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Τρίτη 18 Απριλίου 2017
Cross-national investigation of the drivers of obesity: Re-assessment of past findings and avenues for the future
Source:Appetite, Volume 114
Author(s): Katrien Cooremans, Maggie Geuens, Mario Pandelaere
In this paper we question whether prior cross-national differences in food attitudes still exist and if so, to what extent. Due to societal evolutions such as sedentarism and globalization, international variations in food attitudes may not be as pronounced as currently believed. A cross-sectional web-based survey was carried out in the United States, the United Kingdom, France and Belgium. A total of 2167 respondents (52% women; mean age = 39.0 years, SD = 11.4) participated. To successfully combat obesity, a joint approach focusing on food choice and physical activity is required; therefore we included behavioral measures by means of choice tasks for these two important drivers. Further, the extent to which respondents subscribe to the unhealthy = tasty intuition, together with health and taste interest were investigated. Socio-demographic information and self-reported heights and weights were also incorporated. Logistic regressions were fitted with weight status as the dependent variable and the attitudinal and behavioral measures as independent variables. Our findings indicate that having a higher interest in healthy eating decreases the chance of being overweight (odds = 0.88) and believing that unhealthy food is tasty significantly increases the chance of being obese by 1.18 times. Overall, we find that food attitudes have largely converged across the countries we investigated.
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Consumer motivations toward buying local rice: The case of northern Iranian consumers
Source:Appetite, Volume 114
Author(s): Hassan Rahnama
This research had two purposes. The first aim was to identify Iranian and Non-Iranian rice consumers based on demographic characteristics and examine difference of these features with buying behaviors. The second purpose of study was to investigate consumer's motivation to buy local rice in Iran. The sample were 1500 people (men and women). The data was collected by using questionnaire based on a face-to-face survey. Chi-square, confirmatory factor analysis, and multiple linear regression were applied to assess collected data by a questionnaire survey. Regarding Iranian local rice buyers, 884 people buy local rice. Chi-square test showed that there is a significant difference between gender, having children, and marital status in buying local rice. Habitual Iranian local rice buyers include: female (51%), people who are more than 45 years old (51%), people with children (63%), people who are living urban (61%), married people (48%) and individuals that their monthly income is between 321.5 and 625 Dollars (53%). Regarding non-Iranian rice buyers, 616 people buy it. Also there is a significant difference between gender, location, marital status, and income in buying local rice. For considering consumers motivation toward buying local rice the econometrical model is used. Model had three aspects including; quality aspects (taste, good appearance), economic aspects (price, convenience, consumer's ethnocentrism), and safety aspects (health, not using pesticides and environment protection) and seven subset. The results of analysis indicated that quality aspects, economic aspects and safety aspects have positive effects on buying Iranian local rice. Also, indicative variables including; taste, good appearance, price, convenience, consumer's ethnocentrism, health, not using pesticides and environment have significant effects on buying it.
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Sleep-Induced Apraxia of Eyelid Opening.
Background: Apraxia of eyelid opening (AEO) primarily has been described as bilateral loss of volitional ability to open the eyes at certain times and often associated with neurodegenerative disease. Rarely, it can occur in isolation and as an idiopathic phenomenon. There are a few reports of unilateral AEO only on awakening from sleep. We report an additional 11 patients with this unusual variation of AEO. Methods: Retrospective, observational case series of patients collected from 3 separate neuro-ophthalmology practices. Results: All 11 patients were Caucasian women with a mean age of 59 years (range 35-80 years). All experienced AEO on awakening from sleep. Eight patients had unilateral AEO, and 3 had bilateral symptoms. The duration of episodes ranged from 3 weeks to several years. Ten of the patients reported manually elevating the eyelid to open it, while 1 patient waited for the eyelid to open spontaneously. After initial manual elevation, all patients reported normal function and position of the eyelids for the remainder of the day. Seven patients had a history of autoimmune disease. Slit-lamp and fundus examinations were negative for ocular pathology to explain the patients' symptoms, and 9 patients had unremarkable brain imaging. Conclusions: AEO occurring only on awakening from sleep is a rare entity. Neuroimaging and extensive laboratory testing are not indicated without associated neurologic or ocular findings. There may be a Caucasian female preponderance and autoimmune link in patients with AEO, but further studies are required. (C) 2017 by North American Neuro-Ophthalmology Society
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Optical Coherence Tomography in Neuroretinitis: Epipapillary Infiltrates and Retinal Folds.
Neuroretinitis is a form of papillitis associated with the delayed onset of an exudative macular star among other inflammatory ocular findings. We describe 4 patients with neuroretinitis who displayed several distinctive and novel findings on spectral-domain optical coherence tomography (OCT) that include "epipapillary infiltrates" and an atypical pattern of inner retinal folds. The recognition of these findings on OCT may help in the early diagnosis of neuroretinitis. (C) 2017 by North American Neuro-Ophthalmology Society
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Scholar : These new articles for The Aging Male are available online
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Creating a Global Acute Care Surgery Fellowship to Meet International Need
Publication date: Available online 17 April 2017
Source:Journal of Surgical Education
Author(s): Amina I. Merchant, Camila B. Walters, Julie Valenzuela, Kelly A. McQueen, Addison K. May
IntroductionExisting Acute Care Surgery (ACS) fellowships are positioned to develop well-trained surgeons with specific skills to facilitate improvements in care delivery in Global ACS. Many resident and fellowship programs offer clinical electives that expose trainees to operative experiences, exposing trainees to the needs in resource-challenged settings. However, most lack a focus on long-term development and research designed to enhance the country's local skills, capability, and capacity. The Global Acute Care Surgery (Global ACS) fellowship produces a surgeon who focuses on capacity building and systems development across the world.MethodsAt Vanderbilt University, the current American Association for the Surgery of Trauma-Acute Care Surgery (AAST-ACS) fellowship was adapted to create an academic Global Acute Care Surgery (Global ACS) fellowship. This fellowship specifically enhances fellowship trainee's skills in needs assessment and performing research to facilitate the development and implementation of trauma and acute care surgery systems in low- and middle income countries. This research will foster context-appropriate data, collected and based in low- and middle-income countries, to guide practice and policy.Results and ConclusionTwo fellows have completed the Global ACS fellowship at Vanderbilt University. The fellowship requirements, clinical skills, project development and overall goals are outlined within the article. Challenges, funding, and mentorship must also be addressed to develop a comprehensive fellowship. A sample two-year timeline is provided to complete the fellowship track and meet the defined goals. A structured global acute care surgery fellowship enables fellows to reduce the surgical burden of disease and contribute to surgical systems development at both local and international levels by creating meaningful research and developing sustainable change in LMIC countries.
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Dose to organ at risk and dose prescription in liver SBRT
Publication date: Available online 17 April 2017
Source:Reports of Practical Oncology & Radiotherapy
Author(s): Rives Michel, Izar Françoise, Parent Laure, Modesto Anouchka, Portier Guillaume, Kirzin Sylvain
Stereotactic body radiation therapy (SBRT) is delivered in a curative intent to many primary and secondary tumors.Concerning liver metastasis, SBRT can be safely delivered using one to five fractions. An excellent local control is obtained with doses from 20 to 60Gy. For primary hepatic tumors, results are also good, but the risk of hepatic toxicity related to liver pre-existent pathology must be taken into account. Radiation induced liver disease (RILD) is not frequent in its classical presentation, but modifications of liver enzymes are often observed. Other toxicities of SBRT on the duodenum, small bowel and biliary tract are also described. With respect to contraindications and dose limitations on surrounding structures, SBRT is well tolerated and takes place among curative treatment of liver tumors, as surgery, radiofrequency and embolization.
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Scholar : These new articles for Addiction Research & Theory are available online
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Improving Pressure Ulcer Reconstruction: Our Protocol and the COP (Cone of Pressure) Flap
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Situational prevention of domestic violence: A review of security-based programs
Source:Aggression and Violent Behavior
Author(s): Tim Prenzler, Lauren Fardell
This paper assesses the effectiveness of security-based programs to reduce repeat domestic violence. A systematic search was conducted of the scientific literature, as well as an electronic newspaper database and the Internet, for published reports of domestic violence prevention programs involving security applications. The study was unable to identify cases with full experimental designs showing clear evidence of positive effects. However, five types of applications were identified with promising evidence of reduced violence – Offender GPS tracking, shelter security, home security, personal duress alarms, and combined home security and duress alarms. Within this framework the study identified six specific programs showing evidence of success. An emerging potential model of good practice – which requires further empirical investigation – involves the deployment of home security and mobile duress alarms within a coordinated program of professional support for clients.
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Editorial Board
Source:Critical Reviews in Oncology/Hematology, Volume 113
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Quantitative cancer risk assessment and local mortality burden for ambient air pollution in an eastern Mediterranean City
Abstract
Health risks posed by ambient air pollutants to the urban Lebanese population have not been well characterized. The aim of this study is to assess cancer risk and mortality burden of non-methane hydrocarbons (NMHCs) and particulates (PM) based on two field-sampling campaigns conducted during summer and winter seasons in Beirut. Seventy NMHCs were analyzed by TD-GC-FID. PM2.5 elemental carbon (EC) components were examined using a Lab OC-EC aerosol Analyzer, and polycyclic aromatic hydrocarbons were analyzed by GC-MS. The US EPA fraction-based approach was used to assess non-cancer hazard and cancer risk for the hydrocarbon mixture, and the UK Committee on Medical Effects of Air Pollutants (COMEAP) guidelines were followed to determine the PM2.5 attributable mortality burden. The average cumulative cancer risk exceeded the US EPA acceptable level (10−6) by 40-fold in the summer and 30-fold in the winter. Benzene was found to be the highest contributor to cancer risk (39–43%), followed by 1,3-butadiene (25–29%), both originating from traffic gasoline evaporation and combustion. The EC attributable average mortality fraction was 7.8–10%, while the average attributable number of deaths (AD) and years of life lost (YLL) were found to be 257–327 and 3086–3923, respectively. Our findings provide a baseline for future air monitoring programs, and for interventions aiming at reducing cancer risk in this population.
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Selective adsorption of Pb (II) over the zinc-based MOFs in aqueous solution-kinetics, isotherms, and the ion exchange mechanism
Abstract
Two series of metal–organic frameworks (MOFs) with similar formula units but different central metal ions (M) or organic linkers (L), M-BDC (BDC = terephthalate, M = Zn, Zr, Cr, or Fe), or Zn-L (L = imidazolate-2-methyl, BDC, BDC-NH2), were prepared and employed as the receptors for adsorption lead ions. It was found that the Zn-BDC exhibited a much higher adsorption capacity than the other M-BDC series with various metal ions which have very closely low capacities at same conditions. Furthermore, the Zn-L (L = imidazolate-2-methyl, BDC, BDC-NH2) still have highly efficient adsorption capacity of lead ions, although the adsorption capacity varies with different ligand, as well as the adsorption rate and the equilibrium pH of the solution. This significant high adsorption over Zn-L, different from other M-BDC series with various metal ions (Zr, Cr, or Fe), can be explained by ion exchange between the central metal ions of Zn-L and lead ion in solution. Based on the analysis of FT-IR, X-ray diffraction pattern, the nitrogen adsorption isotherms, the zeta potentials, and the results, a plausible adsorption mechanism is proposed. When equivalent Zn-L were added to equal volume of aqueous solution with different concentration of lead ion, the content of zinc ion in the solution increases with the increase of the initial concentration of lead ions. The new findings could provide a potential way to fabricate new metal organic frameworks with high and selective capacities of the heavy metal ions.
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Individual and combined inhibition of phenol and thiocyanate on microbial activity of partial nitritation
Abstract
This study evaluated the individual and interactive effect of phenol and thiocyanate (SCN−) on partial nitritation (PN) activity using batch test and response surface methodology. The IC50 of phenol and SCN− on PN sludge were 5.6 and 351 mg L−1, respectively. The PN sludge was insensitive to phenol and SCN− at levels lower than 1.77 and 43.3 mg L−1, respectively. A regression model equation was developed and validated to predict the relative specific respiration rate (RSRR) of PN sludge exposed to different phenol and SCN− concentrations. In the range of independent variables, the most severe inhibition was observed with a valley value (17%) for RSRR, when the phenol and SCN− concentrations were 4.08 and 198 mg L−1, respectively. An isobole plot was used to judge the combined toxicity of phenol and SCN−, and the joint inhibitory effect was variable depending on the composition and concentration of the toxic components. Furthermore, the toxic compounds showed independent effects, which is the most common type of combined toxicity.
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Empirical research on coordination evaluation and sustainable development mechanism of regional logistics and new-type urbanization: a panel data analysis from 2000 to 2015 for Liaoning Province in China
Abstract
As the largest developing country in the world, China has witnessed fast-paced urbanization over the past three decades with rapid economic growth. In fact, urbanization has been not only shown to promote economic growth and improve the livelihood of people but also can increase demands of regional logistics. Therefore, a better understanding of the relationship between urbanization and regional logistics is important for China's future sustainable development. The development of urban residential area and heterogeneous, modern society as well regional logistics are running two abreast. The regional logistics can promote the development of new-type urbanization jointly by promoting industrial concentration and logistics demand, enhancing the residents' quality of life and improving the infrastructure and logistics technology. In this paper, the index system and evaluation model for evaluating the development of regional logistics and the new-type urbanization are constructed. Further, the econometric analysis is utilized such as correlation analysis, co-integration test, and error correction model to explore relationships of the new-type urbanization development and regional logistics development in Liaoning Province. The results showed that there was a long-term stable equilibrium relationship between the new-type urbanization and regional logistics. The findings have important implications for Chinese policymakers that on the path towards a sustainable urbanization and regional reverse, this must be taken into consideration. The paper concludes providing some strategies that might be helpful to the policymakers in formulating development policies for sustainable urbanization.
http://ift.tt/2oRwZuo
Response of marine benthic fauna to thin-layer capping with activated carbon in a large-scale field experiment in the Grenland fjords, Norway
Abstract
A field experiment with thin-layer capping was conducted in the Grenland fjords, Norway, for remediation in situ of mercury and dioxin-contaminated sediments. Experimental fields at 30 and 95 m depth were capped with (i) powdered activated carbon (AC) mixed with clay (AC+cla`y), (ii) clay, and (iii) crushed limestone. Ecological effects on the benthic community and species-feeding guilds were studied 1 and 14 months after capping, and a total of 158 species were included in the analyses. The results show that clay and limestone had only minor effects on the benthic community, while AC+clay caused severe perturbations. AC+clay reduced the abundance, biomass, and number of species by up to 90% at both 30 and 95 m depth, and few indications of recovery were found during the period of this investigation. The negative effects of AC+clay were observed on a wide range of species with different feeding strategies, although the suspension feeding brittle star Amphiura filiformis was particularly affected. Even though activated carbon is effective in reducing sediment-to-water fluxes of dioxins and other organic pollutants, this study shows that capping with powdered AC can lead to substantial disturbances to the benthic community.
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Calcite precipitates in Slovenian bottled waters
Abstract
Storage of bottled waters in varying ambient conditions affects its characteristics. Different storage conditions cause changes in the initial chemical composition of bottled water which lead to the occurrence of precipitates with various morphologies. In order to assess the relationship between water composition, storage conditions and precipitate morphology, a study of four brands of Slovenian bottled water stored in PET bottles was carried out. Chemical analyses of the main ions and measurements of the physical properties of water samples were performed before and after storage of water samples at different ambient conditions. SEM/EDS analysis of precipitates was performed after elapsed storage time. The results show that the presence of Mg2+, SO42−, SiO2, Al, Mn and other impurities such as K+, Na+, Ba and Sr in the water controlled precipitate morphology by inhibiting crystal growth and leading to elongated rhombohedral calcite crystal forms which exhibit furrowed surfaces and calcite rosettes. Different storage conditions, however, affected the number of crystallization nuclei and size of calcite crystals. Hollow calcite spheres composed of cleavage rhombohedrons formed in the water with variable storage conditions by a combination of evaporation and precipitation of water droplets during high temperatures or by the bubble templating method.
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Evaluation of passive sampling of gaseous mercury using different sorbing materials
Abstract
Atmospheric mercury monitoring is essential because of its potential human health and ecological impacts. Current automated monitoring systems include limitations such as high cost, complicated configuration, and electricity requirements. Passive samplers require no electric power and are more appropriate for screening applications and long-term monitoring. Sampling rate is a major factor to evaluate the performance of a passive sampler. In this study, laboratory experiments were carried out using an exposure chamber to search for high efficiency sorbents for gaseous mercury. Four types of sorbents, including sulfur-impregnated carbon (SIC), chlorine-impregnated carbon (CIC), bromine-impregnated carbon (BIC), and gold-coated sand (GCS) were evaluated under a wide range of meteorological parameters, including temperature, relative humidity, and wind speed. The results showed that the four sorbents all have a high sampling rate above 0.01 m3g−1 day−1, and wind speed has a positive correlation with the sampling rate. Under different temperature and relative humidity, the sampling rate of SIC keeps stable. The sampling rate of CIC and BIC shows a negative correlation with temperature, and GCS is influenced by all the three meteorological factors. Furthermore, long-term experiments were carried out to investigate the uptake capacity of GCS and SIC. Uptake curves show that the mass amount of sorbent in a passive sampler can influence uptake capacity. In the passive sampler, 0.9 g SIC or 0.9 g GCS can achieve stable uptake efficiency for at least 110 days with gaseous mercury concentration at or below 2 ng/m3. For mercury concentration at or below 21 ng/m3, 0.9 g SIC can maintain stable uptake efficiency for 70 days, and 0.9 g GCS can maintain stability for 45 days.
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Glibenclamide treatment blocks metabolic dysfunctions and improves vagal activity in monosodium glutamate-obese male rats
Abstract
Background/Aims
Autonomic nervous system imbalance is associated with metabolic diseases, including diabetes. Glibenclamide is an antidiabetic drug that acts by stimulating insulin secretion from pancreatic beta cells and is widely used in the treatment of type 2 diabetes. Since there is scarce data concerning autonomic nervous system activity and diabetes, the aim of this work was to test whether glibenclamide can improve autonomic nervous system activity and muscarinic acetylcholine receptor function in pre-diabetic obese male rats.
Methods
Pre-diabetes was induced by treatment with monosodium L-glutamate in neonatal rats. The monosodium L-glutamate group was treated with glibenclamide (2 mg/kg body weight /day) from weaning to 100 days of age, and the control group was treated with water. Body weight, food intake, Lee index, fasting glucose, insulin levels, homeostasis model assessment of insulin resistance, omeostasis model assessment of β-cell function, and fat tissue accumulation were measured. The vagus and sympathetic nerve electrical activity were recorded. Insulin secretion was measured in isolated islets challenged with glucose, acetylcholine, and the selective muscarinic acetylcholine receptor antagonists by radioimmunoassay technique.
Results
Glibenclamide treatment prevented the onset of obesity and diminished the retroperitoneal (18%) and epididymal (25%) fat pad tissues. In addition, the glibenclamide treatment also reduced the parasympathetic activity by 28% and glycemia by 20% in monosodium L-glutamate-treated rats. The insulinotropic effect and unaltered cholinergic actions in islets from monosodium L-glutamate groups were increased.
Conclusion
Early glibenclamide treatment prevents monosodium L-glutamate-induced obesity onset by balancing autonomic nervous system activity.
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Genetic interaction of DGAT2 and FAAH in the development of human obesity
Abstract
Purpose
DGAT2 is the critical catalyzing enzyme for triglyceride biosynthesis, and excess triglyceride accumulation in fat tissues is a fundamental process for obesity. Mutations in DGAT2 or other genes interacting with DGAT2 associated with adiposity have not been reported in human to date.
Methods
DGAT2 mutation was identified based on our in-home database-exome sequencing 227 young obese subjects (body-mass index (BMI), 35.1–61.7 kg/m2) and 219 lean controls (BMI, 17.5–23.0 kg/m2), further validated in 1190 lean subjects and the pedigree of the proband. The trios of the proband were further subjected to whole-exome sequencing to explore the candidate genes for obesity. The mutations in DGAT2 and FAAH were functionally evaluated in vitro.
Results
We detected two rare variants in DGAT2 with no significant difference between obese and lean individuals. One novel heterozygous nonsense variant c.382C > T (p.R128*) was identified in one obese subject but not in 219 lean subjects and another 1190 lean subjects. Notably, in vitro study showed that R128* mutation severely damaged the TG-biosynthesis ability of DGAT2, and all other R128* carriers in the pedigree were lean. Thus, we further identified a loss-of-function variant c. 944G > T (p.R315I) in FAAH in the proband inheriting from his obese father. Importantly, FAAH overexpression inhibited DGAT2 expression and TG synthesis, while R315I mutant largely eliminated this inhibitory effect.
Summary
We first report loss-of-function mutations in DGAT2 and FAAH in one obese subject, which may interact with each other to affect the adiposity penetrance, providing a model of genetic interaction associated with human obesity.
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Hypercoagulability in patients with Cushing disease detected by thrombin generation assay is associated with increased levels of neutrophil extracellular trap-related factors
Abstract
Patients with Cushing disease (CD) are at increased risk of venous thromboembolism (VTE). It was surmised, but not conclusively shown that the risk is related to plasma hypercoagulability secondary to the glucocorticoids effect. This study is aimed at detecting hypercoagulability in patients with CD. Case-control study of 48 CD patients and controls enrolled at two Italian clinics for whom we assessed the thrombin-forming-potential in the presence of optimal activation of protein C obtained by adding into the assay system its main endothelial activator, thrombomodulin. These experimental conditions mimic more closely than any other test the in vivo situation. We observed enhanced thrombin-generation in CD patients, as shown by the modification of thrombin-generation parameters [i.e., shortened lag-time and time-to-peak, increased thrombin peak and endogenous thrombin potential (ETP)]. Moreover, the ETP ratio (with/without thrombomodulin), recognized as an index of hypercoagulability, was increased in patients as compared to controls. We attempted to explain such hypercoagulability by measuring both procoagulant and anticoagulant factors, and some other non-coagulation parameters (i.e., neutrophil extracellular traps (NET), recently associated with the VTE risk and/or increased hypercoagulability. We showed that the hypercoagulability in patients with CD is associated with increased levels of factor VIII and NET-related variables. We detected plasma hypercoagulability in patients with CD and found experimental explanation for its occurrence. Whether this hypercoagulability can entirely explain the occurrence of VTE in patients with CD should be investigated by ad-hoc clinical trials. However, until these studies will be available the evidence supports the concept that patients with CD are candidates for antithrombotic prophylaxis.
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Interference in ACTH immunoassay negatively impacts the management of subclinical hypercortisolism
Abstract
Purpose
Low plasma corticotropin is considered a useful parameter for the diagnosis of subclinical hypercortisolism in patients with an adrenal incidentaloma. However, immunoassays are vulnerable to interference from endogenous antibodies. In this study, subjects who underwent Hypothalamus-pituitary-adrenal axis evaluation for the assessment of subclinical hypercortisolism were evaluated. The objective of the study was to ascertain whether antibody interference in corticotropin immunoassay affected the diagnostic work-up and clinical decisions.
Methods
The 437 consecutive patients with incidentally discovered adrenal adenomas were included in this single centre study. Patients who had a combination of a nonsuppressed corticotropin concentration (>4.4 pmol/L) and a non-suppressed cortisol concentration after 1 mg overnight dexamethasone suppression test (>50 nmol/L) were selected. Eight eligible subjects without specific features of Cushing's syndrome were identified and recruited for interference studies and follow-up. Nine controls including one patient with unilateral adrenalectomy and one patient with Cushing's disease were recruited as well.
Measurements
Eligible subjects and controls were subjected to hormonal tests and investigations for suspected interference. Interference studies included measurement of corticotropin on a different analytical platform, serial dilutions, polyethylene glycol precipitation and heterophilic antibody analysis. Patients were followed with clinical and laboratory parameters for a median duration of 30 (12–90) months.
Results
Antibody interference was identified in four patients. Rheumatoid factor was responsible for the interference in one patient. Clinical management of the patients was affected by the erroneous results. Interference tests were negative in control subjects.
Conclusions
Erroneous results associated with analytical interference negatively impacted on clinical decision making in this patient group. This should be considered particularly in conditions such as subclinical hypercortisolism which decisions depend on laboratory investigations mainly. Analytical interference could explain the high variability observed both in field measurements from patients who were expected to have lower corticotropin concentrations and in subclinical hypercortisolism prevalence reported by different studies. Many problems can be resolved by ensuring good communication between clinical and laboratory staff.
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Alkyne-linked reduction-activated protecting groups for diverse functionalization on the backbone of oligonucleotides
Publication date: Available online 17 April 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Hisao Saneyoshi, Kazuhiko Kondo, Koichi Iketani, Akira Ono
A versatile conjugatable/bioreduction-responsive protecting group for phosphodiester moieties was designed, synthesized and incorporated into oligonucleotide strands. Subsequently, controlled pore glass-supported oligonucleotides were conjugated to a variety of functional molecules using a copper-catalyzed azide-alkyne cycloaddition reaction. The functionalized protecting groups were deprotected by a nitroreductase/NADH reduction system to give "naked" oligonucleotides. This method allowed the synthesis of oligonucleotide prodrugs bearing the functionalized protecting group at the desired sites and desired residues on oligodeoxyribonucleotide (ODN) backbones.
Graphical abstract
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Design, synthesis, and evaluation of multitarget-directed ligands against Alzheimer’s disease based on the fusion of donepezil and curcumin
Publication date: Available online 18 April 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Jun Yan, Jinhui Hu, Anqiu Liu, Lin He, Xingshu Li, Hui Wei
By fusing donepezil and curcumin, a novel series of compounds were obtained as multitarget-directed ligands against Alzheimer's disease. Among them, compound 11b displayed potent acetylcholinesterase (AChE) inhibition (IC50 = 187 nM) and the highest BuChE/AChE selectivity (66.3). Compound 11b also inhibited 45.3% Aβ1−42 self-aggregation at 20 μM and displayed remarkable antioxidant effects. The metal-chelating property of compound 11b was elucidated by determining the 1:1 stoichiometry for the 11b−Cu(II) complex. The excellent blood−brain barrier permeability of 11b also indicated the potential for the compound to penetrate the central nervous system.
Graphical abstract
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A prospective comparison of intra-arterial chemotherapy combined with intravesical chemotherapy and intravesical chemotherapy alone after transurethral resection with a thulium laser in high-risk non-muscle invasive bladder cancer
Abstract
Objective To compare intra-arterial chemotherapy combined with intravesical chemotherapy with intravesical chemotherapy alone in the treatment of high-risk non-muscle invasive bladder cancer (HRBC) after thulium laser resection of a bladder tumor (TmLRBT).
Materials and methods
From January 2009 to December 2013, 283 patients with HRBC were randomly assigned to the combined group (group A, n = 141) or intravesical chemotherapy–alone group (group B, n = 142) after TmLRBT. Intra-arterial chemotherapy was administered after initial TmLRBT, with 3 courses at 4-week intervals. Each course consisted of cisplatin (50 mg/m2) and epirubicin (30 mg/m2). Intravesical chemotherapy was administered in both groups, including an immediate 50 mg of epirubicin instillation after TmLRBT and weekly maintenance for 8 weeks, followed by monthly maintenance for 1 year.
Results
The recurrence rate was 29.1% (41/141) in group A and 42.9% (61/142) in group B, with a significant difference (p = 0.01). The progression rate was 15.6% (22/141) in group A and 25.3% (36/142) in group B, with a significant difference (p = 0.039). Patients with concomitant carcinoma in situ (CIS) also had a lower recurrence rate and progression rate in group A compared to those in group B (p = 0.006 and p = 0.03, respectively). On univariate and multivariate logistic regression analyses, patients with low-grade histology had a higher reccurrence-free rate. Multivariate COX analysis of tumor-related factors suggested that concomitant CIS was the only significant prognostic factor associated with poorer recurrence-free survival and progression-free survival.
Conclusions
Intra-arterial chemotherapy combined with intravesical chemotherapy could reduce the risk of recurrence and progression compared to intravesical chemotherapy alone in HRBC.
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Long-term deterioration of perceived health and functioning in adults with cerebral palsy
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Joyce L. Benner, Sander R. Hilberink, Thessa Veenis, Henk J. Stam, Wilma M.A. van der Slot, Marij E. Roebroeck
ObjectiveTo describe longitudinal change in perceived health, presence of health issues and functional level in adults with cerebral palsy (CP).DesignProspective cohort study.SettingParticipants who completed baseline assessments in 1996 or 2000 were invited for a long-term follow-up in 2010.ParticipantsForty-nine Dutch adults with CP (age 35-45 years, 55% male, 75% spastic) formerly known in pediatric rehabilitation care.InterventionsNot applicable.Main Outcome MeasuresPostal questionnaires were completed by the adults or their proxies (n=9). Health outcomes included perceived health (adapted from SF-36), presence of health issues such as pain, severe fatigue (dichotomized), and functional level (Barthel Index; walking performance).ResultsOver a 10-year period, the percentage of adults with CP worrying about their health increased (29 to 54%, p=0.008) and those indicating that health problems limit their activities increased (19 to 45%, p=0.002). In the same period the majority continued to report good general health (93 to 86%, p=0.148). Presence of some health issues increased over time, such as pain; severe fatigue was a common health issue at follow-up (32%). Over a 14-year period, mobility and self-care deteriorated (Barthel Index 17.1 (SD 4.8) to 16.3 (SD 5.6), p=0.007). Walking performance, specifically indoors declined (83 to 71%, p=0.010).ConclusionsAdults with CP experienced deterioration in health outcomes in the long-term. Most notably, perceived health and functional level decreased. Pain and severe fatigue were the most common health issues in adult CP. More research is required to explore the mechanisms at work in the process of aging among persons with CP. Systematic follow-up of adults with CP appears necessary to timely detect and intervene on health problems and functional decline.
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Objective versus subjective measures of executive functions; predictors of participation and quality of life in Parkinson’s disease?
Publication date: Available online 17 April 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Thialda T. Vlagsma, Janneke Koerts, Oliver Tucha, Hilde T. Dijkstra, Annelien A. Duits, Teus van Laar, Jacoba M. Spikman
ObjectiveTo determine whether objective (neuropsychological tests) and subjective measures (questionnaires) of executive functions (EF) are associated in patients with Parkinson's disease (PD) and to determine to what extent level of participation and QoL of PD patients can be predicted by these measures of EF.DesignCorrelational research design (case-control and prediction design).SettingAssessment took place at departments of Neuropsychology of three medical centers in The Netherlands.Participants42 PD patients and relatives. 94 healthy controls.InterventionsNot applicable.Main Outcome MeasuresA test battery measuring EF. In addition, patients, their relatives and controls completed the DEX, BAFQ and BDEFS-tm questionnaires measuring complaints about EF. Participation and QoL were measured with the IPA and the PDQ-39, respectively.ResultsPD patients showed impairments in EF on objective tests and reported significantly more complaints in EF than healthy controls. No associations were found between patients' performances on objective and subjective measures of EF. However, both objective and subjective measures predicted patients' level of participation. In addition, subjective measures of EF predicted QoL in PD patients.ConclusionsThese findings show that objective and subjective measures of EF are not interchangeable and that both approaches predict level of participation and QoL of PD patients. However, within this context, gender needs to be taken into account.
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Effects of home-based supportive care on improvements in physical function and depressive symptoms in stroke patients: a meta-analysis
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Hui-Chuan Huang, Yi-Chieh Huang, Mei-Feng Lin, Wen-Hsuan Hou, Meei-Ling Shyu, Hsiao-Yean Chiu, Hsiu-Ju Chang
ObjectiveTo examine the effects of home-based supportive care on improvements in physical function and depressive symptoms in home-dwelling patients after a stroke.Data sourcesSeven electronic databases (e.g., Medline, PubMed, CINAL, EMBASE, the Cochrane Central Register of Controlled Trials, ProQuest, and Google Scholar) and four Chinese database (e.g.,Wanfang med online, Chinese Electronic Periodical Services, China Integrated Knowledge Resources Database, and National Central Library) were fully searched for all relevant articles up to June 25, 2016.Study selectionRandomized controlled trials that examining the effects of home-based supportive care on physical function and depression in home-dwelling patients after a stroke were included. Finally, 16 articles in Chinese (n=4) and English (n=12) met inclusion criteria.Data extractionData related to patient characteristics, study characteristics, intervention details, and outcome were extracted. Two reviewers independently extracted data and assessed methodological quality using the Cochrane Risk of Bias tool.Data synthesisHome-based supportive care had a small size effect on physical function (g = 0.17, 95% confidence interval [CI] 0.09∼0.26) and a moderate size effect on depressive symptoms (g = -0.44, 95% CI -0.83 to -0.05) in home-dwelling patients after a stroke. The moderator analysis revealed that some components of study participants and intervention programs improved the effects on physical function and depressive symptoms; however, no significant moderators were further identified to have superiorly improved physical function and depressive symptoms.ConclusionsRegular performance of home-based supportive care should be considered for inclusion as routine care for managing and improving physical function and depressive symptoms in home-dwelling patients after a stroke. The current findings provide further evidence with which to design appropriate supportive interventions for home-dwelling stroke survivors.
http://ift.tt/2pvVZYZ
Chemical and biological properties of a supramolecular complex of tuftsin and cucurbit[7]uril
Publication date: June 2017
Source:International Immunopharmacology, Volume 47
Author(s): Ekaterina A. Kovalenko, Ekaterina A. Pashkina, Lyubov Y. Kanazhevskaya, Alexey N. Masliy, Vladimir A. Kozlov
Cucurbit[7]uril (CB7) is an uncharged and water-soluble macrocyclic host. CB7 binds to doubly protonated tuftsin, which is the tetrapeptide Thr-Lys-Pro-Arg, with moderate affinity (Ka=2.1×103M−1). In this study, the host–guest complexation was confirmed by fluorescence titration. This affinity would allow for easy release of the peptide under physiological conditions. According to density functional theory calculations, the structural binding motif involves hydrogen bonding. The most energetically stable form had the Arg side chain inside the CB7 cavity. The effects of the tuftsin–CB7 complex on the proliferation and cytokine activity of immune cells were studied. The complex had broader spectrum immunomodulation than free peptides, and caused statistically significant (p<0,05) changes in cytokine production (tumor necrosis factor-α, interleukin-2, interferon-γ, and interleukin-10) by mononuclear cells. By contrast, the free peptide only activated tumor necrosis factor-α production.
http://ift.tt/2okhLuK
Neuroprotective effect of three caffeic acid derivatives via ameliorate oxidative stress and enhance PKA/CREB signaling pathway
Source:Behavioural Brain Research SreeTestContent1, Volume 328
Author(s): Wei Fu, Hongyan Wang, Xiuhua Ren, Hengyi Yu, Yongfang Lei, Qian Chen
This study was conducted to elucidate the neuroprotective effect of caffeic acid phenethyl ester (CAPE), (R)-2-Hydroxy-3-(3,4-dihydroxyphenyl) propionic acid (Danshensu) and Curcumin, three caffeic acid derivatives which are contained in fruits, grains and certain dietary supplements.Our results showed that these compounds significantly attenuated H2O2-induced toxicity in PC12 cells in a dose-dependent manner. Furthermore, these compounds significantly improved the behavioral performance of d-gal-treated mice in both step-down avoidance test and Morris water maze test. Biochemical examination and western blot analysis showed that these compounds could ameliorate oxidative stress and facilitate activation of the protein kinase A (PKA)-cyclic AMP response element-binding protein (CREB) pathway.Its beneficial effects may partly relate to enhancing the activity of endogenous antioxidant enzymes and modulating the PKA/CREB signaling pathway. Furthermore, our results also indicated that the presence of 3, 4-dihydroxyphenyl groups in A ring may enhance their neuroprotective activity.
http://ift.tt/2oprZtj
Time-source of neural plasticity in complex bimanual coordinative tasks: Juggling
Source:Behavioural Brain Research SreeTestContent1, Volume 328
Author(s): Marika Berchicci, Federico Quinzi, Andrea Dainese, Francesco Di Russo
Brain plasticity is especially stimulated by complex bimanual tasks, because, as for juggling, they require simultaneous control of multiple movements, high level of bimanual coordination, balance and sustained swapping attention to multiple objects interacting with both hands. Neuroimaging studies on jugglers showed changes in white and grey matter after juggling training, while the very few electroencephalographic (EEG) studies showed changes in the frequency domain. However, no study has focused on the fine temporal brain activations during a bimanual coordinative task in ecological settings. We aimed at understanding the neural correlates of juggling tasks comparing expert jugglers to non-jugglers. Both groups performed two juggling tasks with increasing difficulty (1-ball fountain and 2-ball shower in non-jugglers, 2- and 3-ball shower in expert jugglers), while the EEG was recorded. This design allowed to compare brain activities related to increasing task difficulty within the same group, and the two groups on the same task. The movement-related cortical potentials (MRCPs) for each task were segmented into epochs lasting 4.5s (−1.5/+3.0s). Results showed enhanced prefrontal recruitment with increasing task difficulty in both groups, even before movement onset. Comparing the groups on the same task, non-jugglers showed enhanced activation of prefrontal regions before and during the task execution, whereas jugglers showed enhanced activity in motor-related regions. The results provide a clear indication of practice-induced brain efficiency during the performance of complex bimanual coordinative skills.
http://ift.tt/2pdDfO8
A Novel TP53 Mutation Associated with TWIST1 and SIP1 Expression in an Aggressive Adrenocortical Carcinoma
Abstract
Adrenocortical carcinomas (ACC) are very rare tumors related to TP53 mutations mostly in childhood onset cases. Epithelial-mesenchymal transition (EMT) transcription factors TWIST1 and Smad interacting protein 1 (SIP1) are related to poorer outcomes in other malignancies, but their role in ACC is unknown. We describe a case of an advanced metastatic ACC (Weiss-score of 9) in a patient at age 76. After primary tumor resection, mitotane therapy was started as palliation to low-volume liver metastasis. After a 2-year period of stable disease, the patient died due to brain metastasis. Somatic gene sequencing revealed a novel TP53 mutation in DNA extracted from paraffin-embedded tissue, a deletion of 8bp in exon 8 (c.811_818del8; GAGGTGCG/−) in homo or hemizygosis causing a subsequent frameshift and premature stop codon at position 302. Immunohistochemistry of P53 and p-Ser-15 P53 showed absent tumoral staining. In addition, immunohistochemical analysis showed an increased expression of the mesenchymal markers vimentin and fibronectin. At last, EMT transcription factors TWIST1 and SIP1 were also overexpressed in tumoral cells. This case report describes an aggressive ACC with not only a novel somatic mutation, but also a novel International Agency for Research on Cancer database 8 base-pair deletion in TP53 exon 8. In addition, the expression of EMT inducers TWIST1 and SIP1 have been reported for the first time in an ACC case. Further investigation is needed to clarify the biologic significance of this new TP53 mutation and its role in the EMT process.
http://ift.tt/2pdOIgy
Pathogenesis of Immune Thrombocytopenia
Source:Autoimmunity Reviews
Author(s): Sylvain Audia, Matthieu Mahévas, Maxime Samson, Bertrand Godeau, Bernard Bonnotte
Immune thrombocytopenia (ITP) is a rare autoimmune disease due to an abnormal T cell response, notably supported by splenic T follicular helper cells, that stimulates the proliferation and differentiation of autoreactive B cells. The antiplatelet autoantibodies they produce facilitate platelet phagocytosis by macrophages, essentially in the spleen. Macrophages contribute to the perpetuation of the auto-immune response as the main antigen-presenting cell during ITP. CD8+ T cells also participate to thrombocytopenia by increasing platelet apoptosis. Besides this peripheral platelet destruction, inappropriate bone marrow production also exacerbates thrombocytopenia, due to an immune response against megakaryocytes. Moreover, the level of circulating thrombopoietin, the main growth factor of megakaryocytes, is low during ITP. In this review, the major mechanisms leading to thrombocytopenia, the role of the different immune cells and the different targets of treatments are described.
http://ift.tt/2pxqQ4u
Longitudinal MRI evaluation of neuroprotective effects of pharmacologically induced hypothermia in experimental ischemic stroke
Source:Magnetic Resonance Imaging, Volume 40
Author(s): Silun Wang, Xiaohuan Gu, Ramesh Paudyal, Ling Wei, Thomas A. Dix, Shan P. Yu, Xiaodong Zhang
Pharmacologically induced hypothermia (PIH) shows promising neuroprotective effects after stroke insult. However, the dynamic evolution of stroke infarct during the hypothermic therapy has not been understood very well. In the present study, MRI was utilized to longitudinally characterize the infarct evolution in a mouse model of ischemic stroke treated by PIH using the neurotensin agonist HPI201. Adult male C57BL/6 mice underwent permanent occlusion of the right middle cerebra artery (MCA). Each animal received a vehicle or HPI201 intraperitoneal injection. The temporal changes of stroke lesion were examined using T2-weighted imaging and diffusion-weighted imaging (DWI) in the acute phase (1−3h) and 24h post stroke. Significantly reduced infarct and edema volumes were observed in PIH treated stroke mice, in agreement with TTC staining findings. Also, the TUNEL staining results indicated apoptotic cells were widely distributed among the ischemic cortex in control group but limited in PIH treated mice. Dramatically reduced growth rate of infarction was seen in PIH treated stroke mice. These results demonstrate HPI201 has strong neuroprotection effects during acute stroke. In particular, MRI with the numerical modelling of temporal infarct evolution could provide a unique means to examine and predict the dynamic response of the PIH treatment on infarct evolution.
http://ift.tt/2nZlhPd
Reply to the letter to the editor on “No modulatory effects by tSMS when delivered during a cognitive task”
Source:Brain Stimulation
Author(s): Marco Kufner, Sabrina Brückner, Thomas Kammer
http://ift.tt/2oRtWCu
Subthalamic nucleus deep brain stimulation for the treatment of secondary dystonia: A case series and review of literature
Source:Brain Stimulation
Author(s): Jason Margolesky, Nathan Schoen, Walter Jermakowicz, Samir Sur, Iahn Cajigas, Carlos Singer, Jonathan Jagid, Corneliu Luca
http://ift.tt/2ojUOYJ
Scholar : These new articles for Acta Agriculturae Scandinavica, Section B — Soil & Plant Science are available online
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The G534E variant in HABP2 is not associated with increased risk of familial nonmedullary thyroid cancer in Brazilian Kindreds
Familial nonmedullary thyroid cancer (FNMTC) encompasses a heterogeneous group of diseases that includes both syndromic and nonsyndromic associated tumours. The syndromic group is characterized by a preponderance of nonthyroidal tumours and is associated with Mendelian cancer syndromes. Nonsyndromic groups, which account for 95% of the cases, are characterized by a significantly increased rate of benign or malignant thyroid tumours of follicular-cell origin in the same family and are not associated with other Mendelian cancer syndromes.
This article is protected by copyright. All rights reserved.
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Age-related changes in corticospinal excitability and intracortical inhibition after upper extremity motor learning: a systematic review and meta-analysis
Publication date: July 2017
Source:Neurobiology of Aging, Volume 55
Author(s): Kelly M.M. Berghuis, John G. Semmler, George M. Opie, Aylin K. Post, Tibor Hortobágyi
It is unclear how old age affects the neuronal mechanisms of motor learning. We reviewed the neuronal mechanisms of how healthy old and young adults acquire motor skills as assessed with transcranial magnetic stimulation. Quantitative meta-analyses of 11 studies, involving ballistic and visuomotor tasks performed by upper extremity muscles in 132 healthy old and 128 young adults, revealed that the motor practice–induced increase in corticospinal excitability (CSE) is task-dependent but not age-dependent, with an increase in CSE in both age groups after visuomotor but not ballistic training. In addition, short-interval intracortical inhibition (SICI) is reduced in old but not young adults, but only after visuomotor practice. In addition, correlation analyses in 123 old and 128 young adults showed that the magnitude of motor skill acquisition did not correlate with increases in CSE or decreases in SICI in either age group. Thus, there are subtle age-related differences in use-dependent plasticity but increases in CSE or decreases in SICI are not related to motor skill acquisition in healthy young or old adults.
http://ift.tt/2nZ1GP0
Age and gender effects of 11C-ITMM binding to metabotropic glutamate receptor type 1 in healthy human participants
Publication date: July 2017
Source:Neurobiology of Aging, Volume 55
Author(s): Muneyuki Sakata, Jun Toyohara, Kenji Ishibashi, Kei Wagatsuma, Kenji Ishii, Ming-Rong Zhang, Kiichi Ishiwata
We examined possible age- and gender-related changes in binding of the selective antagonist N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-4-11C-methoxy-N-methylbenzamide (11C-ITMM) to metabotropic glutamate receptor type 1 in healthy human brains. Dynamic 11C-ITMM positron emission tomography scans (90 min) with serial arterial blood sampling were performed in 15 young and 24 older healthy adult volunteers. The total distribution volume (VT) of several brain regions was estimated with 2-tissue compartment model analysis. The VTs of the cerebellar cortex, parietal cortex, putamen, amygdala, and hippocampus in older adult participants were significantly higher than in young participants. The age-related VT increase was only observed in male participants. Our data suggest that an age-dependent increase in metabotropic glutamate receptor type 1 availability in several brain regions may exist predominantly in males.
http://ift.tt/2pxwi7E
Scholar : These new articles for International Journal of Heritage Studies are available online
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Modulation of Anti-tumor T Cell Responses in Cancer Patients Treated by Concomitant Radiochemotherapy
Conditions: Lung Cancer; Head and Neck Cancer
Intervention: Other: Biological samples
Sponsor: Centre Hospitalier Universitaire de Besancon
Not yet recruiting - verified April 2017
http://ift.tt/2pO60wX
Intervention: Other: Biological samples
Sponsor: Centre Hospitalier Universitaire de Besancon
Not yet recruiting - verified April 2017
http://ift.tt/2pO60wX
Topical Histamine Stimulates Repigmentation of Nonsegmental Vitiligo by a Receptor-Dependent Mechanism
Background: Though vitiligo is a common depigmentary disorder, it still represents a substantial therapeutic challenge. Therapeutic options are limited in part due to its uncertain etiology. Objective: Because recent studies suggest that histamine stimulates melanogenesis in vitro, we determined here whether topical histamine stimulates repigmentation in patients with stable, nonsegmental vitiligo. Methods: A total of 23 otherwise normal volunteers with vitiligo, including 14 males and 9 females aged 6-59 years (mean age 29.2 ± 2.8), were enrolled in this study. 1% histamine in distilled water was applied to the lesions twice daily for 5 weeks, while comparable lesions, treated with distilled water alone, served as the controls. The melanin index was measured on the uninvolved and lesional skin sites before and after 5 weeks of treatments using the melanin/erythema probe connected to a Courage-Khazaka MPA5 (Cologne, Germany). Changes in epidermal permeability barrier were also assessed at the same time point. To determine whether histamine-induced repigmentation is receptor-dependent, both ears of C57BL/6J mice were treated topically with 5% cimetidine, a histamine type 2 receptor (H2r) antagonist, twice daily for 10 days. One hour after each cimetidine application, the right ear was treated topically with 10% histamine, while vehicle alone was applied to the left ear. Changes in melanin index were measured 24 h after the last application of histamine and vehicle as described in the human study. Results: In patients with vitiligo treated with vehicle alone for 5 weeks, the melanin index remained unchanged, while topical histamine treatment increased the melanin index by 38% (p 60% reduction in lesion surface area. Moreover, topical histamine accelerated permeability barrier recovery. No adverse events were observed following histamine applications. In mice, topical histamine significantly increased the melanin index, while topical co-applications of the H2r antagonist (cimetidine) prevented the expected histamine-induced increase in melanin index. Conclusions: These studies indicate that topical histamine or an H2r agonist could be useful for treating nonsegmental vitiligo, but further clinical studies in large populations will be required to validate the efficacy and safety of this approach.
Skin Pharmacol Physiol 2017;30:139-145
http://ift.tt/2puVhve
Skin Pharmacol Physiol 2017;30:139-145
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Scholar : These new articles for African Security Review are available online
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Effects of bone marrow on the microenvironment of the human pancreatic islet: A Protein Profile Approach
Source:Molecular and Cellular Endocrinology
Author(s): Joseph William Kim, Souriya Vang, John Luo, William Newton, Luguang Luo
Stem cells are a new therapeutic modality that may support the viability and function of human organs and tissue. Our previous studies have revealed that human allogeneic bone marrow (BM) sustains pancreatic β cell function and survival. This paper examines whether BM creates a microenvironment that supports human pancreatic islets in vitro by evaluating 107 proteins in culture media from BM, islet, and islet/bone marrow (IB) with mass spectrometry. Proteins were considered up- or down-regulated if p-values < 0.05 and fold change was greater than 2 fold I VS. IB. In addition, proteins identified that were uniquely found in islets co-cultured with bone marrow, but not in islets or bone marrow. A 95% protein probability was used as a threshold. Twenty three proteins were upregulated, and sixteen proteins were downregulated. The function of each protein is listed based on the protein database, which include structural proteins (9 upregulated, 4 downregulated); anti-protease and anti-endopeptidase enzymes (8 upregulated); cation binding proteins (6 up-regulated). Six proteins were uniquely identified in islet co-cultured with bone marrow. Three are anti-proteases or anti-endopeptidases, and 1 is a structural protein. These findings suggest that BM, by changing culture media proteins, may be one of mechanisms to maintain human islet function and survival.
http://ift.tt/2pv2ond
Sco2 deficient mice develop increased adiposity and insulin resistance
Source:Molecular and Cellular Endocrinology
Author(s): Shauna Hill, Sathyaseelan S. Deepa, Kavithalakshmi Sataranatarajan, Pavithra Premkumar, Daniel Pulliam, Yuhong Liu, Vanessa Y. Soto, Kathleen E. Fischer, Holly Van Remmen
Cytochrome c oxidase (COX) is an essential transmembrane protein complex (Complex IV) in the mitochondrial respiratory electron chain. Mutations in genes responsible for the assembly of COX are associated with Leigh syndrome, cardiomyopathy, spinal muscular atrophy and other fatal metabolic disorders in humans. Previous studies have shown that mice lacking the COX assembly protein Surf1 (Surf1−/− mice) paradoxically show a number of beneficial metabolic phenotypes including increased insulin sensitivity, upregulation of mitochondrial biogenesis, induction of stress response pathways and increased lifespan. To determine whether these effects are specific to the Surf1 mutation or a more general effect of reduced COX activity, we asked whether a different mutation causing reduced COX activity would have similar molecular and physiologic changes. Sco2 knock-in/knock-out (KI/KO) mice in which one allele of the Sco2 gene that encodes a copper chaperone required for COX activity is deleted and the second allele is mutated, have previously been shown to be viable despite a 30–60% reduction in COX activity. In contrast to the Surf1−/− mice, we show that Sco2 KI/KO mice have increased fat mass, associated with reduced β-oxidation and increased adipogenesis markers, reduced insulin receptor beta (IR-β levels in adipose tissue, reduced muscle glucose transporter 4 (Glut4) levels and a impaired response to the insulin tolerance test consistent with insulin resistance. COX activity and protein are reduced approximately 50% in adipose tissue from the Sco2 KI/KO mice. Consistent with the increase in adipose tissue mass, the Sco2 KI/KO mice also show increased hepatosteatosis, elevated serum and liver triglyceride and increased serum cholesterol levels compared to wild-type controls. In contrast to the Surf1−/− mice, which show increased mitochondrial number, upregulation of the mitochondrial unfolded protein response (UPRMT) pathway and no significant change in mitochondrial respiration in several tissues, Sco2 KI/KO mice do not upregulate the UPRMT, and tissue oxygen consumption and levels of several proteins involved in mitochondrial function are reduced in adipose tissue compared to wild type mice. Thus, the metabolic effects of the Sco2 and Surf1−/− mutations are opposite, despite comparable changes in COX activity, illuminating the complex impact of mitochondrial dysfunction on physiology and pointing to an important role for complex IV in regulating metabolism.
http://ift.tt/2pxausR
Transcriptional co-activator YAP regulates cAMP signaling in Sertoli cells
Source:Molecular and Cellular Endocrinology
Author(s): Souvik Sen Sharma, Subeer S. Majumdar
FSH mediated cyclic AMP (cAMP) signaling is crucial for function of testicular Sertoli cells (Sc) during puberty. Yes-kinase Associated Protein (YAP), a transcriptional co-activator, regulates cell proliferation and differentiation. However, its role in testicular function is not known. In present study, we have identified YAP as an important regulator of cAMP signaling in Sc, in-vitro. Verteporfin, a YAP-inhibitor, down regulated the expression of cAMP responsive genes necessary for spermatogenesis in Sc. Action of forskolin, which acts via cAMP, was also antagonized by verteporfin, limiting expression of these genes. Assessment of cAMP-responsive-element-binding-protein (CREB) phosphorylation revealed that verteporfin augmented the phosphorylation of CREB at Ser133 residue. This effect of verteporfin on CREB phosphorylation was attenuated by H-89, the PKA inhibitor. This clearly suggested involvement of PKA in verteporfin mediated CREB phosphorylation. We provided evidence for the first time that YAP modulates cAMP signaling in Sc which may be critical for testicular function.
http://ift.tt/2pvfjpo
Scholar : These new articles for Arts & Health are available online
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Rate of contamination of hospital privacy curtains on a burns and plastic surgery ward: a cross-sectional study.
| Related Articles |
Rate of contamination of hospital privacy curtains on a burns and plastic surgery ward: a cross-sectional study.
J Hosp Infect. 2017 Mar 16;:
Authors: Shek K, Patidar R, Kohja Z, Liu S, Gawaziuk JP, Gawthrop M, Kumar A, Logsetty S
Abstract
BACKGROUND: Surfaces in the patient environment may play a role in microbial transmission if they become colonized by bacteria. Patient privacy curtains are one such surface that may pose a high risk for transmission because they are high-contact surfaces, are infrequently cleaned, and healthcare workers are less likely to wash their hands after contacting inanimate objects such as curtains.
AIM: To determine the amount and type of bacterial colonization of patient privacy curtains at a regional burns/plastic surgery unit.
METHODS: Privacy curtain contamination on the burns/plastic surgery ward was determined for two separate occasions six months apart: 23 curtains on August 2015 and 26 curtains on January 2016. Dey-Engley neutralizing agar (DENA) replicate organism detection and counting (RODAC) contact plates were used daily to sample curtains near the edge hem where they are most frequently touched. Microbial contamination was reported as cfu/cm(2) and the presence of meticillin-resistant Staphylococcus aureus (MRSA) was determined. Swabs were also taken of any open wounds and from tracheostomy sites on the ward.
FINDINGS: Curtain contamination in August 2015 was 0.7-4.7 cfu/cm(2) with 22% testing positive for MRSA, whereas contamination on January 2016 was 0.6-13.3 cfu/cm(2) with 31% of curtains testing positive for MRSA.
CONCLUSION: Curtains on the burns/plastic surgery ward become colonized with significant quantities of bacteria. Future studies will need to address the rate of colonization and the clinical impact of this colonization to better inform cleaning protocols.
PMID: 28413115 [PubMed - as supplied by publisher]
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Scholar : These new articles for Applied Measurement in Education are available online
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