Benzaldehyde thiosemicarbazone derivatives against replicating and nonreplicating Mycobacterium tuberculosis
Benzaldehyde thiosemicarbazone derivatives against replicating and nonreplicating <i>Mycobacterium tuberculosis</i>, Published online: 21 January 2019; doi:10.1038/s41429-019-0140-9
Benzaldehyde thiosemicarbazone derivatives against replicating and nonreplicating Mycobacterium tuberculosisBiodiesel has been renowned as potential and alternative fuel for years. In order to improve the quality of the conventional fossil fuels, biodiesel, and air pollution from combustion, additives are essential to exploit. In this study, the uses of cerium oxide (CeO2) nanoparticle additive for B20 fuel in a diesel engine are investigated. The CeO2 nanoparticles with cetyl-trimethyl ammonium bromide are doped into the B20 fuel by using ultrasonicator. The purpose of the experimental work was adopted to enhance engine combustion and reduce the emissions with an approach of CeO2 nanoparticle additive. The experiment was conducted on a diesel engine using different propagation of CeO2 nanoparticle in blended mahua methyl ester fuel such as B20 + CeO2 50 ppm, B20 + CeO2 100 ppm, and B20 + CeO2 150 ppm. The obtained results are compared with the diesel and B20 fuels. The minor changes are obtained in B20 fuel properties due to the addition of CeO2 nanoparticles. The performance of brake thermal efficiency and combustion of pressure data is observed to be enhanced by the addition of a metal-based additive. The CO, HC, and smoke are decreased for B20 fuel with nanoparticles. The NOx is reduced by dosing the CeO2 due to the oxidation of unburned CeO2 in the exhaust.
Right ventricular (RV) hypoplasia may develop secondary to pulmonary or tricuspid valve atresia. These patients are usually symptomatic early in life and need prompt intervention. Isolated RV hypoplasia is a rare congenital heart disease. We report a case of 23-year-old twins who have been monitored for the last 14 years for isolated right ventricular hypoplasia. ECHO and MRI studies showed a small, heavily trabeculated, nonapex-forming RV and mild tricuspid valve insufficiency. The girl has a patent foramen ovale (PFO). Otherwise, the cardiac anatomy and function was normal. They have both been completely asymptomatic from the cardiac standpoint. The family history is remarkable for death of father at the age of 30 years with autopsy suggestive of a hypoplastic RV. The paternal uncle also died at the age of 46 years, and his son has an unidentified congenital heart disease. The family history appears to suggest an autosomal dominant pattern of inheritance with variable expressivity. However, the chromosome microarray analysis of the twins did not identify any variations of clinical significance.
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Fine roots play a significant role in regulating the biogeochemical cycles of forest ecosystems, but how fine root biomass (FRB), production (FRP) and turnover rates (FRT) vary with forest origins remains not well understood.
The meta-analysis approach was used to examine the differences in FRB, FRP and FRT between plantations and their adjacent natural forests based on 238 cases reported in 45 published studies.
FRB and FRP were 36.5% and 36.0% lower, respectively, in plantations than in natural forests. FRT was 22.4% higher in plantations relative to natural forests. The decrease in FRB in plantations relative to natural forests varied among plantations with different plant genera and root diameter classes. The general patterns for FRP and FRT in relation to various factors (biogeographic zone, leaf form, leaf seasonality, plant genus in plantations, and root diameter class) did not differ among the groups. The difference in FRB between plantations and natural forests was positively correlated with stand age but negatively related with soil total nitrogen concentration, the difference in FRP was positively affected by diameter at breast height (DBH) and soil pH, and the difference in FRT was positively affected by DBH, tree height, soil bulk density and soil pH and negatively affected by soil organic carbon and total nitrogen concentration.
FRB, FRP and FRT exhibit significant differences between plantations and natural forests and that these differences are partially caused by shifts in stand characteristics and variations in soil properties.
Pseudomonas orientalis and Chaetomium cupreum isolated from metal(oid)s-contaminated soil were characterized to evaluate their role in plant growth promotion and enhance the tolerance of Eucalyptus globulus to copper stress.
We evaluated minimum inhibitory concentration and explored plant-promoting traits under copper stress. Moreover, changes in morphology and the accumulation of metals on the cell surface were determined by scanning electron microscopy images coupled with energy dispersive x-ray spectroscopy (SEM-EDX). The effect of inoculation with P. orientalis and C. cupreum on E. globulus plants established in soils contaminated with copper was determined through root and shoot biomass and antioxidant response.
Both strains showed high tolerance to metal(oid)s, whereas phosphate solubilization was only detected in P. orientalis. Under copper stress, C. cupreum presented a higher production rate of siderophores and indole acetic acid (4.5 mm day−1, 15.042 μg mL−1). SEM images and EDX analysis reflected cellular changes in fungus and proved biosorption of copper. Inoculation of P. orientalis and C. cupreum on Eucalyptus globulus plants significantly increased plant growth and mitigated the toxic effects of copper.
According to these results, both microorganisms contribute positively to stimulated plant growth and to decreasing stress caused by high concentrations of copper in soil, especially C. cupreum.
Our study aimed to evaluate the diagnostic performance of rectal magnetic resonance imaging (MRI) for local restaging in patients with non-metastatic locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy (CRT) using surgical histopathology of total mesorectal excision as the reference standard.
Ninety-five patients with LARC who underwent rectal MRI after CRT between January 2014 and December 2016 were included. Accuracy, sensitivity, specificity, positive, and negative predictive value for local staging regarding T-stage, N-stage, circumferential resection margin, and MRI tumor regression grade (ymriTRG) were calculated, and inter-test agreements were assessed.
22/95 (23.2%) patients had radiological complete response (rCR), whereas 20/95 (21.1%) had pathological complete response (pCR). Among the patients with pCR, 11/20 (55%) had rCR. Fair agreement was demonstrated between ymriTRG and pathological TRG (ypTRG) (κ = 0.255). The sensitivity and specificity for detection of pCR were 61.1% (95% CI 35.7–82.7) and 89.6% (95% CI 80.6–95.4). For the detection of ypTRG grades 1 and 2, the corresponding values were 67.2% (95% CI 54.3–78.4) and 51.6 (95% CI 33.1–69.8). The accuracy of ymriTRG was 24.2% (95% CI 15.6–32.8). Inter-test agreement in TRG between MRI and pathology was overall fair (κ = 0.255) and slight (κ = 0.179), if TRG 1 + 2.
Qualitative assessment on MRI for diagnosing pCR showed moderate sensitivity and high specificity, whereas the diagnosis of TRG had moderate sensitivity and low specificity with slight to fair inter-test agreement when compared with pathological specimens.
This study aimed to evaluate the clinical and radiological findings of hemorrhagic hepatic cysts with enhancing mural nodules.
The radiology databases of five facilities were retrospectively searched for reports indicating hemorrhagic hepatic cysts or hepatic cystic tumors. Cases of hemorrhagic hepatic cysts with enhancing mural nodules based on pathological or radiological findings were identified and reviewed.
We included 14 cases (11 female and 3 male) with a mean patient age of 72.6 years. Up until the enhancing mural nodules were detected, the cysts had decreased in size in all ten cases for which radiological imaging was available for a period of > 3 years previous to detection. Dynamic contrast-enhanced CT or MRI showed focal enhancement in the early phase and progressive centrifugal enhancement in the delayed phase in all 16 mural nodules ≥ 10 mm in diameter. Thirteen of 14 MRI assessable enhancing mural nodules ≥ 10 mm in diameter showed a hypointense rim with central hyperintensity on T2-weighted imaging. All cases showed calcification of the cyst wall. In the three referred cases, 18F-fluorodeoxyglucose (FDG) positron emission tomography/CT demonstrated no intense FDG uptake in the enhancing mural nodules. In the four resected cases, histopathology of the enhancing mural nodules revealed neovascularization within an organized hematoma, including extensive dilated vessels and hemangioma-like lesions.
Features including a decrease in cyst size, a progressive centrifugal enhancing pattern on dynamic contrast-enhanced CT or MRI, a hypointense rim with central hyperintensity on T2-weighted MRI, and cyst wall calcification may indicate a hemorrhagic hepatic cyst.
Chronic low-grade, systemic inflammation is a well-characterized risk factor in the development of chronic metabolic diseases, such as cardiovascular disease, type 2 diabetes, and metabolic syndrome. Diet could be an effective strategy for reducing inflammation associated with chronic disease. While anti-inflammatory properties of isolated dietary bioactive and functional foods have been routinely studied, the evaluation of dietary patterns on inflammation warrants further review—especially given the recent inclusion of dietary pattern recommendations into dietary guidelines and policies. Therefore, the objective of this narrative review is to examine current evidence linking diet to low-grade, systemic inflammation within the context of chronic disease. Specifically, we provide an update on the findings from human trials that have characterized anti-inflammatory properties of dietary patterns, defined by various methods and indexes. Given the complexity of interpreting results from dietary pattern analysis, we further present recent evidence on the anti-inflammatory roles of isolated bioactive nutrients and functional foods that are common components of distinct dietary patterns, in addition to considerations for interpreting dietary pattern research, population-specific dietary recommendations, and future studies. Overall, we observe a vast range of variability in the evidence from observational studies that have evaluated the relationships between healthy dietary patterns and inflammatory markers. These studies highlight the need for additional intervention studies with study designs that account for metabolic status, diversity in populations, breadth of inflammatory measurements, fasting vs. postprandial effects of diet, and control of confounding factors (e.g., genotype, microbiome profiles, and dietary adherence) in order to better understand the effect that diet has, as a whole, on inflammation. These strategies will help to strengthen diet recommendations aimed at reducing inflammation and chronic disease risk.
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Publication date: Available online 19 January 2019
Source: Behavioural Brain Research
Author(s): Darren Story, Emily Chan, Nikolas Munro, Julien Rossignol, Gary L. Dunbar
Publication date: Available online 18 January 2019
Source: Behavioural Brain Research
Author(s): Alisa Pajser, Aaron Limoges, Charday Long, Charles L. Pickens
Previous research in male Long Evans rats has shown a relationship between low voluntary alcohol consumption and high conditioned fear after a single training session. Here, we determined whether chronic intermittent access (CIA) to alcohol during adolescence/early adulthood or during adulthood would alter or be associated with auditory-cued conditioned fear levels using an extended training fear incubation procedure. This training procedure leads to low fear soon after training that grows over one month. Rats received 6 weeks of CIA to 20% alcohol or water from PND 26–66. Ten or eleven days later, the rats began behavioral testing that included 10 sessions of tone-shock pairings. Rats then received 4 weeks of CIA exposure during the 1-month fear incubation period and were tested for conditioned fear 6 days after the end of alcohol access. We found no evidence that voluntary alcohol consumption during adolescence/early adulthood or adulthood altered fear expression. However, we found that rats that consumed more alcohol during early adulthood (PND 54-66) had lower fear than low-consumption rats on day 1 of conditioned fear training and in the day 2 and 1-month tests. This extends associations we previously found between individual differences in alcohol consumption and conditioned fear to a different fear conditioning procedure. Combined with our previous data that show that the rate of instrumental extinction is associated with both alcohol consumption and conditioned fear, these data provide further support for the generality and reliability of a pair of phenotypes that encompass a wide variety of learning traits.
Background. Previously, it was demonstrated that serum levels of tumor markers, CEA and CA19-9, correlated with chemotherapy. Consequently, it has been hypothesized that dynamic monitoring of changes in these markers may predict the shrinkage or growth of colorectal cancers. To test this hypothesis, we analyzed CEA and CA19-9 serum levels in patients with advanced colorectal cancer who received cetuximab in combination with chemotherapy. These levels were evaluated at various time points to identify their potential to serve as early efficacy predictors during treatment and early predictors of disease progression. Patients and Methods. Measurements of tumor markers, CEA and CA 19-9, in patients with metastatic colorectal cancer () who received cetuximab plus folinic acid, fluorouracil, and oxaliplatin or irinotecan (FOLFOX4/FOLFIRI) as a first-line treatment at our center were retrospectively analyzed. These levels were also compared with objective responses according to the World Health Organization criteria. Initially, 65 patients had elevated CEA levels (>5 ng/ml), and 59 patients had elevated levels of CA19-9 (>37 U/ml). A total of 172 cycles and 165 cycles of computed tomography/magnetic resonance imaging observations were available for review from these two patient groups. Results. After completing three cycles of treatment, the best diagnosis of cetuximab resistance was achieved when CEA increased by 35% (efficacy, 83.33%; sensitivity, 75.41%) and when CA19-9 increased by 28% (efficacy, 80.00%; sensitivity, 84.31%). Next, the efficacy of cetuximab at the time of diagnosis (at the first imaging examination/after three cycles of treatment) was evaluated after the first cycle of chemotherapy. When CEA decreased by 60% from its baseline level, the best effective rate and sensitivity were observed (63.64% and 80.95%, respectively). Similarly, when CA19-9 was 45% lower than its baseline level, the best effective rate and sensitivity were observed (84.21% and 93.18%, respectively). To evaluate progression-free survival (PFS), levels of both CEA and CA19-9 were evaluated after the third cycle of chemotherapy. Increases of 35% and 28%, respectively, resulted in a shorter PFS period compared with the other patients (3.15 months vs. 9.10 months, respectively; ). Conversely, when the evaluation was performed after the first cycle of chemotherapy, patients exhibiting a 60% decrease in CEA and a 45% decrease in CA19-9 had a longer PFS period (11.13 months vs. 8.10 months, respectively; ).Conclusions. CEA and CA19-9 are useful indicators of therapeutic curative effect from cetuximab combined with first-line chemotherapy. These markers also helped assess cetuximab resistance and served as early predictors of initial treatment effectiveness. Furthermore, a simultaneous increase or decrease in the levels of both indicators was consistent with the observed differences in PFS.
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Real-World Outcomes of Adjuvant Chemotherapy for Node-Negative and Node-Positive HER2-Positive Breast Cancer.
J Natl Compr Canc Netw. 2019 Jan;17(1):47-56
Authors: Veitch Z, Khan OF, Tilley D, Ribnikar D, Kostaras X, King K, Tang P, Lupichuk S
Abstract
Background: Comparative real-world outcomes for patients with HER2-positive (HER2+) breast cancer receiving adjuvant trastuzumab outside of clinical trials are lacking. This study sought to retrospectively characterize outcomes for patients with node-negative and node-positive breast cancer receiving adjuvant trastuzumab in combination with docetaxel/cyclophosphamide (DCH), docetaxel/carboplatin/trastuzumab (TCH), or fluorouracil/epirubicin/cyclophosphamide followed by docetaxel/trastuzumab (FEC-DH) chemotherapy in Alberta, Canada, from 2007 through 2014. Methods: Disease-free survival and overall survival (OS) analyses for node-negative cohorts receiving DCH (n=111) or TCH (n=371) and node-positive cohorts receiving FEC-DH (n=146) or TCH (n=315) were compared using chi-square, Kaplan-Meier, or Cox multivariable analysis where appropriate. Results: Median follow-up was similar in node-negative (63.9 months) and node-positive (69.0 months) cohorts. The 5-year OS rates in patients with node-negative disease receiving DCH or TCH were similar (95.2% vs 96.9%; P=.268), whereas 5-year OS rates were higher but nonsignificant for patients with node-positive disease treated with FEC-DH compared with TCH (95.2% vs 91.4%; P=.160). Subgroup analysis of node-positive cohorts showed significantly improved OS with FEC-DH versus TCH in patients with estrogen receptor (ER)/progesterone receptor (PR)-positive breast cancer (98.3% vs 91.6%, respectively; P=.014). Conversely, patients with ER/PR-negative disease showed a nonsignificant trend toward higher OS rates with TCH versus FEC-DH (91.6% vs 83.3%, respectively; P=.298). Given the retrospective design, we were unable to capture all potential covariates that may have impacted treatment assignment and/or outcomes. Furthermore, cardiac toxicity data were unavailable. Conclusions: Survival rates of patients with HER2+ breast cancer in our study are comparable to those seen in clinical trials. Our findings support chemotherapy de-escalation in patients with node-negative disease and validate the efficacy of FEC-DH in those with node-positive disease.
PMID: 30659129 [PubMed - in process]
Managing epilepsy in austerity - Evaluating the utility and value of the epilepsy specialist nurse in an open access model of service delivery. Aneurin Bevan Epilepsy Specialist Team (A.B.E.S.T.).
Seizure. 2019 Jan 11;65:98-100
Authors: John K, Tailor S, Anderson J, Lawthom C
Abstract
PURPOSE: Healthcare organisations in the UK primarily measure clinical activity from data collected on numbers of attendances at outpatient clinics, inpatient admissions and procedures performed etc. Telephone contacts with patients are not typically measured as clinical activity. This service evaluation examines the utility and value of the Epilepsy Specialist Nurse (ESN) within an innovative 'Open Access Model', giving a breakdown of clinical workload and outcomes.
METHODS: A retrospective service evaluation analysing all patient encounters made by the ESN and their outcomes, over a 3-month period from the 01/02/2017 to 30/04/2017.
RESULTS: During the 3-month data collection period there were 620 patient encounters with 251 different patients. Nurse-led clinic appointments and telephone calls were the two most common types of encounter. Eighteen percent of ESN time was spent on the phone directly addressing patient concerns (368 encounters). Of these calls, 72% led to prevention of a clinic appointment (268 appointments avoided) while only 22% needed a subsequent clinic appointment. The most common outcome of telephone encounters was 'medication management' (25%).
CONCLUSIONS: The evaluation demonstrates that timely intervention by telephone reduces the need for outpatient appointments and leads to treatment changes being implemented quickly to address individual need.
PMID: 30660000 [PubMed - as supplied by publisher]
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Psychiatric complications after epilepsy surgery… but where are the psychiatrists?
Epilepsy Behav. 2019 Jan 15;:
Authors: Fasano RE, Kanner AM
Abstract
In patients with refractory epilepsy, there is a significant risk of postoperative psychiatric complications after epilepsy surgery. The main risk factors for this phenomenon include a lifetime or family history of psychiatric illness; these risk factors can be easily identified through a preoperative evaluation performed by a psychiatrist. Despite this, very few comprehensive epilepsy centers include a psychiatrist on the treatment team. Preoperative evaluations often fail to identify patients at risk of postoperative psychiatric complications, thus missing the opportunity to counsel and prophylactically treat patients at risk. In this article, we review the risk factors for the development of postoperative psychiatric complications and discuss the reasons why epilepsy centers continue to perform presurgical evaluations without psychiatrists. Additionally, we provide practical solutions for neurologists in the identification and management of postoperative psychiatric disorders. This article is part of the Special Issue entitled "Obstacles of treatment of psychiatric comorbidities in epilepsy".
PMID: 30658895 [PubMed - as supplied by publisher]
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Progress in the Field of Micro-Electrocorticography.
Micromachines (Basel). 2019 Jan 17;10(1):
Authors: Shokoueinejad M, Park DW, Jung YH, Brodnick SK, Novello J, Dingle A, Swanson KI, Baek DH, Suminski AJ, Lake WB, Ma Z, Williams J
Abstract
Since the 1940s electrocorticography (ECoG) devices and, more recently, in the last decade, micro-electrocorticography (µECoG) cortical electrode arrays were used for a wide set of experimental and clinical applications, such as epilepsy localization and brain⁻computer interface (BCI) technologies. Miniaturized implantable µECoG devices have the advantage of providing greater-density neural signal acquisition and stimulation capabilities in a minimally invasive fashion. An increased spatial resolution of the µECoG array will be useful for greater specificity diagnosis and treatment of neuronal diseases and the advancement of basic neuroscience and BCI research. In this review, recent achievements of ECoG and µECoG are discussed. The electrode configurations and varying material choices used to design µECoG arrays are discussed, including advantages and disadvantages of µECoG technology compared to electroencephalography (EEG), ECoG, and intracortical electrode arrays. Electrode materials that are the primary focus include platinum, iridium oxide, poly(3,4-ethylenedioxythiophene) (PEDOT), indium tin oxide (ITO), and graphene. We discuss the biological immune response to µECoG devices compared to other electrode array types, the role of µECoG in clinical pathology, and brain⁻computer interface technology. The information presented in this review will be helpful to understand the current status, organize available knowledge, and guide future clinical and research applications of µECoG technologies.
PMID: 30658503 [PubMed]
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Pitfalls of Diagnosing Left Lower Quadrant Pain Causes: Making the Uncommon Common Again.
Am J Case Rep. 2019 Jan 19;20:78-82
Authors: Saliba C, Diab SH, Nicolas G, El Sayegh JS, Osman D, Azzo JM, Dabbous A, Hmadeh H, Wehbe A, Haidar Ahmad H
Abstract
BACKGROUND Left-sided acute appendicitis, although well described in the literature, is still an easily missed diagnosis. Midgut malrotation and situs inversus are 2 known leading conditions that contribute to misdiagnosis of appendicitis. CASE REPORT Here is the case of a 27-year-old male without any previous medical history, who presented with left lower quadrant tenderness and was misdiagnosed with gastroenteritis as an outpatient and sent home; the patient presented the next day to the emergency department where he was found to have acute appendicitis with situs inversus. He underwent laparoscopic appendectomy where a phlegmon was identified. Pathology came back as peri-appendiceal mucocele with no signs of malignancy. CONCLUSIONS This case report aimed to revisit the idea of left-sided acute appendicitis and discuss the management of a perforated appendiceal mucocele contained by a phlegmon.
PMID: 30659166 [PubMed - in process]
A case of thoracoscopic medial basal segmentectomy.
Int J Surg Case Rep. 2019 Jan 11;55:15-17
Authors: Kawakita N, Toba H, Sakiyama S, Tsuboi M, Takizawa H, Tangoku A
Abstract
INTRODUCTION: Isolated resection of the medial basal segment (S7) is uncommon because of its small volume, and S7 segmentectomy is considered to be difficult due to anatomical variation. We report a case of successful thoracoscopic S7 segmentectomy.
PRESENTATION OF CASE: A 56-year-old man was referred to our hospital with suspected pulmonary metastasis of rectal cancer. A 6-mm nodule was detected in S7. A7 and B7 branched from the basal segmental artery and bronchus, respectively, to run ventral to the inferior pulmonary vein. This made it possible to isolate A7 and B7 by an approach via the interlobar fissure. In addition, V7a and V7b were easily isolated from inferior pulmonary vein. The intersegmental plane was indicated by V7b and was transected along a demarcation line identified by using selective oxygenation via B7.
DISCUSSION: B7 most commonly branches from the basal bronchus and A7 from the basal artery to run ventral to the inferior pulmonary vein. With this anatomical type, when the surgeon approaches via the interlobar fissure during surgery, A7 is identified first, B7 is seen behind A7, and the IPV is posterior to B7. Since the intersegmental plane is located ventral to the IPV, segmentectomy can be completed via the interlobar fissure approach.
CONCLUSION: In patients with this pattern of pulmonary artery and bronchial anatomy, isolated S7 segmentectomy is a feasible treatment option.
PMID: 30660053 [PubMed - as supplied by publisher]
Publication date: Available online 19 January 2019
Source: Magnetic Resonance Imaging
Author(s): Yusuke Takahashi, Hidetaka Kioka, Yasunori Shintani, Akiko Ohki, Seiji Takashima, Yasushi Sakata, Takahiro Higuchi, Shigeyoshi Saito
To establish a brain proton magnetic resonance spectroscopy (1H MRS) experimental system using a mouse model of Leigh syndrome for monitoring intracerebral lactate levels as a biomarker of mitochondrial disease progression.
Brain 1H MRS was performed in the Ndufs4 homozygous knockout (KO) mice, a mouse model of Leigh syndrome, and control mice on a horizontal 7.0-T magnetic resonance imaging system at age 5–9 weeks. In a subset of KO mice, survival analysis was performed according to the median of the intracerebral lactate levels. In addition, in KO mice alive until 9 weeks of age, both 1H MRS and T2-weighted imaging (T2WI) were longitudinally performed in the same individuals at 5, 7, and 9 weeks of age.
Brain 1H MRS demonstrated increased lactate levels in KO mice compared with control mice (6.4 ± 1.2 mM vs. 3.3 ± 0.8 mM, p < 0.0001). The increased intracerebral lactate levels were already observed at 5 weeks of age, while no obvious abnormal findings were detected in T2WI. Notably, an increased lactate level of >5.94 mM at week 5 was associated with a poor prognosis (median survival days: 24.5 vs. 42 days, log-rank p = 0.03). Longitudinal 1H MRS experiments revealed temporal increase of intracerebral lactate levels, peaking at week 7 (mean change: 2.6 ± 0.7 mM, p = 0.001), followed by decrease at week 9 (mean change: −3.8 ± 2.5 mM, p = 0.03), along with further disease progression, with brain lesions being detected on T2WI.
Using brain 1H MRS, we demonstrated significant increase in intracerebral lactate levels in a mouse model of Leigh syndrome. Additionally, we demonstrated that intracerebral lactate is a useful biomarker of mitochondrial disease progression at stages preceding the development of brain lesions.
Longitudinal MRI findings in patients with newly diagnosed glioblastoma after intraoperative radiotherapy.
J Neuroradiol. 2019 Jan 16;:
Authors: Förster A, Böhme J, Maros ME, Brehmer S, Seiz-Rosenhagen M, Hänggi D, Wenz F, Groden C, Pope WB, Giordano FA
Abstract
BACKGROUND AND PURPOSE: Postradiation treatment effects (pseudoprogression/radionecrosis) may bias MRI-based tumor response evaluation. To understand these changes specifically after high doses of radiotherapy, we analyzed MRIs of patients enrolled in the INTRAGO study (NCT02104882), a phase I/II dose-escalation trial of intraoperative radiotherapy (20-40 Gy) in glioblastoma.
METHODS: INTRAGO patients were evaluated and compared to control patients who received standard therapy with focus on contrast enhancement patterns/volume, T2 lesion volume, and mean rCBV.
RESULTS: Overall, 11/15 (73.3%) INTRAGO patients (median age 60 years) were included. Distant failure was observed in 7/11 (63.6%) patients, local tumor recurrence in one patient (9.1%). On the first follow-up MRI all but one patient demonstrated enhancement of varying patterns around the resection cavity which were: in 2/11 (18.2%) patients thin and linear, in 7/11 (63.6%) combined linear and nodular, and in 1/11 (9.1%) voluminous, indistinct, and mesh-like. In the course of treatment, most patients developed the latter two patterns (8/11 [72.7%]). INTRAGO patients demonstrated more often combined linear and nodular and/or voluminous, indistinct, mesh-like components (8/11 [72.7%]) in comparison to control patients (3/12 [25%], p = 0.02). INTRAGO patients demonstrated significantly increasing enhancing lesion (p = 0.001) and T2 lesion volumes (p < 0.001) in the longitudinal nonparametric analysis in comparison to the control group. rCBV showed no significant differences between both groups.
CONCLUSIONS: High doses of radiotherapy to the tumor cavity result in more pronounced enhancement patterns/volumes and T2 lesion volumes. These results will be useful for the response evaluation of patients exposed to high doses of radiotherapy in future studies.
PMID: 30659892 [PubMed - as supplied by publisher]
Use of a new indocyanin-green pooling technique for improved visualization of spinal dural AV-fistula: a single center case series.
World Neurosurg. 2019 Jan 16;:
Authors: Thorsteinsdottir J, Siller S, Dorn F, Briegel J, Tonn JC, Schichor C
Abstract
BACKGROUND: Intra-operative indocyanine green videoangiography (ICG-VAG) is a useful tool in cerebral vascular surgery. In spinal procedures like dural arteriovenous (AV-) fistula, use of ICG-VAG is limited due to lower perfusion pressure. Therefore, we developed a new pooling technique with adapted workflow to improve intraoperative visualization.
METHODS: Patients operated on spinal dAV-fistulas using ICG-VAG were prospectively included. A new workflow for ICG-VAG was applied: 1. Temporary clip placement at suspected fistula point 2. ICG administration during 100% oxygenation 3. ICG pooling proximal of temporary clip 4. Clip removal/ observation of vascular filling. Case records, clinical data, magnetic resonance imaging (MRI), angiography (DSA) and clinical outcome were analysed retrospectively.
RESULTS: 11 patients (median age 68 years, average course of disease 15 months) were included. Optimized, inverted workflow resulted in considerable pooling of ICG in the supplying feeder of the AV-fistula in all cases. Complete obliteration was confirmed in 10 out of 11 patients by post-operative DSA. However, one patient had an additional, preoperative radiologically undetected small feeder which enlarged until postoperative DSA and made successful re-operation necessary. After median follow-up of 33.2 months, Aminoff-Logue-Scale (ALS) was decreased in all patients, McCormick score (modified Rankin score) was improved in 9 (8) patients and remained stable in 2 (3) patients.
CONCLUSIONS: Procedure modification in terms of ICG pooling enabled us to detect more easily the pathological vascular architecture. ICG-VAG is a useful adjunct in surgical treatment of spinal dural AV-fistula since it is a real-time, non-invasive and radiation-free technique with adequate image resolution.
PMID: 30659976 [PubMed - as supplied by publisher]
Letter to the Editor Regarding: "Treatment strategy for tuberculum sellae meningiomas based on a preoperative radiological assessment".
World Neurosurg. 2019 Jan 16;:
Authors: Giammattei L, Starnoni D, Messerer M, Daniel RT
PMID: 30659975 [PubMed - as supplied by publisher]
Spontaneous Regression of Germinomas After Salvage Surgery and Possible Mechanism of Induced Apoptosis.
World Neurosurg. 2019 Jan 16;:
Authors: Doi K, Toyooka T, Wada K, Otani N, Takeuchi S, Tomiyama A, Nakatogawa H, Tanaka T, Shimazaki H, Hayashi K, Mori K
PMID: 30659974 [PubMed - as supplied by publisher]
Mechanical thrombectomy with intra-operative local thrombolysis versus mechanical thrombectomy with continuous thrombolysis for treatment of cerebral venous sinus thrombosis: A Systematic Review of 82 Cases.
World Neurosurg. 2019 Jan 16;:
Authors: Chen C, Li X, Huang L, Chen S, Ye H, Ye Q, Zhang T, Zhang X, Zhang J, Chen Z, Yang C, Liang X
Abstract
OBJECT: The first-line treatment of Cerebral venous sinus thrombosis (CVST) is systemic anticoagulation. However, patients with severe or clinical worsening condition might benefit from mechanical thrombectomy (MT) combined intra-operative thrombolysis (IOT) or MT with continuous thrombolytic infusion (CTI). This study aimed to compare the efficacy and safety of these two endovascular therapeutic methods by performing a systematic review of literature.
METHODS: This systemic review was conducted to identify all cases of CVST performed with MT+IOT or MT+CTI/MT+IOT+CTI from PubMed and Ovid. Recanalization rates, outcome, operation-related complications, sequelae and postoperative hemorrhage were then evaluated.
RESULTS: A total of 28 studies, including 82 patients met the inclusion criteria. Alone MT+IOT was performed in 42 (51%) patients while MT+CTI/MT+IOT+CTI in 40 (49%) patients. Overall, data of outcome were available for 69 patients of which 57 (82%) patients had a good outcome, and 12 (18%) had a poor outcome or died. Data of recanalization were available for 68 patients. Among them, 28 (41%) patients had complete recanalization, 40 (59%) had partial, and no patient had no recanalization. Operation-related complications were reported in five (6%) patients while three of them (4%) occurred postoperative intracerebral hemorrhage. However, there was no significant difference between MT+IOT and MT+CTI/MT+IOT+CTI regarding recanalization and prognosis.
CONCLUSION: Our review suggests that MT with local thrombolysis is relatively safe and there is no significant difference between alone MT+IOT and MT+CTI/MT+IOT+CTI regarding efficacy and safety. But randomized controlled studies are required to provide a definitive answer on it's in patients with CVST.
PMID: 30659973 [PubMed - as supplied by publisher]
Intra-operative neuromonitoring in patients with intramedullary spinal cord tumor: a systematic review, meta-analysis, and case series.
World Neurosurg. 2019 Jan 16;:
Authors: Rijs K, Klimek M, Boer MS, Biesheuvel K, Harhangi BS
Abstract
BACKGROUND: Intramedullary spinal cord tumors (IMSCT) comprise the least common types of spinal neoplasms; surgery is mostly conducted with intraoperative neuromonitoring (IONM). However, although IONM is widely used to prevent neurological damage and many single-center studies have been published, the added value, in terms of overall sensitivity and specificity, of different monitoring techniques used in IMSCT surgery, remains to be clearly defined.
OBJECT: Summarize and review the published evidence on the use of IONM in IMSCT surgery, including our own case series (n=75 patients).
METHODS: We systematically searched literature published from January 2000 to February 2018. Articles included patients with IMSCT who underwent surgery with neuromonitoring. We estimated the sensitivity, specificity, 95% confidence interval, positive likelihood ratio, and negative likelihood ratio.
RESULTS: Out of 1385 eligible articles, 31 were included in the systematic review. 15 of these articles were used for a meta-analysis, complemented with our own case series. All neuromonitoring modalities showed acceptable, but not optimal test characteristics. For the indications used in the different studies, the motor evoked potentials approach showed the highest sensitivity (0.838 95% CI: 0.703-0.919) and the best specificity (0.829 95% CI: 0.668-0.921) for detecting neuronal injury. In our own case series, the extent of resection was significantly smaller in the false positive group than in the true negative group (p=0.045).
CONCLUSIONS: IONM showed high, but not perfect sensitivity and specificity. IONM prevents neurological damage, but can also limit the extent of tumor resection. Prospective studies will have to define the definitive value of IONM.
PMID: 30659972 [PubMed - as supplied by publisher]
The Evolving Concept of Damage Control in Neurotrauma: Application of Military Protocols in Civilian Settings With Limited Resources.
World Neurosurg. 2019 Jan 16;:
Authors: Rubiano AM, Maldonado M, Montenegro JH, Restrepo CM, Khan AA, Monteiro R, Faleiro RM, Carreño JN, Amorim R, Paiva W, Muñoz E, Paranhos J, Soto A, Armonda RA, Rosenfeld JV
Abstract
Damage control surgery has been described as a sequential therapeutic strategy that supports physiological restoration over anatomical repair in patients with critical injuries. The application of this concept in neurosurgery has evolved since early definitions in 1998. Current strategies have been supported by military neurosurgery experience and the concept is being applied in civilian settings with limited resources. The aim of this narrative review is to describe the evolution of the concept, the surgical techniques and the lessons learned from civilian and military neurosurgeons who apply the concept regularly, especially in practice at military hospitals or in civilian institutions with limited resources in low and middle income countries. Damage control in neurotrauma is a therapeutic option for severe traumatic brain injury management in austere environments. In order to apply the concept of damage control in neurotrauma while using an appropriate approach, lessons must be learned from experienced neurosurgeons who use this technique regularly.
PMID: 30659971 [PubMed - as supplied by publisher]
In Reply to the Letter to the Editor Regarding "Lumbar PLIF and Repeated ASD: An Important Issue with Profound Impact".
World Neurosurg. 2019 Jan 16;:
Authors: Nagamoto Y, Okuda S, Matsumoto T, Sugiura T, Takahashi Y, Iwasaki M
PMID: 30659970 [PubMed - as supplied by publisher]
Supraorbital keyhole approach: Lessons learned from 106 operative cases.
World Neurosurg. 2019 Jan 16;:
Authors: Eroglu U, Shah K, Bozkurt M, Kahilogullari G, Yakar F, Dogan I, Ozgural O, Attar A, Unlu A, Caglar S, Cohen Gadol AA, Ugur HC
Abstract
OBJECTIVE: The supraorbital keyhole approach through an eyebrow incision has been a potentially less invasive approach as an alternative to the standard pterional craniotomy. We aimed to review procedures for anterior and middle cranial fossa lesions and identify lessons learned from addressing various pathologies through this approach.
METHODS: We retrospectively reviewed 106 consecutive patients who underwent this approach. We documented patients' age, sex, pathology, clinical results, extent of tumor resection, complications, use of endoscope, and cosmetic results.
RESULTS: Our series addressed a variety of pathologies. Males accounted for 55% of the cohort and mean age was 51.7 (2-79) years old. Notably, 52% of patients underwent resection of extra-axial masses. Gross total resection was achieved in 74.4% of intra-axial lesions according to postoperative imaging. Two (1.9%) patients developed transient ptosis. One patient (0.9%) developed an allergic reaction to titanium. No cerebrospinal fluid fistula or rhinorrhea occurred. Three patients developed temporary diabetes insipidus after resection of parasellar lesions (2 craniopharyngiomas and 1 pituitary adenoma). In 14 patients with olfactory groove meningiomas, 6 (42.8%) suffered from absence or diminished olfaction postoperatively, and 2 (14.2%) developed postoperative anosmia. Five (38.5%) patients underwent re-resection of recurrent glial tumors. Four weeks postoperatively, 95% of patients demonstrated acceptable cosmetic results. Cosmetic results for 6 (5%) patients were unavailable.
CONCLUSIONS: The supraorbital keyhole approach may be safely used for various lesions within the anterior and middle cranial fossa. The effectiveness and limitations of this approach and possible complications are discussed. This is a valuable approach for selected patients.
PMID: 30659969 [PubMed - as supplied by publisher]
Endoscopic Intradural Subtemporal Keyhole Approach with Neuronavigational Assistance to the Petroclival and Ventrolateral Brainstem Regions: Quantitative Analysis of Anatomic Exposure and Surgical Freedom.
World Neurosurg. 2019 Jan 16;:
Authors: Ding Z, Lu X, Wang Q, Li B, Qian X, Liu X
Abstract
OBJECTIVE: The purpose of this study was to evaluate the advantages of endoscopy and navigational assistance in the intradural subtemporal keyhole approach and the intradural Kawase approach by studying anatomic exposure and surgical freedom in the posterior cranial fossa.
METHODS: Twenty endoscopic intradural subtemporal keyhole approaches (EISKA) were performed on 10 cadaveric heads. An intradural Kawase approach and a navigation-assisted intradural Kawase approach were then carried out on a random side of each specimen. Related anatomic structures were observed through a 0° endoscope and a microscope. Anatomic exposure and surgical freedom were measured by transparent graph paper and analyzed.
RESULTS: Compared with the microsurgical technique, the superior, inferior and medial limit of the endoscopic anatomic exposure increased by 2.9, 15.65 and 10.2 mm, while the surgical freedom increased by 2.9, 7.55 and 6 mm (P < 0.05) in the intradural subtemporal keyhole approach. In the intradural Kawase approach and the navigation-assisted intradural Kawase approach, the endoscopic anatomic exposure and surgical freedom also increased (P < 0.05). Using a frameless navigational device, the inferior limit of the anatomic exposure increased 3.8 mm by endoscopy and 3.5 mm by microscopy, while the surgical freedom increased by 2.7 and 2.2mm, respectively (P < 0.05).
CONCLUSIONS: The EISKA provides greater anatomic exposure and surgical freedom primarily in the superior, inferior, and medial directions of the brainstem region. Maximum anatomic exposure and surgical freedom of the posterior cranial fossa was obtained by navigational assistance with fewer complications.
PMID: 30659968 [PubMed - as supplied by publisher]
Balloon-Mounted versus Self-Expanding Stent Outcomes in Symptomatic Middle Cerebral Artery Stenosis Combined with Poor Collaterals in China: a Multicentre Registry Study.
World Neurosurg. 2019 Jan 16;:
Authors: Li G, Wang N, Li X, Ma N, Liu T, Sun Y, Liu P, Miao Z, Zhang Y, study group of the Registry Study of Stenting for Symptomatic Intracranial Artery Stenosis in China
PMID: 30659967 [PubMed - as supplied by publisher]
"Neuro-oncology research in Nigeria: a great untapped potential".
World Neurosurg. 2019 Jan 16;:
Authors: Adekanmbi A, Peters KB, Razis E, Adeolu AA, Lukas RV, Balogun JA
Abstract
BACKGROUND: Nigeria has the largest population in Africa and has sub-optimal access to neuro-oncology care. It has been estimated that there is approximately 1 neurosurgeon to 2.4 million people in the country, with only few of these trained in the neuro-oncology sub-specialty and no dedicated medical or radiation neurooncologists. There is a paucity of information on the field of neuro-oncology in Nigeria. This manuscript aims to provide an overview of the current state of neuro-oncology literature in Nigeria.
METHODS: A systematic literature review was performed, utilizing Google Scholar, PubMed, and African Journals Online, to search for articles related to neuro-oncology in Nigeria, from 1963-2018. Articles were reviewed and categorized.
RESULTS: Sixty-three relevant articles were identified. They comprised original research in basic science (N= 1), clinical science (N = 59), and reviews (n=3). Retrospective case series were the most common type of publication. Categorizing according to histology, articles focused on meningioma (N=12), pituitary tumors (N=10), glioma (N=7), CNS metastases (N=6), multiple histologic types (N=25) and other types of tumors (N=3). Eight pediatric neuro-oncology publications were amongst these. Two manuscripts, focusing on surgical subjects, specifically addressed issues on neuro-oncology clinical practice in Nigeria. Of the total manuscripts, 26 were published in Nigerian based journals, and 37 in journals outside Nigeria. The majority of the journals were low impact factor journals. An increasing number of publications over time was noted.
CONCLUSIONS: There is a small but growing scholarly literature in neuro-oncology from Nigeria. However, there continues to be room for growth in neuro-oncology research output. With Nigeria's large patient population, there is potential to learn and add to the academic literature. While there are logistical obstacles to both patient care and research in neuro-oncology in Nigeria, there is promise for favorable advancement.
PMID: 30659966 [PubMed - as supplied by publisher]
Surgical outcomes of single level bilateral selective dorsal rhizotomy for spastic diplegia in 150 consecutive patients.
World Neurosurg. 2019 Jan 16;:
Authors: Jeffery SM, Markia B, Pople IK, Aquilina K, Smith J, Mohamed AZ, Burchell A, Jenkins L, Walsh P, Clark N, Sacree J, Cramp M, Babiker MOE, Atherton WG, Clarke A, Edwards RJ
Abstract
OBJECTIVES: Selective dorsal rhizotomy (SDR) is used to improve spasticity, gait and pain in children with spastic diplegia. There is growing evidence supporting its long-term benefits in terms of functional outcomes, independence and quality of life. There is, however, little contemporary work describing the surgical morbidity of this irreversible procedure. The purpose of this study is to evaluate the surgical outcomes and complications of SDR at a single UK centre.
METHODS: Demographics, surgical, postoperative and follow-up data for all patients undergoing SDR between 2011 and 2016 were collected from medical records.
RESULTS: Preoperative Gross Motor Function Classification System (GMFCS) levels in 150 consecutive patients were II (35%), III (65%) and IV (1%). Median age was 6 years and 58% were male. There were no deaths, CSF leaks, returns to theatre or readmissions within 30 days. There were no new motor or sphincter deficits. Postoperative neuropathic pain was reported by 5.3% and sensory symptoms by 8.7%. Other complications included: postoperative nausea and vomiting (19.3%), superficial wound infection (3.3%), urinary retention (1.3%), headache (6.7%) and urine/chest infection (4.7%). Follow-up data were available for all patients (93% to 12 months, 72% to 24 months). Persistent neuropathic symptoms were reported in 6.5% at 24 months.
CONCLUSION: SDR using a single level approach is a safe procedure with low surgical morbidity. This study complements the growing evidence base in support of SDR for spastic diplegia and should help inform decisions when considering treatment options.
PMID: 30659965 [PubMed - as supplied by publisher]
Surgical Treatment of Extra-Foraminal Gas Containing Pseudocyst Compressing L5 Nerve Root by Using Unilateral Biportal Endosopy: A Case Report.
World Neurosurg. 2019 Jan 16;:
Authors: An JW, Lee CW
Abstract
BACKGOUND: Most gaseous lumbar pseudocysts have been previously reported to be located in the spinal canal and successfully treated by several therapeutic methods. By comparison, a gas containing pseudocyst in lumbar extra-foraminal area is very rare. Here, the authors report a case of symptomatic gas containing cyst located in lumbar foramen. It was successfully treated with unilateral biportal endoscopic (UBE) surgery.
CASE DESCRIPTION: a 75-year-old man presented with severe left leg pain and tingling sensation refractory to conservative treatment that aggravated with weight bearing and position change. Computed tomography and magnetic resonance imaging showed a gas containing cyst compressing the left L5 nerve root ganglion in the foramina area at L5-S1 level. Gaseous extra-foraminal pseudocyst was successfully removed by UBE surgery via para-spinal approach. Vivid and clear endoscopic operative imaging of pseudocyst in detail was obtained during operation. The patient's symptom was significantly improved after the operation.
CONCLUSIONS: Gas containing pseudocyst in lumbar foraminal area is not common. Combined use of pre-operative MRI and CT can help diagnose gaseous pseudocyst and differentiate other pathologies. UBE technique which provides good operative visualization and delicate operative manipulation is a less invasive therapeutic method to treat foraminal gas containing pseudocyst.
PMID: 30659964 [PubMed - as supplied by publisher]
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18F-Fluorocholine PET/CT and Parathyroid 4D Computed Tomography for Primary Hyperparathyroidism: The Challenge of Reoperative Patients.
World J Surg. 2019 Jan 18;:
Authors: Amadou C, Bera G, Ezziane M, Chami L, Delbot T, Rouxel A, Leban M, Herve G, Menegaux F, Leenhardt L, Kas A, Trésallet C, Ghander C, Lussey-Lepoutre C
Abstract
BACKGROUND: To evaluate FCH-PET/CT and parathyroid 4D-CT so as to guide surgery in patients with primary hyperparathyroidism (pHPT) and prior neck surgery.
METHODS: Medical records of all patients referred for a FCH-PET/CT in our institution were systematically reviewed. Only patients with pHPT, a history of neck surgery (for pHPT or another reason) and an indication of reoperation were included. All patients had parathyroid ultrasound (US) and Tc-99m-sestaMIBI scintigraphy, and furthermore, some patients had 4D-CT. Gold standard was defined by pathological findings and/or US-guided fine-needle aspiration with PTH level measurement in the washing liquid.
RESULTS: Twenty-nine patients were included in this retrospective study. FCH-PET/CT identified 34 abnormal foci including 19 ectopic localizations. 4D-CT, performed in 20 patients, detected 11 abnormal glands at first reading and 6 more under FCH-PET/CT guidance. US and Tc-99m-sestaMIBI found concordant foci in 8/29 patients. Gold standard was obtained for 32 abnormal FCH-PET/CT foci in 27 patients. On a per-lesion analysis, sensitivity, specificity, positive and negative predictive values were, respectively, 96%, 13%, 77% and 50% for FCH-PET/CT, 75%, 40%, 80% and 33% for 4D-CT. On a per-patient analysis, sensitivity was 85% for FCH-PET/CT and 63% for 4D-CT. FCH-PET/CT results made it possible to successfully remove an abnormal gland in 21 patients, including 12 with a negative or discordant US/Tc-99m-sestaMIBI scintigraphy result, with a global cure rate of 73%.
CONCLUSION: FCH-PET/CT is a promising tool in the challenging population of reoperative patients with pHPT. Parathyroid 4D-CT appears as a confirmatory imaging modality.
PMID: 30659347 [PubMed - as supplied by publisher]
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Evaluation of Parathyroid Glands with Indocyanine Green Fluorescence Angiography After Thyroidectomy.
World J Surg. 2019 Jan 18;:
Authors: Rudin AV, McKenzie TJ, Thompson GB, Farley DR, Lyden ML
Abstract
BACKGROUND: Indocyanine green fluorescence angiography (ICGA) is a new adjunct that has been used in surgical procedures to assess blood flow. This study evaluated the utility of ICGA compared to visual inspection to predict parathyroid function, guide autotransplantation and potentially decrease permanent hypoparathyroidism.
METHODS: This was a retrospective study of patients who underwent total or near-total thyroidectomy (T-NT) between January 2015 and March 2018. Patients with preoperative hyperparathyroidism and those undergoing reoperation were excluded. Patients who had ICGA were compared to T-NT patients without ICGA. Data were analyzed to assess the frequency of autotransplantation and incidence of hypoparathyroidism between groups.
RESULTS: In total, 210 patients underwent T-NT: 86 with ICGA and 124 without. Autotransplantation was more common in the ICGA group at 36% compared to 12% in the control (p = 0.0001). There was no correlation with at least one normal parathyroid gland on ICGA and postoperative PTH levels (p = 0.75). There was a difference in having normal postoperative PTH when there were at least two normal parathyroid glands (n = 50) compared to patients with less than two normal ICGA glands (n = 36, p = 0.044). Visual assessment and ICGA assessment of vascularity were in agreement, 245/281 (87%). There were 19 glands (6.8%) that would have undergone autotransplant based on visual inspection that had adequate blood supply on ICGA. Transient hypoparathyroidism was present in 45 out of 124 controls (36%) and 32 out of 86 (37%) in the ICG group.
CONCLUSIONS: ICGA is a novel technique that may improve the assessment of parathyroid gland blood supply compared to visual inspection. ICGA can guide more appropriate autotransplantation without compromising postoperative parathyroid function. At least two vascularized glands on ICGA may predict postoperative parathyroid gland function.
PMID: 30659346 [PubMed - as supplied by publisher]
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Efficacy of Hepatic Segmental Visualization Using Indocyanine Green Photodynamic Eye Imaging.
World J Surg. 2019 Jan 18;:
Authors: Nanashima A, Yano K, Tobinaga S
Abstract
BACKGROUND: To clarify the usefulness of identification of hepatic segmentation stained with an indocyanine green-photodynamic eye (ICG-PDE) system, we sequentially investigated the matching of visualization during hepatectomy in 40 patients at two institutions between 2009 and 2017.
METHODS: A low dose of ICG was administered into the portal flow to stain the estimated segments of the liver to be resected during hepatectomy, and segmentation images were observed using a PDE camera. Intraoperative ICG-PDE could be carried out for all patients without side effects.
RESULTS: Complete segmental identification of the liver by blue dye stain and ICG-PDE was achieved in 30 (75%) and 35 (88%) patients, respectively, but the prevalence between them was not significantly different (p = 0.302). ICG-PDE segmentation in the estimated area was incomplete in three patients, and complete failure (no staining) was observed in two patients. The border between the posterior section and the caudate was identified in two patients.
CONCLUSION: This preliminary study showed ICG-PDE to be a useful tool for clearly determining liver segmentation to estimate the area for resection.
PMID: 30659345 [PubMed - as supplied by publisher]
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Impact of Tumor Location on Postoperative Outcome of Intraductal Papillary Neoplasm of the Bile Duct.
World J Surg. 2019 Jan 18;:
Authors: Matsumoto T, Kubota K, Hachiya H, Sakuraoka Y, Shiraki T, Shimizu T, Mori S, Iso Y, Kato M, Yamagishi H, Imai Y, Aoki T
Abstract
BACKGROUND: The concept of intraductal papillary neoplasm of the bile duct (IPNB) has been proposed to be the biliary equivalent of intraductal papillary mucinous neoplasm (IPMN) of the pancreas. While the classification of IPMNs is based on their location of duct involvement, such classification has not been fully evaluated for IPNBs. The aim of this study is to investigate the value of IPNB classification based on its location.
METHODS: A total of 306 consecutive patients who underwent surgical resection with a diagnosis of bile duct tumor were enrolled. Among these patients, 21 were diagnosed as having IPNB. The IPNBs were classified into two groups as follows: extrahepatic IPNB, which located in the distal or perihilar bile duct, and intrahepatic IPNB, which located more peripherally than the hilar bile duct. The clinicopathological features of the two groups were then compared.
RESULTS: Extrahepatic IPNB tended to show more invasive characteristics than intrahepatic IPNB (presence of invasive component: 40.0 vs. 9.1%, p = 0.084). Moreover, patients with extrahepatic IPNB showed significantly poorer relapse-free survival (RFS) than those with intrahepatic IPNB [5-year RFS rate (%): 81.8 vs. 16.2, p = 0.014].
CONCLUSION: Patients with intrahepatic IPNB show more favorable pathological characteristics and postoperative survival outcomes than those with extrahepatic IPNB.
PMID: 30659344 [PubMed - as supplied by publisher]
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Identifying Information Gaps in a Surgical Capacity Assessment Tool for Developing Countries: A Methodological Triangulation Approach.
World J Surg. 2019 Jan 18;:
Authors: Nwanna-Nzewunwa OC, Ajiko MM, Motwani G, Kabagenyi F, Carvalho M, Feldhaus I, Kirya F, Epodoi J, Dicker R, Juillard C
Abstract
BACKGROUND: Surgical capacity assessment in low- and middle-income countries (LMICs) is challenging. The Surgeon OverSeas' Personnel Infrastructure Procedure Equipment and Supplies (PIPES) survey tool has been proposed to address this challenge. There is a need to examine the gaps in veracity and context appropriateness of the information obtained using the PIPES tool.
METHODS: We performed a methodological triangulation by comparing and contrasting information obtained using the PIPES tool with information obtained simultaneously via three other methods: time and motion study (T&M); provider focus group discussions (FGDs); and a retrospective review of hospital records.
RESULTS: In its native state, the PIPES survey does not capture the role of non-physician clinicians who contribute immensely to surgical care delivery in LMICs. The surgical workforce was more accurately captured by the FGDs and T&M. It may also not reflect the improvisations (e.g., patients sharing beds, partitioning the operating theater, and using preoperative rooms for surgery, etc.) that occur to expand surgical capacity to overcome the limited infrastructure and equipment.
CONCLUSIONS: The PIPES tool captures vital surgical capacity information but has gaps that can be filled by modifying the tool and/or using ancillary methodologies. The interests of the researcher and the local stakeholders' perspectives should inform such modifications.
PMID: 30659343 [PubMed - as supplied by publisher]
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Does Induction Therapy Increase Anastomotic Complications in Bronchial Sleeve Resections?
World J Surg. 2019 Jan 18;:
Authors: Comacchio GM, Schiavon M, Azzolina D, Mammana M, Marulli G, Zuin A, Verderi E, Monaci N, Bonanno L, Pasello G, Rea F
Abstract
BACKGROUND: Sleeve lobectomy represents a safe and effective treatment for central NSCLC to avoid the risks of pneumonectomy. Induction therapy (IT) may be indicated in advanced stages; however, the effect of IT on bronchial anastomoses remains uncertain. The purpose of the study was to evaluate the impact of IT on the complications of the anastomoses.
METHODS: Between 2000 and 2012, 159 consecutive patients were submitted to sleeve lobectomy for NSCLC at our Institution. We retrospectively compared the results of patients who underwent IT before operation with those who received upfront surgery.
RESULTS: In the study period, 49 (30.8%) patients received IT (37 chemotherapy, 1 radiotherapy and 11 chemo-radiotherapy) and 110 (69.2%) patients were directly submitted to surgery (S). The two groups were comparable for sex, age, comorbidities, ASA score, pulmonary function, side, type of procedure and histology. Pathological stage was statistically higher for IT group (p = 0.001). No differences between IT and S groups were observed in terms of post-operative mortality (2% vs 0%, p = NS), morbidity (45% vs 38%, p = NS), including early (6% vs 9%, p = NS) and long-term (16% vs 14%, p = NS) bronchial complication rates. Patients undergoing induction mediastinal radiotherapy, however, are at higher risk of bronchial complications.
CONCLUSION: In our experience, the use of induction chemotherapy did not significantly increase mortality and morbidity rates, in particular, neither for early nor for late anastomotic complications. We, therefore, conclude that sleeve lobectomy after induction chemotherapy is safe and reliable procedure for the treatment of locally advanced NSCLC.
PMID: 30659342 [PubMed - as supplied by publisher]
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Intestinal Perforation Secondary to Pits of Jujube Ingestion: A Single-Center Experience with 18 Cases.
World J Surg. 2019 Jan 18;:
Authors: Li F, Zhou X, Wang B, Guo L, Ma Y, Wang D, Wang L, Zhang L, Wang H, Zhang L, Tian M, Tao M, Xiu D, Fu W
Abstract
BACKGROUND: Ingestion of jujube pits is a common clinical problem, which can be difficult to diagnose and life-threatening if accompanied with intestinal perforation and peritonitis. In this study, 18 cases of intestinal perforation caused by ingestion of jujube pits were reviewed and summarized to discuss the clinical characteristics, diagnosis and treatments.
METHODS: From 2012 to 2018, a total of 18 patients diagnosed as intestinal perforation due to ingested pits of jujube in our center were retrospectively reviewed and the manifestations, laboratory tests, imaging examinations and treatment strategies were summarized.
RESULTS: The patients comprised of 11 males and 7 females with an average age of 63.5 years. The main clinical manifestation was abdominal pain. Twelve patients (67%) presented to the emergency department with signs of localized peritonitis. CT imaging revealed positive findings in 17 (94%) patients. Conservative treatments were attempted in 3 patients, and the other 15 patients received emergency surgical exploration, where 7 patients had more than one perforation identified during surgery. Five patients were admitted in the surgical intensive care unit after surgery. The average length of stay of all 18 patients was 9.8 days (range 5-24 days).
CONCLUSION: Ingestion of jujube pits is a common clinical problem and potentially leads to intestinal perforation and peritonitis. CT imaging is the first imaging modality of choice. Patients with milder symptoms might be managed with cautious conservative treatment, and patients with more than one perforation can be identified during surgery.
PMID: 30659341 [PubMed - as supplied by publisher]
Cellular senescence in bone.
Bone. 2019 Jan 16;:
Authors: Farr JN, Khosla S
Abstract
Cellular senescence refers to a process induced by various types of stress that causes irreversible cell cycle arrest and distinct cellular alterations, including profound changes in gene expression, metabolism, and chromatin organization as well as activation/reinforcement of anti-apoptotic pathways and development of a pro-inflammatory secretome or senescence-associated secretory phenotype (SASP). However, because of challenges and technical limitations in identifying and characterizing senescent cells in living organisms, only recently have some of the diverse in vivo roles of these unique cells been discovered. New findings indicate that senescent cells and their SASP can have acute beneficial functions, such as in tissue regeneration and wound healing. However, in contrast, when senescent cells accumulate in excess chronically at sites of pathology or in old tissues they drive multiple age-associated chronic diseases. Senotherapeutics that selectively eliminate senescent cells ("senolytics") or inhibit their detrimental SASP ("senomorphics") have been developed and tested in aged preclinical models. These studies have established that targeting senescence is a powerful anti-aging strategy to improve "healthspan" - i.e., the healthy period of life free of chronic disease. The roles of senescence in mediating age-related bone loss have been a recent focus of rigorous investigation. Studies in mice and humans demonstrate that with aging, at least a subset of most cell types in the bone microenvironment become senescent and develop a heterogeneous SASP. Furthermore, age-related bone loss can be alleviated in old mice, with apparent advantages over anti-resorptive therapy, by reducing the senescent cell burden genetically or pharmacologically with the first class of senolytics or a senomorphic. Collectively, these findings point to targeting senescence as a transformational strategy to extend healthspan, therefore providing strong rationale for identifying and optimizing senotherapeutics to alleviate multiple chronic diseases of aging, including osteoporosis, and set the stage for translating senotherapeutics to humans, with clinical trials currently ongoing.
PMID: 30659978 [PubMed - as supplied by publisher]
A novel ent-kaurane diterpenoid analog, DN3, selectively kills human gastric cancer cells via acting directly on mitochondria.
Eur J Pharmacol. 2019 Jan 16;:
Authors: Ma YC, Zhu YL, Su N, Ke Y, Fan XX, Shi XJ, Liu HM, Wang AF
Abstract
Targeting mitochondria using proper pharmacological agents is considered an attractive strategy for cancer control and management. Herein, we report a newly synthetic triazole analog of Jaridonin, DN3, which exhibits more potent antitumor activity via acting directly on mitochondria. DN3 potently reduced viabilities of gastric cancer cell lines HGC-27 and MGC-803 through inducing apoptosis and cell cycle arrest. But, normal human gastric epithelial cell line GES-1 is more resistant to the growth inhibition by DN3 compared with gastric cancer cells. DN3 induced mitochondrial membrane potential (MMP) decrease and cytochrome c release in intact gastric cancer cell lines. Meanwhile, the DN3 treatment also caused the release of cytochrome c from mitochondria isolated from cancer cell lines in a mitochondrial permeability transition pore complex (PTPC) mediated manner, but not from mitochondria isolated from normal gastric epithelial cell. The induction of mitochondrial PTPC proteins voltage-dependent anion channel (VDAC) and cyclophilin D (CypD) were also observed in DN3-treated cells. More interestingly, DN3 mediated MMP decrease, release of cytochrome c, the expression of VDAC and CypD and apoptosis were blocked by the pretreatment of VDAC1 inhibitor (4, 4'-diisothiocyanatostilbene-2,2'-disulfonic acid, DIDS) and CypD inhibitor (cyclosporine A, CsA). In a mouse xenograft model of human gastric cancer, the treatment of 5mg/kg DN3 led to significant tumor regression without affecting body weight. In conclusion, our findings indicate that DN3 is a potential agent for the treatment of gastric cancer through acting directly on mitochondria, and would be useful for us to design more and better anti-cancer compounds.
PMID: 30659827 [PubMed - as supplied by publisher]
Epithelial DNA methyltransferase-1 regulates cell survival, growth and maturation in developing prostatic buds.
Dev Biol. 2019 Jan 16;:
Authors: Joseph DB, Chandrashekar AS, Abler LL, Chu LF, Thomson JA, Vezina CM
Abstract
DNA methyltransferase 1 (DNMT1) is required for embryogenesis but roles in late forming organ systems including the prostate, which emerges from the urethral epithelium, have not been fully examined. We used a targeted genetic approach involving a Shhcre recombinase to demonstrate requirement of epithelial DNA methyltransferase-1 (Dnmt1) in mouse prostate morphogenesis. Dnmt1 mutant urethral cells exhibit DNA hypomethylation, DNA damage, p53 accumulation and undergo cell cycle arrest and apoptosis. Urethral epithelial cells are disorganized in Dnmt1 mutants, leading to impaired prostate growth and maturation and failed glandular development. We evaluated oriented cell division as a mechanism of bud elongation and widening by demonstrating that mitotic spindle axes typically form parallel or perpendicular to prostatic bud elongation axes. We then deployed a ShhcreERT allele to delete Dnmt1 from a subset of urethral epithelial cells, creating mosaic mutants with which to interrogate the requirement for cell division in specific prostatic bud epithelial populations. DNMT1- cell distribution within prostatic buds is not random as would be expected in a process where DNMT1 was not required. Instead, replication competent DNMT1+ cells primarily accumulate in prostatic bud margins and tips while replication impeded DNMT1- cells accumulate in prostatic bud cores. Together, these results highlight the role of DNMT1 in regulating epithelial bud formation by maintaining cell cycle progression and survival of rapidly dividing urethral epithelial cells, which can be extended to the study of other developing epithelial organs. In addition, our results show that prostatic buds consist of two epithelial cell populations with distinct molecular and functional characteristics that could potentially contribute to specialized lineages in the adult prostate.
PMID: 30659795 [PubMed - as supplied by publisher]
Recent Advances on Cytotoxic Sesquiterpene Lactones.
Curr Pharm Des. 2019 Jan 18;:
Authors: Quintana J, Estévez F
Abstract
Sesquiterpene lactones are naturally occurring compounds that have attracted considerable attention because to their vast array of biological activities. These plant-derived compounds contain the α-methylene-γ-butyrolactone functional group, which is the structural requirement for their pharmacological activities. Many of them exhibit cancer cell cytotoxicity and are promising anticancer agents through multiple mechanisms of action. Sesquiterpene lactones are alkylating agents that form covalent adducts in vivo and inhibit enzymes and key proteins. They are also potent apoptotic inducers in several cancer cells. This kind of cell death is recognized as a property that is useful for identifying anticancer drugs. This review focuses on the advances on cytotoxic sesquiterpene lactones and specifically the signal transduction pathways of cell death triggered in cancer cells.
PMID: 30659534 [PubMed - as supplied by publisher]
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Molecular targeting of HER2-overexpressing biliary tract cancer cells with trastuzumab emtansine, an antibody-cytotoxic drug conjugate.
Cancer Chemother Pharmacol. 2019 Jan 18;:
Authors: Yamashita-Kashima Y, Yoshimura Y, Fujimura T, Shu S, Yanagisawa M, Yorozu K, Furugaki K, Higuchi R, Shoda J, Harada N
Abstract
PURPOSE: Trastuzumab emtansine (T-DM1) provides clinical benefit in breast cancers overexpressing human epidermal growth factor receptor 2 (HER2). However, its efficacy against biliary tract cancers (BTC) has not been evaluated. In this study, the effectiveness of T-DM1 in various BTC cell lines and xenograft models with different levels of HER2 expression was investigated.
METHODS: HER2 expression status in xenografts and patient tissue microarrays was assessed by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH). Cell-surface HER2 expression levels and cell growth inhibition in response to T-DM1 were examined in 17 BTC cell lines. The antitumor activity of T-DM1 was evaluated in four xenograft mouse models with different levels of HER2 expression. The effects of T-DM1 on HER2 signaling, antibody-dependent cell-mediated cytotoxicity (ADCC), cell cycle, and apoptosis were assessed in vitro.
RESULTS: Cell-surface expression of HER2 was observed in both gallbladder carcinoma and cholangiocarcinoma tissues. The anti-proliferative activity of T-DM1 was higher in BTC cell lines and breast cancer cell lines with higher levels of HER2 expression. The HER2 status (IHC score|HER2-to-CEP17 ratio by FISH testing) of each BTC xenograft was 3 +|8.3 for KMCH-1, 2 +|4.7 for Mz-ChA-1, 1 +/0|1.4 for OCUG-1, and 0|1.1 for KKU-100, and T-DM1 showed antitumor activity in proportion to the HER2 status. T-DM1 inhibited HER2 signaling and induced ADCC, mitotic arrest, and apoptosis in KMCH-1 cells.
CONCLUSIONS: T-DM1 exhibited preclinical activity in HER2-overexpressing BTC. Further evaluation in clinical studies is warranted.
PMID: 30659304 [PubMed - as supplied by publisher]
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The natural anticancer agent cantharidin alters GPI-anchored protein sorting by targeting Cdc1-mediated remodeling in endoplasmic reticulum.
J Biol Chem. 2019 Jan 18;:
Authors: Sahu PK, Tomar RS
Abstract
Cantharidin (CTD) is a potent anticancer small molecule produced by several species of blister beetle. It has been a traditional medicine for the management of warts and tumors for many decades.CTD suppresses tumor growth by inducing apoptosis, cell cycle arrest, and DNA damage and inhibits protein phosphatase 2 phosphatase activator (PP2A) and protein phosphatase 1 (PP1). CTD also alters lipid homeostasis, cellwall integrity, endocytosis, adhesion, and invasion in yeast cells. In this study, we identified additional molecular targets of CTD using a Saccharomyces cerevisiae strain that expresses a cantharidin resistance gene (CRG1), encoding a SAM-dependent methyltransferase that methylates and inactivates CTD. We found that CTD specifically affects phosphatidylethanolamine (PE)-associated functions that can be rescued by supplementing the growth media with ethanolamine (ETA). CTD also perturbed endoplasmic reticulum (ER) homeostasis and cell wall integrity by altering the sorting of glycophosphatidylinositol (GPI)-anchored proteins. A CTD-dependent genetic interaction profile of CRG1 revealed that activity of the lipid phosphatase cell division control protein 1 (Cdc1) in GPI-anchor remodeling is the key target of CTD, independently of PP2A and PP1 activities. Furthermore, experiments with human cells further suggested that CTD functions through a conserved mechanism in higher eukaryotes. Altogether, we conclude that CTD induces cytotoxicity by targeting Cdc1activity in GPI-anchor remodeling in the ER.
PMID: 30659098 [PubMed - as supplied by publisher]
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d-amino acid oxidase promotes cellular senescence via the production of reactive oxygen species.
Life Sci Alliance. 2019 Feb;2(1):
Authors: Nagano T, Yamao S, Terachi A, Yarimizu H, Itoh H, Katasho R, Kawai K, Nakashima A, Iwasaki T, Kikkawa U, Kamada S
Abstract
d-amino acid oxidase (DAO) is a flavin adenine dinucleotide (FAD)-dependent oxidase metabolizing neutral and polar d-amino acids. Unlike l-amino acids, the amounts of d-amino acids in mammalian tissues are extremely low, and therefore, little has been investigated regarding the physiological role of DAO. We have recently identified DAO to be up-regulated in cellular senescence, a permanent cell cycle arrest induced by various stresses, such as persistent DNA damage and oxidative stress. Because DAO produces reactive oxygen species (ROS) as byproducts of substrate oxidation and the accumulation of ROS mediates the senescence induction, we explored the relationship between DAO and senescence. We found that inhibition of DAO impaired senescence induced by DNA damage, and ectopic expression of wild-type DAO, but not enzymatically inactive mutant, enhanced it in an ROS-dependent manner. Furthermore, addition of d-amino acids and riboflavin, a metabolic precursor of FAD, to the medium potentiated the senescence-promoting effect of DAO. These results indicate that DAO promotes senescence through the enzymatic ROS generation, and its activity is regulated by the availability of its substrate and coenzyme.
PMID: 30659069 [PubMed]
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Chain conformation and biological activities of hyperbranched fucoidan derived from brown algae and its desulfated derivative.
Carbohydr Polym. 2019 Mar 15;208:86-96
Authors: Wei X, Cai L, Liu H, Tu H, Xu X, Zhou F, Zhang L
Abstract
A fucoidan derived from marine brown algae has great potential in biomedical filed. Herein, the fucoidan was successfully isolated and purified by using chitosan microspheres, resulting in the sulfate fucoidan (CF) with degree of sulfation (DS) of 0.94. CF was identified to be highly branched, consisting of fucose (77.4%) and galactose (13.9%), etc., supported by the results of GCMS and light scattering with the structure-sensitive parameter of 0.98 in 0.15 M aqueous NaNO3. The individual CF and its desulfated derivative chains adopted sphere-like conformation in water, observed by atomic force microscopy. CF exhibited higher antiangiogenesis than the desulfated one and strong antileukemia activities through inhibiting cell proliferation and inducing cell apoptosis via cell cycle arrest at G1 phase in vitro. This work provided important information that ester sulfate groups of polysaccharide played an important role in the enhancing of bioactivities of fucoidan, and put forward to a potential drug to treat acute myelocytic leukemia (AML) and tumors.
PMID: 30658835 [PubMed - in process]
Publication date: Available online 19 January 2019
Source: Allergologia et Immunopathologia
Author(s): Jorge Sánchez, Andres Sánchez
The variety of foods and methods of preparation are part of the cultural identity of each population, and thus the main foods that cause symptoms vary among different regions. Due to their increasing frequency, Adverse Reactions to Food (AFR) have been the subject of extensive study, especially in North America and Europe but few studies have been conducted in other areas, especially in populations located in the tropics and subtropics. In this article, we review available information on the epidemiology of food sensitization and food allergies in tropical regions and explore the different epidemiological data considering the major food involved, the underlying immune mechanism and clinical symptoms partners. In addition, we identify the possible limitations and questions that arise from studies conducted in tropical countries, which helps to generate objectives for future research.
Accessory spleen (AS) is a condition found in about 20% of patients and is most commonly located in the hilar region of the spleen. It is more often asymptomatic, single, and smaller than 2 cm. In the present study, we report the rare case of a 13-year-old boy with giant accessory spleen underwent spontaneous intrasplenic hemorrhage who presented with recurrent abdominal pain. Contrast-enhanced MRI was mandatory for the diagnosis before surgical procedure.
from A via a.sfakia on Inoreader http://bit.ly/2DoMzof
Publication date: 15 May 2019
Source: Talanta, Volume 197
Author(s): María Cruz-Alonso, Beatriz Fernandez, Ana Navarro, Susana Junceda, Aurora Astudillo, Rosario Pereiro
Laser ablation inductively coupled plasma - mass spectrometry (LA-ICP-MS) is proposed for a better understanding of metals and proteins distribution in micrometre structures of human brain tissues. Simultaneous absolute quantitative imaging of Fe and ferroportin (FPN), in 5 µm thick tissue sections of the stratum pyramidale of hippocampus CA1 region, was carried out for Alzheimer disease (AD) patients and healthy controls (HC). For the imaging of FPN by LA-ICP-MS, antibodies were labelled via carbodiimide crosslinking with fluorescent gold nanoclusters (AuNCs) of 2.2 nm diameter, enabling a high amplification (314 gold atoms per NC). Laboratory made gelatin standards containing Fe and Au were used for LA-ICP-MS calibration. Results showed that iron presents an increased concentration in AD donors compared with HC donors, whereas similar concentrations of FPN in AD donors with respect to HC donors were obtained. The average absolute FPN concentrations in selected areas obtained with the proposed AuNCs method were compared with the levels obtained by densitometric analysis with a traditional IHC approach, observing a similar trend in all cases.
Publication date: 15 May 2019
Source: Talanta, Volume 197
Author(s): Chao Chang, Lei Han, Yanfang Zhao, Feng Li
Furfural content is considered as index to estimate transformer remnant life. Therefore, low cost, highly sensitive methods for determination of furfural are highly desirable. In the present work, we describe a new strategy for furfural detection by tracing the "off-on" fluorescence signals of fluorescent organic nanoparticles (FONPs). Significant H+-dependent emission characteristics in aprotic organic solvent was found for our synthesized poly(DOPA)-FONPs. The fluorescence of poly(DOPA)-FONPs can be quickly quenched by hydroxylamine hydrochloride. Furfural can react with hydroxylamine hydrochloride to produce furan-2-carbaldehyde oxime and release proton in a 1:1 proportion. Then H+ produced by the reaction caused the fluorescence intensity at 520 nm to increase as a linear function of furfural concentrations. Under the optimum conditions, the linear working concentration range was found to be 0.01–30 mg L-1 and the LOD for the determination of furfural was 0.0015 mg L-1. The proposed method was used to determine furfural in transformer oil samples satisfactorily, providing a convenient alternative to conventional techniques.
Poly(DOPA) fluorescent organic nanoparticles (FONPs) exhibited pH-sensitive fluorescence property in aprotic organic solvent and were successfully applied on simple, sensitive, low-cost and fast detection of furfural in transformer oil.
Publication date: 15 May 2019
Source: Talanta, Volume 197
Author(s): Yaroslav Dubrovskii, Ekaterina Murashko, Olga Chuprina, Petr Beltyukov, Andrey Radilov, Nikolay Solovyev, Vladimir Babakov
Organophosphates' toxic effect causes covalent binding to serine-198 in the active site of human plasma butyrylcholinesterase (BChE) with loss of enzymatic function (covalent inhibition). Mass spectrometric detection of modified FGESAGAAS peptide at the active site is a powerful exposure biomarker tool. The aim of this study was to develop mass spectrometry-based method for BChE adduct formation screening, avoiding the use of standard peptides. Immunomagnetic separation of proteins from plasma was optimized. Commercially available anti-butyrylcholinesterase monoclonal antibodies, immobilized on magnetic beads, resulted in stable and reusable affinity sorbent. The method was tested on horse serum BChE and real human plasma from healthy donors, treated with Russian VX (VR). The BChE isolated from blood plasma was digested with pepsin and analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). The method was evaluated by using synthetic peptides and by comparison to the enzymatic activity Ellman's assay. The minimum concentration of VR exposure, resulting in detectable VR-adduct, was 0.2 ng/mL, which corresponded to the relative BChE inhibition of less than 2%. Adduct formation assessment was performed via monitoring of decrease in non-modified peptide LC-MS/MS signal and increase in VR-modified peptide signal. The designed approach was tested in a pilot study with 5 blood samples from healthy volunteers. Mass spectrometry-based method for BChE adduct formation was found to be in agreement with Ellman's inhibition assay, so the method is applicable for direct BChE inhibition assessment.
Publication date: 15 May 2019
Source: Talanta, Volume 197
Author(s): Nuno Rodrigues, Ítala M.G. Marx, Susana Casal, Luís G. Dias, Ana C.A. Veloso, José A. Pereira, António M. Peres
Olive oil is highly appreciated due to its nutritional and organoleptic characteristics. However, a huge compositional variation is observed between olive oils, requiring the use of diverse analytical techniques for its classification including titration, spectrophotometry and chromatography, as well as sensory analysis. Chemical analysis is usually time-consuming, expensive and require skilled technicians, while the sensorial ones are dependent upon individual subjective evaluations, even if performed by trained panellists. This work evaluated and demonstrated the feasibility of using a potentiometric electronic tongue, comprising non-specific lipid polymeric and cross-sensitive sensor membranes, coupled with chemometric tools based on different sub-sets of sensors (from 11 to 14 sensors), to predict key quality parameters of olive oils based on single-run assays. The multivariate linear models established for 23 centenarian olive trees from different cultivars allowed predicting peroxide value, oxidative stability, total phenols and tocopherols contents, CIELAB scale parameters (L*, a* and b* values), as well as 11 gustatory-retronasal positive attributes (green, sweet, bitter, pungent, tomato and tomato leaves, apple, banana, cabbage, fresh herbs and dry fruits) with satisfactory accuracy (0.90 ± 0.07 ≤ R2 ≤ 0.98 ± 0.02 for the repeated K-fold-CV procedure, which ensured that 25% of the data was used for internal-validation purposes). The electronic tongue device had an accuracy statistically similar to that achieved with standard analytical techniques, pointing out the versatility of the device for the fast and simultaneous chemical and sensory analysis of olive oil.
Publication date: 15 May 2019
Source: Talanta, Volume 197
Author(s): Chongxin Xu, Xiaoqin Liu, Yuan Liu, Xiao Zhang, Cunzheng Zhang, Jianhong Li, Xianjin Liu
Microcystin-LR (MC-LR) is one of common high-toxic biotoxins produced by cyanobacteria in waterbody. A high sensitive and convenient detection method is necessary for monitoring for MC-LR. To establish a high sensitive indirect competitive enzyme-linked immunosorbent assay (IC-ELISA) based on single chain variable fragment (scFv) for detecting MC-LR, 16 positive anti-MC-LR phage scFv particles were screened out from a MC-LR-immunized mouse phage scFv library, which was successfully constructed with the capacity of 8.67 × 107 CFU/mL. The most positive anti-MC-LR phage scFv (MscFv7) was successfully expressed in Escherichia coli (E.coli) HB2151. The molecular weight (M.W.) of expressed protein was about 30 kDa, and the concentration of purified protein was 512.6 μg/mL analyzed by SDS-PAGE and protein quantitative respectively. The IC-ELISA based on MscFv7-scFv for MC-LR shows a half-maximum inhibition (IC50) of 0.471 μg/L and a limit of detection (LOD) of 0.044 μg/L, which is below the maximum residue limit standard (MRLs) of 1.0 μg/L in drinking water. The MscFv7-scFv has a strong cross-recognition for MC-RR and MC-YR with cross-reactivity (CRs) of 93.1% and 85.9%, respectively, but weak for MC-LW with that of 9.7%, even non-recognition for MC-WR, MC-LF and MC-LY. The recovery rates of IC-ELISA to detect MC-LR spiked in different cleanliness of water samples were 81.2–106.3% with CVs of 2.62–10.22% at intra-assay and inter-assay. The results showed that we obtained a high sensitive anti-MC-LR scFv, and the established IC-ELISA based on MscFv7-scFv should be promising for ultrasensitive monitoring MC-LR, MC-RR and MC-YR in water samples.
