Intracellular Concentration Gradients That Mirror External Gradients in Microfluidic Flows: A Computational Analysis

Abstract

The generation of stable intracellular concentration gradients is a useful method for local control of cell function, selective manipulation of cellular structures and testing hypotheses related to dynamical intracellular processes. Cell culture in a microfluidic device allows the presentation of a stable gradient of small molecules across a single cell. This method has been used to selectively label mitochondria in portions of the cell, trypsinize specific cellular domains, and trigger receptor-mediated endocytosis in specific portions of the cell. Given the small length scales of a typical cell (~30 μm) and short cytoplasmic diffusive time scales of small molecules, it is surprising that cells can be labeled locally with this method. Here we developed models to explore the parametric space over which stable intracellular concentration gradients can be maintained in a microfluidic device. We show that gradients can develop and be maintained indefinitely for high rates of mass transfer across the membrane compared with diffusion, that is, for Sherwood number greater than 1. We show how these gradients can result in gradients in ligand–receptor binding and enzyme substrate binding. This analysis can help interpret and design microfluidic experiments for cytoplasmic partitioning.

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CT-perfusion measurements in pancreatic carcinoma with different kinetic models: Is there a chance for tumour grading based on functional parameters?

Abstract

Background

To evaluate the interchangeability of perfusion parameters obtained with help of models used for post-processing of perfusion-CT images in pancreatic adenocarcinoma and to determine the mean values and ranges of perfusion in different tumour gradings.

Methods

Perfusion-CT imaging was performed prospectively in 48 consecutive patients with pancreatic adenocarcinoma. In 42 patients biopsy-proven tumor grading was available (4 × G1/24 × G2/14 × G3/6× unknown). Images were post-processed using a model based on the maximum-slope (MS) approach (blood flow-BFMS) + Patlak analysis (P) (blood volume [BVP] and permeability [k-transP]), as well as a model with deconvolution-based (D) analysis (BFD, BVD and k-transD). 50 mL contrast agent were applied with a delay time of 7 s. Perfusion parameters were compared using intraclass correlation coefficient (ICC), the Wilcoxon matched-pairs test and Bland-Altman plots.

Results

Forty eight VOIs of tumours were outlined and analysed. Moderate to good ICC values were found for the perfusion parameters (ICC = 0.62–0.75). Wilcoxon matched-pairs revealed significantly lower values (P < .001 and 0.008), for the BF and BV values obtained using the maximum-slope approach + Patlak analysis compared to deconvolution based analysis. For k-trans measurement, deconvolution revealed significantly lower values (P < 0.001). Different histologic subgroups (G1-G3) did not show significantly different functional parameters.

Conclusion

There were significant differences in the perfusion parameters obtained using the different calculation methods, and therefore these parameters are not directly interchangeable. However, the magnitude of pairs of parametric values is in constant relation to each other enabling the use of any of these methods. VPCT parameters did not allow for histologic classification.

http://ift.tt/2hExnJP

Auslöser von Arzneiexanthemen: Absetzen, durchbehandeln oder desensibilisieren?

Zusammenfassung

Arzneimittelüberempfindlichkeitsreaktionen betreffen über 7% der Bevölkerung und sind ein Problem für Patienten und Ärzte. Viele solcher Reaktionen treten in Form von Arzneimittelexanthemen auf. Klinische Manifestationen von Arzneimittelexanthemen sind sehr variabel und reichen von einem lokalisierten fixen Arzneimittelexanthem zu lebensbedrohlichen schweren bullösen oder systemischen Überempfindlichkeitsreaktionen. Entsprechend dem hier vorgeschlagenen Algorithmus sollte bei Verdacht auf ein Arzneimittelexanthem zunächst eine Kausalitätsprüfung erfolgen. Wenn sowohl der zeitliche Ablauf als auch die klinische Manifestation für ein Arzneimittelexanthem sprechen, ist das auslösende Arzneimittel zu meiden. Nur bei dringender Therapieindikation, fehlenden alternativen Arzneimitteln und nach sorgfältiger, individueller Risiko-Nutzen-Analyse sollte eine Durchbehandlung oder eine Toleranzinduktion durch „Desensibilisierung" erwogen werden.

http://ift.tt/2gV1MlG

Phenylephrine increases near-infrared spectroscopy determined muscle oxygenation in men

Abstract

Phenylephrine increases mean arterial pressure (MAP) by enhanced total peripheral resistance (TPR) but near-infrared spectroscopy (NIRS) determined muscle oxygenation (S_mO₂) increases. We addressed that apparent paradox during supine rest and head-up tilt (HUT). Variables were determined ± phenylephrine in males during supine rest (n = 17) and 40° HUT (n = 7). MAP, stroke volume (SV), heart rate (HR), and TPR were derived by Modelflow^® and NIRS determined biceps S_mO₂ and (tibial) bone oxygenation (S_tibialO₂). For ten subjects, cardiac filling and the diameter of the inferior caval vein (ICV collapsibility index: ((ICV_expiration − ICV_inspiration)/ICV_expiration) × 100) were assessed by ultrasound. Pancreatic polypeptide (PP) and atrial natriuretic peptide (proANP) in plasma were determined by immunoassay. Brachial artery blood flow was assessed by ultrasound and skin oxygenation (S_skinO₂) monitored by white light spectroscopy. Phenylephrine increased MAP by 34% and TPR (62%; P < 0.001) during supine rest. The ICV collapsibility index decreased (24%; P < 0.001) indicating augmented cardiac preload although volume of the left atrium and ventricle did not change. SV increased (18%; P < 0.001) as HR decreased (24%; P < 0.001). ProANP increased by 9% (P = 0.002) with unaffected PP. Brachial artery blood flow tended to decrease while S_skinO₂ together with S_tibialO₂ decreased by 11% (P = 0.026) and 20% (P < 0.001), respectively. Conversely, phenylephrine increased S_mO₂ (9%) and restored the HUT elicited decrease in S_mO₂ (by 19%) along with SV (P = 0.02). Phenylephrine reduces skin and bone oxygenation and tends to reduce arm blood flow, suggesting that the increase in S_mO₂ reflects veno-constriction with consequent centralization of the blood volume.

http://ift.tt/2gKXt9e

Systemic air embolism during pleural lavage for empyema

Abstract

Pleural lavage has been considered a convenient and safe method that is often performed for empyema. We report a case of systemic air embolism that developed during pleural lavage. A 53-year-old man with empyema in the organizing phase suddenly developed paralysis of the left side of the body and altered level of consciousness during pleural lavage, which was performed in a sitting position without negative pressure suction. Systemic air embolism was diagnosed based on computed tomography. In this case, use of fibrinolytic agents, positioning during pleural lavage, and pressure in an empyema cavity may have predisposed to development of systemic air embolism. Conversion from thoracoscopic therapy to open decortication or fenestration should be considered to prevent this type of complication.

http://ift.tt/2hEToFy

A Statewide Quality Improvement Initiative to Reduce Non-Medically Indicated Scheduled Deliveries

Abstract

Objectives To evaluate a large two-phase, statewide quality improvement (QI) collaborative to decrease non-medically indicated (N-MI) deliveries scheduled between 36 and 38 weeks gestation (early). Methods The New York State Department of Health (NYSDOH) convened a Perinatal Quality Collaborative to devise a two-phase QI initiative using a rapid cycle incremental learning model. Phase 1 included Regional Perinatal Centers (RPCs), and Phase 2 added their affiliated perinatal hospitals. Maternal demographics, delivery characteristics, medical indications, and stillbirths were collected on scheduled inductions and cesarean section (CS) deliveries between 36 and 38 weeks. Results There were 35,091 scheduled 36–38 week deliveries reported during the collaborative's 4 years. The percentage of early N-MI scheduled deliveries decreased 41-fold in RPCs (Phase 1 and Phase 2), and 17-fold in affiliates (Phase 2). There was a significant statewide increase in deliveries at ≥39 weeks (P < 0.001), with an estimated 23,732 early deliveries averted. Stillbirths did not increase over time (P = 0.42), although reporting was incomplete. Conclusions A two-phase, statewide QI collaborative in a large state with regionalized perinatal care effectively lowered the number of N-MI deliveries scheduled between 36 and 38 weeks gestation. Associated improvements in neonatal and early childhood developmental outcomes should translate to significant cost savings. This model can effectively be used for similar as well as other obstetrical QI.

http://ift.tt/2gUQhdS

Ultrasound follow-up of an unusual giant urinoma in a newborn

Abstract

Urinoma, defined as an encapsulation of urine caused by urine extravasation into the perirenal space either through rupture of a calyceal fornix or a tear in the renal parenchyma, is an uncommon finding in prenatal diagnosis and the neonatal period. Urinoma can be associated with any urinary tract obstruction, or, as reported in several published cases, related to vesicoureteral reflux, kidney dysplasia, or complication arising during amniocentesis. We report on a newborn with a perinatal urinoma, with initial slight corpusculated fluid associated with nonobstructive and nonrefluxing megaureter, and no signs of kidney dysplasia. Close sonography follow-up of the urinoma allowed complex differential diagnoses, including cystic, septated, and solid perirenal masses, due to dissimilar and peculiar ultrasound images during urinoma evolution stages.

http://ift.tt/2hELRa8

Association of SNPs in dopamine and serotonin pathway genes and their interacting genes with temperament traits in Charolais cows

Abstract

Cattle temperament is a complex trait, and molecular studies aimed at defining this trait are scarce. We used an interaction networks approach to identify new genes (interacting genes) and to estimate their effects and those of 19 dopamine- and serotonin-related genes on the temperament traits of Charolais cattle. The genes proopiomelanocortin (POMC), neuropeptide Y (NPY), solute carrier family 18, member 2 (SLC18A2) and FBJ murine osteosarcoma viral oncogene homologue (FOSFBJ) were identified as new candidates. Their potential to be associated with temperament was estimated according to their reported biological activities, which included interactions with neural activity, receptor function, targeting or synthesis of neurotransmitters and association with behaviour. Pen score (PS) and exit velocity (EV) measures were determined from 412 Charolais cows to calculate their temperament score (TS). Based on the TS, calm (n = 55; TS, 1.09 ± 0.33) and temperamental (n = 58; TS, 2.27 ± 0.639) cows were selected and genotyped using a 248 single-nucleotide variation (SNV) panel. Of the 248 variations in the panel, only 151 were confirmed to be polymorphic (single-nucleotide polymorphisms; SNPs) in the tested population. Single-marker association analyses between genotypes and temperament measures (EV, PS and/or TS) indicated significant associations of six SNPs from four candidate genes. The markers rs109576799 and rs43696138, located in the DRD3 and HTR2A genes, respectively, were significantly associated with both EV and TS traits. Four markers, rs110365063 and rs137756569 from the POMC gene and rs110365063 and rs135155082 located in SLC18A2 and DRD2, respectively, were associated with PS. The variant rs110365063 located in bovine SLC18A2 causes a change in the amino acid sequence from Ala to Thr. Further studies are needed to confirm the association of genetic profile with cattle temperament; however, our study represents important progress in understanding the regulation of cattle temperament by different genes with divergent functions.

http://ift.tt/2gL0OW0

Zystische Pankreastumoren

Zusammenfassung

Der Begriff zystischer Pankreastumor umfasst heterogene Erkrankungen neoplastischen oder nichtneoplastischen Ursprungs, die sich in Bezug auf das maligne Entartungspotenzial, die Behandlung und Prognose deutlich unterscheiden. Ihre Inzidenz ist hoch. Während muzinöse Zysten (intraduktale papillär-muzinöse [IPMN] und muzinös-zystische Neoplasie [MCN]) maligne transformieren können, ist dies bei serösen Zysten meist nicht der Fall. Die Prävalenz der IPMN liegt bei 26 Fällen pro 100.000 Einwohner. IPMN und MCN sind meist ein asymptomatischer Zufallsbefund. MCN, Hauptgang- und „Mixed-type" IPMN sollten aufgrund des hohen Risikos einer malignen Entartung operativ behandelt werden. Auch bei Seitengang-IPMN liegt ein malignes, jedoch geringeres Entartungsrisiko als bei anderen muzinösen Zysten vor. Hier hängt das individuelle Vorgehen von evtl. vorliegenden Risikofaktoren der Entartung der Zyste, vom Alter, der Komorbidität und dem Wunsch des Patienten sowie vom interdisziplinären Konsens ab.

http://ift.tt/2hEdnXJ

Look who’s talking—the crosstalk between oxidative stress and autophagy supports exosomal-dependent release of HCV particles

Abstract

Autophagy is a highly conserved and regulated intracellular lysosomal degradation pathway that is essential for cell survival. Dysregulation has been linked to the development of various human diseases, including neurodegeneration and tumorigenesis, infection, and aging. Besides, many viruses hijack the autophagosomal pathway to support their life cycle. The hepatitis C virus (HCV), a major cause of chronic liver diseases worldwide, has been described to induce autophagy. The autophagosomal pathway can be further activated in response to elevated levels of reactive oxygen species (ROS). HCV impairs the Nrf2/ARE-dependent induction of ROS-detoxifying enzymes by a so far unprecedented mechanism. In line with this, this review aims to discuss the relevance of HCV-dependent elevated ROS levels for the induction of autophagy as a result of the impaired Nrf2 signaling and the described crosstalk between p62 and the Nrf2/Keap1 signaling pathway. Moreover, autophagy is functionally connected to the endocytic pathway as components of the endosomal trafficking are involved in the maturation of autophagosomes. The release of HCV particles is still not fully understood. Recent studies suggest an involvement of exosomes that originate from the endosomal pathway in viral release. In line with this, it is tempting to speculate whether HCV-dependent elevated ROS levels induce autophagy to support exosome-mediated release of viral particles. Based on recent findings, in this review, we will further highlight the impact of HCV-induced autophagy and its interplay with the endosomal pathway as a novel mechanism for the release of HCV particles.

http://ift.tt/2hQOyIe

Isolation and Characterization of Altererythrobacter sp. DT for Biotreatment of and Sulfur Production from Thiosulfate-Bearing Industrial Wastewater

Abstract

The objectives of the present study are to isolate thiosulfate-degrading bacterium and optimize its degradative conditions including temperature, pH, and thiosulfate concentrations required for bioremediation purposes. A heterotrophic thiosulfate-degrading bacterial strain DT was successfully isolated from saline soil and identified as Altererythrobacter sp. based on its physicochemical properties and 16S rDNA sequence analysis. It was a naturally occurring methionine auxotrophic strain that utilized only peptone, yeast extract, or several amino acids as the sole carbon source. Altererythrobacter sp. DT degraded thiosulfate via a distinctive disproportionation reaction which was characterized by accumulation of sulfate and elemental sulfur at a molar ratio of 1:1. Optimal conditions for both bacterial growth and thiosulfate metabolism were 25–30 °C and pH 6, respectively. In a fed-batch treatment system receiving liquid polysulfide wastewater, a high degradation rate of 407.3 mg S₂O₃²⁻/(L h) and an elemental sulfur yield of nearly 50% were achieved for immobilized DT cells, indicating great potential of strain DT for future application in the treatment of and microbial production of elemental sulfur from thiosulfate-bearing industrial wastewater.

http://ift.tt/2gUYrmz

A surgical department for intensified care

Abstract

Purpose

The growing pressure to rationalize costs in the healthcare system demands the development of new healthcare models aimed at allowing patients to receive the best treatment, without ignoring the rising costs.

Methods

In the Healthcare Unit 2 located in the Abruzzo region in Italy, a new model of intensified care surgical department was designed in January 2013. The department was based on the selection of the degree of patient disease. Patients requiring a medium-low degree surgery were treated in the peripheral unit, in the Ortona hospital, while more complex surgical procedures, most cancer cases (including stomach, liver, pancreas, colon-rectum or multi-organ resections), were performed in the central unit in the Chieti hospital.

Results

The value of production at the peripheral unit, in Ortona, increased by 299.4% along with an increase in discharges of 112.6%, with an average DRG weight from 1.02 to 1.45. At the central unit, in Chieti, the average DRG weight produced was 3.328. In relation to quality assessment, pancreatic surgery morbidity was 27.0% and mortality was 1.7 % due to resection and 2.2% for other causes. Likewise, for colon-rectal surgery, a global morbidity of 35.0% and anastomotic leakage of 3.9% was seen.

Conclusions

The 24-month preliminary results show that new models of intensified care surgical departments can be created. In addition, results clearly show that such model significantly improves both services and surgical results. This original model allows optimal use of resources favouring both service quality and patient satisfaction.

http://ift.tt/2hQzzOG

The feasibility of laparoscopic pancreaticoduodenectomy—a stepwise procedure and learning curve

Abstract

Background

Laparoscopic pancreaticoduodenectomy (LPD) has been proven feasible and safe. The artery-first approach emerged as a standard procedure in pancreatic surgery. In this manuscript, we describe both our stepwise, artery-first technique for LPD and methods for accumulating experience during the initial learning stage.

Method

This is a retrospective review of 12 patients who underwent LPD between 2012 and 2015. We classified the first five patients as the early group and the remaining seven as the late group. Here, we present our stepwise procedure for LPD, along with the perioperative results and postoperative prognoses for the two groups.

Results

The mean operative time for the 12 patients undergoing LPD was 408.3 ± 97.5 min. The average blood loss was 146.7 ± 90.2 mL. The dissection time (T_D) was significantly shorter in the late group compared with the early group (140 vs. 200 min, respectively; p = 0.006). However, there was no difference in the reconstruction time (T_R) between the two groups (220 vs. 200 min; p = 0.807).

Conclusion

Artery-first LPD is a feasible procedure for selected patients and has acceptable results. Using this stepwise procedure, the operative time could be reduced, mainly by reducing the time required for dissection.

http://ift.tt/2gL0SVr

Graves’ orbitopathy, idiopathic orbital inflammatory pseudotumor and Epstein–Barr virus infection: a serological and molecular study

Abstract

Objective

One of the hypotheses on the pathogenesis of autoimmune diseases, including Graves' disease (GD) and Graves' orbitopathy (GO), involves bacterial or viral infections. Recently, Epstein–Barr virus (EBV) has been proposed to play a role in the pathogenesis of idiopathic orbital inflammatory pseudotumor (IOIP) in Asians. The aim of the present study was to investigate the possible association of GO with EBV infection/exposure, as compared with IOIP, using serum and tissue samples, as well as primary cultures of orbital fibroblasts.

Methods

Thirty-one patients were studied, including four with IOIP, ten with GO, nine with GD without GO and eight control patients without IOIP, GD and GO. All patients with IOIP and GO underwent orbital decompression. Control patients underwent palpebral surgery. Fibroadipose orbital tissue samples were collected. Serum anti-EBV antibodies were measured in all patients. EBV-DNA was measured in blood samples, orbital tissue samples and primary cultures of orbital fibroblasts.

Results

Serum assays showed that the vast majority of patients have had a previous exposure to EBV, but no one had an acute infection. EBV-DNA was detected in ~40% of blood samples from GO, GD and control patients, but in none of the IOIP samples. EBV-DNA was not detected in any of the orbital tissue samples tested or in primary cultures of orbital fibroblasts.

Conclusions

EBV infection does not seem to be associated with GD, GO and IOIP in Caucasians. Whether EBV is involved in IOIP in Asians or other populations remains to be confirmed.

http://ift.tt/2gUmjbW

Vitamin D Treatment Attenuates Neuroinflammation and Dopaminergic Neurodegeneration in an Animal Model of Parkinson’s Disease, Shifting M1 to M2 Microglia Responses

Abstract

Microglia-mediated neuroinflammation has been described as a common hallmark of Parkinson's disease (PD) and is believed to further exacerbate the progressive degeneration of dopaminergic neurons. Current therapies are unable to prevent the disease progression. A significant association has been demonstrated between PD and low levels of vitamin D in patients serum, and vitamin D supplement appears to have a beneficial clinical effect. Herein, we investigated whether vitamin D administered orally in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced preclinical animal model of PD protects against glia-mediated inflammation and nigrostriatal neurodegeneration. Vitamin D significantly attenuated the MPTP-induced loss of tyrosine hydrlase (TH)-positive neuronal cells, microglial cell activation (Iba1-immunoreactive), inducible nitric oxide synthase (iNOS) and TLR-4 expression, typical hallmarks of the pro-inflammatory (M1) activation of microglia. Additionally, Vitamin D was able to decrease pro-inflammatory cytokines mRNA expression in distinct brain areas of the MPTP mouse. Importantly, we also assessed the anti-inflammatory property of vitamin D in the MPTP mouse, in which it upregulated the anti-inflammatory cytokines (IL-10, IL-4 and TGF-β) mRNA expression as well as increasing the expression of CD163, CD206 and CD204, typical hallmarks of alternative activation of microglia for anti-inflammatory signalling (M2). Collectively, these results demonstrate that vitamin D exhibits substantial neuroprotective effects in this PD animal model, by attenuating pro-inflammatory and up-regulating anti-inflammatory processes.

http://ift.tt/2hYiwWS

Matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS) for rapid identification of micro-organisms in the routine clinical microbiology laboratory

Abstract

The study evaluates the utility of matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) Vitek MS for identification of microorganisms in the routine clinical microbiology laboratory. From May 2013 to April 2014, microbial isolates recovered from various clinical samples were identified by Vitek MS. In case of failure to identify by Vitek MS, the isolate was identified using the Vitek 2 system (bioMerieux, France) and serotyping wherever applicable or otherwise by nucleic acid-mediated methods. All the moulds were identified by Lactophenol blue mounts, and mycobacterial isolates were identified by molecular identification systems including AccuProbe (bioMerieux, France) or GenoType Mycobacterium CM (Hain Lifescience, Germany). Out of the 12,003 isolates, the Vitek MS gave a good overall ID at the genus and or species level up to 97.7% for bacterial isolates, 92.8% for yeasts and 80% for filamentous fungi. Of the 26 mycobacteria tested, only 42.3% could be identified using the Saramis RUO (Research Use Only) database. VITEK MS could not identify 34 of the 35 yeast isolates identified as C. haemulonii by Vitek 2. Subsequently, 17 of these isolates were identified as Candida auris (not present in the Vitek MS database) by 18S rRNA sequencing. Using these strains, an in-house superspectrum of C. auris was created in the VITEK MS database. Use of MALDI-TOF MS allows a rapid identification of aerobic bacteria and yeasts in clinical practice. However, improved sample extraction protocols and database upgrades with inclusion of locally representative strains is required, especially for moulds.

http://ift.tt/2htnpKw

Evaluation of the novel artus C. difficile QS-RGQ, VanR QS-RGQ and MRSA/SA QS-RGQ assays for the laboratory diagnosis of Clostridium difficile infection (CDI), and for vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) screening

Abstract

Clostridium difficile, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) are worldwide prevalent healthcare-associated pathogens. We have evaluated three Qiagen artus QS-RGQ assays for the detection of these pathogens. We examined 200 stool samples previously tested for C. difficile infection (CDI), 94 rectal swabs previously screened for VRE and 200 MRSA screening nasal swabs. With the routine diagnostic laboratory results being adopted as the gold standard, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the artus C. difficile assay were 100%, for the artus VanR QS-RGQ assay, 95, 68, 44 and 98%, and for the artus MRSA/SA assay, 80, 94, 93 and 83%, respectively. The artus VanR assay detected the vanA and/or vanB genes in 32% of culture-negative VRE screens; in 71% of these cases, only vanB was detected. An over-estimation of the rate of faecal VRE colonisation could be due to a patient population with high rates of faecal carriage of non-enterococcal species carrying vanB. Based on our findings, we conclude that all three artus QS-RGQ assays could be a useful addition to a diagnostic laboratory, and that the optimal choice of assay should be determined according to user needs.

http://ift.tt/2hEJAvz

Selective susceptibility to nanosecond pulsed electric field (nsPEF) across different human cell types

Abstract

Tumor ablation by nanosecond pulsed electric fields (nsPEF) is an emerging therapeutic modality. We compared nsPEF cytotoxicity for human cell lines of cancerous (IMR-32, Hep G2, HT-1080, and HPAF-II) and non-cancerous origin (BJ and MRC-5) under strictly controlled and identical conditions. Adherent cells were uniformly treated by 300-ns PEF (0–2000 pulses, 1.8 kV/cm, 50 Hz) on indium tin oxide-covered glass coverslips, using the same media and serum. Cell survival plotted against the number of pulses displayed three distinct regions (initial resistivity, logarithmic survival decline, and residual resistivity) for all tested cell types, but with differences in LD₅₀ spanning as much as nearly 80-fold. The non-cancerous cells were less sensitive than IMR-32 neuroblastoma cells but more vulnerable than the other cancers tested. The cytotoxic efficiency showed no apparent correlation with cell or nuclear size, cell morphology, metabolism level, or the extent of membrane disruption by nsPEF. Increasing pulse duration to 9 µs (0.75 kV/cm, 5 Hz) produced a different selectivity pattern, suggesting that manipulation of PEF parameters can, at least for certain cancers, overcome their resistance to nsPEF ablation. Identifying mechanisms and cell markers of differential nsPEF susceptibility will critically contribute to the proper choice and outcome of nsPEF ablation therapies.

http://ift.tt/2hauL2E

Graphene Oxide as a Novel Evenly Continuous Phase Matrix for TOF-SIMS

Abstract

Using matrix to enhance the molecular ion signals for biomolecule identification without loss of spatial resolution caused by matrix crystallization is a great challenge for the application of TOF-SIMS in real-world biological research. In this report, graphene oxide (GO) was used as a matrix for TOF-SIMS to improve the secondary ion yields of intact molecular ions ([M + H]⁺). Identifying and distinguishing the molecular ions of lipids (m/z >700) therefore became straightforward. The spatial resolution of TOF-SIMS imaging could also be improved as GO can form a homogeneous layer of matrix instead of crystalline domain, which prevents high spatial resolution in TOF-SIMS imaging. Lipid mapping in presence of GO revealed the delicate morphology and distribution of single vesicles with a diameter of 800 nm. On GO matrix, the vesicles with similar shape but different chemical composition could be distinguished using molecular ions. This novel matrix holds potentials in such applications as the analysis and imaging of complex biological samples by TOF-SIMS.

Graphical Abstract

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Insulated-tip knife endoscopic polypectomy for difficult pedunculated colorectal polyps: a prospective pilot study

Abstract

Background

Endoscopic polypectomy is widely used for colorectal polyps. However, for giant pedunculated colorectal polyps (≥3 cm), conventional techniques are so difficult with en bloc resection that patients had to be transferred to surgery. We had firstly reported our first experience with an insulated-tip knife to successfully remove a giant pedunculated polyp in the sigmoid colon. In this study, our aim was to explore safety and feasible of insulated-tip knife endoscopic polypectomy (IT-EP) for difficult pedunculated colorectal polyps.

Methods

A total of seven consecutive patients with giant pedunculated colorectal polyps (≥3 cm) were prospectively enrolled. IT-EP was conducted with the help of clips for all the seven patients, and data of them was recorded and analyzed.

Results

Of seven patients, five were men and two were women with a mean age 61 years (49–72 years). The mean diameter of polyp head and stalk was 36.4 ± 4.9 mm (30–42 mm) and 14.6 ± 3.6 mm (10–20 mm), respectively. All the polyps were successfully removed with IT-EP, with a mean operation time of 14.9 ± 3.5 min (11–20 min). No serious bleeding or perforation was experienced, and no surgery was needed. There was no recurrence or residual of polyps at a mean 8.1-month follow-up.

Conclusions

Insulated-tip knife endoscopic polypectomy is a safe and feasible alternative for difficult pedunculated colorectal polyps.

http://ift.tt/2gUFfFJ

Cost of persistent asthma in Italy

Abstract

Background

Asthma is a common disease of the airways with a significant burden for the society and for patients' quality of life. The Social Impact of Respiratory Integrated Outcomes (SIRIO) study estimated a mean cost of 1,177.40 € per patient/year in Italy, in 2007. The aim of the present study was to update the cost of persistent asthma patients in Italy.

Methods

An observational, retrospective, bottom-up analysis was carried out starting from the data base operating in the Lung Unit of the Specialist Medical Centre (CEMS), Verona (Italy), over the period June 2013-December 2015. Patients' data were recorded over the 12 ± 2 months before the enrollment and during 12 ± 2 months of follow-up. The prospective was the Italian National Health Service and the broad Italian society. Clinical data were measured in terms of forced expiratory volume in 1 s (FEV₁%) and number of relapses. Healthcare resources (namely; number of hospitalizations and/or ER admissions; number of visits; drug use and duration, and indirect costs) were recorded.

Results

The cohort consisted of 817 patients with persistent asthma of different severity. They had a 42.96% male prevalence; a mean (±SE) age of 49.06 (±0.64) years; a mean 87.47% (±0.81) FEV₁% pred. in baseline, and 69.16% of subjects had comorbidities. The mean (±SE) number of relapses was 0.91 (±0.09) per patient/year before the enrolment. After 12 months, FEV₁% significantly improved by +6.31% (±0.45) from the corresponding baseline value (p  < 0.001). The number of relapses decreased of −0.46 (±0.09) (p  < 0.001). The estimated total annual cost per asthmatic patient was 1,183.14 € (±65.79 €) during the 12 months before the enrolment, and 1,290.89 € (±68.74 €) throughout the follow-up. The increase was mostly due to the significantly increased duration of therapeutic strategies. The costs of hospitalization, general practitioner and rescue medications were significantly decreased.

Conclusions

The periodic update of cost analysis is a key to monitor the trend of main asthma outcomes and related expenditure over time. It allows to plan the most convenient actions in terms of prevention strategies and effective interventions, with the aim of optimizing the healthcare resources consumption and maximizing the impact on clinical outcomes and patients' quality of life. The role of an appropriate pharmacological strategy still proves crucial in minimizing asthma morbidity and the corresponding socio-economic impact.

http://ift.tt/2haofZO

DNA damage and repair capacity in lymphocyte of chronic obstructive pulmonary diseases patients during physical exercise with oxygen supplementation

Abstract

Background

We hypothesized that the use of oxygen supplementation during aerobic exercise induces less DNA damage than exercise alone.

The aim of this study is to assess the level of DNA damage induced by physical exercise with and without oxygen supplementation in chronic obstructive pulmonary diseases (COPD) patients.

Methods

Peripheral blood was collected before and after aerobic exercise in two conditions: (I) aerobic exercise without oxygen supplementation (AE group) and (II) with oxygen supplementation (AE-O₂ group). Lymphocytes were collected to perform the alkaline version of the Comet Assay. To assess the susceptibility to exogenous DNA damage, the lymphocytes were treated with methyl methanesulphonate (MMS) for 1-h or 3-h. After 3-h treatment, the percentage of residual damage was calculated assuming the value of 1-h MMS treatment as 100%.

Results

AE group showed lower induced damage (1 h of MMS treatment) and consequently less DNA repair compared to AE-O₂ group. AE-O₂ group showed an increase in the induced DNA damage (1 h of MMS treatment) and an increased DNA repair capacity. Within the AE-O₂ group, in the post-exercise situation the induced DNA damage after 1 h of MMS treatment was higher (p = 0.01) than in the pre-exercise.

Conclusion

COPD patients who performed physical exercise associated with oxygen supplementation had a better response to DNA damage induced by MMS and a better DNA repair when compared to the condition of physical exercise without oxygen supplementation.

Trial registration

UNISC N374.298. Registered 04 JUN 2013 (retrospectively registered).

http://ift.tt/2gU8wBX

A case of combined laparoscopic reduction and open preperitoneal mesh repair for incarcerated small bowel in a retroperitoneal hernia between the external and internal iliac vessels

Abstract

We report a rare case of an incarcerated retroperitoneal hernia with or involving the small bowel through the orifice between the right external and internal iliac vessels. A 39-year-old woman was admitted to our hospital because of vomiting and abdominal pain. She had a history of right oophorocystectomy and appendectomy. Abdominal computed tomography revealed small bowel obstruction resulting from an incarcerated retroperitoneal hernia. The small bowel herniated into the retroperitoneal fossa through the orifice between the right external and internal iliac vessels. Laparoscopic reduction of the small bowel was performed, followed by ligation of the sac and placement of a mesh prosthesis through the preperitoneal approach, using a lower midline incision along the previous laparotomy scar. Her postoperative course was uneventful and no recurrence has been observed after surgery.

http://ift.tt/2gU7HJx

Uric Acid Is Protective After Cerebral Ischemia/Reperfusion in Hyperglycemic Mice

Abstract

Hyperglycemia at stroke onset is associated with poor long-term clinical outcome in numerous studies. Hyperglycemia induces intracellular acidosis, lipid peroxidation, and peroxynitrite production resulting in the generation of oxidative and nitrosative stress in the ischemic tissue. Here, we studied the effects of acute hyperglycemia on in vivo intercellular adhesion molecule-1 (ICAM-1) expression, neutrophil recruitment, and brain damage after ischemia/reperfusion in mice and tested whether the natural antioxidant uric acid was protective. Hyperglycemia was induced by i.p. administration of dextrose 45 min before transient occlusion of the middle cerebral artery. Magnetic resonance imaging (MRI) was performed at 24 h to measure lesion volume. A group of normoglycemic and hyperglycemic mice received an i.v. injection of micron-sized particles of iron oxide (MPIOs), conjugated with either anti-ICAM-1 antibody or control IgG, followed by T2*w MRI. Neutrophil infiltration was studied by immunofluorescence and flow cytometry. A group of hyperglycemic mice received an i.v. infusion of uric acid (16 mg/kg) or the vehicle starting after 45 min of reperfusion. ICAM-1-targeted MPIOs induced significantly larger MRI contrast-enhancing effects in the ischemic brain of hyperglycemic mice, which also showed more infiltrating neutrophils and larger lesions than normoglycemic mice. Uric acid reduced infarct volume in hyperglycemic mice but it did not prevent vascular ICAM-1 upregulation and did not significantly reduce the number of neutrophils in the ischemic brain tissue. In conclusion, hyperglycemia enhances stroke-induced vascular ICAM-1 and neutrophil infiltration and exacerbates the brain lesion. Uric acid reduces the lesion size after ischemia/reperfusion in hyperglycemic mice.

http://ift.tt/2hHu3uk

National survey of pediatric hospitalizations due to Kawasaki disease and coronary artery aneurysms in the USA

Abstract

Several studies revealed the epidemiology of Kawasaki disease-related hospitalizations among children in the USA and other countries. However, disparities of developing coronary artery aneurysms by race/ethnicity, patient socioeconomic status, and geographic locations remain unknown in the USA. Hospital discharge record data of patients with Kawasaki disease aged 19 years or younger were obtained from the 2003, 2006, 2009, and 2012 Kid's Inpatient Database. The data were weighted to estimate the annual hospitalization rates with respect to age, gender, and race/ethnicity in the USA. Multivariable logistic regression was conducted to ascertain the factors associated with the development of coronary artery aneurysms. Total annual hospitalization rates of Kawasaki disease showed a decreasing trend, ranging from 6.54 per 100,000 children in 2003 to 6.11 per 100,000 children in 2012 (p < 0.001). The proportions of coronary artery aneurysms among patients with Kawasaki disease ranged from 2.25 to 3.20%. Factor associated with the development of coronary artery aneurysms was hospitals in West (OR 2.15, 95% CI 1.42–3.26). Race/ethnicity, health insurance status, and household income were not associated with the development of coronary artery aneurysms. Total hospitalization rates of Kawasaki disease showed a decreasing trend. Children admitted to hospitals in West region were more likely to develop coronary artery aneurysms.

http://ift.tt/2hHpSyI

Interleukin (IL)-1 inhibition with anakinra and canakinumab in Behçet’s disease-related uveitis: a multicenter retrospective observational study

Abstract

This study aimed to evaluate the role of interleukin (IL)-1 inhibitors anakinra (ANA) and canakinumab (CAN) in the treatment of Behçet's disease (BD)-related uveitis. Multicenter retrospective observational study includes 19 consecutive BD patients (31 affected eyes) received treatment with anti-IL-1 agents. Data were analyzed at baseline and at 3 and 12 months. The primary endpoint is the reduction of ocular inflammatory flares (OIF). The secondary endpoints are improvement of best corrected visual acuity (BCVA); reduction of macular thickness defined by optical coherence tomography (OCT) and of vasculitis identified with fluorescein angiography (FA); evaluation of statistically significant differences between patients treated with IL-1 inhibitors as monotherapy, subjects also administered with disease modifying anti-rheumatic drugs (DMARDs) and/or corticosteroids as well as between patients administered with IL-1 inhibitors as first line biologic treatment and those previously treated with TNF-α inhibitors. At 12 months, OIF significantly decreased from 200 episodes/100 patients/year to 48.87 episodes/100 patients/year (p < 0.0001). The frequency of retinal vasculitis identified by FA significantly decreased between baseline and 3- and 12-month follow-up visits (p < 0.0001 and p = 0.001, respectively). OIF rate was significantly higher in patients co-administered with DMARDs (81.8 episodes/100 patients/year) than in patients undergoing IL-1 inhibitors as monotherapy (0.0 episodes/100 patients/year) (p = 0.03). No differences were identified on the basis of corticosteroid use and between patients administered with IL-1 inhibitors as first line biologic approach or second line. Steroid dosage was significantly decreased at 12-month visit compared to baseline (p = 0.02). Treatment with IL-1 inhibitors is effective in the management of BD-related uveitis and provides a long-term control of ocular inflammation in refractory and long-lasting cases.

http://ift.tt/2hDRLdI

Twelfth degree spline with application to quadrature

In this paper existence and uniqueness of twelfth degree spline is proved with application to quadrature. This formula is in the class of splines of degree 12 and continuity order ...

http://ift.tt/2hHjW8S

Cooperative Decision-Making Under Uncertainties for Multi-Target Surveillance with Multiples UAVs

Abstract

Surveillance is an interesting application for Unmanned Aerial Vehicles (UAVs). If a team of UAVs is considered, the objective is usually to act cooperatively to gather as much information as possible from a set of moving targets in the surveillance area. This is a decision-making problem with severe uncertainties involved: relying on imperfect sensors and models, UAVs need to select targets to monitor and determine the best actions to track them. Partially Observable Markov Decision Processes (POMDPs) are quite adequate for optimal decision-making under uncertainties, but they lack scalability in multi-UAV scenarios, becoming tractable only for toy problems. In this paper, we take a step forward to apply POMDP methods in real situations, where the team needs to adapt to the circumstances during the mission and foster cooperation among the team-members. We propose to split the original problem into simpler behaviors that can be modeled by scalable POMDPs. Then, those behaviors are auctioned during the mission among the UAVs, which follow different policies depending on the behavior assigned. We evaluate the performance of our approach with extensive simulations and propose an implementation with real quadcopters in a testbed scenario.

http://ift.tt/2htjtcO

Autonomous Navigation of UAV in Foliage Environment

Abstract

This paper presents a navigation system that enables small-scale unmanned aerial vehicles to navigate autonomously using a 2D laser range finder in foliage environment without GPS. The navigation framework consists of real-time dual layer control, navigation state estimation and online path planning. In particular, the inner loop of a quadrotor is stabilized using a commercial autopilot while the outer loop control is implemented using robust perfect tracking. The navigation state estimation consists of real-time onboard motion estimation and trajectory smoothing using the GraphSLAM technique. The onboard real-time motion estimation is achieved by a Kalman filter, fusing the planar velocity measurement from matching the consecutive scans of a laser range finder and the acceleration measurement of an inertial measurement unit. The trajectory histories from the real-time autonomous navigation together with the observed features are fed into a sliding-window based pose-graph optimization framework. The online path planning module finds an obstacle-free trajectory based the local measurement of the laser range finder. The performance of the proposed navigation system is demonstrated successfully on the autonomous navigation of a small-scale UAV in foliage environment.

http://ift.tt/2hExd2i

Rolling Horizon Path Planning of an Autonomous System of UAVs for Persistent Cooperative Service: MILP Formulation and Efficient Heuristics

Abstract

A networked system consisting of unmanned aerial vehicles (UAVs), automated logistic service stations (LSSs), customer interface software, system orchestration algorithms and UAV control software can be exploited to provide persistent service to its customers. With efficient algorithms for UAV task planning, the UAVs can autonomously serve the customers in real time. Nearly uninterrupted customer service may be accomplished via the cooperative hand-off of customer tasks from weary UAVs to ones that have recently been replenished at an LSS. With the goal of enabling the autonomy of the task planning tasks, we develop a mixed integer linear programming (MILP) formulation for the problem of providing simultaneous. UAV escort service to multiple customers across a field of operations with multiple sharable LSSs. This MILP model provides a formal representation of our problem and enables use in a rolling horizon planner via allowance of arbitrary UAV initial locations and consumable reservoir status (e.g., battery level). As such, it enables automation of the orchestration of system activities. To address computational complexity, we develop efficient heuristics to rapidly derive near optimal solutions. A receding horizon task assignment (RHTA) heuristic and sequential task assignment heuristic (STAH) are developed. STAH exploits properties observed in optimal solutions obtained for small problems via CPLEX. Numerical studies suggest that RHTA and STAH are 45 and 2100 times faster than solving the MILP via CPLEX, respectively. Both heuristics perform well relative to the optimal solution obtained via CPLEX. An example demonstrating the use of the approach for rolling horizon planning is provided.

http://ift.tt/2htdK6Y

On the Guidance of Multiple UAV using a Centralized Formation Control Scheme and Delaunay Triangulation

Abstract

This manuscript presents an application of the multi-layer control scheme to guide a formation of unmanned aerial vehicles (UAV) in positioning and trajectory tracking missions. In such case, each part of the formation control problem is dealt by an individual layer, which is independent module dealing with a specific part of the navigation problem. These layers are responsible to generate the desired path of the formation, to provide the desired posture of the robots, and to establish the control signal of each robot to reach their desired positions. The formation controller here introduced is able to coordinate the robots to the desired formation, including the possibility of time-varying position and/or shape, while a nonlinear underactuated controller previously proposed is responsible to guide the UAVs to their desired positions. The stability analysis of the closed-loop system is demonstrated in the sense of Lyapunov, resulting that the formation errors are ultimately bounded. In the sequel, a strategy to guide a formation of multiple unmanned aerial vehicles (MUAV) to accomplish positioning and trajectory-tracking tasks is also proposed. Delaunay triangulation is here used to split the platoon of UAVs in N-triangles, which are individually guided by the multi-layer control scheme (MLCS). The advantage of the MLCS in such proposal is the maintenance of the the Jacobian matrix order, regardless of the number of robots in the formation, which reduces the complexity of the control problem. Simulation results demonstrate the ability to accomplish the aforementioned tasks, thus validating the proposal.

http://ift.tt/2hEvzhr

Collision Avoidance for Multiple UAVs Using Rolling-Horizon Policy

Abstract

This paper addresses the problem of collision avoidance in scenarios with multiple aerial vehicles and proposes a method based on a Legendre pseudospectral collocation in order to compute the solution trajectories and guarantee that the safety distance between them is always maintained. The method uses a rolling horizon policy in which trajectories are planned up to a given time horizon, thus considering a much smaller problem space. Then, the system is applied iteratively. Studies have been performed to set the values of the look-ahead time and the number of collocations points. The computational load and scalability of the method are also studied in randomly generated scenarios to test its application in real time. Experiments have been also carried out in the multivehicle aerial testbed of the Center for Advanced Aerospace Technologies (Seville, Spain).

http://ift.tt/1MJ4ikE

Expression patterns indicate that BMP2/4 and Chordin, not BMP5-8 and Gremlin, mediate dorsal–ventral patterning in the mollusk Crassostrea gigas

Abstract

Though several bilaterian animals use a conserved BMP2/4–Chordin antagonism to pattern the dorsal–ventral (DV) axis, the only lophotrochozoan species in which early DV patterning has been studied to date, the leech Helobdella robusta, appears to employ BMP5-8 and Gremlin. These findings call into question the conservation of a common DV patterning mechanism among bilaterian animals. To explore whether the unusual DV patterning mechanism in H. robusta is also used in other lophotrochozoan species, we investigated the expression of orthologous genes in the early embryo of a bivalve mollusk, Crassostrea gigas. Searching of the genome and phylogenetic analysis revealed that C. gigas possesses single orthologs of BMP2/4, Chordin, and BMP5-8 and no Gremlin homolog. Whole mount in situ hybridization revealed mRNA localization of BMP2/4 and Chordin on the opposite sides of embryos, suggesting the potential involvement of a BMP2/4–Chordin antagonism in DV patterning in this species. Furthermore, universal BMP5-8 expression and the absence of a Gremlin homolog in the C. gigas genome called into question any major contribution by BMP5-8 and Gremlin to early DV patterning in this species. Additionally, we identified seven genes showing asymmetric expression along the DV axis, providing further insight into DV patterning in C. gigas. We present the first report of a Chordin gene in a lophotrochozoan species and of the opposite expression of BMP2/4 (dorsal) and Chordin (ventral) along the D/V axis of a lophotrochozoan embryo. The findings of this study further the knowledge of axis formation in lophotrochozoan species and provide insight into the evolution of the animal DV patterning mechanism.

http://ift.tt/2gKsD0x

Comprehensive characterization of a theophylline riboswitch reveals two pivotal features of Shine-Dalgarno influencing activated translation property

Abstract

Tuneable gene expression controlled by synthetic biological elements is of great importance to biotechnology and synthetic biology. The synthetic riboswitch is a pivotal type of elements that can easily control the heterologous gene expression in diverse bacteria. In this study, the theophylline-dependent synthetic riboswitch and the corresponding variants with varied spacings between Shine-Dalgarno (SD) sequence and start codon were employed to comprehensively characterize the induction and regulation properties through combining a strong promoter aprE in Bacillus subtilis. Amongst the sets of newly constructed expression elements, the expression element with 9-bp spacing exhibited the higher expression level, a superior induction fold performance, and a considerably lower leaky expression than those with longer or shorter spacings. The riboswitch expression element with 9-bp spacing showed an approximately linear dose dependence from 0 to 8 mM of theophylline. Modification of the SD sequence through the insertion of a single A base prior to the native sequence enables the increase of the expression level post induction while decreasing the induction fold as a result of the elevated leaky level. The riboswitch elements with the engineered SD and the optimal 9-bp spacing exhibit an altered dose dependency in which the approximately linear range shifts to 0–4 mM, although it has a similar profile to the induction process. These results not only provide comprehensive data for the induced expression by a theophylline riboswitch combined with a strong native promoter from B. subtilis but also provide the two pivotal features of SD essential to the modular design of other synthetic riboswitches.

http://ift.tt/2hDDvSx

Bacterial community structure within an activated sludge reactor added with phenolic compounds

Abstract

Biodegradation of phenolic compounds in bioreactors is well documented, but the changes in the bacterial populations dynamics during degradation were not that often. A glass bubble column used as reactor was inoculated with activated sludge, spiked with 2-chlorophenol, phenol and m-cresol after 28 days and maintained for an additional 56 days, while the 16S rRNA gene from metagenomic DNA was monitored. Proteobacteria (68.1%) dominated the inoculum, but the bacterial composition changed rapidly. The relative abundance of Bacteroidetes and Firmicutes decreased from 4.8 and 9.4 to <0.1 and 0.2% respectively, while that of Actinobacteria and TM7 increased from 4.8 and 2.0 to 19.2 and 16.1% respectively. Phenol application increased the relative abundance of Proteobacteria to 94.2% (mostly Brevundimonas 17.6%), while that of Bacteroidetes remained low (1.2%) until day 42. It then increased to 47.3% (mostly Leadbetterella 46.9%) at day 84. It was found that addition of phenolic compounds did not affect the relative abundance of the Alphaproteobacteria initially, but it decreased slowly while that of the Bacteroidetes increased towards the end.

http://ift.tt/2gTut2i

Recombinant expression and characterization of a l -amino acid oxidase from the fungus Rhizoctonia solani

Abstract

l-Amino acid oxidases (L-AAOs) catalyze the oxidative deamination of l-amino acids to the corresponding α-keto acids, ammonia, and hydrogen peroxide. l-AAOs are homodimeric enzymes with FAD as a non-covalently bound cofactor. They are of potential interest for biotechnological applications. However, heterologous expression has not succeeded in producing large quantities of active recombinant l-AAOs with a broad substrate spectrum so far. Here, we report the heterologous expression of an active l-AAO from the fungus Rhizoctonia solani in Escherichia coli as a fusion protein with maltose-binding protein (MBP) as a solubility tag. After purification, it was possible to remove the MBP-tag proteolytically without influencing the enzyme activity. MBP-rsLAAO1 and 9His-rsLAAO1 converted basic and large hydrophobic l-amino acids as well as methyl esters of these l-amino acids. The progress of the conversion of l-phenylalanine and l-leucine into the corresponding α-keto acids was determined by HPLC and ¹H-NMR analysis of reaction mixtures, respectively. Enzymatic activity was stimulated 50–100-fold by SDS treatment. K _m values ranging from 0.9–10 mM and v _max values from 3 to 10 U mg⁻¹ were determined after SDS activation of 9His-rsLAAO1 for the best substrates. The enzyme displayed a broad pH optimum between pH 7.0 and 9.5. In summary, a successful overexpression of recombinant l-AAO in E. coli was established that results in a promising enzymatic activity and a broad substrate spectrum for biotechnological application.

http://ift.tt/2hH15uM

Retrograde suction decompression of a large internal carotid aneurysm using a balloon guide catheter combined with a blood-returning circuit and STA-MCA bypass: a technical note

Abstract

It is difficult to treat large internal carotid aneurysms with simple surgical clipping. Here, we present a retrograde suction decompression (RSD) procedure for large internal carotid aneurysms using a balloon guide catheter combined with a blood-returning circuit and a superficial temporal artery to middle cerebral artery (STA-MCA) bypass.

All patients underwent an STA-MCA bypass before the temporary occlusion of the internal carotid artery (ICA). A 6-French sheath was inserted into the common carotid artery (CCA), and a 6-French Patrive balloon catheter was placed into the ICA 5 cm past the bifurcation. Aneurysm exposure was obtained; temporary clips were placed on the proximal M1, A1, and posterior communicating (Pcom) segments; and an extension tube was then connected to the balloon catheter. A three-way stopcock was placed, and aspiration was performed through the device to collapse the aneurysm. The aspirated blood was returned to a venous line with an added heparin to prevent anemia after aspiration. During the decompression, the blood flow to the cortical area was supplied through the STA-MCA bypass. After the aneurysm collapse, the surgeon carefully dissected the perforating artery from the aneurysm dome or neck, and permanent clips were then placed on the aneurysm neck. Our procedure has several advantages, such as STA-MCA bypass without external carotid artery occlusion for preventing ischemic complications of the cortical area, anemia may be avoided because of the return of the aspirated blood, and a hybrid operation room is not required to perform this method.

http://ift.tt/2gU92hO

Early permanent disappearance of abnormal muscle response during microvascular decompression for hemifacial spasm: a retrospective clinical study

Abstract

The objective of this study is to explore the cause of early abnormal muscle response (AMR) disappearance during microvascular decompression for hemifacial spasm and the clinical outcomes of these patients. Three hundred seventy-two patients received microvascular decompression (MVD) under intraoperative electrophysiological monitoring in Nanjing Drum Tower Hospital in 2014; the characteristic AMR of HFS was observed in 359 patients during the operation. And the 359 patients were divided into two groups based on whether AMR had remained before the beginning of the decompression procedure for offending vessels. Thirty-three patients who showed a permanent disappearance of AMR before the beginning of decompression were regarded as group I. Dural opening and the succeeding CSF drainage produced a permanent disappearance of AMR in 13. During the dissection of lateral cerebellomedullary cistern, a permanent disappearance of AMR was found in 20 patients. Thirty-two patients were cured immediately; delayed resolution (7 days after surgery) was found in one patient. No complications were observed and no recurrence was found during the follow-up period in the 33 patients. In the other 326 patients (group II), AMR disappeared temporarily before the beginning of the decompression procedure for offending vessels in 42 patients. After decompression, AMR disappeared completely in 305 patients. Two hundred sixty-seven patients were cured immediately and 57 patients got a delayed resolution (2 days to 45 weeks after surgery). The two left did not get a complete abolition of spasm. Three cases of hearing loss, one hoarseness, and nine delayed facial paralysis were observed. The reason of early abnormal muscle response disappearance may be that the degree of neurovascular compression was not serious; these patients were more likely to get an immediate cure. Continuous intraoperative electrophysiological monitoring of AMR is necessary.

http://ift.tt/2hXTQ0y

Präklinische Validierung der Sicherheit von Chloralhydrat zur topischen Applikation am Beispiel des psoriatischen Pruritus

Zusammenfassung

Hintergrund

Die Psoriasis wird heute als T‑Zell vermittelte autoimmunologische Systemerkrankung verstanden. Das chronisch entzündliche Geschehen bezieht auch neuroimmunologische Faktoren ein, die nicht nur für verschiedene Fassetten einer psychiatrisch-neurologischen Komorbidität, sondern auch für neurosensorische Symptome, allen voran den Pruritus verantwortlich gemacht werden. Unter anderem wird in diesem Zusammenhang die Bedeutung von GABA_A-Rezeptoren diskutiert. Die topische Anwendung in halbfesten Zubereitungen zur antipruriginösen Therapie geht auf Neisser zurück und erfährt derzeit eine Renaissance in der magistralen Rezeptur. Bisher ist allerdings unbekannt, ob die aus der systemischen Anwendung von Chloralhydrat bekannten unerwünschten Wirkungen auch für die topische Anwendung praktische Relevanz besitzen.

Zielsetzung

Aus Mangel an klinischen Sicherheitsdaten zur topischen Anwendung wurden präklinische Untersuchungen zur kutanen Zytotoxizität, zur kutanen Verträglichkeit und Berechnungen zur systemischen Bioverfügbarkeit nach topischer Applikation vorgenommen.

Ergebnisse

Zusammenfassend kann festgestellt werden, dass die erarbeiteten Daten relevante Sicherheitsbedenken bei kontrollierter Applikation von Chloralhydrat mit der favorisierten Rezeptur aus dem Neues Rezepturformularium (NRF) (sog. 1‑2-3-Creme) nicht vollständig ausräumen können. Eine Anwendung der 1‑2-3-Creme bei maximal 2‑mal täglicher Applikation auf bis zu 10 % der Körperoberfläche kann aber als unproblematisch angesehen werden. Um darüber hinaus eine verbesserte Bewertung der Unbedenklichkeit zu erreichen, wären die Untersuchung der kutanen Bioverfügbarkeit (Konzentrations-Zeit-Profil) von Chloralhydrat nach epikutaner Applikation an Humanhaut bzw. klinische Studien notwendig.

http://ift.tt/2hGPtb8

Nichtvirale sexuell übertragene Infektionen – Epidemiologie, Klinik, Labordiagnostik und Therapie

Zusammenfassung

Chlamydia trachomatis ist der weltweit am häufigsten sexuell übertragene bakterielle Infektionserreger. Jährlich rechnet man in Deutschland mit etwa 300.000 Neuinfektionen. Die Erkrankungen treten fast ausschließlich postpubertär auf. Der Altersgipfel liegt in der Altersgruppe 15 bis 25 Jahre. Da die Infektion überwiegend asymptomatisch verläuft, wird die Diagnose mittels Nukleinsäureamplifikationstechniken (NAT) oft nur durch ein Screening oder erst bei Auftreten einer Komplikation gestellt. Zur Behandlung kommt an erster Stelle Doxycyclin 2‑mal 100 mg p. o. über 7 Tage zum Einsatz. Alternativ wird Azithromycin 1,5 g p. o. als 1‑malige Gabe empfohlen. Partneruntersuchung und -therapie sind zu beachten. Genitale Mykoplasmen-Infektionen werden durch Ureaplasma urealyticum (Urethritis- und Vaginitiserreger), Ureaplasma parvum (meist saprophytär, selten Urethritiserreger) und Mycoplasma hominis (fakultativ pathogen) verursacht. Eine relativ neue, durch sexuellen Kontakt übertragene Mykoplasmen-Art ist Mycoplasma genitalium. Doxycyclin ist wirksam bei Ureaplasma-Infektionen, alternativ Clarithromycin oder Azithromycin. Doxycyclin kann bei Mycoplasma-hominis-Infektionen versagen, eine Alternative stellt Clindamycin dar. Die Urethritis durch Mycoplasma genitalium sollte heute molekularbiologisch mittels Polymerasekettenreaktion diagnostiziert und mit Azithromycin behandelt werden.

http://ift.tt/2hDkb7S

Nichtvirale sexuell übertragene Infektionen – Epidemiologie, Klinik, Labordiagnostik und Therapie

Zusammenfassung

Die Weltgesundheitsorganisation (WHO) schätzt, dass weltweit pro Tag 1 Mio. Menschen mit einer STI („sexually transmitted infection") infiziert werden. Die Gonorrhö wird nahezu ausschließlich sexuell übertragen und betrifft vornehmlich die Schleimhaut des Urogenitaltraktes, möglich sind jedoch auch extragenitale Lokalisationen (Anorektalbereich). Laut Infektionsschutzgesetz (IfSG) sind heute in Deutschland nur Syphilis und HIV-Nachweis zu melden. In Sachsen gilt die erweiterte Meldeverordnung laut IfSG, sodass neben der Syphilis auch Neisseria-gonorrhoeae-, Chlamydia trachomatis- und genitale Mykoplasmennachweise meldepflichtig sind. Seit 2009 kam es in Sachsen zu einer eindrucksvollen Zunahme der gemeldeten Infektionen durch Neisseria gonorrhoeae, im Jahr 2015 waren es 824 Meldungen. Besorgniserregend ist die Zunahme der Resistenz von Neisseria gonorrhoeae gegenüber Penicillin, Doxycyclin, Ciprofloxacin und neuerdings auch gegenüber Azithromycin und Drittgenerationscephalosporinen. Der ursprünglich in Japan aufgetretene sog. Superbug („Superbazillus") von Neisseria gonorrhoeae mit Multiresistenz gegenüber den meisten verfügbaren oralen Antibiotika ist mittlerweile auch in Europa angekommen. Die Standardtherapie der Gonorrhö erfolgt heute mit Ceftriaxon (i. v. oder i. m.) zusammen mit Azithromycin p. o., beides als Einmalgabe.

http://ift.tt/2hGJZNH

Pro-differentiating effects of a synthetic flavagline on human teratocarcinomal cancer stem-like cells

Abstract

As initiators of the carcinogenic process, cancer stem cells (CSCs) are considered as new targets for anti-cancer therapies. However, these cells are hidden in the cancer bulk and remain relatively insensitive to chemotherapy, which targets their proliferative capacities. Alternatively, growing evidences have pointed out that a differentiation therapy could adversely affect these cells, which consequently should lose their self-renewal properties and become less aggressive. In order to evaluate the differentiation potential of an emerging class of anti-cancer drugs, we used the poorly differentiated teratocarcinomal cell as a model of Oct4-expressing CSC and determined the molecular mechanisms induced by the highly active flavagline FL3. The drug, administrated at sublethal concentration and for long period, was able to downregulate the expression levels of the stemness factors Oct4 and Nanog at both transcriptional and translational levels, concomitantly with a decrease of clonogenicity. The appearance of specific neural markers further demonstrated the differentiation properties of FL3. Interestingly, an expression of active caspase-3 and an upregulation of the expression of the germ cell nuclear factor were observed in treated cells; this suggests that the suppression of Oct4 expression required for the induction of differentiation involves overlapping mechanisms of protein degradation and gene repression. Finally, this study shows that FL3, like all-trans retinoic acid (ATRA), acts as a differentiation inducer of teratocarcinomal cells. Thus, FL3 offers an alternative possibility for cancer treatment since it could target the carcinogenic process by inducing the differentiation of ATRA-resistant and Oct4-expressing CSCs, without toxic side effects on normal cells.

http://ift.tt/2hE87ki

Lung morphometry: the link between structure and function

Abstract

The study of the structural basis of gas exchange function in the lung depends on the availability of quantitative information that concerns the structures establishing contact between the air in the alveoli and the blood in the alveolar capillaries, which can be entered into physiological equations for predicting oxygen uptake. This information is provided by morphometric studies involving stereological methods and allows estimates of the pulmonary diffusing capacity of the human lung that agree, in experimental studies, with the maximal oxygen consumption. The basis for this "machine lung" structure lies in the complex design of the cells building an extensive air-blood barrier with minimal cell mass.

http://ift.tt/2gTIoFU

Erratum to: Cementogenic genes in human periodontal ligament stem cells are downregulated in response to osteogenic stimulation while upregulated by vitamin C treatment

http://ift.tt/2hXthZC

Tissue remodelling in pulmonary fibrosis

Abstract

Many lung diseases result in fibrotic remodelling. Fibrotic lung disorders can be divided into diseases with known and unknown aetiology. Among those with unknown aetiology, idiopathic pulmonary fibrosis (IPF) is a common diagnosis. Because of its progressive character leading to a rapid decline in lung function, it is a fatal disease with poor prognosis and limited therapeutic options. Thus, IPF has motivated many studies in the last few decades in order to increase our mechanistic understanding of the pathogenesis of the disease. The current concept suggests an ongoing injury of the alveolar epithelium, an impaired regeneration capacity, alveolar collapse and, finally, a fibroproliferative response. The origin of lung injury remains elusive but a diversity of factors, which will be discussed in this article, has been shown to be associated with IPF. Alveolar epithelial type II (AE2) cells play a key role in lung fibrosis and their crucial role for epithelial regeneration, stabilisation of alveoli and interaction with fibroblasts, all known to be responsible for collagen deposition, will be illustrated. Whereas mechanisms of collagen deposition and fibroproliferation are the focus of many studies in the field, the awareness of other mechanisms in this disease is currently limited to biochemical and imaging studies including quantitative assessments of lung structure in IPF and animal models assigning alveolar collapse and collapse induration crucial roles for the degradation of the lung resulting in de-aeration and loss of surface area. Dysfunctional AE2 cells, instable alveoli and mechanical stress trigger remodelling that consists of collapsed alveoli absorbed by fibrotic tissue (i.e., collapse induration).

http://ift.tt/2gTPfiv

Evaluation of a commercial electro-kinetically pumped sheath-flow nanospray interface coupled to an automated capillary zone electrophoresis system

Abstract

Capillary zone electrophoresis-electrospray ionization-mass spectrometry (CZE-ESI-MS) is attracting renewed attention for proteomic and metabolomic analysis. An important reason for this interest is the maturation and commercialization of interfaces for coupling CZE with ESI-MS. One of these interfaces is an electro-kinetically pumped sheath flow nanospray interface developed by the Dovichi group, in which a very low sheath flow is generated based on electroosmosis within a glass emitter. CMP Scientific has commercialized this interface as the EMASS-II ion source. In this work, we compared the performance of the EMASS-II ion source with our in-house system. The performance of the systems is equivalent. We also coupled the EMASS-II ion source with a PrinCE Next|480 capillary electrophoresis autosampler and an Orbitrap mass spectrometer, and analyzed this system's performance in terms of sensitivity, reproducibility, and separation performance for separation of tryptic digests, intact proteins, and amino acids. The system produced reproducible analysis of BSA digest; the RSDs of peptide intensity and migration time across 24 runs were less than 20 and 6%, respectively. The system produced a linear calibration curve of intensity across a 30-fold range of tryptic digest concentration. The combination of a commercial autosampler and electrospray interface efficiently separated amino acids, peptides, and intact proteins, and only required 5 μL of sample for analysis.

Graphical Abstract

The commercial and locally constructed versions of the interface provide similar numbers of protein identifications from a Xenopus laevis fertilized egg digest

http://ift.tt/2hGDSc0

SPRi-MALDI MS: characterization and identification of a kinase from cell lysate by specific interaction with different designed ankyrin repeat proteins

Abstract

We report on the direct coupling of surface plasmon resonance imaging (SPRi) with matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) for the investigation of specific, non-covalent interactions, using the example of designed ankyrin repeat proteins (DARPins) and ribosomal protein S6 kinase 2 (RPS6KA2) directly from lysate of SH-SY5Y cells, derived from human bone marrow. Due to an array format, tracing of binding kinetics of numerous DARPins simultaneously and in real time becomes possible. By optimizing both the proteolytic digest directly on the SPRi chip (amount of trypsin, incubation time, and temperature) as well as the MALDI matrix application (concentration of matrix and number of spray cycles), we are able to identify the specific interaction with RPS6KA2 directly from the cell lysate at a surface coverage of only 0.8 fmol/mm².

Graphical Abstract

Workflow of the direct coupling of SPRi with MALDI mass spectrometry

http://ift.tt/2hGF2o7

Phosphoproteomics of colon cancer metastasis: comparative mass spectrometric analysis of the isogenic primary and metastatic cell lines SW480 and SW620

Abstract

The contributions of phosphorylation-mediated signaling networks to colon cancer metastasis are poorly defined. To interrogate constitutive signaling alterations in cancer progression, the global phosphoproteomes of patient-matched SW480 (primary colon tumor origin) and SW620 (lymph node metastasis) cell lines were compared with TiO₂ and immobilized metal affinity chromatography phosphopeptide enrichment followed by liquid chromatography–tandem mass spectrometry. Network analysis of the significantly altered phosphosites revealed differential regulation in cellular adhesion, mitosis, and messenger RNA translational machinery. Messenger RNA biogenesis and splicing, transport through the nuclear pores, initiation of translation, and stability and degradation were also affected. Although alterations in these processes have been associated with oncogenic transformation, control of messenger RNA stability has typically not been associated with cancer progression. Notably, the single phosphosite with the greatest relative change in SW620 cells was Ser2 on eukaryotic translation initiation factor 2 subunit 2, suggesting that SW620 cells translate faster or with greater efficiency than SW480 cells. These broad changes in the regulation of translation also occur without overexpression of eukaryotic translation initiation factor 4E. The findings suggest that metastatic cells exhibit constitutive changes to the phosphoproteome, and that messenger RNA stability and translational efficiency may be important targets of deregulation during cancer progression.

http://ift.tt/2hGEG0u

Identifying known unknowns using the US EPA’s CompTox Chemistry Dashboard

Abstract

Chemical features observed using high-resolution mass spectrometry can be tentatively identified using online chemical reference databases by searching molecular formulae and monoisotopic masses and then rank-ordering of the hits using appropriate relevance criteria. The most likely candidate "known unknowns," which are those chemicals unknown to an investigator but contained within a reference database or literature source, rise to the top of a chemical list when rank-ordered by the number of associated data sources. The U.S. EPA's CompTox Chemistry Dashboard is a curated and freely available resource for chemistry and computational toxicology research, containing more than 720,000 chemicals of relevance to environmental health science. In this research, the performance of the Dashboard for identifying known unknowns was evaluated against that of the online ChemSpider database, one of the primary resources used by mass spectrometrists, using multiple previously studied datasets reported in the peer-reviewed literature totaling 162 chemicals. These chemicals were examined using both applications via molecular formula and monoisotopic mass searches followed by rank-ordering of candidate compounds by associated references or data sources. A greater percentage of chemicals ranked in the top position when using the Dashboard, indicating an advantage of this application over ChemSpider for identifying known unknowns using data source ranking. Additional approaches are being developed for inclusion into a non-targeted analysis workflow as part of the CompTox Chemistry Dashboard. This work shows the potential for use of the Dashboard in exposure assessment and risk decision-making through significant improvements in non-targeted chemical identification.

Graphical abstract

Identifying known unknowns in the US EPA's CompTox Chemistry Dashboard from molecular formula and monoisotopic mass inputs

http://ift.tt/2hD8NZO

Third-ventricle enterogenous cyst presentation mimicking a colloid cyst: uncommon presentation of a rare disease and literature review

Abstract

Enterogenous cysts (ECs) are endodermal lesions resulting from splitting anomalies in the neuroenteric canal. We report the case of a 64-year-old patient who presented with a sudden headache followed by collapse. Brain computed tomography revealed a hyperdense lesion in the anterior part of the third ventricle with obstructive hydrocephalus. A presumptive diagnosis of colloid cyst was made and he underwent a right transcortical approach for lesion resection. The histopathological examination revealed an EC. ECs are common lesions in the cervical-thoracic spine but rare in the supratentorial compartment with only two previously described cases occurring in the third ventricle.

http://ift.tt/2hDcmil

Gender-associated comorbidities in rheumatoid arthritis and their impact on outcome: data from GENIRA

Abstract

GENIRA [Gender in Rheumatoid Arthritis (RA)] is a comprehensive project aimed at studying gender differences in RA patients and how these differences impact on these patient outcomes. We are now reporting such data. Seventy RA patients of each gender were cross-sectionally evaluated following a preestablished protocol. Univariate and multivariate analyses focused in the different gender-associated comorbidity profiles and how they impact in the quality of life and disability of RA patients as assessed by the SF-36 and the Modified Health Assessment Questionnaire (M-HAQ), respectively. Both groups were comparable regarding their main demographic and clinical features. Different comorbidity profiles were found in both genders, with higher frequencies of diabetes mellitus, peptic ulcer, ischemic heart disease, smoking and chronic obstructive pulmonary disease among men and of depression and osteoporosis among women. The M-HAQ was lower in women than in men (0.89 ± 2.6 vs 0.22 ± 0.9, p = 0.04) as there were some sub-scales of the SF-36 [mental health (63.7 ± 22.0 vs 71.8 ± 21.1; p = 0.02), general health (41.3 ± 21.7 vs 50.0 ± 24.3; p = 0.02), physical functioning (PF) (57.7 ± 22.1 vs 67.3 ± 22.7; p = 0.01) and the physical summary component (PSC) (39.3 ± 8.9 vs 42.4 ± 9.3, p = 0.04)]. Multivariate analysis indicated the independent association between depression and osteoporosis rather than gender with the M-HAQ, PSC and PF and of only depression with the MH and GH. Women with RA present significantly worse disability and QOL outcomes than men; these differences can be explained by female gender-associated comorbidities such as depression and osteoporosis rather than gender per se.

http://ift.tt/2hCSSKY

The effects of a skeletal muscle titin mutation on walking in mice

Abstract

Titin contributes to sarcomere assembly, muscle signaling, and mechanical properties of muscle. The mdm mouse exhibits a small deletion in the titin gene resulting in dystrophic mutants and phenotypically normal heterozygotes. We examined the effects of this mutation on locomotion to assess how, and if, changes to muscle phenotype explain observed locomotor differences. Mutant mice are much smaller in size than their siblings and gait abnormalities may be driven by differences in limb proportions and/or by changes to muscle phenotype caused by the titin mutation. We quantified differences in walking gait among mdm genotypes and also determined whether genotypes vary in limb morphometrics. Mice were filmed walking, and kinematic and morphological variables were measured. Mutant mice had a smaller range of motion at the ankle, shorter stride lengths, and shorter stance duration, but walked at the same relative speeds as the other genotypes. Although phenotypically similar to wildtype mice, heterozygous mice frequently exhibited intermediate gait mechanics. Morphological differences among genotypes in hindlimb proportions were small and do not explain the locomotor differences. We suggest that differences in locomotion among mdm genotypes are due to changes in muscle phenotype caused by the titin mutation.

http://ift.tt/2h9poRf

Prophylactic antibiotic treatment following laparoscopic robot-assisted radical prostatectomy for the prevention of catheter-associated urinary tract infections: did the AUA guidelines make a difference?

Abstract

We sought to evaluate the effectiveness of the American Urological Association (AUA) antibiotic prophylaxis guidelines in patients undergoing robot-assisted laparoscopic radical prostatectomy (RALP). Our prospective registry database was reviewed for all RALP cases. The following variables were evaluated: age, associated comorbidities, body mass index (BMI), total operative time, length of stay (LOS), prostate weight, pathological grade and stage. Until 11/2011, RALP patients were treated with antibiotics administered in the operating room and continued until urethral catheter removal. Since 11/2011, all patients were treated with a single intravenous dose of Cephalosporin and Aminoglycoside given within 30 min of surgical incision. The rate of catheter-associated urinary tract infection (CAUTI) was evaluated in both groups. 229 RALP patients were identified. The first 60 patients (26.2%) were treated according to the old protocol (Group 1) while the remaining 169 (73.8%) were treated according to the new protocol (Group 2). Group match was identified in all categories but LOS. Moreover, LOS was found to be longer in Group 1 compared with Group 2 (5.8 vs. 4.5 days, p < 0.001). CAUTI rate was similar in both groups (8.3 vs. 8.9%, respectively, p = 0.89). Logistic regression analysis did not demonstrate any association between treatment protocol and potential risk for CAUTI. Therefore, a single preoperative dose of antibiotics does not increase the rate of CAUTI following RALP compared with prolonged antibiotic treatment. Moreover, it was found to be associated with shorter LOS. Complying with the AUA guidelines may reduce morbidity and medical costs.

http://ift.tt/2hGrjxl

Removal and Recovery of Chromium from Aqueous Solutions by Reduction-Absorption Microreactor

Abstract

A rutin-Cr(III) loaded alginate microspheres, which can act as reduction-adsorption microreactor, was designed to reduce Cr(VI) to Cr(III) and recover it. Different from the rutin-Cr(III) complex in alginate-chitosan microcapsule we previously reported, which can sustained release rutin-Cr(III) and reduce Cr(VI) to Cr(III), this microreactor can not only reduce Cr(VI) but also adsorb/recover Cr(III) in aqueous solution. This microreactor was prepared by loading metal complex of rutin into alginate microsphere. It was found that Cr(VI) was initially reduced to Cr(III) by rutin-Cr(III), and then the product Cr(III) was absorbed in the microspheres. Both Cr(VI) reduction rate and Cr(III) adsorption rate were pH-dependent. Cr(VI) can be completely reduced to Cr(III) at pH 1–4 with a reduction capability of 1.27 (±0.078) mmol/g (pH 1, 4 h). The highest blank alginate microsphere adsorption capacity was 1.82 (±0.042) mmol/g at pH 4. It was assumed that reduction-adsorption was the mechanism of total Cr removal by the reduction-absorption microreactor. Recovery experiment showed that 93% and 98% of Cr(III) can be recovered by EDTA and sodium citrate, respectively.

http://ift.tt/2gTwax2

Sphincter-Preserving Surgery for Low Rectal Cancer: Do We Overshoot the Mark?

Abstract

Purpose

Intersphincteric resection (ISR) is an alternative to abdominoperineal resection (APR) for a selected subset of patients with low rectal cancer, combining equivalent oncological outcome and sphincter preservation. However, functional results are heterogeneous and often imperfect. The aim of the present investigation was to determine the long-term functional results and quality of life after ISR.

Methods

One hundred forty-three consecutive patients who underwent surgery for low rectal cancer were analysed. Sixty patients received ISR and 83 patients APR, respectively. Kaplan-Meier estimate was used to analyse patients' survival. The EORTC QLQ-C30, -C29 and the Wexner score were used to determine functional outcome and quality of life.

Results

ISR and APR were both associated with comparable morbidity and no mortality. Patients' disease- and recurrence-free survival after ISR and APR were similar (p = 0.2872 and p = 0.4635). Closure of ileostomy was performed in 73% of all patients after ISR. Long-term outcome showed a rate of incontinence (Wexner score ≥10) in 66% of the patients. Despite this, patients' quality of life was significantly better after ISR compared to APR in terms of abdominal complaints and psycho-emotional functioning.

Conclusions

ISR is technically feasible with acceptable postoperative morbidity rates. Functional results following ISR are compromised by incontinence as the most important complication. However, long-term quality of life is superior to APR, which should be considered when selecting patients for ISR.

http://ift.tt/2gTuELc

Conversion Surgery Post-Intraperitoneal Paclitaxel and Systemic Chemotherapy for Gastric Cancer Carcinomatosis Peritonei. Are We Ready?

Abstract

Peritoneal metastasis is common in gastric cancer. It is difficult to treat and carries a poor prognosis. Intraperitoneal (IP) delivery of chemotherapy can attain a higher drug exposure in the peritoneal cavity but with reduced systemic toxicity. Therefore, we hypothesized that IP paclitaxel with systemic chemotherapy would be clinically beneficial for gastric cancer with peritoneal metastases. Patients with unresectable and/or recurrent gastric adenocarcinoma with peritoneal dissemination and/or positive peritoneal washing cytology were recruited. They underwent eight cycles of IP paclitaxel and systemic XELOX. The primary endpoint was 1-year overall survival rate and secondary endpoints were safety, response rate, and peritoneal cytological response. Patients who subsequently had no distant metastases and two consecutive negative peritoneal cytologies underwent conversion gastrectomy if there was no macroscopic evidence of peritoneal disease at diagnostic laparoscopy. Twenty-two patients were enrolled, receiving at least one cycle of IP paclitaxel at the time of reporting (data cutoff—March 11, 2016). The median number of cycles was 7.5. The median overall survival was 18.8 months, and the 1-year survival rate was 72.2%. One patient died of neutropenic sepsis. Of 19 evaluable patients with measurable disease, 7 (36.8%) achieved PR, 8 (42.1%) achieved SD, and 4 (21.1%) experienced PD. Peritoneal cytology turned negative in 11 of 17 (64.7%) patients. Six patients underwent conversion gastrectomy (4 R0, 2 R1) with a median survival of 21.6 months (range = 8.7–29.9 months). XELOX and IP paclitaxel appears to be an effective regimen in gastric cancer with peritoneal metastases. Conversion gastrectomy may be considered in patients with a favorable response.

http://ift.tt/2hX06WH

Risk factors for postoperative mortality in congenital diaphragmatic hernia: a single-centre observational study

Abstract

Background

The management of congenital diaphragmatic hernia (CDH) is a major challenge. The mortality is dependent on associated malformations, the severity of pulmonary hypoplasia, pulmonary hypertension and iatrogenic lung injury associated with aggressive mechanical ventilation. The aims of the study were to investigate the mortality over time in a single paediatric surgical centre, to compare the results with recent reports and to define the risk factors for mortality.

Methods

The medical records of infants with CDH from two time periods: 1995–2005 and 2006–2016 were reviewed. Cox regression was used for statistical analysis.

Results

The study included 113 infants. The mortality rate was significantly decreased in the later time period, compared to the earlier, 4.4 and 17.9%, respectively. At the early time period five patients (7.5%) were treated with ECMO and in the later time period ECMO was used in three patients (6.5%). The mortality in ECMO-treated patients was 50% in both time periods. Prenatal diagnosis, intrathoracic liver, low Apgar score and low birth weight were defined as independent risk factors for mortality.

Conclusion

Despite no significant differences in the incidence of independent risk factors and the use of ECMO between the two time periods, mortality decreased over time. The mortality was lower than previously reported. The results indicate that there are many important factors involved in a successful outcome after CDH repair. Large multicentre studies are necessary to define those critical factors and to determine optimal treatment strategies.

http://ift.tt/2hG3vJU

Thoracic outlet syndrome: wide literature for few cases. Status of the art

Abstract

Despite its low prevalence and incidence, considerable debate exists in the literature on thoracic outlet syndrome (TOS). From literature analysis on nerve entrapments, we realized that TOS is the second most commonly published entrapment syndrome in the literature (after carpal tunnel syndrome) and that it is even more reported than ulnar neuropathy at elbow, which, instead, is very frequent. Despite the large amount of articles, there is still controversy regarding its classification, clinical picture, diagnostic objective findings, diagnostic modalities, therapeutical strategies and outcomes. While some experts believe that TOS is underrated, overlooked and very frequent, others even doubt its existence as a nosological entity. In the attempt to shed more light on this condition, we performed a systematic review of the literature and report evidence and opinions around this controversial subject. Only articles focused on neurogenic TOS were considered. Understanding the status of the art and the underlying reasons of doubts and weaknesses could help clinical practice and set the stage for future research.

http://ift.tt/2hGcZF2

Laparoscopic-assisted versus open total gastrectomy for Siewert type II and III esophagogastric junction carcinoma: a propensity score-matched case-control study

Abstract

Background

Few studies have evaluated the outcomes of laparoscopic-assisted total gastrectomy (LATG) for Siewert type II and III adenocarcinoma of the esophagogastric junction (AEG). Thus, aim of this study was to investigate the surgical outcomes of LATG for Siewert type II and III AEG.

Methods

Clinical data for 700 Siewert type II and III AEG patients were analyzed retrospectively. The short- and long-term outcomes were compared between the matched groups using a propensity score matching method.

Results

Before matching, the comorbidities, Siewert classifications and tumor invasion depths significantly differed between the LATG and open total gastrectomy (OTG) groups. After matching, the clinicopathologic characteristics were well balanced between the two groups. In addition, after matching, decreases in the operative time, amount of blood loss, time to resumption of a semifluid diet, and length of hospital stay and an increased number of lymph nodes (LNs) retrieved were observed in the LATG group compared with the OTG group. Further, a significantly higher 3-year overall survival rate (81.3 vs 66.4%; P = 0.011) and disease-free survival rate (77.5 vs 63.8%; P = 0.040) were observed for the Siewert type II AEG patients in the LATG group compared with those in the OTG group; however, the survival rates were similar for the Siewert type III AEG patients in the two groups (P = 0.853 and P = 0.844, respectively).

Conclusions

LATG is associated with better short-term outcomes for Siewert type II and III AEG. In addition, it may result in an increased number of retrieved LNs and better long-term survival for Siewert type II AEG patients in particular.

http://ift.tt/2hCHEWR

Management of super–super obese patients: comparison between one anastomosis (mini) gastric bypass and Roux-en-Y gastric bypass

Abstract

Background

Gastric bypass can be technically challenging in super–super obese patients. Both Roux-en-Y gastric bypass (RYGB) and one anastomosis (mini) gastric bypass (OAGB/MGB) have been described in these patients, but direct comparisons are lacking. The purpose of this study was to compare the early outcomes with these two procedures in patients with body mass index (BMI) of ≥60 kg/m² in our unit.

Methods

We identified all super–super obese patients who underwent either OAGB/MGB or RYGB from our prospectively maintained database. Information was also obtained from the case notes and from hospital computerized records. We obtained data regarding patient demographics, operative details, complications, and weight loss, in both groups, and compared them using standard statistical methods.

Results

This study compares our results with 19 OAGB/MGB and 47 RYGB super–super obese patients performed in our unit between October 2012 and June 2015. OAGB/MGB group patients had a significantly higher weight and body mass index. There was no mortality or major complication in either group. There were two late complications in the OAGB/MGB group compared to six in the RYGB group. One patient in the OAGB/MGB group needed conversion to RYGB for persistent reflux symptoms. OAGB/MGB patients achieved a significantly higher EWL of 70.4% at 2 years compared to 57.1% in the RYGB group. The difference between TWL of 44.4 and 33.4%, respectively, was also significant at 2 years. TWL of 43.0 and 29.3%, respectively, in OAGB/MGB and RYGB groups at 18 months was also significantly different, but the difference in EWL at 18 months did not reach significance.

Conclusion

One anastomosis (mini) gastric bypass yields superior weight loss at 18 and 24 months in comparison with Roux-en-Y gastric bypass in patients with BMI of ≥60 kg/m². Findings need confirmation in larger randomized studies.

http://ift.tt/2hGdnDC

LINX ® magnetic esophageal sphincter augmentation versus Nissen fundoplication for gastroesophageal reflux disease: a systematic review and meta-analysis

Abstract

Background

The LINX^® magnetic sphincter augmentation system (MSA) is a surgical technique with short-term evidence demonstrating efficacy in the treatment of medically refractory or chronic gastroesophageal reflux disease (GERD). Currently, the Nissen fundoplication is the gold-standard surgical treatment for GERD. We are the first to systematically review the literature and perform a meta-analysis comparing MSA to the Nissen fundoplication.

Methods

A comprehensive search of electronic databases (e.g., MEDLINE, EMBASE, SCOPUS, Web of Science and the Cochrane Library) using search terms "Gastroesophageal reflux or heartburn" and "LINX or endoluminal or magnetic" and "fundoplication or Nissen" was completed. All randomized controlled trials, non-randomized comparison study and case series with greater than 5 patients were included. Five hundred and forty-seven titles were identified through primary search, and 197 titles or abstracts were screened after removing duplicates. Meta-analysis was performed on postoperative quality of life outcomes, procedural efficacy and patient procedural satisfaction.

Results

Three primary studies identified a total of 688 patients, of whom 273 and 415 underwent Nissen fundoplication and MSA, respectively. MSA was statistically superior to LNF in preserving patient's ability to belch (95.2 vs 65.9%, p < 0.00001) and ability to emesis (93.5 vs 49.5%, p < 0.0001). There was no statistically significant difference between MSA and LNF in gas/bloating (26.7 vs 53.4%, p = 0.06), postoperative dysphagia (33.9 vs 47.1%, p = 0.43) and proton pump inhibitor (PPI) elimination (81.4 vs 81.5%, p = 0.68).

Conclusion

Magnetic sphincter augmentation appears to be an effective treatment for GERD with short-term outcomes comparable to the more technically challenging and time-consuming Nissen fundoplication. Long-term comparative outcome data past 1 year are needed in order to further understand the efficacy of magnetic sphincter augmentation.

http://ift.tt/2hCEfqU

Bezerromycetales and Wiesneriomycetales ord. nov. (class Dothideomycetes), with two novel genera to accommodate endophytic fungi from Brazilian cactus

Abstract

During a survey of endophytic fungi from the cactus Tacinga inamoena in a Brazilian tropical dry forest (Caatinga) some undescribed ascomycetous fungi were isolated. These fungi are characterized by superficial and immersed, globose to subglobose, smooth or hairy ascomata, bitunicate asci, and muriformly septate, ellipsoidal ascospores. Multigene phylogenetic analyses using sequences from partial ITS, SSU and LSU nrDNA and the translation elongation factor 1-alpha gene (tef1) demonstrated a monophyletic clade accommodating these endophytic fungi in the class Dothideomycetes, closely related to the order Tubeufiales. Based on morphological features and phylogenetic analyses, these fungi could not be placed in the order Tubeufiales, in the new order Wiesneriomycetales, or any other known genus in the class Dothideomycetes. Thus, two new genera (Bezerromyces, with B. brasiliensis and B. pernambucoensis, and Xiliomyces with X. brasiliensis), a new family (Bezerromycetaceae) and a new order (Bezerromycetales) are introduced to accommodate these novel taxa. Our phylogenetic analyses also demonstrated that the clade accommodating Wiesneriomycetaceae represents a new order, here introduced as Wiesneriomycetales.

http://ift.tt/2hDtUZu

Radiation-induced rectovaginal fistulas in locally advanced gynaecological malignancies—new patients, old problem?

Abstract

Purpose

Radiation-induced rectovaginal fistula (RI-RVF) is a chronic and serious condition with a significant influence on quality of life. The aim of this study is to evaluate the results of surgical treatment of rectovaginal fistulas of patients previously undergoing radiotherapy.

Methods

Fifty patients treated in the Gynaecological Radiotherapy Unit for gynaecologic malignancy and in the Department of General and Colorectal Surgery for RI-RVF between 2003 and 2013 were enrolled into a prospectively maintained database and underwent regular follow-up examinations in an outpatient clinic, during which surgical outcomes were assessed.

Results

Median age was 60 years (range 40–84 years). Cervical cancer was the most common cause of radiotherapy. Median time of fistula development after radiotherapy was 20 months (range 5–240 months). In 48 (96%) patients, only faecal diversion could be performed, while two patients underwent rectal resection. The fistula healed in six patients. Factors that correlated with fistula healing were a distance from the anal verge above 7 cm (p = 0.007 OR 18 95%CI 2.2609–14.3062) and creation of loop ileostomy (p = 0.08 OR 17 95%CI 1.2818–23.9701), whereas a prolonged course of radiotherapy of more than 6 weeks (p = 0.047) correlated negatively. In multivariate analysis, only distance from the anal verge remained significant (p = 0.031 OR 2.35 95%CI 1.0422–5.2924).

Conclusions

The treatment of radiation-induced rectovaginal fistulas needs to be tailored individually to each patient. Faecal diversion remains the simplest and safest method of treating RI-RVF, especially in the group of patients who cannot undergo complicated surgical procedures, and offers acceptable quality of life.

http://ift.tt/2hCAOQZ

Fall Composition of Storage Lipids is Associated with the Overwintering Strategy of Daphnia

Abstract

Diapause, which occurs through the production of dormant eggs, is a strategy used by some zooplankton to avoid winter months of persistent low temperatures and low food availability. However, reports of active zooplankton under the ice indicate that other strategies also exist. This study was aimed at evaluating whether the composition of storage lipids in the fall differs between diapausing and active overwintering Daphnia. We assessed the quantity of storage lipids and fatty acid (FA) composition of Daphnia species, along with FA content of seston, in six boreal, alpine and subarctic lakes at the onset of winter, and evaluated the association between storage lipids and Daphnia overwintering strategy. We found that active overwintering Daphnia had >55% body fat and the highest FA concentrations. Polyunsaturated FA, especially stearidonic acid (18:4n-3; SDA) and high ratios of n-3:n-6, were preferentially retained to a greater extent in active overwintering Daphnia than in those that entered diapause. Daphnia FA composition was independent of that of the seston diet, indicating that Daphnia adjusted their storage lipids according to the physiological requirements of a given overwintering strategy. The occurrence of an active overwintering strategy has consequences for zooplankton community structure, and can have important implications for the transfer of high-quality energy at higher trophic levels.

http://ift.tt/2hDjBEL

Anti-obesity effects of resveratrol: comparison between animal models and humans

Abstract

The prevalence of obesity has increased rapidly during recent years and has reached epidemic proportions. As a result, the scientific community is interested in active biomolecules which are naturally present in plants and foodstuffs and may be useful in body weight management. In recent years, polyphenols have made up one of the most frequently studied groups among these molecules. Numerous studies have been carried out on animals to analyse the potential anti-obesity effects of resveratrol, a non-flavonoid polyphenol, and a general consensus concerning the body-fat-lowering effect of this compound exists. By contrast, studies in humans have been few so far. Moreover, in these studies, the effectiveness of resveratrol is low. The aims of the present review are to summarize the results reported so far on this topic and to justify the differences observed between animals and humans. It seems that the reduced response to resveratrol in humans cannot be attributed to the use of lower doses in humans because the doses that induce body-fat-lowering effects in rodents are in the same range as those used in human studies. With regard to the experimental period length, treatments were longer in animal studies than in human studies. This can be one of the reasons contributing to the reduced responses observed in humans. Moreover, animals used in the reported studies are young while volunteers participating in human studies are adults, suggesting that resveratrol may be more efficient in young individuals. In addition to differences in the experimental designs, metabolic differences between animals and human cannot be discarded.

http://ift.tt/2hFWtF5