The RET E616Q Variant is a Gain of Function Mutation Present in a Family with Features of Multiple Endocrine Neoplasia 2A

Abstract

The REarranged during Transfection (RET) proto-oncogene is a receptor tyrosine kinase involved in growth and differentiation during embryogenesis and maintenance of the urogenital and nervous systems in mammals. Distinct mutations across hotspot RET exons can cause Multiple Endocrine Neoplasia Type 2A (MEN2A) characterised by development of medullary thyroid cancer (MTC), phaeochromocytoma (PCC) and primary hyperparathyroidism (PHPT), with a strong correlation between genotype and phenotype. Here, we report a 42-year-old man presented in the clinic with a unilateral PCC, with subsequent investigations revealing a nodular and cystic thyroid gland. He proceeded to thyroidectomy, which showed bilateral C-cell hyperplasia (CCH) without evidence of MTC. His brother had neonatal Hirschsprung disease (HSCR). Genetic testing revealed the presence of a heterozygous variant of unknown significance (VUS) in the cysteine-rich region of exon 10 in the RET gene (c.1846G>C, p.E616Q), in both affected siblings and their unaffected mother. Exon 10 RET mutations are known to be associated with HSCR and MEN2. Variants in the cysteine-rich region of the RET gene, outside of the key cysteine residues, may contribute to the development of MEN2 in a less aggressive manner, with a lower penetrance of MTC. Currently, a VUS in RET cannot be used to inform clinical management and direct future care. Analysis of RET^E616Q reveals a gain of function mutant phenotype for this variant, which has not previously been reported, indicating that this VUS should be considered at risk for future clinical management.

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MATERNAL CORTICAL RESPONSE TO BABY PAIN AND POSTPARTUM DEPRESSIVE SYMPTOMS

Publication date: Available online 5 October 2016
Source:Biological Psychology
Author(s): Stefano Bembich, Cristina Vecchiet, Gabriele Cont, Cristina Sustersic, Francesca Valencak, Sergio Demarini
Decreased maternal empathic abilities toward infants have been reported with postpartum depression (PPD). The aims of this study were: 1) To identify mothers' cortical regions activated by the observation of their own newborn pain; 2) To study the relation between such cortical activation and PPD symptoms. By optical topography, a functional neuroimaging system, we assessed mothers' cortical activation when watching their own newborns during a heel-prick. PPD symptoms and newborn's pain expression were also assessed. Watching their newborn in pain activated mothers' left somatosensory cortex (P=0.003) and right superior temporal cortex (P=0.002). PPD score showed a negative correlation with left somatosensory cortex activation (rs=−0.41; P=0.026), that decreased as PPD symptoms increased. To conclude, an activation of cortical areas, previously associated with empathy for pain, can be demonstrated in the mother shortly after birth. Such response appeared to be dampened by PPD symptoms.



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Pulse Duration as Well as Current Direction Determines the Specificity of Transcranial Magnetic Stimulation of Motor Cortex during Contraction

Publication date: Available online 5 October 2016
Source:Brain Stimulation
Author(s): Ricci Hannah, John C Rothwell
BackgroundPrevious research suggested that anterior-posterior (AP) directed currents induced by TMS in motor cortex (M1) activate different interneuron circuits than posterior-anterior currents (PA). The present experiments provide evidence that pulse duration also determines the activation of specific interneuron circuits.ObjectiveTo use single motor unit (SMU) recordings to confirm the difference in onset latencies of motor-evoked potentials (MEPs) evoked by different current directions and pulse durations: AP30, AP120, PA30 and PA120. To test whether the amplitude of the MEPs is differentially influenced by somatosensory inputs from the hand (short-latency afferent inhibition, SAI), and examine the sensitivity of SAI to changes in cerebellar excitability produced by direct current stimulation (tDCSCb).MethodsSurface electromyograms and SMUs were recorded from the first dorsal interosseous muscle. SAI was tested with an electrical stimulus to median or digital nerves ~20-25ms prior to TMS delivered over the M1 hand area via a controllable pulse parameter TMS (cTMS) device. SAI was also tested during the application of anodal or sham tDCSCb. Because TMS pulse specificity is greatest at low stimulus intensities, most experiments were conducted with weak voluntary contraction to reduce stimulus threshold.ResultsAP30 currents recruited the longest latency SMU and surface MEP responses. During contraction SAI was greater for AP30 responses versus all other pulses. Online anodal tDCSCb reduced SAI for the AP30 currents only.ConclusionsAP30 currents activate an interneuron circuit with different functional properties to those activated by other pulse types. Pulse duration and current direction determine what is activated in M1 with TMS.



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Direct Current Stimulation Modulates LTP and LTD: Activity Dependence and Dendritic Effects

Publication date: Available online 5 October 2016
Source:Brain Stimulation
Author(s): Greg Kronberg, Morgan Bridi, Ted Abel, Marom Bikson, Lucas C. Parra
BackgroundTranscranial direct current stimulation (tDCS) has been reported to improve various forms of learning in humans. Stimulation is often applied during training, producing lasting enhancements that are specific to the learned task. These learning effects are thought be mediated by altered synaptic plasticity. However, the effects of DCS during the induction of endogenous synaptic plasticity remain largely unexplored.Objective/Hypothesis: Here we are interested in the effects of DCS applied during synaptic plasticity induction.MethodsTo model endogenous plasticity we induced long-term potentiation (LTP) and depression (LTD) at Schaffer collateral synapses in CA1 of rat hippocampal slices. Anodal and cathodal DCS at 20 V/m were applied throughout plasticity induction in both apical and basal dendritic compartments.ResultsWhen DCS was paired with concurrent plasticity induction, the resulting plasticity was biased towards potentiation, such that LTP was enhanced and LTD was reduced. Remarkably, both anodal and cathodal stimulation can produce this bias, depending on the dendritic location and type of plasticity induction. Cathodal DCS enhanced LTP in apical dendrites while anodal DCS enhanced LTP in basal dendrites. Both anodal and cathodal DCS reduced LTD in apical dendrites. DCS did not affect synapses that were weakly active or when NMDA receptors were blocked.ConclusionsThese results highlight the role of DCS as a modulator, rather than inducer of synaptic plasticity, as well as the dependence of DCS effects on the spatial and temporal properties of endogenous synaptic activity. The relevance of the present results to human tDCS should be validated in future studies.



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Discontinuities in ethnographic time: A view from Africa

Publication date: Available online 5 October 2016
Source:Journal of Anthropological Archaeology
Author(s): Robert K. Hitchcock
While there is evidence of discontinuities in the sequences of some archaeological sites that exhibit long-term occupation and use over time in southern Africa, there is less evidence of such discontinuity in the ethnographic record. Drawing on long-term interdisciplinary studies of southern African peoples in the Kalahari Desert, this paper examines the evidence of discontinuities in the historical and ethnographic records. Attention is focused primarily on two southern African San populations for which detailed diachronic data exist: (1) the Ju/'hoansi of northwestern Kalahari, and (2) the !Xóõ San of the southwestern Kalahari region of Botswana and Namibia. From an ethnographer's perspective it might at first appear as though there was a fair amount of continuity in the Kalahari. It is shown, however, that there have been complex changes over time in the period from 1850 to the present, which occurred as a result of a combination of factors, including short-term and long-term ecological changes, in-migration and out-migration of various groups, cycles of population growth and decline, colonization, technological shifts, and implementation of development and conservation programs. The two cases illustrate the complex ways that activities, mobility, technology, land use, and demographic patterns can change over time as a result of both internal and external forces, resulting in discontinuities in the ethnographic record.



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Evaluation of the improvement effect of laser acupuncture biostimulation in asthmatic children by exhaled inflammatory biomarker level of nitric oxide

Abstract

Variable therapy of asthma is not sufficient yet to achieve good asthma control. Therapy decision requires serial investigations. Low-level laser acupuncture is a suitable non-invasive modality of complementary medicine. The exhaled breath condensate (EBC) is easy and useful to evaluate the efficacy of drugs or novel therapy. This study aimed to evaluate the effectiveness of low-level laser biostimulation of acupuncture points on asthma improvement in children. Forty-eight asthmatic children were subdivided into case (laser) group, which received 12 direct contact low-power laser acupuncture sessions (three sessions/week) on specific traditional Chinese acupuncture points for bronchial asthma, and control asthmatic group, which received sham laser acupuncture on the same acupoints and number of sessions of the case (laser) group. Low-power Multichannel Aculas-AM laser (grade II) of wave length 780 nm, output power 800 mw, and beam spot size 0.1 cm² with continuous mode was used. Eighteen acupoints were stimulated for 2 min, giving energy of 9.6 J/cm²/acupoint. The total session time was 3 min. Both groups were evaluated pre- and post-laser acupuncture intervention by recording levels of asthma control, pulmonary function, and EBC nitric oxide. In the case (laser) group, 91.7 % of patients experienced an improvement in the level of asthma control versus 25 % in the control group (p < 0.001). This was associated with a significant decrease of the breath condensate FENO concentration (p < 0.001) and significant increase of spirometry parameters (p < 0.001) in the case (laser) group. Application of laser acupuncture treatment given with conventional therapy can effectively improve bronchial asthma more than prescription of medications alone could.

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Photodynamic therapy decrease immune-inflammatory mediators levels during periodontal maintenance

Abstract

Antimicrobial photodynamic therapy (aPDT) was introduced as a promising adjuvant therapy on the periodontal treatment. The aim of this study was to evaluate the effect of aPDT on inflammatory mediator levels in residual periodontal pockets of patients with severe chronic periodontitis under periodontal maintenance, during 12 months follow-up. A randomized controlled trial study was conducted in 28 patients with severe chronic periodontitis. After non-surgical periodontal treatment, patients with at least four teeth with residual pocket probing depth (PPD) ≥4 mm were randomly assigned to either aPDT or control group. The aPDT (low power laser: 660 nm, 40 mW, 90 J/cm², methylene blue 0.01 %) was performed at baseline and 3, 6, and 9 months. Clinical parameters were collected before and 3 and 12 months after the intervention, and gingival crevicular fluid was collected in the same times, including 1 week after the intervention. Immunological evaluation was carried out using the Luminex assay which quantified the expression of ten cytokines: interleukin (IL)-1α, IL-1β, IL-8, IL-1ra, fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-4, and IL-10. All clinical variables showed significant improvement for both groups, but there was no statistical difference between groups with no clinical benefits. IL-1α, IL-1β, IL-8, and VEGF showed significant differences (p < 0.05) between groups, whereas IL-1ra mediators, IFN-γ, and IL-10 demonstrated a statistical difference (p < 0.01) over time in the same group. At any time, FGF, IL-4, and TNF-α showed no statistical difference between groups (p > 0.05). aPDT therapy can improve the benefits on inflammation control during the periodontal maintenance.

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Cleaner processing: a sulphide—free approach for depilation of skins

Abstract

The conventional unhairing process in leather making utilises large amount of lime and sodium sulphide which is hazardous and poses serious waste disposal concerns. Under acidic conditions, sodium sulphide liberates significant quantities of hydrogen sulphide which causes frequent fatal accidents. Further, the conventional unhairing process involves destruction of the hair leading to increased levels of biological oxygen demand (BOD), chemical oxygen demand (COD), total dissolved solids (TDS) and total suspended solids (TSS) in the effluent. A safe approach is needed to overcome such environmental and health problems through an eco-benign process. The present study deals with a clean technology in which the keratinous body is detached from the dermis using enzymes produced from Bacillus crolab MTCC 5468 by solid state fermentation (SSF) as an alternative to noxious chemicals. Complete unhairing of skin could be achieved with an enzyme concentration of 1.2 % (w/w). The bio-chemical parameters of the spent liquor of the enzymatic process were environmentally favourable when compared with conventional method. The study indicates that the enzymatic unhairing is a safe process which could be used effectively in leather processing to alleviate pollution and health problems.

http://ift.tt/2dRG3bf

Trend and variability of atmospheric ozone over middle Indo-Gangetic Plain: impacts of seasonality and precursor gases

Abstract

Ozone dynamics in two urban background atmospheres over middle Indo-Gangetic Plain (IGP) were studied in two contexts: total columnar and ground-level ozone. In terms of total columnar ozone (TCO), emphases were made to compare satellite-based retrieval with ground-based observation and existing trend in decadal and seasonal variation was also identified. Both satellite-retrieved (Aura Ozone Monitoring Instrument-Differential Optical Absorption Spectroscopy (OMI-DOAS)) and ground-based observations (IMD-O₃) revealed satisfying agreement with OMI-DOAS observation over predicting TCO with a positive bias of 7.24 % under all-sky conditions. Minor variation between daily daytime (r = 0.54; R ² = 29 %; n = 275) and satellite overpass time-averaged TCO (r = 0.58; R ² = 34 %; n = 208) was also recognized. A consistent and clear seasonal trend in columnar ozone (2005–2015) was noted with summertime (March–June) maxima (Varanasi, 290.9 ± 8.8; Lucknow, 295.6 ± 9.5 DU) and wintertime (December–February) minima (Varanasi, 257.4 ± 10.1; Lucknow, 258.8 ± 8.8 DU). Seasonal trend decomposition based on locally weighted regression smoothing technique identified marginally decreasing trend (Varanasi, 0.0084; Lucknow, 0.0096 DU year⁻¹) especially due to reduction in monsoon time minima and summertime maxima. In continuation to TCO, variation in ground-level ozone in terms of seasonality and precursor gases were also analysed from September 2014 to August 2015. Both stations registered similar pattern of variation with Lucknow representing slightly higher annual mean (44.3 ± 30.6; range, 1.5–309.1 μg/m³) over Varanasi (38.5 ± 17.7; range, 4.9–104.2 μg/m³). Variation in ground-level ozone was further explained in terms water vapour, atmospheric boundary layer height and solar radiation. Ambient water vapour content was found to associate negatively (r = −0.28, n = 284) with ground-level ozone with considerable seasonal variation in Varanasi. Implication of solar radiation on formation of ground-level ozone was overall positive (Varanasi, 0.60; Lucknow, 0.26), while season-specific association was recorded in case of atmospheric boundary layer.

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Bioaccumulation of natural radionuclides in molluscs from the Ebro Delta area

Abstract

²¹⁰Po, ²¹⁰Pb, ²³⁴U, ²³⁸U, ²³²Th and ²³⁰Th were analysed in the edible part of four different species of bivalves typically produced and consumed in the Ebro Delta area. The results show that the main contributor to the radioactive content in these species was ²¹⁰Po, with values ranging between 263.1 ± 26.6 and 813.0 ± 72.9 Bq/kg (d.w.), which are higher than the usual reported activity levels in other geographical areas. This can probably be attributed to the activities of a phosphate industrial plant located upstream on the Ebro River, which may lead to enhanced levels of naturally occurring radioactive isotopes in the aquatic ecosystem. To determine the possible impact on health, the committed effective doses through the consumption of the different species were evaluated and the cumulative total annual effective dose for their consumption was estimated to 187.6 μSv/year, which is in the range of 200–1000 μSv/year given by UNSCEAR.

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Endosulfan inducing apoptosis and necroptosis through activation RIPK signaling pathway in human umbilical vascular endothelial cells

Abstract

Endosulfan, an organochlorine pesticide, was found in human blood, and its possible cardiovascular toxicity has been suggested. However, the mechanism about endothelial cell injuries induced by endosulfan has remained unknown. In the present study, human umbilical vein endothelial cells (HUVECs) were chosen to explore the toxicity mechanism and were treated with 0, 1, 6, and 12 μg/mL⁻¹ endosulfan for 24 h, respectively. The results showed that exposure to endosulfan could inhibit the cell viability, increase the release of lactate dehydrogenase (LDH), damage the ultrastructure, and lead to apoptosis and necroptosis in HUVECs. Furthermore, endosulfan upregulated the expressions of receptor-interacting protein kinase 1 (RIPK1), receptor-interacting protein kinase 3 (RIPK3), mixed lineage kinase domain-like (MLKL), caspase 8, and caspase 3, which means the activation of RIPK1 pathways. In addition, endosulfan promoted the increases of ROS, IL-1α, and IL-33 levels while antioxidant N-acetyl-l-cysteine (NAC) effectively attenuated the cytotoxicity from endosulfan. Taken together, these results have demonstrated that endosulfan induces the apoptosis and necroptosis of HUVECs, where the RIPK pathway plays a pro-necroptotic role and NAC plays an anti-necroptotic role. Our results may contribute to understanding cellular mechanisms for endosulfan-induced cardiovascular toxicity.

http://ift.tt/2cTAjM9

Nutrient changes and biodynamics of Eisenia fetida during vermicomposting of water lettuce ( Pistia sp.) biomass: a noxious weed of aquatic system

Abstract

This paper reports the results of vermicomposting of water lettuce biomass (WL) spiked with cow dung at ratios of 20, 40, 60, and 80 % employing Eisenia fetida. A total of four treatments were established and changes in chemical properties of mixtures were observed. Vermicomposting caused a decrease in pH, TOC, volatile solids, and C/N ratio by 1.01–1.08-fold, 0.85–0.92-fold, 0.94–0.96-fold, 0.56–0.70-fold, respectively, but increase in EC, _totN, _totP, _totK, _totCa, _totZn, _totFe, and _totCu, by 1.19–1.42-fold, 1.33–1.68-fold, 1.38–1.69-fold, 1.13–1.24-fold, 1.04–1.11-fold, 1.16–1.37-fold, 1.05–1.113-fold, 1.10–1.27-fold, respectively. Overall, the treatment with 60–80 % of WL showed the maximum decomposition and mineralization rates. The earthworm showed the growth and reproduction rate in considerable ranges in all treatment setups but setups with 60–80 % WL proportion exhibited the optimum results. Results reveal that biomass of water lettuce can be utilized effectively for production of valuable manure through vermicomposting system.

http://ift.tt/2dKUMIY

Intoxication and biochemical responses of freshwater snail Bellamya aeruginosa to ethylbenzene

Abstract

No acute toxic data of ethylbenzene on gastropod is available in literature. In the present study, the acute toxicity of ethylbenzene was assessed on a freshwater snail Bellamya aeruginosa, which was exposed to ethylbenzene concentration from 1 to 100 mg/L for 96 h. No mortality occurred, but a manifestation of intoxication (distress syndrome) was observed in part of exposed snails, and meanwhile, another part was moved normally. The distress syndrome showed clear dose- and time-dependent effects, and the 96-h EC₅₀ value for distress syndrome was 13.3 mg/L in snail. The biochemical responses induced by ethylbenzene to the snail, including acetylcholinesterase (AChE) in the whole body and superoxide dismutase (SOD), catalase (CAT), glutathione S-transferases (GST), and reduced glutathione (GSH) in the hepatopancreas, were evaluated both for distressed snail and moved snail. The AChE activity of distressed snail was all inhibited more than 45 %, and the inhibition of AChE activity in the moved snail was all less than 30 % and more than 20 %, demonstrating that ethylbenzene exerted nervous toxicity to both distressed snail and moved snail. Meanwhile, the difference for AChE activity between the two different response snails was significant. Among the antioxidant biomarkers (SOD, CAT, GST, and GSH), only GST displayed significant difference between the distressed snail and moved snail. However, the activities of enzymes (SOD, CAT, and GST) in the moved snail were greater than those in the distressed snail, no matter significantly or insignificantly, which indicated that the ability of antioxidant defense in the distressed snail was weaker than that in the moved snail. The findings here reported manifest that ethylbenzene exerted nervous toxicity to snail, and the snail with intoxication response (distress syndrome) presented larger inhibition on AChE activity and weaker antioxidant ability in comparison with the moved snail.

http://ift.tt/2cTAuaa

Dissipation and residue of clothianidin in granules and pesticide fertilizers used in cabbage and soil under field conditions

Abstract

The single application of 0.5 % clothianidin granules, a novel formulation, was used to control pests in vegetables under a high dose. In this article, residues of clothianidin in cabbage and soil samples under field conditions from Guangzhou, Nanning, and Qianjiang were determined by HPLC. The terminal residues of clothianidin in cabbage were less than the limit of detection (<LOD) at pre-harvest intervals of 30 days, and these values were lower than the maximum residue limit of 0.2 mg kg⁻¹ in cabbage set by the Codex Alimentarius Commission. To test on the influence of the pesticide fertilizers' effect on clothianidin residual, clothianidin granules and fertilizers of chicken manure, urea, and organic fertilizer were mixed into different pesticide fertilizers through their normal field using dosage and evaluate residual influence of clothianidin in different formula. After analysis of variance of the effect factors, the effect of different pesticide types on half-life was not significant, but the effect of sample types was significant. Clothianidin granules and pesticide fertilizers could be safely applied in cabbage under a single high-dose administration.

http://ift.tt/2ds1Zvt

The effect of TSH change per year on the risk of incident chronic kidney disease in euthyroid subjects

Abstract

The objective of this study is to evaluate the predictive values of baseline thyroid-stimulating hormone and the rate of thyroid-stimulating hormone change within the euthyroid state on the development of chronic kidney disease. We conducted a longitudinal study in 17,067 Korean adults with normal thyroid function and no history of thyroid disease. Incident chronic kidney disease was defined as an estimated glomerular filtration rate <60 ml/min/1.73 m². The rate of thyroid-stimulating hormone change was determined by subtracting the baseline thyroid-stimulating hormone level from the thyroid-stimulating hormone level measured at the last visit prior to the diagnosis of chronic kidney disease or at the final visit in subjects without chronic kidney disease, divided by the observation period (years). Subjects were stratified into quintiles according to rates of thyroid-stimulating hormone change. During 86,583 person-years of follow-up (median follow-up 5.2 years), there were 561 incident cases of chronic kidney disease. The risk of incident chronic kidney disease was significantly higher in subjects with rapid increases (quintile 5) or decreases (quintile 1) in thyroid-stimulating hormone levels compared to the reference group (quintile 3). In fully adjusted models, the hazard ratios of quintiles 1 and 5 were 3.15 (95 % confidence interval 2.34 to 4.24; p < 0.001) and 3.37 (95 % confidence interval 2.52 to 4.51; p < 0.001), respectively. However, there was no significant association between baseline thyroid-stimulating hormone and risk of incident chronic kidney disease. The development of chronic kidney disease is associated with the rate of changes in thyroid-stimulating hormone level rather than with baseline thyroid-stimulating hormone levels.

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Erratum to: Proprotein convertase subtilisin/kexin type 9 (PCSK9) and metabolic syndrome: insights on insulin resistance, inflammation, and atherogenic dyslipidemia

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External ear invasion from an anaplastic thyroid cancer

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Multiparametric ultrasonography and ultrasound elastography in the differentiation of parathyroid lesions from ectopic thyroid lesions or lymphadenopathies

Abstract

To evaluate the accuracy of ultrasound elastography with Elastoscan^TM Core Index in the differential diagnosis of parathyroid lesions from ectopic thyroid nodules and lymph nodes. Seventy nine patients with repeatedly high levels of circulating intact parathyroid hormone, normal vitamin D and renal function tests, with an ultrasound scan showing a neck lesion, sharply demarcated from the thyroid lobules, were consecutively enrolled. Ultrasound with and without Color Doppler and ultrasound elastography were performed before histological examination. All ultrasound features, vascularization and ultrasound elastography diagnostic performance were assessed using ROC curves. Histological examination confirmed 47 parathyroid lesions, 18 thyroid ectopic nodules and 14 reactive lymph nodes. In distinguishing parathyroid from thyroid nodules, shape had a 100 % sensitivity (95 % CI 92.4–100) and 50 % specificity (95 % CI 37.2–64.7), cleavage had a 85.1 % sensitivity (95 % CI 72.3–92.6) and 77.8 % specificity (95 % CI 65.1–88) while peripheral vascularization had a sensitivity of 91.5 (95 % CI 79.6–97.6) and specificity of 72.2 (95 % CI 46.5–90.3). An Elastoscan^TM Core Indexof 1.28 was 46 % sensitive (95 % CI 33.4–58.7) and 77 % specific (95 % CI 66.2–89.1) in discriminating parathyroid lesions from thyroid nodules. An Elastoscan^TM Core Index of 1.0 was 78 % sensitive (95 % CI 65.1–88) and 71 % specific (95 % CI 56–81.3) in discriminating parathyroid lesions from lymph nodes (p = 0.045). An Elastoscan^TM Core Index greater than 2.58 had a 100 % sensitivity (95 % CI 43.8–100) and 95.4 % specificity (95 % CI 38.3–99.7) in discriminating malignant from benign parathyroid nodules. Elastoscan^TM Core Index was significantly higher in thyroid nodules than in reactive lymph nodes (1.18 ± 0.62, p = 0.008). The ultrasound features of cleavage and peripheral vascularization help to differentiate parathyroid from thyroid nodules. Elastoscan^TM Core Index can improve ultrasound discrimination of parathyroid lesions from lymph nodes. The Elastoscan^TM Core Index is significantly higher in malignant than in benign parathyroid lesions.

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Prospective, long-term study of the effect of cabergoline on valvular status in patients with prolactinoma and idiopathic hyperprolactinemia

Abstract

Since the 1990's cabergoline has been the treatment of choice in prolactinoma, as it permits rapid and effective hormonal and tumor control in most cases. Evidence of cardiac valvulopathy was demonstrated in Parkinson's disease patients treated with dopamine agonists. Retrospective studies in prolactinoma patients treated with cabergoline at lower doses did not show such an effect. However, few prospective data with long-term follow-up are available. The aim of this study was to assess the safety of cabergoline regarding cardiac valvular status during prospective follow-up in patients treated for prolactinoma or idiopathic hyperprolactinemia. We report here a series of 100 patients (71F; median age at diagnosis: 41.5 years) treated with cabergoline for endocrine diseases (prolactinoma n = 89, idiopathic hyperprolactinemia n = 11). All patients underwent complete transthoracic echocardiographic studies at baseline and during long-term prospective surveillance using the same equipment and performed by the same technicians. The median interval between baseline and last follow-up echocardiographic studies while on cabergoline was 62.5 months (interquartile range: 34.75–77.0). The median total duration of cabergoline treatment was 124.5 months (interquartile range: 80.75–188.75) and the median cumulative total dose of cabergoline was 277.8 mg (interquartile range : 121.4–437.8 mg) at last follow-up. We found no clinically relevant alterations in cardiac valve function or valvular calcifications with cabergoline treatment. Our data suggest that findings from retrospective analyses are correct and that cabergoline is a safe chronic treatment at the doses used typically in endocrinology.

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Natural history of graves’ orbitopathy after treatment

Abstract

Intravenous glucocorticoids are used for Graves' orbitopathy, alone or associated with/followed by additional treatments (orbital radiotherapy, orbital decompression, palpebral or eye surgery). However, the relation between associated/additional treatments and other variables with Graves' orbitopathy outcome following intravenous glucocorticoids is not clear. Thus, the present study was conducted to investigate retrospectively the impact of associated/additional treatments and other variables on Graves' orbitopathy outcome after intravenous glucocorticoids. We evaluated 226 untreated Graves' orbitopathy patients. Following first observation, patients were given intravenous glucocorticoids and re-examined after a median of 46.5 months. The end-points were the relation between Graves' orbitopathy outcome, outcome of NOSPECS score and of the single Graves' orbitopathy features with several variables, including associated/additional treatments. All Graves' orbitopathy features improved significantly after treatment. Overall, Graves' orbitopathy improved in ~60 % of patients (responders), whereas it was stable or worsened in ~40 % of patients (non-responders). Time between first and last observation and clinical activity score at first observation correlated significantly with Graves' orbitopathy outcome. The outcomes of NOSPECS, eyelid aperture, clinical activity score and diplopia correlated with time between the first and last observation. The NOSPECS outcome correlated with gender. The outcomes of proptosis, eyelid aperture and visual acuity correlated with orbital decompression. The outcome of diplopia correlated with orbital radiotherapy. Taking into account the limitations of retrospective investigations, our findings confirm that time (i.e. the natural history of Graves' orbitopathy) is a key factor in determining the long-term outcome of Graves' orbitopathy, radiotherapy is effective for diplopia, and orbital decompression is followed by an amelioration of several Graves' orbitopathy features.

http://ift.tt/2dec8Jl

Identifying the culprit lesion in tumor induced hypophosphatemia, the solution of a clinical enigma

Abstract

Tumor-induced osteomalacia is a rare acquired metabolic bone disorder characterized by isolated renal phosphate wasting due to abnormal tumor production of fibroblast growth factor 23. We report the case of a 59 year old woman referred to our department with a long history of progressive diffuse muscle weakness and pain, generalized bone pains and multiple insufficiency fractures of heels, ankles and hips due to a hypophosphatemic osteomalacia. A fibroblast growth factor 23-producing phosphaturic mesenchymal tumor localized in the left quadriceps femoris muscle was identified 7 years after onset of symptoms. Excision of the tumor resulted in normalization of serum phosphate and fibroblast growth factor 23 levels and in complete resolution of the clinical picture with disappearance of all musculoskeletal symptoms. This case illustrates the diagnostic difficulties in establishing a diagnosis tumor-induced osteomalacia and in identifying the responsible tumor. Our case underscores the clinical need to investigate all patients with persistent musculoskeletal symptoms for hypophosphatemia. A systematic approach is of pivotal importance because early recognition and treatment of the metabolic abnormality can prevent deleterious effects of osteomalacia on the skeleton.

http://ift.tt/2dE5z62

Projections from the lowest lumbar and sacral-caudal segments to the cerebellar cortex in the rat: an anterograde tracing study

Publication date: Available online 5 October 2016
Source:Neuroscience Research
Author(s): Matsuo Matsushita
The crossed spinocerebellar tracts originate from neurons in the basolateral part of lamina V, the sacral nuclei of Stilling and the ventrolateral part of the ventral horn of the L6 to caudal segments. The present study examined their projection areas in the cerebellar cortex by using anterograde labeling of mossy fiber terminals with biotinylated dextran in the rat. Labeled terminals were distributed bilaterally in lobules I–V of the anterior lobe. They were most abundant in the apical parts of the lateral vermis and the intermediate region of lobules Ib and IIa, and the rostral side of lobule IIb. The number of labeled terminals in lobules Ib-IIb accounted for 56% and 81%, respectively, of the total 9,783 and 7,045 labeled terminals. The number of labeled terminals decreased in lobules III to V. In the posterior lobe labeled terminals were distributed exclusively to lobules VIIIa and VIIIb and copula pyramidis. The present study demonstrates that spinocerebellar neurons of the sacral-caudal segments project primarily to the lateral part of lobules I and II, and less densely to lobules III–V and VIII, and copula pyramidis. The projection pattern was essentially similar to that observed in the cat.



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Physiological contribution of P2X receptors in postreceptoral signal processing in the mouse retina

Publication date: Available online 5 October 2016
Source:Neuroscience Research
Author(s): Sho Ichinohe, Toshiyuki Ishii, Hiroshi Takahashi, Makoto Kaneda
ATP activates P2X receptors and acts as a neurotransmitter in the nervous system. We have previously reported that P2X receptors modulate the firing rate of retinal ganglion cells. Since many subtypes of P2X receptors are distributed in the mouse retina, it is likely that the modulatory effects of P2X receptor-mediated signaling can occur at multiple synaptic levels in the retina. In this study, we investigated whether P2X receptors expressed between the photoreceptor layer and the inner nuclear layer in the mouse retina were physiologically functional, by electroretinography (ERG). In the combined rod-cone ERG and the scotopic ERG, intravitreal injection of PPADS, an antagonist of P2X receptors, had no effects on the amplitude of the a-wave, but decreased the amplitude of the b-wave. In the photopic ERG, intravitreal injection of PPADS significantly decreased the amplitude of both the a-wave and the b-wave. In ex vivo recordings, a decrease in the b-wave amplitude was observed at 20μM PPADS, confirming that the inhibition of the b-wave by intravitreal injection of PPADS is due to the inhibition of P2X receptors. Our findings suggest that P2X receptor-mediated signaling has a physiological effect in both the rod and the cone pathways in postreceptoral processing.



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Synthesis, characterization and liver targeting evaluation of self-assembled hyaluronic acid nanoparticles functionalized with glycyrrhetinic acid

Publication date: 1 January 2017
Source:European Journal of Pharmaceutical Sciences, Volume 96
Author(s): Xiaodan Wang, Xiangqin Gu, Huimin Wang, Yujiao Sun, Haiyang Wu, Shirui Mao
Recently, polymeric materials with multiple functions have drawn great attention as the carrier for drug delivery system design. In this study, a series of multifunctional drug delivery carriers, hyaluronic acid (HA)-glycyrrhetinic acid (GA) succinate (HSG) copolymers were synthesized via hydroxyl group modification of hyaluronic acid. It was shown that the HSG nanoparticles had sub-spherical shape, and the particle size was in the range of 152.6–260.7nm depending on GA graft ratio. HSG nanoparticles presented good short term and dilution stability. MTT assay demonstrated all the copolymers presented no significant cytotoxicity. In vivo imaging analysis suggested HSG nanoparticles had superior liver targeting efficiency and the liver targeting capacity was GA graft ratio dependent. The accumulation of DiR (a lipophilic, NIR fluorescent cyanine dye)-loaded HSG-6, HSG-12, and HSG-20 nanoparticles in liver was 1.8-, 2.1-, and 2.9-fold higher than that of free DiR. The binding site of GA on HA may influence liver targeting efficiency. These results indicated that HSG copolymers based nanoparticles are potential drug carrier for improved liver targeting.

Graphical abstract

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Enhanced in vitro cytotoxicity and anti-tumor activity of vorinostat-loaded pluronic micelles with prolonged release and reduced hepatic and renal toxicities

Publication date: 1 January 2017
Source:European Journal of Pharmaceutical Sciences, Volume 96
Author(s): Elham Abdelmonem Mohamed, Irhan Ibrahim Abu Hashim, Rehab Mohammad Yusif, Ghada Mohamed Suddek, Ahmed Abdel Aziz Shaaban, Farid Abd Elreheem Badria
Vorinostat is the first histone deacetylase inhibitor approved by US FDA for use in cancer therapy. However, its limited aqueous solubility, low permeability, and suboptimal pharmacokinetics hinder its delivery. Thus, in this study, micelles of vorinostat with each of pluronic F68 (PF68) and pluronic F127 (PF127) were developed and optimized based on drug loading and entrapment. The optimized micelles were characterized using Fourier transform infrared spectroscopy (FT-IR), X-ray diffractometry (XRD), differential scanning calorimetry (DSC), zeta analyzer, and electron transmission microscopy. Their in vitro release, stability, in vitro cytotoxicity against HepG2, Caco-2, and MCF-7 cell lines, and finally, in vivo antitumor activity in mice bearing Ehrlich Ascites Carcinoma (EAC) were assessed. The highest entrapment efficiency was 99.09±2.16% and 94.19±2.37% for micelles of 1:50 drug to polymer ratio with each of PF127 and PF68, respectively. These micelles were nearly spherical with nanoscopic mean diameters of 72.61±10.66nm for PF68 and 91.88±10.70nm for PF127 with narrow size distribution. The micelles provided prolonged release at phosphate buffer saline pH7.4 up to 24h for PF68 and 72h for PF127. Potentiation of in vitro cytotoxicity of vorinostat was more pronounced with PF127 micelles particularly against MCF-7 cells. Compared with free vorinostat, the micelles with PF127 were more effective in inhibiting tumor growth as well as exhibiting significantly (p<0.05) diminished hepatic and renal toxicities. In conclusion, 1:50 vorinostat-PF127 micelles may facilitate i.v. formulations and can be suggested as a promising stable and safe nanoparticulate delivery system with prolonged release and potentiated cytotoxicity.

Graphical abstract

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Development and evaluation of silver sulfadiazine loaded microsponge based gel for partial thickness (second degree) burn wounds

Publication date: 1 January 2017
Source:European Journal of Pharmaceutical Sciences, Volume 96
Author(s): P. Mahesh Kumar, Animesh Ghosh
Silver sulfadiazine has been frequently used as an antibacterial agent for topical treatment of partial thickness burn wounds. In this study, we present the preparation of silver sulfadiazine microsponges by w/o/w emulsion solvent evaporation method. Formulation variables were optimized by using 3² factorial design. The optimized microsponges were characterized by FTIR, DSC, PXRD, particle size analysis, SEM analysis and mercury intrusion porosimetry studies. Viscosity, texture analysis and ex vivo drug deposition study of optimized microsponge loaded gel were also evaluated. The safety of the optimized gel was assessed by MTT assay using epidermal keratinocyte (HaCaT) and mouse embryonic fibroblast (NIH-3T3) cell lines. In vitro antibacterial studies were carried out to compare the antibacterial inhibitory efficiency of the optimized gel against the commercial product. The efficacy of the optimized gel was evaluated by the partial thickness (second degree) burn wound model in mice. Optimized microsponge loaded gel enhanced the drug retaining capacity in the skin layers, by 3 fold higher to that of a commercial product. The antibacterial inhibitory efficiency of optimized gel was similar to the commercial product against the Staphylococcus aureus and Pseudomonas aeruginosa. Optimized gel showed reduced frequency of application, no skin irritation, low cytotoxicity on dermal cell lines and enhanced wound contraction.

Graphical abstract

http://ift.tt/2dxwePV

Do CAD/CAM dentures really release less monomer than conventional dentures?

Abstract

Objectives

Computer-aided design (CAD)/computer-aided manufacturing (CAM) dentures are assumed to have more favourable material properties than conventionally fabricated dentures, among them a lower methacrylate monomer release. The aim of this study was to test this hypothesis.

Materials and methods

CAD/CAM dentures were generated from ten different master casts by using four different CAD/CAM systems. Conventional, heat-polymerised dentures served as control group. Denture weight and volume were measured; the density was calculated, and the denture surface area was assessed digitally. The monomer release after 7 days of water storage was measured by high-performance liquid chromatography.

Results

Whole You Nexteeth and Wieland Digital Dentures had significantly lower mean volume and weight than conventional dentures. Baltic Denture System and Whole You Nexteeth had a significantly increased density. Baltic Denture System had a significantly smaller surface area. None of the CAD/CAM dentures released significantly less monomer than the control group.

Conclusions

All tested dentures released very low amounts of methacrylate monomer, but not significantly less than conventional dentures. A statistically significant difference might nevertheless exist in comparison to other, less recommendable denture base materials, such as the frequently used autopolymerising resins.

Clinical relevance

CAD/CAM denture fabrication has numerous advantages. It enables the fabrication of dentures with lower resin volume and lower denture weight. Both could increase the patient comfort. Dentures with higher density might exhibit more favourable mechanical properties. The hypothesis that CAD/CAM dentures release less monomer than conventional dentures could, however, not be verified.

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The regulation of human globin promoters by CCAAT box elements and the recruitment of NF-Y

Publication date: Available online 5 October 2016
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Gabriella E. Martyn, Kate G.R. Quinlan, Merlin Crossley
CCAAT boxes are motifs found within the proximal promoter of many genes, including the human globin genes. The highly conserved nature of CCAAT box motifs within the promoter region of both α-like and β-like globin genes emphasises the functional importance of the CCAAT sequence in globin gene regulation. Mutations within the β-globin CCAAT box result in β-thalassaemia, while mutations within the distal γ-globin CCAAT box cause the Hereditary Persistence of Foetal Haemoglobin, a benign condition which results in continued γ-globin expression during adult life. Understanding the transcriptional regulation of the globin genes is of particular interest, as reactivating the foetal γ-globin gene alleviates the symptoms of β-thalassaemia and sickle cell anaemia. NF-Y is considered to be the primary activating transcription factor which binds to globin CCAAT box motifs. Here we review recruitment of NF-Y to globin CCAAT boxes and the role NF-Y plays in regulating globin gene expression. This article is part of a Special Issue entitled: Nuclear Factor Y in Development and Disease, edited by Prof. Roberto Mantovani.



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BET bromodomain is a novel regulator of TAZ and its activity

Publication date: Available online 4 October 2016
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Qiong Duan, Yi Xiao, Zhenzhen Liu, Xiaoxiao Mao, Zhengxiang Zhou, Chaonan Liao, Jinxing Cai, Fulian Huang, Zehao Liu, Jian Zeng, Ke Xia, Cheng Chang, Jun Qi, Zihua Chen, He Huang, Tianlun Yang
Transcriptional coactivator with PDZ-binding motif (TAZ) is a key transcriptional mediator of Hippo signaling that has been recently reported to mediate Wnt-activated transcription and serve as a component to suppress canonical Wnt/β-catenin activity. The Bromodomain and Extra-terminal domain (BET) family of proteins can recognize the acetylated lysine chain on histones and plays a critical role in transcriptional regulation. However, the mechanisms underlying transcriptional repression by the BET bromodomain are poorly understood. Here, we found that BET bromodomain inhibition upregulated TAZ protein and its transcriptional output, independent of its well-established role as a mediator of Hippo and Wnt signaling. Additionally, JQ1, a synthetic BET inhibitor, suppressed Wnt/β-catenin activity by upregulating TAZ. Although JQ1 upregulated TAZ, which is known to promote cell proliferation, it drastically suppressed the growth of colon cancer cells by inducing cell cycle arrest. Collectively, our study identified an unexpected transcriptional repression function of the BET bromodomain and a novel mechanism for TAZ upregulation.



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Scholar : These new articles for Cartography and Geographic Information Science are available online

The online platform for Taylor & Francis Online content New for Cartography and Geographic Information Science and online now on Taylor & Francis Online: Original Articles Geosocial capta in geographical research – a critical analysis Michal Rzeszewski Pages: 1-13 | DOI: 10.1080/15230406.2016.1229221 How has social media affected Earth Science? Find out with our Social Media Research collection now available with free access! This message is personalised to your status as a society member. Please do not forward this email. To recommend content, please use the social sharing tools on the website. To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Shear-wave Elastography: Could it Be Helpful for the Diagnosis of Non-Mass-like Breast Lesions?

Publication date: Available online 4 October 2016
Source:Ultrasound in Medicine & Biology
Author(s): Zhi Li Wang, Ye Li, Wen Bo Wan, Nan Li, Jie Tang
The goal of this study was to analyze the diagnostic performance of shear wave elastography (SWE) in differentiation of benign and malignant non-mass-like (NML) breast lesions. Three hundred sixteen consecutive breast lesions in 305 patients who have been scheduled for ultrasound (US)-guided core needle biopsy or vacuum-assisted biopsy or surgical excision between January 2013 and August 2013 were initially included in this study. Finally, 63 patients with 67 lesions classified as NML lesions comprised our study population. The features of SWE and its diagnostic performance in NML lesions were analyzed. Among the 67 NML lesions, 33 were malignant and 34 were benign. The maximum elastic modulus, mean elastic modulus, minimum elastic modulus, elastic modulus ratio and stiff rim sign of the malignant lesions were all significantly higher than those of benign lesions (p < 0.05). The combination of conventional US with maximum elastic modulus and stiff rim sign got significantly higher diagnostic specificity and positive predictive value (PPV) than conventional US (p < 0.05 for both). In the benign lesions, 23 (67.6%) unnecessary biopsies could have been eliminated after the combination of conventional US and SWE. SWE could increase diagnostic specificity and positive predictive values of NML breast lesions. The combination of conventional US and SWE could reduce unnecessary benign biopsies of NML lesions.



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Video Coaching as an Efficient Teaching Method for Surgical Residents—A Randomized Controlled Trial

Publication date: Available online 5 October 2016
Source:Journal of Surgical Education
Author(s): Mikael L. Soucisse, Kerianne Boulva, Lucas Sideris, Pierre Drolet, Michel Morin, Pierre Dubé
BackgroundAs surgical training is evolving and operative exposure is decreasing, new, effective, and experiential learning methods are needed to ensure surgical competency and patient safety. Video coaching is an emerging concept in surgery that needs further investigation.DesignIn this randomized controlled trial conducted at a single teaching hospital, participating residents were filmed performing a side-to-side intestinal anastomosis on cadaveric dog bowel for baseline assessment. The Surgical Video Coaching (SVC) group then participated in a one-on-one video playback coaching and debriefing session with a surgeon, during which constructive feedback was given. The control group went on with their normal clinical duties without coaching or debriefing. All participants were filmed making a second intestinal anastomosis. This was compared to their first anastomosis using a 7-category-validated technical skill global rating scale, the Objective Structured Assessment of Technical Skills. A single independent surgeon who did not participate in coaching or debriefing to the SVC group reviewed all videos. A satisfaction survey was then sent to the residents in the coaching group.SettingDepartment of Surgery, HôpitalMaisonneuve-Rosemont, tertiary teaching hospital affiliated to the University of Montreal, Canada.ParticipantsGeneral surgery residents from University of Montreal were recruited to take part in this trial. A total of 28 residents were randomized and completed the study.ResultsAfter intervention, the SVC group (n = 14) significantly increased their Objective Structured Assessment of Technical Skills score (mean of differences 3.36, [1.09-5.63], p = 0.007) when compared to the control group (n = 14) (mean of differences 0.29, p = 0.759). All residents agreed or strongly agreed that video coaching was a time-efficient teaching method.ConclusionsVideo coaching is an effective and efficient teaching intervention to improve surgical residents' technical skills.



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Changing the Learning Curve in Novice Laparoscopists: Incorporating Direct Visualization into the Simulation Training Program

Publication date: Available online 4 October 2016
Source:Journal of Surgical Education
Author(s): Mark T. Dawidek, Victoria A. Roach, Michael C. Ott, Timothy D. Wilson
ObjectiveA major challenge in laparoscopic surgery is the lack of depth perception. With the development and continued improvement of 3D video technology, the potential benefit of restoring 3D vision to laparoscopy has received substantial attention from the surgical community. Despite this, procedures conducted under 2D vision remain the standard of care, and trainees must become proficient in 2D laparoscopy. This study aims to determine whether incorporating 3D vision into a 2D laparoscopic simulation curriculum accelerates skill acquisition in novices.DesignPostgraduate year-1 surgical specialty residents (n = 15) at the Schulich School of Medicine and Dentistry, at Western University were randomized into 1 of 2 groups. The control group practiced the Fundamentals of Laparoscopic Surgery peg-transfer task to proficiency exclusively under standard 2D laparoscopy conditions. The experimental group first practiced peg transfer under 3D direct visualization, with direct visualization of the working field. Upon reaching proficiency, this group underwent a perceptual switch, changing to standard 2D laparoscopy conditions, and once again trained to proficiency.ResultsIncorporating 3D direct visualization before training under standard 2D conditions significantly (p < 0.0.5) reduced the total training time to proficiency by 10.9 minutes or 32.4%. There was no difference in total number of repetitions to proficiency. Data were also used to generate learning curves for each respective training protocol.ConclusionsAn adaptive learning approach, which incorporates 3D direct visualization into a 2D laparoscopic simulation curriculum, accelerates skill acquisition. This is in contrast to previous work, possibly owing to the proficiency-based methodology employed, and has implications for resource savings in surgical training.



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Penetrating Keratoplasty Performed by Residents Compared With an Experienced Cornea Transplant Surgeon

Publication date: Available online 4 October 2016
Source:Journal of Surgical Education
Author(s): Machiko Shimmura-Tomita, Shigeto Shimmura, Kazuo Tsubota, Jun Shimazaki
BackgroundReports on keratoplasty by residents are rare compared to those on cataract surgery. The aim of this study was to compare the results and surgery time of penetrating keratoplasty performed by residents and an experienced cornea surgeon.MethodsThe medical records and surgery videos of the first 5 penetrating keratoplasty procedures by 4 residents were reviewed and compared with those in 20 penetrating keratoplasty procedures by an experienced cornea surgeon. Patients underwent penetrating keratoplasty at the Department of Ophthalmology, Tokyo Dental College, Chiba, Japan. The main outcome measures are graft survival, best-corrected visual acuity, postoperative astigmatism, decreased rate of graft endothelial cell density, and details of surgery time.ResultsGraft survival, best-corrected visual acuity, and postoperative astigmatism were not significantly different between residents group and the experienced surgeon group. The average decrease of graft endothelial cell density owing to surgery in residents and the experienced surgeon were 19.0 ± 17.5 and 18.5 ± 12.1%, respectively (p = 0.27, Mann-Whitney U test). The average surgery time taken by residents was 66.9 ± 18.1 minutes, and that by the experienced surgeon it was 28.2 ± 7.9 minutes (p = 0.0071, Mann-Whitney U test). Residents required the most time for running suture technique.ConclusionsThe results of keratoplasty by residents were similar with those done by the experienced surgeon. Surgery time was the only statistically significant difference (p = 0.0071), which did not influence surgical results.



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How Informative are the Plastic Surgery Residency Websites to Prospective Applicants?

Publication date: Available online 4 October 2016
Source:Journal of Surgical Education
Author(s): Asra Hashmi, Rohan Policherla, Hector Campbell, Faraz A. Khan, Adam Schumaier, Faisal Al-Mufarrej
ObjectiveTo evaluate the comprehensiveness of plastic surgery program websites.DesignAmerican Medical Association interactive database was accessed for the list of integrated plastic surgery programs, in June 2015. Since then, 67 plastic surgery program websites were accessed and searched for the presence or absence of 31 criteria, which were further grouped into 5 categories: First, program contact information; second, training and research; third, program setup; fourth, benefits and facilities; and fifth, information for applicants. Programs were categorized based on US census bureau designated regions, and number of residency positions available. One-way ANOVA test was used for comparison.ResultsOnly 25% (17) program website had information available on more than two-thirds (21 or more of 31) of the criteria. The 3 least factors commonly available by program websites were: operative log (10%), contract (10%), and information on night float (25%). The 3 most commonly available factors included: coordinator information (92%), number of residents (92%), and comprehensive faculty list (88%). Less than 50% of the programs provided information regarding fellowship opportunities, active and previous research projects, and operative logs. There was no difference in amount of information on program websites when analyzed for program size or program geographic location.ConclusionPrograms should consider revising their websites to include aforementioned 31 criteria. This would make applicants and potential resident physicians better informed of the programs before the interview process such that they would be more likely to apply to only those programs that match their specific aspirations.



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Does the H Index Correlate With Academic Rank Among Full-Time Academic Craniofacial Surgeons?

Publication date: Available online 4 October 2016
Source:Journal of Surgical Education
Author(s): Srinivas M. Susarla, Erin M. Rada, Joseph Lopez, Edward W. Swanson, Devin Miller, Richard J. Redett, Anand R. Kumar
ObjectiveTo assess the relationship between the H index and the academic rank among full-time academic craniofacial surgeons.DesignThis was a cross-sectional study of full-time academic craniofacial surgeons.SettingData were compiled and analyzed at the Department of Plastic and Reconstructive Surgery, Johns Hopkins Hospital.ResultsThe study sample included 127 full-time academic craniofacial surgeons. Overall, 89% were men, the mean number of years since completion of training was 16.2 ± 11.2 years. Most surgeons had a background in plastic and reconstructive surgery. Approximately 75% had completed formal fellowship training. The mean H index for the sample was 12.4 ± 9.9. The H index was strongly correlated with academic rank (rs = 0.62, p < 0.001). In a multiple linear regression model, adjusting for multiple confounders/effect modifiers, including number of years since training and total number of publications, the H index was significantly associated with academic rank (coefficient = 0.33, p = 0.04).ConclusionsAmong full-time academic craniofacial surgeons, the H index is strongly correlated with the academic rank.



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Construct Validity, Assessment of the Learning Curve, and Experience of Using a Low-Cost Arthroscopic Surgical Simulator

Publication date: Available online 5 October 2016
Source:Journal of Surgical Education
Author(s): Henry B. Colaco, Katie Hughes, Eyiyemi Pearse, Magnus Arnander, Duncan Tennent
ObjectiveWe have developed a low-cost, portable shoulder simulator designed to train basic arthroscopic skills. This study aimed to establish the construct validity of the simulator by determining which parameters discriminated between experience levels and to assess the experience of using the simulator.DesignParticipants were given an introductory presentation and an untimed practice run of a 6-step triangulation task using hooks and rubber bands. A total of 6 consecutive attempts at the task were timed, and the number of times the participant looked at their hands during the task was recorded. Participants then completed a questionnaire on their experience of using the simulator.SettingSt George's Hospital, London and the South West London Elective Orthopaedic Centre, Surrey.ParticipantsMedical students, trainee doctors and surgeons, and consultant surgeons were approached to use the simulator. Participation was voluntary and nonincentivized. In total, 7 orthopedic consultants, 12 trainee doctors (ranging from foundation year 1 to clinical fellow post-Certificate of Completion of Training), and 9 medical students were recruited.ResultsThe average time for medical students to complete the task was 161 seconds, compared to 118 seconds for trainees, and 84 seconds for consultants. The average fastest time for medical students was 105 seconds, 73 seconds for trainees, and 52 seconds for consultants. Students were significantly slower than trainees (p = 0.026) and consultants (p = 0.001). However, times did not differ significantly between trainees and consultants. Consultants looked at their hands 0.7 times on average during the task compared with 2.8 and 3.4 times for trainees and students, respectively. More than 95% of participants found the exercise interesting and agreed or strongly agreed that the simulator was easy to use, easily portable, and well designed and constructed.DiscussionThis study has established construct validity of the simulator by demonstrating the ability to distinguish between surgical experience levels. The learning curve shows improvement in individuals with or without arthroscopic or surgical experience. Simulation is becoming increasingly important in the training of medical students and surgical trainees; this study has established that low-cost portable arthroscopic box trainers may play a significant role.



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Evaluation of Procedural Simulation as a Training and Assessment Tool in General Surgery—Simulating a Laparoscopic Appendectomy

Publication date: Available online 4 October 2016
Source:Journal of Surgical Education
Author(s): Flemming Bjerrum, Jeanett Strandbygaard, Susanne Rosthøj, Teodor Grantcharov, Bent Ottesen, Jette Led Sorensen
BackgroundLaparoscopic appendectomy is a commonly performed surgical procedure, but few training models have been described for it. We examined a virtual reality module for practising a laparoscopic appendectomy.MethodsA prospective cohort study with the following 3 groups of surgeons (n = 45): novices (0 procedures), intermediates (10-50 procedures), and experienced (>100 procedures). After being introduced to the simulator and 1 familiarization attempt on the procedural module, the participants practiced the module 20 times. Movements, task time, and procedure-specific parameters were compared over time.ResultsThe time and movement parameters were significantly different during the first attempt, and more experienced surgeons used fewer movements and less time than novices (p < 0.01), although only 2 parameters were significantly different between novices and intermediates. All 3 groups improved significantly over 20 attempts (p < 0.0001). The intraclass correlation coefficient varied between 0.55 and 0.68 and did not differ significantly between the 3 groups (p > 0.05).When comparing novices with experienced surgeons, novices had a higher risk of burn damage to cecum (odds ratio [OR] = 3.0 [95% CI: 1.3; 7.0] p = 0.03), pressure damage to appendix (OR = 3.1 [95% CI: 2.0; 4.9] p < 0.0001), and grasping of the appendix (OR = 2.9 [95% CI: 1.8; 4.7] p < 0.0001). The risk of causing a perforation was not significantly different among the different experience levels (OR = 1.9 [95% CI: 0.9; 3.8] p = 0.14). Only 3 out of 5 error parameters differed significantly when comparing novices and experienced surgeons. Similarly, when comparing intermediates and novices, it was only 2 of the parameters that differed.DiscussionThe simulator module for practising laparoscopic appendectomy may be useful as a training tool, but further development is required before it can be used for assessment purposes. Procedural simulation may demonstrate more variation for movement parameters, and future research should focus on developing better procedure-specific parameters.



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Effect of Home-Call on Otolaryngology Resident Education: A Pilot Study

Publication date: Available online 4 October 2016
Source:Journal of Surgical Education
Author(s): Lisa Caulley, Alexandra E. Quimby, Nick Barrowman, Katherine Moreau, Jean-Philippe Vaccani
ObjectiveTo inform institutional policies regarding call encounters through an evaluation of the effect of home-call on academic experience and fatigue among surgical residents. This study conducted an assessment of the nature of resident call encounters premidnight and postmidnight and a comparative analysis of sleep deprivation and efficiency in residents during home-call and off call.Design, Setting, and ParticipantsAll Otolaryngology—Head and Neck Surgery residents (n = 9) at single Canadian institution were asked to establish the time and nature of call encounters during home-call. Residents completed the Stanford Sleepiness Scale precall and postcall to measure sleepiness and wore an Actigraph device to measure sleep efficiency to establish fatigue in the setting of home-call as compared with residents off call. Home-call and off call patterns were studied using a random computer-generated selection of days for participants in both study groups. Analysis was conducted from December 1, 2013 to December 30, 2014.ResultsResidents received on average 7 pages per night, of which 78.5% of pages were for nonurgent issues. On an average, change in sleep deprivation scores postcall was 3.0 points higher (95% CI: 2.48–3.57, p < 0.0001) in residents who were qualified for a postcall day compared with residents who did not qualify for a postcall day and residents off call according to the Stanford Sleepiness Scale. Postcall sleep deprivation was significantly associated with number of encounters managed after midnight, regardless of management through telephone or in-hospital (p = 0.01). The Actigraph device identified a significant decrease in sleep efficiency in residents who were qualified for a postcall day compared with residents off call (mean = −31.1; 95% CI: −38.9, −23.4; p < 0.001).ConclusionsThis is the first study to evaluate surgical residents' home-call experience. We identified a high proportion of nonurgent encounters that residents managed on call and increased postcall fatigue associated with postmidnight telephone encounters. This study highlights the detrimental effects of frequent sleep interruptions because of encounters on call and suggests the need for institutional guidelines to help minimize these interruptions.



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Contribution of amygdala to the pressor response elicited by microinjection of angiotensin II into the bed nucleus of the stria terminalis

Publication date: Available online 5 October 2016
Source:Brain Research Bulletin
Author(s): Marzieh Kafami, Ali Nasimi
The bed nucleus of the stria terminalis (BST) is part of the limbic system located in the rostral forebrain. BST is involved in behavioral, neuroendocrine and autonomic functions, including cardiovascular regulation. The amygdala, plays an important role in mediating the behavioral and physiological responses associated with fear and anxiety, including cardiovascular responses. In a previous study, we showed that microinjection of AngII into the BST produced a pressor and two types of single-unit responses in the BST, short excitatory and long inhibitory. This study was performed to find possible involvement of amygdala in cardiovascular responses elicited by microinjection of AngII into the BST, using blockade of the central nucleus of amygdala (CeA) and single unit recording from the CeA, while injecting AngII into the BST in anesthetized rat. Blockade of CeA attenuated the pressor response to microinjection of AngII into the BST. Eighty-six AngII microinjections were given into the BST and 198 single unit responses were recorded from CeA simultaneously, from which 89 showed a short duration excitatory response and 109 showed no responses. In conclusion, microinjection of AngII into the BST produces a short excitatory single unit response in the CeA, resulting in contribution of amygdala to the resulted pressor response. Taken together, our study and previous studies suggest a plausible hypothesis that these two nuclei perform their cardiovascular functions in cooperation with each other.



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Piecing Together the Patchwork of Contact Sites

Publication date: Available online 4 October 2016
Source:Trends in Cell Biology
Author(s): Alberto T. Gatta, Tim P. Levine
Contact sites are places where two organelles join together to carry out a shared activity requiring nonvesicular communication. A large number of contact sites have been discovered, and almost any two organelles can contact each other. General rules about contacts include constraints on bridging proteins, with only a minority of bridges physically creating contacts by acting as 'tethers'. The downstream effects of contacts include changing the physical behaviour of organelles, and also forming biochemically heterogeneous subdomains. However, some functions typically localized to contact sites, such as lipid transfer, have no absolute requirement to be situated there. Therefore, the key aspect of contacts is the directness of communication, which allows metabolic channelling and collective regulation.



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Interest of Pregabalin (Lyrica) on the Treatment of Reflex Earache in Head and Neck Cancer.

Condition:   Earache
Interventions:   Drug: Pregabalin;   Drug: Placebo
Sponsor:   University Hospital, Lille
Recruiting - verified October 2016

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Phase II Trial of Neoadjuvant Treatment and Minimal Invasive Surgery for Esophageal and GEJ Cancer

Conditions:   Esophageal Cancer;   Induction Chemotherapy
Intervention:   Drug: carboplatin paclitaxel
Sponsor:   Instituto Nacional de Cancer, Brazil
Not yet recruiting - verified October 2016

http://ift.tt/2drKb6f

Effect of veliparib (ABT-888) on cardiac repolarization in patients with advanced solid tumors: a randomized, placebo-controlled crossover study

Abstract

Purpose

Veliparib (ABT-888) is an orally bioavailable potent inhibitor of poly(ADP-ribose) polymerase (PARP)-1 and PARP-2. This phase 1 study evaluated the effect of veliparib on corrected QT interval using Fridericia's formula (QTcF).

Methods

Eligible patients with advanced solid tumors received single-dose oral veliparib (200 mg or 400 mg) or placebo in a 6-sequence, 3-period crossover design. The primary endpoint was the difference in the mean baseline-adjusted QTcF between 400 mg veliparib and placebo (∆∆QTcF) at six post-dose time points. Absence of clinically relevant QTcF effect was shown if the 95 % upper confidence bound (UCB) for the mean ∆∆QTcF was <10 ms for all time points. An exposure–response analysis was also performed.

Results

Forty-seven patients were enrolled. Maximum mean ∆∆QTcF of veliparib 400 mg was 6.4 ms, with a 95 % UCB of 8.9 ms; for veliparib 200 mg, the maximum mean ∆∆QTcF was 3.6 ms, with a 95 % UCB of 6.1 ms. No patient had a QTcF value >480 ms or change from baseline in QTcF interval >30 ms. Treatment-emergent adverse events (TEAEs) were experienced by 36.2, 48.9, and 47.8 % of patients while receiving veliparib 200 mg, veliparib 400 mg, and placebo, respectively. Most common TEAEs were nausea (12.8 %) and myalgia (8.5 %) after veliparib 200 mg, nausea (8.5 %) and vomiting (8.5 %) after veliparib 400 mg, and nausea (6.5 %) after placebo.

Conclusions

Single-dose veliparib (200 mg or 400 mg) did not result in clinically significant QTc prolongation and was well tolerated in patients with advanced solid tumors.

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Scholar : These new articles for Journal of Tourism and Cultural Change are available online

The online platform for Taylor & Francis Online content New for Journal of Tourism and Cultural Change and online now on Taylor & Francis Online: Original Articles Tourism as a discipline in light of the non-classical sociology of science Leszek Butowski Pages: 1-19 | DOI: 10.1080/14766825.2016.1237959 Time and tide wait for no man (or woman). Explore the multidisciplinary TIME Collection now. This message is personalised to your status as a society member. Please do not forward this email. To recommend content, please use the social sharing tools on the website. To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Inhibition of aryl hydrocarbon receptor signaling and induction of NRF2-mediated antioxidant activity by cinnamaldehyde in human keratinocytes

Publication date: Available online 4 October 2016
Source:Journal of Dermatological Science
Author(s): Hiroshi Uchi, Mao Yasumatsu, Saori Morino-Koga, Chikage Mitoma, Masutaka Furue
BackgroundDioxins and other environmental pollutants are toxic and remain in biological tissues for a long time leading to various levels of oxidative stress. Although the toxicity of these agents has been linked to activation of the aryl hydrocarbon receptor (AHR), no effective treatment has been developed.ObjectiveTo explore novel phytochemicals that inhibit AHR activation in keratinocytes.MethodsKeratinocytes were used in this study because the skin is one of the organs most affected by dioxin and other environmental pollutants. HaCaT cells, which are a human keratinocyte cell line, and normal human epidermal keratinocytes were stimulated with benzo[a]pyrene to induce AHR activation, and the effects of traditional Japanese Kampo herbal formulae were analyzed. Quantification of mRNA, western blotting, immunofluorescence localization of molecules, siRNA silencing, and visualization of oxidative stress were performed.ResultsCinnamomum cassia extract and its major constituent cinnamaldehyde significantly inhibited the activation of AHR. Cinnamaldehyde also activated the NRF2/HO1 pathway and significantly alleviated the production of reactive oxygen species in keratinocytes. The inhibition of AHR signaling and the activation of antioxidant activity by cinnamaldehyde operated in a mutually independent manner as assessed by siRNA methods In addition, AHR signaling was effectively inhibited by traditional Kampo formulae containing C. cassia.ConclusionCinnamaldehyde has two independent biological activities; namely, an inhibitory action on AHR activation and an antioxidant effect mediated by NRF2/HO1 signaling. Through these dual functions, cinnamaldehyde may be beneficial for the treatment of disorders related to oxidative stress such as dioxin intoxication, acne, and vitiligo.



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Inside front cover

Publication date: October 2016
Source:Journal of Anxiety Disorders, Volume 43





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Enterococcus hirae and Barnesiella intestinihominis Facilitate Cyclophosphamide-Induced Therapeutic Immunomodulatory Effects

Publication date: Available online 4 October 2016
Source:Immunity
Author(s): Romain Daillère, Marie Vétizou, Nadine Waldschmitt, Takahiro Yamazaki, Christophe Isnard, Vichnou Poirier-Colame, Connie P.M. Duong, Caroline Flament, Patricia Lepage, Maria Paula Roberti, Bertrand Routy, Nicolas Jacquelot, Lionel Apetoh, Sonia Becharef, Sylvie Rusakiewicz, Philippe Langella, Harry Sokol, Guido Kroemer, David Enot, Antoine Roux, Alexander Eggermont, Eric Tartour, Ludger Johannes, Paul-Louis Woerther, Elisabeth Chachaty, Jean-Charles Soria, Encouse Golden, Silvia Formenti, Magdalena Plebanski, Mutsa Madondo, Philip Rosenstiel, Didier Raoult, Vincent Cattoir, Ivo Gomperts Boneca, Mathias Chamaillard, Laurence Zitvogel
The efficacy of the anti-cancer immunomodulatory agent cyclophosphamide (CTX) relies on intestinal bacteria. How and which relevant bacterial species are involved in tumor immunosurveillance, and their mechanism of action are unclear. Here, we identified two bacterial species, Enterococcus hirae and Barnesiella intestinihominis that are involved during CTX therapy. Whereas E. hirae translocated from the small intestine to secondary lymphoid organs and increased the intratumoral CD8/Treg ratio, B. intestinihominis accumulated in the colon and promoted the infiltration of IFN-γ-producing γδT cells in cancer lesions. The immune sensor, NOD2, limited CTX-induced cancer immunosurveillance and the bioactivity of these microbes. Finally, E. hirae and B. intestinihominis specific-memory Th1 cell immune responses selectively predicted longer progression-free survival in advanced lung and ovarian cancer patients treated with chemo-immunotherapy. Altogether, E. hirae and B. intestinihominis represent valuable "oncomicrobiotics" ameliorating the efficacy of the most common alkylating immunomodulatory compound.

Graphical abstract

Teaser

Cyclophosphamide (CTX) is an immunomodulatory anticancer compound. Daillère et al. show that the antitumoral efficacy of CTX relies on two gut commensal species, Enterococcus hirae and Barnesiella intestinihominis in a NOD2-dependent manner. These two bacteria changed the tumor microenvironment, reducing regulatory T cells and stimulating cognate antitumor CTL responses.


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Reversed T Cell Receptor Docking on a Major Histocompatibility Class I Complex Limits Involvement in the Immune Response

Publication date: Available online 4 October 2016
Source:Immunity
Author(s): Stephanie Gras, Jesseka Chadderton, Claudia M. Del Campo, Carine Farenc, Florian Wiede, Tracy M. Josephs, Xavier Y.X. Sng, Michiko Mirams, Katherine A. Watson, Tony Tiganis, Kylie M. Quinn, Jamie Rossjohn, Nicole L. La Gruta
The anti-viral T cell response is drawn from the naive T cell repertoire. During influenza infection, the CD8⁺ T cell response to an H-2D^b-restricted nucleoprotein epitope (NP366) is characterized by preferential expansion of T cells bearing TRBV13⁺ T cell receptors (TCRs) and avoidance of TRBV17⁺ T cells, despite the latter dominating the naive precursor repertoire. We found two TRBV17⁺ TCRs that bound H-2D^b-NP366 with a 180° reversed polarity compared to the canonical TCR-pMHC-I docking. The TRBV17 β-chain dominated the interaction and, whereas the complementarity determining region-3 (CDR3) loops exclusively mediated contacts with the MHC-I, peptide specificity was attributable to germline-encoded recognition. Nevertheless, the TRBV17⁺ TCR exhibited moderate affinity toward H-2D^b-NP366 and was capable of signal transduction. Thus, the naive CD8⁺ T cell pool can comprise TCRs adopting reversed pMHC-I docking modes that limit their involvement in the immune response.

Teaser

Gras et al. show that TCRs from the naive repertoire recognize pMHC-I in a reversed orientation in comparison to the consensus TCR-pMHC-I docking. This reversed docking was associated with poor CD8⁺ T cell responses. Thus, naive T cells may exhibit a range of unconventional TCR-pMHC-I docking modes.


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Scholar : These new articles for Behavioral Sciences of Terrorism and Political Aggression are available online

The online platform for Taylor & Francis Online content New for Behavioral Sciences of Terrorism and Political Aggression and online now on Taylor & Francis Online: Original Articles Cumulative extremism: escalation of movement–countermovement dynamics in Northern Ireland between 1967 and 1972 Alexander James Carter Pages: 1-15 | DOI: 10.1080/19434472.2016.1236830 Routledge Journals Gerontology Portfolio - find out more here: http://ift.tt/2crU79K This message is personalised to your status as a society member. Please do not forward this email. To recommend content, please use the social sharing tools on the website. To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.