvascular disease, dysregulated lipid metabolism, mitochondrial dysfunction, astrocytic gliosis, neuro-inflammation, and loss of synapses vis-à-vis growth of dystrophic neurites, is not readily accounted for by Aβ42 accumulations, but could be explained by dysregulated insulin/IGF-1 signaling with attendant impairments in signal transduction and gene expression. This review covers the diverse range of brain abnormalities in AD and discusses how insulins, incretins, and insulin sensitizers could be utilized to treat at different stages of neurodegeneration.



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Current Pharmacological Approaches to Reduce Chorea in Huntington’s Disease

Abstract

There are currently no effective pharmacological agents available to stop or prevent the progression of Huntington's disease (HD), a rare hereditary neurodegenerative disorder. In addition to psychiatric symptoms and cognitive impairments, HD causes progressive motor disturbances, in particular choreiform movements, which are characterized by unwanted contractions of the facial muscles, trunk and extremities. Management of choreiform movements is usually advised if chorea interferes with daily functioning, causes social isolation, gait instability, falls, or physical injury. Although drugs to reduce chorea are available, only few randomized controlled studies have assessed the efficacy of these drugs, resulting in a high variety of prescribed drugs in clinical practice. The current pharmacological treatment options to reduce chorea in HD are outlined in this review, including the latest results on deutetrabenazine, a newly developed pharmacological agent similar to tetrabenazine, but with suggested less peak dose side effects. A review of the existing literature was conducted using the PubMed, Cochrane and Medline databases. In conclusion, mainly tetrabenazine, tiapride (in European countries), olanzapine, and risperidone are the preferred first choice drugs to reduce chorea among HD experts. In the existing literature, these drugs also show a beneficial effect on motor symptom severity and improvement of psychiatric symptoms. Generally, it is recommended to start with a low dose and increase the dose with close monitoring of any adverse effects. New interesting agents, such as deutetrabenazine and pridopidine, are currently under development and more randomized controlled trials are warranted to assess the efficacy on chorea severity in HD.



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Single-Dose Dalbavancin: A Review in Acute Bacterial Skin and Skin Structure Infections

Abstract

Intravenous dalbavancin (Dalvance®, Xydalba®), first approved as a two-dose regimen for the treatment of acute bacterial skin and skin structure infections (ABSSSI), has now been additionally approved as a single-dose regimen. This narrative review discusses the pharmacological properties of intravenous dalbavancin and its clinical efficacy and tolerability as a single-dose regimen in the treatment of adult patients with ABSSSI. Single-dose dalbavancin is an effective and generally well tolerated treatment option for adults with ABSSSI, with noninferior efficacy to the two-dose dalbavancin regimen with regard to early clinical response (at 48–72 h) and low rates of adverse events. Clinical success rates at days 14 and 28 also did not significantly differ between the single- and two-dose dalbavancin regimens; neither did clinical success rates at day 14 when analysed by baseline pathogen. It has a broad spectrum of activity against common ABSSSI-related pathogens, and a favourable pharmacokinetic profile allowing for the convenience of single-dose administration. Thus, dalbavancin presents a promising alternative to conventional antibacterials for the treatment of ABSSSI in adult patients.



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Release-Active Antibodies to S100 Protein Can Correct the Course of Experimental Allergic Encephalomyelitis

Objective. To study the efficacy of release-active forms of antibody to S100 protein in an animal model of multiple sclerosis. Materials and methods. The study was performed on 60 female rats aged 12 weeks. Experimental allergic encephalomyelitis was induced by administration of spinal cord homogenate at the base of the tail. Female rats then received intragastric solution of release-active antibodies to S100 protein (Tenoten) at a dose of 2.5 ml/kg/day or distilled water for 30 days. Positive controls received i.m. injections of glatiramer acetate at a dose of 4 mg/kg/day (Copaxone). Results and discussion. Administration of release-active forms of antibody to S100 increased the latent period of disease onset, decreased in peak disease intensity, and compensated for weight loss in the animals, as compared with controls. The effect of the agents was comparable with that of the Copaxone group.



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Neuroprotective Therapy of Chronic Cerebral Ischemia in Out-Patient Conditions

Objectives. To conduct a differential analysis of the efficacy of combined treatment using drugs with different mechanisms of action (Mexidol, aescusan, Halidor) in patients with chronic cerebral ischemia (CCI) stages I, II, and III in out-patient conditions. Materials and methods. The study included 50 patients with diagnoses of chronic cerebral ischemia stages I–III of atherosclerotic, hypertensive, and mixed origin (20 patients with stage I, 20 with stage II, and 10 with stage III). On the background of basal treatment, patients received three courses of combined therapy with Mexidol, Halidor, and aescusan for six weeks with three-month intervals between courses. Changes in patients' subjective complaints and objective clinical signs were evaluated after each course. Results and conclusions. Clinical neurological investigations demonstrated the therapeutic efficacy of prolonged complex treatment with different courses of antioxidants. Use of the combination of Mexidol, aescusan, and Halidor promoted improvements in cognitive, adaptive, and motor functions in patients with CCI stages I and II. Increases in treatment efficacy were obtained in patients with CCI stage III by supplementing the neuroprotective actions of the drugs used with agents improving cognitive functions.



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Effects of an Agonist and an Antagonist of α2-Adrenoreceptors on Selection of Reinforcement Value in Rats with Different Levels of Impulsivity

The effects of an agonist and an antagonist of α2-adrenoreceptors – clonidine and yohimbine, respectively – were studied in rats with different levels of impulsivity identified using the "right to choose" the value of a food reinforcement (delay discounting paradigm). Selection of either an immediate but low-value or a delayed but high-value reinforcement was used to divide rats into three groups. Rats selecting the high-value, delayed reinforcement in more than 60% of trials were placed in the low-impulsivity (self-controlled) group, in contrast to animals mainly choosing the low-value immediate reinforcement, which formed the high-impulsivity group. Rats not defined by their choices were placed in the ambivalent group. Systemic administration of the α2-adrenoreceptor agonist clonidine led to a statistically significant increase in the choice of responses with the low-value immediate reinforcement in low-impulsivity rats and an increase in the number of missed reactions in high-impulsivity animals. Shortening of the latent period of moving the feeder curtain was seen in all groups of animals. Administration of the α2-adrenoreceptor blocker yohimbine produced no changes in the previously selected behavioral strategy in any of the groups of animals, but did lead to a decrease in the number of missed reactions in highly impulsive rats. The results suggest that the influences on α2-adrenoreceptors of the pharmacological agents used here depend on the individual-typological characteristics of the rats, particularly high and low levels of impulsivity.



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Changes in the Spatial Synchronization of Oscillations of Cortical Potentials in the α Range after Conditioning Go/No-Go Stimuli

Studies in healthy subjects (n = 35) using a model based on a cognitive set to an angry facial expression showed that use of positive and inhibitory Go/No-Go stimuli during the interstimulus period can produce marked changes in the top-down inhibitory influences of the prefrontal cortex on cortical areas involved in visual recognition, thus influencing set plasticity. The cortical topography of top-down influences in response to No-Go stimuli was determined in terms of local changes in the power of oscillations in potentials in the α range. Changes in spatial synchronization of α oscillations occurred only in the low-frequency range and depended on the level of set plasticity. In rigid forms of the set, coherence connections between the prefrontal cortex and other cortical zones were clearly more marked in the left hemisphere. In rigid forms of cognitive activity, left-hemisphere activation, with greater involvement of the speech and semantic functions, appears to play a compensatory role.



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Effects of a GABA C Receptor Blocker on the Formation of Evoked Potentials in Neuronal Columns in the Rat Somatosensory Cortex

Microelectrode studies of the evoked activity of neuronal columns in the barrel cortex in rats showed that the GABAC receptor blocker 1,2,5,6-tetrahydropyridin-4-ylmethylphosphonic acid (TPMPA) had an activatory effect on the secondary components of evoked potentials (EP) mainly of the upper afferent modules of columns as compared with the lower efferent layers. This is evidence that GABAC receptors are located on the presynaptic terminals of thalamocortical glutamatergic afferents and ascending apical dendrites of pyramidal cells. Blockade of GABAC influences with TPMPA led to dose-dependent depolarization of afferents with development of presynaptic inhibition and suppression of the primary responses (PR) of EP. The different effects of the GABAC receptor blocker on the secondary components of EP in the upper layers of the cortex are due to the development of afterhyperpolarization of neurons after high-amplitude PR and afterdepolarization after low-amplitude responses, with subsequent activation of different voltage-gated channels and the formation of different gradients in the direct current (DC) potential of the cortex.



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Distant recurrences limit the survival of patients with thalamic high-grade gliomas after successful resection

Abstract

The indications of surgery for thalamic high-grade gliomas are not well established. The present study investigated the outcome of 21 patients treated by surgery and reports the high incidence of distant recurrences including disseminations after successful removal. Twenty-one patients with thalamic high-grade gliomas not invading the pyramidal tract or midbrain underwent cytoreductive surgery at our institute from June 1997 to August 2015. Surgery was performed with the aid of a neuronavigation system, electrophysiological monitoring, and fluorescence navigation. Tumor histology included 12 cases of the World Health Organization grade III and nine cases of grade IV. Gross total resection was achieved in six cases, subtotal in 13, and partial in two. Motor weakness accompanied by sensory disturbance deteriorated immediately after surgery in 13 patients. However, five patients were determined to show deterioration at 2 months after surgery. Postoperative radiation and chemotherapy were given to every patient, and median progression-free survival of patients with grade III and IV tumors was 12.1 and 7.0 months, respectively. Median overall survival of patients with grade III and IV tumors was 25.6 and 12.6 months, respectively. High incidence of distant recurrences was found, with distant lesions at recurrence in 13 of 19 patients with recurrence, suggesting the life-restricting factor in these patients. Thalamic high-grade glioma without invasion into the pyramidal tract and brainstem can be considered as a candidate for surgical resection. Distant lesion limits the survival of patients after successful resection.



http://ift.tt/2gWJssy

Novel portable platform for molecular detection of toxigenic Clostridium difficile in faeces: a diagnostic accuracy study

Abstract

Background

A novel portable platform for nucleic acid amplification enables rapid detection of diarrhoea causing toxigenic Clostridium difficile directly from faeces, even in resource-limited settings. We evaluated the accuracy and precision of the new commercial molecular test system.

Methods

One thousand one hundred and sixty faecal samples from patients suspected of having Clostridium difficile infection (CDI) were analysed using the Orion GenRead C. difficile test system (Orion Diagnostica Oy, Espoo, Finland) and comparative methods in three teaching hospital laboratories in Finland and France. The precision of the Orion GenRead C. difficile test system was evaluated in a reproducibility study with a set of blind-coded samples. The test system is based on a new isothermal amplification technology (Strand Invasion Based Amplification, SIBA®) and detection of the tcdB gene of C. difficile. We calculated the sensitivity, specificity, and the overall agreement according to Clinical and Laboratory Standards Institute recommendations.

Findings

The overall agreement of the Orion GenRead C. difficile test when compared to the comparative methods in routine use in the participating laboratories was between 96.7% and 98.8%. In the reproducibility study; the total percent agreement between three laboratories was 99.8%.

Interpretation

The identification of toxigenic C. difficile from faeces with the light-weight portable Orion GenRead test system was highly sensitive and specific, and the results were reproducible in the participating laboratories. This platform could enable fast and accurate molecular pathogen detection even in resource-limited or point-of-care settings.



http://ift.tt/2hGuKad

Remodeling of the gut microbiota and structural shifts in Preeclampsia patients in South China

Abstract

Preeclampsia (PE) is one of the pregnancy metabolic diseases. Since Gut microbiota play important roles in the hosts' metabolism, it is necessary to investigate the gut microbiota in PE patients, so that some intestinal dysbiosis might be detected as a biomarker for PE early diagnosis or as a target for intervention. One hundred subjects were categorized into four groups: 26 PE patients in late pregnancy, healthy individuals in early, middle, and late pregnancy (26/24/24 women). Gut microbiota were analyzed by sequencing the V4 region of the 16S rDNA gene using Illuminal MiSeq. Data were analyzed by multivariate statistics. Bacteroidetes was the dominant bacterium (47.57–52.35%) in the pregnant women in South China. Tenericutes increased while Verrucomicrobia almost disappeared in late pregnancy. In the PE patients, there was an overall increase in pathogenic bacteria, Clostridium perfringens (p = 0.03) and Bulleidia moorei (p = 0.00) but a reduction in probiotic bacteria Coprococcus catus (p = 0.03). Our research suggests that there is a significant structural shift of the gut microbiota in PE patients, which might be associated with the occurrence and development of the disease. However, further studies are required to understand the underlying mechanisms.



http://ift.tt/2hKy7dj

ATM mutations for surgeons

Abstract

The ataxia-telangiectasia mutated (ATM) gene encodes a protein kinase involved in DNA repair. Heterozygotic carriers are at an increased risk of developing breast cancer. As the use of genetic testing increases, identification of at-risk patients will also increase. The aim of this study is to review two cases of heterozygous ATM mutation carriers and review the literature to clarify the cancer risks and suggested management for breast surgeons who will be intimately involved in the care of these patients.



http://ift.tt/2hGoeAe

Outcomes following sclerotherapy for mucosal rectal prolapse with oily phenol injection: single-centre review

Abstract

Aim of the study

To review the outcomes of injection sclerotherapy with oily phenol for mucosal rectal prolapse.

Methods

Retrospective case note review of all children who underwent sclerotherapy with oily phenol injection as primary surgical intervention for mucosal rectal prolapse, from January 2007 to December 2015.

Main results

A total of 31 patients were identified. Mean age at presentation was 4.8 years (range 5 months–12 years). 23 patients with mucosal rectal prolapse underwent injection sclerotherapy with oily phenol as primary procedure. Patients with full-thickness rectal prolapse (n = 6) and 2 with mucosal prolapse who had Thiersch stitch were excluded from the study. The cause for mucosal rectal prolapse was considered to be due to constipation (n = 15), idiopathic (n = 7), spina bifida (n = 1). Follow-up was for minimum 6 months (median = 4 years; range 6 months–17 years). Recurrence following injection sclerotherapy with oily phenol requiring further procedures was 30.4% (7/23).

Conclusions

Injection sclerotherapy with oily phenol is a safe, effective and minimally invasive primary treatment option for mucosal rectal prolapse not responding to conservative management. In case of recurrence, a cautious re-examination under anaesthesia should be undertaken to exclude a missed full-thickness rectal prolapse before reinjecting.



http://ift.tt/2gWKMNu

Advances in understanding functional variations in the Hirschsprung disease spectrum (variant Hirschsprung disease)

Abstract

Hirschsprung disease (HSCR) is a fairly well understood congenital, genetically based functional obstruction due to the congenital absence of ganglion cells in the distal bowel. However, although over 90% of Hirschsprung cases conform to the normally accepted histological diagnostic criteria, it has become increasingly clear that in addition to HSCR, there is a group of functional disturbances relating to a number of other congenital neurodysplastic conditions causing some degree of gastrointestinal tract malfunction. Although these represent a variety of possibly separate conditions of the enteric nervous system, this spectrum it would appear to be also influenced by similar developmental processes. The term "variant Hirschsprung" is commonly used to describe these conditions, but ganglion cells are mostly present if abnormal in number and distribution. These conditions are a problem group being amongst the most difficult to diagnose and treat with possible practical and legal consequences. The problem appears to be possibly one of definition which has proven difficult in the relative paucity of normal values, especially when correlated to age and gestation. It is the purpose of this paper to review the current position on these conditions and to explore possible shared common pathogenetic and genetic mechanisms. This article explores those conditions where a similar pathogenetic mechanisms to HSCR can be demonstrated (e.g. hypoganglionosis) as well as other neural features, which appear to represent separate conditions possibly linked to certain syndromes.



http://ift.tt/2hcHfXs

Cracking and healing in poly(methyl methacrylate): effect of solvent

Abstract

In this work, the solvent-induced structural changes of PMMA (poly(methyl methacrylate)) are studied via desorpon of methanol in 2-ethylhexyl alcohol. The desorption of methanol from PMMA specimens causes the shrinking (mass loss) and cracking of the PMMA specimens. The crack density of the cracks induced by the methanol desorption increases with the increase of the immersion time and temperature and approaches plateau. The absorption-induced crack healing of the cracked PMMA specimens is observed via absorption of methanol, resulting in the increase in tensile strength. The cracked PMMA specimens immersed in methanol at higher temperatures have higher tensile strength than at lower temperatures due to the healing of more cracks. The possibility of introducing functional particles, such as quantum dots, into PMMA through absorption-induced migration of particles has been demonstrated via the absorption-induced embedment of carbon particles in the cracked PMMA.



http://ift.tt/2gVFIrm

Critical appraisal of some factors pertinent to the functional designs of the gas exchangers

Abstract

Respiration acquires O2 from the external fluid milieu and eliminates CO2 back into the same. Gas exchangers evolved under certain immutable physicochemical laws upon which their elemental functional design is hardwired. Adaptive changes have occurred within the constraints set by such laws to satisfy metabolic needs for O2, environmental conditions, respiratory medium utilized, lifestyle pursued and phylogenetic level of development: correlation between structure and function exists. After the inaugural simple cell membrane, as body size and structural complexity increased, respiratory organs formed by evagination or invagination: the gills developed by the former process and the lungs by the latter. Conservation of water on land was the main driver for invagination of the lungs. In gills, respiratory surface area increases by stratified arrangement of the structural components while in lungs it occurs by internal subdivision. The minuscule terminal respiratory units of lungs are stabilized by surfactant. In gas exchangers, respiratory fluid media are transported by convection over long distances, a process that requires energy. However, movement of respiratory gases across tissue barriers occurs by simple passive diffusion. Short distances and large surface areas are needed for diffusion to occur efficiently. Certain properties, e.g., diffusion of gases through the tissue barrier, stabilization of the respiratory units by surfactant and a thin tripartite tissue barrier, have been conserved during the evolution of the gas exchangers. In biology, such rare features are called Bauplans, blueprints or frozen cores. That several of them (Bauplans) exist in gas exchangers almost certainly indicates the importance of respiration to life.



http://ift.tt/2hvmOIf

Systematic review of rheumatic disease phenotypes and outcomes in the Indigenous populations of Canada, the USA, Australia and New Zealand

Abstract

We performed a systematic review designed to characterize clinical phenotypes and outcomes in Indigenous populations with rheumatic disease to enhance the understanding of how rheumatic disease presents in Indigenous populations and allow for better projection of the healthcare needs of the communities affected. A systematic search was performed in medical (Medline, EMBASE, CINAHL), Indigenous and conference abstract databases (to June 2015). Search terms for Indigenous populations were combined with terms for inflammatory arthritis conditions, connective tissue disorders, crystal arthritis and osteoarthritis. Studies were included if they reported on disease features, disease activity measures, or patient-reported outcomes in Canadian, American, Australian or New Zealand Indigenous populations. Data were extracted in duplicate, and a narrative summary was prepared. A total of 5269 titles and abstracts were reviewed, of which 504 underwent full-text review and 85 met inclusion criteria. Nearly all the studies described outcomes in the North American populations (n = 77), with only four studies from Australia and four studies from New Zealand. The majority of studies were in rheumatoid arthritis (n = 31) and systemic lupus erythematosus (n = 19). Indigenous patients with rheumatoid arthritis had higher disease activity and reported more significant impact on patient-reported outcomes and quality of life than non-Indigenous patients. Spondyloarthropathy features were described in North American populations, with most patients having advanced manifestations. In systemic lupus erythematosus, nephritis was more frequent in Indigenous populations. Gout and osteoarthritis were more severe in New Zealand Maori populations. The existing literature supports differences in disease phenotype and severity in Indigenous populations of Canada, America, Australia and New Zealand. We encourage investigators in this area of research to undertake contemporary studies that disentangle differences between phenotype and severity that are biologic in etiology or merely reflecting differences in access to care and that provide a longitudinal assessment of outcomes in more diverse populations.



http://ift.tt/2hKiv9W

Clarity™ digital PCR system: a novel platform for absolute quantification of nucleic acids

Abstract

In recent years, digital polymerase chain reaction (dPCR) has gained recognition in biomedical research as it provides a platform for precise and accurate quantification of nucleic acids without the need for a standard curve. However, this technology has not yet been widely adopted as compared to real-time quantitative PCR due to its more cumbersome workflow arising from the need to sub-divide a PCR sample into a large number of smaller partitions prior to thermal cycling to achieve zero or at least one copy of the target RNA/DNA per partition. A recently launched platform, the Clarity™ system from JN Medsys, simplifies dPCR workflow through the use of a novel chip-in-a-tube technology for sample partitioning. In this study, the performance of Clarity™ was evaluated through quantification of the single-copy human RNase P gene. The system demonstrated high precision and accuracy and also excellent linearity across a range of over 4 orders of magnitude for the absolute quantification of the target gene. Moreover, consistent DNA copy measurements were also attained using a panel of different probe- and dye-based master mixes, demonstrating the system's compatibility with commercial master mixes. The Clarity™ was then compared to the QX100™ droplet dPCR system from Bio-Rad using a set of DNA reference materials, and the copy number concentrations derived from both systems were found to be closely associated. Collectively, the results showed that Clarity™ is a reliable, robust and flexible platform for next-generation genetic analysis.



http://ift.tt/2hv0EG9

Development of a fast method for simultaneous determination of hippuric acid, mandelic acid, and creatinine in urine by capillary zone electrophoresis using polymer multilayer-coated capillary

Abstract

This paper reports the development of a fast separation method employing capillary zone electrophoresis for the simultaneous determination of hippuric acid, mandelic acid, and creatinine in samples of urine using a coated capillary. The background electrolyte was composed of 10 mmol L−1 tris(hydroxymethyl)aminomethane and 30 mmol L−1 2-hydroxy-isobutyric acid at pH 3.6. The internal standard was 3,5-dihydroxybenzoic acid. Separations were performed in a fused silica capillary (32 cm total length, 8.5 cm effective length, and 50 μm internal diameter) coated with crosslinked hydroxypropyltrimethyl ammonium chloride chitosan and κ-carrageenan. Direct UV detection was performed at a wavelength of 200 nm. Samples and standards were injected hydrodynamically (−50 mbar, 3 s) using the short-end injection procedure. The electrophoretic system was operated under constant voltage of 30 kV with positive polarity on the injection side. The separation time for hippuric acid, mandelic acid, and creatinine was less than 70 s. The evaluation of some analytical parameters of the method for the three analytes showed good linearity (R 2 > 0.99), limit of detections of 0.21 to 0.63 mg L−1, inter-day precision better than 3.0% (peak area), and recovery in the range of 98 to 106%. The method developed was applied in the analysis of the three analytes in urine samples.

Graphical Abstract

New method using capillary zone electrophoresis for analysis of creatinine, hippuric acid and mandelic acid in urine


http://ift.tt/2hGvdHb

Comparison of Four Protocols to Generate Chondrocyte-Like Cells from Human Induced Pluripotent Stem Cells (hiPSCs)

Abstract

Stem cells (SCs) are a promising approach to regenerative medicine, with the potential to treat numerous orthopedic disorders, including osteo-degenerative diseases. The development of human-induced pluripotent stem cells (hiPSCs) has increased the potential of SCs for new treatments. However, current methods of differentiating hiPSCs into chondrocyte-like cells are suboptimal and better methods are needed. The aim of the present study was to assess four different chondrogenic differentiation protocols to identify the most efficient method of generating hiPSC-derived chondrocytes. For this study, hiPSCs were obtained from primary human dermal fibroblasts (PHDFs) and differentiated into chondrocyte-like cells using four different protocols: 1) monolayer culture with defined growth factors (GF); 2) embryoid bodies (EBs) in a chondrogenic medium with TGF-β3 cells; 3) EBs in chondrogenic medium conditioned with human chondrocytes (HC-402-05a cell line) and 4) EBs in chondrogenic medium conditioned with human chondrocytes and supplemented with TGF-β3. The cells obtained through these four protocols were evaluated and compared at the mRNA and protein levels. Although chondrogenic differentiation of hiPSCs was successfully achieved with all of these protocols, the two fastest and most cost-effective methods were the monolayer culture with GFs and the medium conditioned with human chondrocytes. Both of these methods are superior to other available techniques. The main advantage of the conditioned medium is that the technique is relatively simple and inexpensive while the directed method (i.e., monolayer culture with GFs) is faster than any protocol described to date because it is does not require additional steps such as EB formation.



http://ift.tt/2hGpssP

Determinants of Change in Physical Activity in Children 0–6 years of Age: A Systematic Review of Quantitative Literature

Abstract

Background

Understanding the determinants of children's health behaviours is important to develop successful behaviour-change interventions.

Objective

We aimed to synthesise the evidence around determinants ('preceding predictors') of change in physical activity (PA) in young children (0–6 years of age).

Methods

As part of a suite of reviews, prospective quantitative studies investigating change in physical activity in children aged 0–6 years were identified from eight databases (to October 2015): MEDLINE, Embase, CINAHL, PsycINFO, Web of Knowledge, British Nursing Index, Applied Social Sciences Index and Abstracts, and Sociological Abstracts. Determinants and direction of association were extracted, described and synthesised according to the socio-ecological model (individual, interpersonal, organisational, community, policy).

Results

Forty-four determinants, predominantly in the interpersonal and organisational domains, were reported across 44 papers (six prospective cohort, 38 interventional); 14 determinants were assessed in four or more papers. Parental monitoring showed a consistent positive association with change in PA; provider training was positively associated with change in children's moderate-to-vigorous PA only. Five (sex, parental goal setting, social support, motor skill training and increased time for PA) showed no clear association. A further seven (child knowledge, parental knowledge, parental motivation, parenting skills, parental self-efficacy, curriculum materials and portable equipment) were consistently not associated with change in children's PA. Maternal role-modelling was positively associated with change in PA in all three studies in which it was examined.

Conclusions

A range of studied determinants of change in young children's PA were identified, but only parental monitoring was found to be consistently positively associated. More evidence dealing with community and policy domains from low-/middle-income countries and about lesser-explored modifiable family- and childcare-related determinants is required.

International Prospective Register for Systematic Reviews (PROSPERO) Registration Number

CRD42012002881.



http://ift.tt/2gWo4oZ

Cognitive Functioning and Heat Strain: Performance Responses and Protective Strategies

Abstract

Despite the predominance of research on physical performance in the heat, many activities require high cognitive functioning for optimal performance (i.e. decision making) and/or health purposes (i.e. injury risk). Prolonged periods of demanding cognitive activity or exercise-induced fatigue will incur altered cognitive functioning. The addition of hot environmental conditions will exacerbate poor cognitive functioning and negatively affect performance outcomes. The present paper attempts to extract consistent themes from the heat–cognition literature to explore cognitive performance as a function of the level of heat stress encountered. More specifically, experimental studies investigating cognitive performance in conditions of hyperthermia, often via the completion of computerised tasks (i.e. cognitive tests), are used to better understand the relationship between endogenous thermal load and cognitive performance. The existence of an inverted U-shaped relationship between hyperthermia development and cognitive performance is suggested, and highlights core temperatures of ~38.5 °C as the potential 'threshold' for hyperthermia-induced negative cognitive performance. From this perspective, interventions to slow or blunt thermal loads and protect both task- and hyperthermia-related changes in task performances (e.g. cooling strategies) could be used to great benefit and potentially preserve cognitive performance during heat strain.



http://ift.tt/2gVbgz7

Comparison of 8-frame and 16-frame thallium-201 gated myocardial perfusion SPECT for determining left ventricular systolic and diastolic parameters

Abstract

The myocardial perfusion single photon emission computed tomography synchronized with the electrocardiogram (gated SPECT) has been widely used for the assessment of left ventricular (LV) systolic and diastolic functions using Quantitative gated SPECT. The aim of this study was to compare the effects of 8-frame and 16-frame thallium-201 (Tl-201) gated SPECT for determining LV systolic and diastolic parameters. The study population included 42 patients with suspected coronary artery disease who underwent gated SPECT by clinical indication. LV systolic and diastolic parameters were assessed on 8-frame and 16-frame gated SPECT. There were good correlations in end-diastolic volume (r = 0.99, p < 0.001), end-systolic volume (ESV) (r = 0.97, p < 0.001) and ejection fraction (EF) (r = 0.95, p < 0.001) between 8-frame and 16-frame gated SPECT. Bland–Altman plot showed a significant negative slope of −0.08 in EDV indicating a larger difference for larger EDV. Eight-frame gated SPECT overestimated ESV by 2.3 ml, and underestimated EF by −4.2% than 16-frame gated SPECT. There were good correlations in peak filling rate (PFR) (r = 0.87, p < 0.001), one third mean filling rate (r = 0.87, p < 0.001) and time to PFR (r = 0.61, p < 0.001) between 8-frame and 16-frame gated SPECT. Eight-frame gated SPECT underestimated PFR by −0.22 than 16-frame gated SPECT. Eight-frame gated SPECT estimated as much MFR/3 and TPFR as 16-frame gated SPECT. According to the data, the study suggested that 8-frame Tl-201 gated SPECT could underestimate systolic and/or diastolic parameter when compared with 16-frame gated SPECT.



http://ift.tt/2i0br8m

Factors affecting the postoperative morbidity and survival of patients with liver cirrhosis following colorectal cancer surgery

Abstract

Purpose

Data are lacking on the appropriate risk stratification of patients undergoing surgery for colorectal cancer (CRC). This study aimed to evaluate the predictive factors for perioperative morbidity and oncological outcomes in CRC patients with liver cirrhosis (LC).

Methods

A retrospective analysis of prospectively collected data was conducted. A total of 161 LC patients who underwent surgery for CRC were identified between January 2001 and December 2010.

Results

The mean patient age was 60 ± 10 years, and the median follow-up period was 54.0 months (range 0.5–170.0). The proportions of patients with Child-Pugh classifications for LC were as follows: A (n = 118; 73.3%), B (n = 39; 24.2%), and C (n = 4; 2.5%). The median model for end-stage liver disease (MELD) score was 8 (range 6–21). The postoperative morbidity rate was 37.3% (60/161). Hyperbilirubinemia (p = 0.002), prothrombin time (PT) prolongation (p = 0.020), and intraoperative transfusion (p = 0.003) were the significant factors for postoperative morbidity in multivariate analysis. The postoperative mortality rate was 3.1% (5/161), and the 5-year cancer-specific and 5-year overall survival rates were 86.1 and 59.9%, respectively. The significant clinical risk factors by multivariate analysis that influenced overall survival were the TNM stage of CRC (p = 0.035), MELD score (>8 points) (p < 0.001), and the coexistence of hepatocellular carcinoma (HCC) (p = 0.012).

Conclusions

Hyperbilirubinemia, PT prolongation, and intraoperative transfusion are significant risk factors for postoperative morbidity in LC patients who undergo surgery for CRC. Additionally, not only advanced TNM stage but also a high MELD score and the coexistence of HCC are associated with poor overall survival in CRC patients with LC.



http://ift.tt/2hSzEl4

Surveillance of Adverse Events After Seasonal Influenza Vaccination in Pregnant Women and Their Infants in the Vaccine Adverse Event Reporting System, July 2010–May 2016

Abstract

Introduction

Routine immunization of pregnant women with seasonal inactivated influenza vaccines (IIVs) is recommended in all trimesters of pregnancy. A review of the Vaccine Adverse Event Reporting System (VAERS) during 1990–2009 did not find any unexpected patterns of pregnancy complications or fetal outcomes after administration of IIV or live attenuated influenza vaccines (LAIVs). During the 2009–2010 pandemic influenza A (H1N1) vaccination campaign, a study noted that the number of VAERS reports from pregnant women who received the H1N1 2009 inactivated monovalent vaccine (n = 288) increased compared with 1990–2009 seasonal IIV pregnancy reports (n = 148).

Objectives

The objective of this study was to assess the safety of seasonal influenza vaccines in pregnant women and their infants whose reports were submitted to VAERS during 2010–2016.

Methods

We searched VAERS for US reports of adverse events (AEs) in pregnant women who received IIV or LAIV from 1 July 2010 through 6 May 2016. Clinicians reviewed reports and available medical records and assigned a primary clinical category for each report. Reports were coded as serious based on the Code of Federal Regulations.

Results

We identified 671 reports after seasonal influenza vaccines administered to pregnant women: 544 after IIV and 127 after LAIV. Serious events occurred among 61 (11.2%) reports following IIV and one (0.8%) report following LAIV. No deaths were reported. Among reports with trimester information (n = 296), IIV was administered during the first trimester in 116 (39.2%). Among IIV reports, the most frequent pregnancy-specific AE was spontaneous abortion in 62 (11.4%) reports, followed by stillbirth in ten (1.8%) and preterm delivery in six (1.1%). The most common non-pregnancy-specific AEs were injection-site reactions (55 [10.1%]). Neonatal or infant outcomes were reported in 22 (4.0%) reports, seven of which had major birth defects of different types and no neonatal deaths.

Conclusion

As in 2009–2010, no new or unexpected patterns in maternal or fetal outcomes were observed during 2010–2016.



http://ift.tt/2gWcc4x

Proactive Regional Pharmacovigilance System Versus National Spontaneous Reporting for Collecting Safety Data on Concerning Off-Label Prescribing Practices: An Example with Baclofen and Alcohol Dependence in France

Abstract

Introduction

Off-label prescribing (OLP) may raise serious safety concerns that traditional spontaneous reporting of adverse drug reactions (ADRs) may not identify in a timely manner. In France, the 'Multidisciplinary Consultation Service for Off-Label Prescribing in Addiction Medicine' (CAMTEA) is a proactive regional system established to identify ADRs associated with the OLP of baclofen for alcohol dependence.

Objective

The aim was to demonstrate, using the French pharmacovigilance database (FPVD), that CAMTEA allowed for the reporting of a substantial amount of ADRs, comparable in nature to those provided via spontaneous reporting.

Method

The 2012–2013 FPVD notifications associated with baclofen OLP were extracted. The ten most frequent types of ADRs among 'serious' and 'non-serious' reports were listed. The frequency of each type of ADR was compared between CAMTEA and spontaneous reporting, and the magnitudes of the differences were assessed using standardized differences.

Results

A total of 428 baclofen reports (1043 ADRs) were identified, among which 221 (51.64%) originated from CAMTEA. The ten most frequent ADRs in 'serious' reports were (1) confusion (17.3%), (2) seizures (11.5%), (3) drowsiness/sedation (11.5%), (4) agitation (10.9%), (5) coma (9.6%), (6) hallucinations (7.7%), (7) falls (7.1%), (8) behavioral disorders (5.8%), (9) withdrawal syndrome (5.1%), and (10) space–time disorientation (5.1%). A standardized difference of <0.2 was identified for six out of the ten most frequent 'serious' ADRs, and eight of the ten 'non-serious' ADRs.

Conclusion

A proactive regional pharmacovigilance system could collect a substantial amount of safety data on a specific OLP practice. The profile of the ADRs collected was similar to that seen in the nationwide spontaneous reporting system.



http://ift.tt/2hZXAiq

Single site robotic-assisted apical lateral suspension (SS R-ALS) for advanced pelvic organ prolapse: first case reported

Abstract

While single-port laparoscopy for gynecological surgery is technically challenging, the Da Vinci Single-Site® robotic surgery platform may help to overcome some of the difficulties of this rapidly evolving technique. The authors of this article present the first case of single-incision, robotic apical lateral suspension (R-ALS) using this device in pelvic organ prolapse (POP) surgery. A 71-year-old female with advanced symptomatic anterior and apical prolapse (POP-Q stage III/III) was operated with a single-site approach using the Da Vinci Single-Site® robotic surgery device. After docking the robot, the complete surgery was performed by robotic approach; only abdominal sub-peritoneal passages of the lateral arms of the mesh were performed extra-corporeally as described in the canonical surgical technique of R-ALS. The procedure was successfully completed in 155 min. No surgical complications occurred during the intervention and the postoperative stay and no conversion to laparotomy or additional trocars were required. To the best of our knowledge, this is the first case of R-ALS using the Da Vinci Single-Site robotic surgery platform to be reported. The procedure is feasible and safe and its main advantages are reduced instrument clashes and less surgical scars for the patient. Restoration of triangulation and the lack of monopolar scissors are still limits which are partially overcome by the degrees of freedom of robotic instruments.



http://ift.tt/2hZZ6RC

Bridges to Better Health and Wellness: An Adapted Health Care Manager Intervention for Hispanics with Serious Mental Illness

Abstract

This study examined the feasibility, acceptability, and initial impact of bridges to better health and wellness (B2BHW), a culturally-adapted health care manager intervention for Hispanics with serious mental illness (SMI). Thirty-four Hispanics with SMI and at risk for cardiovascular disease were enrolled. Mixed-linear models were used to examine changes over 12-months on patient activation, self-efficacy, patient-rated quality of care, receipt of preventive primary care services, and quality of life. The majority of participants completed the intervention (85%) with high satisfaction. Significant improvements were found for patient activation, self-efficacy, patients' ratings of quality of care, and receipt of preventive primary care.



http://ift.tt/2gMjpko

Design and development of a simple instrumentation system for detection of secondary cosmic rays at ground level

Abstract

The paper describes a simple and low cost instrumentation system for ground based cosmic ray air shower experiments. It is designed and fabricated at Gauhati University as part of a larger and more sophisticated instrumentation for a proposed 10 m × 10 m array to carry out a series of studies on cosmic rays. The system is tested on a 4-detector small prototype array with LED coincidence pulses. It is then used to determine the rate of omnidirectional air showers incident on the array. The dependence of 4-fold coincidence rate on array size is also investigated. The results of the tests are presented in the paper.



http://ift.tt/2hFHk9T

Egg hatching response to a range of ultraviolet-B (UV-B) radiation doses for four predatory mites and the herbivorous spider mite Tetranychus urticae

Abstract

Egg hatchability of four predatory mites—Phytoseiulus persimilis Athias-Henriot, Iphiseius [Amblyseius] degenerans Berlese, Amblyseius swirskii Athias-Henriot, and Euseius finlandicus Oudemans (Acari: Phytoseiidae)—and the spider mite Tetranychus urticae Koch (Acari: Tetranychidae) was determined under various UV-B doses either in constant darkness (DD) or with simultaneous irradiation using white light. Under UV-B irradiation and DD or simultaneous irradiation with white light, the predator's eggs hatched in significantly lower percentages than in the control non-exposed eggs, which indicates deleterious effects of UV-B on embryonic development. In addition, higher hatchability percentages were observed under UV-B irradiation and DD in eggs of the predatory mites than in eggs of T. urticae. This might be caused by a higher involvement of an antioxidant system, shield effects by pigments or a mere shorter duration of embryonic development in predatory mites than in T. urticae, thus avoiding accumulative effects of UV-B. Although no eggs of T. urticae hatched under UV-B irradiation and DD, variable hatchability percentages were observed under simultaneous irradiation with white light, which suggests the involvement of a photoreactivation system that reduces UV-B damages. Under the same doses with simultaneous irradiation with white light, eggs of T. urticae displayed higher photoreactivation and were more tolerant to UV-B than eggs of the predatory mites. Among predators variation regarding the tolerance to UV-B effects was observed, with eggs of P. persimilis and I. degenerans being more tolerant to UV-B radiation than eggs of A. swirskii and E. finlandicus.



http://ift.tt/2hFofVa

Facile control of silica nanoparticles using a novel solvent varying method for the fabrication of artificial opal photonic crystals

Abstract

In this work, the Stöber process was applied to produce uniform silica nanoparticles (SNPs) in the meso-scale size range. The novel aspect of this work was to control the produced silica particle size by only varying the volume of the solvent ethanol used, whilst fixing the other reaction conditions. Using this one-step Stöber-based solvent varying (SV) method, seven batches of SNPs with target diameters ranging from 70 to 400 nm were repeatedly reproduced, and the size distribution in terms of the polydispersity index (PDI) was well maintained (within 0.1). An exponential equation was used to fit the relationship between the particle diameter and ethanol volume. This equation allows the prediction of the amount of ethanol required in order to produce particles of any target diameter within this size range. In addition, it was found that the reaction was completed in approximately 2 h for all batches regardless of the volume of ethanol. Structurally coloured artificial opal photonic crystals (PCs) were fabricated from the prepared SNPs by self-assembly under gravity sedimentation.

Figure

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http://ift.tt/2hZChh1

The magnetization reversal in CoFe 2 O 4 /CoFe 2 granular systems

Abstract

The temperature-dependent field cooling (FC) and zero-field cooling (ZFC) magnetizations, i.e., M FC and M ZFC, measured under different magnetic fields from 500 Oe to 20 kOe have been investigated on two exchange–spring CoFe2O4/CoFe2 composites with different relative content of CoFe2. Two samples exhibit different magnetization reversal behaviors. With decreasing temperature, a progressive freezing of the moments in two composites occurs at a field-dependent irreversible temperature T irr. For the sample with less CoFe2, the curves of −d(M FC − M ZFC)/dT versus temperature T exhibit a broad peak at an intermediate temperature T 2 below T irr , and the moments are suggested not to fully freeze till the lowest measuring temperature 10 K. However, for the −d(M FC − M ZFC)/dT curves of the sample with more CoFe2, besides a broad peat at an intermediate temperature T 2, a rapid rise around the low temperature T 1~15 K is observed, below which the moments are suggested to fully freeze. Increase of magnetic field from 2 kOe leads to the shift of T 2 and T irr towards a lower temperature, and the shift of T 2 is attributable to the moment reversal of CoFe2O4.

Graphical abstract

CoFe2O4/CoFe2 composites with different relative content of CoFe2 were prepared by reducing CoFe2O4 in H2 for 4 h (S4H) and 8 h (S8H). The temperature-dependent FC and ZFC magnetizations, i.e., M FC and M ZFC, under different magnetic fields from 500 Oe to 20 kOe have been investigated. Two samples exhibit different magnetization reversal behaviors. With decreasing temperature, a progressive freezing of the moments in two composites occurs at field-dependent irreversible temperature T irr. For the S4H sample, the curves of −d(M FC − M ZFC)/dT versus temperature T exhibit a broad and field-dependent relaxing peak at T 2 below T irr (figure a), and the moments were suggested not to fully freeze till the lowest measuring temperature 10 K. However, for the S8H sample, it exhibits the reentrant spin-glass state around 50 K, as evidenced by a peak in the M FC curve (inset in figure b) and as a result of the cooperative effects of the random anisotropy of CoFe2O4, exchange–spring occurring at the interface of CoFe2O4 and CoFe2 together with the inter-particle dipolar interaction (figure c); in −d(M FC − M ZFC)/dT curves, besides a broad relaxing peat at T 2, a rapid rise around the low-temperature T 1~15 K is observed, below which the moments are suggested to fully freeze. Increase of magnetic field from 2 kOe leads to the shift of T 2 and T irr towards a lower temperature, and the shift of T 2 is attributable to the moment reversal of CoFe2O4.


http://ift.tt/2hZDLI6

The upconversion luminescence and magnetism in Yb 3+ /Ho 3+ co-doped LaF 3 nanocrystals for potential bimodal imaging

Abstract

Biocompatible upconversion nanoparticles with multifunctional properties can serve as potential nanoprobes for multimodal imaging. Herein, we report an upconversion nanocrystal based on lanthanum fluoride which is developed to address the imaging modalities, upconversion luminescence imaging and magnetic resonance imaging (MRI). Lanthanide ions (Yb3+ and Ho3+) doped LaF3 nanocrystals (LaF3 Yb3+/Ho3+) are fabricated through a rapid microwave-assisted synthesis. The hexagonal phase LaF3 nanocrystals exhibit nearly spherical morphology with average diameter of 9.8 nm. The inductively coupled plasma mass spectrometry (ICP-MS) analysis estimated the doping concentration of Yb3+ and Ho3+ as 3.99 and 0.41%, respectively. The nanocrystals show upconversion luminescence when irradiated with near-infrared (NIR) photons of wavelength 980 nm. The emission spectrum consists of bands centred at 542, 645 and 658 nm. The stronger green emission at 542 nm and the weak red emissions at 645 and 658 nm are assigned to 5S2 → 5I8 and 5F5 → 5I8 transitions of Ho3+, respectively. The pump power dependence of luminescence intensity confirmed the two-photon upconversion process. The nanocrystals exhibit paramagnetism due to the presence of lanthanide ion dopant Ho3+ and the magnetization is 19.81 emu/g at room temperature. The nanocrystals exhibit a longitudinal relaxivity (r 1) of 0.12 s−1 mM−1 and transverse relaxivity (r 2) of 28.18 s−1 mM−1, which makes the system suitable for developing T2 MRI contrast agents based on holmium. The LaF3 Yb3+/Ho3+ nanocrystals are surface modified by PEGylation to improve biocompatibility and enhance further functionalisation. The PEGylated nanocrystals are found to be non-toxic up to 50 μg/mL for 48 h of incubation, which is confirmed by the MTT assay as well as morphological studies in HeLa cells. The upconversion luminescence and magnetism together with biocompatibility enables the adaptability of the present system as a nanoprobe for potential bimodal imaging.



http://ift.tt/2hZOfad

Enhanced thermoelectric properties of PEDOT/PSS/Te composite films treated with H 2 SO 4

Abstract

Firstly, tellurium (Te) nanorods with a high Seebeck coefficient have been integrated into a conducting polymer PEDOT/PSS to form PEDOT/PSS/Te composite films. The Seebeck coefficient of the PEDOT/PSS/Te (90 wt.%) composite films is ~191 μV/K, which is about 13 times greater than that of pristine PEDOT/PSS. Then, H2SO4 treatment has been used to further tune the thermoelectric properties of the composite films by adjusting the doping level and increasing the carrier concentration. After the acid treatment, the electrical conductivity of the composite films has increased from 0.22 to 1613 S/cm due to the removal of insulating PSS and the structural rearrangement of PEDOT. An optimized power factor of 42.1 μW/mK2 has been obtained at room temperature for a PEDOT/PSS/Te (80 wt.%) sample, which is about ten times larger than that of the untreated PEDOT/PSS/Te composite film.



http://ift.tt/2gVRT7q

A comparative study on the performance of hybrid solar cells containing ZnSTe QDs in hole transporting layer and photoactive layer

Abstract

In this paper, ZnSTe quantum dots-based hybrid solar cells (HSC) with two different device architectures have been investigated. The improved performance of the poly(3-hexylthiophene) (P3HT) and [6,6]phenyl C71 butyric acid methyl ester (PC71BM)-based bulk heterojunction (BHJ) solar cells by the incorporation of ZnSTe quantum dots (QDs) with an average size of 2.96 nm in PEDOT:PSS layer and active layer that have been demonstrated. Although the efficiency of both types of devices is almost the same, a close comparison reveals different reasons behind their improved performance. The device prepared with QDs in the HTL has shown reduced series resistance, increased shunt resistance, and improved mobility. On the other hand, QDs in the photoactive layer demonstrates increased photo-generation leading to improved efficiency.



http://ift.tt/2hZETeK

Risk of parkinsonism induced by flunarizine or cinnarizine: a population-based study

Abstract

Purpose

This retrospective cohort study used a population-based dataset to test the risk for parkinsonism in patients receiving flunarizine and cinnarizine, compared with matched controls.

Methods

Data were obtained from the National Health Insurance Research Dataset of Taiwan. Patients receiving flunarizine or cinnarizine for more than 1 month between 2000 and 2005 were enrolled. Exclusion criteria included receiving flunarizine, cinnarizine, or antipsychotics for more than 1 month during 1997–1999, a history of neurodegenerative diseases, and an age of less than 30 years. One matched control for each patient was selected. Each participant was followed for diagnosis of parkinsonism within a 3-year observation period. Stroke, diabetes mellitus, total prescription days, and doses of flunarizine or cinnarizine were recorded.

Results

The study and control groups consisted of 9830 subjects. In the study group, 280 patients (2.9 %) were diagnosed with parkinsonism with a median observation period of 1.2 years, and 49 participants (0.5 %) were diagnosed in the control group with a median observation period of 1.9 years. The adjusted hazard ratio for parkinsonism among patients receiving flunarizine and cinnarizine was 5.117 (95 % CI = 3.758–6.967). Age, stroke, and diabetes mellitus were significant risk factors, but female sex and total doses of the study drugs were not.

Conclusions

This study demonstrates that flunarizine and cinnarizine significantly increase the risk for parkinsonism. The treatment benefits of these two agents should be balanced with this adverse effect. Physicians must look carefully for early signs of parkinsonism in patients treated with flunarizine and cinnarizine.



http://ift.tt/2hFzEle

Biosocial Conservation: Integrating Biological and Ethnographic Methods to Study Human–Primate Interactions

Abstract

Biodiversity conservation is one of the grand challenges facing society. Many people interested in biodiversity conservation have a background in wildlife biology. However, the diverse social, cultural, political, and historical factors that influence the lives of people and wildlife can be investigated fully only by incorporating social science methods, ideally within an interdisciplinary framework. Cultural hierarchies of knowledge and the hegemony of the natural sciences create a barrier to interdisciplinary understandings. Here, we review three different projects that confront this difficulty, integrating biological and ethnographic methods to study conservation problems. The first project involved wildlife foraging on crops around a newly established national park in Gabon. Biological methods revealed the extent of crop loss, the species responsible, and an effect of field isolation, while ethnography revealed institutional and social vulnerability to foraging wildlife. The second project concerned great ape tourism in the Central African Republic. Biological methods revealed that gorilla tourism poses risks to gorillas, while ethnography revealed why people seek close proximity to gorillas. The third project focused on humans and other primates living alongside one another in Morocco. Incorporating shepherds in the coproduction of ecological knowledge about primates built trust and altered attitudes to the primates. These three case studies demonstrate how the integration of biological and social methods can help us to understand the sustainability of human–wildlife interactions, and thus promote coexistence. In each case, an integrated biosocial approach incorporating ethnographic data produced results that would not otherwise have come to light. Research that transcends conventional academic boundaries requires the openness and flexibility to move beyond one's comfort zone to understand and acknowledge the legitimacy of "other" kinds of knowledge. It is challenging but crucial if we are to address conservation problems effectively.



http://ift.tt/2hFxVMP

Salivary oxidative stress biomarkers in chronic periodontitis and acute coronary syndrome

Abstract

Objectives

The study aimed at assessing oxidative stress (OS) biomarker levels in the saliva of patients with chronic periodontitis (CP) and acute coronary syndrome (ACS) and establishing their correlation to periodontal parameters and markers for cardiovascular events.

Materials and methods

The present study enrolled 24 patients with ACS and CP (the ACSCP group), 24 patients with ACS only (the ACS group), 24 patients with CP only (the CP group), and 24 healthy controls. Plaque index (PI), gingival index, bleeding on probing, probing pocket depth (PPD), and clinical attachment loss were recorded. Markers for cardiovascular events included serum high sensitivity C-reactive protein (hsCRP) and plasma fibrinogen. 8-Hydroxydeoxyguanosine (8-OHdG), protein carbonyl (PC), malondialdehyde (MDA), and total antioxidant capacity (TAOC) were used as OS biomarkers.

Results

Salivary 8-OHdG, MDA, and PC levels were significantly higher in the ACSCP, ACS, and CP groups than in healthy controls (p < 0.05). There were significant correlations between salivary PC levels and PI or PPD (p < 0.05) as well as between salivary 8-OHdG levels and all periodontal parameters (p < 0.05). TAOC levels in saliva were correlated to both serum hsCRP and plasma fibrinogen (p < 0.05). Salivary MDA levels were correlated to all periodontal parameters and biomarkers for cardiovascular events (p < 0.05).

Conclusions

Salivary OS biomarker levels were higher in diseased groups compared to control. They also correlated to clinical periodontal parameters and markers for cardiovascular events in ACS patients, with or without CP.

Clinical relevance

Salivary OS biomarkers could potentially serve as diagnostic tools for cardiovascular and/or periodontal diseases.



http://ift.tt/2gVGtRf

Predictors of Attrition Before and After Bariatric Surgery



http://ift.tt/2hF1rVk

Description and phylogeny of a new microsporidium from the elm leaf beetle, Xanthogaleruca luteola Muller, 1766 (Coleoptera: Chrysomelidae)

Abstract

This study describes a new genus and species of microsporidia which is a pathogen of the elm leaf beetle, Xanthogaleruca luteola Muller, 1776 (Coleoptera: Chrysomelidae). The beetles were collected from Istanbul in Turkey. All developmental stages are uninucleate and in direct contact with the host cell cytoplasm. Giemsa-stained mature spores are oval in shape and measured 3.40 ± 0.37 μm in length and 1.63 ± 0.20 μm in width. These uninucleate spores have an isofilar polar filament with 11 turns. The spore wall was trilaminar (75 to 115 nm) with a rugose, electron-dense exospore (34 to 45 nm) and a thickened, electron-lucent endospore (65 to 80 nm) overlaying the plasmalemma. Morphological, ultrastructural, and molecular features indicate that the described microsporidium is dissimilar to all known microsporidian taxa and confirm that it has different taxonomic characters than other microsporidia infecting X. luteola and is named here as Rugispora istanbulensis n. gen., n. sp.



http://ift.tt/2hRXnBA

Diet regulates liver autophagy differentially in murine acute Trypanosoma cruzi infection

Abstract

Chagas disease is a tropical parasitic disease caused by the protozoan Trypanosoma cruzi, which affects about ten million people in its endemic regions of Latin America. After the initial acute stage of infection, 60–80% of infected individuals remain asymptomatic for several years to a lifetime; however, the rest develop the debilitating symptomatic stage, which affects the nervous system, digestive system, and heart. The challenges of Chagas disease have become global due to immigration. Despite well-documented dietary changes accompanying immigration, as well as a transition to a western style diet in the Chagas endemic regions, the role of host metabolism in the pathogenesis of Chagas disease remains underexplored. We have previously used a mouse model to show that host diet is a key factor regulating cardiomyopathy in Chagas disease. In this study, we investigated the effect of a high-fat diet on liver morphology and physiology, lipid metabolism, immune signaling, energy homeostasis, and stress responses in the murine model of acute T. cruzi infection. Our results indicate that in T. cruzi-infected mice, diet differentially regulates several liver processes, including autophagy, a stress response mechanism, with corresponding implications for human Chagas disease patients.



http://ift.tt/2gLFWxU