Electroconvulsive seizures influence dendritic spine morphology and BDNF expression in a neuroendocrine model of depression

Publication date: Available online 6 April 2018
Source:Brain Stimulation
Author(s): Kristen. R. Maynard, John W. Hobbs, Sumita Rajpurohit, Keri Martinowich
BackgroundElectroconvulsive therapy (ECT) is a rapid and effective treatment for major depressive disorder. Chronic stress-induced depression causes dendrite atrophy and deficiencies in brain-derived neurotrophic factor (BDNF), which are reversed by anti-depressant drugs. Electroconvulsive seizures (ECS), an animal model of ECT, robustly increase BDNF expression and stimulate dendritic outgrowth.ObjectiveThe present study aims to understand cellular and molecular plasticity mechanisms contributing to the efficacy of ECS following chronic stress-induced depression.MethodsWe quantify Bdnf transcript levels and dendritic spine density and morphology on cortical pyramidal neurons in mice exposed to vehicle or corticosterone and receiving either Sham or ECS treatment.ResultsECS rescues corticosterone-induced defects in spine morphology and elevates Bdnf exon 1 and exon 4-containing transcripts in cortex.ConclusionsDendritic spine remodeling and induction of activity-induced BDNF in the cortex represent important cellular and molecular plasticity mechanisms underlying the efficacy of ECS for treatment of chronic stress-induced depression.



https://ift.tt/2qbBWOz

Overlap of large-scale brain networks may explain the similar cognitive improvement of single-site vs multi-site rTMS in Alzheimer's disease

Publication date: Available online 6 April 2018
Source:Brain Stimulation
Author(s): Ruth Alcalá-Lozano, Eduardo A. Garza-Villarreal




https://ift.tt/2IAGQv8

Opposite effects of lateralised transcranial alpha versus gamma stimulation on auditory spatial attention

Publication date: Available online 6 April 2018
Source:Brain Stimulation
Author(s): Malte Wöstmann, Johannes Vosskuhl, Jonas Obleser, Christoph S. Herrmann
BackgroundSpatial attention relatively increases the power of neural 10-Hz alpha oscillations in the hemisphere ipsilateral to attention, and decreases alpha power in the contralateral hemisphere. For gamma oscillations (>40 Hz), the opposite effect has been observed. The functional roles of lateralised oscillations for attention are currently unclear.HypothesisIf lateralised oscillations are functionally relevant for attention, transcranial stimulation of alpha versus gamma oscillations in one hemisphere should differentially modulate the accuracy of spatial attention to the ipsi-versus contralateral side.Methods20 human participants performed a dichotic listening task under continuous transcranial alternating current stimulation (tACS, vs sham) at alpha (10 Hz) or gamma (47 Hz) frequency. On each trial, participants attended to four spoken numbers on the left or right ear, while ignoring numbers on the other ear. In order to stimulate a left temporo-parietal cortex region, which is known to show marked modulations of alpha power during auditory spatial attention, tACS (1 mA peak-to-peak amplitude) was applied at electrode positions TP7 and FC5 over the left hemisphere.ResultsAs predicted, unihemispheric alpha-tACS relatively decreased the recall of targets contralateral to stimulation, but increased recall of ipsilateral targets. Importantly, this spatial pattern of results was reversed for gamma-tACS.ConclusionsResults provide a proof of concept that transcranially stimulated oscillations can enhance spatial attention and facilitate attentional selection of speech. Furthermore, opposite effects of alpha versus gamma stimulation support the view that states of high alpha are incommensurate with active neural processing as reflected by states of high gamma.



https://ift.tt/2qc7EeL

Transcutaneous nerve stimulation via the tragus: are we stimulating the vagus nerve?

Publication date: Available online 5 April 2018
Source:Brain Stimulation
Author(s): Andreas M. Burger, Bart Verkuil




https://ift.tt/2EqLzgL

Short trains of transcutaneous auricular vagus nerve stimulation (taVNS) have parameter-specific effects on heart rate

Publication date: Available online 6 April 2018
Source:Brain Stimulation
Author(s): Bashar W. Badran, Oliver J. Mithoefer, Caroline E. Summer, Nicholas T. LaBate, Chloe E. Glusman, Alan W. Badran, William H. DeVries, Philipp M. Summers, Christopher W. Austelle, Lisa M. McTeague, Jeffrey J. Borckardt, Mark S. George
BackgroundOptimal parameters of transcutaneous auricular vagus nerve stimulation (taVNS) are still undetermined. Given the vagus nerve's role in regulating heart rate (HR), it is important to determine safety and HR effects of various taVNS parameters.ObjectiveWe conducted two sequential trials to systematically test the effects of various taVNS parameters on HR.Methods15 healthy individuals participated in the initial two-visit, crossover exploratory trial, receiving either tragus (active) or earlobe (control) stimulation each visit. Nine stimulation blocks of varying parameters (pulse width: 100 μs, 200 μs, 500 μs; frequency: 1 Hz, 10 Hz, 25 Hz) were administered each visit. HR was recorded and analyzed for stimulation-induced changes. Using similar methods and the two best parameters from trial 1 (500μs 10 Hz and 500μs 25 Hz), 20 healthy individuals then participated in a follow-up confirmatory study.ResultsTrial 1- There was no overall effect of the nine conditions on HR during stimulation. However multivariate analysis revealed two parameters that significantly decreased HR during active stimulation compared to control (500μs 10 Hz and 500μs 25 Hz; p < 0.01). Additionally, active taVNS significantly attenuated overall sympathetic HR rebound (post-stimulation) compared to control (p < 0.001). Trial 2-For these two conditions, active taVNS significantly decreased HR compared to control (p = 0.02), with the strongest effects at 500μs 10 Hz (p = 0.032).ConclusionThese studies suggest that 60s blocks of tragus stimulation are safe, and some specific parameters modulate HR. Of the nine parameters studied, 500μs 10 Hz induced the greatest HR effects.



https://ift.tt/2Er4qs9

Transcranial direct current stimulation improves long-term memory deficits in an animal model of attention-deficit/hyperactivity disorder and modulates oxidative and inflammatory parameters

Publication date: Available online 5 April 2018
Source:Brain Stimulation
Author(s): Douglas Teixeira Leffa, Bruna Bellaver, Artur Alban Salvi, Carla de Oliveira, Wolnei Caumo, Eugenio Horacio Grevet, Felipe Fregni, André Quincozes-Santos, Luis Augusto Rohde, Iraci L.S. Torres
BackgroundTranscranial direct current stimulation (tDCS) is a technique that modulates neuronal activity and has been proposed as a potential therapeutic tool for attention-deficit/hyperactivity disorder (ADHD) symptoms. Although pilot studies have shown evidence of efficacy, its mechanism of action remains unclear.Objective/HypothesisWe evaluated the effects of tDCS on behavioral (working and long-term memory) and neurochemical (oxidative and inflammatory parameters) outcomes related to ADHD pathophysiology. We used the most widely accepted animal model of ADHD: spontaneously hypertensive rats (SHR). The selected behavioral outcomes have been shown to be altered in both ADHD patients and animal models, and were chosen for their relation to the proposed mechanistic action of tDCS.MethodsAdult male SHR and their control, the Wistar Kyoto rats (WKY), were subjected to 20 min of bicephalic tDCS or sham stimulation for 8 consecutive days. Working memory, long-term memory, and neurochemical outcomes were evaluated.ResultsTDCS improved long-term memory deficits presented by the SHR. No change in working memory performance was observed. In the hippocampus, tDCS increased both the production of reactive oxygen species in SHR and the levels of the antioxidant molecule glutathione in both strains. TDCS also modulated inflammatory response in the brains of WKY by downregulating pro-inflammatory cytokines.ConclusionTDCS had significant effects that were specific for strain, type of behavioral and neurochemical outcomes. The long-term memory improvement in the SHR may point to a possible therapeutic role of tDCS in ADHD that does not seem to be mediated by inflammatory markers. Additionally, the anti-inflammatory effects observed in the brain of WKY after tDCS needs to be further explored.



https://ift.tt/2qaCDYi

A case of extensive acquired progressive lymphangioma

Pediatric Dermatology, EarlyView.


https://ift.tt/2Hi9z8Y

Occult dysraphism presenting with acro‐osteolysis

Pediatric Dermatology, EarlyView.


https://ift.tt/2Es0Uxm

Compound heterozygous mutations in desmoplakin associated with skin fragility, follicular hyperkeratosis, alopecia, and nail dystrophy

Pediatric Dermatology, EarlyView.


https://ift.tt/2Hi9qSY

Evidence‐based dosing of maintenance subcutaneous immunotherapy: a contemporary review of state‐of‐the‐art practice

International Forum of Allergy &Rhinology, EarlyView.


https://ift.tt/2qdWMwP

Better kitchens and toilets: both needed for better health

Abstract

Both poor water, sanitation, hygiene (WaSH) and household air pollution (HAP) adversely affect the health of millions of people each year around the globe and specifically in developing countries. The objective of current work is to highlight the importance of HAP in parallel to WaSH for decision making to achieve better health specially in developing countries. There are examples, where developing countries are strengthening efforts to tackle the issue of poor water and sanitation such as 'Clean India Mission' was recently launched by the Government of India. However, there is lack of actions to address the issue related to HAP—to extend the coverage of clean fuel, efficient stoves and ventilated kitchens to the deprived population under the 'Clean India Mission'. Most of the rural household and urban slums in developing countries have only a single room, where people cook and sleep. This leads them to exposure to toxic HAP, which can be minimized by developing country specific indoor air quality guidelines and action framework. Hence, there should be policies to provide them not only the subsidy for clean fuel but also to build properly ventilated kitchens along with the promotion of clean toilets and water supplies. There is a need to strengthen global efforts, to jointly address the challenges associated with the risks related to WaSH and HAP in order to efficiently reduce the global burden of disease. Further, this will also help to timely attain the sustainable development goals for better health and environment.

https://ift.tt/2GEiog5

Increased associated effects of topography and litter and soil nutrients on soil enzyme activities and microbial biomass along vegetation successions in karst ecosystem, southwestern China

Abstract

Studying the influence of topography and litter and soil nutrients on soil enzymes and microbial biomass is important to the understanding of soil nutrient transformation and cycling, but these relationships in heterogeneous soils of karst ecosystem remains poorly understood. We determined environment factors influencing the urease (URS) and alkaline phosphatase (ALP) activity and microbial biomass C and N (MBC and MBN) with advancing vegetation succession. The results showed that ALP increased but URS decreased with the advancing vegetation succession. The MBC and MBN were highest in shrubland, but both were lowest in grassland. The URS was positively correlated with the surface cover of rock outcrops (SRO) but negatively correlated with litter N, and soil available N and pH. Conversely, ALP was positively correlated with litter N, soil organic carbon (SOC), and soil available N and pH, but negatively correlated with soil total N. The MBC was positively related to litter quantities and SOC but negatively related to soil pH; the MBN was positively related to slope gradient (SLG), SOC, and soil total P and available P. Additionally, the trends of the index URS/MBN were grassland > secondary forest > shrubland > primary forest, but the index ALP/MBN increased with advancing vegetation succession. It indicated that soil microorganism mainly exudate extracellular URS and ALP to soils. We also found the interactions of topography (SLG and SRO), litter (nutrients and quantity), and soil (nutrients and pH) explained 42.00, 87.00, and 66.00% of the variations in URS, ALP, and microbial biomass, respectively. Path analysis showed that the topography had a directly positive effect on litter nutrients and quantities, but not on soil nutrients; the litter nutrients and quantities had direct positive effect on soil nutrients, which had direct effect on soil enzymes and microbial biomass; the relationships (R²) between the independent variable and enzymes activities and microbial biomass increased with advancing successions. Thus, it suggested that high SLG and SRO are good for collecting litters back to soils and then the topography, litter, and soil factors increased its controlling effect on soil enzymes activities and microbial biomass with advancing successions in karst ecosystem.

https://ift.tt/2qdsY2p

Immunohistochemistry in Diagnostic Parathyroid Pathology

Abstract

Pathologists are usually readily able to diagnose parathyroid tissues and diseases, particularly when they have knowledge of the clinical information, laboratory findings, and radiographic imaging studies. However, the identification of parathyroid tissue or lesions can be difficult in small biopsies, ectopic locations, supranumerary glands, and in some oxyphil/oncocytic lesions. Widely available immunohistochemical studies such as chromogranin-A, synaptophysin, keratin, parathyroid hormone, thyroglobulin, and thyroid transcription factor-1 can help in difficult cases. One of the most difficult diagnostic aspects faced by the pathologist in evaluating parathyroid is distinguishing between parathyroid adenoma, particularly atypical adenoma, and parathyroid carcinoma. Many markers have and continue to be evaluated for diagnostic utility, and are even beginning to be studied for prognostic utility. Single immunohistochemical markers such as parafibromin and Ki-67 are among the most studied and most utilized, but many additional markers have and continue to be evaluated such as galectin-3, PGP9.5, Rb, bcl2, p27, hTERT, mdm2, and APC. Although not widely available in many laboratories, a panel of immunohistochemical markers may prove most useful as an adjunct in the evaluation of challenging parathyroid tumors.

https://ift.tt/2GIqwIr

Indoor/outdoor relationships, sources and cancer risk assessment of NPAHs and OPAHs in PM2.5 at urban and suburban hotels in Jinan, China

Publication date: June 2018
Source:Atmospheric Environment, Volume 182
Author(s): Yanyan Li, Lingxiao Yang, Xiangfeng Chen, Pan Jiang, Ying Gao, Junmei Zhang, Hao Yu, Wenxing Wang
Paired indoor and outdoor measurements of 16 NPAHs and 5 OPAHs in PM2.5 were conducted at urban and suburban sites during January 2016 in Jinan, China. The concentrations of both indoor and outdoor NPAHs and OPAHs were higher at the urban site compared with the suburban site. 9N-ANT (16–42%), 2+3N-FLA (15–51%), 2N-PYR (6–20%), and 1N-PYR (4–6%) were the dominant NPAHs at all sites, and 9-FO (61–81%) was the most abundant OPAHs. Solid fuel combustion, motor vehicle exhausts, and secondary generation were the main sources of the PAH derivatives in this study area. The I/O ratios of 90% of NPAHs and OPAHs at the first urban indoor site (abbreviated as URI¹, Green Tree Inn) and the suburban indoor site (abbreviated as SUI, the Seven Star Hotel) were <1.00 indicating that many of the compounds measured indoors originated from outdoor sources. At the second urban indoor site (abbreviated as URI², Shandong University Hotel), the I/O ratios of 2- and 3-ring NPAHs and OPAHs were >1.00, which was likely due to cooking activities occurring near the measurement site. Measurements of outdoor 2+3N-FLA/1N-PYR revealed mainly primary emission at the urban site and secondary sources at the suburban site, the average ratios were 3.76 and 12.22, respectively. The average ratio of 2+3N-FLA/2N-PYR at all sites was 3.3, indicating that the OH-initiated reaction was the dominant secondary formation pathway. Nighttime ratios of 2+3N-FLA/1N-PYR were significantly higher than the daytime ratios at all sites. The difference was especially pronounced during heavily polluted conditions at the suburban site, which suggests that heavy pollution and nighttime conditions promote secondary production. Additionally, the cancer risk was highest in urban outdoor (abbreviated as URO) when the population expose to the level as the outdoor air in the urban. The risk suggested that adults may be at a higher cancer risk.



https://ift.tt/2qe74fH

Analysis of spatial-temporal heterogeneity in remotely sensed aerosol properties observed during 2005–2015 over three countries along the Gulf of Guinea Coast in Southern West Africa

Publication date: June 2018
Source:Atmospheric Environment, Volume 182
Author(s): Mangamana Aklesso, K. Raghavendra Kumar, Lingbing Bu, Richard Boiyo
In the present study, the spatial-temporal distribution and estimation of trends of different aerosol optical properties, and related impact factors were investigated over three countries: Ghana, Togo, and Benin along the Gulf of Guinea Coast in Southern West Africa (SWA). For this purpose, long-term satellite derived aerosol optical properties (aerosol optical depth at 550 nm; AOD550, Ångström exponent at 470–660 nm; AE470-660, and absorption aerosol index; AAI) retrieved from the Moderate-resolution Imaging Spectroradiometer (MODIS) and Ozone Monitoring Instrument (OMI) during January 2005–December 2015 were utilized. The annual mean spatial distribution of AOD550 was found to be high (>0.55) over the southern coastal area, moderate-to-high (0.35–0.55) over the central, and low (<0.35) over northern parts of the study domain. The seasonal mean variations showed high (low) values of AOD550 and AAI during the Harmattan or dry (wet) season. Whereas, low (high) AE470-660 values were characterized during the Harmattan (wet) season. Linear trend analysis revealed a decreasing trend in AOD550 and AAI, and increasing trend in AE470-660. Further, an investigation on the potential drivers to AOD distribution over the SWA revealed that precipitation, NDVI, and terrain were negatively correlated with AOD. Finally, the HYSPLIT derived back trajectory analyses revealed diverse transport pathways originated from the North Atlantic Ocean, Sahara Desert, and Nigeria along with locally generated aerosols.

Graphical abstract

https://ift.tt/2GEB4MT

Techno-economic and environmental assessment of biogas production from banana peel ( Musa paradisiaca ) in a biorefinery concept

Abstract

Two scenarios for the biogas production using Banana Peel as raw material were evaluated. The first scenario involves the stand-alone production of biogas and the second scenario includes the biogas production together with other products under biorefinery concept. In both scenarios, the influence of the production scale on the process economy was assessed and feasibility limits were defined. For this purpose, the mass and energy balances were established using the software Aspen Plus along with kinetic models reported in the literature. The economic and environmental analysis of the process was performed considering Colombian economic conditions. As a result, it was found that different process scales showed great potential for biogas production. Thus, plants with greater capacity have a greater economic benefit than those with lower capacity. However, this benefit leads to high-energy consumption and greater environmental impact.

https://ift.tt/2GIhak0

Assessment of toxicity of heavy metal-contaminated soils toward Collembola in the paddy fields supported by laboratory tests

Abstract

Effects on soil Collembola of Cu, Zn, Pb, and Cd pollution from Cu smelters over 40 years were investigated in paddy fields from an area of Eastern China. We compared the field effects to those observed in single-species laboratory tests employing the hemiedaphic collembolan Folsomia candida and the epedaphic Sinella curviseta obtained from laboratory cultures and exposed to field-collected polluted soil. The results indicated that different collembolan species responded differently to the pollution in the fields and could be divided into sensitive, indifferent, and tolerant types accordingly. The abundance of sensitive species decreased as the pollution increased, but this was not the same for indifferent and tolerant species. The dominant species changed from sensitive to tolerant species as the pollution increased. The reproduction of F. candida and S. curviseta was most sensitive to the contaminated soil compared to growth and survival; the sensitivity of the two species was similar. The growth was more sensitive than the survival for F. candida but not for S. curviseta. The growth and survival of F. candida were much more sensitive than those of S. curviseta. Sensitivity of field populations of F. candida (EC₁₀ 31 [15–46]) and hemiedaphic species Folsomia quadrioculata (EC₁₀ 52 [0.7–102]) were comparable with sensitivity of the reproduction of F. candida in the single-species tests (EC₁₀ 21 [14–27]), suggesting that single-species test based on laboratory cultures and field soil could be used to link laboratory and field data and then reflect the field situation. S. curviseta could be used as an epedaphic species in single-species tests and F. quadrioculata as an indicator species for assessment of field effect.

https://ift.tt/2qdQeO5

Figs, pollinators, and parasites: A longitudinal study of the effects of nematode infection on fig wasp fitness

Publication date: Available online 6 April 2018
Source:Acta Oecologica
Author(s): Justin Van Goor, Finn Piatscheck, Derek D. Houston, John D. Nason
Mutualisms are interactions between two species in which the fitnesses of both symbionts benefit from the relationship. Although examples of mutualism are ubiquitous in nature, the ecology, evolution, and stability of mutualism has rarely been studied in the broader, multi-species community context in which they occur. The pollination mutualism between figs and fig wasps provides an excellent model system for investigating interactions between obligate mutualists and antagonists. Compared to the community of non-pollinating fig wasps that develop within fig inflorescences at the expense of fig seeds and pollinators, consequences of interactions between female pollinating wasps and their host-specialist nematode parasites is much less well understood. Here we focus on a tri-partite system comprised of a fig (Ficus petiolaris), pollinating wasp (Pegoscapus sp.), and nematode (Parasitodiplogaster sp.), investigating geographical variation in the incidence of attack and mechanisms through which nematodes may limit the fitness of their wasp hosts at successive life history stages. Observational data reveals that nematodes are ubiquitous across their host range in Baja California, Mexico; that the incidence of nematode infection varies across seasons within- and between locations, and that infected pollinators are sometimes associated with fitness declines through reduced offspring production. We find that moderate levels of infection (1–9 juvenile nematodes per host) are well tolerated by pollinator wasps whereas higher infection levels (≥10 nematodes per host) are correlated with a significant reduction in wasp lifespan and dispersal success. This overexploitation, however, is estimated to occur in only 2.8% of wasps in each generation. The result that nematode infection appears to be largely benign – and the unexpected finding that nematodes frequently infect non-pollinating wasps – highlight gaps in our knowledge of pollinator-Parasitodiplogaster interactions and suggest previously unappreciated ways in which this nematode may influence fig and pollinator fitness, mutualism persistence, and non-pollinator community dynamics.



https://ift.tt/2qgAkCC

Detecting the elusive cost of parasites on fig seed production

Publication date: Available online 6 April 2018
Source:Acta Oecologica
Author(s): Simon T. Segar, Ani Mardiastuti, Philip M. Wheeler, James M. Cook
Mutualisms provide essential ecosystem functions such as pollination and contribute considerably to global biodiversity. However, they are also exploited by parasites that remove resources and thus impose costs on one or both of the mutualistic partners. The fig/pollinator interaction is a classic obligate mutualism; it is pantropical and involves >750 Ficus species and their host-specific pollinating wasps (family Agaonidae). Figs also host parasites of the mutualism that should consume pollinators or seeds, depending on their larval ecology. We collected data from a large crop of figs on Ficus glandifera var. brachysyce in a Sulawesi rainforest with an unusually high number of Eukoebelea sp. parasites. We found that these parasites have a significant negative correlation with fig seed production as well as with pollinator offspring production. Eukoebelea wasps form the basal genus in subfamily Sycophaginae (Chalcidoidea) and their larval biology is considered unknown. Our analysis suggests that they feed as flower gallers and impose direct costs on the fig tree, but a strategy including the consumption of pollinator larvae cannot be ruled out. We also present baseline data on the composition of the fig wasp community associated with F. glandifera var brachysyce and light trap catch data.



https://ift.tt/2GFoXyO

Who Are the Noisiest Neighbors in the Hood? Using Error Analyses to Study the Acquisition of Letter-Position Processing.

Author: Marinus, Eva; Kezilas, Yvette; Kohnen, Saskia; Robidoux, Serje; Castles, Anne

DOI: 10.1037/xlm0000524

Publication Date: POST AUTHOR CORRECTIONS, 5 April 2018

https://ift.tt/2GHjEze

Predictability and Parafoveal Preview Effects in the Developing Reader: Evidence From Eye Movements.

Author: Johnson, Rebecca L.; Oehrlein, Elizabeth C.; Roche, William L.

DOI: 10.1037/xhp0000506

Publication Date: POST AUTHOR CORRECTIONS, 5 April 2018

https://ift.tt/2GFHyGV

Visual Search With Varying Versus Consistent Attentional Templates: Effects on Target Template Establishment, Comparison, and Guidance.

Author: Goldstein, Rebecca R.; Beck, Melissa R.

DOI: 10.1037/xhp0000520

Publication Date: POST AUTHOR CORRECTIONS, 5 April 2018

https://ift.tt/2qa6EHW

New Visions and Current Evidence for Safety in Anesthesia

No abstract available

https://ift.tt/2qbiaCO

American Society for Enhanced Recovery: Advancing Enhanced Recovery and Perioperative Medicine

As the population ages, the increasing surgical volume and complexity of care are expected to place additional care delivery burdens in the perioperative setting. In this age of integrated multidisciplinary care of the surgical patients, there is increasing recognition that an evidence-based perioperative pathway is associated with the optimal outcomes. These pathways, collectively referred to as Enhanced Recovery Pathways, have resulted in shortened length of hospital stay, reduced complications, and variance in outcomes, as well as earlier return to baseline activities. The American Society for Enhanced Recovery (ASER) is a multispecialty, nonprofit international organization, dedicated to the practice of enhanced recovery in perioperative patients through education and research. Perioperative Quality Initiatives were formed whose intent is to organize a series of consensus conferences on topics of interest related to perioperative medicine. The journal affiliation between American Society for Enhanced Recovery and Anesthesia& Analgesia will enable these evidence-based practices to be disseminated widely and swiftly to the practicing perioperative health care professionals so they can be adopted to improve the quality of perioperative surgical care. Accepted for publication March 12, 2018. Funding: None. Conflicts of Interest: See Disclosures at the end of the article. Reprints will not be available from the authors. Address correspondence to Tong J. Gan, MD, MBA, MHS, FRCA, Department of Anesthesiology, Stony Brook University, HSC Level 4, Rm 060, Stony Brook, NY 11794. Address e-mail to tong.gan@stonybrookmedicine.edu. © 2018 International Anesthesia Research Society

https://ift.tt/2uRHhj3

Dezocine Alleviates Morphine-Induced Dependence in Rats

BACKGROUND: Opioid dependence is a major public health issue without optimal therapeutics. This study investigates the potential therapeutic effect of dezocine, a nonaddictive opioid, in opioid dependence in rat models. METHODS: Dezocine was administered intraperitoneally to a morphine-dependent rat model to investigate its effect on withdrawal and conditioned place preference (CPP). Effect of dezocine on morphine withdrawal syndrome and CPP was analyzed using 2-way analysis of variance (ANOVA) followed by Tukey's post hoc test. Buprenorphine and vehicle solution containing 20% (v/v) dimethyl sulfoxide were used for positive and negative control, respectively. The astrocytes activation in nucleus accumbens was assessed by immunofluorescence assay of glial fibrillary acidic protein. Effect of dezocine and buprenorphine on the internalization of κ opioid receptor (KOR) was investigated using Neuro2A expressing KOR fused to red fluorescent protein tdTomato (KOR-tdT). Buprenorphine and dezocine were screened against 44 G-protein–coupled receptors, ion channels, and transporter proteins using radioligand-binding assay to compare the molecular targets. RESULTS: The mean withdrawal score was reduced in rats treated with 1.25 mg·kg−1 dezocine compared to vehicle-treated control animals starting from the day 1 (mean difference: 7.8; 95% confidence interval [CI], 6.35–9.25; P

https://ift.tt/2JsGb02

Case Studies in Adult Intensive Care Medicine

No abstract available

https://ift.tt/2uQZFs2

Lack of Evidence for Ceiling Effect for Buprenorphine Analgesia in Humans

No abstract available

https://ift.tt/2JsG6JM

Diagnostic Accuracy of Point-of-Care Gastric Ultrasound

BACKGROUND: Pulmonary aspiration of gastric contents is associated with significant perioperative morbidity and mortality. Previous studies have investigated the validity, reliability, and possible clinical impact of gastric ultrasound for the assessment of gastric content at the bedside. In the present study, we examined the accuracy (evaluated as sensitivity, specificity, and likelihood ratios) of point-of-care gastric ultrasound to detect a "full stomach" in a simulated scenario of clinical equipoise. METHODS: After a minimum fasting period of 8 hours, 40 healthy volunteers were randomized in a 1:1 ratio to either remain fasted or ingest a standardized quantity of clear fluid or solid. Each subject was randomized twice on 2 independent study sessions at least 24 hours apart. A gastric ultrasound examination was performed by a blinded sonographer following a standardized scanning protocol. Using a combination of qualitative and quantitative findings, the result was summarized in a dichotomous manner as positive (any solid or >1.5 mL/kg of clear fluid) or negative (no solid and ≤1.5 mL/kg of clear fluid) for full stomach. RESULTS: Data from 80 study sessions were analyzed. In this simulated clinical scenario with a pretest probability of 50%, point-of-care gastric ultrasound had a sensitivity of 1.0 (95% confidence interval [CI], 0.925–1.0), a specificity of 0.975 (95% CI, 0.95–1.0), a positive likelihood ratio of 40.0 (95% CI, 10.33–∞), a negative likelihood ratio of 0 (95% CI, 0–0.072), a positive predictive value of 0.976 (95% CI, 0.878–1.0), and a negative predictive value of 1.0 (95% CI, 0.92–1.0). CONCLUSIONS: Our results suggest that bedside gastric ultrasound is highly sensitive and specific to detect or rule out a full stomach in clinical scenarios in which the presence of gastric content is uncertain. Accepted for publication February 27, 2018. Funding: This study was supported by a peer-reviewed grant from Physician Services Incorporated, Ontario, Canada. Conflicts of Interest: See Disclosures at the end of the article. Trial Registry Number: Registration ID: NCT02588495. Reprints will not be available from the authors. Address correspondence to Anahi Perlas, MD, FRCPC, Department of Anesthesia and Pain Management, Toronto Western Hospital, University Health Network, Department of Anesthesia, University of Toronto, 399 Bathurst St, McLaughlin Pavilion 2–405, Toronto, ON M5T 2S8, Canada. Address e-mail to anahi.perlas@uhn.ca. © 2018 International Anesthesia Research Society

https://ift.tt/2qbEFrq

In Response

No abstract available

https://ift.tt/2uRBfPd

Reduced Ketobemidone Usage in Quadratus Lumborum Block Patients After Cesarean Delivery: Clinical Pharmacology Views

No abstract available

https://ift.tt/2JrNiWM

Profound Intraoperative Hypotension Associated With Transfusion via the Belmont Fluid Management System

This retrospective observational case series conducted at 2 large academic centers over a 4-year period consists of 15 cases of profound hypotension in surgical patients immediately after initiation of the Belmont Fluid Management System for rapid transfusion of blood products. Halting the infusion and administering vasoactive agents led to resolution of hypotension. Repeat transfusion with the Belmont system resulted in repeat hypotension unless counteracted with vasopressors. No etiology was elucidated. This represents the largest documented association of acute hypotensive transfusion reaction with any rapid infusion system in surgical patients. Accepted for publication February 1, 2018. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Joanna Miller, MD, Mount Sinai Hospital, 1 Gustave Levy Pl, New York, NY 10129. Address e-mail to joanna.miller@mountsinai.org. © 2018 International Anesthesia Research Society

https://ift.tt/2ErII71

Flupirtine, an Effective Analgesic, but Hepatotoxicity Should Limit Its Use

No abstract available

https://ift.tt/2qbEwnS

Injectable hyaluronic acid based microrods provide local micromechanical and biochemical cues to attenuate cardiac fibrosis after myocardial infarction

Publication date: July 2018
Source:Biomaterials, Volume 169
Author(s): Long V. Le, Priya Mohindra, Qizhi Fang, Richard E. Sievers, Michael A. Mkrtschjan, Christopher Solis, Conrad W. Safranek, Brenda Russell, Randall J. Lee, Tejal A. Desai
Repairing cardiac tissue after myocardial infarction (MI) is one of the most challenging goals in tissue engineering. Following ischemic injury, significant matrix remodeling and the formation of avascular scar tissue significantly impairs cell engraftment and survival in the damaged myocardium. This limits the efficacy of cell replacement therapies, demanding strategies that reduce pathological scarring to create a suitable microenvironment for healthy tissue regeneration. Here, we demonstrate the successful fabrication of discrete hyaluronic acid (HA)-based microrods to provide local biochemical and biomechanical signals to reprogram cells and attenuate cardiac fibrosis. HA microrods were produced in a range of physiological stiffness and shown to degrade in the presence of hyaluronidase. Additionally, we show that fibroblasts interact with these microrods in vitro, leading to significant changes in proliferation, collagen expression and other markers of a myofibroblast phenotype. When injected into the myocardium of an adult rat MI model, HA microrods prevented left ventricular wall thinning and improved cardiac function at 6 weeks post infarct.



https://ift.tt/2GE1U7H

Nanoparticle co-delivery of wortmannin and cisplatin synergistically enhances chemoradiotherapy and reverses platinum resistance in ovarian cancer models

Publication date: July 2018
Source:Biomaterials, Volume 169
Author(s): Maofan Zhang, C. Tilden Hagan, Yuangzeng Min, Hayley Foley, Xi Tian, Feifei Yang, Yu Mi, Kin Man Au, Yusra Medik, Kyle Roche, Kyle Wagner, Zachary Rodgers, Andrew Z. Wang
Most ovarian cancer patients respond well to initial platinum-based chemotherapy. However, within a year, many patients experience disease recurrence with a platinum resistant phenotype that responds poorly to second line chemotherapies. As a result, new strategies to address platinum resistant ovarian cancer (PROC) are needed. Herein, we report that NP co-delivery of cisplatin (CP) and wortmannin (Wtmn), a DNA repair inhibitor, synergistically enhances chemoradiotherapy (CRT) and reverses CP resistance in PROC. We encapsulated this regimen in FDA approved poly(lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA-PEG) NPs to reduce systemic side effects, enhance cellular CP uptake, improve Wtmn stability, and increase therapeutic efficacy. Treatment of platinum-sensitive ovarian cancer (PSOC) and PROC murine models with these dual-drug loaded NPs (DNPs) significantly reduced tumor burden versus treatment with combinations of free drugs or single-drug loaded NPs (SNPs). These results support further investigation of this NP-based, synergistic drug regimen as a means to combat PROC in the clinic.



https://ift.tt/2q90WVU

Second near-infrared emissive lanthanide complex for fast renal-clearable in vivo optical bioimaging and tiny tumor detection

Publication date: July 2018
Source:Biomaterials, Volume 169
Author(s): Youbin Li, Xiaolong Li, Zhenluan Xue, Mingyang Jiang, Songjun Zeng, Jianhua Hao
In vivo optical imaging by using a new imaging window located at short-wavelength infrared region (1000–1700 nm, named as NIR II) presents an unprecedented improvement in imaging sensitivity and spatial resolution over the traditional visible and near-infrared light. However, the most developed NIR II-emitters are hardly excreted from live animals, leading to unknown long-term toxicity concerns, which hinder the widespread applications of this advanced imaging technology. Here, we developed a new generation molecular NIR II-emitting probe based on Nd-diethylene triamine pentacetate acid (DTPA) complex. The designed molecular Nd-DTPA probe with bright narrow band emission at 1330 nm is successfully used for highly sensitive in vivo NIR II bioimaging with rapid renal excretion, high biocompatibility and optical-guided tiny tumor (down to ∼3 mm) detection for the first time. Moreover, the Nd-DPTA complex also holds great promise as an X-ray contrast agent. These findings open up the possibility for designing a new generation of multi-modal small molecular probe for early tumor diagnosis and favor the clinic translation of the advanced NIR II imaging method.



https://ift.tt/2GE1LRH

Ultra-thin, aligned, free-standing nanofiber membranes to recapitulate multi-layered blood vessel/tissue interface for leukocyte infiltration study

Publication date: July 2018
Source:Biomaterials, Volume 169
Author(s): Sang Min Park, HyeMi Kim, Kwang Hoon Song, Seongsu Eom, HyoungJun Park, Junsang Doh, Dong Sung Kim
Leukocyte infiltration plays critical roles in tissue inflammation for pathogen clearance and tumor eradication. This process is regulated by complex microenvironments in blood vessels, including inflamed endothelium, blood flow, and perivascular components. The role of perivascular components in leukocyte infiltration has not been systematically investigated until recently mostly due to lack of technology. In this work, we developed a three-dimensional multi-layered blood vessel/tissue model with a nanofiber membrane, enabling real-time visualization of dynamic leukocyte infiltration and subsequent interaction with perivascular macrophages. We directly fabricated a highly aligned, free-standing nanofiber membrane with an ultra-thin thickness of ∼1 μm in microfluidic systems. Coating the nanofiber membrane with matrigel showed synergetic topographical and biochemical effects on the reconstitution of a well-aligned endothelial monolayer on the membrane. Our 3D multi-layered blood vessel/tissue model will offer a powerful and versatile tool for investigating the mechanism of leukocyte tissue infiltration and subsequent immune responses.



https://ift.tt/2qdF8sp

Using Synthetic CT for Partial Brain Radiation Therapy: Impact on Image Guidance

Publication date: Available online 6 April 2018
Source:Practical Radiation Oncology
Author(s): Eric D. Morris, Ryan G. Price, Joshua Kim, Lonni Schultz, M. Salim Siddiqui, Indrin Chetty, Carri Glide-Hurst
PurposeRecent advancements in synthetic computed tomography (synCTs) from MRI data have made MR-only treatment planning feasible in brain, although synCT performance for IGRT is not well understood. This work compares geometric equivalence of digitally reconstructed radiographs (DRRs) from CTs and synCTs for brain cancer patients and quantifies performance for partial brain IGRT.MethodsTen brain cancer patients (12 lesions, 7 post-surgical) underwent MR-SIM and CT-SIM. SynCTs were generated by combining ultra-short echo time, T1, T2, and FLAIR datasets using voxel-based weighted summation. SynCT and CT DRRs were compared using patient-specific thresholding and assessed via overlap index (OI), Dice similarity coefficient (DSC), and Jaccard index (JI). Planar IGRT images for 22 fractions were evaluated to quantify differences between CT-generated DRRs and synCT-generated DRRs in 6 quadrants. Previously validated software was implemented to perform 2D-2D rigid registrations using normalized mutual information (NMI). Absolute (planar image/DRR registration) and relative (differences between synCT and CT DRR registrations) shifts were calculated for each axis and 3D vector difference. 1490 rigid registrations were assessed.ResultsDRR agreements in anterior–posterior and lateral views for OI, DSC, and JI were>0.95. NMI results were equivalent in 75% of quadrants. Rotational registration results were negligible (<0.07°). Statistically significant differences between CT and synCT registrations were observed in 9/18 matched quadrants/axes (p<0.05). The population average absolute shifts were 0.77±0.58mm and 0.76±0.59mm for CT and synCT, respectively for all axes/quadrants. 3D vectors were<2mm in 77.7±10.8% and 76.5±7.2% of CT and synCT registrations, respectively. SynCT DRRs were sensitive in post-surgical cases (vector displacements >2mm in affected quadrants).ConclusionDRR synCT geometry was robust. Although statistically significant differences were observed between CT and synCT registrations, results were not clinically significant. Future work will address synCT generation in post-surgical settings.



https://ift.tt/2GIY89f

Data on the radiometric survey over a kaolinitic terrain in Dahomey Basin, Nigeria

Publication date: June 2018
Source:Data in Brief, Volume 18
Author(s): T.A. Adagunodo, O.S. Hammed, M.R. Usikalu, W.A. Ayara, R. Ravisankar
This article consists the in situ data sets of activity concentrations of radionuclides (K-40, Th-232 and U-238) and gamma radiation dose rates measured about 1 m above a kaolinitic terrain in Ifonyintedo, Dahomey Basin, SW Nigeria. Nineteen (19) data points were randomly occupied at the lower axis of the kaolin field using a hand-held detector known as Super-Spec (RS 125). At each data point, the measurements were taken four times, while their averages and standard deviations were estimated in order to ensure accuracy. The radiometric survey was carried out between December, 2017 and January, 2018. The data sets were processed and analyzed via a descriptive statistics. The data can be explored further by estimating the radiological risks to the miners on the field, and to correlate the activity concentrations of the data with the activity concentrations of the tiles that are produced from the kaolin deposits in Ifonyintedo. Furthermore, the data from this article could be compared with other data acquired over a kaolinitic terrain across the globe.



https://ift.tt/2GIWzrT

“Free or Perforator-Pedicled Propeller Flaps in Lower Extremity Reconstruction: Defining the Coverage Failure”: Response

J reconstr Microsurg
DOI: 10.1055/s-0038-1639601

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Full text

https://ift.tt/2JqDg8n

Sternal Reconstruction with the Omental Flap—Acute and Late Complications, Predictors of Mortality, and Quality of Life

J reconstr Microsurg
DOI: 10.1055/s-0038-1629918

Background The omental flap is a reliable flap for the coverage of sternal defects. However, little is known about the predictors of mortality and the long-term outcome in such patients. Methods We, therefore, performed a retrospective study from 2002 to 2013, including all patients that underwent sternal reconstruction with the omental flap. Results A total of 50 patients was identified and mean follow-up was 3.8 years. Patient data was collected from the charts and 14 patients were available for telephone interviews. The majority of patients suffered from deep sternal wound infections. There was no complete flap loss and an overall success rate was 96%. In-hospital mortality was 14% and overall survival over follow-up was 50%. Significant predictors of mortality were age > 65, American Society of Anesthesiologists' status, defect size, prolonged ventilation, and the need for tracheotomy. Postoperative quality of life was reduced compared with other cohorts, especially with regard to bodily function. Pain was also a major problem for most patients along with herniation. Conclusion The omental flap is a safe option even in patients with severe comorbidities. However, based on the data in this study, we would recommend the omental flap as a reserve option rather than first-line treatment for sternal defects.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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

https://ift.tt/2Iy3y7g

Proximal versus Distal Recipient Vessels in Lower Extremity Reconstruction: A Retrospective Series and Systematic Review

J reconstr Microsurg
DOI: 10.1055/s-0037-1621746

Background Recipient vessels proximal to the zone of injury have traditionally been preferred for lower extremity reconstruction. However, more recent data have shown mixed outcomes when performing anastomoses distal to the zone of injury. We investigated the impact of recipient vessel location on free flap outcomes. Methods Retrospective review (1979–2016); 312 soft tissue free flaps for open tibia fractures met inclusion criteria. Flap characteristics and perioperative outcomes were examined. Systematic review identified articles evaluating anastomosis location and flap outcomes; pooled data analysis was performed. Results More anastomoses were performed proximal to the zone of injury (80.7%) than distal (19.3%). Distal anastomoses were not associated with increased take back rates (19.6%) compared with proximal (23.8%) anastomoses (p = 0.356). Regression analysis comparing proximal and distal anastomoses found no difference in partial flap failures (7.4% vs 11.9%; p = 0.978) or total flap failures (9.3% vs 9.3%; p = 0.815) when controlling for the presence of arterial injury, flap type, and time from injury to coverage. Systematic review yielded 11 articles with 1,245 proximal and 127 distal anastomoses for comparison. Pooled analysis (p = 0.58) and weighted comparative analysis (p = 0.39) found no difference in flap failure rates between proximal and distal groups. Conclusion Our results are congruent with the current lower extremity literature and demonstrate no difference in perioperative complication rates between anastomoses performed proximal or distal to the zone of injury. These findings suggest that anastomotic location choice should be based primarily on recipient vessel quality/flow and ease of access/exposure rather than orientation relative to the zone of injury.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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

https://ift.tt/2JqD5Kf

Urban versus Rural Residency and Allergy Prevalence among Adult Women: Iowa Women's Health Study

The association between residence and allergy has been well studied in children living on a farm; however, studies of this association in late adulthood are lacking.

https://ift.tt/2uQNf3o

Treatment of nevoid hyperkeratosis of the areola and nipple with topical tacalcitol: A case report

Dermatologic Therapy, EarlyView.


https://ift.tt/2ErHN6K

Reconstruction of a buttock defect after excision of inflammatory linear verrucous epidermal nevus

Dermatologic Therapy, EarlyView.


https://ift.tt/2HhChqw

Reconstruction of a buttock defect after excision of inflammatory linear verrucous epidermal nevus

Dermatologic Therapy, EarlyView.


https://ift.tt/2HhChqw

Impact of oncogene panel results on surgical management of cytologically indeterminate thyroid nodules

Head &Neck, EarlyView.


https://ift.tt/2qc5ZVz

Rotationally-invariant mapping of scalar and orientational metrics of neuronal microstructure with diffusion MRI

Publication date: 1 July 2018
Source:NeuroImage, Volume 174
Author(s): Dmitry S. Novikov, Jelle Veraart, Ileana O. Jelescu, Els Fieremans
We develop a general analytical and numerical framework for estimating intra- and extra-neurite water fractions and diffusion coefficients, as well as neurite orientational dispersion, in each imaging voxel. By employing a set of rotational invariants and their expansion in the powers of diffusion weighting, we analytically uncover the nontrivial topology of the parameter estimation landscape, showing that multiple branches of parameters describe the measurement almost equally well, with only one of them corresponding to the biophysical reality. A comprehensive acquisition shows that the branch choice varies across the brain. Our framework reveals hidden degeneracies in MRI parameter estimation for neuronal tissue, provides microstructural and orientational maps in the whole brain without constraints or priors, and connects modern biophysical modeling with clinical MRI.



https://ift.tt/2EqkOZX

Lighting up the brain: genetically encoded fluorescent sensors for imaging neurotransmitters and neuromodulators

Publication date: June 2018
Source:Current Opinion in Neurobiology, Volume 50
Author(s): Huan Wang, Miao Jing, Yulong Li
Measuring the precise dynamics of specific neurotransmitters and neuromodulators in the brain is essential for understanding how information is transmitted and processed. Thanks to the development and optimization of various genetically encoded sensors, we are approaching the stage in which a few key neurotransmitters/neuromodulators can be imaged with high cell specificity and good signal-to-noise ratio. Here, we summarize recent progress regarding these sensors, focusing on their design principles, properties, potential applications, and current limitations. We also highlight the G protein-coupled receptor (GPCR) scaffold as a promising platform that may enable the scalable development of the next generation of sensors, enabling the rapid, sensitive, and specific detection of a large repertoire of neurotransmitters/neuromodulators in vivo at cellular or even subcellular resolution.

Graphical abstract

https://ift.tt/2IACfcB

The Original Social Network: White Matter and Social Cognition

Publication date: Available online 5 April 2018
Source:Trends in Cognitive Sciences
Author(s): Yin Wang, Ingrid R. Olson
Social neuroscience has traditionally focused on the functionality of gray matter regions, ignoring the critical role played by axonal fiber pathways in supporting complex social processes. In this paper, we argue that research on white matter is essential for understanding a range of topics in social neuroscience, such as face processing, theory of mind, empathy, and imitation, as well as clinical disorders defined by aberrant social behavior, such as prosopagnosia, autism, and schizophrenia. We provide practical advice on how best to carry out these studies, which ultimately will substantially deepen our understanding of the neurobiological basis of social behavior.



https://ift.tt/2uUfgHu

Role of Mitochondria-Associated ER Membranes in Calcium Regulation in Cancer-Specific Settings

Publication date: May 2018
Source:Neoplasia, Volume 20, Issue 5
Author(s): Giampaolo Morciano, Saverio Marchi, Claudia Morganti, Luigi Sbano, Mart Bittremieux, Martijn Kerkhofs, Mariangela Corricelli, Alberto Danese, Agnieszka Karkucinska-Wieckowska, Mariusz R. Wieckowski, Geert Bultynck, Carlotta Giorgi, Paolo Pinton
Mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) are highly specialized subcellular compartments that are shaped by ER subdomains juxtaposed to mitochondria but are biochemically distinct from pure ER and pure mitochondria. MAMs are enriched in enzymes involved in lipid synthesis and transport, channels for calcium transfer, and proteins with oncogenic/oncosuppressive functions that modulate cell signaling pathways involved in physiological and pathophysiological processes. The term "cancer" denotes a group of disorders that result from uncontrolled cell growth driven by a mixture of genetic and environmental components. Alterations in MAMs are thought to account for the onset as well as the progression and metastasis of cancer and have been a focus of investigation in recent years. In this review, we present the current state of the art regarding MAM-resident proteins and their relevance, alterations, and deregulating functions in different types of cancer from a cell biology and clinical perspective.



https://ift.tt/2Hghovw

Efficacy of ONC201 in Desmoplastic Small Round Cell Tumor

Publication date: May 2018
Source:Neoplasia, Volume 20, Issue 5
Author(s): Andrea A. Hayes-Jordan, Xiao Ma, Brian A. Menegaz, Salah-Eddine Lamhamedi-Cherradi, Charles V. Kingsley, Jalen A. Benson, Pamela E. Camacho, Joseph A. Ludwig, Cynthia R. Lockworth, Gloria E. Garcia, Suzanne L. Craig
Desmoplastic Small Round Cell Tumor (DSRCT) is a rare sarcoma tumor of adolescence and young adulthood, which harbors a recurrent chromosomal translocation between the Ewing's sarcoma gene (EWSR1) and the Wilms' tumor suppressor gene (WT1). Patients usually develop multiple abdominal tumors with liver and lymph node metastasis developing later. Survival is poor using a multimodal therapy that includes chemotherapy, radiation and surgical resection, new therapies are needed for better management of DSRCT. Triggering cell apoptosis is the scientific rationale of many cancer therapies. Here, we characterized for the first time the expression of pro-apoptotic receptors, tumor necrosis-related apoptosis-inducing ligand receptors (TRAILR1-4) within an established human DSRCT cell line and clinical samples. The molecular induction of TRAIL-mediated apoptosis using agonistic small molecule, ONC201 in vitro cell-based proliferation assay and in vivo novel orthotopic xenograft animal models of DSRCT, was able to inhibit cell proliferation that was associated with caspase activation, and tumor growth, indicating that a cell-based delivery of an apoptosis-inducing factor could be relevant therapeutic agent to control DSRCT.



https://ift.tt/2Eqdq0C

Novel Regulatory Roles of Wnt1 in Infection-Associated Colorectal Cancer

Publication date: May 2018
Source:Neoplasia, Volume 20, Issue 5
Author(s): Jianwei Wang, Rong Lu, Xinghui Fu, Zhou Dan, Yong-Guo Zhang, Xinxia Chang, Qisha Liu, Yinglin Xia, Xingyin Liu, Jun Sun
Salmonella infection is a major public health concern, and colonization in humans can be chronic and increases the risk of cancers. Wnt signaling is a key pathway for intestinal renewal and development, inflammation, and tumorigenesis. In the current study, we report a novel role of Wnt1 in infection and colon cancer using cell culture models, a Salmonella-colitis colon cancer model, and human samples. In contrast to the bacteria-induced increases in Wnt2 and Wnt11, Salmonella colonization significantly reduced the level of Wnt1 in intestinal epithelial cells in vivo and in vitro. The bacterial AvrA protein is known to activate the canonical Wnt pathway. Wnt1 expression level was downregulated by AvrA-expressing Salmonella but stabilized by AvrA-deficient Salmonella in the intestine of Salmonella-colitis mice. In a chronic Salmonella-infected cancer model, the Wnt1 protein level was decreased in the AvrA+ infected group. Thus, we further assessed the functional role of Wnt1 downregulation in the inflammatory response and colorectal cancer (CRC) progression. Moreover, downregulation of Wnt1 by the Crispr-Cas9 method promoted cancer cell invasion and migration. Interestingly, we found that Wnt1 was downregulated in human CRC tissue, and Wnt1 downregulation may be correlated with cancer progression. Our study provides insights into mechanisms by which enteric bacteria regulate Wnt1 expression and potentially contribute to infection-associated colon cancer.



https://ift.tt/2HeO3lp

Redox biosensors in a context of multiparameter imaging

Publication date: Available online 6 April 2018
Source:Free Radical Biology and Medicine
Author(s): Alexander I. Kostyuk, Anastasiya S. Panova, Dmitry S. Bilan, Vsevolod V. Belousov
A wide variety of genetically encoded fluorescent biosensors are available to date. Some of them have already contributed significantly to our understanding of biological processes occurring at cellular and organismal levels. Using such an approach, outstanding success has been achieved in the field of redox biology. The probes allowed researchers to observe, for the first time, the dynamics of important redox parameters in vivo during embryogenesis, aging, the inflammatory response, the pathogenesis of various diseases, and many other processes. Given the differences in the readout and spectra of the probes, they can be used in multiparameter imaging in which several processes are monitored simultaneously in the cell. Intracellular processes form an extensive network of interactions. For example, redox changes are often accompanied by changes in many other biochemical reactions related to cellular metabolism and signaling. Therefore, multiparameter imaging can provide important information concerning the temporal and spatial relationship of various signaling and metabolic processes. In this review, we will describe the main types of genetically encoded biosensors, the most frequently used readout, and their use in multiplexed imaging mode.

Graphical abstract

https://ift.tt/2qaPtpA

Reversal of the hair loss phenotype by modulating the estradiol-ANGPT2 axis in the mouse model of female pattern hair loss

Publication date: Available online 6 April 2018
Source:Journal of Dermatological Science
Author(s): Yujiro Endo, Yuko Obayashi, Tomoji Ono, Tetsushi Serizawa, Michiaki Murakoshi, Manabu Ohyama
BackgroundDespite high demand for a remedy, the treatment options for female pattern hair loss (FPHL) are limited. FPHL is frequent in postmenopausal women. In ovariectomized (OVX) mice, which lack β-estradiol (E2) and manifest hair loss mimicking FPHL, E2 supplementation has been shown to increase hair density. However, the mechanism by which E2 exhibits its biological activity remains elusive.ObjectiveTo identify the downstream targets of E2 in the context of FPHL pathophysiology and discover a potential therapeutic agent for the E2-dependent subtype of FPHL.MethodsHuman dermal papilla cells (hDPCs) were cultured with E2, and a microarray analysis was performed to identify the genes regulated by E2. Using OVX mice, the identified gene product was intradermally administered and then quantitative image analysis of hair density was conducted. In silico analysis to link E2 and the identified gene was performed.ResultsGlobal gene expression and bioinformatics analyses revealed that the genes associated with the angiopoietin-2 (ANGPT2) pathway were upregulated by E2 in hDPCs. ANGPT2 was significantly downregulated in OVX mice than in sham-operated mice (P < 0.01). Importantly, hair density was higher in OVX mice treated with ANGPT2 than in control mice (P < 0.05). In silico analysis showed DNA sequences with high possibility of estrogen receptor binding in the promoter region of ANGPT2.ConclusionThe E2-ANGPT2 axis is present in hair follicles. ANGPT2 provides a strategy for the management of E2-dependent and postmenopausal subsets of FPHL.



https://ift.tt/2uNLfsK

Role of neopterin as a biochemical marker for peripheral neuropathy in pediatric patients with type 1 diabetes: Relation to nerve conduction studies

Publication date: June 2018
Source:International Immunopharmacology, Volume 59
Author(s): Nancy Samir Elbarbary, Eman Abdel Rahman Ismail, Rana Ahmed El-Hilaly, Fatma Salama Ahmed
BackgroundNeopterin, a marker of inflammation and cellular immune response, is elevated in conditions of T-cell or macrophages activation. Diabetic peripheral neuropathy (DPN) is associated with inflammatory/immune processes and therefore, we hypothesized that neopterin could be used as a marker of neuropathy in type 1 diabetes mellitus (T1DM).AimTo measure neopterin levels in children and adolescents with T1DM and assess its possible relation to DPN and nerve conduction studies (NCS).MethodsSixty patients aged ≤18 years and >5 years disease duration were subjected to neurological assessment by neuropathy disability score (NDS) and NCS for median, ulnar, posterior tibial and common peroneal nerves. Mean fasting blood glucose, lipid profile, HbA1c, high sensitivity C-reactive protein (hs-CRP) and serum neopterin levels were assessed. Patients were compared with 30 age- and sex-matched healthy controls.ResultsThe frequency of DPN according to NDS was 40 (66.7%) patients out of 60 while NCS confirmed that only 30 of those 40 patients had this complication (i.e. 50% out of the total studied patients). Neopterin levels were significantly higher in patients with DPN than those without (median [IQR], 53.5 [35–60] nmol/L versus 17 [13−32] nmol/L) and healthy controls (5.0 [3.2–7.0] nmol/L) (p < 0.001). Significant positive correlations were found between neopterin levels and HbA1c (r = 0.560, p = 0.005), serum creatinine (r = 0.376, p = 0.003), total cholesterol (r = 0.405, p = 0.026) and hs-CRP (r = 0.425, p = 0.012) among patients with DPN. Neopterin levels were positively correlated to motor latency of tibial and common peroneal nerves as well as motor and sensory latencies of median and ulnar nerves. Logistic regression analysis revealed that neopterin was a significant independent variable related to DPN (Odds ratio, 2.976). Neopterin cutoff value 32 nmol/L could differentiate patients with and without DPN with 100% sensitivity and 96.7% specificity.ConclusionsNeopterin could be used as an early reliable serum biomarker for DPN in pediatric patients with T1DM.



https://ift.tt/2GEBnTK

Transcriptome analyses reveal FOXA1 dysregulation in mammary and extramammary Paget's disease

Publication date: Available online 6 April 2018
Source:Human Pathology
Author(s): Ruiqin Mai, Songxia Zhou, Shuqin Zhou, Weixiang Zhong, Liangli Hong, Yuanyuan Wang, Shanming Lu, Jikai Pan, Yuansheng Huang, Mingwan Su, Richard Crawford, Youwen Zhou, Guohong Zhang
Paget's disease (PD) is an uncommon intraepithelial adenocarcinoma with unknown pathogenesis. There are two anatomic subtypes: mammary (MPD) and extramammary (EMPD). Little is known about their molecular characteristics. Our objective was to discover novel molecular markers for PD and its subtypes. In the discovery phase, we used transcriptome analyses to uncover the most differentially expressed genes and pathways in EMPD biopsies compared with normal skin. In the validation phase, we performed immunohistochemistry analyses on the most promising marker (FOXA1) and other markers selected from a literature review (GATA3, estrogen receptor [ER], and androgen receptor [AR]) on independent biopsies of MPD (n=86), EMPD (n=59), and normal skin (n=21). Transcriptome analyses revealed 210 genes differentially expressed more than 10-fold between EMPD and normal skin. These genes are involved in mammary and sweat gland development (FOXA1) and immune regulation, as well as epidermal differentiation. Immunohistochemistry staining revealed that FOXA1 was positive in 88% of both MPD and EMPD, whereas GATA3 was positive in 67% of MPD and 77% of EMPD, and ER was positive in 9% of MPD and 19% of EMPD. Finally, AR was positive in 33% of PD and 54% of EMPD. Mammary Paget's disease and EMPD share dysregulation of the glandular developmental regulator gene FOXA1, suggesting similarity in cell-specific transcriptional regulation. Further, FOXA1 may be a useful molecular target for developing PD therapies.



https://ift.tt/2JpJ8hW

Somatic polymerase epsilo mutations as another route leading to loss of DNA MMR protein expression in endometrial carcinoma—reply

Publication date: Available online 6 April 2018
Source:Human Pathology





https://ift.tt/2IBoKcL

Behaviors of active sunbeds users and their knowledge on the potential health risks; results of cross‐sectional study in Poland

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2GCqmX7

Behaviors of active sunbeds users and their knowledge on the potential health risks; results of cross‐sectional study in Poland

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2GCqmX7

Effect of voice therapy on vocal fold polyp treatment

Abstract

Purpose

To investigate the role of voice therapy (VT) and factors that may affect the response to VT in the treatment of vocal fold polyps, especially as a complement to phonosurgery.

Methods

Retrospective review of patients with vocal fold polyp undergoing surgery and/or VT in a tertiary medical center. The demographic data, phoniatric history, videolaryngostroboscopic findings, polyp characteristics, VHI-10 and GRB scores, and voice analysis data were recorded before and after the treatment. The patients were grouped as those who had undergone endolaryngeal microsurgery only (Group S), those who had first received VT then undergone surgery due to inadequate VT outcome (Group VTpS), and those who had only undergone VT with a follow-up plan (Group VT).

Results

Data were reviewed from 211 (108 M, 103 F) patients with a mean age of 41.3 ± 11 years. The improvement in all voice-related variables observed in the S and VTpS groups was significantly greater compared to the VT group despite the degree of improvement achieved in this group. At the end of the treatment period, improvements in G-R-B, VHI-10 and stroboscopy scores were significantly greater in the VTpS group than in the S and VT groups.

Conclusion

Voice therapy can improve voice quality to some extent during the treatment of vocal fold polyps. However, VT alone is unsatisfactory compared to surgery alone. Pre-surgical VT can enhance the ultimate success of treatment. A young age, small polyps, and short duration of dysphonia may increase the possibility of benefiting from VT.

https://ift.tt/2Hg2plu

Molecular markers in well-differentiated thyroid cancer

Abstract

Purpose

Thyroid nodules are of common occurrence in the general population. About a fourth of these nodules are indeterminate on aspiration cytology placing many a patient at risk of unwanted surgery. The purpose of this review is to discuss various molecular markers described to date and place their role in proper perspective. This review covers the fundamental role of the signaling pathways and genetic changes involved in thyroid carcinogenesis. The current literature on the prognostic significance of these markers is also described.

Methods

PubMed was used to search relevant articles. The key terms "thyroid nodules", "thyroid cancer papillary", "carcinoma papillary follicular", "carcinoma papillary", "adenocarcinoma follicular" were searched in MeSH, and "molecular markers", "molecular testing", mutation, BRAF, RAS, RET/PTC, PAX 8, miRNA, NIFTP in title and abstract fields. Multiple combinations were done and a group of experts in the subject from the International Head and Neck Scientific Group extracted the relevant articles and formulated the review.

Results

There has been considerable progress in the understanding of thyroid carcinogenesis and the emergence of numerous molecular markers in the recent years with potential to be used in the diagnostic algorithm of these nodules. However, their precise role in routine clinical practice continues to be a contentious issue. Majority of the studies in this context are retrospective and impact of these mutations is not independent of other prognostic factors making the interpretation difficult.

Conclusion

The prevalence of these mutations in thyroid nodule is high and it is a continuously evolving field. Clinicians should stay informed as recommendation on the use of these markers is expected to evolve.

https://ift.tt/2uQiYSp

New Gene Test Reduces Skin Reactions to Carbamazepine

A new gene variant test to guide treatment decisions led to reductions in the incidence of cutaneous adverse reactions to carbamazepine, a new study shows.
Medscape Medical News

https://ift.tt/2EjVmFj

Gastric Emptying During the Labour

Conditions:   Pregnancy;   Healthy Volunteers;   Parturition
Intervention:   Other: Ultrasound assessment of gastric emptying of a flavoured yoghourt.
Sponsor:   Hospices Civils de Lyon
Not yet recruiting

https://ift.tt/2uN286M

Avelumab With Chemoradiation for Stage II/III Resectable Esophageal Cancer

Condition:   Resectable Esophageal Cancer
Interventions:   Combination Product: Avelumab combined with Chemoradiation;   Drug: Carboplatin;   Drug: Paclitaxel;   Radiation: Radiation
Sponsors:   University of Wisconsin, Madison;   National Cancer Institute (NCI)
Not yet recruiting

https://ift.tt/2HgsmBw

Gastric Emptying During the Labour

Conditions:   Pregnancy;   Healthy Volunteers;   Parturition
Intervention:   Other: Ultrasound assessment of gastric emptying of a flavoured yoghourt.
Sponsor:   Hospices Civils de Lyon
Not yet recruiting

https://ift.tt/2uN286M

Avelumab With Chemoradiation for Stage II/III Resectable Esophageal Cancer

Condition:   Resectable Esophageal Cancer
Interventions:   Combination Product: Avelumab combined with Chemoradiation;   Drug: Carboplatin;   Drug: Paclitaxel;   Radiation: Radiation
Sponsors:   University of Wisconsin, Madison;   National Cancer Institute (NCI)
Not yet recruiting

https://ift.tt/2HgsmBw

Topical timolol for Kaposi sarcoma: An innovation

Australasian Journal of Dermatology, EarlyView.


https://ift.tt/2GCE5NI

Topical timolol for Kaposi sarcoma: An innovation

Australasian Journal of Dermatology, EarlyView.


https://ift.tt/2GCE5NI

Alleged “sonic attack” supported by poor Neuropsychology

Publication date: Available online 5 April 2018
Source:Cortex
Author(s): Sergio Della Sala, Roberto Cubelli




https://ift.tt/2IAxaAP

Cardioprotective effect of β-d-mannuronic acid (M2000) as a novel NSAID on gene expression of oxLDL scavenger receptors in the experimental diabetic model.

Cardioprotective effect of β-d-mannuronic acid (M2000) as a novel NSAID on gene expression of oxLDL scavenger receptors in the experimental diabetic model.

Immunopharmacol Immunotoxicol. 2018 Apr 05;:1-6

Authors: Mortazavi-Jahromi SS, Alizadeh S, Javanbakht MH, Mirshafiey A

Abstract
CONTEXT: The investigations have shown that patients with diabetes have the elevated levels of glucose and oxLDL. These two play an important role in increased expression levels of oxLDL scavenger receptors on the surface of macrophages and endothelial cells that leads to deposition of oxLDL and macrophages in vascular walls.
OBJECTIVE: The present study intends to show the effects of β-d-mannuronic acid (M2000) on the expression profile of ox-LDL scavenger receptors (including SR-A, LOX-1, CD36, and CD68) in an experimental model of diabetes.
MATERIALS AND METHODS: Eighteen Sprague-Dawley rats were randomly divided into three 6-member groups of the healthy control, diabetic control, and treated rats by M2000. Diabetes was induced in rats by intraperitoneal (IP) administration of 60 mg/kg streptozotocin. The treated rats were given daily intraperitoneal injections of M2000 with a dose of 25 mg/kg for 28 days and at the end of the 28th day, their aortas were removed. The qRT-PCR technique was then used to evaluate the expression levels of the proposed gene.
RESULTS: The gene expression levels of the SR-A, LOX-1, CD36, and CD68 significantly declined in the diabetic group that received M2000 compared with untreated diabetic rats.
CONCLUSIONS: The M2000, as a novel NSAID is able to modify by lowering the gene expression levels of SR-A, LOX-1, CD36, and CD68 in treated rats compared to the untreated diabetic group, which may play an important role in preventing the complications that could lead to a cardioprotective efficacy.

PMID: 29619884 [PubMed - as supplied by publisher]

https://ift.tt/2Jn2OmK

Intratympanic Gentamicin for Intractable Ménière's Disease - A Review and Analysis of Audiovestibular Impact.

Related Articles

Intratympanic Gentamicin for Intractable Ménière's Disease - A Review and Analysis of Audiovestibular Impact.

Int Arch Otorhinolaryngol. 2018 Apr;22(2):190-194

Authors: Yetişer S

Abstract
Introduction  Intratympanic gentamicin regulates the symptoms in most patients with incapacitating Ménière's disease. The treatment protocols have changed over the years from medical labyrinthectomy to preservation of vestibular function. Objectives  This study aims to review the audiovestibular response related to the effect of the drug in controlling vertigo. Data Synthesis  Articles were identified by means of a search in the PubMed database using the key words Meniere and intratympanic or transtympanic gentamicin . Total 144 articles were reviewed after excluding those that were technical reports, those based on experimental animal studies, those that focused on outcomes other than vertigo (tinnitus or aural fullness), those with delivery methods other than tympanic membrane injection, and those with bilateral cases. If there was more than one article by the same author(s) or institution, only the most recent one matching the aforementioned criteria and those that were not overlapping were included. Conclusion  Titration methods or multiple injections on a daily basis can be preferred if the patients have profound or non-serviceable hearing, since these methods have significant incidence of hearing loss. Treatment protocols with a frequency of injection not shorter than once a week, or those with injections on a monthly basis as "needed" provide the same level of vertigo control with better preservation of hearing. Caloric testing is not an ideal tool to analyze the correlation between vertigo control and the effect of gentamicin as compared with gain asymmetry of the vestibulo-ocular reflex. Vestibular-evoked myogenic potentials and the head thrust test are more reliable than other vestibular tests for the follow-up of patients undergoing gentamicin treatment.

PMID: 29619111 [PubMed]

https://ift.tt/2HfNVSE

Efficacy of Chitosan-Based Dressing for Control of Bleeding in Excisional Wounds.

Related Articles

Efficacy of Chitosan-Based Dressing for Control of Bleeding in Excisional Wounds.

Eplasty. 2018;18:e14

Authors: Stricker-Krongrad AH, Alikhassy Z, Matsangos N, Sebastian R, Marti G, Lay F, Harmon JW

Abstract
Introduction: Excessive bleeding is a complication of wound debridement in patients receiving anticoagulation treatment. Chitosan is a linear, positively charged polysaccharide that has potential as a hemostatic topical dressing. This study examined the hemostatic efficacy of the chitosan based Opticell dressing (Medline Industries, Chicago, Ill) in heparinized rats with excisional wounds mimicking debridement. Methods: Three paired 12-mm excisional wounds were created on the dorsum of 600-g Sprague-Dawley rats 2 hours after intraperitoneal injection of heparin 800 IU/kg. Opticell or gauze dressings were applied with 3 seconds of gentle pressure. Results:Total Bleeding: The dressings were left in place until cessation of bleeding. Ten minutes was enough time for complete bleeding cessation in both groups. Gauze and Opticell were weighed before and after bleeding cessation, with the difference representing blood loss. Total blood loss was 627 ± 47 mg/10 min with the standard gauze, but 247 ± 47 mg/10 min with Opticell (P = .002 Mann-Whitney). N = 6 wounds per group. Rate of Bleeding: Gauze and Opticell dressings were removed and instantly replaced with 3 seconds of gentle pressure every minute until bleeding cessation. The removed dressings were weighed before and after application. There was less bleeding in the Opticell group at minutes 1, 2, and 3. Gauze: 183 ± 40, 140 ± 30, and 109 ± 15 mg/min vs Opticell: 91 ± 17, 54 ± 8, and 57 ± 11 mg/min). Analysis of variance, Tukey's test, P < .05. N = 12 wounds per group. Conclusion: Topical application of Opticell dressing with chitosan has hemostatic effects that could be a useful tool to control bleeding associated with wound debridement.

PMID: 29619144 [PubMed]

https://ift.tt/2GGDerg

Prevalence of Escherichia coli Resistant to Beta-Lactam Antibiotics among Patients with Chronic Obstructive Pulmonary Disease and Urinary Tract Infection.

Related Articles

Prevalence of Escherichia coli Resistant to Beta-Lactam Antibiotics among Patients with Chronic Obstructive Pulmonary Disease and Urinary Tract Infection.

Tohoku J Exp Med. 2018;244(4):271-277

Authors: Nikolić E, Brandmajer T, Bokan V, Ulyashova M, Rubtsova M

Abstract
Urinary tract infection (UTI), which is typically caused by Escherichia coli (E. coli), is an insufficiently recognized co-morbidity among patients with chronic obstructive pulmonary disease (COPD). Adequate treatment can be complicated by resistance of the causative pathogen to beta-lactam antibiotics, which often produce beta-lactamase enzymes that destroy the antibiotic. The beta-lactamase family of enzymes is extremely diverse, including different types of enzyme and mutant forms. In this study, we analyzed 580 patients with COPD (236 females and 344 males) and thus found 218 patients with co-morbid UTIs, including 58 patients with UTI caused by E. coli (38 females and 20 males). We also investigated cases of uncomplicated symptomatic and asymptomatic UTI caused by E. coli and the presence of resistance to beta-lactam antibiotics among those patients. The E. coli strains resistant to beta-lactam antibiotics were selected for their ability to grow on selective media, before DNA microarrays were applied for specific identification of three beta-lactamase gene types (i.e., TEM, SHV and CTX-M). Overall, 83% of E. coli strains responsible for UTIs in COPD patients carried extended-spectrum beta-lactamase genes. The most prevalent were those producing CTX-M, with CTX-M-15 being predominant. The rare CTX-M-27 and TEM-15 genes were also detected in two samples. Three samples contained several extended-spectrum beta-lactamase genes simultaneously (CTX-M-15 or CTX-M-14 plus SHV-5 or TEM-15). This high prevalence of resistant E. coli strains necessitates rational antibiotic selection when treating UTI to prevent COPD exacerbations. Additionally, antibiotic therapy should be aligned with and adapted to existing and potential COPD co-morbidities.

PMID: 29618675 [PubMed - in process]

https://ift.tt/2JrLeOr

2q24 deletion in a 9-month old girl with anal atresia, hearing impairment, and hypotonia

Publication date: June 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 109
Author(s): Peiwei Zhao, Bing Mao, Xiaonan Cai, Jun Jiang, Zhisheng Liu, Jun Lin, Xuelian He
Deletion of 2q24.2 is a rare cytogenetic aberration in patients, exhibiting heterogeneous clinical features, and common phenotypes included developmental delay, intellectual disability, hypotonia, and mild dysmorphic features. Hearing impairment and anal atresia are rarely described. Here we described a 9-month-old female patient with hypotonia in all four limbs, developmental delay, and intellectual disability. In addition, congenital anal atresia was diagnosed and treated after birth, and hearing impairment was found in right ear. Single nucleotide polymorphisms (SNP) array detected a 5.2 Mb deletion on 2q24.2q24.3, including 19 genes (ITGB6; TBR1; SLC4A10; KCNH7 SCN3A; SCN2A et al.). Among these genes, it is affirmative that TBR1 is a causative gene for intellectual disability; however, the pathogenic genes of other phenotypes remain unclear. We briefly review the knowledge of genes likely involved in these clinical features, including hearing impairment, anal atresia, and developmental delay.



https://ift.tt/2Iz1tbi

The start of a human life program

Publication date: Available online 5 April 2018
Source:Journal of Genetics and Genomics
Author(s): Falong Lu




https://ift.tt/2GEYQIo

Differences in recurrence and survival of extremity liposarcoma subtypes

Publication date: Available online 6 April 2018
Source:European Journal of Surgical Oncology
Author(s): M. Vos, H. Koseła-Paterczyk, P. Rutkowski, G.J.L.H. van Leenders, M. Normantowicz, A. Lecyk, S. Sleijfer, C. Verhoef, D.J. Grünhagen
BackgroundLiposarcomas can be divided into four subtypes and are most frequently located in the extremities. There are currently no studies comparing the clinical outcomes, such as local recurrence and distant metastasis, between the distinct subtypes of primary LPS of the extremity specifically.MethodsRetrospective databases of two expertise centres (Rotterdam-R, Warsaw-W) of patients with liposarcoma located in the extremities from 1985-2015 were used to analyse 5-year local recurrence-free survival (5y-LRFS), 5-year distant metastasis-free survival (5y-DMFS) and 5-year overall survival (5y-OS).ResultsWe identified 456 patients: 192 well-differentiated liposarcomas (WDLPS), 172 myxoid liposarcomas (MLPS), 54 pleomorphic liposarcomas (PLPS), 23 dedifferentiated liposarcomas (DDLPS) and 15 other subtypes. The frequency of (neo)adjuvant radiotherapy (R: 34.5% vs. W: 78.4%) and R0-resections (R: 41.0% vs. W: 84.1%) differed between the datasets. Local recurrences (LR) were observed most frequently in DDLPS (5y-LRFS 62.4%), followed by PLPS (71.4%), WDLPS (77.0%) and MLPS (84.5%, p=0.054). Distant metastases (DM) were most commonly observed in PLPS (5y-DMFS 46.9%), followed by MLPS (74.0%), DDLPS (86.3%) and WDLPS (97.3%). 5y-OS was poorest in patients with PLPS (47.6%) and DDLPS (54.4%), followed by MLPS (79.7%) and WDLPS (92.4%, p<0.001). Male gender significantly increased the risk of LR and DM. The subtypes MLPS and PLPS were significant prognostic factors for DM and OS. Additionally, DDLPS and age had significant impact on OS.ConclusionIn the largest cohort of extremity LPS patients reported to date, LPS subtypes show distinct patterns of LR, DM and OS, stressing that 'extremity LPS' is not a single entity. Parts of this abstract were presented as a poster at the annual meeting of the CTOS in Lisbon, November 2016 and at the annual meeting of the ESMO in Madrid, September 2017 where it was awarded with the 'Best Poster' award.



https://ift.tt/2uQ4H8h

Long-term outcomes of laparoscopic versus open D3 dissection for stage II/III colon cancer: Results of propensity score analyses

Publication date: Available online 5 April 2018
Source:European Journal of Surgical Oncology
Author(s): Dai Shida, Hiroki Ochiai, Shunsuke Tsukamoto, Yukihide Kanemitsu
BackgroundNon-inferiority of the laparoscopic approach for stage II/III colon cancer has not been clearly established. This study aimed to evaluate the long-term outcomes of laparoscopic versus open D3 surgery.MethodsSubjects were 1230 consecutive patients with stage II/III colon cancer, who were referred to the National Cancer Center Hospital from 2004 to 2013. Open surgery was performed in 821 (67%) patients, and laparoscopic surgery was performed in 409 (33%). Propensity score analyses with overall survival as the primary endpoint were performed in three different propensity score methods.ResultsRegression adjustment using the propensity score as a linear predictor in the model showed similar overall survival between laparoscopic and open surgeries [hazard ratio (HR), 0.98 (95% CI [0.64 – 1.46]; p=0.916)]. Stratification analysis of the entire cohort revealed that, among five strata, only the highest stratum (clinical T2/T3, clinical N0/N1, tumor size <6 cm, and body mass index (BMI) < 28) had an HR of <1 (0.37). In the other four strata, open surgery was favored as reflected by HRs of >1 (1.13-1.26). The propensity score-matched cohort (365 matched pairs), from which patients with advanced disease and high BMI were excluded, yielded an HR of 0.93 (95% CI [0.57 – 1.52]; p=0.772).ConclusionsLaparoscopic surgery appeared to be a safe and reasonable option for patients with stage II/III colon cancer in general. Patients with high BMI, clinical N2 and T4 disease, and tumor size ≥6 cm might require prudent selection of surgical approach.



https://ift.tt/2qaUnTE

Contribution of lymph node staging method and prognostic factors in malignant ovarian sex cord-stromal tumors: a world wide database analysis

Publication date: Available online 6 April 2018
Source:European Journal of Surgical Oncology
Author(s): Jieyu Wang, Jun Li, Ruifang Chen, Xin Lu
ObjectiveTo investigate the clinicopathologic prognostic factors in patients with malignant sex cord-stromal tumors (SCSTs) with lymph node dissection, and at the same time, to evaluate the influence of the log odds of positive lymph nodes (LODDS) on their survival.MethodsPatients diagnosed with malignant SCSTs who underwent lymph node dissection were extracted from the 1988-2013 Surveillance, Epidemiology, and End Results (SEER) database. Overall survival (OS) and cancer-specific survival (CSS) were estimated by Kaplan-Meier curves. The Cox proportional hazards regression model was used to identify independent predictors of survival.Results576 patients with malignant SCSTs and with lymphadenectomy were identified, including 468 (81.3%) patients with granulosa cell tumors (GCTs) and 80 (13.9%) patients with Sertoli-Leydig cell tumors (SLCTs). 399 (69.3%) patients and 118 (20.5%) patients were in the LODDS˂-1 group and -1≤LODDS˂-0.5 group, respectively. The 10-year OS rate was 80.9% and CSS was 87.2% in the LODDS˂-0.5 group, whereas the survival rates for other groups were 68.5% and 73.3%. On multivariate analysis, age 50 years or less (p˂0.001), tumor size of 10cm or less (p˂0.001), early-stage disease (p<0.001), and GCT histology (p≤0.001) were the significant prognostic factors for improved survival. LODDS ˂-0.5 was associated with a favorable prognosis (OS: p = 0.051; CSS:P = 0.055).ConclusionsYounger age, smaller tumor size, early stage, and GCT histologic type are independent prognostic factors for improved survival in patients with malignant SCST with lymphadenectomy. Stratified LODDS could be regarded as an effective value to assess the lymph node status, and to predict the survival status of patients.



https://ift.tt/2IuR0xx

Engineering improved balance confidence among older adults with complex health care needs: Learning from the Muscling Up Against Disability study

Publication date: Available online 5 April 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Sharon Hetherington, Tim Henwood, Paul Swinton, Justin Keogh, Paul Gardiner, Anthony Tuckett
ObjectiveTo investigate the associations of balance confidence with physical and cognitive markers of wellbeing among older adults receiving government-funded aged care services, and whether progressive resistance plus balance training could positively influence change.DesignIntervention study.SettingCommunity-based older-adult-specific exercise clinic.ParticipantsOlder adults (N=245) with complex care needs who were receiving government aged care support.Intervention24 weeks of twice-weekly progressive resistance plus balance training carried out under the supervision of accredited exercise physiologists.Main Outcome MeasuresThe primary measure was the Activity-specific Balance Confidence score. Secondary measures included the Short Physical Performance Battery, fall history, hierarchical timed balance tests, Geriatric Anxiety Index, Geriatric Depression Score, FRAIL scale and EuroQol 5D 3L.ResultsAt baseline, higher physical performance (r = 0.54, p < .01) and quality of life (r = 0.52, p < .01) predicted better balance confidence. In contrast, at baseline, higher levels of frailty predicted worse balance confidence (r = -0.55, p < .01). Change in balance confidence following the exercise intervention was accompanied by improved physical performance (+12%) and decreased frailty (-11%). Baseline balance confidence was identified as the most consistent negative predictor of change scores across the intervention.ConclusionsThis study shows that reduced physical performance and quality of life, and increasing frailty, are predictive of poor balance confidence among older adults with aged care needs. However, when a targeted intervention of resistance and balance exercise is implemented, that reduces frailty and increases physical performance, balance confidence will also improve. Given the influence of balance confidence on a raft of wellbeing determinants, including the capacity for positive physical and cognitive change, this study offers important insight to those looking to reduce falls among older adults.



https://ift.tt/2qariaL

The Effectiveness of Oral Pain Medication and Corticosteroid Injections for Carpal Tunnel Syndrome–A Systematic Review

Publication date: Available online 5 April 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Bionka MA. Huisstede, Manon S. Randsdorp, Janneke van den Brink, Thierry PC. Franke, Bart W. Koes, Peter Hoogvliet
ObjectiveTo present an evidence-based overview of the effectiveness of oral pain medication and corticosteroid injections to treat carpal tunnel syndrome (CTS).Data SourcesThe Cochrane Library, PubMed, EMBASE, CINAHL, and PEDro were searched for relevant systematic reviews and randomized controlled trials (RCTs).Data Selection and ExtractionTwo reviewers independently selected the studies, extracted the data on pain (VAS), function or recovery and assessed the methodological quality.Data SynthesisA best-evidence synthesis was performed to summarize the results of the included studies. Four reviews and nine RCTs were included. For oral pain medication strong and moderate evidence was found for the effectiveness of oral steroids versus placebo in the short-term. Moderate evidence was found in favor of oral steroids versus splinting in the short-term. No evidence was found for the effectiveness of oral steroids in the long-term. For corticosteroid injections, strong evidence was found in favor of a corticosteroid injection versus a placebo injection and moderate evidence was found in favor of corticosteroid injection versus oral steroids in the short-term. Also in short-term, moderate evidence was found in favor of a local versus a systematic corticosteroid injection. Higher doses of corticosteroid injections seem to be more effective in the midterm, however the benefits of corticosteroid injections were not maintained in the long-term.ConclusionThe reviewed evidence supports that oral steroids and corticosteroid injections benefit patient with CTS particular in the short-term. Although a higher dose of steroid injections seems to be more effective in the midterm, the benefits of oral pain medication and corticosteroid injections were not maintained in the long-term.



https://ift.tt/2GEKIPm

A contemporary analysis of radiotherapy effect in surgically treated retroperitoneal sarcoma

Publication date: Available online 6 April 2018
Source:Radiotherapy and Oncology
Author(s): Sebastiano Nazzani, Marco Bandini, Michele Marchioni, Felix Preisser, Zhe Tian, Denis Soulières, Emanuele Montanari, Gloria Motta, Pietro Acquati, Alberto Briganti, Shahrokh F. Shariat, Firas Abdollah, Luca Carmignani, Pierre I. Karakiewicz
Background and purposeContemporary data regarding the benefit of radiotherapy in surgically treated retroperitoneal sarcoma are scarce. The aim of the study was to evaluate the effect of radiotherapy on cancer specific mortality in surgically treated patients according to tumor size, histological subtype and grade.Material and methodsWithin Surveillance, Epidemiology, and End Results database (2004–2014), we identified 1226 patients with non-metastatic retroperitoneal sarcoma. Univariable and multivariable logistic regression models tested for predictors of radiotherapy delivery. Univariable and multivariable Cox regression models tested the effect of radiotherapy on cancer specific mortality in the overall population. Subgroup analyses explored the result of tumor grade and tumor size on radiotherapy effect. All analyses were repeated after adjustment according to inverse probability of treatment. Additionally, all analyses were subjected to 1000 bootstrap resamples for internal validation.ResultsRadiotherapy was delivered in 372 patients (30.3%). In univariable and multivariable logistic regression models high grade (OR: 1.46, CI:1.12–1.90; p = 0.006), and leiomyosarcoma histologic subtype (OR: 2.14, CI: 1.55–2.95; p < 0.001) predicted radiotherapy delivery. In the overall population multivariable Cox regression models showed lower cancer specific mortality (HR: 0.73, CI: 0.55–0.96; p = 0.025) with radiotherapy. In subgroup analyses multivariable Cox regression models showed radiotherapy benefit predominantly in high grade, large tumor size retroperitoneal sarcomas (HR 0.51: C.I.: 0.30–0.86; p = 0.02).ConclusionsIn this retrospective report, delivery of radiotherapy was associated with lower cancer specific mortality in high grade, large tumor size retroperitoneal sarcoma patients. Our findings are predominantly representative of liposarcomas and leiomyosarcomas that accounted for 90% of study population. Further study is needed to evaluate the role of radiotherapy in retroperitoneal sarcoma patients.



https://ift.tt/2IA3CDD

Fatigue, insomnia and hot flashes after definitive radiochemotherapy and image-guided adaptive brachytherapy for locally advanced cervical cancer: An analysis from the EMBRACE study

Publication date: Available online 5 April 2018
Source:Radiotherapy and Oncology
Author(s): Stéphanie Smet, Richard Pötter, Christine Haie-Meder, Jacob C. Lindegaard, Ina Schulz-Juergenliemk, Umesh Mahantshetty, Barbara Segedin, Kjersti Bruheim, Peter Hoskin, Bhavana Rai, Fleur Huang, Rachel Cooper, Erik van Limbergen, Kari Tanderup, Kathrin Kirchheiner
ObjectiveTo evaluate the pattern of manifestation of fatigue, insomnia and hot flashes within the prospective, observational, multi-center EMBRACE study.MethodsMorbidity was prospectively assessed according to CTCAE v.3 and patient-reported outcome with EORTC QLQ-C30/CX24 at baseline and regular follow-up. Analyses of crude incidence, prevalence rates and actuarial estimates were performed.ResultsA total of 1176 patients were analyzed with a median follow-up of 27 months. At baseline, CTCAE G1/G2 prevalence rates for fatigue were 29%/6.2%, for insomnia 18%/3.1% and for hot flashes 7.9%/1.6% with respective 3-year prevalence rates of 29%/6.8%, 17%/4.4% and 19%/5.9%. Similar patterns of manifestation were seen in patient-reported EORTC outcomes. The 3-year actuarial estimates for G ≥ 3 CTCAE fatigue, insomnia and hot flashes were 5.5%, 4.7% and 1.9%. Younger age was associated with significantly higher risk for fatigue, insomnia and hot flashes.ConclusionFatigue, insomnia and hot flashes occurred mainly in the mild to moderate range. Fatigue and insomnia were already present before treatment and showed minor fluctuations or recovery during follow-up, whereas hot flashes showed a considerable increase after treatment. More research is needed to evaluate contributing risk factors in order to define intervention strategies.



https://ift.tt/2qapVJ9

Functional-guided radiotherapy using knowledge-based planning

Publication date: Available online 5 April 2018
Source:Radiotherapy and Oncology
Author(s): Austin M. Faught, Lindsey Olsen, Leah Schubert, Chad Rusthoven, Edward Castillo, Richard Castillo, Jingjing Zhang, Thomas Guerrero, Moyed Miften, Yevgeniy Vinogradskiy
Background and purposeThere are two significant challenges when implementing functional-guided radiotherapy using 4DCT-ventilation imaging: (1) lack of knowledge of realistic patient specific dosimetric goals for functional lung and (2) ensuring consistent plan quality across multiple planners. Knowledge-based planning (KBP) is positioned to address both concerns.Material and methodsA KBP model was created from 30 previously planned functional-guided lung patients. Standard organs at risk (OAR) in lung radiotherapy and a ventilation contour delineating areas of high ventilation were included. Model validation compared dose-metrics to standard OARs and functional dose-metrics from 20 independent cases that were planned with and without KBP.ResultsA significant improvement was observed for KBP optimized plans in V20Gy and mean dose to functional lung (p = 0.005 and 0.001, respectively), V20Gy and mean dose to total lung minus GTV (p = 0.002 and 0.01, respectively), and mean doses to esophagus (p = 0.005).ConclusionThe current work developed a KBP model for functional-guided radiotherapy. Modest, but statistically significant, improvements were observed in functional lung and total lung doses.



https://ift.tt/2IyrxmP