Are Anemia and Hypotension Causally Related to Perioperative Ischemic Optic Neuropathy?.

No abstract available

http://ift.tt/2hOAwV0

Early Alterations of Hippocampal Neuronal Firing Induced by Abeta42

We studied the effect of Amyloid β 1-42 oligomers (Abeta42) on Ca²⁺ dependent excitability profile of hippocampal neurons. Abeta42 is one of the Amyloid beta peptides produced by the proteolytic processing of the amyloid precursor protein and participates in the initiating event triggering the progressive dismantling of synapses and neuronal circuits. Our experiments on cultured hippocampal network reveal that Abeta42 increases intracellular Ca²⁺ concentration by 46% and inhibits firing discharge by 19%. More precisely, Abeta42 differently regulates ryanodine (RyRs), NMDA receptors (NMDARs), and voltage gated calcium channels (VGCCs) by increasing Ca²⁺ release through RyRs and inhibiting Ca²⁺ influx through NMDARs and VGCCs. The overall increased intracellular Ca²⁺ concentration causes stimulation of K⁺ current carried by big conductance Ca²⁺ activated potassium (BK) channels and hippocampal network firing inhibition. We conclude that Abeta42 alters neuronal function by means of at least 4 main targets: RyRs, NMDARs, VGCCs, and BK channels. The development of selective modulators of these channels may in turn be useful for developing effective therapies that could enhance the quality of life of AD patients during the early onset of the pathology.

http://ift.tt/2hUcpDT

Spatiotemporal Dynamics of Attention Networks Revealed by Representational Similarity Analysis of EEG and fMRI

The fronto-parietal attention networks have been extensively studied with functional magnetic resonance imaging (fMRI), but spatiotemporal dynamics of these networks are not well understood. We measured event-related potentials (ERPs) with electroencephalography (EEG) and collected fMRI data from identical experiments where participants performed visual and auditory discrimination tasks separately or simultaneously and with or without distractors. To overcome the low temporal resolution of fMRI, we used a novel ERP-based application of multivariate representational similarity analysis (RSA) to parse time-averaged fMRI pattern activity into distinct spatial maps that each corresponded, in representational structure, to a short temporal ERP segment. Discriminant analysis of ERP-fMRI correlations revealed 8 cortical networks—2 sensory, 3 attention, and 3 other—segregated by 4 orthogonal, temporally multifaceted and spatially distributed functions. We interpret these functions as 4 spatiotemporal components of attention: modality-dependent and stimulus-driven orienting, top-down control, mode transition, and response preparation, selection and execution.

http://ift.tt/2hPdG1D

Delta-Band Oscillations in Motor Regions Predict Hand Selection for Reaching

Current models hold that action selection is achieved by competitive interactions between co-existing motor representations associated with each potential action. Critically, selection via competition requires biasing signals to enable one of these alternatives to be selected. This study tested the hypothesis that selection is related to the prestimulus excitability of neuronal ensembles in which movements are encoded, as assessed through the phase of delta-band oscillations (2–4 Hz). Electroencephalography was recorded while participants performed speeded reaches toward appearing visual targets using the hand of their choice. The target locations were controlled such that only targets for which the left and right hands were selected equally often were used for analysis. Results revealed that hand selection as well as reach reaction times strongly depended upon the instantaneous phase of delta at the moment of target onset. This effect was maximal over contralateral motor regions, and occurred in the absence of prestimulus alpha- (8–12 Hz) and beta-band (15–30 Hz) amplitude modulations. These findings demonstrate that the excitability of motor regions acts as a modulatory factor for hand choice during reaching. They extend current models by showing that action selection is related to the underlying brain state independently of previously known decision variables.

http://ift.tt/2hUnWmK

Activity-Independent Effects of CREB on Neuronal Survival and Differentiation during Mouse Cerebral Cortex Development

Neuronal survival and morphological maturation depends on the action of the transcription factor calcium responsive element binding protein (CREB), which regulates expression of several target genes in an activity-dependent manner. However, it remains largely unknown whether CREB-mediated transcription could play a role at early stages of neuronal differentiation, prior to the establishment of functional synaptic contacts. Here, we show that CREB is phosphorylated at very early stages of neuronal differentiation in vivo and in vitro, even in the absence of depolarizing agents. Using genetic tools, we also show that inhibition of CREB-signaling affects neuronal growth and survival in vitro without affecting cell proliferation and neurogenesis. Expression of A-CREB or M-CREB, 2 dominant-negative inhibitors of CREB, decreases cell survival and the complexity of neuronal arborization. Similar changes are observed in neurons treated with protein kinase A (PKA) and Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) inhibitors, which also show decreased levels of pCREBSer133. Notably, expression of CREB-FY, a Tyr134Phe CREB mutant with a lower Km for phosphorylation, partly rescues the effects of PKA and CaMKII inhibition. Our data indicate that CREB-mediated signaling play important roles at early stages of cortical neuron differentiation, prior to the establishment of fully functional synaptic contacts.

http://ift.tt/2i9XSDu

Renal complications of immune checkpoint blockade

Publication date: Available online 19 December 2016
Source:Current Problems in Cancer
Author(s): Naoka Murakami, Shveta Motwani, Leonardo V. Riella
Immune checkpoint inhibitors have been approved for a variety of cancer species. Renal complications in use of these agents are not very common compared with other immune related adverse events (irAE). However, it is crucial for physicians to recognize and manage renal manifestations of irAE. In this review, we will summarize the up-to-date knowledge of the clinical presentation, pathological features and management of renal irAE. In addition, we will discuss the safety of immune checkpoint inhibitors in patients with chronic kidney disease as well as in kidney transplant recipients.



http://ift.tt/2hPbvey

Toxicity of concurrent stereotactic radiotherapy and targeted therapies or immunotherapy: a systematic review.

Publication date: Available online 19 December 2016
Source:Cancer Treatment Reviews
Author(s): Stephanie G.C. Kroeze, Corinna Fritz, Morten Hoyer, Simon S. Lo, Umberto Ricardi, Arjun Sahgal, Rolf Stahel, Roger Stupp, Matthias Guckenberger
Background and PurposeBoth stereotactic radiotherapy (SRT) and immune- or targeted therapy play an increasingly important role in personalized treatment of metastatic disease. Concurrent application of both therapies is rapidly expanding in daily clinical practice. In this systematic review we summarize severe toxicity observed after concurrent treatment.Material and MethodsPubMed and EMBASE databases were searched for English literature published up to april 2016 using keywords "radiosurgery", "local ablative therapy", "gamma knife" and "stereotactic", combined with "bevacizumab", "cetuximab", "crizotinib", "erlotinib", "gefitinib", "ipilimumab", "lapatinib", "sorafenib", "sunitinib", "trastuzumab", "vemurafenib", "PLX4032", "panitumumab", "nivolumab", "pembrolizumab", "alectinib", "ceritinib", "dabrafenib", "trametinib", "BRAF", "TKI", "MEK", "PD1", "EGFR", "CTLA-4" or "ALK". Studies performing SRT during or within 30 days of targeted/immunotherapy, reporting severe (⩾Grade 3) toxicity were included.ResultsConcurrent treatment is mostly well tolerated in cranial SRT, but high rates of severe toxicity were observed for the combination with BRAF-inhibitors. The relatively scarce literature on extra-cranial SRT shows a potential risk of increased toxicity when SRT is combined with EGFR-targeting tyrosine kinase inhibitors and bevacizumab, which was not observed for cranial SRT.ConclusionsThis review gives a best-possible overview of current knowledge and its limitations and underlines the need for a timely generation of stronger evidence in this rapidly expanding field.



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Reliability and minimal detectable change of transcranial magnetic stimulation outcomes in healthy adults: A systematic review

Publication date: Available online 19 December 2016
Source:Brain Stimulation
Author(s): Louis-David Beaulieu, Véronique H. Flamand, Hugo Massé-Alarie, Cyril Schneider
BackgroundTranscranial magnetic stimulation (TMS) is used worldwide for noninvasively testing human motor systems but its psychometric properties remain unclear.Objective/Hypothesis. This work systematically reviewed studies on the reliability of TMS outcome measures of primary motor cortex (M1) excitability in healthy humans, with an emphasis on retrieving minimal detectable changes (MDC).MethodsThe literature search was performed in three databases (Pubmed, CINAHL, Embase) up to June 2016 and additional studies were identified through hand-searching. French and English-written studies had to report the reliability of at least one TMS outcome of M1 in healthy humans. Two independent raters assessed the eligibility of potential studies, and eligible articles were reviewed using a structured data extraction form and two critical appraisal scales.ResultsA total of 34 articles met the selection criteria, which tested the intra- and inter-rater reliability (relative and absolute subtypes) of several TMS outcomes. However, our critical appraisal of studies raised concerns on applicability and generalization of results because of methodological and statistical pitfalls. Importantly, MDC were generally large and likely affected by various factors, especially time elapsed between sessions and number of stimuli delivered.ConclusionsThis systematic review underlined that the evidence about the reliability of TMS outcomes is scarce and affected by several methodological and statistical problems. Data and knowledge of the review provided however relevant insights on the ability of TMS outcomes to track plastic changes within an individual or within a group, and recommendations were made to level up the quality of future work in the field.



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The critical role of the dorsomedial frontal cortex in voluntary action inhibition: a TMS study

Publication date: Available online 19 December 2016
Source:Brain Stimulation
Author(s): Stefania C. Ficarella, Lorella Battelli
BackgroundAction inhibition is a complex decision process that can be triggered by external factors (exogenous) or internal decisions (endogenous). While the neuronal underpinnings of exogenous action inhibition have been extensively investigated, less is known about the brain areas responsible for endogenous action inhibition. Objective. We used inhibitory repetitive transcranial magnetic stimulation (rTMS) to test the causal role of two brain areas, the left dorsal Frontal Medial Cortex (dFMC) and the right Inferior Frontal Cortex (rIFC) in exogenous and endogenous action inhibition. Methods. The exogenous condition was a modified version of the Go/NoGo paradigm, where a green stimulus served as a cue to perform an action (a button press, Exogenous-Go), while a magenta stimulus indicated that action should be withheld (Exogenous-NoGo). Crucially, for the endogenous condition we psychophysically generated a shade of color that participants randomly categorized as green or magenta. This unique stimulus, randomly intermixed with green and magenta stimuli, forced participants to perform an endogenous (internally-driven) choice to either execute or inhibit the action. Results. In the endogenous condition, at baseline participants executed the action on half the trials; however, after 1-Hz rTMS over the dFMC they responded significantly more frequently, indicating a reduced response inhibition. The effect was selective for the dFMC stimulation and sustained in time. Moreover, no significant effects were found in the exogenous condition. Conclusions. These results support the causal role of the left dFMC in endogenous action inhibition and, more generally, the notion of separate brain circuits for endogenous and exogenous action inhibition.



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Graphene oxide destabilizes myoglobin and alters its conformation

Publication date: Available online 19 December 2016
Source:Carbon
Author(s): Zhaohua Zhu, Yanqing Wang, Yijun Kang, Hongmei Zhang, Zhengming Zhang, Zhenghao Fei, Jian Cao
In this work, a series of biophysical assays were performed in order to analyze the effects of a novel two-dimensional carbon nano-material graphene oxide (GO) on the conformational changes of myoglobin (Mb). This study, for the first time, reveals the molecular interactions of GO with Mb. The conformation of the protein is obviously affected due to the binding interaction of GO with Mb. GO has high ability in disturbing the secondary of Mb by forming the Mb-GO conjunction. Multi-noncovalent interactions including hydrophobic, hydrogen bonds, van der Waals interactions and electrostatic forces contribute to the formation of Mb-GO conjunction. Our findings also show that the existence of GO can obviously decrease the thermal stability of protein. In addition, molecular modeling was used to analyze the lowest energy binding mode of GO with Mb. Taken together, this work can provide an insight into the biological interaction GO-heme protein in some biological applications.

Graphical abstract

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Influences of O2 and O3 on the heterogeneous photochemical reaction of NO2 with humic acids

Publication date: March 2017
Source:Atmospheric Environment, Volume 152
Author(s): Chong Han, Wangjin Yang, He Yang, Xiangxin Xue
Oxidizing components in the atmosphere may play competitive roles in the heterogeneous photochemical reaction of NO2 with humic acids (HA). Effects of O2 and O3 on the conversion of NO2 to HONO on HA under simulated sunlight were investigated using a flow tube reactor. The uptake coefficient (γ) of NO2 and the HONO formation rate decreased with the increase of the O2 content (0%–20%) and the O3 concentration (0–100 ppb). The HONO yield was observed to be independent of the O2 content, whereas it inversely depended on the O3 concentration. In addition, the aging process of HA by O2 and O3 under irradiation resulted in the decrease in the reactivity of HA toward NO2, as shown by lower γ and HONO formation rate, while it has little influence on the HONO yield. Finally, the mechanism of role of O2 and O3 in the photochemical reaction of NO2 with HA was discussed in detail.



http://ift.tt/2hOVIfP

Genesis of the Zinkgruvan stratiform Zn-Pb-Ag deposit and associated dolomite-hosted Cu ore, Bergslagen, Sweden

Publication date: April 2017
Source:Ore Geology Reviews, Volume 82
Author(s): N.F. Jansson, A. Zetterqvist, R.L. Allen, K. Billström, L. Malmström
Zinkgruvan, a major stratiform Zn-Pb-Ag deposit in the Paleoproterozoic Bergslagen region, south-central Sweden, was overprinted by polyphase ductile deformation and high-grade metamorphism (including partial melting of the host succession) during the 1.9–1.8Ga Svecokarelian orogeny. This complex history of post-ore modification has made classification of the deposit difficult. General consensus exists on a syngenetic-exhalative origin, yet the deposit has been variably classified as a volcanogenic massive sulfide (VMS) deposit, a sediment-hosted Zn (SEDEX) deposit, and a Broken Hill-type (BHT) deposit. Since 2010, stratabound, cobaltiferous and nickeliferous Cu ore, comprising schlieren and impregnations of Cu, Co and Ni sulfide minerals in dolomitic marble, is mined from the stratigraphic footwall to the stratiform Zn-Pb-Ag ore. This ore type has not been fully integrated into any of the existing genetic models. Based on a combination of 1) widespread hematite-staining and oxidizing conditions (Fe2O3>FeO) in the stratigraphic footwall, 2) presence of graphite and reducing conditions (Fe2O3<FeO) in the ore horizon and hangingwall and 3) intense K-feldspar alteration and lack of feldspar-destructive alteration in the stratigraphic footwall, we suggest that both the stratiform Zn-Pb-Ag and the dolomite-hosted Cu ore can be attributed to the ascent and discharge of an oxidized, saline brine at near neutral pH. Interaction of this brine with organic matter below the seafloor, especially within limestone, formed stratabound, disseminated Cu ore, and exhalation of the brine into a reduced environment on the sea floor produced a brine pool from which the regionally extensive (>5km) Zn-Pb-Ag ore was precipitated.Both ore types are characterized by significant spread in δ³⁴S, with the sulfur in the Cu ore and associate marble-hosted Zn mineralization on average being somewhat heavier (δ³⁴S=−4.7 to +10.5‰, average 3.9‰) than that in the stratiform Zn-Pb-Ag ore (δ³⁴S=−6 to +17‰, average 2.0‰). The ranges in δ³⁴S are significantly larger than those observed in syn-volcanic massive sulfide deposits in Bergslagen, for which simple magmatic/volcanic sulfur sources have been invoked. Mixing of magmatic-volcanic sulfur leached from underlying volcanic rocks and sulfur sourced from abiotic or bacterial sulfate reduction in a mixing zone at the seafloor could explain the range observed at Zinkgruvan.A distinct discontinuity in the stratigraphy, at which key stratigraphic units stop abruptly, is interpreted as a syn-sedimentary fault. Metal zonation in the stratiform ore (decreasing Zn/Pb from distal to proximal) and the spatial distribution of Cu mineralization in underlying dolomitic marble suggest that this fault was a major feeder to the mineralization. Our interpretation of ore-forming fluid composition and a dominant redox trap rather than a pH and/or temperature trap differs from most VMS models, with Selwyn-type SEDEX models, and most BHT models. Zinkgruvan has similarities to both McArthur-type SEDEX deposits and sediment-hosted Cu deposits in terms of the inferred ore fluid chemistry, yet the basinal setting has more similarities to BHT and felsic-bimodal VMS districts. We speculate that besides an oxidized footwall stratigraphy, regionally extensive banded iron formations and limestone horizons in the Bergslagen stratigraphy may have aided in buffering ore-forming brines to oxidized, near-neutral conditions. In terms of fluid chemistry, Zinkgruvan could comprise one of the oldest known manifestations of Zn and Cu ore-forming systems involving oxidized near-neutral brines following oxygenation of the Earth's atmosphere.

Graphical abstract

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Fabrication and properties of pure-phase Cu2O co-doped with zinc and indium

Publication date: 15 March 2017
Source:Journal of Alloys and Compounds, Volume 697
Author(s): Xing-Min Cai, Xiao-Qiang Su, Fan Ye, V.A.L. Roy, Dong-Ping Zhang, Jing-Ting Luo, Ping Fan, Zhuang-Hao Zheng, Guang-Xing Liang, Jun-Jun Xiao
Cuprous oxide (Cu2O) thin films co-doped with zinc (Zn) and indium (In) were fabricated with direct current (DC) magnetron sputtering. The sputtering voltage of the Cu target was fixed while that of the alloy target of Zn and In was varied. It is found that when the alloy target voltage is below 310 V, pure-phase Cu2O can be obtained while a further increase in the alloy target voltage will result in the presence of metallic copper. The surface morphologies, the atomic ratios of the Zn and In, and the grain size do not have a linear dependence on the sputtering voltage of the alloy target. Higher concentration doping will decrease the lattice constant of Cu2O. Pure-phase samples doped with Zn and In have relatively higher transmittance and larger optical band gaps. The n-type conduction of Cu2O co-doped with Zn and In is realized when the sputtering voltage of the alloy target is 310 V. Zn and In atoms are found to exist as Zn²⁺ and In³⁺ in the films and they are possible donors for the n-type conduction.



http://ift.tt/2hNSbMr

Islet adaptations in fetal sheep persist following chronic exposure to high norepinephrine

Complications in pregnancy elevate fetal norepinephrine (NE) concentrations. Previous studies in NE-infused sheep fetuses revealed that sustained exposure to high NE resulted in lower expression of α₂-adrenergic receptors in islets and increased insulin secretion responsiveness after acutely terminating the NE infusion. In this study, we determined if the compensatory increase in insulin secretion after chronic elevation of NE is independent of hyperglycemia in sheep fetuses and whether it is persistent in conjunction with islet desensitization to NE. After an initial assessment of glucose-stimulated insulin secretion (GSIS) at 129 ± 1 days of gestation, fetuses were continuously infused for seven days with NE and maintained at euglycemia with a maternal insulin infusion. Fetal GSIS studies were performed again on days 8 and 12. Adrenergic sensitivity was determined in pancreatic islets collected at day 12. NE infusion increased (P < 0.01) fetal plasma NE concentrations and lowered (P < 0.01) basal insulin concentrations compared to vehicle-infused controls. GSIS was 1.8-fold greater (P < 0.05) in NE-infused fetuses compared to controls at both one and five days after discontinuing the infusion. Glucose-potentiated arginine-induced insulin secretion was also enhanced (P < 0.01) in NE-infused fetuses. Maximum GSIS in islets isolated from NE-infused fetuses was 1.6-fold greater (P < 0.05) than controls, but islet insulin content and intracellular calcium signaling were not different between treatments. The half-maximal inhibitory concentration for NE was 2.6-fold greater (P < 0.05) in NE-infused islets compared to controls. These findings show that chronic NE exposure and not hyperglycemia produce persistent adaptations in pancreatic islets that augment β-cell responsiveness in part through decreased adrenergic sensitivity.

http://ift.tt/2hNY0cI

INF-{gamma} encoding plasmid administration triggers bone loss and disrupts bone marrow microenvironment

IFN- is a pleotropic cytokine produced in the bone microenvironment. Although IFN- is known to play a critical role on bone remodeling, its function is not fully elucidated. Consistently, outcomes on the effects of IFN- recombinant protein on bone loss are contradictory among reports. In our work we explored, for the first time, the role of IFN- encoding plasmid (pIFN-) in a mouse model of osteopenia induced by ovariectomy and in the sham-operated counterpart to estimate its effects in skeletal homeostasis. Ovariectomy produced a dramatic decrease of bone mineral density (BMD). pINF- injected mice showed a pathologic bone and bone marrow phenotype; the disrupted cortical and trabecular bone microarchitecture was accompanied by an increased release of pro-inflammatory cytokine by bone marrow cells. Moreover, mesenchymal stem cells' (MSCs) commitment to osteoblast was found impaired, as evidenced by the decline of osterix-positive (Osx⁺) cells within the mid-diaphyseal area of femurs. For instance, a reduction and redistribution of CXCL12 cells have been found, in accordance with bone marrow morphological alterations. As similar effects were observed both in sham-operated and in ovariectomized mice, our studies proved that an increased IFN- synthesis in bone marrow might be sufficient to induce inflammatory and catabolic responses even in the absence of pathologic predisposing substrates. In addition, the obtained data might raise questions about pIFN-'s safety when it is used as vaccine adjuvant.

http://ift.tt/2hC4TQh

17{beta}-estradiol improves hepatic mitochondrial biogenesis and function through PGC1B

Sexual dimorphism in mitochondrial biogenesis and function has been described in many rat tissues, with females showing larger and more functional mitochondria. The family of the peroxisome proliferator-activated receptor gamma coactivator 1 (PGC1) plays a central role in the regulatory network governing mitochondrial biogenesis and function, but little is known about the different contribution of hepatic PGC1A and PGC1B in these processes. The aim of this study was to elucidate the role of 17β-estradiol (E2) in mitochondrial biogenesis and function in liver and assess the contribution of both hepatic PGC1A and PGC1B as mediators of these effects. In ovariectomized (OVX) rats (half of which were treated with E2) estrogen deficiency led to impaired mitochondrial biogenesis and function, increased oxidative stress, and defective lipid metabolism, but was counteracted by E2 treatment. In HepG2 hepatocytes, the role of E2 in enhancing mitochondrial biogenesis and function was confirmed. These effects were unaffected by the knockdown of PGC1A, but were impaired when PGC1B expression was knocked down by specific siRNA. Our results reveal a widespread protective role of E2 in hepatocytes, which is explained by enhanced mitochondrial content and oxidative capacity, lower hepatic lipid accumulation, and a reduction of oxidative stress. We also suggest a novel hepatic protective role of PGC1B as a modulator of E2 effects on mitochondrial biogenesis and function supporting activation of PGC1B as a therapeutic target for hepatic mitochondrial disorders.

http://ift.tt/2hNTomJ

11{beta}-hydroxysteroid dehydrogenase-1 deficiency alters the gut microbiome response to Western diet

The enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD) interconverts active glucocorticoids and their intrinsically inert 11-keto forms. The type 1 isozyme, 11β-HSD1, predominantly reactivates glucocorticoids in vivo and can also metabolise bile acids. 11β-HSD1-deficient mice show altered inflammatory responses and are protected against the adverse metabolic effects of a high-fat diet. However, the impact of 11β-HSD1 on the composition of the gut microbiome has not previously been investigated. We used high-throughput 16S rDNA amplicon sequencing to characterise the gut microbiome of 11β-HSD1-deficient and C57Bl/6 control mice, fed either a standard chow diet or a cholesterol- and fat-enriched 'Western' diet. 11β-HSD1 deficiency significantly altered the composition of the gut microbiome, and did so in a diet-specific manner. On a Western diet, 11β-HSD1 deficiency increased the relative abundance of the family Bacteroidaceae, and on a chow diet, it altered relative abundance of the family Prevotellaceae. Our results demonstrate that (i) genetic effects on host–microbiome interactions can depend upon diet and (ii) that alterations in the composition of the gut microbiome may contribute to the aspects of the metabolic and/or inflammatory phenotype observed with 11β-HSD1 deficiency.

http://ift.tt/2hCgNtF

Direct induction of neural progenitor cells transiently passes through a partially reprogrammed state

Publication date: March 2017
Source:Biomaterials, Volume 119
Author(s): Rui Gao, Wenchao Xiu, Linfeng Zhang, Ruge Zang, Lei Yang, Chenfei Wang, Min Wang, Mingzhu Wang, Li Yi, Yuanyuan Tang, Yawei Gao, Hong Wang, Jiajie Xi, Wenqiang Liu, Yixuan Wang, Xuejun Wen, Yongchun Yu, Yong Zhang, Liang Chen, Jiayu Chen, Shaorong Gao
The generation of functional neural progenitor cells (NPCs) holds great promise for both research and clinical applications in neurodegenerative diseases. Traditionally, NPCs are derived from embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), or NPCs can be directly converted from somatic cells by sets of transcription factors or by a combination of chemical cocktails and/or hypoxia. However, the ethical issues of ESCs, the risk of tumorigenesis from iPSCs and transgenic integration from exogenous genes as well as complicated manipulation and time-consuming of chemical induced NPCs (ciNPCs) limit the applications of these strategies. Here, we describe a novel method for generating growth factor-induced neural progenitor cells (giNPCs) from mouse embryonic and adult fibroblasts by using inductive and/or permissive signaling culture conditions. These giNPCs closely resemble brain-derived NPCs in terms of transcription networks and neural lineage differentiation potentials. Moreover, this somatic cell to NPC induction is a gradual process that includes initiation, intermediate, maturation and stabilization stages. Importantly, gene expression and histone modification analyses further indicate a partially reprogrammed state during the generation process of induced NPCs, in which lineage specific genes and pluripotency associated genes are transiently activated. Our study therefore describes the potential safety problems that also exist in the transgene-free direct induction strategy and highlights the importance of excluding the possibility of residual partially reprogrammed and/or teratoma-like cells from the generated NPCs for future clinical trials.



http://ift.tt/2hibuMB

Different doses of dexmedetomidine reduce plasma cytokine production, brain oxidative injury, PARP and caspase expression levels but increase liver oxidative toxicity in cerebral ischemia-induced rats

Publication date: Available online 19 December 2016
Source:Brain Research Bulletin
Author(s): Orhan Akpınar, Mustafa Nazıroğlu, Hatice Akpınar
Cerebral ischemia-induced progression of brain, liver, and erythrocyte oxidative injuries might be modulated by dexmedetomidine (DEX) as a potent antioxidant and anti-inflammatory drug. The present study was conducted to explore whether two different doses of DEX protect against plasma cytokine and brain, liver and erythrocyte oxidative toxicity and apoptosis in cerebral ischemia-induced rats.Forty-two rats were equally divided into 7 groups. The first and second groups were used as untreated and sham controls, respectively. The third (DEX4) and fourth (DEX40) groups received 4mg/kg and 40mg/kg DEX treatments. The fifth, sixth and seventh group were operated on to induce cerebral ischemia. The fifth, sixth and seventh groups are used to represent cerebral ischemia, cerebral ischemia+DEX4, and cerebral ischemia+DEX40, respectively. DEX was intraperitoneally given to the DEX groups at the 3rd, 24th and 48th hour.Brain and erythrocyte lipid peroxidation (MDA) levels and plasma IL-1β and TNF-α levels were high in the cerebral ischemia group although they were low in the DEX4 and DEX40 groups. Decreased glutathione peroxidase (GSH-Px) and reduced glutathione (GSH) values in the brain and erythrocyte of the cerebral ischemia group were increased by the DEX treatments, although PARP, and the caspase 3 and 9 expressions in the brain were further decreased. Conversely, the cerebral ischemia-induced decrease in the liver vitamin A, vitamin E, GSH, and GSH-Px were further decreased by the DEX treatments, although MDA level, PARP, and caspase 3 and 9 expressions were further increased by the DEX treatments.In conclusion, DEX induced protective effects against cerebral ischemia-induced brain and erythrocyte oxidative injuries through regulation of the antioxidant level and cytokine production. However, both doses of DEX induced oxidative toxicity and apoptotic effects in the rats' livers.



http://ift.tt/2hBZ0m6

Resuscitation Science in Circulation: A Timely Topic.

Author: Diercks, Deborah B. MD; Al-Khatib, Sana M. MD, MHS; Link, Mark S. MD

Page: 2033-2034

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Stop Randomizing All Cardiac Arrests.

Author: Weisfeldt, Myron L. MD

Page: 2035-2036

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Doubling Cardiac Arrest Survival by 2020: Achieving the American Heart Association Impact Goal.

Author: Neumar, Robert W. MD, PhD

Page: 2037-2039

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Improving Care of Out-of-Hospital Cardiac Arrest: Next Steps.

Author: Jollis, James G. MD; Granger, Christopher B. MD

Page: 2040-2042

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Measured Progress in Cardiopulmonary Resuscitation.

Author: Hazinski, Mary Fran RN, MSN

Page: 2043-2045

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Duration of Prehospital Cardiopulmonary Resuscitation and Favorable Neurological Outcomes for Pediatric Out-of-Hospital Cardiac Arrests: A Nationwide, Population-Based Cohort Study.

Author: Goto, Yoshikazu MD, PhD; Funada, Akira MD, PhD; Goto, Yumiko MD, PhD

Page: 2046-2059

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Conventional Versus Compression-Only Versus No-Bystander Cardiopulmonary Resuscitation for Pediatric Out-of-Hospital Cardiac Arrest.

Author: Fukuda, Tatsuma MD, PhD; Ohashi-Fukuda, Naoko MD; Kobayashi, Hiroaki MD; Gunshin, Masataka MD; Sera, Toshiki MD, PhD; Kondo, Yutaka MD, PhD; Yahagi, Naoki MD, PhD

Page: 2060-2070

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Is It Time to Stop Teaching Bystanders Ventilation as Part of Pediatric Cardiopulmonary Resuscitation?.

Author: de Caen, Allan MD; Tijssen, Janice A. MD

Page: 2071-2073

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Identifying Patients at Risk for Prehospital Sudden Cardiac Arrest at the Early Phase of Myocardial Infarction: The e-MUST Study (Evaluation en Medecine d'Urgence des Strategies Therapeutiques des infarctus du myocarde).

Author: Karam, Nicole MD, MPH; Bataille, Sophie MD; Marijon, Eloi MD, PhD; Giovannetti, Olivier MD, MPH; Tafflet, Muriel MPH; Savary, Dominique MD; Benamer, Hakim MD; Caussin, Christophe MD; Garot, Philippe MD; Juliard, Jean-Michel MD; Pires, Virginie MD; Boche, Thevy MD; Dupas, Francois MD; Le Bail, Gaelle MD; Lamhaut, Lionel MD, MPH; Laborne, Francois MD; Lefort, Hugues MD; Mapouata, Mireille MD; Lapostolle, Frederic MD; Spaulding, Christian MD, PhD; Empana, Jean-Philippe MD, PhD; Jouven, Xavier MD, PhD; Lambert, Yves MD; For the e-MUST Study Investigators

Page: 2074-2083

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Association Between Duration of Resuscitation and Favorable Outcome After Out-of-Hospital Cardiac Arrest: Implications for Prolonging or Terminating Resuscitation.

Author: Reynolds, Joshua C. MD, MS; Grunau, Brian E. MD; Rittenberger, Jon C. MD, MS; Sawyer, Kelly N. MD, MS; Kurz, Michael C. MD, MS; Callaway, Clifton W. MD, PhD

Page: 2084-2094

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Association of Bystander Cardiopulmonary Resuscitation and Survival According to Ambulance Response Times After Out-of-Hospital Cardiac Arrest.

Author: Rajan, Shahzleen MD; Wissenberg, Mads MD, PhD; Folke, Fredrik MD, PhD; Hansen, Steen Moller MD; Gerds, Thomas A. PhD; Kragholm, Kristian MD, PhD; Hansen, Carolina Malta MD, PhD; Karlsson, Lena MD; Lippert, Freddy K. MD; Kober, Lars MD, DSc; Gislason, Gunnar H. MD, PhD; Torp-Pedersen, Christian MD, DSc

Page: 2095-2104

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Hospital Variation in Time to Epinephrine for Nonshockable In-Hospital Cardiac Arrest.

Author: Khera, Rohan MD; Chan, Paul S. MD, MSc; Donnino, Michael MD; Girotra, Saket MD, SM; For the American Heart Association's Get With The Guidelines-Resuscitation Investigators

Page: 2105-2114

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Neuroprotective Effects of the Glucagon-Like Peptide-1 Analog Exenatide After Out-of-Hospital Cardiac Arrest: A Randomized Controlled Trial.

Author: Wiberg, Sebastian MD; Hassager, Christian MD, DMSc; Schmidt, Henrik MD, DMSc; Thomsen, Jakob Hartvig MD; Frydland, Martin MD; Lindholm, Matias Greve MD, PhD; Hofsten, Dan Eik MD, PhD; Engstrom, Thomas MD, PhD, DMSc; Kober, Lars MD, DMSc; Moller, Jacob Eifer MD, PhD, DMSc; Kjaergaard, Jesper MD, PhD, DMSc

Page: 2115-2124

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Late-Breaking Clinical Trial Abstracts From the American Heart Association's Scientific Sessions 2016.

Author:

Page: e702-e708

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Late-Breaking Clinical Science Special Reports Abstracts From the American Heart Association's Scientific Sessions 2016.

Author:

Page: e709-e715

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Late-Breaking Abstracts in Resuscitation Science From the Resuscitation Science Symposium 2016.

Author:

Page: e716-e720

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Factors Associated With Pulmonary Embolism-Related Sudden Cardiac Arrest.

Author: Bougouin, Wulfran MD; Marijon, Eloi MD, PhD; Planquette, Benjamin MD; Karam, Nicole MD; Dumas, Florence MD, PhD; Celermajer, David S. PhD; Jost, Daniel MD; Lamhaut, Lionel MD, PhD; Beganton, Frankie MS; Cariou, Alain MD, PhD; Meyer, Guy MD, PhD; Jouven, Xavier MD, PhD; On behalf of the Sudden Death Expertise Center

Page: 2125-2127

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Ticagrelor Versus Clopidogrel in Comatose Survivors of Out-of-Hospital Cardiac Arrest Undergoing Percutaneous Coronary Intervention and Hypothermia: A Randomized Study.

Author: Steblovnik, Klemen MD, PhD; Blinc, Ales MD, PhD; Mijovski, Mojca Bozic PhD; Fister, Misa MD, PhD; Mikuz, Ursa MD; Noc, Marko MD, PhD

Page: 2128-2130

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Association of Mechanical Cardiopulmonary Resuscitation Device Use With Cardiac Arrest Outcomes: A Population-Based Study Using the CARES Registry (Cardiac Arrest Registry to Enhance Survival).

Author: Buckler, David G. NRP; Burke, Rita V. PhD, MPH; Naim, Maryam Y. MD; MacPherson, Andrew MD; Bradley, Richard N. MD; Abella, Benjamin S. MD, MPhil; Rossano, Joseph W. MD, MS; For the CARES Surveillance Group

Page: 2131-2133

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Advantages of time-resolved fluorescent nanobeads compared with fluorescent submicrospheres, quantum dots, and colloidal gold as label in lateral flow assays for detection of ractopamine

Publication date: 15 May 2017
Source:Biosensors and Bioelectronics, Volume 91
Author(s): Li-Ming Hu, Kai Luo, Jun Xia, Guo-Mao Xu, Cheng-Hui Wu, Jiao-Jiao Han, Gang-Gang Zhang, Miao Liu, Wei-Hua Lai
Label selection is a critical factor for improving the sensitivity of lateral flow assay. Time-resolved fluorescent nanobeads, fluorescent submicrospheres, quantum dots, and colloidal gold-based lateral flow assay (TRFN-LFA, FM-LFA, QD-LFA, and CG-LFA) were first systematically compared for the quantitative detection of ractopamine in swine urine based on competitive format. The limits of detection (LOD) of TRFN-LFA, FM-LFA, QD-LFA, and CG-LFA were 7.2, 14.7, 23.6, and 40.1pg/mL in swine urine samples, respectively. The sensitivity of TRFN-LFA was highest. In the quantitative determination of ractopamine (RAC) in swine urine samples, TRFN-LFA exhibited a wide linear range of 5pg/mL to 2500pg/mL with a reliable coefficient of correlation (R²=0.9803). Relatively narrow linear ranges of 10–500pg/mL (FM-LFA) and 25–2500pg/mL (QD-LFA and CG-LFA) were acquired. Approximately 0.005µg of anti-RAC poly antibody (pAb) was used in each TRFN-LFA test strip, whereas 0.02, 0.054, and 0.15µg of pAb were used in each of the FM-LFA, QD-LFA, and CG-LFA test strips, respectively. In addition, TRFN-LFA required the least RAC-BSA antigens and exhibited the shortest detection time compared with the other lateral flow assays. Analysis of the RAC in swine urine samples showed that the result of TRFN-LFA was consistent with that of liquid chromatography-tandem mass spectrometry (LC-MS/MS) and a commercial enzyme-linked immunosorbent assay (ELISA) kit.



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Antidiabetic activity of Ganoderma lucidum polysaccharides F31 down-regulated hepatic glucose regulatory enzymes in diabetic mice

Publication date: 20 January 2017
Source:Journal of Ethnopharmacology, Volume 196
Author(s): Chun Xiao, Qingping Wu, Jumei Zhang, Yizhen Xie, Wen Cai, Jianbin Tan
Ethnopharmacological relevanceGanoderma lucidum (Lin Zhi) has been used to treat diabetes in Chinese folk for centuries. Our laboratory previously demonstrated that Ganoderma lucidum polysaccharides (GLPs) had hypoglycemic effects in diabetic mice. Our aim was to identify the main bioactives in GLPs and corresponding mechanism of action.Materials and methodsFour polysaccharide-enriched fraction were isolated from GLPs and the antidiabetic activities were evaluated by type 2 diabetic mice. Fasting serum glucose (FSG), fasting serum insulin (FSI) and epididymal fat/BW ratio were measured at the end of the experiment. In liver, the mRNA levels of hepatic glucose regulatory enzymes were determined by quantitative polymerase chain reaction (qPCR) and the protein levels of phospho-AMP-activated protein kinase (p-AMPK)/AMPK were determined by western blotting test. In epididymal fat tissue, the mRNA and protein levels GLUT4, resistin, fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC1) were determined by qPCR and immuno-histochemistry. The structure of polysaccharide F31 was obtained from GPC, FTIR NMR and GC–MS spectroscopy,ResultsF31 significantly decreased FSG (P<0.05), FSI and epididymal fat/BW ratio (P<0.01). In liver, F31 decreased the mRNA levels of hepatic glucose regulatory enzymes, and up-regulated the ratio of phospho-AMP-activated protein kinase (p-AMPK)/AMPK. In epididymal fat tissue, F31 increased the mRNA levels of GLUT4 but decreased fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC1) and resistin. Immuno-histochemistry results revealed F31 increased the protein levels of GLUT4 and decreased resistin.ConclusionData suggested that the main bioactives in GLPs was F31, which was determined to be a β-heteropolysaccharide with the weight-average molecular weight of 15.9kDa. The possible action mechanism of F31 may be associated with down-regulation of the hepatic glucose regulated enzyme mRNA levels via AMPK activation, improvement of insulin resistance and decrease of epididymal fat/BW ratio. These results strongly suggest that F31 has antidiabetic potential.

Graphical abstract

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Spasmogenic and spasmolytic activities of Agastache mexicana ssp. mexicana and A. mexicana ssp. xolocotziana methanolic extracts on the guinea pig ileum

Publication date: 20 January 2017
Source:Journal of Ethnopharmacology, Volume 196
Author(s): Rosa Ventura-Martínez, Rodolfo Rodríguez, María Eva González-Trujano, Guadalupe E. Ángeles-López, Myrna Déciga-Campos, Claudia Gómez
Ethnopharmacological relevanceAgastache mexicana has been used in traditional medicine for relief of abdominal pain and treatment of other diseases. Two subspecies have been identified: A. mexicana ssp. mexicana (AMM) and A. mexicana ssp. xolocotziana (AMX) and both are used traditionally without distinction or in combination.Aim of the studyTo determine the effect of methanol extracts of A. mexicana ssp. mexicana and A. mexicana ssp. xolocotziana on gut motility and their possible mechanism of action.Materials and methodsThe effect of AMM and AMX methanol extracts were tested on the spontaneous activity in the isolated guinea pig ileum and on tissues pre-contracted with KCl, electrical field stimulation (EFS) or ACh. In addition, the possible mechanism of action of each subspecies on gut motility was analyzed in the presence of hexametonium, indomethacin, L-NAME, verapamil, atropine or pyrylamine. A comparative chromatographic profile of these extracts was also done to indicate the most abundant flavonoids presents in methanol extracts of both subspecies.ResultsAMM, but not AMX, induced a contractile effect in the guinea pig ileum. This spasmogenic effect was partially inhibited by atropine, antagonist of muscarinic receptors; and pyrilamine, antagonist of H1 receptors. In contrast, AMX, but not AMM, diminished the contractions induced by KCl, EFS or ACh. The spasmolytic activity of AMX was partially inhibited by hexamethonium, ganglionic blocker; and indomethacin, inhibitor of the synthesis of prostaglandins; but not by L-NAME, inhibitor of nitric oxide synthase. In addition, AMX diminished the maximal contraction induced by CaCl2 in a calcium-free medium. Chromatographic analyses of these methanol extracts showed the presence of acacetin and tilanin in both.ConclusionsThese results suggest that in folk medicine only AMX should be used as spasmolytic, and not in combination with AMM as traditionally occurs, due to the spasmogenic effects of the latter. In addition, activation of nicotinic receptors, prostaglandins and calcium channels, but not nitric oxide mechanisms, could be responsible for the spasmolytic activity of AMX. On the other hand, release of ACh and histamine could be involved in the spasmogenic effect induced by AMM. Acacetin and tilanin are present in methanol extracts of both subspecies and both flavonoids were more abundant in AMX than AMM. Our findings contribute to the validation of the traditional use of Agastache mexicana in relieving gastrointestinal disorders, but indicate that the subspecie that should be used for this effect is A. mexicana ssp. xolocotziana.

Graphical abstract

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Thyroid High-Impact Articles

FREE ACCESS through January 2, 2017.
Read Now:

Thyronamines and Derivatives: Physiological Relevance, Pharmacological Actions, and Future Research Directions
Carolin Stephanie Hoefig, Riccardo Zucchi, Josef Köhrle

Circulating 3-T1AM and 3, 5-T2 in Critically Ill Patients: A Cross-Sectional Observational Study
Lies Langouche, Ina Lehmphul, Sarah Vander Perre, Josef Köhrle, Greet Van den Berghe

Selenium Supplementation Significantly Reduces Thyroid Autoantibody Levels in Patients with Chronic Autoimmune Thyroiditis: A Systematic Review and Meta-Analysis
Johanna Wichman, Kristian Hillert Winther, Steen Joop Bonnema, Laszlo Hegedüs

Cervical Lymph Node Metastases After Thyroidectomy for Papillary Thyroid Carcinoma Usually Remain Stable for Years
Chisato Tomoda, Kiminori Sugino, Kenichi Matsuzu, Takashi Uruno, Keiko Ohkuwa, Wataru Kitagawa, Mitsuji Nagahama, Koichi Ito

Reference Intervals of Thyroid Function During Pregnancy: Self-Sequential Longitudinal Study Versus Cross-Sectional Study
Xiaomei Zhang, Baoting Yao, Chenyan Li, Jinyuan Mao, Weiwei Wang, Xiaochen Xie, Xiaochun Teng, Cheng Han, Weiwei Zhou, Chenyang Li, Bin Xu, Lihua Bi, Tao Meng, Jianling Du, Shaowei Zhang, Zhengnan Gao, Liu Yang, Chenling Fan, Weiping Teng, Zhongyan Shan

The post Thyroid High-Impact Articles appeared first on American Thyroid Association.

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Concomitant alterations of metabolic parameters, cardiovascular risk factors and altered cortisol secretion in patients with adrenal incidentalomas during prolonged follow-up

Abstract

Objective

Adrenal incidentalomas (AI) are associated with metabolic and hormonal abnormalities, most commonly autonomous cortisol secretion (ACS). Data regarding alterations of insulin resistance (IR), and ACS after prolonged follow-up are limited. We investigated the evolution of IR, cortisol secretion and ACS development in patients with AI during prolonged follow-up.

Design

Prospective study in a tertiary hospital.

Patients and Measurements

Seventy-one patients with AI, (51 non-functioning [NFAI], 20 ACS), and 5.54±1.7 year follow-up underwent testing for autonomous cortisol secretion, Oral Glucose Tolerance Test to determine IR indices and adrenal imaging.

Results

At follow-up, 16/51 (31%) NFAI patients converted to ACS, while 2 with previous ACS reverted to NFAI; 21% (7/33) of patients who did not covert to ACS exhibited high urinary free cortisol (H-UFC) levels. All AI patients developed deterioration of IR irrespective of their cortisol secretory status. Eight patients developed newly diagnosed type 2 diabetes (9.8% NFAI and 15% ACS, respectively) and 14 IR (17.6% NFAI and 25% ACS, respectively). Adenoma size increased from 2.1±0.8 to 2.3±0.8cm, whereas IR correlated with post-dexamethasone cortisol level and adenoma size increase. IR showed an incremental continuum trend from normal UFC (Ν-UFC), to H-UFC, to C-ACS and ACS patients.

Conclusions

New-onset ACS developed in 31% patients with NFAI whereas 21% of NFAI patients had H-UFC levels. All AI patients as a group and the subgroups of N-UFC, H-UFC, C-ACS and ACS patients developed deterioration of metabolic parameters during follow-up that was more prominent in ACS patients.

This article is protected by copyright. All rights reserved.

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Effectiveness of an Educational Intervention on Reducing Misconceptions among Ethnic Minorities with Complicated Mild to Severe Traumatic Brain Injury

Publication date: Available online 19 December 2016
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Monique R. Pappadis, Angelle M. Sander, Beata Łukaszewska, Margaret A. Struchen, Patrick Leung, Dennis W. Smith
ObjectiveTo evaluate the effectiveness of an educational intervention designed to reduce TBI-related misconceptions among Blacks and Latinos with complicated mild to severe TBI.DesignA randomized controlled trial with masked one-month follow-up.SettingCommunity.Participants52 persons with complicated mild to severe TBI (Mean Best day 1 GCS=11.27; SD=3.89) were randomly recruited from 141 eligible participants (Mean age=37.71, SD=13.88, age range, 19-66; Mean months post injury=24.69, SD=11.50). 48.1% of participants were Black and 51.9% were Hispanic/Latino. Of the Hispanic/Latino participants, 66.7% were non-U.S. born and 44.4% spoke Spanish as their primary language. Twenty-seven individuals were randomized to the educational intervention group and 25 were randomized to the wait-list control group.InterventionsA single-session educational intervention with written materials provided in English or Spanish.Main Outcome Measures40-item Common Misconceptions about Traumatic Brain Injury Questionnaire (CM-TBI) administered at baseline and one-month follow-up.ResultsAfter controlling for ethnic-language group, a significant between-group main effect (p=.010) and a significant time-group interaction for the CM-TBI was noted, Wilks'Λ=0.89, F(1,46)=6.00, p=.02. The intervention group showed a decrease in TBI misconception percentages, while the wait-list control group maintained similar percentages. At one-month follow-up, the wait-list control group reported more misconceptions than the intervention group (p = .019).ConclusionsAn educational intervention developed to address the recovery process, common symptoms, and ways to handle the symptoms provides promise as a tool to decrease TBI misconceptions among persons from ethnically and educationally diverse backgrounds. The influence of therapist characteristics and the client-therapist relationship on outcomes should be further explored.



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Functional Goals and Predictors of their Attainment in Low-Income Community-Dwelling Older Adults

Publication date: Available online 19 December 2016
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Brian W. Waldersen, Jennifer L. Wolff, Laken Roberts, Allysin E. Bridges, Laura N. Gitlin, Sarah L. Szanton
ObjectiveTo describe functional goals and factors associated with goal attainment among low-income older adults with disabilities living in the community.DesignSecondary analysis from two studies of CAPABLE. Functional goals were coded using the International Classification of Functioning, Disability, and Health (ICF) framework. The percentage of goals attained at five months follow-up was computed within each ICF domain. Multivariate logistic regression was used to identify factors associated with goal attainment.SettingParticipants' homes in Baltimore, MarylandParticipantsCAPABLE participants (n=226)InterventionsA five-month, home-based, person-directed, structured program delivered by an inter-professional team: occupational therapist (OT), registered nurse (RN), and handyman.Main Outcome Measure(s)Process of OT goal setting and attainment at the final OT visit.ResultsParticipants identified 728 functional goals (average of 3.2 per participant), most commonly related to transferring (22.0%, n=160 goals), changing or maintaining body position (21.4%, n=156 goals), and stairclimbing (13.0%, n= 95 goals). Participants attained 73.5% (n=535) of goals. Goal attainment was highest for stairclimbing (86.3%), transferring (85.6%), and self-care (84.6%); walking goals were less likely attained (54.0%). Goal attainment was not associated with age, gender, education, depressive symptoms, function, or health-related quality of life but was less likely among participants who had severe pain compared to those without pain (aOR: 0.38, 95% CI: 0.17, 0.86). When participant readiness to change (RTC) score increases by one point on the four-point scale, goal attainment was 62% more likely (aOR 1.62; 95% CI: 1.14-2.29).ConclusionHome-based collaborative goal-setting between older adults and OTs is feasible and particularly effective when individuals are ready or willing to adopt new strategies to achieve identified goals.



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A Delphi Study to Determine Rehabilitation Research Priorities for Older Adults with Cancer

Publication date: Available online 19 December 2016
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Kathleen Doyle Lyons, Mary Vining Radomski, Catherine M. Alfano, Marsha Finkelstein, Alix G. Sleight, Timothy F. Marshall, Raymond McKenna, Jack B. Fu
ObjectiveTo solicit expert opinions and develop consensus around the research that is needed to improve cancer rehabilitation for older adults.DesignDelphi methods provided a structured process to elicit and prioritize research questions from national experts.SettingNational, web-based survey.ParticipantsThirty-two members of the American Congress of Rehabilitation Medicine completed at least one of three investigator-developed surveys.InterventionsNot applicable.Main outcomesIn the first survey, participants identified up to five research questions that needed to be answered to improve cancer rehabilitation for older adults. In two subsequent surveys, participants viewed the compilation of questions, rated the importance of each question, and identified the five most important questions. This generated priority scores for each question. Consensus scores were created to describe the degree of agreement around the priority of each question.ResultsHighest priority research concerns the epidemiology and measurement of function and disability in older adult cancer survivors; the effects of cancer rehabilitation interventions on falls, disability, participation survival, costs, quality of care, and healthcare utilization; and testing models of care that facilitate referrals from oncology to rehabilitation providers as part of coordinated, multi-component care.ConclusionsA multi-pronged approach is needed to fill these gaps including targeted funding opportunities developed with an advisory panel of cancer rehabilitation experts, the development of a research network to facilitate novel collaborations and grant proposals, and coordinated efforts of clinical groups to advocate for funding, practice change, and policy change.



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Pseudohypoparathyroidism: one gene, several syndromes

Abstract

Pseudohypoparathyroidism (PHP) and pseudopseudohypoparathyroidism (PPHP) are caused by mutations and/or epigenetic changes at the complex GNAS locus on chromosome 20q13.3 that undergoes parent-specific methylation changes at several sites. GNAS encodes the alpha-subunit of the stimulatory G protein (Gsα) and several splice variants thereof. Heterozygous inactivating mutations involving the maternal GNAS exons 1–13 cause PHP type Ia (PHP1A). Because of much reduced paternal Gsα expression in certain tissues, such as the proximal renal tubules, thyroid, and pituitary, there is little or no Gsα protein in the presence of maternal GNAS mutations, thus leading to PTH-resistant hypocalcemia and hyperphosphatemia. When located on the paternal allele, the same or similar GNAS mutations are the cause of PPHP. Besides biochemical abnormalities, patients affected by PHP1A show developmental abnormalities, referred to as Albrights hereditary osteodystrophy (AHO). Some, but not all of these AHO features are encountered also in patients affected by PPHP, who typically show no laboratory abnormalities. Autosomal dominant PHP type Ib (AD-PHP1B) is caused by heterozygous maternal deletions within GNAS or STX16, which are associated with loss-of-methylation (LOM) at exon A/B alone or at all maternally methylated GNAS exons. LOM at exon A/B and the resulting biallelic expression of A/B transcripts reduces Gsα expression, thus leading to hormonal resistance. Epigenetic changes at all differentially methylated GNAS regions are also observed in sporadic PHP1B, the most frequent disease variant, which remains unresolved at the molecular level, except for rare cases with paternal uniparental isodisomy or heterodisomy of chromosome 20q (patUPD20q).

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ACE inhibitors and the risk of fractures: a meta-analysis of observational studies

Abstract

A meta-analysis was conducted to evaluate the effect of treatment with angiotensin-converting enzyme inhibitors on the risk of fractures. All the included articleswere retrieved from MEDLINE, EMBASE and the Cochrane Database. Trial eligibility and methodological quality were assessed before data extraction. Relative risk (RR) with corresponding 95% confidence intervals (95% CI) were used to assess the effect. Six case-control studies with11,387,668 participants met the inclusion criteria and were included in the meta-analysis. A small but significant risk effect on fractures was shown in the overall analysis of angiotensin-converting enzyme inhibitor users compared with nonusers (Pooled RR 1.27; 95% CI 1.01–1.60), although a relatively high heterogeneity was found across studies. In the stratified analysis, therewas no statistically significant association in the subgroups of hip fracture (Pooled RR 1.14; 95% CI 0.73–1.76) and the study quality (Pooled RR 1.13; 95% CI 0.89–1.44), while the over 65-year-old angiotensin-converting enzyme inhibitor users showed a stronger risk effect on fractures (Pooled RR 2.06; 95% CI 1.53–3.17). Moreover, age was found to be contributed a large part of the high heterogeneity across the included studies. This study demonstrated that the use of angiotensin-converting enzyme inhibitors might have a small but significant risk effect on fractures, especially for the over 65-year-old users. These results should be interpreted with caution as the relatively high heterogeneity across studies. Additional multiple observational studies and high quality data from randomized controlled trials are needed to confirm these findings.

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Adrenal crises: perspectives and research directions

Abstract

Adrenal crises are life-threatening complications of adrenal insufficiency. These events have an estimated incidence of between 5 and 10  adrenal crises/100 patient years and are responsible for some of the increased morbidity and excess mortality experienced by patients with adrenal insufficiency. Treatment involves urgent administration of IV/IM hydrocortisone and IV fluids. Patient education regarding preventive measures, such as increasing the dose of replacement therapy ("stress dosing") when sick, using parenteral hydrocortisone as necessary and accessing medical assistance promptly, is still considered the best approach to averting the onset of an adrenal crisis at times of physiological stress, most commonly an infection. However, recent evidence has demonstrated that patient education does not prevent many adrenal crisis events and the reasons for this are not fully understood. Furthermore, there is no widely accepted definition of an adrenal crisis. Without a validated adrenal crisis definition it is difficult to interpret variations in the incidence of adrenal crises and determine the effectiveness of preventive measures. This article aims to review the clinical aspects of adrenal crisis events, to explore the epidemiology, and to offer a definition of an adrenal crisis and to offer a perspective on future directions for research into adrenal crisis prevention.

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Idiopathic hypophosphatemic osteomalacia: recurrent pseudofracture of the proximal femur in a 65-year-old man

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Phase I study of nab-paclitaxel plus carboplatin and concurrent thoracic radiotherapy in patients with locally advanced non-small cell lung cancer

Abstract

Background

The aim of our study was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus carboplatin in combination with thoracic radiotherapy for patients with locally advanced stage III non-small cell lung cancer (NSCLC).

Methods

Weekly nab-paclitaxel plus carboplatin was administered intravenously for 6 weeks. Doses of each drug were planned as follows: level 1, 40/2; level 2, 60/2; level 3, 80/2 (nab-paclitaxel [mg/m²]/carboplatin [area under the plasma concentration time curve mg/ml/min]). Concurrent thoracic radiotherapy was administered in 2-Gy fractions 5 times weekly, to a total dose of 60 Gy.

Results

Fourteen patients were enrolled in the present study. Eleven (78%) patients received full cycles (6 cycles) of chemotherapy, and 12 (86%) patients received 60 Gy of thoracic radiotherapy. At level 1, none of 3 patients experienced a dose-limiting toxicity (DLT). At level 2, 2 of 7 patients developed grade 3 diarrhea, grade 3 hyponatremia, grade 3 fatigue, and grade 3 esophagitis. Therefore, 4 patients were started at dose level 3 and none developed a DLT. No pulmonary toxicities, such as interstitial pneumonitis and treatment-related deaths, were observed at either level. Therefore, level 3 was considered the MTD and level 3 was defined as the RD. An objective response was observed in 71.4% of all patients.

Conclusions

This regimen is feasible and well tolerated for the treatment of patients with unresectable locally advanced NSCLC.

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Gamma Knife Radiosurgery of Brainstem Cavernous Malformations

Background/Aims: Our study aimed to evaluate the efficiency and morbidity of Gamma Knife radiosurgery (GKS) in the treatment of hemorrhagic brainstem cavernous malformations (CMs). Methods: We included in this study all patients who underwent GKS for the treatment of a hemorrhagic brainstem CM(s) in our institution between January 2007 and December 2012. The GKS was privileged when the surgical procedure was evaluated as very risky. The mean dose of radiation was 14.8 Gy, and the mean target volume was 0.282 cm³. All patients participated in a scheduled clinical follow-up. The posttreatment MRI was performed after 6 months and after 1 year, and then all patients had an annual MRI follow-up. Results: There were 19 patients with a mean age of 36.7 years. The mean follow-up period was 51.2 months. The annual hemorrhage rate (AHR) was 27.31% before GKS, 2.46% during the first 2 years following the GKS, and 2.46% after the first 2 years following the GKS. The decrease in AHR after GKS was significant (p Conclusion: GKS should be suggested when the surgical procedure harbors a high risk of neurological morbidity in patients with brainstem CM. Compared to prior literature results, a lower dose than applied in this study could be discussed.
Stereotact Funct Neurosurg 2016;94:397-403

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Production of methyl ester from two microalgae by two-step transesterification and direct transesterification

Abstract

The efficiency of oil extraction from Chlorella sp. and Scenedesmus sp. using different cell disruption and solvent system was investigated. The ultrasound cell disruption method showed the maximum oil extraction in both algae. Oil extraction with hexane resulted in maximum oil yield for both algae. The kinetic parameters were studied and the extraction followed the first-order kinetics. The activation energy and thermodynamic activation parameters were calculated for both microalgae and the results suggested that the extraction was endothermic, irreversible and spontaneous. The methyl ester yields by two-step transesterification and direct transesterification were 95 and 96% for Scenedesmus sp. and 89 and 92% for Chlorella sp. respectively. Both methods had similar net energy consumption suitable for industrial application. The methyl ester properties were analysed in comparison with those of American Society for Testing and Materials (ASTM) D6751 standards.

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Isolation and purification of antialgal compounds from the red alga Gracilaria lemaneiformis for activity against common harmful red tide microalgae

Abstract

Seven antialgal compounds (1–7) were successfully isolated from the red alga Gracilaria lemaneiformis through a combination of silica gel column chromatography and repeated preparative thin-layer chromatography. On the basis of the spectral data, the compounds were identified as gossonorol (1), 7,10-epoxy-ar-bisabol-11-ol (2), glycerol monopalmitate (3), stigmasterol (4), 15-hydroxymethyl-2, 6, 10, 18, 22, 26, 30-heptamethyl-14-methylene-17-hentriacontene (5), 4-hydroxyphenethyl alcohol (6), and margaric acid (7). These seven compounds were isolated from G. lemaneiformis for the first time, while the compounds 4, 6, and 7 were isolated from marine macroalgae for the first time. Furthermore, a quantitative relationship between the inhibition of algal growth and the concentration of each antialgal compound was determined and important parameters for future practical HAB control, e.g., EC_50-96h, were also obtained. The results indicated that isolated compounds 1–7 possess selective antialgal activity against the growth of several red tide microalgae (including Amphidinium carterae, Heterosigma akashiwo, Karenia mikimitoi, Phaeocystis globsa, Prorocentrum donghaiense, and Skeletonema costatum). Their antialgal activity against test red tide microalgae has not been previously reported. Furthermore, the EC_50-96h of one or more of the compounds towards the tested red microalgae was not only significantly less than 10 μg/mL but also was smaller than that of the characteristic antialgal agent potassium dichromate. The study demonstrates that compounds 1–7 possess significant application potential as antialgal agents against several harmful red tide microalgae.

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Phenylpropanoids are key players in the antioxidant defense to ozone of European ash, Fraxinus excelsior

Abstract

Physiological and biochemical responses to ozone (O₃) (150 ppb, 8 h day⁻¹, 35 consecutive days) of two Italian provenances (Piedmont and Tuscany) of Fraxinus excelsior L. were evaluated, with special attention to the role of phenylpropanoids. Our results indicate (i) the high O₃ sensitivity especially of Piedmont provenance (in terms of visible injury, water status, and photosynthetic apparatus); (ii) although the intra-specific sensitivity to O₃ between provenances differs (mainly due to different stomatal behaviors since only Tuscany plants partially avoided the uptake of the pollutant gas), both provenances showed detoxification and defense mechanisms; (iii) the crucial participation of phenylpropanoids, with a key role played by flavonoids (especially quercitrin): among this class of metabolites, isoquercitrin is the principal player in the lower O₃ sensitivity of Tuscany plants, together with lignins; (iv) although coumarins (typical compounds of Fraxinus) were severely depressed by O₃, isofraxidin was triggered suggesting a key role in reactive oxygen species (ROS) detoxification, as well as trans-chalcone. Furthermore, the different behavior of verbascoside and oleuropein among provenances lead us to speculate on their influence in the tentatively repair or acclimation shown by Piedmont plants at the end of the exposure. Finally, the intra-specific O₃ sensitivity may be also due to de novo peaks triggered by O₃ not yet associated to some chemicals.

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Spatio-temporal variability of fluorescent dissolved organic matter in the Rhône River delta and the Fos-Marseille marine area (NW Mediterranean Sea, France)

Abstract

The spatio-temporal variability of fluorescent dissolved organic matter (FDOM) and its relationships with physical (temperature, salinity) and chemical (nutrients, chlorophyll a, dissolved and particulate organic carbon, nitrogen and phosphorus) parameters were investigated in inland waters of the Rhône River delta and the Fos-Marseille marine area (northwestern Mediterranean, France). Samples were taken approximately twice per month in two inland sites and three marine sites from February 2011 to January 2012. FDOM was analysed using fluorescence excitation-emission matrices (EEMs) coupled with parallel factor analysis (PARAFAC). In inland waters, humic-like components C1 (λ_Ex/λ_Em: 250 (330)/394 nm) and C3 (λ_Ex/λ_Em: 250 (350)/454 nm) dominated over one tryptophan-like component C2 (λ_Ex/λ_Em: 230 (280)/340 nm), reflecting a background contribution of terrigenous material (~67% of total fluorescence intensity, in quinine sulphate unit (QSU)) throughout the year. In marine waters, protein-like material, with tyrosine-like C4 (λ_Ex/λ_Em: <220 (275)/<300 nm) and tryptophan-like C5 (λ_Ex/λ_Em: 230 (280)/342 nm), dominated (~71% of total fluorescence intensity, in QSU) over a single humic-like component C6 (λ_Ex/λ_Em: 245 (300)/450 nm). In inland waters of the Rhône River delta, humic-like components C1 and C3 were more abundant in autumn-winter, very likely due to inputs of terrestrial organic matter from rainfalls, runoffs and wind-induced sediment resuspension. In marine sites, intrusions of the Berre Lagoon and Rhône River waters had a significant impact on the local biogeochemistry, leading to higher fluorescence intensities of humic- and protein-like components in spring-summer. On average, the fluorescence intensities of FDOM components C4, C5 and C6 increased by 33–81% under lower salinity. This work highlights the complex dynamics of FDOM in coastal waters and confirms the link between marine FDOM and the Rhône River freshwater intrusions on larger spatial and temporal scales in the Fos-Marseille marine area.

http://ift.tt/2gVb0eu

Cd inhibition and pH improvement via a nano-submicron mineral-based soil conditioner

Abstract

Cd contamination of rice in recent years has aroused a nationwide concern on the potential health risk to people in China. A significant increase of soil acidification in major Chinese croplands improves available Cd content by crops, and this further pushes a heavier burden on controlling Cd contamination. Therefore, it is urgent to find a workable and green way to control Cd contamination, i.e., decrease Cd content in rice, for people's health in China, as other countries in the world. From chemical and economic points, stabilizing/solidifying Cd may be a feasible way except in-situ ways such as removing it by the absorption of special plants and ex-situ ones such as removing the contaminated soil and treating it by special equipment. Then, it is very important how to choose a green solidifying agent. By simulating a rock-weathering process, a nano-submicron mineral-based soil conditioner (NSC) was prepared through environmentally friendly hydrothermal reaction. The application of NSC not only decreased Cd content in rice, i.e., inhibited Cd absorption, and increased pH of the soil, but also improved the content of healthy nutrients such as organic matter, available Ca, available K, available P, and available Si in the soil. The mechanism why NSC showed such good performance was also discussed in this study.

http://ift.tt/2i2DLuV

ACE inhibitors and the risk of fractures: a meta-analysis of observational studies

Abstract

A meta-analysis was conducted to evaluate the effect of treatment with angiotensin-converting enzyme inhibitors on the risk of fractures. All the included articleswere retrieved from MEDLINE, EMBASE and the Cochrane Database. Trial eligibility and methodological quality were assessed before data extraction. Relative risk (RR) with corresponding 95% confidence intervals (95% CI) were used to assess the effect. Six case-control studies with11,387,668 participants met the inclusion criteria and were included in the meta-analysis. A small but significant risk effect on fractures was shown in the overall analysis of angiotensin-converting enzyme inhibitor users compared with nonusers (Pooled RR 1.27; 95% CI 1.01–1.60), although a relatively high heterogeneity was found across studies. In the stratified analysis, therewas no statistically significant association in the subgroups of hip fracture (Pooled RR 1.14; 95% CI 0.73–1.76) and the study quality (Pooled RR 1.13; 95% CI 0.89–1.44), while the over 65-year-old angiotensin-converting enzyme inhibitor users showed a stronger risk effect on fractures (Pooled RR 2.06; 95% CI 1.53–3.17). Moreover, age was found to be contributed a large part of the high heterogeneity across the included studies. This study demonstrated that the use of angiotensin-converting enzyme inhibitors might have a small but significant risk effect on fractures, especially for the over 65-year-old users. These results should be interpreted with caution as the relatively high heterogeneity across studies. Additional multiple observational studies and high quality data from randomized controlled trials are needed to confirm these findings.

http://ift.tt/2hk98wO

Adrenal crises: perspectives and research directions

Abstract

Adrenal crises are life-threatening complications of adrenal insufficiency. These events have an estimated incidence of between 5 and 10  adrenal crises/100 patient years and are responsible for some of the increased morbidity and excess mortality experienced by patients with adrenal insufficiency. Treatment involves urgent administration of IV/IM hydrocortisone and IV fluids. Patient education regarding preventive measures, such as increasing the dose of replacement therapy ("stress dosing") when sick, using parenteral hydrocortisone as necessary and accessing medical assistance promptly, is still considered the best approach to averting the onset of an adrenal crisis at times of physiological stress, most commonly an infection. However, recent evidence has demonstrated that patient education does not prevent many adrenal crisis events and the reasons for this are not fully understood. Furthermore, there is no widely accepted definition of an adrenal crisis. Without a validated adrenal crisis definition it is difficult to interpret variations in the incidence of adrenal crises and determine the effectiveness of preventive measures. This article aims to review the clinical aspects of adrenal crisis events, to explore the epidemiology, and to offer a definition of an adrenal crisis and to offer a perspective on future directions for research into adrenal crisis prevention.

http://ift.tt/2h54UNv

Idiopathic hypophosphatemic osteomalacia: recurrent pseudofracture of the proximal femur in a 65-year-old man

http://ift.tt/2hk2xmh

Commentary on Some Recent Theses Relevant to Combating Aging: December 2016

Rejuvenation Research Dec 2016, Vol. 19, No. 6: 525-530.


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Pharmaceutical Rejuvenation of Age-Associated Decline in Spatial Memory

Rejuvenation Research Dec 2016, Vol. 19, No. 6: 521-524.


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Rejuvenation Research Dec 2016, Vol. 19, No. 6: 531-536.

Rejuvenation Research Dec 2016, Vol. 19, No. 6: 531-536.


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Don't Call Aging a Risk Factor for Age-Related Disease

Rejuvenation Research Dec 2016, Vol. 19, No. 6: 445-446.


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Correction

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Circulating Long Noncoding RNAs in Personalized Medicine: Response to Pioglitazone Therapy in Type 2 Diabetes

http://ift.tt/2hB8Cxu

High-Sensitivity Cardiac Troponin, Statin Therapy, and Risk of Coronary Heart Disease

AbstractBackground

Cardiac troponin is an independent predictor of cardiovascular mortality in individuals without symptoms or signs of cardiovascular disease. The mechanisms for this association are uncertain, and a role for troponin testing in the prevention of coronary heart disease has yet to be established.

Objectives

This study sought to determine whether troponin concentration could predict coronary events, be modified by statins, and reflect response to therapy in a primary prevention population.

Methods

WOSCOPS (West of Scotland Coronary Prevention Study) randomized men with raised low-density lipoprotein cholesterol and no history of myocardial infarction to pravastatin 40 mg once daily or placebo for 5 years. Plasma cardiac troponin I concentration was measured with a high-sensitivity assay at baseline and at 1 year in 3,318 participants.

Results

Baseline troponin was an independent predictor of myocardial infarction or death from coronary heart disease (hazard ratio [HR]: 2.3; 95% confidence interval [CI]: 1.4 to 3.7) for the highest (≥5.2 ng/l) versus lowest (≤3.1 ng/l) quarter of troponin (p < 0.001). There was a 5-fold greater reduction in coronary events when troponin concentrations decreased by more than a quarter, rather than increased by more than a quarter, for both placebo (HR: 0.29; 95% CI: 0.12 to 0.72 vs. HR: 1.95; 95% CI: 1.09 to 3.49; p < 0.001 for trend) and pravastatin (HR: 0.23; 95% CI: 0.10 to 0.53 vs. HR: 1.08; 95% CI: 0.53 to 2.21; p < 0.001 for trend). Pravastatin reduced troponin concentration by 13% (10% to 15%; placebo adjusted, p < 0.001) and doubled the number of men whose troponin fell more than a quarter (p < 0.001), which identified them as having the lowest risk for future coronary events (1.4% over 5 years).

Conclusions

Troponin concentration predicts coronary events, is reduced by statin therapy, and change at 1 year is associated with future coronary risk independent of cholesterol lowering. Serial troponin measurements have major potential to assess cardiovascular risk and monitor the impact of therapeutic interventions.

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Statin Therapy on the Basis of HOPE: A European Perspective

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High-Sensitivity Cardiac Troponin and Primary Prevention: An Important New Role

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Reply: Risk Prediction in Acute Myocardial Infarction

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Sex-Based Differences in Outcomes With Transcatheter Aortic Valve Therapy: TVT Registry From 2011 to 2014

AbstractBackground

A differential impact of sex has been observed in transcatheter aortic valve replacement (TAVR) outcomes from small observational studies and subgroup analyses of randomized trials.

Objectives

The goal of this study was to compare the in-hospital and 1-year outcomes in male and female subjects from the U.S. nationwide TAVR registry.

Methods

National data from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry were used for in-hospital outcomes, and data linked from the Centers for Medicare & Medicaid Services were used to provide 1-year events. Multivariable logistic regression adjustment was performed for in-hospital outcomes. Fine-Gray models were used for nonfatal 1-year outcomes to account for the competing risk of death.

Results

From 2011 to 2014, a total of 11,808 (49.9%) women and 11,844 (51.1%) men underwent TAVR. Compared with male patients, female patients were older, with a lower prevalence of coronary artery disease, atrial fibrillation, and diabetes but a higher rate of porcelain aorta, lower glomerular filtration rate, and higher mean Society of Thoracic Surgeons score (9.0% vs. 8.0%; all p < 0.001). Women were treated more often by using nontransfemoral access than men (45.0% vs. 34.0%). Despite using smaller device sizes, women achieved valve cover index ≥8% more often than men (66% vs. 54%). In-hospital vascular complications were higher in women (8.27% vs. 4.39%; adjusted hazard ratio [HR]: 1.70; 95% CI: 1.34 to 2.14; p < 0.001) and a trend toward higher bleeding (8.01% vs 5.96%; adjusted HR: 1.19; 95% CI: 0.99 to 1.44; p = 0.06) was observed; however, 1-year mortality was lower (21.3% vs. 24.5%; adjusted HR: 0.73; 95% CI: 0.63 to 0.85; p < 0.001) in women than in men.

Conclusions

Female patients undergoing TAVR had a different risk profile compared with male patients. Notwithstanding a greater adjusted risk for in-hospital vascular complications, 1-year adjusted survival was superior in female patients.

http://ift.tt/2hMRLWG

Left Anterior Descending Artery Myocardial Bridging: A Clinical Approach

Abstract

A myocardial bridge (MB) is the term for the muscle overlying the intramyocardial segment of the epicardial coronary artery (referred to as a tunneled artery). Although MBs can be found in any epicardial artery, most of them involve the left anterior descending artery. These congenital coronary anomalies have long been recognized anatomically, and are traditionally considered a benign condition; however, the association between myocardial ischemia and MBs has increased their clinical relevance. This review summarizes the prevalence, pathophysiology, and diagnostic findings, including morphological, functional assessment, and treatment of patients with MB involving the left anterior descending artery, suggesting a pragmatic clinical approach to this entity.

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Transcatheter Aortic Valve Replacement: Only One of the Advantages of Being Female

http://ift.tt/2hMKWnL

Prospective Evaluation of the Eyeball Test for Assessing Frailty in Patients With Valvular Heart Disease

http://ift.tt/2hB7CcP

HotBalloon Ablation of the Pulmonary Veins for Paroxysmal AF: A Multicenter Randomized Trial in Japan

AbstractBackground

Point-by-point catheter ablation is an established treatment for drug-refractory paroxysmal atrial fibrillation (PAF). However, it is time consuming, requires excellent technique to achieve complete pulmonary vein (PV) isolation, and is associated with severe complications.

Objectives

The purpose of this study was to evaluate the safety and effectiveness of a HotBalloon ablation (HBA) compared with antiarrhythmic drug therapy (ADT) for the treatment of PAF.

Methods

A prospective multicenter randomized controlled study was conducted in Japan. Patients with symptomatic PAF refractory to antiarrhythmic drugs (Class I to IV) were randomized to HBA or ADT at a 2:1 ratio and assessed for effectiveness in a comparable 9-month follow-up period.

Results

A total of 100 patients in the HBA group and 43 patients in the ADT group received treatment at 17 sites. HBA procedure produced acute complete PV isolation in 98.0% (392 of 400) of the PVs and in 93.0% (93 of 100) of patients in the HBA group. The chronic success rates after the 9-month effective evaluation period were 59.0% in the HBA group (n = 100) and 4.7% in the ADT group (n = 43; p < 0.001). The incidence of major complications was 11.2% (15 of 134 patients). The incidences of PV stenosis (>70%) and transient phrenic nerve injury were 5.2% and 3.7%, respectively. The mean fluoroscopy time was 49.4 ± 26.6 min (n = 134), and the mean procedure duration was 113.9 ± 31.9 min (n = 133).

Conclusions

This study demonstrates the superiority of HBA compared with ADT for treatment of patients with PAF, and a favorable safety profile.

http://ift.tt/2hMNUJh

Reply: Trimethylamine N-Oxide in Seafood: Rotten or Forgotten?

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Overview of Balloon Approaches to AF Ablation: Some Like it Hot?

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Correction

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Phenotypic Characterization of Genetically Lowered Human Lipoprotein(a) Levels

AbstractBackground

Genomic analyses have suggested that the LPA gene and its associated plasma biomarker, lipoprotein(a) (Lp[a]), represent a causal risk factor for coronary heart disease (CHD). As such, lowering Lp(a) levels has emerged as a therapeutic strategy. Beyond target identification, human genetics may contribute to the development of new therapies by defining the full spectrum of beneficial and adverse consequences and by developing a dose–response curve of target perturbation.

Objectives

The goal of this study was to establish the full phenotypic impact of LPA gene variation and to estimate a dose–response curve between genetically altered plasma Lp(a) and risk for CHD.

Methods

We leveraged genetic variants at the LPA gene from 3 data sources: individual-level data from 112,338 participants in the U.K. Biobank; summary association results from large-scale genome-wide association studies; and LPA gene sequencing results from case subjects with CHD and control subjects free of CHD.

Results

One SD genetically lowered Lp(a) level was associated with a 29% lower risk of CHD (odds ratio [OR]: 0.71; 95% confidence interval [CI]: 0.69 to 0.73), a 31% lower risk of peripheral vascular disease (OR: 0.69; 95% CI: 0.59 to 0.80), a 13% lower risk of stroke (OR: 0.87; 95% CI: 0.79 to 0.96), a 17% lower risk of heart failure (OR: 0.83; 95% CI: 0.73 to 0.94), and a 37% lower risk of aortic stenosis (OR: 0.63; 95% CI: 0.47 to 0.83). We observed no association with 31 other disorders, including type 2 diabetes and cancer. Variants that led to gain of LPA gene function increased the risk for CHD, whereas those that led to loss of gene function reduced the CHD risk.

Conclusions

Beyond CHD, genetically lowered Lp(a) levels are associated with a lower risk of peripheral vascular disease, stroke, heart failure, and aortic stenosis. As such, pharmacological lowering of plasma Lp(a) may influence a range of atherosclerosis-related diseases.

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Instructions For Authors

http://ift.tt/2hB34TC

Using Human Genetics to Predict the Effects and Side Effects of Lipoprotein(a) Lowering Drugs

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A View From the New Membership Committee

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Genetic and Pharmacological Inhibition of TREM-1 Limits the Development of Experimental Atherosclerosis

AbstractBackground

Innate immune responses activated through myeloid cells contribute to the initiation, progression, and complications of atherosclerosis in experimental models. However, the critical upstream pathways that link innate immune activation to foam cell formation are still poorly identified.

Objectives

This study sought to investigate the hypothesis that activation of the triggering receptor expressed on myeloid cells (TREM-1) plays a determinant role in macrophage atherogenic responses.

Methods

After genetically invalidating Trem-1 in chimeric Ldlr^–/–Trem-1^–/– mice and double knockout ApoE^–/–Trem-1^–/– mice, we pharmacologically inhibited Trem-1 using LR12 peptide.

Results

Ldlr^–/– mice reconstituted with bone marrow deficient for Trem-1 (Trem-1^–/–) showed a strong reduction of atherosclerotic plaque size in both the aortic sinus and the thoracoabdominal aorta, and were less inflammatory compared to plaques of Trem-1^+/+ chimeric mice. Genetic invalidation of Trem-1 led to alteration of monocyte recruitment into atherosclerotic lesions and inhibited toll-like receptor 4 (TLR 4)-initiated proinflammatory macrophage responses. We identified a critical role for Trem-1 in the upregulation of cluster of differentiation 36 (CD36), thereby promoting the formation of inflammatory foam cells. Genetic invalidation of Trem-1 in ApoE^–/–/Trem-1^–/– mice or pharmacological blockade of Trem-1 in ApoE^–/– mice using LR-12 peptide also significantly reduced the development of atherosclerosis throughout the vascular tree, and lessened plaque inflammation. TREM-1 was expressed in human atherosclerotic lesions, mainly in lipid-rich areas with significantly higher levels of expression in atheromatous than in fibrous plaques.

Conclusions

We identified TREM-1 as a major upstream proatherogenic receptor. We propose that TREM-1 activation orchestrates monocyte/macrophage proinflammatory responses and foam cell formation through coordinated and combined activation of CD36 and TLR4. Blockade of TREM-1 signaling may constitute an attractive novel and double-hit approach for the treatment of atherosclerosis.

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Improving Peer Mentorship: A Novel Fellow "House" Program

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Risk Factors for Surgical Site Infections Following Neurosurgical Spinal Fusion Operations: A Case Control Study.

Related Articles

Risk Factors for Surgical Site Infections Following Neurosurgical Spinal Fusion Operations: A Case Control Study.

Infect Control Hosp Epidemiol. 2016 Dec 19;:1-8

Authors: Walsh TL, Querry AM, McCool S, Galdys AL, Shutt KA, Saul MI, Muto CA

Abstract
OBJECTIVE To determine risk factors for the development of surgical site infections (SSIs) in neurosurgery patients undergoing spinal fusion. DESIGN Retrospective case-control study. SETTING Large, academic, quaternary care center. PATIENTS The study population included all neurosurgery patients who underwent spinal fusion between August 1, 2009, and August 31, 2013. Cases were defined as patients in the study cohort who developed an SSI. Controls were patients in the study cohort who did not develop an SSI. METHODS To achieve 80% power with an ability to detect an odds ratio (OR) of 2, we performed an unmatched case-control study with equal numbers of cases and controls. RESULTS During the study period, 5,473 spinal fusion procedures were performed by neurosurgeons in our hospital. With 161 SSIs recorded during the study period, the incidence of SSIs associated with these procedures was 2.94%. While anterior surgical approach was found to be a protective factor (OR, 0.20; 95% confidence interval [CI], 0.08-0.52), duration of procedure (OR, 1.58; 95% CI, 1.29-1.93), American Society of Anesthesiologists score of 3 or 4 (OR, 1.79; 95% CI, 1.00-3.18), and hospitalization within the prior 30 days (OR, 5.8; 95% CI, 1.37-24.57) were found in multivariate analysis to be independent predictors of SSI following spinal fusion. Prior methicillin-resistant Staphylococcus aureus (MRSA) nares colonization was highly associated with odds 20 times higher of SSI following spinal fusion (OR, 20.30; 95% CI, 4.64-8.78). CONCLUSIONS In additional to nonmodifiable risk factors, prior colonization with MRSA is a modifiable risk factor very strongly associated with development of SSI following spinal fusion. Infect Control Hosp Epidemiol 2016;1-8.

PMID: 27989249 [PubMed - as supplied by publisher]

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Outcomes of an inpatient refeeding protocol in youth with Anorexia Nervosa and atypical Anorexia Nervosa at Children’s Hospitals and Clinics of Minnesota

Abstract

Background

Historically, inpatient protocols have adopted relatively conservative approaches to refeeding in Anorexia Nervosa (AN) in order to reduce the risk of refeeding syndrome, a potentially fatal constellation of symptoms. However, increasing evidence suggests that patients with AN can tolerate higher caloric prescriptions during treatment, which may result in prevention of initial weight loss, shorter hospital stays, and less exposure to the effects of severe malnutrition. Therefore the present study sought to examine the effectiveness of a more accelerated refeeding protocol in an inpatient AN and atypical AN sample.

Methods

Participants were youth (ages 10–22) with AN (n = 113) and atypical AN (n = 16) who were hospitalized for medical stabilization. A retrospective chart review was conducted to assess changes in calories, weight status (percentage of median BMI, %mBMI), and indicators of refeeding syndrome, specifically hypophosphatemia, during hospitalization. Weight was assessed again approximately 4 weeks after discharge.

Results

No cases of refeeding syndrome were observed, though 47.3 % of participants evidenced hypophosphatemia during treatment. Phosphorous levels were monitored in all participants, and 77.5 % were prescribed supplemental phosphorous at the time of discharge. Higher rates of caloric changes were predictive of greater changes in %mBMI during hospitalization. Rates of caloric and weight change were not related to an increased likelihood of re-admission.

Conclusions

Results suggest that a more accelerated approach to inpatient refeeding in youth with AN and atypical AN can be safely implemented and is not associated with refeeding syndrome, provided there is close monitoring and correction of electrolytes. These findings suggest that this approach has the potential to decrease length of stay and burden associated with inpatient hospitalization, while supporting continued progress after hospitalization.

http://ift.tt/2h3peNG

Role of Simulation in Endovascular Aneurysm Repair (EVAR) Training: A Preliminary Study

Publication date: Available online 18 December 2016
Source:European Journal of Vascular and Endovascular Surgery
Author(s): A. Saratzis, T. Calderbank, D. Sidloff, M.J. Bown, R.S. Davies
BackgroundEndovascular aneurysm repair (EVAR) requires a high-level of technical-competency to avoid device-related complications. Virtual reality simulation-based training (SBT) may offer an alternative method of psychomotor skill acquisition; however, its role in EVAR training is undefined. This study aimed to: a) benchmark competency levels using EVAR SBT, and b) investigate the impact of supervised SBT on trainee performance.MethodsEVAR procedure-related metrics were benchmarked by six experienced consultants using a Simbionix Angiomentor EVAR simulator. Sixteen vascular surgical trainees performing a comparable EVAR before and after structured SBT (>4 teaching sessions) were assessed utilising a modified Likert-scale score. These were benchmarked for comparison against the standard set by the consultant body.ResultsMedian procedural-time for consultants was 43.5 min (IQR 7.5). A significant improvement in trainee procedural-time following SBT was observed (median procedural time 77 min [IQR 20.75] vs. 56 min [IQR: 7.00], p < .0001). The mean (SD) trainee Likert score pre- and post-SBT improved (16.6 [SD 1.455] vs. 28.63 [SD 2.986], p < .0001). Fewer endoleaks were observed (p = .0063) and trainees chose an appropriately sized device more often after SBT.ConclusionThis study suggests that EVAR-SBT should be considered as an adjunct to standard psychomotor skill teaching techniques for EVAR within the vascular surgery training curricula.



http://ift.tt/2hMwUmg

A Review of Open and Endovascular Treatment of Superior Vena Cava Syndrome of Benign Aetiology

Publication date: Available online 19 December 2016
Source:European Journal of Vascular and Endovascular Surgery
Author(s): G.S. Sfyroeras, C.N. Antonopoulos, G. Mantas, K.G. Moulakakis, J.D. Kakisis, E. Brountzos, C.R. Lattimer, G. Geroulakos
BackgroundThe widespread use of central venous catheters, ports, pacemakers, and defibrillators has increased the incidence of benign superior vena cava syndrome (SVCS). This study aimed at reviewing the results of open and endovascular treatment of SVCS.MethodMedical literature databases were searched for relevant studies. Studies with more than five adult patients, reporting separate results for the SVC were included. Nine studies reported the results of endovascular treatment of SVCS including 136 patients followed up for a mean of 11–48 months. Causes of SVCS were central venous catheters and pacemakers (80.6%), mediastinal fibrosis (13.7%), and other (5.6%). Percutaneous transluminal angioplasty (PTA) and stenting was performed in 73.6%, PTA only in 17.3%, and thrombolysis, PTA, and stenting in 9%. Four studies reported the results of open repair of SVCS including 87 patients followed up between 30 months and 10.9 years. The causes were mediastinal fibrosis (58.4%), catheters and pacemakers (28.5%), and other (13%). Operations performed included a spiral saphenous interposition graft, other vein graft, PTFE graft, and human allograft. Thirteen patients required re-operations (15%) before discharge mainly for graft thrombosis.ResultsIn the endovascular group technical success was 95.6%. Thirty day mortality was 0%. Regression of symptoms was reported in 97.3%. Thirty-two patients (26.9%) underwent 58 secondary procedures. In the open group the 30 day mortality was 0%. Symptom regression was reported in 93.5%. Twenty-four patients (28.4%) underwent a total of 33 secondary procedures.ConclusionsEndovascular is the first line treatment for SVCS caused by intravenous devices, whereas surgery is most often performed for mediastinal fibrosis. Both treatments show good results regarding regression of the symptoms and mid-term primary patency, with a significant incidence of secondary interventions.



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Recreating the Cardiac Microenvironment in Pluripotent Stem Cell Models of Human Physiology and Disease

Publication date: Available online 19 December 2016
Source:Trends in Cell Biology
Author(s): Ayhan Atmanli, Ibrahim John Domian
The advent of human pluripotent stem cell (hPSC) biology has opened unprecedented opportunities for the use of tissue engineering to generate human cardiac tissue for in vitro study. Engineering cardiac constructs that recapitulate human development and disease requires faithful recreation of the cardiac niche in vitro. Here we discuss recent progress in translating the in vivo cardiac microenvironment into PSC models of the human heart. We review three key physiologic features required to recreate the cardiac niche and facilitate normal cardiac differentiation and maturation: the biochemical, biophysical, and bioelectrical signaling cues. Finally, we discuss key barriers that must be overcome to fulfill the promise of stem cell biology in preclinical applications and ultimately in clinical practice.



http://ift.tt/2h2wgSQ

RGMs: Structural Insights, Molecular Regulation, and Downstream Signaling

Publication date: Available online 19 December 2016
Source:Trends in Cell Biology
Author(s): Christian Siebold, Toshihide Yamashita, Philippe P. Monnier, Bernhard K. Mueller, R. Jeroen Pasterkamp
Although originally discovered as neuronal growth cone-collapsing factors, repulsive guidance molecules (RGMs) are now known as key players in many fundamental processes, such as cell migration, differentiation, iron homeostasis, and apoptosis, during the development and homeostasis of many tissues and organs, including the nervous, skeletal, and immune systems. Furthermore, three RGMs (RGMa, RGMb/DRAGON, and RGMc/hemojuvelin) have been linked to the pathogenesis of various disorders ranging from multiple sclerosis (MS) to cancer and juvenile hemochromatosis (JHH). While the molecular details of these (patho)biological effects and signaling modes have long remained unknown, recent studies unveil several exciting and novel aspects of RGM processing, ligand–receptor interactions, and downstream signaling. In this review, we highlight recent advances in the mechanisms-of-action and function of RGM proteins.



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Risk factors that affect metabolic health status in obese children

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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Leg ulcers in sickle-cell disease: factors predictive of healing A multicenter, prospective, cohort study

Summary

Background

Leg ulcers (LUs) are a chronic and severe complication of sickle-cell disease (SCD). A prospective study identifying SCD patients' factors associated with LU complete healing and recurrence is lacking.

Objectives

To determine clinical and biological factors associated with SCD-LU complete healing and recurrence.

Methods

This prospective, observational cohort study conducted at two Adult SCD Referral Center sites (2009–2015), included 98 consecutive patients with ≥ 1 LU(s) lasting ≥ 2 weeks. The primary endpoints compared patients with healed vs. non-healed LUs at week 24 (W24) and patients with vs. without recurrence during follow-up.

Results

Median LU area, duration and follow-up were, respectively, 6·2 cm² [interquartile range 3–12·8], 9 [4–26] weeks and 65·8 [23·8–122·1] weeks. At W24, LUs were healed for 46·5% of patients, 49·3% of LUs recurred. Univariate analyses identified inclusion LU area < 8 cm² (81·6% vs. 34·8%; P < 0·0001), inclusion LU duration < 9 weeks (65% vs. 35%; P = 0·0013), high median hemoglobin F level (P = 0·008) and low lactate dehydrogenase level (P = 0·038) as being significantly associated with complete healing at W24. Multivariate analyses retained LU area < 8 cm² (OR 6·7 [95% CI 2·35–19· 31]; P = 0·0004) and < 9 weeks' duration (OR 3·19 [1·16–8·76]; P = 0·024) as being independently associated with healing at W24. Factors independently associated with recurrence could not be identified.

Conclusions

SCD-LU complete healing is independently associated with LU clinical characteristics rather than SCD clinical or biological characteristics.

This article is protected by copyright. All rights reserved.

http://ift.tt/2i04Grj

Morphology of rare exogenous materials in dermatopathology.

Abstract

Dermatopathologists are occasionally challenged by exogenous materials found in their biopsies. Recognition of most of the structures and morphological parts of foreign materials is not always easy because most of the literature thus far has focused on the study of the histological and histopathological aspects of human tissues, as well as on the granulomatous response elicited by such foreign bodies. However, there are some cases of rare exogenous material in biopsies, mainly published as case reports; and dermatopathologists often lose precious time searching for information about such cases. In the current report, we examine the morphology of the following elements: alimentary detritus, cacti barbs, cotton fibers, silica particles, nail polish, maggots, sea urchin spines, and honey bee stings.

http://ift.tt/2hMaggn