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Πέμπτη 24 Αυγούστου 2017
Scholar : Canadian Journal of Remote Sensing, Volume 43, Issue 4, July 4, 2017 is now available online on Taylor & Francis Online
The roles of microRNA-34b-5p in angiogenesis of thyroid carcinoma
Abstract
Purpose
This study aims to determine the expression of miR-34b-5p in thyroid carcinomas and to investigate the role of miR34b-5p in the modulation of proteins involved in angiogenesis of thyroid carcinoma cells.
Methods
The expressions of miR-34b-5p levels in five cell lines and 65 tissue samples from thyroid carcinomas were examined by real-time polymerase chain reaction. An exogenous miR-34b-5p (mimic) transiently overexpress miR-34b-5p in theses thyroid carcinoma cells. The effects of miR-34b-5p overexpression on the proteins involved in angiogenesis and cell cycle regulations (VEGF-A, Bcl-2 and Notch1) were investigated by Western blot, immunofluorescence, enzyme-linked immunosorbent assay followed by cell cycle analysis and apoptosis assays.
Results
miR-34b-5p is markedly downregulated in all thyroid carcinoma cell lines and tissues samples when compared with non-neoplastic immortalised thyroid cell line and non-neoplastic thyroid tissues, respectively. The expression levels of miR-34b were significantly associated with T-stages of thyroid carcinomas (p = 0.042). Downregulation of VEGF-A, Bcl-2 and Notch1 proteins in thyroid carcinoma cells were noted in cells that transiently transfected with miR-34b-5p mimic. In addition, enzyme-linked immunosorbent assay confirmed the decreased expression of VEGF in thyroid carcinoma cells after transfection with miR-34b-5p mimic. Furthermore, miR-34b-5p mimic transfection induces significant accumulation of cells in G0-G1 of the cell cycle by blocking of their entry into the S transitional phase as well as increasing the total apoptosis.
Conclusions
miR-34b-5p functions as a potent regulator of angiogenesis, apoptosis and cell proliferation via modulation of VEGF-A, Bcl-2 and Notch1 proteins. It could be a target for developing treatment strategies of thyroid carcinoma with aggressive clinical behaviour.
http://ift.tt/2xve0ak
Exploitation of agro-climatic environment for selection of 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase producing salt tolerant indigenous plant growth promoting rhizobacteria
Source:Microbiological Research
Author(s): Sankalp Misra, Vijay Kant Dixit, Mohammad Haneef Khan, Shashank Kumar Mishra, Gyanendra Dviwedi, Sumit Yadav, Alok Lehri, Puneet Singh Chauhan
A comprehensive survey for 09 agro-climatic zones of Uttar Pradesh, India was conducted to isolate and characterize salt tolerant 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase possessing plant growth promoting (PGP) rhizobacteria for salt stress amelioration in rice. Here, we have isolated 1125 bacteria having the ability to tolerate 1M NaCl and out of those, 560 were screened for utilizing ACC as sole nitrogen source. 560 isolates were subjected for bacteria coated seed germination assay under 100mM salt (NaCl) stress resulting to 77 isolates which were further evaluated for seed germination assay, PGP and abiotic stress tolerance ability in vitro. This evaluation revealed 15 potent rhizobacteria representing each agro-climatic zone and salt stress mitigation in vitro. In particular, the biomass obtained for bacteria coated rice seedlings were corroborated with the performance of isolates exhibiting maximum average indole acetic acid (IAA) production respective to the agro-climatic zone. Surprisingly based on 16S rRNA, much of the propitious isolates belonged to same specific epithet exhibited variedly in their characteristics. Overall, Bacillus spp. was explored as dominant genera in toto with highest distribution in Western Plain zone followed by Central zone. Therefore, this study provides a counter-intuitive perspective of selection of native microflora for their multifarious PGP and abiotic stress tolerance abilities based on the agro-climatic zones to empower the establishment and development of more suitable inoculants for their application in agriculture under local stress environments.
http://ift.tt/2vihDQ8
Influence of Amaranth dye concentration on the efficiency of hybrid system of photocatalytic fuel cell and Fenton process
Abstract
A novel sustainable hybrid system of photocatalytic fuel cell (PFC) and Fenton process is an alternative wastewater treatment technology for energy-saving and efficient treatment of organic pollutants. The electrons generated from PFC photoanode are used to produce H2O2 in the Fenton reactor and react with the in situ generation of Fe2+ from sacrificial iron for hydroxyl radical formation. In this study, the effect of different initial Amaranth dye concentrations on degradation and electricity generation were investigated. ZnO/Zn photoanode was prepared by anodizing method and characterized by X-ray diffraction (XRD) and scanning electron microscope (SEM). Results revealed that the maximum power density (9.53 mW/m2) and current density (0.0178 mA/m2) were achieved at 10 mg/L of Amaranth. The correlation between dye degradation, voltage output, and kinetic photocatalytic degradation were also investigated and discussed.
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PCDD/F formation during thermal desorption of chlorobenzene contaminated soil
Abstract
Unintentional formation of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) is observed and investigated during the thermal desorption in an airflow of a sandy soil, doped artificially with either 1,2-dichlorobenzene (1,2-DiCBz) or hexachlorobenzene (HCBz) using a lab-scale experimental set-up. At all temperatures investigated (200, 250, 300, 350 and 400 °C), this thermal treatment creates significant amounts of PCDD, PCDF and polychlorinated biphenyls (PCB), starting from 1,2-DiCBz. The highest yield of PCDD/F formed from 1,2-DiCBz occurs at 250 °C, with a total (gas + residual soil) output of 117 and 166 pg/g PCDD and PCDF, respectively. Most output reports to the gas phase and the PCDD/F signature is significantly different for residue and gas phase. Also PCB are formed, at a scale of 224 ng/g (300 °C). Compared with 1,2-DiCBz, HCBz converts into PCDD/F even more actively at 350 and 400 °C: the total PCDD/F output created attains 967 pg/g PCDD and 465 pg/g PCDF at 350 °C. As a precursor, 1,2-DiCBz favours formation of PCDF, while PCDD predominates, when the HCBz contaminated soil is treated.
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Comparison of conventional and bio-treated methods as dust suppressants
Abstract
Dust is an environmental, geotechnical, health, and economical hazard. Fugitive dust emanating along transportation systems such as roads, railways, and airports especially can have significant impacts on health, safety, material loss, cost of maintenance, and interfere with the facilities. Quantitative studies on the effectiveness of the proper dust palliatives and their environmental impact have been studied with a number of biological and chemical methods. The objective of this study was to establish a method for using the microbial Induced calcium carbonate precipitation (MICP) approach to reduce the percent of mass loss against erosive force of wind regarding to the concentration and characteristics of aggregate used, climate, and traffic amounts. The results of this study showed that the required precipitation for dust control of sand by 70% is less than 15 g CaCO3/m2 between sand grains in bio-treated sand. The wind tunnel test results of this study also indicate that the effectiveness of the bio-treatment method for dust control depends on many variables, such as the percent of precipitated calcium carbonate and tensile strength.
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Corrigendum to “Knemometry assessment of short-term growth in children with asthma receiving fluticasone furoate for 2 weeks: a randomized, placebo-controlled, cross-over trial” Clin Ther 2017;39:1191–1199
Source:Clinical Therapeutics
Author(s): Ole D. Wolthers, Sally Stone, Philippe Bareille, Susan Tomkins, Sanjeev Khindri
http://ift.tt/2vrjAZL
Progress and Works in Progress: Update on Flavivirus Vaccine Development
Source:Clinical Therapeutics, Volume 39, Issue 8
Author(s): Matthew H. Collins, Stefan W. Metz
Most areas of the globe are endemic for at least one flavivirus, putting billions at risk for infection. This diverse group of viral pathogens causes a range of manifestations in humans from asymptomatic infection to hemorrhagic fever to encephalitis to birth defects and even death. Many flaviviruses are transmitted by mosquitos and have expanded in geographic distribution in recent years, with dengue virus being the most prevalent, infecting approximately 400 million people each year. The explosive emergence of Zika virus in Latin America in 2014 refocused international attention on this medically important group of viruses. Meanwhile, yellow fever has caused major outbreaks in Africa and South America since 2015 despite a reliable vaccine. There is no vaccine for Zika yet, and the only licensed dengue vaccine performs suboptimally in certain contexts. Further lessons are found when considering the experience with Japanese encephalitis virus, West Nile virus, and tickborne encephalitis virus, all of which now have protective vaccination in human or veterinary populations. Thus, vaccination is a mainstay of public health strategy for combating flavivirus infections; however, numerous challenges exist along the path from development to delivery of a tolerable and effective vaccine. Nevertheless, intensification of investment and effort in this area holds great promise for significantly reducing the global burden of disease attributable to flavivirus infection.
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Prospects and Challenges in the Development of a Norovirus Vaccine
Source:Clinical Therapeutics, Volume 39, Issue 8
Author(s): Nicolas W. Cortes-Penfield, Sasirekha Ramani, Mary K. Estes, Robert L. Atmar
PurposeNorovirus is the leading cause of acute epidemic gastroenteritis among children under the age of 5 years and adults in the United States and in adults worldwide, accounting for an estimated 20% of episodes of acute gastroenteritis across all ages. No effective vaccine is presently available. This article provides an overview of the current state of norovirus vaccine development, emphasizing barriers and challenges in the development of an effective vaccine, correlates of protection used to assess vaccine efficacy, and the results of clinical trials of the major candidate vaccines.MethodsWe performed an unstructured literature review of published articles listed in PubMed in the field of norovirus vaccine development, with an emphasis on studies in humans.FindingsTwo candidate vaccines have reached clinical trials, and a number of other candidates are in the preclinical stages of development. Multivalent vaccination may be effective in inducing broadly neutralizing antibodies protective against challenge with novel and heterologous norovirus strains. Most identified correlates of protection have not been validated in large-scale challenge studies, nor have the degrees to which these correlates covary been assessed.ImplicationsImmune correlates of protection against norovirus infection need to be further developed to facilitate additional studies of the tolerability and efficacy of candidate norovirus vaccines in humans.
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Editorial Board
Source:Clinical Therapeutics, Volume 39, Issue 8
http://ift.tt/2v8RTJZ
Vaccine Hesitancy: Where We Are and Where We Are Going
Source:Clinical Therapeutics, Volume 39, Issue 8
Author(s): Catherine C. McClure, Jessica R. Cataldi, Sean T. O'Leary
PurposeVaccines represent one of the most important aspects of pediatric preventive care. However, parents are increasingly questioning the safety of and need for vaccines, and as a result, vaccination rates have fallen to dangerously low levels in certain communities. The effects of vaccine hesitancy are widespread. Community pediatricians who interact regularly with vaccine-hesitant parents report higher levels of burnout and lower levels of job satisfaction. Not surprisingly, vaccine hesitancy has also had direct influence on vaccination rates, which in turn are linked to increased emergency department use, morbidity, and mortality.MethodsLiterature from 1999 to 2017 regarding vaccines and vaccine hesitancy was reviewed.FindingsFew evidence-based strategies exist to guide providers in their discussions with vaccines-hesitant parents. Recent research has shown a presumptive approach (ie, the provider uses language that presumes the caregiver will vaccinate his or her child) is associated with higher vaccination uptake. Motivational interviewing is a promising technique for more hesitant parents.ImplicationsAt the community level, evidence-based communication strategies to address vaccine hesitancy are needed. The practice of dismissing families from pediatric practices who refuse to vaccinate is common, although widely criticized. Other controversial and rapidly evolving topics include statewide vaccination mandates and school exemption policies. Electronic interventions, such as text-messaging services and social media, have recently emerged as effective methods of communication and may become more important in coming years.
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Real-world Effectiveness of Biologic Disease-modifying Antirheumatic Drugs for the Treatment of Rheumatoid Arthritis After Etanercept Discontinuation in the United Kingdom, France, and Germany
Publication date: August 2017
Source:Clinical Therapeutics, Volume 39, Issue 8
Author(s): Nanxin Li, Keith A. Betts, Andrew J. Messali, Martha Skup, Vishvas Garg
PurposeThe purpose of this study was to assess the real-world effectiveness of patients with rheumatoid arthritis (RA) who discontinued etanercept treatment and subsequently received another tumor necrosis factor α (TNF-α) inhibitor or a non–TNF-α biologic in the United Kingdom, France, and Germany.MethodsMedical record data of patients with RA were collected from a panel of rheumatologists in the United Kingdom, France, and Germany. Patients were required to have a diagnosis of RA, be ≥18 years old, and have initiated use of another TNF-α inhibitor (adalimumab, certolizumab pegol, golimumab, or infliximab) or a non–TNF-α biologic (abatacept or tocilizumab) between January 2014 and May 2015 after discontinuing use of etanercept. Reasons for discontinuing use of etanercept and selecting a second biologic disease-modifying antirheumatic drug (DMARD) were described. Study outcomes included European League Against Rheumatism (EULAR) response and change in Clinical Disease Activity Index (CDAI) score. The study outcomes were compared among treatment groups (ie, TNF-α inhibitors and non–TNF-α biologics) using descriptive and multivariable-adjusted analyses. As a secondary analysis, the study outcomes were also descriptively compared between each of the TNF-α inhibitors. Because adalimumab is one of the most commonly used TNF-α inhibitor to treat RA, a secondary analysis was conducted to compare the outcomes among adalimumab, other TNF-α inhibitors, and non–TNF-α inhibitors.FindingsPatient characteristics before initiating treatment with a second DMARD were similar across treatment groups (all TNF-α inhibitors [n = 296] and non–TNF-α biologics [n = 276]). The most common reasons for discontinuing etanercept treatment were inadequate response, adverse effects, and patient preference. After etanercept, TNF-α inhibitors overall were associated with a significantly lower EULAR good response rate (56.0% vs. 64.4%, P < 0.05) and smaller CDAI score change (−6.3 vs −7.3, P = .06) relative to non–TNF-α biologics. However, the proportion of patients achieving an EULAR good response was numerically higher for adalimumab versus other TNF-α inhibitors (61.1% vs 51.6%, P = 0.11) and comparable versus non–TNF-α biologics (61.1% vs 64.4%, P = 0.52). Adalimumab was also associated with a CDAI score change significantly greater than that of other TNF-α inhibitors (−7.1 vs −5.8, P < 0.05) and comparable to that of non–TNF-α biologics (−7.1 vs −7.3, P = 0.79). The results were consistent in the multivariable-adjusted analysis and secondary analysis.ImplicationsIn this retrospective analysis of patients with RA in the United Kingdom, France, and Germany, after discontinuation of etanercept treatment, TNF-α inhibitors as a class were overall less effective as second biologic DMARDs relative to non–TNF-α biologics; however, adalimumab was more or as effective as other TNF-α inhibitors and non–TNF-α biologics.
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Efficacy and Tolerability of Combination Therapy Versus Monotherapy with Candesartan and/or Amlodipine for Dose Finding in Essential Hypertension: A Phase II Multicenter, Randomized, Double-blind Clinical Trial
Publication date: August 2017
Source:Clinical Therapeutics, Volume 39, Issue 8
Author(s): Il Suk Sohn, Chong-Jin Kim, Taehoon Ahn, Ho-Joong Youn, Hui-Kyung Jeon, Sang Hyun Ihm, Eun Joo Cho, Woo-Baek Chung, Shung Chull Chae, Woo-Shik Kim, Chang-Wook Nam, Seong-Mi Park, Ji-Yong Choi, Young-Kwon Kim, Taek-Jong Hong, Hae-Young Lee, Jang-Hyun Cho, Eun-Seok Shin, Jung-Han Yoon, Tae-Hyun Yang, Myung-Ho Jeong, Jun-Hee Lee, Joong-Il Park
PurposeIntensive blood pressure (BP) lowering is important for the treatment of hypertension; however, it has been a challenge to achieve target BP in many patients. The purpose of this study was to explore the optimal dosage of a fixed-dose combination of candesartan cilexetil (CAN) and amlodipine besylate (AML), by examining the tolerability and efficacy of CAN/AML combination therapy compared with those of monotherapy with either drug in patients with essential hypertension.MethodsThis Phase II multicenter, randomized, double-blind clinical trial enrolled patients aged 19 years or older with essential hypertension, defined as a mean sitting diastolic BP (msDBP) between 95 and 115 mm Hg, and a mean sitting systolic BP (msSBP) of <200 mm Hg after a 2-week placebo run-in period. A total of 635 patients were screened, of whom 439 were randomized to receive treatment; 425 patients were included in the full analysis set (combination therapy, 212; monotherapy, 213). Participants were randomly assigned to receive 1 of 8 treatments: CAN (8 or 16 mg), AML (5 or 10 mg), CAN/AML (8 mg/5 mg, 8 mg/10 mg, 16 mg/5 mg, or 16 mg/10 mg), once daily for 8 weeks.FindingsAfter 8 weeks of treatment, changes in msDBP were significantly greater in the groups receiving CAN/AML combination therapies compared with monotherapies at matched doses, with the exception of CAN 8 mg/AML 10 mg versus AML 10 mg. The response to treatment and the achievement of target BP (both msSBP and msDBP) at week 8 were significantly greater overall in the groups that received combination therapy versus monotherapy. All medications were relatively well tolerated in each group.ImplicationsEight-week administration of CAN/AML (8 mg/5 mg, 16 mg/5 mg, and 16 mg/10 mg) resulted in a significantly greater BP reduction than that with CAN or AML monotherapy, and was determined to be well tolerated. ClinicalTrials.gov identifier: NCT02944734.
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Prophylactic Vaccines, Successes, Errors, and Complications
Source:Clinical Therapeutics, Volume 39, Issue 8
Author(s): Richard Shader
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Vigabatrin Lacks Proarrhythmic Potential: Results from a Thorough QT/QTc Study in Healthy Volunteers
Source:Clinical Therapeutics, Volume 39, Issue 8
Author(s): Dwain Tolbert, Susan Reid, Stuart Harris, Ihor Bekersky
PurposeA thorough QT study was performed to assess the proarrhythmic potential of vigabatrin, an antiepileptic drug approved in the United States for the treatment of infantile spasms and refractory complex partial seizures.MethodsIn this Phase I, randomized, double-blind, placebo- and active-controlled (moxifloxacin), 4-sequence, crossover study conducted at a single center, healthy participants received 1 of 4 randomly assigned treatments: 3.0g vigabatrin solution (therapeutic dose) and 1 moxifloxacin placebo tablet; 6.0g vigabatrin solution (supratherapeutic dose) and 1 moxifloxacin placebo tablet; 400 mg moxifloxacin and vigabatrin placebo solution; moxifloxacin placebo tablet and vigabatrin placebo solution.FindingsMean changes from baseline in placebo-corrected QTcF, QTcB, and QTcI with vigabatrin 3.0 g and 6.0 g indicated no signal for any QTc effect relative to baseline. All 1-sided upper 95% confidence intervals for the differences between each vigabatrin dose and placebo were <10 ms at all time points. QTcF was unaffected by increasing plasma vigabatrin concentrations; no arrhythmias were observed in any treatment group. Low rates of first-degree atrioventricular block, sinus tachycardia, and sinus bradycardia occurred in all treatment groups. Most adverse events were mild.ImplicationsThe findings from this thorough QT study are consistent with existing clinical data and confirm a lack of proarrhythmic potential of vigabatrin.
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Clinical Outcome and Antimicrobial Therapeutic Drug Monitoring for the Treatment of Infections in Acute Burn Patients
Publication date: August 2017
Source:Clinical Therapeutics, Volume 39, Issue 8
Author(s): Anna Silva Machado, Maura S. Oliveira, Cristina Sanches, Carlindo Vieira da Silva Junior, David S. Gomez, Rolf Gemperli, Silvia Regina Cavani Jorge Santos, Anna S. Levin
PurposeIn critical burn patients, the pharmacokinetic parameters (absorption, distribution, metabolism, and excretion) of many classes of drugs, including antibiotics, are altered. The aim of this study was to compare 2 groups of burn patients undergoing treatment for health care–associated infections with and without therapeutic drug monitoring.MethodsA retrospective analysis of a clinical intervention (ie, a before/after study) was conducted with patients with health care–associated pneumonia, burn infection, bloodstream infection, and urinary tract infection in the burn intensive care unit of a tertiary care hospital. The patients were divided into 2 groups: (1) those admitted from May 2005 to October 2008 who received conventional antimicrobial dose regimens; and (2) those admitted from November 2008 to June 2011 who received antibiotics (imipenem, meropenem, piperacillin, and vancomycin) with doses adjusted according to plasma monitoring and pharmacokinetic modeling. General characteristics of the groups were analyzed, as were clinical outcomes and 14-day and in-hospital mortality.FindingsSixty-three patients formed the conventional treatment group, and 77 comprised the monitored treatment group. The groups were homogeneous, median age was 31 years (range: 1–90) and 66% were male. Improvement occurred in 60% of the patients under monitored treatment (vs 52% with conventional treatment); 14-day mortality was 16% vs 14%; and the in-hospital mortality was similar between groups (39% vs 36%). In the final multivariate models, variables significantly associated with in-hospital mortality were total burn surface area ≥30%, older age, and male sex. Treatment group did not affect the prognosis.ImplicationsTherapeutic drug monitoring of antimicrobial treatment did not alter the prognosis of these burn patients. More trials are needed to support the use of therapeutic drug monitoring to optimize treatment in burn patients.
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Patient and Provider Factors Affecting Clinical Inertia in Patients With Type 2 Diabetes on Metformin Monotherapy
Publication date: August 2017
Source:Clinical Therapeutics, Volume 39, Issue 8
Author(s): Rohan Mahabaleshwarkar, Frank Gohs, Holly Mulder, Nick Wilkins, Andrea DeSantis, William E. Anderson, Flavia Ejzykowicz, Swapnil Rajpathak, H. James Norton
PurposeOur aim was to determine the extent of clinical inertia and the associated patient and provider factors in patients with type 2 diabetes on metformin monotherapy (MM) at a large integrated health care system in the United States.MethodsThe study cohort included patients with type 2 diabetes aged 18 to 85 years, on MM between January 2009 and September 2013, who experienced MM failure (had an uncontrolled glycosylated hemoglobin [HbA1c] reading (≥8.0% [64 mmol/mol]) after at least 90 days of MM). Clinical inertia was defined as absence of treatment intensification with an add-on therapy within 180 days after the MM failure (index date). The impact of patient and provider factors on clinical inertia was determined using generalized estimating equations.FindingsThe study cohort consisted of 996 patients; 58% were men and 59% were white, with a mean age of 53 (11.8) years. Of these, 49.8% experienced clinical inertia. Lower HbA1c at index date, absence of liver diseases, absence of renal diseases, and greater provider age were associated with clinical inertia. The clinical inertia rate in a secondary analysis considering HbA1c <7.0% (53 mmol/mol) as glycemic control was 67.9%. Greater patient age, lower HbA1c at index date, greater provider age, and being a primary care physician were associated with clinical inertia.ImplicationsConsiderable clinical inertia rates were observed in our real-world patient population, suggesting the need of interventions to reduce clinical inertia in clinical practice. Information about patient and provider factors affecting clinical inertia provided by this study could help healthcare policymakers plan and implement such interventions.
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Vaccines
Source:Clinical Therapeutics, Volume 39, Issue 8
Author(s): Ravi Jhaveri
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Efficacy and Safety of Delayed-release Dimethyl Fumarate for Relapsing-remitting Multiple Sclerosis in Prior Interferon Users: An Integrated Analysis of DEFINE and CONFIRM
Publication date: August 2017
Source:Clinical Therapeutics, Volume 39, Issue 8
Author(s): Óscar Fernández, Gavin Giovannoni, Robert J. Fox, Ralf Gold, J. Theodore Phillips, James Potts, Macaulay Okwuokenye, Jing L. Marantz
PurposeIn Phase III studies (DEFINE [Determination of the Efficacy and Safety of Oral Fumarate in Relapsing-Remitting MS]/CONFIRM [Comparator and an Oral Fumarate in Relapsing-Remitting Multiple Sclerosis]), delayed-release dimethyl fumarate (DMF) demonstrated significant efficacy and a favorable benefit-risk profile in patients with relapsing-remitting multiple sclerosis (RRMS). Post hoc analyses of integrated data from DEFINE/CONFIRM were conducted to evaluate the effect of DMF in patients previously treated with interferon (IFN) beta.MethodsPatients (age 18–55 years; Expanded Disability Status Scale score, 0–5.0) were randomized to receive DMF 240 mg BID or TID, placebo, or glatiramer acetate (CONFIRM only) for up to 2 years. Previous IFN users received at least 1 IFN treatment >3 months before randomization. Data for DMF 240 mg BID (approved dosing regimen) are reported.FindingsIn the integrated intention-to-treat population, 172 and 169 patients receiving DMF or placebo, respectively, had received ≥1 prior IFN. In this subgroup, significant reductions with DMF versus placebo were observed for the annualized relapse rate (rate ratio, 0.55 [95% CI, 0.40–0.77]), new/newly enlarging T2-hyperintense lesions (lesion mean ratio, 0.16 [95% CI, 0.09–0.29]), odds of having more gadolinium-enhancing lesions (odds ratio, 0.17 [95% CI, 0.07–0.44]), and new T1-hypointense lesions (lesion mean ratio, 0.25 [95% CI, 0.14–0.45]). Median Expanded Disability Status Scale scores remained stable during the study period. Adverse events associated with DMF included flushing and gastrointestinal events.ImplicationsIn this post hoc analysis in patients with previous IFN treatment, DMF demonstrated significant efficacy over 2 years versus placebo and an adverse event profile consistent with the overall population of DEFINE/CONFIRM. ClinicalTrials.gov identifiers: DEFINE, NCT00420212; and CONFIRM, NCT00451451.
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The association between Staphylococcus aureus nasal colonization and symptomatic infection in children in Korea where ST72 is the major genotype: A prospective observational study.
The association between Staphylococcus aureus nasal colonization and symptomatic infection in children in Korea where ST72 is the major genotype: A prospective observational study.
Medicine (Baltimore). 2017 Aug;96(34):e7838
Authors: Kang S, Lee J, Kim M
Abstract
This study was performed to investigate the concordance in terms of molecular characteristics and antimicrobial susceptibility between colonizing and clinical Staphylococcus aureus isolates obtained from children in Korea, where ST72 is the major genotype.This was a prospective observational descriptive study of culture-confirmed S aureus infections obtained from children ≤18 years old admitted to Asan Medical Center Children's Hospital in Seoul, Korea, from March 2014 to April 2015. Molecular studies including multilocus sequence typing (MLST), SCCmec typing, polymerase chain reaction amplification of the Panton-Valentine leukocidin (PVL) genes, and antibiotic susceptibility tests were performed on S aureus isolates obtained from nares and clinical specimens.During the study period, 126 clinically significant S aureus infections were identified. Nasal swab cultures were made from 113 of the 126 children, and 46.0% (52/113) showed S aureus colonization. The overall concordance between colonizing and clinical isolates by methicillin susceptibility was 94.2% (49/52); all 3 discordant cases were HA-MSSA cases with nasal MRSA. Among the 37 pairs of colonizing and clinical S aureus isolates included in the genotyping analysis, ST72-SCCmec type IV was the most prevalent clone and the PVL genes were positive in 2 patients. Among the 31 pairs of healthcare-associated cases, concordance rates by methicillin susceptibility and sequence type (ST) were 90.3% (28/31) and 84% (26/31), respectively. For the 6 pairs of community-associated (CA) S aureus including 3 CA-MRSA cases, 100% concordance was observed by methicillin susceptibility and ST.The concordance between isolates obtained from children who required medical services was relatively high in Korean children where ST72-SCCmec type IV is the predominant clone as the colonizer and the pathogen. It is suggested that decolonization and continuous care to prevent transmission could be effective in managing and preventing both HA- and CA-SA infections in our setting.
PMID: 28834892 [PubMed - in process]
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Systematic Literature Review and Meta-analysis of Tumor Necrosis Factor–Alpha Experienced Rheumatoid Arthritis
Publication date: August 2017
Source:Clinical Therapeutics, Volume 39, Issue 8
Author(s): Alvin F. Wells, Jeffrey R. Curtis, Keith A. Betts, Kevin Douglas, Ella Xiaoyan Du, Arijit Ganguli
PurposeThe goal of this study was to compile all available evidence regarding the efficacy of tumor necrosis factor–α (TNF) inhibitors, non-TNF biologics, and tofacitinib for TNF-experienced patients who have rheumatoid arthritis (RA).MethodsA systematic literature review of MEDLINE, EMBASE, and rheumatology conference abstracts was performed to identify observational studies and randomized controlled trials (RCTs) reporting American College of Rheumatology response rates (ACR 20/50/70) for adult patients with RA who switched from at least 1 TNF to another TNF or a non-TNF therapy. A direct random effects meta-analysis was performed to evaluate ACR 20/50/70 response rates for TNF and non-TNF therapies. Separate analyses were conducted among 3-, 6-, and 12-month observational studies and for 6-month RCTs.FindingsA total of 18 observational studies and 6 RCTs were selected. Among 3-month observational studies, the percentages of ACR20/50/70 responders switching to another TNF were similar to those switching to a non-TNF biologic (ACR20, 54.5% vs 58.6%; ACR50, 33.3% vs 33.3%; and ACR70, 13.0% vs 14.6%, respectively). Among 6-month observational studies, the percentages of TNF ACR20/50/70 responders were higher than those of non-TNF responders (ACR20, 67.7% vs 50.4%; ACR50, 50.4% vs 26.6%; and ACR70, 24.9% vs 11.6%). Among 6-month RCTs, the percentages of non-TNF biologic ACR20/50/70 responders were similar to those in the 6-month non-TNF observational studies (ACR20, 50.7% vs 50.4%; ACR50, 27.5% vs 26.6%; and ACR70, 11.9% vs 11.6%). For 12-month observational studies, TNF biologic ACR20/50/70 percentages were higher than those of non-TNF therapies (ACR20, 72.2% vs 57.0%; ACR50, 42.1% vs 28.9%; and ACR70, 22.9% vs 10.0%).ImplicationsFor TNF-experienced patients with RA, subsequent TNF therapy and non-TNF biologic therapy have comparable efficacy.
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Methicillin-resistant Staphylococcus aureus in cystic fibrosis patients: do we need to care? A cohort study.
Methicillin-resistant Staphylococcus aureus in cystic fibrosis patients: do we need to care? A cohort study.
Sao Paulo Med J. 2017 Aug 21;:0
Authors: Cohen RWF, Folescu TW, Daltro P, Boechat MCB, Lima DF, Marques EA, Leão RS
Abstract
CONTEXT AND OBJECTIVE:: The prevalence of a variety of potentially pathogenic microorganisms in cystic fibrosis patients, such as methicillin-resistant Staphylococcus aureus (MRSA), has increased over the past decade. Given the increasing prevalence of MRSA and the few data available in the literature, better understanding of the clinical repercussions of colonization by this bacterium in cystic fibrosis patients becomes essential. This study aimed to evaluate the repercussions of chronic colonization by MRSA in cystic fibrosis patients.
DESIGN AND SETTING:: Retrospective cohort study from January 2004 to December 2013 in a cystic fibrosis reference center.
METHODS:: Each patient with cystic fibrosis was evaluated for nutritional status (body mass index, BMI, and BMI percentile), pulmonary function and tomographic abnormalities (modified Bhalla scores) at the time of chronic colonization by MRSA or methicillin-susceptible Staphylococcus aureus (MSSA) and throughout the study period.
RESULTS:: Twenty pairs of patients were included. There were no significant differences between the groups regarding nutritional characteristics. Spirometric data showed a trend towards greater obstruction of the airways in patients with MRSA. Patients with MRSA presented greater structural damage to their lungs, demonstrated not only by the total Bhalla score but also by its parameters individually.
CONCLUSIONS:: Patients colonized by MRSA presented greater functional and structural respiratory impairment at the time of chronic colonization. Disease progression was also faster in patients chronically colonized by MRSA than in those with MSSA. This was shown through comparisons that avoided possible confounding variables.
PMID: 28832807 [PubMed - as supplied by publisher]
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Prevalence of methicillin-resistant Staphylococcus aureus carriage on admission among patients attending regional hospitals in Dar es Salaam, Tanzania.
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Prevalence of methicillin-resistant Staphylococcus aureus carriage on admission among patients attending regional hospitals in Dar es Salaam, Tanzania.
BMC Res Notes. 2017 Aug 22;10(1):417
Authors: Joachim A, Moyo SJ, Nkinda L, Majigo M, Mbaga E, Mbembati N, Aboud S, Lyamuya EF
Abstract
BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen responsible for hospital and community acquired infection. Colonization with MRSA is associated with a high risk of developing infection. This study aimed to determine the rate of MRSA carriage on admission and the associated risk factors among patients attending regional hospitals, in Dar es Salaam, Tanzania.
RESULTS: A total of 258 patients were included in this study. Nasal swabs were collected on admission to the hospital and after 48 h of hospital stay for detection of MRSA. Of 258 patients enrolled, 89 (34.5%) were colonized with S. aureus and out them 22 (24.7%) were carriers of MRSA, giving an overall MRSA nasal carriage rate of 8.5% (22/258). One patient acquired MRSA while admitted in the hospital. Most of the S. aureus isolates 85 (95.5%) were resistant to penicillin. Resistance to gentamycin, ciprofloxacin, kanamycin, linezolid and mupirocin were 14.6, 11.2, 11.2, 3.4 and 1.1%, respectively. The prevalence of inducible clindamycin resistance, constitutive clindamycin resistance, MS phenotype (resistance to erythromycin alone), and multidrug resistance was 21.3, 3.4, 12.4, and 16.9%, respectively. We observed a statistically significant association between MRSA and multiple drugs resistance among S. aureus isolates (p = 0.001). Of the risk factors investigated none were statistically significant associated with MRSA.
CONCLUSION: There is a high prevalence of MRSA among patients on admission at the two municipal hospitals in Dar es Salaam. The high prevalence of MRSA and the increased rates of resistance to commonly used antimicrobials among MRSA isolates call for attention to the importance of including the screening of MRSA in our hospitals setting in order to prevent further spread of MRSA strains to other patients and to the communities. Control and prevention strategies should be emphasized including decolonization.
PMID: 28830510 [PubMed - in process]
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Peripheral physiological responses to subliminally presented negative affective stimuli: A systematic review
Source:Biological Psychology
Author(s): Melanie M. van der Ploeg, Jos F. Brosschot, Anke Versluis, Bart Verkuil
Negative affective information may be presented outside of awareness and change physiological activity. By increasing peripheral physiological activity, subliminally presented negative affective information may contribute to the development of disease. The current systematic review evaluated 65 studies in which negative affective stimuli were presented subliminally to a healthy sample while cardiovascular, electrodermal, electromyographical, hormonal, or immunological activity was measured. Overall, 41% of the tested contrasts indicated significant increases due to negative affective stimuli compared to control stimuli. These effects were most pronounced in fear-conditioning studies measuring skin conductance response amplitude and priming studies measuring systolic blood pressure. However, across the included studies the methodology varied substantially and the number of contrasts per physiological parameter was limited. Thus, although some evidence exists that subliminally presented negative affective stimuli can induce adverse peripheral physiological changes, this has not yet been addressed sufficiently.
http://ift.tt/2w0bU43
Are there mode-specific and fatigue-related electromechanical delay responses for maximal isokinetic and isometric muscle actions?
Publication date: December 2017
Source:Journal of Electromyography and Kinesiology, Volume 37
Author(s): Cory M. Smith, Terry J. Housh, Ethan C. Hill, Joshua L. Keller, Glen O. Johnson, Richard J. Schmidt
This study used a combined electromyographic, mechanomyographic, and force approach to identify electromechanical delay (EMD) from the onsets of the electromyographic to force signals (EMDE-F), onsets of the electromyographic to mechanomyogrpahic signals (EMDE-M), and onsets of mechanomyographic to force signals (EMDM−F). The purposes of the current study were to examine: (1) differences in EMDE-M, EMDM−F, and EMDE-F from the vastus lateralis between maximal isokinetic and maximal concentric isometric leg extensions; and (2) the effects of fatigue and recovery on EMDE-M, EMDM−F, and EMDE-F. These EMD measures were obtained from twelve men during maximal concentric isokinetic and isometric leg extensions pretest, posttest, and after 3-min and 5-min of recovery from 25 maximal isokinetic leg extensions at 60°s−1. The results indicated no differences between maximal isokinetic and isometric muscle actions for EMDE-M, EMDM-F, or EMDE-F during the pretest, posttest, 3-min recovery, and 5-min recovery measurements. These findings support the comparison of voluntary EMD measures between studies with different modes of exercise as long as the methodology for the determination of EMD are consistent. There were, however, fatigue-induced pretest to posttest increases in EMDE-M, EMDM-F, and EMDE-F which remained elongated after 3-min of recovery, but returned to pretest values after 5-min of recovery.
http://ift.tt/2itkfsw
Standards for Reporting EMG Data
Source:Journal of Electromyography and Kinesiology, Volume 36
http://ift.tt/2g7mcKe
Muscle synergies underlying sit-to-stand tasks in elderly people and their relationship with kinetic characteristics
Source:Journal of Electromyography and Kinesiology
Author(s): Hiroki Hanawa, Keisuke Kubota, Takanori Kokubun, Tatsuya Marumo, Fumihiko Hoshi, Akira Kobayashi, Naohiko Kanemura
BackgroundPhysiological evidence suggests that the nervous system controls motion by using a low-dimensional synergy organization for muscle activation. Because the muscle activation produces joint torques, kinetic changes accompanying aging can be related to changes in muscle synergies.ObjectivesWe explored the effects of aging on muscle synergies underlying sit-to-stand tasks, and examined their relationships with kinetic characteristics.MethodsFour younger and three older adults performed the sit-to-stand task at two speeds. Subsequently, we extracted the muscle synergies used to perform these tasks. Hierarchical cluster analysis was used to classify these synergies. We also calculated kinetic variables to compare the groups.ResultsThree independent muscle synergies generally appeared in each subject. The spatial structure of these synergies was similar across age groups. The change in motion speed affected only the temporal structure of these synergies. However, subject-specific muscle synergies and kinetic variables existed.ConclusionsOur results suggest common muscle synergies underlying the sit-to-stand task in both young and elderly adults. People may actively change only the temporal structure of each muscle synergy. The precise subject-specific structuring of each muscle synergy may incorporate knowledge of the musculoskeletal kinetics.
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Scholar : These new articles for Research in Drama Education: The Journal of Applied Theatre and Performance are available online
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Methane Detection Scheme based upon the Changing Optical Constants of a Zinc Oxide/Platinum Matrix created by a Redox Reaction and their effect upon Surface Plasmons
Publication date: Available online 23 August 2017
Source:Sensors and Actuators B: Chemical
Author(s): Thomas Allsop, Vojtěch Kundrat, Kyriacos Kalli, Graham B. Lee, Ron Neal, Peter Bond, Baogul Shi, John Sullivan, Phil Culverhouse, David J. Webb
We detect changes in the optical properties of a metal oxide semiconductor (MOS), ZnO, in a multi-thin-film matrix with platinum in the presence of the hydrocarbon gas methane. A limit of detection of 2% by volume with concentrations from 0 to 10% and maximum resolution of 0.15% with concentrations ranging from 30% to 80% at room temperature are demonstrated along with a selective chemical response to methane over carbon dioxide and the other alkane gases. The device yields the equivalent maximum bulk refractive index spectral sensitivity of 1.8×105nm/RIU. This is the first time that the optical properties of MOS have been monitored to detect the presence of a specific gas. This single observation is a significant result, as MOS have a potentially large number of target gases, thus offering a new paradigm for gas sensing using MOSs.
http://ift.tt/2xv0VO4
Self-cleaving ribozymes enable the production of guide RNAs from unlimited choices of promoters for CRISPR/Cas9 mediated genome editing
Source:Journal of Genetics and Genomics
Author(s): Yubing He, Tao Zhang, Ning Yang, Meilian Xu, Lang Yan, Lihao Wang, Rongchen Wang, Yunde Zhao
http://ift.tt/2xeFv8L
New photobiomodulation protocol prevents oral mucositis in hematopoietic stem cell transplantation recipients—a retrospective study
Abstract
Oral mucositis (OM) is an adverse side effect among hematopoietic stem cell transplantation (HSCT) recipients. The objective of this retrospective study was to evaluate the preventive effect of photobiomodulation (PBM) applied three times per week versus seven times per week in patients undergoing HSCT. The risk factors related to the incidence and severity of OM were also assessed. This was a retrospective study that evaluated 99 HSCT recipients who received different PBM protocols. Group I received three sessions per week, and group II received daily treatment. PBM was applied using a continuous-wave diode laser (InGaAlP; MM Optics, São Carlos, SP, Brazil) at a wavelength of 660 nm (visible-red) and a total radiant energy of 0.24 J per point. The baseline disease, type of transplant, type of conditioning, prophylaxis against graft-versus-host disease, OM grade, absolute leukocyte and platelet counts, and levels of liver and renal function markers were collected from medical records. The patients' age ranged from 13 to 71 years (mean/SD, 40.54 ± 16.45). No significant difference was observed between groups I and II regarding sex, age, ethnic, diagnosis, donor type, and conditioning treatment. Both PBM protocols were equally efficient in preventing OM (p = 0.34, ANOVA). Independent of the PBM protocol used, patients who received allogeneic transplant (p < 0.01—Fischer's exact test), total body irradiation (TBI-12Gy) (p = 0.01—chi-square test), busulfan + cyclophosphamide (p < 0.01—chi-square test), or methotrexate-containing regimens (p < 0.01—Fischer's exact test) demonstrated higher OM incidence and severity. Myelosuppression (p < 0.01—Mann-Whitney test) and impaired renal function (p = 0.02—Mann-Whitney test) were also considered risk factors for OM. Based on this retrospective data, PBM was effective in preventing OM in patients undergoing HSCT even when it was applied three times a week. A prospective study might be necessary to confirm these findings.
http://ift.tt/2xvhQAi
cDNA microarray analysis of human keratinocytes cells of patients submitted to chemoradiotherapy and oral photobiomodulation therapy: pilot study
Abstract
Oral mucositis is an acute toxicity that occurs in patients submitted to chemoradiotherapy to treat head and neck squamous cell carcinoma. In this study, we evaluated differences in gene expression in the keratinocytes of the oral mucosa of patients treated with photobiomodulation therapy and tried to associate the molecular mechanisms with clinical findings. From June 2009 to December 2010, 27 patients were included in a randomized double-blind pilot study. Buccal smears from 13 patients were obtained at days 1 and 10 of chemoradiotherapy, and overall gene expression of samples from both dates were analyzed by complementary DNA (cDNA) microarray. In addition, samples from other 14 patients were also collected at D1 and D10 of chemoradiotherapy for subsequent validation of cDNA microarray findings by qPCR. The expression array analysis identified 105 upregulated and 60 downregulated genes in our post-treatment samples when compared with controls. Among the upregulated genes with the highest fold change, it was interesting to observe the presence of genes related to keratinocyte differentiation. Among downregulated genes were observed genes related to cytotoxicity and immune response. The results indicate that genes known to be induced during differentiation of human epidermal keratinocytes were upregulated while genes associated with cytotoxicity and immune response were downregulated in the laser group. These results support previous clinical findings indicating that the lower incidence of oral mucositis associated with photobiomodulation therapy might be correlated to the activation of genes involved in keratinocyte differentiation.
http://ift.tt/2wAoPLJ
Crowding-out effect of coal industry investment in coal mining area: taking Shanxi province in China as a case
Abstract
The rapid development of coal industry in Shanxi province in China has important effects on its economic development. A large amount of money has been invested into the coal industry and other related industries during the recent years. However, research on the investment effect of Shanxi's coal industry was rare. In order to analyze the investment effect of coal industry, based on the crowding-out effect model, cointegration test, and the data available in Shanxi Statistical Yearbooks, this paper calculates the effect between coal industry investment and other 17 industry investment. The results show that the investment of coal industry produces crowding-out effect on food industry, building materials industry, and machinery industry. Increasing 1% of the coal industry investment can reduce 0.25% of the food industry investment, or 0.6% of building materials industry investment, or 0.52% of the machinery industry investment, which implies that Shanxi province should adjust coal industrial structure, promote the balance development of coal industry and other industries, so as to promote its economic growth.
http://ift.tt/2vhZJNh
Meta-analysis of chromosomal aberrations as a biomarker of exposure in healthcare workers occupationally exposed to antineoplastic drugs
Publication date: Available online 24 August 2017
Source:Mutation Research/Reviews in Mutation Research
Author(s): Christine Roussel, Kristine L. Witt, Peter B. Shaw, Thomas H. Connor
Many antineoplastic drugs used to treat cancer, particularly alkylating agents and topoisomerase inhibitors, are known to induce genetic damage in patients. Elevated levels of chromosomal aberrations, micronuclei, and DNA damage have been documented in cancer patients. Elevations in these same biomarkers of genetic damage have been reported in numerous studies of healthcare workers, such as nurses and pharmacists, who routinely handle these drugs, but results vary across studies. To obtain an overall assessment of the exposure effect, we performed a meta-analysis on data obtained from peer-reviewed publications reporting chromosomal aberration levels in healthcare workers exposed to antineoplastic drugs. A literature search identified 39 studies reporting on occupational exposure to antineoplastic drugs and measurement of chromosomal aberrations in healthcare workers. After applying strict inclusion criteria for data quality and presentation, data from 17 studies included in 16 publications underwent meta-analysis using Hedges' bias-corrected g and a random-effects model. Results showed the level of chromosomal aberrations in healthcare workers exposed to antineoplastic drugs was significantly higher than in controls. The standardized mean differences (difference of means divided by within sd) from all studies were pooled, yielding a value 1.006 (unitless) with p <0.001. Thus, in addition to the documented genotoxic effects of antineoplastic drugs in cancer patients, this meta-analysis confirmed a significant association between occupational exposure to antineoplastics during the course of a normal work day and increases in chromosomal aberrations in healthcare workers. Based on the studies reviewed, we were unable to accurately assess whether appropriate use of protective measures might reduce the incidence of genetic damage in healthcare workers. However, given the potential for increased cancer risk linked to increases in chromosomal aberrations, the results of this study support the need to limit occupational exposure of healthcare workers to antineoplastic drugs as much as possible.
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Identification of pathogenic retrotransposon insertions in cancer predisposition genes
Source:Cancer Genetics
Author(s): Yaping Qian, Debora Mancini-DiNardo, Thaddeus Judkins, Hannah C. Cox, Krystal Brown, Maria Elias, Nanda Singh, Courtney Daniels, Jayson Holladay, Bradford Coffee, Karla R. Bowles, Benjamin B. Roa
Cancer risks have been previously reported for some retrotransposon element (RE) insertions; however, detection of these insertions is technically challenging and very few oncogenic RE insertions have been reported. Here we evaluate RE insertions identified during hereditary cancer genetic testing using a comprehensive testing strategy. Individuals who had single-syndrome or pan-cancer hereditary cancer genetic testing from February 2004 to March 2017 were included. RE insertions were identified using Sanger sequencing, Next Generation Sequencing, or multiplex quantitative PCR, and further characterized using targeted PCR and sequencing analysis. Personal cancer history, ancestry, and haplotype were evaluated. A total of 37 unique RE insertions were identified in 10 genes, affecting 211 individuals. BRCA2 accounted for 45.9% (17/37) of all unique RE insertions. Several RE insertions were detected with high frequency in populations of conserved ancestry wherein up to 100% of carriers share a high degree of haplotype conservation, suggesting founder effects. Our comprehensive testing strategy resulted in a substantial increase in the number of reported oncogenic RE insertions, several of which may have possible founder effects. Collectively, these data show that the detection of RE insertions is an important component of hereditary cancer genetic testing and may be more prevalent than previously reported.
http://ift.tt/2irBvOJ
Addition of 3-day aprepitant to ondansetron and dexamethasone for prophylaxis of chemotherapy-induced nausea and vomiting among patients with diffuse large B cell lymphoma receiving 5-day cisplatin-based chemotherapy
Publication date: Available online 24 August 2017
Source:Journal of the Egyptian National Cancer Institute
Author(s): Raafat Abdel-Malek, Noha Abbas, Kyrillus S. Shohdy, Mohamed Ismail, Radwa Fawzy, Dalal S. Salem, Ezzat Safwat
BackgroundNeurokinin-1 receptor antagonists, such as aprepitant are currently emerging as powerful prophylactic agents for chemotherapy-induced nausea and vomiting (CINV). Therefore, it is important to adjust the anti-emetic regimens based on personal risk factors of the patient, duration of the chemotherapy regimen and cost-effectiveness.PurposeTo determine the efficacy of the 3-day aprepitant along with ondansetron and dexamethasone in controlling CINV in patients with large B cell lymphoma receiving multiday-cisplatin regimen chemotherapy.MethodsThis is a pilot prospective cross-over trial. Patients were allocated to either aprepitant 125mg on day 1 and 80mg on days 2 & 3 or placebo in the first 2 cycles, with crossover to the opposite treatment in the 3rd and 4th cycles. The primary end point was complete response (CR) of both acute (days 1–5) and delayed (days 6–8) CINV. CR means neither to develop emetic episodes nor to use rescue anti-emetics medication.ResultsTwelve of the 15 patients recruited for the study were fully evaluable and completed 4 cycles of ESHAP regimen with a total of 48 cycles given. In the cycles with aprepitant and those without the CR were 83.3% and 0% respectively (p<0.05). Patients receiving aprepitant in the first 2 cycles recorded less nausea in subsequent cycles that were given without aprepitant. This was not statistically significant.ConclusionThis triple anti-emetic regimen showed efficacy in controlling the multi-day cisplatin-induced nausea and vomiting. Further randomized controlled trials are needed to compare between 3-day and 7-day aprepitant for multi-day cisplatin regimens.
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Alveolar soft part sarcoma of orbit: A rare diagnosis
Publication date: Available online 23 August 2017
Source:Journal of the Egyptian National Cancer Institute
Author(s): Pritee B. Chaudhari, Sushmita Pathy, Suryanarayana S.V. Deo, Bhavna Chawla, Asit Ranjan Mridha
ObjectiveAlveolar soft part sarcoma (ASPS) is an aggressive, rare tumour with unique morphological and histopathological features.MethodsWe report a rare case of orbital ASPS and its management in a young male who presented with painless proptosis and progressive loss of vision.ResultTwenty-two year male presented with a history of gradually increasing proptosis with loss of vision since 12months. He underwent radical re-excision of mass with right orbital exenteration and reconstruction using temporalis muscle flap. Adjuvant radiotherapy to a dose of 64Gy in 32 fractions over 6.5weeks was planned in view of positive surgical margins. Patient is free of disease and currently under follow up in multidisciplinary clinic.ConclusionFunction preserving surgery remains the standard treatment approach in localised disease however the complex anatomy and locally aggressive nature makes it difficult to achieve clear surgical margin. Adjuvant radiotherapy has shown to improve local control in patients with positive surgical margins.
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Impact of CYP1A1, GSTP1 and XRCC1 genes polymorphisms on toxicity and response to chemotherapy in childhood acute lymphoblastic leukemia
Publication date: Available online 24 August 2017
Source:Journal of the Egyptian National Cancer Institute
Author(s): Asmaa Abo-Bakr, Ghada Mossallam, Nevin El Azhary, Hanafy Hafez, Ragia Badawy
BackgroundAcute lymphoblastic leukemia (ALL) is the most common childhood malignancy. The interindividual genetic variations in drug metabolizing enzymes and DNA repair genes influence the efficacy and toxicity of numerous chemotherapeutic drugs affecting the treatment outcome.Aim of the workThe aim of the study was to investigate the impact of drug metabolizing CYP1, GSTP1 and DNA repair (XRCC1) genes polymorphisms on the toxicity and response to chemotherapy in childhood ALL.Patients and methodologyNinety seven ALL pediatric patients were genotyped for CYP1A1, GSTP1 ILe105Val and XRCC1 Arg194Tryp single nucleotide polymorphisms (SNPs) using PCR-RFLP.ResultsNo statistically significant differences were observed between the wild and variant (homozygous and heterozygous) genotypes of the polymorphisms studied in CYP1A1, GSTP1 or XRCC1 genes regarding age, total leukocyte count, immunophenotyping, cytogenetic or risk group. The SNPs in CYP1A1, GSTP1 and XRCC1 genes did not show significant association with complete remission (CR) rate, overall survival (OS) or event free survival (EFS). However, XRCC1 Arg194Trp SNP was associated with higher drug toxicity; carriers of variant genotypes (CT and TT) had a significantly higher frequency of myelosuppression compared to those with the wild CC genotype (21/43[48.8%]) compared to (14/54[25.9%]) (p=0.020). The analysis of the combined effect of studied SNPs did not show any significant association with patient outcome.ConclusionOur study reported a significant association between the DNA repair gene polymorphism and myelosuppression in childhood ALL patients. Adjustment of the dose of chemotherapeutic agents according to XRCC1 Arg194Trp polymorphism may improve outcome in cases with risk of toxicity.
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Bioengineered II–VI semiconductor quantum dot–carboxymethylcellulose nanoconjugates as multifunctional fluorescent nanoprobes for bioimaging live cells
Publication date: 15 January 2018
Source:Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, Volume 189
Author(s): Alexandra A.P. Mansur, Herman S. Mansur, Rafael L. Mansur, Fernanda G. de Carvalho, Sandhra M. Carvalho
Colloidal semiconductor quantum dots (QDs) are light-emitting ultra-small nanoparticles, which have emerged as a new class of nanoprobes with unique optical properties for bioimaging and biomedical diagnostic. However, to be used for most biomedical applications the biocompatibility and water-solubility are mandatory that can achieved through surface modification forming QD-nanoconjugates. In this study, semiconductor II–VI quantum dots of type MX (M=Cd, Pb, Zn, X=S) were directly synthesized in aqueous media and at room temperature using carboxymethylcellulose sodium salt (CMC) behaving simultaneously as stabilizing and surface biofunctional ligand. These nanoconjugates were extensively characterized using UV–visible spectroscopy, photoluminescence spectroscopy, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, transmission electron microscopy, dynamic light scattering and zeta potential. The results demonstrated that the biopolymer was effective on nucleating and stabilizing the colloidal nanocrystals of CdS, ZnS, and PbS with the average diameter ranging from 2.0 to 5.0nm depending on the composition of the semiconductor core, which showed quantum-size confinement effect. These QD/polysaccharide conjugates showed luminescent activity from UV–visible to near-infrared range of the spectra under violet laser excitation. Moreover, the bioassays performed proved that these novel nanoconjugates were biocompatible and behaved as composition-dependent fluorescent nanoprobes for in vitro live cell bioimaging with very promising perspectives to be used in numerous biomedical applications and nanomedicine.
Graphical abstract
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Immune checkpoint blockade for unresectable or metastatic uveal melanoma: a systematic review
Source:Cancer Treatment Reviews
Author(s): Markus V. Heppt, Theresa Steeb, J. Gabriel Schlager, Stefanie Rosumeck, Corinna Dressler, Thomas Ruzicka, Alexander Nast, Carola Berking
BackgroundThe use of immune checkpoint blockade (ICB) for uveal melanoma (UM) is little established. The aim of this review was to provide a comprehensive overview on the efficacy, safety, and tolerability of ICB in patients with UM.MethodsWe performed a systematic literature research covering MEDLINE, Embase and CENTRAL. Abstracts of pertinent conferences and trial registers were handsearched for relevant studies.ResultsOut of 1,327 records initially identified, 12 eligible studies were included in the qualitative synthesis. They comprised 7 expanded access or named patient programs (n=162), 4 phase II trials (n=171), and 1 phase Ib trial (sample size unknown), while no randomized controlled trial was found. Ipilimumab monotherapy was assessed at 3 mg/kg in 5 trials (n=186) with a response rate of 0-5%. Two reports investigated ipilimumab at 10 mg/kg (n=45) with radiological responses observed in 0-6.5%. The median progression-free survival (PFS) was below 3 months and the median overall survival was 5.2-9.8 months for ipilimumab monotherapy. Severe immune-related adverse events occurred at a frequency comparable to cutaneous melanoma (6-36%). Two studies investigated pembrolizumab (2 mg/kg) and nivolumab (3 mg/kg) with overall response rates of 30% and 6%, respectively. Data on combined ipilimumab and programmed cell death protein 1 inhibition were available from one expanded access program, but no response was observed with a median PFS of 2.9 months.ConclusionsUM is little responsive to ipilimumab regardless of dosage schemes. Sound randomized clinical trials are needed to evaluate the efficacy of combined ICB in patients with UM.
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Immunosenescence and immunecheckpoint inhibitors in non-small cell lung cancer patients: does age really matter?
Source:Cancer Treatment Reviews
Author(s): Roberto Ferrara, Laura Mezquita, Edouard Auclin, Nathalie Chaput, Benjamin Besse
Immunotherapy has dramatically changed the therapeutic scenario in non-small cell lung cancer (NSCLC), extending overall survival, with a favorable safety profile. However, there is still a gap of knowledge about the efficacy of immune checkpoint inhibitors (ICIs) in elderly patients. Data from randomized clinical trials testing ICIs are conflicting and often lack adequate statistical power. Although two large meta-analyses suggested an absence of a significant survival benefit in patients older than 75 years, expanded access programs and retrospective cohort studies of ICIs in the real-life setting, showed comparable survival outcomes and safety profiles between older and younger patients. In this complex scenario, a further unresolved issue is the potential correlation between older age and immunotherapy primary resistance, a phenomenon probably linked to the continuous and progressive remodeling of immune functions with ageing, known as immunosenescence. Defining the role of ICIs in elderly NSCLC patients and exploring the molecular mechanisms underlying a possible lack of benefit or even accelerated tumor growth during immunotherapy are two major challenges for future research in this field of cancer treatment. In this review, we describe the major hallmarks of immunosenescence and we summarize the existing clinical data of ICIs in elderly NSCLC patients.
http://ift.tt/2irrAbZ
Healthcare cost of HER2-positive and negative breast tumors in the United States (2012−2035)
Source:Cancer Treatment Reviews
Author(s): Francesca Tartari, Matteo Santoni, Mirco Pistelli, Rossana Berardi
BackgroundIn this study, we estimated the current and future costs related to the use of targeted agents in patients with HER2-positive and negative advanced breast cancer (BC), aimed at identifying the subgroup associated with the higher cost in the coming years.MethodsWe calculated the patient cost considering an ideal patient who received therapeutic sequences including all approved agents for HER2-positive or negative BC. The duration of treatment was estimated by the median Progression-Free Survival (PFS) reported in the phase III trials which have led to the approval of these drugs by the US Food and Drug Administration. The estimated number of BC patients in the US from 2012 to 2035 refers to data published by the World Health Organization.ResultsThe per patient cost was $292,155 for HER2-positive and $224,955 for negative tumors, respectively. The total cost for HER2-positive patients was estimated for 2012 at $2,719,542,347, with an annual increase ranged from 4.3 (for 2035) to 7.7% (for 2020), leading to a total expense of $3,648,232,975 in 2035. Otherwise, the total cost for HER2-negative patients in 2012 was estimated as $8,376,028,459, with an increase of more than $2.5 billion from 2012 to 2035. The estimated cost for HER2-negative patients was $5.6 billion higher that for HER2-positive tumors, raising to $7.6 billion to 2035.ConclusionsOur data strongly suggest that cost-analyses should be carefully evaluated in the coming years, in particular in patients with HER2-negative tumors.
http://ift.tt/2g6DHKV
Pancreatic Ductal Adenocarcinoma: State-of-the-Art 2017 and New Therapeutic Strategies
Source:Cancer Treatment Reviews
Author(s): Marta Chiaravalli, Michele Reni, Eileen M. O'Reilly
Pancreatic ductal adenocarcinoma (PDAC) is a fatal malignancy with an overall 5-year survival of 8% for all stages combined. The majority of patients present with stage IV disease at diagnosis and these patients have an overall 5-year survival of 3%. Currently, the standard of care for metastatic pancreas adenocarcinoma is combination cytotoxic therapy, namely FOLFIRINOX or gemcitabine plus nab-paclitaxel for good performance status patients. Given the challenges and the rising incidence of PDAC expected to become the second leading cause of cancer-related death by 2030, there is a major unmet need to develop more effective therapies. In this setting, the molecular and genomic characterization of PDAC have underpinned the use of targeted therapies. To date, the results from targeted agent evaluation have been disappointing with some exceptions. Novel promising strategies depend on biomarker identification and patient selection e.g. germline mutations in DNA repair or mismatch repair genes, where the addition of a platinum agent or checkpoint inhibitor can have a positive impact on survival. This article will review the state-of-the-art treatment of metastatic pancreatic cancer with an emphasis on novel promising therapeutic strategies and an overview on emerging biomarkers.
http://ift.tt/2it7kqw
Modulation of gene expression by nutritional state and hormones in Bombyx larvae in relation to its growth period
Source:Gene Expression Patterns
Author(s): Bembem Thounaojam, Bela Keshan
Insect growth and development are mainly regulated via synchronization of many extrinsic and intrinsic factors such as nutrition and hormones. Previously we have demonstrated that larval growth period influences the effect of insulin on the accumulation of glycogen in the fat body of Bombyx larvae. In the present study we demonstrate that Bombyx larvae at the terminal growth period (TGP, after critical weight) had a significantly greater increase in the expression level of Akt in the fat body than at the active growth period (AGP, before critical weight). The larvae at TGP also showed an increase in the expression level of ecdysone receptors (EcRB1 and USP1) and ecdysone-induced early genes (E75A and broad). The treatment of bovine insulin and methoprene to larvae at AGP induced the transcript levels of Akt, irrespective of the nutritional status of the larvae. However, in larvae at TGP, insulin repressed the transcript level of Akt. On contrary, 20-hydroxyecdysone induced the expression level of Akt in TGP larvae, but at feeding only. Insulin and 20E thus showed an antagonistic action on the Akt expression level in TGP larvae under feeding. The studies thus showed that larval growth period influences the expression level of Akt and ecdysone receptors in Bombyx. Further, the growth period and nutrition modulate the effect of exogenous hormones on Akt expression.
http://ift.tt/2w6kRYb
Ki-67 and the Chromosome Periphery Compartment in Mitosis
Publication date: Available online 23 August 2017
Source:Trends in Cell Biology
Author(s): Daniel G. Booth, William C. Earnshaw
The chromosome periphery is a complex network of proteins and RNA molecules (many derived from nucleoli) that covers the outer surface of chromosomes and whose function remains mysterious. Although it was first described over 130 years ago, technological advances and the recent discovery that Ki-67 acts as an organiser of this region have allowed the chromosome periphery to be dissected in previously unattainable detail, leading to a revival of interest in this obscure chromosomal compartment. Here, we review the most recent advances into the composition, structure and function of the chromosome periphery, discuss possible roles of Ki-67 during mitosis and consider why this structure is likely to remain the focus of ongoing attention in the future.
http://ift.tt/2vrL8OI
Fretting behaviors of interface between CFRP and coated titanium alloy in composite interference-fit joints under service condition
Publication date: 15 November 2017
Source:Materials & Design, Volume 134
Author(s): Junshan Hu, Kaifu Zhang, Qingda Yang, Hui Cheng, Shunuan Liu, Yu Yang
This paper describes an experimental study on the fretting behaviors and tribological mechanism of interface between carbon fiber reinforced polymer (CFRP) composites and titanium alloy in composite interference-fit joints under service condition. A ball-on-flat configuration was employed in the fretting tests where the effect of fiber orientation, ambient temperature, surface treatment and interface condition were evaluated. The coefficients of friction (COFs), 3D surface morphologies and microstructures of worn scars were presented to characterize corresponding fretting mechanisms. An obvious tribological anisotropy was observed in the CFRP specimens where the longitudinal surface possessed much smaller COFs and less wear damage than the normal surface. The wear damage and anisotropic properties can be reduced to a certain extent by surface treatment through improving wear resistance or serving as solid lubricant respectively. The fretting behaviors also show strong temperature dependence. The increasing temperature exaggerates deformation in longitudinal surface and aggravates abrasion in normal surface by softening matrix resin. Wet service condition contributes to reducing COF and wear owing to the formation of a tribofilm on the interface.
Graphical abstract
http://ift.tt/2vi843t
Effect of atopic dermatitis on quality of life and its psychosocial impact in Asian adolescents
Abstract
Background/Objectives
Atopic dermatitis (AD) is a common condition affecting up to 20% of the paediatric population in Singapore. It is often associated with significant psychosocial morbidity and can affect patients' quality of life (QOL) tremendously. This study investigated the varying lifestyle impacts, and psychosocial domains most affected by AD in adolescent children in Singapore.
Methods
A prospective study evaluating the impact of AD on the QOL of adolescents was conducted over a 6-month period from July to December 2014. Adolescents aged 11–16 years with varying eczema severity were recruited. Eczema severity was determined by using the eczema area and severity index (EASI) scores. Lifestyle impact of AD was evaluated using patient-reported children's dermatology life quality index (CDLQI) scores. Statistical analysis was performed using an analysis of one-way variance and Student's t-test.
Results
A total of 50 patients were enrolled and divided into three groups: mild (<10.3), moderate (10.3–20.9) and severe (>20.9) eczema based on EASI scores. Patients with mild and moderate eczema had lower CDLQI scores. Adolescents were most affected by the disruption that their symptoms had on their leisure and physical activities and sleep as a result of itch and scratching, respectively.
Conclusion
Chronic sufferers of severe eczema experience poorer QOL than those with mild or moderate eczema. They also experience significant psychosocial impact as a consequence of their condition.
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Removal of BCG artefact from concurrent fMRI-EEG recordings based on EMD and PCA
Source:Journal of Neuroscience Methods
Author(s): Ehtasham Javed, Ibrahima Faye, Aamir Saeed Malik, Jafri Malin Abdullah
BackgroundSimultaneous electroencephalography (EEG) and functional magnetic resonance image (fMRI) acquisitions provide better insight into brain dynamics. Some artefacts due to simultaneous acquisition pose a threat to the quality of the data. One such problematic artefact is the ballistocardiogram (BCG) artefact.MethodsWe developed a hybrid algorithm that combines features of empirical mode decomposition (EMD) with principal component analysis (PCA) to reduce the BCG artefact. The algorithm does not require extra electrocardiogram (ECG) or electrooculogram (EOG) recordings to extract the BCG artefact.ResultsThe method was tested with both simulated and real EEG data of 11 participants. From the simulated data, the similarity index between the extracted BCG and the simulated BCG showed the effectiveness of the proposed method in BCG removal. On the other hand, real data were recorded with two conditions, i.e. resting state (eyes closed dataset) and task influenced (event-related potentials (ERPs) dataset). Using qualitative (visual inspection) and quantitative (similarity index, improved normalized power spectrum (INPS) ratio, power spectrum, sample entropy (SE)) evaluation parameters, the assessment results showed that the proposed method can efficiently reduce the BCG artefact while preserving the neuronal signals.Comparison with existing methodsCompared with conventional methods, namely, average artefact subtraction (AAS), optimal basis set (OBS) and combined independent component analysis and principal component analysis (ICA-PCA), the statistical analyses of the results showed that the proposed method has better performance, and the differences were significant for all quantitative parameters except for the power and sample entropy.ConclusionsThe proposed method does not require any reference signal, prior information or assumption to extract the BCG artefact. It will be very useful in circumstances where the reference signal is not available.
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Flow characterization and patch clamp dose responses using jet microfluidics in a tubeless microfluidic device
Source:Journal of Neuroscience Methods
Author(s): Pedro J. Resto, Abhishek Bhat, Eric Stava, Chong Lor, Elliot Merriam, Ruben E. Diaz-Rivera, Robert Pearce, Robert Blick, Justin C. Williams
BackgroundSurface tension passive pumping is a way to actuate flow without the need for pumps, tubing or valves by using the pressure inside small drop to move liquid via a microfluidic channel. These types of tubeless devices have typically been used in cell biology. Herein we present the use of tubeless devices as a fluid exchange platform for patch clamp electrophysiology.New MethodInertia from high-speed droplets and jets is used to create flow and perform on-the-fly mixing of solutions. These are then flowed over GABA transfected HEK cells under patch in order to perform a dose response analysis.ResultsTIRF imaging and electrical recordings are used to study the fluid exchange properties of the microfluidic device, resulting in 0–90% fluid exchange times of hundreds of milliseconds. COMSOL is used to model flow and fluid exchange within the device. Patch-clamping experiments show the ability to use high-speed passive pumping and its derivatives for studying peak dose responses, but not for studying ion channel kinetics.Comparison with Existing Method(s)Our system results in fluid exchange times slower than when using a standard 12-barrel application system and is not as stable as traditional methods, but it offers a new platform with added functionality.ConclusionsSurface tension passive pumping and tubeless devices can be used in a limited fashion for electrophysiology. Users may obtain peak dose responses but the system, in its current form, is not capable of fluid exchange fast enough to study the kinetics of most ion channels.
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Chemopreventive and remediation effect of Adansonia digitata L. Baobab (Bombacaceae) stem bark extracts in mouse model malaria
Publication date: Available online 24 August 2017
Source:Journal of Ethnopharmacology
Author(s): A.O. Adeoye, C.O. Bewaji
Ethnopharmacological relevanceAdansonia digitata L. Baobab (Bombacaceae) solvent extracts have been reported to possess medicinal properties and are currently been used traditionally for the treatment of malaria and several other diseases and infection; however few reports exist in literature that provides supportive scientific evidence in favour of its medicinal use.Aim of the studyThis study investigated the efficacy of Adansonia digitata stem bark extract in offering protection against experimental malaria and also examined its remediation effect when administered after established infection.Materials and methodsWeanling albino mice were used in the study. The mice were transfected intraperitonially with an inoculums size of 1× 107 of chloroquine susceptible strain of plasmodium berghei infected erythrocytes. Mechanisms of action of the extract were investigated by measuring the degree of tissue peroxidation and tissue antioxidant status. Severity of malaria was determined by measuring the serum C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and serum and tissue Alkaline phosphatase (ALP) activity.ResultsThere was a significant increase in serum CRP, TNF-α concentrations and serum and tissue ALP activity in the control mice following Plasmodium berghei infection. All the treatment had effect on the growth of Plasmodium berghei parasites in mice. The extracts showed a significant dose dependent increase packed cell volume (PCV), percentage chemosupression/clearance and a significant decrease in percentage parasitemia at the two doses when administered after established infection. Methanolic extract (MEAD) at 400mg/kg exhibited the highest chemosupressive activity. The extract significantly reduced the degree of tissue peroxidation, increased the level of reduced glutathione (GSH), catalase and superoxide dismutase activity. Administration of the extract after established infection reduced serum CRP and TNF-α concentrations and serum and tissue ALP activity.ConclusionOur study suggests that Adansonia digitata protects against Plasmodium berghei induced-malaria, and that administration of the extract after established infection reduced malaria progression.
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Phytochemical analysis, molecular docking and antiamnesic effects of methanolic extract of Silybum marianum (L.) Gaertn seeds in scopolamine induced memory impairment in mice
Publication date: Available online 24 August 2017
Source:Journal of Ethnopharmacology
Author(s): Nausheen Nazir, Nasiara Karim, Heba Abdel-Halim, Imran Khan, Syed Fazal Wadood, Muhammad Nisar
Ethnopharmacological relevanceSilybum marianum (L.) Gaertn and its main component silymarin have been extensively studied and have been found effective in various neurological disorders.Aims of the studyThe aim of the current study is to identify phytoconstituents in the methanolic extract (Me.Ext) of Silybum marianum (L.) Gaertn seeds and to study in-vivo the anti-amnesic effects along with in vitro antioxidant and acetylcholinesterase (AChE) and buteryl cholinesterase (BChE) inhibition potential. Induced fir docking (IFD) results have confirmed that quercetin, morin and rutin showed good affinity when docked into AChE binding site.Materials and methodsThe present study investigates the in-vitro AChE and BChE inhibition potential of the Me-Ext of Silybum marianum (L.) Gaertn at various concentrations (31.25, 62.50, 125, 250, 500, 1000µg/ml) using Ellman's spectrophotometric analysis, while antioxidant potential against DPPH and ABTS were determined using Brand-Williams spectrophotometric method. Furthermore, the in-vivo anti-amnesic effects of Me.Ext at the dose level of 50, 100 and 200mg/kg were also evaluated using scopolamine -induced memory impairment in mice in the novel object recognition test (NORT) and Y-maze test.ResultsThe Me.Ext showed a concentration dependent inhibition of AChE and BChE with IC50 values of 110 and 130µg/mL respectively and antioxidant activity against DPPH and ABTS with IC50 values 280 and 220µg/mL, respectively. In mice, Me.Ext reversed the amnesia induced by scopolamine as indicated by a dose-dependent increase in spontaneous alternation performance in the Y-maze task (p<0.05 versus scopolamine) and increase in the discrimination index in the NORT comparable to the standard drug donepezil 2mg/kg. HPLC-UV analysis showed the presence of quercetin, rutin and morin. Induced fit docking (IFD) was performed using quercetin, rutin and morin, Glide Gscore and IFD score of all compounds were consistent with their experimental AChE inhibitory activities.ConclusionThe results indicate that Silybum marianum (L.) Gaertn could be a new source for the isolation of phytoconstituents useful in cognition and memory disorders such as Alzheimer's disease.
Graphical abstract
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Gangjihwan, a polyherbal composition, inhibits fat accumulation through the modulation of lipogenic transcription factors SREBP1C, PPARγ and C/EBPα
Publication date: Available online 24 August 2017
Source:Journal of Ethnopharmacology
Author(s): Jaewoong Jang, Yoonju Jung, Seyeon Chae, Soo Hyun Cho, Michung Yoon, Heejung Yang, Soon Shik Shin, Yoosik Yoon
Ethnopharmacological relevanceGangjihwan (DF) which is composed of Ephedra intermedia, Lithospermum erythrorhizon, and Rheum palmatum has been used for the treatment of obesity in traditional medical clinics in Korea.Aim of the studyThis study was conducted to standardize DF and elucidate its mechanism of action for inhibiting fat accumulation in adipocytes and adipose tissues.Materials and MethodsThe herbal ingredients of DF were extracted in water, 30% ethanol or 70% ethanol and freeze-dried followed by HPLC analyses. 3T3-L1 adipocytes and high-fat diet-induced obese mice were treated with each of the three DF preparations. Messenger RNA and protein expression levels were measured by real-time qPCR and Western blotting. RNA-Seq analyses were conducted to examine the effects of DF treatment on whole transcriptome of adipocyte.Results(-)-Ephedrine and (+)-pseudoephedrine from E. intermedia, aloe-emodin and chrysophanol from R. palmatum and shikonin from L. erythrorhizon were identified as phytochemical components of DF. DF caused dose-dependent inhibition of fat accumulation in 3T3-L1 adipocytes. It also significantly reduced adipose tissue mass and adipocyte size in high-fat diet-induced obese mice. DF was found to down-regulate the expressions of the lipogenic transcription factors such as sterol regulatory element binding protein 1C (SREBP1C), peroxisome proliferator activated receptor gamma (PPARγ), and CCAAT/enhancer binding protein alpha (C/EBPα). Among the three preparations of DF, the 70% ethanol extract was the most effective. RNA-Seq analyses showed that DF treatment decreased the expression levels of up-regulators and increased those of down-regulators of lipogenic transcription factors.ConclusionsDF preparations, among which 70% ethanol extract was the most effective, reduced fat accumulation in 3T3-L1 adipocytes and high-fat diet-induced obese mice through the down-regulation of lipogenic transcription factors SREBP1C, PPARγ and C/EBPα.
Graphical abstract
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The genus Psiadia: Review of traditional uses, phytochemistry and pharmacology
Publication date: Available online 24 August 2017
Source:Journal of Ethnopharmacology
Author(s): Keshika Mahadeo, Isabelle Grondin, Hippolyte Kodja, Joyce Soulange Govinden, Sabina Jhaumeer Laulloo, Michel Frederich, Anne Gauvin-Bialecki
Ethnopharmacological relevanceThe genus Psiadia Jacq. ex. Willd. belongs to the Asteraceae family and includes more than 60 species. This genus grows in tropical and subtropical regions, being especially well represented in Madagascar and the Mascarene Islands (La Réunion, Mauritius and Rodrigues). Several Psiadia species have been used traditionally for their medicinal properties in Africa and the Mascarene Islands. Based on traditional knowledge, various phytochemical and pharmacological studies have been conducted. However there are no recent papers that provide an overview of the medicinal potential of Psiadia species. Therefore, the aim of this review is to provide a comprehensive summary of the botany, phytochemistry and pharmacology of Psiadia and to highlight the gaps in our knowledge for future research opportunities.Materials and methodsThe available information on traditional uses, phytochemistry and biological activities of the genus Psiadia was collected from scientific databases through a search using the keyword 'Psiadia' in 'Google Scholar', 'Pubmed', 'Sciencedirect', 'SpringerLink', 'Web of Science', 'Wiley' and 'Scifinder'. Additionally, published books and unpublished PhD and MSc dissertations were consulted for botanical information and chemical composition.ResultsHistorically, species of the genus Psiadia have been used to treat a wide range of ailments including abdominal pains, colds, fevers, bronchitis, asthma, rheumatoid arthritis, skin infections and liver disorders among others. Phytochemical works led to the isolation of flavonoids, phenylpropanoids, coumarins and terpenoids. Furthermore, phytochemical compositions of the essential oils of some species have been evaluated. Crude extracts, essential oils and isolated molecules showed in vitro pharmacological activities, such as antimicrobial, anti-viral, anti-inflammatory, antiplasmodial and antileishmanial activities. Crude extracts of Psiadia dentata and Psiadia arguta have specifically been found to be potentially useful for inhibition of growth of Plasmodium falciparum.However, pharmacological data on this particular genus is quite limited. Further research is necessary to determine the active compounds and the underlying mechanisms.
Graphical abstract
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Anti-inflammatory effect of stem bark of Paulownia tomentosa Steud. in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and LPS-induced murine model of acute lung injury
Publication date: Available online 24 August 2017
Source:Journal of Ethnopharmacology
Author(s): Jae-Won Lee, Kyeong-Hwa Seo, Hyung Won Ryu, Heung Joo Yuk, Hyun Ah Park, YouRim Lim, Kyung-Seop Ahn, Sei-Ryang Oh
Ethnopharmacological relevanceThe leaves, bark, and flowers of Paulownia tomentosa Steud. have been widely used as a traditional medicine in East Asia to treat inflammatory and infectious diseases.Aim of the studyWe investigated the protective effect of the methanol stem bark extract of P. tomentosa using an animal model of lipopolysaccharide (LPS)-induced acute lung injury (ALI).Materials and methodsThe UPLC Q-TOF-MS profiles for the methanol extract of of P. tomentosa stem bark showed that verbascoside and isoverbascoside were the predominant compounds. Raw 264.7 cells were used for inhibitory effects of cytokine production in vitro. C57BL/6N mice were administered intranasally with LPS (10μg/per mouse) to induce ALI. H&E staining was used to evaluate histological changes in the lung.ResultsTreatment with P. tomentosa stem bark extract (PTBE) suppressed the production of IL-6 and TNF-α in LPS-stimulated RAW 264.7 macrophages, and therecruitment of neutrophils and macrophages in the BALF of mice with LPS-induced ALI. PTBE also decreased the levels of reactive oxygen species (ROS) and pro-inflammatory cytokines in the BALF. PTBE reduced the levels of nitric oxide (NO) in the serum and of inducible nitric oxide synthase (iNOS) in the lung of ALI mice. PTBE also attenuated the infiltration of inflammatory cells and the expression of monocyte chemoattractant protein-1 (MCP-1) in the lung. In addition, PTBE suppressed the activation of NF-κB and the reduced expression of superoxide dismutase 3 (SOD3) in the lung.ConclusionThe results suggest that PTBE has a protective effect on LPS-induced ALI.
Graphical abstract
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Τετάρτη 23 Αυγούστου 2017
Table of Contents
Publication date: September 2017
Source:Magnetic Resonance Imaging, Volume 41
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Editorial Board
Publication date: September 2017
Source:Magnetic Resonance Imaging, Volume 41
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Spiral MR fingerprinting at 7T with simultaneous B1 estimation
Publication date: September 2017
Source:Magnetic Resonance Imaging, Volume 41
Author(s): Guido Buonincontri, Rolf F. Schulte, Mirco Cosottini, Michela Tosetti
Magnetic resonance fingerprinting is an efficient, new approach for quantitative imaging with MR. We aimed to extend this technique to cases with B1+ inhomogeneities within the imaging volume.Previous approaches have used abrupt changes in flip angles to estimate the B1+ field simultaneously with T1 and T2, using a Cartesian approach in a small-animal scanner at 4.7T. Here, we evaluated whether a similar approach would be suitable for imaging human brains using spiral readouts with a 7T scanner.We found that our modified scheme could significantly reduce the adverse effects of B1+ inhomogeneities even in extreme cases, reducing both the bias and the variance in T2 estimations by an order of magnitude when compared to literature methods. Acquisitions used less than 1.5W/kg SAR and could be performed in 12s per slice.In conclusion, our approach can be used to perform quantitative imaging of the brain at 7T in a short time, simultaneously estimating the B1+ profile.
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Publication date: September 2017 Source: Free Radical Biology and Medicine, Volume 110 Author(s): Lucía Fernández-del-Río, Anish Nag, Elen...
