Παρασκευή, 23 Ιουνίου 2017

Liver Transplantation for Hepatocellular Carcinoma: “Experience of Memorial Sisli Hospital”



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Hepatocellular Cancer: Is Recurrence Inevitable?



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A case of atypical type A thymoma with vascular invasion and lung metastasis

Abstract

We present a case of type A thymoma with invasion of the left brachiocephalic vein and lung metastases. An 84-year-old man underwent extended thymectomy combined with left brachiocephalic vein reconstruction and resection of a lung metastasis. Histological examination showed vascular invasion by the tumor. The lung metastasis had high mitotic activity and slight nuclear enlargement, the so-called "atypical" features, but the main part of the primary tumor did not. However, the intravascular portion of the tumor had "atypical" histological features like the lung metastasis. It seems that "atypical" histological features are related to clinically malignant behavior.



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Les « herboristes »



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Notes de lecture



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Structural and morphological characterization of CdSe:Mn thin films

Abstract

CdSe:Mn thin films were grown by chemical bath deposition. The pH of the solution was maintained at 11. Dry films so obtained were annealed in vacuum ( \(10^{-1}\,\hbox {Torr}\) ) for about 2 h at \(400^{\circ }\hbox {C}\) . The annealed samples were subjected to morphological and structural characterization using scanning electron microscope and XRD. XRD was used for structural characterization whereas scanning electron microscope shows the surface morphology of the films. XRD spectra reveal that the grown CdSe films are polycrystalline in nature and have cubic structure. The average particle size decreases on doping CdSe with Mn ions. The FE-SEM images show spherical particles having uniform distribution. Optical characterization was done using PL studies and UV–Visible spectrophotometer. PL spectra show an increase in PL intensity on doping. Optical band gap also decreases on doping.



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Microscopic theory of substrate-induced gap effect on real AFM susceptibility in graphene

Abstract

We address here a tight-binding model study of frequency-dependent real part of antiferromagnetic susceptibility for the graphene systems. The Hamiltonian consists of electron hopping upto third nearest-neighbours, substrate and impurity effects in the presence of electron–electron interactions at A and B sublattices. To calculate susceptibility, we evaluate the two-particle electron Green's function by using Zubarev's Green's function technique. The frequency-dependent real part of antiferromagnetic susceptibility of the system is computed numerically by taking \(1000 \times 1000\) grid points of the electron momentum. The susceptibility displays a sharp peak at the neutron momentum transfer energy at low energies and another higher energy peak appearing at substrate-induced gap. The evolution of these two peaks is investigated by varying neutron wave vector, Coulomb correlation energy, substrate-induced gap, electron hopping integrals and A- and B-site electron doping concentrations.



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Dielectric constant of graphene-on-polarized substrate: A tight-binding model study

Abstract

We report here a microscopic tight-binding theoretical study of the dynamic dielectric response of graphene-on-polarizable substrate with impurity. The Hamiltonian consists of first, second and third nearest-neighbour electron hopping interactions besides doping and substrate-induced effects on graphene. We have introduced electron–electron correlation effect at A and B sublattices of graphene which is considered within Hartree–Fock mean-field approximation. The electron occupancies at both sublattices are calculated and solved self-consistently and numerically for both up- and down-spin orientations. The polarization function appearing in the dielectric function is a two-particle Green's function which is calculated by using Zubarev's Green's function technique. The temperature and optical frequency-dependent dielectric function is evaluated and compared with experimental data by varying Coulomb correlation energy, substrate-induced gap and impurity concentrations.



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Interventional Radiology in the Combat Environment

Abstract

Purpose of Review

The role of radiology in the combat environment has been redefined recently by the conflicts in the Middle East. The current situation of interventional radiology in the deployed setting is indeterminate. This paper seeks to advocate the use of interventional radiology as a deployable specialty.

Recent Findings

The role of interventional radiology in the deployed setting is not yet fully outlined. To our knowledge, this is the first review of the role of interventional radiology in the combat environment in the US Army.

Summary

The role of interventional radiology in the combat environment needs further exploration by the US military as it is often overlooked by military planners. In the future, interventional radiologists should be deployed in a manner that maximizes their skill sets.



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Ovarian Cancer Knowledge in Women and Providers Following Education with Inside Knowledge Campaign Materials

Abstract

Because no effective methods for preventing or screening for ovarian cancer exist, symptom recognition is integral to its early detection. The Centers for Disease Control and Prevention's Inside Knowledge: Get the Facts about Gynecologic Cancer campaign was developed to raise awareness and educate women and providers about risk factors, symptoms, recommended screening, and prevention strategies for the five main gynecologic cancers, including ovarian cancer. Inside Knowledge campaign materials were utilized by CDC's National Comprehensive Cancer Control Program grantees to educate women and providers about gynecologic cancer from 2014 to 2015. Grantees recruited participants and held educational sessions using Inside Knowledge materials. Questionnaires were given before and after the sessions to assess changes in awareness, confidence, and behavioral intentions around gynecologic cancer information and analyzed in 2016. This analysis focused on an assessment of changes related to ovarian cancer information. Participants' knowledge increased after educational sessions. Among women, there were increases in correctly identifying that the Papanicolaou (Pap) test does not screen for ovarian cancer (89.2%) and that genetic testing is available (77.9%). There was a lower increase in knowledge that HPV is not a cause of ovarian cancer (56.4%). Providers and women reported significant increases in their confidence in their ability to talk to each other about gynecologic cancer post-session. Ovarian cancer awareness, confidence, and related behaviors increased in participants exposed to Inside Knowledge materials. Using these materials to increase knowledge could lead to more empowered patients, better provider-patient communications, and improved care for gynecologic cancers, including ovarian cancer.



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National Survey Among Radiation Oncology Residents Related to Their Needs in Geriatric Oncology

Abstract

Currently, there is no formal curriculum addressing geriatric oncology within Canadian radiation oncology (RO) residency programs. Knowledge related to geriatric medicine may help radiation oncologists modify RT based on frailty status and geriatric considerations. Understanding specific learning needs allow program coordinators to align the current curriculum with residents' geriatric oncology learning needs. The purpose of this study is to determine the geriatric oncology educational needs of the Canadian RO residents and to inform Canadian RO residency training. A cross-sectional survey, with Likert, multiple choice, and open-ended questions, was pretested and distributed electronically by program directors to Canadian RO residents over 6 weeks. Responses were analyzed with descriptive statistics and common themes. One-hundred and thirty-five Canadian RO residents were contacted and 63 responded (47%). Half (49%) lacked confidence managing the elderly with multiple comorbidities, polypharmacy, functional and cognitive impairment, and challenging social circumstances;73% agreed additional training would be helpful. Forty-four percent lacked confidence regarding psychogeriatric referrals, fall prevention, palliative and hospice care, and community resources preventing re-hospitalization; 63% agreed additional training would be helpful. Seventy-six percent believed discussion groups, continuing education, geriatric oncology electives, and journal clubs would provide learning opportunities. Seventy-one percent agreed integrating geriatric assessment into RO curricula would improve care. Seventy-nine percent believed geriatric oncology principles have not been adequately integrated into radiation oncology curricula. There are significant gaps specific to geriatric assessment and management of older cancer patients in the current Canadian RO curricula. Most residents agreed that it is important to integrate geriatric oncology training to improve and personalize the care of older cancer patients.



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Characterization of Adipose-Derived Stem Cells Following Burn Injury

Abstract

Severe burns induce a prolonged inflammatory response in subcutaneous adipose tissue that modulates signaling in adipose-derived stem cells (ASCs), which hold potential for healing burn wounds or generating skin substitutes. Using a 60% rat scald burn model, we conducted a series of experiments to determine which cells isolated from the adipose tissue produced inflammatory mediators and how these changes affect ASC fate and function. The stromal vascular fraction (SVF), adipocytes, and ASCs were isolated from adipose tissue at varying times up to 4 weeks postburn and from non-injured controls. Endpoints included inflammatory marker expression, expression of ASC-specific cell-surface markers, DNA damage, differentiation potential, and proliferation. Inflammatory marker expression was induced in adipocytes and the SVF at 24 and 48 h postburn; expression of inflammatory marker mRNA transcripts and protein returned to normal in the SVF isolated 1 week postburn. In enriched ASCs, burns did not alter cell-surface expression of stem cell markers, markers of inflammation, differentiation potential, or proliferative ability. These results suggest that adipocytes and the SVF produce large quantities of inflammatory mediators, but that ASCs do not, after burns and that ASCs are unaffected by burn injury or culturing procedures.. They also suggest that cells isolated over 48 h after injury are best for cell culture or tissue engineering purposes.



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MicroRNA Changes in Preconditioning-Induced Neuroprotection

Abstract

Preconditioning is a paradigm in which sublethal stress–prior to a more injurious insult–induces protection against injury. In the central nervous system (CNS), preconditioning against ischemic stroke is induced by short durations of ischemia, brief seizures, exposure to anesthetics, and other stresses. Increasing evidence supports the contribution of microRNAs (miRNAs) to the pathogenesis of cerebral ischemia and ischemic tolerance induced by preconditioning. Studies investigating miRNA changes induced by preconditioning have to date identified 562 miRNAs that change expression levels after preconditioning, and 15% of these changes were reproduced in at least one additional study. Of miRNAs assessed as changed by preconditioning in more than one study, about 40% changed in the same direction in more than one study. Most of the studies to assess the role of specific miRNAs in the neuroprotective mechanism of preconditioning were performed in vitro, with fewer studies manipulating individual miRNAs in vivo. Thus, while many miRNAs change in response to preconditioning stimuli, the mechanisms underlying their effects are not well understood. The data does suggest that miRNAs may play significant roles in preconditioning-induced neuroprotection. This review focuses on the current state of knowledge of the possible role of miRNAs in preconditioning-induced cerebral protection.



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Feeding Jejunostomy-Associated Small Bowel Necrosis After Elective Esophago-Gastric Resection

Abstract

Background

Feeding jejunostomy has increasingly become a standard adjunctive procedure during major esophago-gastric resections. They provide nutritional support during the post-operative period as required. However, significant early complications have been reported, most notably small bowel necrosis. Literature reports have been restricted to case reports or series. This study aims to determine the frequency of this complication in a cohort of patients undergoing esophago-gastric resection, and identify any difference in the risk of this complication between patients undergoing esophagectomy and gastrectomy.

Methods

Consecutive patients who had esophago-gastric resections for malignancy and who had a feeding jejunostomy placed were identified from a prospectively maintained database at Leicester Royal Infirmary during the years 2009–2015. Case notes were reviewed to extract information relating to demographics, presenting features and clinical outcome.

Results

The study included 360 patients, 285 of which had esophagectomy and 75 had gastrectomy. There were no small bowel complications among esophagectomy patients (0%), while six patients who had total gastrectomy developed small bowel ischemia or necrosis (8%), p = 0.05, in spite of an identical feeding regimen. Every patient that developed the complication underwent surgery with five out six having resection of the infarcted segment and double-barrel stoma formation. A 6–8-week period of parenteral nutrition was required before stoma reversal. One patient had leucocytosis on the day of diagnosis. The other five patients showed no derangements in biochemical or clinical parameters in the preceding 48 h. Five of the six patients survived.

Conclusions

Small bowel necrosis and perforation is a life-threatening complication of feeding jejunostomy. In our cohort, it happened exclusively in total gastrectomy patients. Antecedent signs were lacking. The condition requires prompt attention with earlier use of CT scanning and a return to the operating room. The presence of pneumatosis intestinalis on CT scan should prompt surgical intervention that improves survival.



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Extent of Mediastinal Lymphadenectomy and Survival in Superficial Esophageal Squamous Cell Carcinoma

Abstract

Background

The aim of this study is to investigate the utility of total mediastinal lymphadenectomy (ML) in superficial esophageal squamous cell carcinoma (ESCC).

Methods

The medical records of 129 patients who underwent esophagectomy and lymph node dissection for pathologically confirmed pT1 ESCC between July 2006 and December 2014 were retrospectively reviewed. Limited ML, such as traditional 2-field or transhiatal esophagectomy, was performed in 42 patients (group 1), and total ML, including the bilateral recurrent laryngeal nerve nodes, was performed in 87 patients (group 2).

Results

R0 resection was achieved in all patients, and the number of dissected nodes was 28.0 ± 11.4 and 44.8 ± 16.1 in groups 1 and 2 (p < 0.001), respectively. The complication profile was similar in the two groups, but there were two operative mortalities in group 2. During a median follow-up of 32.4 months, loco-regional failure was found in 14.3% of group 1 and 3.5% of group 2 (p = 0.001). There was a significant difference in the 3-year overall survival (95.1% in group 2 vs. 83.3% in group 1, p = 0.043), and the 3-year disease-free survival rates (92.3% in group 2 vs. 73.7% in group 1, p = 0.001). On multivariate analysis, the extent of ML (HR, 5.200; 95% CI, 1.532 ~ 17.645; p = 0.008) and pT1b lesion classification (HR, 4.747; 95% CI, 1.024 ~ 21.997; p = 0.047) was a factor predictive of disease-free survival.

Conclusions

Total ML might be beneficial, especially in cases of pT1b ESCC, because it could lead to a lower incidence of recurrence and longer survival times.



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Latinas’ Colorectal Cancer Screening Knowledge, Barriers to Receipt, and Feasibility of Home-Based Fecal Immunochemical Testing

Abstract

Latinas' high colorectal cancer (CRC) mortality makes them a priority population for CRC screening. CRC screening knowledge, perceived barriers, and feasibility of using the Fecal Immunochemical Test (FIT) was assessed among Latinas in Utah. Participants aged ≥50 (n = 95) were surveyed about knowledge and barriers to CRC screening. 27 participants completed a FIT and evaluation survey. Fisher's exact tests assessed sociodemographic correlates of CRC screening outcomes. Most participants were overdue for CRC screening (n = 81, 85%). Age, acculturation, education, and employment were significantly associated with CRC screening status and/or reasons for being overdue (e.g., not knowing about the test, cost). All participants who received a FIT completed it, felt it was easy to use, and reported they would use it again. Latinas had limited awareness of CRC, CRC screenings, and experienced barriers to CRC screening (e.g., limited access, cost), but were willing to utilize a low-cost home-based FIT.



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Rhesus Cochlear and Vestibular Functions Are Preserved After Inner Ear Injection of Saline Volume Sufficient for Gene Therapy Delivery

Abstract

Sensorineural losses of hearing and vestibular sensation due to hair cell dysfunction are among the most common disabilities. Recent preclinical research demonstrates that treatment of the inner ear with a variety of compounds, including gene therapy agents, may elicit regeneration and/or repair of hair cells in animals exposed to ototoxic medications or other insults to the inner ear. Delivery of gene therapy may also offer a means for treatment of hereditary hearing loss. However, injection of a fluid volume sufficient to deliver an adequate dose of a pharmacologic agent could, in theory, cause inner ear trauma that compromises functional outcome. The primary goal of the present study was to assess that risk in rhesus monkeys, which closely approximates humans with regard to middle and inner ear anatomy. Secondary goals were to identify the best delivery route into the primate ear from among two common surgical approaches (i.e., via an oval window stapedotomy and via the round window) and to determine the relative volumes of rhesus, rodent, and human labyrinths for extrapolation of results to other species. We measured hearing and vestibular functions before and 2, 4, and 8 weeks after unilateral injection of phosphate-buffered saline vehicle (PBSV) into the perilymphatic space of normal rhesus monkeys at volumes sufficient to deliver an atoh1 gene therapy vector. To isolate effects of injection, PBSV without vector was used. Assays included behavioral observation, auditory brainstem responses, distortion product otoacoustic emissions, and scleral coil measurement of vestibulo-ocular reflexes during whole-body rotation in darkness. Three groups (N = 3 each) were studied. Group A received a 10 μL transmastoid/trans-stapes injection via a laser stapedotomy. Group B received a 10 μL transmastoid/trans-round window injection. Group C received a 30 μL transmastoid/trans-round window injection. We also measured inner ear fluid space volume via 3D reconstruction of computed tomography (CT) images of adult C57BL6 mouse, rat, rhesus macaque, and human temporal bones (N = 3 each). Injection was well tolerated by all animals, with eight of nine exhibiting no signs of disequilibrium and one animal exhibiting transient disequilibrium that resolved spontaneously by 24 h after surgery. Physiologic results at the final, 8-week post-injection measurement showed that injection was well tolerated. Compared to its pretreatment values, no treated ear's ABR threshold had worsened by more than 5 dB at any stimulus frequency; distortion product otoacoustic emissions remained detectable above the noise floor for every treated ear (mean, SD and maximum deviation from baseline: −1.3, 9.0, and −18 dB, respectively); and no animal exhibited a reduction of more than 3 % in vestibulo-ocular reflex gain during high-acceleration, whole-body, passive yaw rotations in darkness toward the treated side. All control ears and all operated ears with definite histologic evidence of injection through the intended site showed similar findings, with intact hair cells in all five inner ear sensory epithelia and intact auditory/vestibular neurons. The relative volumes of mouse, rat, rhesus, and human inner ears as measured by CT were (mean ± SD) 2.5 ± 0.1, 5.5 ± 0.4, 59.4 ± 4.7 and 191.1 ± 4.7 μL. These results indicate that injection of PBSV at volumes sufficient for gene therapy delivery can be accomplished without destruction of inner ear structures required for hearing and vestibular sensation.



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Identifying the D-Pentoses Using Water Adduction to Lithium Cationized Molecule

Abstract

A method has been developed that is capable of distinguishing an exhaustive list of underivatized D-pentoses with only a mass spectrometer. Electrospray ionization (ESI) of a solution containing a pentose and a lithium salt yields [Pentose + Li]+. These lithiated pentoses adduct water in a quadrupole ion trap. The reaction rate of water adduction is unique for several of the pentose isomers. Additionally, there are multiple potential gas-phase lithiation sites to form [Pentose + Li]+. A mixture of ions with at least one reactive (water adducting) and at least one unreactive (non-adducting) lithiation site is formed for each pentose. The water adduction reaction rate along with the unreactive fraction of lithiated pentose can be used to completely discriminate all D-pentoses.

Graphical Abstract



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Design of a TW-SLIM Module for Dual Polarity Confinement, Transport, and Reactions

Abstract

Here we describe instrumental approaches for performing dual polarity ion confinement, transport, ion mobility separations, and reactions in structures for lossless ion manipulations (SLIM). Previous means of ion confinement in SLIM, based upon rf-generated pseudopotentials and DC fields for lateral confinement, cannot trap ions of opposite polarity simultaneously. Here we explore alternative approaches to provide simultaneous lateral confinement of both ion polarities. Traveling wave ion mobility (IM) separations experienced in such SLIM cause ions of both polarities to migrate in the same directions and exhibit similar separations. The ion motion (and relative motion of the two polarities) under both surfing and IM separation conditions are discussed. In surfing conditions the two polarities are transported losslessly and non-reactively in their respective potential minima (higher absolute voltage regions confine negative polarities, and lower absolute potential regions are populated by positive polarities). In separation mode, where ions roll over an overtaking traveling wave, the two polarities can interact during the rollovers. Strategies to minimize overlap of the two ion populations to prevent reactive losses during separations are presented. A theoretical treatment of the time scales over which two populations (injected into a DC field-free region of the dual polarity SLIM device) interact is considered, and SLIM designs for allowing ion/ion interactions and other manipulations with dual polarities at 4 Torr are presented.

Graphical Abstract



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2016 ASMS Workshop Review: Next Generation LC/MS: Critical Insights and Future Perspectives



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Collisional Cross-Sections with T-Wave Ion Mobility Spectrometry without Experimental Calibration

Abstract

A method for relating traveling-wave ion mobility spectrometry (TWIMS) drift times with collisional cross-sections using computational simulations is presented. This method is developed using SIMION modeling of the TWIMS potential wave and equations that describe the velocity of ions in gases induced by electric fields. The accuracy of this method is assessed by comparing the collisional cross-sections of 70 different reference ions obtained using this method with those obtained from static drift tube ion mobility measurements. The cross-sections obtained here with low wave velocities are very similar to those obtained using static drift (average difference = 0.3%) for ions formed from both denaturing and buffered aqueous solutions. In contrast, the cross-sections obtained with high wave velocities are significantly greater, especially for ions formed from buffered aqueous solutions. These higher cross-sections at high wave velocities may result from high-order factors not accounted for in the model presented here or from the protein ions unfolding during TWIMS. Results from this study demonstrate that collisional cross-sections can be obtained from single TWIMS drift time measurements, but that low wave velocities and gentle instrument conditions should be used in order to minimize any uncertainties resulting from high-order effects not accounted for in the present model and from any protein unfolding that might occur. Thus, the method presented here eliminates the need to calibrate TWIMS drift times with collisional cross-sections measured using other ion mobility devices.

Graphical Abstract



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Peter John Derrick (1945–2017)



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Analyzing Glycopeptide Isomers by Combining Differential Mobility Spectrometry with Electron- and Collision-Based Tandem Mass Spectrometry

Abstract

Differential mobility spectrometry (DMS) has been employed to separate isomeric species in several studies. Under the right conditions, factors such as separation voltage, temperature, the presence of chemical modifiers, and residence time can combine to provide unique signal channels for isomeric species. In this study, we examined a set of glycopeptide isomers, MUC5AC-3 and MUC5AC-13, which bear an N-acetyl-galactosamine (GalNAc) group on either threonine-3 or threonine-13. When analyzed as a mixture, the resulting MS and MS/MS spectra yield fragmentation patterns that cannot discern these convolved species. However, when DMS is implemented during the analysis of this mixture, two features emerge in the DMS ionogram representing the two glycopeptide isomers. In addition, by locking in DMS parameters at each feature, we could observe several low intensity CID fragments that contain the GalNAc functionality-specific amino acid residues – identifying the DMS separation of each isomer without standards. Besides conventional CID MS/MS, we also implemented electron-capture dissociation (ECD) after DMS separation, and clearly resolved both isomers with this fragmentation method, as well. The electron energy used in these ECD experiments could be tuned to obtain maximum sequence coverage for these glycopeptides; this was critical as these ions were present as doubly protonated species, which are much more difficult to fragment efficiently via electron-transfer dissociation (ETD). Overall, the combination of DMS with electron- or collision-based MS/MS methods provided enhanced separation and sequence coverage for these glycopeptide isomers.

Graphical Abstract



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Dual-Polarity Ion Trap Mass Spectrometry: Dynamic Monitoring and Controlling Gas-phase Ion–Ion Reactions

Abstract

A dual-polarity linear ion trap (LIT) mass spectrometer was developed in this study, and the method for simultaneously controlling and detecting cations and anions was proposed and realized in the LIT. With the application of an additional dipolar DC field on the ejection electrodes of an LIT, dual-polarity mass spectra could be obtained, which include both the mass-to-charge (m/z) ratio and charge polarity information of an ion. Compared with conventional method, the ion ejection and detection efficiency could also be improved by about one-fold. Furthermore, ion–ion reactions within the LIT could be dynamically controlled and monitored by manipulating the distributions of ions with opposite charge polarities. This method was then used to control and study the reaction kinetics of ion–ion reactions, including electron transfer dissociation (ETD) and charge inversion reactions. A dual-polarity collision-induced dissociation (CID) experiment was proposed and performed to enhance the sequence coverage of a peptide ion. Ion trajectory simulations were also carried out for concept validation and system optimization.

Graphical Abstract



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Charge Transfer Dissociation (CTD) Mass Spectrometry of Peptide Cations: Study of Charge State Effects and Side-Chain Losses

Abstract

1+, 2+, and 3+ precursors of substance P and bradykinin were subjected to helium cation irradiation in a 3D ion trap mass spectrometer. Charge exchange with the helium cations produces a variety of fragment ions, the number and type of which are dependent on the charge state of the precursor ions. For 1+ peptide precursors, fragmentation is generally restricted to C−CO backbone bonds (a and x ions), whereas for 2+ and 3+ peptide precursors, all three backbone bonds (C−CO, C−N, and N−Cα) are cleaved. The type of backbone bond cleavage is indicative of possible dissociation channels involved in CTD process, including high-energy, kinetic-based, and ETD-like pathways. In addition to backbone cleavages, amino acid side-chain cleavages are observed in CTD, which are consistent with other high-energy and radical-mediated techniques. The unique dissociation pattern and supplementary information available from side-chain cleavages make CTD a potentially useful activation method for the structural study of gas-phase biomolecules.

Graphical Abstract



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Gas-phase Reactivity of meta -Benzyne Analogs Toward Small Oligonucleotides of Differing Lengths

Abstract

The gas-phase reactivity of two aromatic carbon-centered σ,σ-biradicals (meta-benzyne analogs) and a related monoradical towards small oligonucleotides of differing lengths was investigated in a Fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometer coupled with laser-induced acoustic desorption (LIAD). The mono- and biradicals were positively charged to allow for manipulation in the mass spectrometer. The oligonucleotides were evaporated into the gas phase as intact neutral molecules by using LIAD. One of the biradicals was found to be unreactive. The reactive biradical reacts with dinucleoside phosphates and trinucleoside diphosphates mainly by addition to a nucleobase moiety followed by cleavage of the glycosidic bond, leading to a nucleobase radical (e.g., base-H) abstraction. In some instances, after the initial cleavage, the unquenched radical site of the biradical abstracts a hydrogen atom from the neutral fragment, which results in a net nucleobase abstraction. In sharp contrast, the related monoradical mainly undergoes facile hydrogen atom abstraction from the sugar moiety. As the size of the oligonucleotides increases, the rate of hydrogen atom abstraction from the sugar moiety by the monoradical was found to increase due to the presence of more hydrogen atom donor sites, and it is the only reaction observed for tetranucleoside triphosphates. Hence, the monoradical only attacks sugar moieties in these substrates. The biradical also shows significant attack at the sugar moiety for tetranucleoside triphosphates. This drastic change in reactivity indicates that the size of the oligonucleotides plays a key role in the outcome of these reactions. This finding is attributed to more compact conformations in the gas phase for the tetranucleoside triphosphates than for the smaller oligonucleotides, which result from stronger stabilizing interactions between the nucleobases.

Graphical Abstract



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Bridging the spectral gap using image synthesis: a study on matching visible to passive infrared face images

Abstract

We propose an approach that bridges the gap between the visible and IR band of the electromagnetic spectrum, namely the mid-wave infrared or MWIR (3–5  \(\upmu \hbox {m}\) ) and the long-wave infrared or LWIR (8–14  \(\upmu \hbox {m}\) ) bands. Specifically, we investigate the benefits and limitations of using synthesized visible face images from thermal and vice versa, in cross-spectral face recognition systems when utilizing canonical correlation analysis and manifold learning dimensionality reduction. There are four primary contributions of this work. First, we assemble a database of frontal face images composed of paired VIS-MWIR and VIS-LWIR face images (using different methods for pre-processing and registration). Second, we formulate a image synthesis framework and post-synthesis restoration methodology, to improve face recognition accuracy. Third, we explore cohort-specific matching (per gender) instead of blind-based matching (when all images in the gallery are matched against all in the probe set). Finally, by conducting an extensive experimental study, we establish that the proposed scheme increases system performance in terms of rank-1 identification rate. Experimental results suggest that matching visible images against images acquired with passive infrared spectrum, and vice-versa, are feasible with promising results.



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A vision-based system to support tactical and physical analyses in futsal

Abstract

This paper presents a vision-based system to support tactical and physical analyses of futsal teams. Most part of the current analyses in this sport are manually performed, while the existing solutions based on automatic approaches are frequently composed of costly and complex tools, developed for other kind of team sports, making it difficult their adoption by futsal teams. Our system, on the other hand, represents a simple yet efficient dedicated solution, which is based on the analyses of image sequences captured by a single stationary camera used to obtain top-view images of the entire court. We use adaptive background subtraction and blob analysis to detect players, as well as particle filters to track them in every video frame. The system determines the distance traveled by each player, his/her mean and maximum speeds, as well as generates heat maps that describe players' occupancy during the match. To present the collected data, our system uses a specially developed mobile application. Experimental results with image sequences of an official match and a training match show that our system provides data with global mean tracking errors below 40 cm, demanding on 25 ms to process each frame and, thus, demonstrating its high application potential.



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Assessing Preference-Based Outcome Measures for Overactive Bladder: An Evaluation of Patient-Reported Outcome Data from the BESIDE Clinical Trial

Abstract

Objectives

The aim of this study was to compare outcomes using two preference-based measures of health status (EQ-5D-5L and OAB-5D) in patients with overactive bladder (OAB) treated with solifenacin plus mirabegron or solifenacin monotherapy in the BESIDE trial.

Methods

Patients with OAB who remained incontinent after 4 weeks' treatment with solifenacin 5 mg were randomized 1:1:1 to combination treatment (solifenacin 5 mg plus mirabegron [25 mg for the first 4 weeks/50 mg for the last 8 weeks]), solifenacin 5 mg, or solifenacin 10 mg. EQ-5D-5L and OAB-q were administered at baseline, weeks 4, 8, 12, and end of treatment (EoT). OAB-5D scores were derived from OAB-q results. Responder analysis was carried out using several definitions of minimally important difference.

Results

A total of 2054 patients received one or more doses of study treatment (combination, n = 694; solifenacin 5 mg, n = 684; solifenacin 10 mg, n = 676). EQ-5D-5L Index mean score changes (from baseline to EoT) were greater with combination (0.059) than with solifenacin 5 mg (0.040) and 10 mg (0.044) monotherapy, but the differences were not statistically significant. A significantly greater improvement was observed for combination on OAB-5D (0.107 vs 0.085 for 5 mg, and 0.087 for 10 mg; p ≤ 0.01). The dimensions most improved overall were anxiety/depression, pain/discomfort, and usual activities on EQ-5D-5L, and urge, urine loss, and coping on OAB-5D. The proportion of responders was significantly greater with combination compared with monotherapy using OAB-5D only.

Conclusions

Improvements were observed in all study arms on both the EQ-5D-5L and OAB-5D, although only the OAB-5D showed a statistically significant benefit for combination versus solifenacin monotherapy. Combining generic and condition-specific preference-based health status measures allowed for assessment of dimensions that were particularly relevant to this patient population, while permitting comparison with outcomes from other studies, treatments, and populations via EQ-5D.



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A double-quadratic model for predicting Vibrio species in water environments of Japan

Abstract

Vibrio spp. are natural inhabitants of marine and estuarine environments. Vibrio cholerae, Vibrio parahaemolyticus, and Vibrio vulnificus are the major infectious agents for humans. Their densities are affected by environmental factors such as water temperature and salinity. The detailed contribution of each factor still remains to be elucidated. Here we conducted multi-coastal study in a 21-month period to examine relationships between environmental factors and V. cholerae, V. parahaemolyticus and V. vulnificus densities in sea surface water in eight coastal sites of four prefectures in Japan. Vibrio densities were measured by a most-probable-number with PCR method which is highly sensitive and quantitative (3/100 ml of detection limit). Vibrio densities were analyzed with environmental factors including water temperature, salinity, total dissolved substance, and pH, and their quadratics. A linear regression model suited best for prediction of V. cholerae density. A novel double-quadratic model suited best for the prediction of V. parahaemolyticus and V. vulnificus densities.



http://ift.tt/2sKbxaU

Purification of the exopolysaccharide produced by Alteromonas infernus : identification of endotoxins and effective process to remove them

Abstract

Alteromonas infernus bacterium isolated from deep-sea hydrothermal vents can produce by fermentation a high molecular weight exopolysaccharide (EPS) called GY785. This EPS described as a new source of glycosaminoglycan-like molecule presents a great potential for pharmaceutical and biotechnological applications. However, this unusual EPS is secreted by a Gram-negative bacterium and can be therefore contaminated by endotoxins, in particular the lipopolysaccharides (LPS). Biochemical and chemical analyses of the LPS extracted from A. infernus membranes have shown the lack of the typical LPS architecture since 3-deoxy-d-manno-oct-2-ulopyranosonic acid (Kdo), glucosamine (GlcN), and phosphorylated monosaccharides were not present. Unlike for other Gram-negative bacteria, the results revealed that the outer membrane of A. infernus bacterium is most likely composed of peculiar glycolipids. Furthermore, the presence of these glycolipids was also detected in the EPS batches produced by fermentation. Different purification and chemical detoxification methods were evaluated to efficiently purify the EPS. Only the method based on a differential solubility of EPS and glycolipids in deoxycholate detergent showed the highest decrease in the endotoxin content. In contrast to the other tested methods, this new protocol can provide an effective method for obtaining endotoxin-free EPS without any important modification of its molecular weight, monosaccharide composition, and sulfate content.



http://ift.tt/2t39BwY

Post-diagnosis serum insulin-like growth factors in relation to dietary and lifestyle changes in the Prostate testing for cancer and Treatment (ProtecT) trial

Abstract

Purpose

The insulin-like growth factor (IGF) system is modifiable by diet and lifestyle, and has been linked to prostate cancer development and progression.

Methods

We conducted a prospective cohort study of 621 men diagnosed with localized prostate cancer to investigate the associations of dietary and lifestyle changes with post-diagnosis circulating levels of IGF-I and IGFBP-3. We used analysis of covariance to estimate the associations, controlling for baseline IGF-I or IGFBP-3, respectively.

Results

Mean IGF-I levels were 6.5% (95% CI −12.8, −0.3%, p = 0.04) lower in men who decreased their protein intake after diagnosis compared to men who did not change. Men who changed their fruit and vegetable intake had lower IGF-I levels compared to non-changers [Decreased intake: −10.1%, 95% CI −18.4, −1.8%, p = 0.02; Increased intake: −12.0%, 95% CI −18.4, −1.8%, p = 0.002]. IGFBP-3 was 14.6% (95% CI −24.5, −4.8%, p = 0.004) lower in men who achieved a healthy body mass index after diagnosis. Men who became inactive had 9.5% higher average IGF-I levels (95% CI 0.1, 18.9%, p = 0.05).

Conclusions

Decreased protein intake and body mass index, and increased physical activity and fruit and vegetable intake, following a prostate cancer diagnosis were associated with reduced post-diagnosis serum IGF-I and IGFBP-3. Counterintuitively, reduced fruit and vegetable intake was also associated with reduced IGF-I, but with weak statistical support, possibly implicating chance. If confirmed in other studies, our findings may inform potential lifestyle interventions in prostate cancer. ProtecT was registered at International Standard Randomised Controlled Trial Registry, http://isrctn.org as ISRCTN20141297.



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Human nucleus pulposus intervertebral disc cells becoming senescent using different treatments exhibit a similar transcriptional profile of catabolic and inflammatory genes

Abstract

Purpose

Chronic low back pain has been associated with intervertebral disc (IVD) degeneration, which is characterized by the accumulation of extracellular matrix (ECM)-degrading proteases and inflammatory molecules in the degenerate tissue. IVD degeneration could be the outcome of natural organismal ageing and/or of the exposure of the disc to cumulative stressful environmental stimuli and is accompanied by an increased population of senescent cells in the tissue. On the other hand, senescent cells are known to secrete proteolytic enzymes and inflammatory molecules, which can contribute to ECM catabolism. The aim of this study was to investigate the transcriptional profile of selected metalloproteinases (MMPs) and inflammatory mediators in human nucleus pulposus IVD cells that became senescent using three different approaches: serial subculturing, exposure to ionizing radiation and p16INK4a overexpression.

Methods

Gene expression was assessed using quantitative RT-PCR and protein levels were determined by western blot analysis. The proliferative potential of the cells, as well as the percentage of senescent cells in the population were estimated by nuclear BrdU incorporation and by senescence-associated β galactosidase staining, respectively.

Results

All senescent cells showed a similar regulation of MMP-1, -2, -3, -9, interleukin (IL) 6, IL8 and interferon γ at the level of transcription, with only some quantitative differentiations observed in p16INK4a-overexpressing cells.

Conclusions

Data described here suggest that senescent cells may have similar functions in IVD homeostasis, irrespective of the origin of senescence induction.



http://ift.tt/2tWUC3X

Delta neutrophil index (DNI) as a novel diagnostic and prognostic marker of infection: a systematic review and meta-analysis

Abstract

Objective

Delta neutrophil index (DNI) representing the number of immature granulocytes is an emerging marker used in diagnosis of infections and prediction of mortality in infected patients. The present study evaluated the diagnostic accuracy of DNI as a predictive and prognostic factor in infected patients.

Methods

We performed a PubMed search on January 1st, 2017 and identified studies that evaluated DNI as either a predictive or prognostic factor in infected patients. Studies with appropriate information to construct 2 × 2 contingency tables were extracted. We calculated pooled sensitivity and specificity. Meta-analysis of the multivariate logistic regression data set was performed to assess whether DNI functions as an independent factor.

Results

Overall, 12 articles fulfilled the inclusion criteria and a total of 499 cases and 9549 controls were examined. As a predictive factor of infection, DNI's pooled sensitivity was 0.67 (95% CI 0.62–0.71, I 2 = 86.0%) and pooled specificity was 0.94 (95% CI 0.94–0.95, I 2 = 92.8%). Area under the receiver operating characteristics (ROC) curve was 0.89. As a prognostic factor for death in infected patients, DNI's pooled sensitivity was 0.70 (95% CI 0.56–0.81, I 2 = 0.0%) and pooled specificity was 0.78 (95% CI 0.73–0.83, I 2 = 26.6%). Area under the ROC curve was 0.84. Meta-analysis of the multivariate logistic regression data set showed insignificant results.

Conclusions

DNI is a potentially useful diagnostic tool and predicts mortality among infected patients and should be more widely used in the clinical practice.



http://ift.tt/2sK0RsL

Using Comics to Promote Colorectal Cancer Screening in the Asian American and Pacific Islander Communities

Abstract

There are unaesthetic aspects in teaching people about the early detection of colorectal cancer using the fecal immunochemical test. Comics were seen as a way to overcome those unaesthetic aspects. This study used the Asian grocery store-based cancer education venue to pilot-test the clarity, cultural acceptability, and alignment of five colorectal cancer education comics intended for publication in Asian American and Pacific Islander (API) community newspapers. After developing the colorectal cancer education comics, API students asked shoppers to review a comic from their collection and provide feedback on how to make the comic clearer and more culturally pertinent to API readers. To evaluate viewers' responses, the students gathered such unobtrusive data as: (1) how many of the predetermined salient information points were discussed as the student educators interacted with shoppers and (2) how many comics the shoppers were willing to review. Shoppers were also asked to evaluate how effective the comics would be at motivating colorectal cancer screening among APIs. The students were able to cover all of the salient information points with the first comic. As evidence of the comics' capacity to engage shoppers' interest, shoppers willingly evaluated all five comics. Using multiple comics enabled the educators to repeatedly address the four salient colorectal cancer information points. Thus, the comics helped student educators to overcome the unesthetic elements of colorectal cancer discussions, while enabling them to engage shoppers in animated discussions, for far more time than with their conventional didactic educational methods.



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IFSO 2017 22 nd World Congress



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Stainless Steel Hollow Microspheres for Arterial Embolization Hyperthermia

Abstract

To find a novel microscaled mediator suitable for arterial embolization hyperthermia (AEH). Stainless steel microspheres including both hollow (H1) and solid ones (S1) were produced with dispersing molten steel stream by water jet. Theoretically analyzing the power absorption of them in alternating magnetic field revealed that larger size and smaller permeability led to more heat generation. Higher field intensity and frequency also improved the heating power. Given the same condition, heating power per unit mass was greater in hollow microsphere than solid one. Microscopic observations of H1 and S1 were conducted along with particle size distribution, magnetization curve and heating power measurement. In vivo heating test, in vitro hyperthermia test and in vitro biocompatibility test were conducted for the finally selected mediator H1. The measured heating power of H1 and S1 met the theoretical values in low intensity field, but was considerably below expectation in strong field. Power density of H1 was clearly greater than that of S1 as theoretically predicted. The temperature of a rabbit ear in magnetic field injected with H1 maintained 50 °C for 10 min. In vitro hyperthermia test showed its outstanding treatment effectiveness for cancer cells. Cytotoxicity of H1 was categorized as Grade I, which is regarded as no cytotoxicity. Stainless steel hollow microsphere H1 was a promising mediator for AEH for its high efficiency in heating tumor region and killing cancer cells as well as good biocompatibility.



http://ift.tt/2rKp29d

Suitability of GPUs for real-time control of large astronomical adaptive optics instruments

Abstract

Adaptive optics (AO) is a technique for correcting aberrations introduced when light propagates through a medium, for example, the light from stars propagating through the turbulent atmosphere. The components of an AO instrument are: (1) a camera to record the aberrations, (2) a corrective mechanism to correct them, (3) a real-time controller (RTC) that processes the camera images and steers the corrective mechanism on milliseconds timescales. We have accelerated the image processing for the AO RTC with the use of graphics processing units (GPUs). It is crucial that the image is processed before the atmospheric turbulence has changed, i.e., in one or two milliseconds. The main task is to transfer the images to the GPU memory with a minimum delay. The key result of this paper is a demonstration that this can be done fast enough using commercial frame grabbers and standard CUDA tools. Our benchmarking image consists of \(1.6 \times 10^6\) pixels out of which \(1.2 \times 10^6\) are used in processing. The images are characterized and reduced into a set of 9248 numbers; about one-third of the total processing time is spent on this characterization. This set of numbers is then used to calculate the commands for the corrective system, which takes about two-third of the total time. The processing rate achieved on a single GPU is about 700 frames per second (fps). This increases to 1100 fps (1565 fps) if we use two (four) GPUs. The variation in processing time (jitter) has a root-mean-square value of 20–30 \(\upmu \) s and about one outlier in a million cycles.



http://ift.tt/2rJXJvz

Microbial transformations of selenite by methane-oxidizing bacteria

Abstract

Methane-oxidizing bacteria are well known for their role in the global methane cycle and their potential for microbial transformation of wide range of hydrocarbon and chlorinated hydrocarbon pollution. Recently, it has also emerged that methane-oxidizing bacteria interact with inorganic pollutants in the environment. Here, we report what we believe to be the first study of the interaction of pure strains of methane-oxidizing bacteria with selenite. Results indicate that the commonly used laboratory model strains of methane-oxidizing bacteria, Methylococcus capsulatus (Bath) and Methylosinus trichosporium OB3b, are both able to reduce the toxic selenite (SeO32−) but not selenate (SeO42−) to red spherical nanoparticulate elemental selenium (Se0), which was characterized via energy-dispersive X-ray spectroscopy (EDXS), X-ray absorption near-edge structure (XANES) and extended X-ray absorption fine structure (EXAFS). The cultures also produced volatile selenium-containing species, which suggests that both strains may have an additional activity that can transform either Se0 or selenite into volatile methylated forms of selenium. Transmission electron microscopy (TEM) measurements and experiments with the cell fractions cytoplasm, cell wall and cell membrane show that the nanoparticles are formed mainly on the cell wall. Collectively, these results are promising for the use of methane-oxidizing bacteria for bioremediation or suggest possible uses in the production of selenium nanoparticles for biotechnology.



http://ift.tt/2tWnn0U

The Changing Landscape of Alopecia Areata: The Translational Landscape

Abstract

Recent genetic and preclinical studies have increased our understanding of the immunopathogenesis of alopecia areata (AA). This has allowed expedited development of targeted therapies for the treatment of AA, and a paradigm shift in our approach and understanding of autoimmunity and the hair follicle. The synergy between preclinical studies, animal models, and translational studies has led to unprecedented advances in the treatment options for AA, ultimately benefiting patients who have had little recourse. In this review, we summarize the scientific field of contemporary AA research, and look forward to potential new technologies and developments.



http://ift.tt/2t2AsJG

The Changing Landscape of Alopecia Areata: The Therapeutic Paradigm

Abstract

Alopecia areata (AA), a prevalent inflammatory cause of hair loss, lacks FDA-approved therapeutics for extensive cases, which are associated with very poor rates of spontaneous hair regrowth and major psychological distress. Current treatments for severe cases include broad immune-suppressants, which are associated with significant adverse effects, precluding long-term use, with rapid hair loss following treatment termination. As a result of the extent of the disease in severe cases, topical contact sensitizers and intralesional treatments are of limited use. The pathogenesis of AA is not yet fully understood, but recent investigations of the immune activation in AA skin reveal Th1/IFN-γ, as well as Th2, PDE4, IL-23, and IL-9 upregulations. Tissue analyses of both animal models and human lesions following broad-acting and cytokine-specific therapeutics (such as JAK inhibitors and ustekinumab, respectively) provide another opportunity for important insights into the pathogenesis of AA. As reviewed in this paper, numerous novel therapeutics are undergoing clinical trials for AA, emphasizing the potential transformation of the clinical practice of AA, which is currently lacking. Dermatologists are already familiar with the revolution in disease management of psoriasis, stemming from better understanding of immune dysregulations, and atopic dermatitis will soon follow a similar path. In light of these recent developments, the therapeutic arena of AA treatments is finally getting more exciting. AA will join the lengthening list of dermatologic diseases with mechanism-targeted drugs, thus changing the face of AA.



http://ift.tt/2tBU3NH

The Changing Landscape of Alopecia Areata: An Introduction

Abstract

Alopecia areata is an extremely common autoimmune condition affecting hair. Severe forms of alopecia areata exist, with existing treatments consisting of systemic immunosuppressants with numerous side effects. Recently, breakthroughs have been made in both understanding the pathogenesis of alopecia areata and the treatment thereof, which hold the promise of being able to target severe cases of alopecia areata with more efficacy and better tolerability. This article serves as an introduction to review papers from two of the leading researchers in the field of alopecia areata.



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JC virus granule cell neuronopathy onset two months after chemotherapy for low-grade lymphoma

Abstract

Background

Granule cell neuronopathy (GCN) is a rare disease caused by the JC virus, leading to degeneration of cerebellar granule cell neurons. Primarily described in patients with AIDS, it has also been diagnosed in patients with lymphoproliferative diseases and after long-term treatment with immune-suppressing medications such as natalizumab.

Case presentation

A 69 year old woman presented with progressive ataxia which began 2 months after initiation of treatment for follicular low-grade B cell lymphoma with rituximab/bendamustine, and progressed for 2 years prior to admission. Extensive prior evaluation included MRI that showed atrophy of the cerebellum but normal CSF analysis and serum studies. Neurologic exam on admission was notable for severe appendicular ataxia and fatigable end-gaze direction-changing horizontal nystagmus. FDG-PET/CT scan was unremarkable and repeat lumbar puncture revealed 2 WBCs/mm3, 148 RBCs/mm3, glucose 70 mg/dL, protein 37.7 mg/dL and negative flow cytometry/cytopathology. Standard CSF JC virus PCR testing was negative, but ultrasensitive TaqMan real-time JC virus PCR testing was positive, consistent with JC virus-related GCN.

Conclusions

Because of the diagnostic challenges in identifying GCN, a high threshold of suspicion should be maintained in patients with an immune-suppressing condition such as lymphoma or on immune-suppressing agents such as rituximab, even shortly after initiation of therapy.



http://ift.tt/2sZ43Tj

Cerebello-pontine angle eosinophilic granuloma; a reappraisal in the management of intracranial eosinophilic granuloma



http://ift.tt/2rYMof7

Eftrenonacog Alfa: A Review in Haemophilia B

Abstract

Eftrenonacog alfa (Alprolix™) is a recombinant fusion protein comprising human factor IX (FIX) covalently linked to the constant region (Fc) domain of human IgG1 (i.e. rFIXFc). The presence of the Fc domain extends the terminal half-life (t½) of rFIXFc, permitting prolonged treatment intervals. rFIXFc is available for intravenous use for the prophylaxis and treatment of bleeding in patients with haemophilia B. In two multinational, phase III studies in previously treated children, adolescents and adults with severe haemophilia B, rFIXFc prophylaxis resulted in low median annualized bleeding rates (ABRs), and was associated with reductions in median weekly factor consumption and dosing frequency compared with pre-study FIX regimens. Preliminary data from an extension of both studies indicated sustained efficacy, as demonstrated by low median ABRs, with longer-term rFIXFc prophylaxis. rFIXFc was also effective in the treatment of bleeding episodes and when used in the perioperative setting in all age groups. rFIXFc was well tolerated in clinical studies in previously treated patients, with the majority of treatment-emergent adverse events considered to be unrelated to rFIXFc; there were no reports of inhibitor development. In conclusion, rFIXFc provides an effective alternative to plasma-derived and recombinant FIX products for the management of patients with haemophilia B, with its extended t½ permitting a less frequent administration schedule and potentially providing a prolonged protective haemostatic effect, which eases the treatment burden on the patient.



http://ift.tt/2sJy3kb

Erratum to: Recent advances in capsule-based dry powder inhaler technology



http://ift.tt/2sJDaAN

The Oswestry Disability Index, confirmatory factor analysis in a sample of 35,263 verifies a one-factor structure but practicality issues remain

Abstract

Purpose

To analyze the factor structure of the Oswestry Disability Index (ODI) in a large symptomatic low back pain (LBP) population using exploratory (EFA) and confirmatory factor analysis (CFA).

Methods

Analysis of pooled baseline ODI LBP patient data from the international Spine Tango registry of EUROSPINE, the Spine Society of Europe. The sample, with n = 35,263 (55.2% female; age 15–99, median 59 years), included 76.1% of patients with a degenerative disease, and 23.9% of the patients with various other spinal conditions. The initial EFA provided a hypothetical construct for consideration. Subsequent CFA was considered in three scenarios: the full sample and separate genders. Models were compared empirically for best fit.

Results

The EFA indicated a one-factor solution accounting for 54% of the total variance. The CFA analysis based on the full sample confirmed this one-factor structure. Sub-group analyses by gender achieved good model fit for configural and partial metric invariance, but not scalar invariance. A possible two-construct model solution as outlined by previous researchers: dynamic-activities (personal care, lifting, walking, sex and social) and static-activities (pain, sleep, standing, travelling and sitting) was not preferred.

Conclusions

The ODI demonstrated a one-factor structure in a large LBP sample. A potential two-factor model was considered, but not found appropriate for constructs of dynamic and static activity. The use of the single summary score for the ODI is psychometrically supported. However, practicality limitations were reported for use in the clinical and research settings. Researchers are encouraged to consider a shift towards newer, more sensitive and robustly developed instruments.



http://ift.tt/2t34Tih

Answer to the Letter to the Editor of A. Piazzolla et al. concerning, “The Surgical Algorithm for the AOSpine, Thoracolumbar Spine Injury Classification System” by A. R. Vaccaro et al.; Eur Spine J (2016); 25(4):1087–1094



http://ift.tt/2rK3Pfp

SOP – Subkutane Medikamentengabe und Infusionen in der erwachsenen Palliativmedizin



http://ift.tt/2sy5ibn

15. Internationale St.-Gallen-Konsensus-Konferenz: Behandlung des frühen Mammakarzinoms

Zusammenfassung

Hintergrund

Seit über 30 Jahren findet regelmäßig die internationale St.-Gallen-Konferenz zur Behandlung des primären Mammakarzinoms statt. Bei diesem Konsens handelt es sich um ein Meinungsbild von Experten unterschiedlicher Länder und Fachdisziplinen.

Rationale

Vor diesem Hintergrund wurden die Abstimmungsergebnisse des internationalen St.-Gallen-Konsensus-Panels von einer deutschen Arbeitsgruppe führender Brustkrebsexperten für den Klinikalltag in Deutschland diskutiert. Fünf der Brustkrebsexperten aus Deutschland sind zugleich Mitglieder des diesjährigen St.-Gallen-Panels.

Grundlage

Grundlage der Diskussion für den deutschen Klinikalltag sind die jährlich aktualisierten Therapieempfehlungen der Arbeitsgemeinschaft Gynäkologische Onkologie (AGO-Mamma 2017) sowie die deutsche S3-Leitlinie, die im Jahre 2017 ebenfalls aktualisiert wird. S3-Leitlinie und AGO-Empfehlungen sind jeweils evidenzbasiert.

Ergebnis

Die diesjährige 15. St.-Gallen-Konsensus-Konferenz stand unter dem Motto „Escalating and De-Escalating", das sich durch alle Therapiebereiche zog, die zur Abstimmung standen. Ziel war und ist es, Patientinnen individuellere Therapieoptionen anzubieten und das Risiko einer Über- bzw. Untertherapie zu vermindern.



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Surgery for pancreatic ductal adenocarcinoma

Abstract

Surgical resection is the only potentially curative option in the treatment of pancreatic ductal adenocarcinoma. Preoperative radiological imaging allows to rule out the presence of metastases. Three resectability categories are established based on the radiological findings depending on the degree of contact between the tumor and the blood vessels. Histological confirmation of malignancy is only required in cases of borderline or non-resectable tumors, prior to neoadjuvant treatment initiation. Diagnostic laparoscopy is recommended in the presence of large tumors of the body or tail and in borderline tumors to explore the possibility of resection and to apply treatment with curative intent, as well as in those cases with high level of biomarkers to rule out peritoneal involvement. Prior to surgery preoperative nutritional measures as well as endoscopic biliary drainage can be applied to optimize patient's conditions. Cephalic pancreaticoduodenectomy is the recommended surgical technique in tumors located in the head of the pancreas. The benefits from pyloric preservation, type or reconstruction (one vs. two loops), type of anastomosis (pancreaticojejunostomy vs. pancreaticogastrostomy), intraoperative biopsy of the pancreatic resection margin or the use of intraperitoneal drainages are inconclusive. Total pancreatectomy and/or portal resection should only be performed in particular cases; however, arterial resections have shown no benefits. Radical antegrade modular pancreaticosplenectomy, that can be performed laparoscopically, is the technique used for those tumors located in the pancreatic body-tail.



http://ift.tt/2tBX8xd

Sinonasal malignancies: incidence and histological distribution in Jamaica, 1973–2007

Abstract

Purpose

To determine the histological distribution and trends in incidence of sinonasal malignancies in Jamaica.

Methods

Cases of all sinonasal malignancies diagnosed between 1973 and 2007 were extracted from the archives of the Jamaica Cancer Registry. Data recorded for each case included age at diagnosis, sex, year of diagnosis, topography, and histology. Data were used to calculate frequencies, age-specific incidence rates, and age-standardized incidence rates (ASRs). Linear regression analysis was used to determine significance of trends in incidence rates; p values of ≤0.05 were significant.

Results

Sinonasal malignancies were commoner in males (male: female ratio, 1.1:1), and the median ages were 62 (males) and 66 years (females). Most were located in either the maxillary sinus (61.3%) or nasal cavity (24.3%). The commonest histological types were squamous cell carcinoma (SCC) (55.9%) and non-Hodgkin's lymphoma (17.1%), which were predominantly of T-cell immunophenotype, in both the nasal cavity and sinuses. There was no documentation in registry data regarding separation into NK/T and peripheral T-subtypes. The ASRs in males and females were consistently less than 1.5 per 100,000 per year. In males, there was a significant decrease in SCC ASR (p = 0.014) over time.

Conclusions

The age, gender, and anatomical and histological distribution patterns of sinonasal malignancies in Jamaica are similar to those reported internationally, and the low ASRs are in keeping with previous global reports. Broader local immunohistochemistry panels are warranted for further delineation of sinonasal T-cell lymphomas. Investigation into factors contributing to the decreasing incidence of sinonasal SCC is also required.



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A case report of thoracolumbar paraspinal myopathy as the cause of camptocormia in a patient with atypical parkinsonism

Abstract

Background

Camptocormia is severe flexion of the thoracolumbar spine, exaggerated during standing and walking but minimized in supine position. Even though camptocormia is a relatively common condition during the course of Parkinson's disease, there is ongoing controversy concerning its mechanisms. The most widely accepted and yet still disputed one is dystonia. However, based on myopathic changes observed in the paraspinal muscle biopsies of some PD patients with camptocormia, the attempt to attribute camptocormia to myopathy has continued. This case presents evidence for paraspinal myopathy as the cause of camptocormia in a patient with atypical parkinsonism.

Case presentation

A patient presented with a relatively acute onset of camptocormia and new-onset back pain. Upon examination, she had asymmetric parkinsonism. Magnetic resonance imaging of the lumbar spine revealed alterations in muscle signal intensity in the right paraspinal muscles at the L1–2 level. In the presence of persistent back pain, repeat imaging done two months later showed diffuse enlargement and patchy enhancement of the paraspinal muscles on T1-weighted imaging from T4 through sacrum bilaterally. About fifteen months after the onset of camptocormia, she underwent ultrasound-guided gun biopsy of the paraspinal muscles for evaluation of focal atrophy of the back muscles on the right. The biopsy revealed unmistakable myopathic changes, marked endomysial and perimysial fibrosis of the muscles, and merely mild infiltration of inflammatory cells but no clues regarding the cause of myopathy. On account of persistent back pain and MRI results indicative of ongoing inflammation, she was prescribed glucocorticoid, which she refused to take. Now merely two and a half years after the onset of camptocormia, she is in Hoehn and Yahr stage 4.

Conclusions

The coincidence of back pain with the appearance of camptocormia and the imaging and pathology findings supportive of myopathy give strong evidence for paraspinal myopathy as the cause of the deformity in this patient. When a patient presents with a relatively acute onset of camptocormia accompanied by back pain, the clinician should not overlook the possibility of myopathy of paraspinal muscles, which may be one of the few treatable causes of camptocormia.



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Akuter Mesenterialarterienverschluss

Zusammenfassung

Hintergrund

Die Mortalität der akuten mesenterialen Ischämie ist nach wie vor sehr hoch. Auch bei einem standardisierten viszeral- und gefäßchirurgischen Vorgehen sinkt sie nicht unter 40 %. Deshalb ist eine weitere Optimierung des diagnostischen und therapeutischen Behandlungspfades erforderlich.

Fragestellung

Kann die endovaskuläre Therapie die Prognose der akuten mesenterialen Ischämie verbessern?

Material und Methode

Anhand eigener Ergebnisse und aktueller Literaturrecherchen wurde eine Analyse der offen chirurgischen und endovaskulären Therapie der akuten mesenterialen Ischämie vorgenommen.

Ergebnisse

Endovaskuläre Behandlungen sind bei akuter mesenterialer Ischämie nur bei arteriellen Verschlussprozessen ohne große Thrombuslast und ohne Peritonitis indiziert. Bei guten vaskulären Soforterfolgen sind die Früh- und Spätergebnisse stentgestützter Eingriffe noch nicht zufriedenstellend. Die standardisierte offene Rekonstruktion der Mesenterialarterien ist dagegen in den meisten Fällen mit einer geringeren Zeitverzögerung und stabilen Langzeiterfolgen verbunden.

Schlussfolgerungen

Die offene Chirurgie der Mesenterialarterien bleibt trotz der höheren Invasivität im akuten Ischämiestadium mit massiver Gefäßthrombose und Peritonitis das Verfahren der 1. Wahl. Endovaskuläre Behandlungsversuche haben trotz einzelner Erfolge die Prognose dieser Klientel nicht verbessern können. Prospektiv-randomisierte Studien sind dringend erforderlich, um geeignete Indikationsfelder der beiden Therapien abzustecken.



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The Antihypertensive Efficacy of the Triple Fixed Combination of Perindopril, Indapamide, and Amlodipine: The Results of the PETRA Study

Abstract

Introduction

The etiology of essential hypertension is multifactorial. Therefore, treatment with combinations of antihypertensive agents acting on multiple targets is necessary for successful therapy in the majority of patients. According to the experience and clinical data accumulated so far, combination therapy with three agents from different pharmacological classes is required in approx. 30% of patients in order to achieve long-term blood pressure control. The primary objective of the PETRA study was to evaluate the efficacy of blood pressure (BP) control with once daily administration of the different dosage strengths of the once-daily, triple fixed combination of perindopril, indapamide, and amlodipine. The evaluation was based on office BP readings and ambulatory blood pressure monitoring (ABPM) data gathered in routine clinical practice.

Methods

Data from 11,209 hypertensive patients (the proportion of female subjects was 47.6%) were processed and interpreted in a 3-month-long prospective, observational, non-interventional, open-label study conducted in 997 centers in Hungary.

Results

Mean baseline office BP was 156.58 ± 16.10/91.56 ± 9.33 mmHg (mean ± SD), whereas the mean duration of hypertension was 9.48 ± 7.19 years. Mean office BP decreased by 24.81 ± 15.47/11.41 ± 9.90 mmHg after switching to the triple fixed combination of perindopril, indapamide, and amlodipine (p < 0.0001). At the final visit 45.1% of patients took the 5/1.25/5 mg, 33.5% of them 10/2.5/5 mg, and 21.4% of them 10/2.5/10 mg strength of the perindopril/indapamide/amlodipine triple fixed combination. The 24-h blood pressure was obtained in 76 subjects. The mean 24-h BP decreased from 155.51 ± 17.43/85.28 ± 11.48 to 134.63 ± 12.51/77.83 ± 8.99 mmHg (p < 0.0001). Statistically significant (p < 0.0001) and clinically relevant improvement of a number of metabolic parameters—including total cholesterol (−8.6%), LDL-cholesterol (−11.4%), triglyceride (−12.1%), and fasting blood glucose (−6.6%) levels—was observed over the 3-month study period.

Conclusions

During the 3 months of the PETRA study, the outstanding 24-h antihypertensive efficacy of the triple fixed combination of perindopril, indapamide, and amlodipine was confirmed both by office BP readings and by ABPM recordings. This combination may offer a new therapeutic option for hypertensive patients who have failed to achieve the desired BP target on their previous dual combination therapy.

Funding

EGIS Pharmaceuticals PLC.



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Rifaximin Re-treatment in Patients with Irritable Bowel Syndrome: Feels Like the First Time?



http://ift.tt/2rJ8SN7

A case of malignant peritoneal mesothelioma suggesting the utility of combining double-contrast radiography and endoscopy with computed tomography for diagnosis

Abstract

A 68-year-old woman presented with abdominal pain, weight loss, and vomiting. Enhanced computed tomography (CT) showed slightly increased density in the mesentery and edema of the third portion of the duodenum and proximal jejunum. Little ascites, but no primary lesion, lymph node metastases, or distant metastases, were observed. Endoscopic findings included erythema and edema in the distal duodenum and proximal jejunum without epithelial lesions. Double-contrast radiography revealed transverse ridging with convergence, suggesting a serosal lesion. We suspected disease involving the serosa, such as mesenteric panniculitis. However, the lesion was definitively diagnosed as malignant peritoneal mesothelioma based on a biopsy specimen obtained at laparotomy. The combination of transverse ridging with convergence on double-contrast radiography and mucosal edema without epithelial lesions on endoscopy was consistent with a disorder involving the serosa. Transverse ridging with convergence is helpful to diagnose serosal pathology such as malignant peritoneal mesothelioma. Combining the findings of double-contrast radiography and endoscopy with computed tomography may facilitate diagnosis of malignant peritoneal mesothelioma. Thus, in case of increased density of mesentery and wall thickness on CT image with transverse ridging with convergence on double-contrast radiography and without epithelial lesion on endoscopy, malignant peritoneal mesothelioma must be considered.



http://ift.tt/2rYomRy

Effects of Carvacrol on Survival, Mesenteric Blood Flow, Aortic Function and Multiple Organ Injury in a Murine Model of Polymicrobial Sepsis

Abstract

Carvacrol (CRV) has strong cytoprotective, antioxidant, and anti-inflammatory properties. We aimed to demonstrate the possible protective effects of CRV on survival, mesenteric artery blood flow (MBF), vascular reactivity, and oxidative and inflammatory injuries in a murine model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). Wistar rats were allocated into the following four groups: Sham, CLP, Sham + CRV, and CLP + CRV. The animals were orally administered with CRV (80 mg/kg/day) or vehicle (corn oil; 1 mL/kg/day) for 7 days. At the eighth day, Sham or CLP procedure was applied. Twenty hours after the operations, MBF and contractile responses of isolated aortic preparations to phenylephrine were measured. Tissue samples were obtained for biochemical and histopathological assessments. Additionally, survival rates were recorded throughout 96 h. CRV administration improved the mesenteric perfusion, contractile function of aorta, and survival after CLP. CRV substantially prevented the elevations in the levels of LDH, BUN, Cr, and inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 beta and interleukin-6) but could not prevent the elevations of AST and ALT after CLP. The decreased liver, kidney, and spleen glutathione levels and increased liver, kidney, lung, and spleen malondialdehyde levels induced by CLP were substantially restored by CRV. Also, histopathological protective effects of CRV on multiple organ damage due to CLP were observed. CRV possesses strong ameliorative effects on sepsis due to its protective effects on mesenteric perfusion and aortic function and its antioxidative and anti-inflammatory effects.



http://ift.tt/2rJwW2t

Tanshinone IIA Attenuates Atherosclerosis in Apolipoprotein E Knockout Mice Infected with Porphyromonas gingivalis

Abstract

Tanshinone IIA (TSA), a pharmacologically active component isolated from Danshen, may prevent cardiovascular diseases due to its anti-inflammatory, anti-oxidative, and anti-adipogenic effects. Porphyromonas gingivalis, a major periodontal pathogen, may contribute to the progression of atherosclerosis. Here, we studied the effects of TSA on atherosclerosis in ApoE−/− mice with P. gingivalis infection. Eight-week-old ApoE−/− mice were randomized to (a) phosphate-buffered saline (PBS), (b) P. gingivalis, and (c) P. gingivalis + TSA (60 mg kg−1 day−1). The mice were injected with (a) PBS, or (b) and (c) P. gingivalis 3 times per week for a total of 10 times. After 8 weeks, atherosclerotic risk factors in serum and in heart, aorta, and liver tissues were analyzed in all mice using Oil Red O, atherosclerosis cytokine antibody arrays, enzyme-linked immunosorbent assay (ELISA), real-time PCR, and microRNA array. CD40, G-CSF, IFN-γ, interleukin (IL)-1β, IL-6, MCP-1, MIP-3α, tumor necrosis factor-α (TNF-α), and VEGF were attenuated by TSA in atherosclerosis cytokine antibody arrays. TSA-treated mice showed a significant reduction of C-reactive protein (CRP), ox-LDL, IL-1β, IL-6, IL-12, and TNF-α in ELISA data. Real-time PCR analyses showed that TSA decreased the expression of CCL-2, CD40, IL-1β, IL-6, TNF-α, and MMP-2 in heart and aorta tissues. Moreover, hepatic CRP was downregulated by TSA, although FASN and HMG-CoA were not. The relative expressions of miR-146b and miR-155 were elevated by P. gingivalis infection and were downregulated by TSA treatment. These results suggest that TSA was a potential therapeutic agent that may have the ability to prevent P. gingivalis-induced atherosclerosis associated with anti-inflammatory and anti-oxidative effects.



http://ift.tt/2t2w2C8

The Role of Health Plans in Supporting Behavioral Health Integration

Abstract

Health plan policies can influence delivery of integrated behavioral health and general medical care. This study provides national estimates for the prevalence of practices used by health plans that may support behavioral health integration. Results indicate that health plans employ financing and other policies likely to support integration. They also directly provide services that facilitate integration. Behavioral health contracting arrangements are associated with use of these policies. Delivery of integrated care requires systemic changes by both providers and payers thus health plans are key players in achieving this goal.



http://ift.tt/2t1zSM3

Martin Heinrich Rathke (1793–1860) and his pouch and cyst



http://ift.tt/2s2Cjcn

Neonatal AAV delivery of alpha-synuclein induces pathology in the adult mouse brain

Abstract

Abnormal accumulation of alpha-synuclein (αsyn) is a pathological hallmark of Lewy body related disorders such as Parkinson's disease and Dementia with Lewy body disease. During the past two decades, a myriad of animal models have been developed to mimic pathological features of synucleinopathies by over-expressing human αsyn. Although different strategies have been used, most models have little or no reliable and predictive phenotype. Novel animal models are a valuable tool for understanding neuronal pathology and to facilitate development of new therapeutics for these diseases. Here, we report the development and characterization of a novel model in which mice rapidly express wild-type αsyn via somatic brain transgenesis mediated by adeno-associated virus (AAV). At 1, 3, and 6 months of age following intracerebroventricular (ICV) injection, mice were subjected to a battery of behavioral tests followed by pathological analyses of the brains. Remarkably, significant levels of αsyn expression are detected throughout the brain as early as 1 month old, including olfactory bulb, hippocampus, thalamic regions and midbrain. Immunostaining with a phospho-αsyn (pS129) specific antibody reveals abundant pS129 expression in specific regions. Also, pathologic αsyn is detected using the disease specific antibody 5G4. However, this model did not recapitulate behavioral phenotypes characteristic of rodent models of synucleinopathies. In fact no deficits in motor function or cognition were observed at 3 or 6 months of age. Taken together, these findings show that transduction of neonatal mouse with AAV-αsyn can successfully lead to rapid, whole brain transduction of wild-type human αsyn, but increased levels of wildtype αsyn do not induce behavior changes at an early time point (6 months), despite pathological changes in several neurons populations as early as 1 month.



http://ift.tt/2s2B5xO

Zika virus tropism and interactions in myelinating neural cell cultures: CNS cells and myelin are preferentially affected

Abstract

The recent global outbreak of Zika virus (ZIKV) infection has been linked to severe neurological disorders affecting the peripheral and central nervous systems (PNS and CNS, respectively). The pathobiology underlying these diverse clinical phenotypes are the subject of intense research; however, even the principal neural cell types vulnerable to productive Zika infection remain poorly characterised. Here we used CNS and PNS myelinating cultures from wild type and Ifnar1 knockout mice to examine neuronal and glial tropism and short-term consequences of direct infection with a Brazilian variant of ZIKV. Cell cultures were infected pre- or post-myelination for various intervals, then stained with cell-type and ZIKV-specific antibodies. In bypassing systemic immunity using ex vivo culture, and the type I interferon response in Ifnar1 deficient cells, we were able to evaluate the intrinsic infectivity of neural cells. Through systematic quantification of ZIKV infected cells in myelinating cultures, we found that ZIKV infection is enhanced in the absence of the type I interferon responses and that CNS cells are considerably more susceptible to infection than PNS cells. In particular, we demonstrate that CNS axons and myelinating oligodendrocytes are especially vulnerable to injury. These results have implications for understanding the pathobiology of neurological symptoms associated with ZIKV infection. Furthermore, we provide a quantifiable ex vivo infection model that can be used for fundamental and therapeutic studies on viral neuroinvasion and its consequences.



http://ift.tt/2sxBPyw

A nationwide survey of aortic valve surgery in Japan: current status of valve preservation in cases with aortic regurgitation

Abstract

Objective

Although aortic valve-sparing operations are performed throughout Japan, the indications, specific repair techniques, and outcomes have not been reported in full. Thus, we conducted the first nationwide survey of aortic valve-sparing surgery.

Methods

We mailed a questionnaire to 508 institutions across Japan to obtain information on elective aortic valve and aortic root surgeries performed in 2014. Included in the mailing was a secondary questionnaire that sought further information from institutions reporting aortic valve-sparing surgeries.

Results

Two hundred and fifty (49%) institutions responded and reported a total of 7859 aortic valve operations and 771 aortic root operations. Aortic valve operations performed strictly for aortic regurgitation totaled 2080, 156 (8%) of which were aortic valve repairs. Of the 699 aortic root surgeries performed for aortic regurgitation, 236 (34%) were valve-sparing root replacement surgeries. The valve-sparing root replacement surgeries comprised aortic valve reimplantation (n = 173, 73%) and aortic root remodeling (n = 63, 27%). Five of 57 (9%) institutions were responsible for 42% (99/233) of the total aortic valve-sparing surgeries performed. Detailed information that was obtained for 233 patients who underwent aortic valve repair or valve-sparing root replacement showed 30-day mortality and reoperation for regurgitation after aortic valve repair (n = 97), aortic root remodeling (n = 37), and aortic valve reimplantation (n = 99) to be 1, 0, and 1% and 3, 3, and 1%, respectively.

Conclusion

To date, aortic valve-sparing operations have been performed for limited patients at limited institution in Japan, but the early outcomes have been excellent.



http://ift.tt/2t24rkp

Textural features of 18 F-FDG PET after two cycles of neoadjuvant chemotherapy can predict pCR in patients with locally advanced breast cancer

Abstract

Objective

This study was designed to evaluate the utility of textural features for predicting pathological complete response (pCR) to neoadjuvant chemotherapy (NAC).

Methods

Sixty-one consecutive patients with locally advanced breast cancer underwent 18F-FDG PET/CT scanning at baseline and after the second course of NAC. Changes to imaging parameters [maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG)] and textural features (entropy, coarseness, skewness) between the 2 scans were measured by two independent radiologists. Pathological responses were reviewed by one pathologist, and the significance of the predictive value of each parameter was analyzed using a Chi-squared test. Receiver operating characteristic curve analysis was used to compare the area under the curve (AUC) for each parameter.

Results

pCR was observed more often in patients with HER2-positive tumors (22 patients) than in patients with HER2-negative tumors (5 patients) (71.0 vs. 16.7%, p < 0.001). ∆ %SUVmax, ∆ %entropy and ∆ %coarseness were significantly useful for differentiating pCR from non-pCR in the HER2-negative group, and the AUCs for these parameters were 0.928, 0.808 and 0.800, respectively (p = 0.003, 0.032 and 0.037). In the HER2-positive group, ∆ %SUVmax and ∆ %skewness were moderately useful for predicting pCR, and the respective AUCs were 0.747 and 0.758 (p = 0.033 and 0.026). Although there was no significant difference in the AUCs between groups for these parameters, an additional 3/22 patients in the HER2-positive group with pCR were identified when ∆ %skewness and ∆ %SUVmax were considered together (p = 0.031). The absolute values for each parameter before NAC and after 2 cycles cannot predict pCR in our patients. Neither ∆ %MTV nor ∆ %TLG was efficiently predictive of pCR in any group.

Conclusions

The early changes in the textural features of 18F-FDG PET images after two cycles of NAC are predictive of pCR in both HER2-negative and HER2-positive patients; this evidence warrants confirmation by further research.



http://ift.tt/2sxEpo6

Colorectal Cancer Surveillance: What Is the Optimal Frequency of Follow-up and Which Tools Best Predict Recurrence?

Abstract

Purpose of Review

Up to 50% of patients with stage II or III colon cancer are estimated to develop locoregional recurrence, distant metastasis, or metachronous colon cancers within 5 years of initial treatment. Given the high risk of recurrence, surveillance is critical, but what is the optimal frequency and testing of surveillance, and is it possible to tailor surveillance plans based on risk prediction tools?

Recent Findings

We reviewed the current national guidelines from 6 reputable oncologic organizations, as well as 10 randomized controlled trials and numerous meta-analyses in the last 22 years evaluating more intensive to less intensive surveillance to answer this question. Currently available adjunct testing, such as genomic testing, and risk calculators were also evaluated.

Summary

Overall, high-frequency surveillance, to a limit, has been established as superior to less frequency surveillance. Future research will likely demonstrate evidence for adjunct testing for personalized surveillance screening based on individual recurrence risk.



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Growing Concerns: A 3-Year-Old Girl with Multiple Hepatic Masses and Gastrointestinal Bleeding



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CD4 T Cells in IBD: Crossing the Line?



http://ift.tt/2sXZfNW

Psychiatrische Versorgung von Flüchtlingen in Afrika und dem Nahen Osten

Zusammenfassung

Gewalt, Flucht, Hungersnot und Naturkatastrophen sowie das Fehlen eines psychosozialen Gesundheitssystems sind große Belastungen für Flüchtlinge. Das Niveau psychiatrischer Versorgungsmöglichkeiten ist in Entwicklungsländern besonders niedrig. Binnenvertriebene und Flüchtlinge haben jedoch hohe Anforderungen an das Versorgungssystem, weil sie häufig unter psychischen Erkrankungen wie Depression, posttraumatischer Belastungsstörung und Abhängigkeitserkrankungen leiden. Wir berichten über Ansätze zur Verbesserung der psychiatrischen Versorgung in Flüchtlingslagern in drei ausgewählten Ländern (Äthiopien, Kenia, Sudan). Darüber hinaus gewährt der Beitrag einen Einblick in die Arbeit eines im Nordirak und in Deutschland angesiedelten Projektes zur Behandlung von durch den Terror des sog. Islamischen Staates (IS) schwersttraumatisierten Menschen.



http://ift.tt/2sxyhwk

Nitrogen-doped carbon dots embedded in a SiO 2 monolith for solid-state fluorescent detection of Cu 2+ ions

Abstract

We describe the simple fabrication of SiO2 sol-gel monoliths embedding highly luminescent carbon nanodots (CDs) sensitive to metal ions. The pristine CDs we synthesize display an intense dual emission consisting in two fluorescence bands in the green and violet region, and we demonstrate that this photoluminescence is substantially unchanged when the dots are incorporated in the SiO2 matrix. The emission of these CDs is quenched by interactions with Cu2+ ions, which can be used to detect these ions with a detection limit of 1 μM. The chromophores remain accessible to diffusing Cu2+ ions even after embedding CDs in the sol-gel monolith, where their detection capabilities are preserved. Such a result provides the proof-of-principle of a new sensing scheme, where CDs are exploited as active sensing centers of metal transition ions within a solid-state device. The different interaction mechanisms of CDs with copper, in liquid and solid phase, are analyzed in detail and discussed in terms of different accessibility of their chromophores when the dots are incorporated in the SiO2 matrix.



http://ift.tt/2rJ4jTc

Airway Management in Combat Trauma

Abstract

Purpose of Review

Airway compromise remains a leading cause of death in battlefield trauma. The purpose of this review is to examine the impact of airway compromise on survival in the combat trauma population and assess the challenges in providing effective airway management in the combat environment when contrasted with the civilian peacetime environment.

Recent Findings

Management approaches in the civilian trauma setting are not necessarily applicable in the combat environment due to differences in injury patterns and extent of prehospital airway operator training. Although outcomes with airway management in both combat and civilian trauma environments are improved when more skilled providers are involved, this is not always a feasible option in the combat environment.

Summary

The prehospital setting represents the area of greatest difference in planning and practice between the civilian and combat trauma systems. Further research is necessary to improve training strategies and equipment used in combat airway management.



http://ift.tt/2rY6VAu

The Cathinones MDPV and α-PVP Elicit Different Behavioral and Molecular Effects Following Acute Exposure

Abstract

Since the mid-to-late 2000s, synthetic cathinones have gained popularity among drug users due to their psychostimulant effects greater than those produced by cocaine and amphetamine. Among them, 3,4-methylenedioxypyrovalerone (MDPV) and 1-phenyl-2-(pyrrolidin-1-yl)pentan-1-one (α-PVP) are ones of the most popular cathinones available in the clandestine market as "bath salts" or "fertilizers." Pre-clinical studies indicate that MDPV and α-PVP induced psychomotor stimulation, affected thermoregulation, and promoted reinforcing properties in rodents. However, a direct comparative analysis on the effects caused by MDPV and α-PVP on the behavior and neuronal activation in rodents is still lacking. Behavioral analyses revealed that both MDPV and α-PVP affect spontaneous and stimulated motor responses. In particular, MDPV showed a greater psychomotor effect than α-PVP in line with its higher potency in blocking the dopamine transporter (DAT). Notably, MDPV was found to be more effective than α-PVP in facilitating spontaneous locomotion and it displayed a biphasic effect in contrast to the monophasically stimulated locomotion induced by α-PVP. In addition to the behavioral results, we also found a different modulation of immediate early genes (IEGs) such as Arc/Arg3.1 and c-Fos in the frontal lobe, striatum, and hippocampus, indicating that these drugs do impact brain homeostasis with changes in neuronal activity that depend on the drug, the brain area analyzed, and the timing after the injection. These results provide the first discrimination between MDPV and α-PVP based on behavioral and molecular data that may contribute to explain, at least in part, their toxicity.



http://ift.tt/2rXvEFr

Bubble removal with the use of a vacuum pressure generated by a converging-diverging nozzle

Abstract

Bubbles are an intrinsic problem in microfluidic devices and they can appear during the initial filling of the device or during operation. This report presents a generalizable technique to extract bubbles from microfluidic networks using an adjacent microfluidic negative pressure network over the entire microfluidic channel network design. We implement this technique by superimposing a network of parallel microchannels with a vacuum microfluidic channel and characterize the bubble extraction rates as a function of negative pressure applied. In addition, we generate negative pressure via a converging-diverging (CD) nozzle, which only requires inlet gas pressure to operate. Air bubbles generated during the initial liquid filling of the microfluidic network are removed within seconds and their volume extraction rate is calculated. This miniaturized vacuum source can achieve a vacuum pressure of 7.23 psi which corresponds to a bubble extraction rate of 9.84 pL/s, in the microfluidic channels we characterized. Finally, as proof of concept it is shown that the bubble removal system enables bubble removal on difficult to fill microfluidic channels such as circular or triangular shaped channels. This method can be easily integrated into many microfluidic experimental protocols.



http://ift.tt/2rIYODZ

The relationship between circulating adiponectin, leptin and vaspin with bone mineral density (BMD), arterial calcification and stiffness: a cross-sectional study in post-menopausal women

Abstract

Objective

To explore the relationship between circulating adiponectin, leptin and vaspin with bone mineral density (BMD), arterial stiffness and vascular calcification in post-menopausal women. We hypothesised that adipokines produced by adipose tissue may be mediators of bone and cardiovascular disease (CVD) and explain, in part, the observed association between osteoporosis and CVD.

Design

We studied 386 ambulant community dwelling postmenopausal women aged (mean [SD] 61 [6.4] years). BMD at the lumbar spine, femoral neck (FN), and total hip (TH), body composition; fat mass (FM) and lean mass (LM) as well as abdominal aortic calcification (AAC) were determined by dual energy X-ray absorptiometry. Pulse wave velocity (PWV) and augmentation index, markers of arterial stiffness were measured. Fasting adiponectin, leptin and vaspin were quantified in serum.

Results

A positive independent association was observed between vaspin and BMD at the FN (p = 0.009), TH (p = 0.037) in the whole study population adjusted for confounders including age, FM, LM and lifestyle variables. Using the same model, a negative association was seen between adiponectin and BMD at the FN in women with osteoporosis (p = 0.043). Serum adiponectin was significantly higher in women with fractures (20.8 [9.3] µg/ml compared to those without (18.5 [8.6] µg/ml, p = 0.018) and associated with a significant increased risk of fracture (HR 1.032, 95% CI 1.003–1.063, p = 0.032). Leptin was not associated with BMD or fracture risk after adjustment. Adiponectin was independently associated with AAC (p = 0.007) and significantly higher in women with AAC scores > 1; (19.2[9.2]) compared to those with no or low AAC scores (<1); 16.8 [8.0], p = 0.018). In adjusted analyses, PWV velocity was positively associated with circulating vaspin (p = 0.039) and AI was negatively associated with serum leptin (p = 0.002).

Conclusion

Adiponectin, leptin, vaspin are related to markers of bone and vascular health and may contribute to the observed association between osteoporosis and CVD.



http://ift.tt/2sxpCK6

Mesenchymal stem cell therapy for acute and chronic pancreatitis

Abstract

Mesenchymal stem cells (MSCs) have attracted attention as a cell source for regenerative medicine. In particular, MSCs have an anti-inflammatory effect by secreting several kinds of bioactive molecules. MSC therapy is now being applied to various gastrointestinal diseases, such as graft-versus-host disease, inflammatory bowel disease, and liver cirrhosis. Therefore, MSC therapy has the potential to be a novel treatment for acute and chronic pancreatitis by suppressing inflammation. Several studies have investigated the effect of MSC therapy on acute and chronic pancreatitis, but the underlying mechanisms remain unknown. In this review, we summarize the present status of MSC therapy for acute and chronic pancreatitis.



http://ift.tt/2tAFM3O

Recommandations européennes sur la prise en charge endoscopique de l’endobrachyoesophage



http://ift.tt/2sxiddS

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