Computer-assisted stereology and automated image analysis for quantification of tumor infiltrating lymphocytes in colon cancer

Precise prognostic and predictive variables allowing improved post-operative treatment stratification are missing in patients treated for stage II colon cancer (CC). Investigation of tumor infiltrating lymphoc...

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Authors' Reply: "Organ Transplantation in Australia: Inequities in Access and Outcome for Indigenous Australians".

No abstract available

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Organ Transplantation in Australia: Inequities in Access and Outcome for Indigenous Australians.

No abstract available

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Lung Retransplantation: Practical and Ethical Considerations Raised by the Hannover Protocol.

No abstract available

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Midterm Outcomes of 12 Renal Transplant Recipients Treated With Eculizumab to Prevent Atypical Hemolytic Syndrome Recurrence.

Background: Atypical hemolytic uremic syndrome (aHUS) is an orphan disease with a high rate of recurrence after kidney transplantation. However, reports of successful prevention of posttransplant aHUS recurrence with eculizumab emerged a few years ago. To further delineate its optimal use, we describe the largest series of kidney transplant recipients treated with prophylactic eculizumab. Methods: Twelve renal transplant recipients with aHUS-related end stage renal disease received eculizumab: 10 from day 0 and 2 at the time of recurrence (days 6 and 25). Clinical and histological features, complement assessment and free eculizumab measurements were analyzed. The median follow-up was 24.6 months. Results: 5 patients had failed at least 1 previous renal transplant from aHUS. A genetic mutation was identified in 9 patients, anti-H antibodies were found in 2. No patient demonstrated biological recurrence of thrombotic microangiopathy (TMA) under treatment. Three antibody-mediated rejections (ABMRs) occurred without detectable C5 residual activity. ABMR was associated with subclinical TMA in 2 patients. One patient lost his graft after several complications, including ABMR. One patient experienced post-transplant C3 glomerulonephritis. The last median serum creatinine was 128.2 +/- 40.8 [mu]mol/l. Conclusions: These data confirm that eculizumab is highly effective in preventing posttransplantation aHUS recurrence, yet may not fully block ABMR pathogenesis. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Resection accuracy of patient-specific cutting guides in total knee replacement

Background

Patient-specific guides (PSGs) have been thoroughly investigated with regards to reconstitution of mechanical alignment in total knee arthroplasty (TKA). The ability to replicate the preoperative surgical plan is essential for optimal outcomes but intraoperative measurements to confirm accurate progression through the operation are limited. This leads to our clinical question: can PSGs replicate the planned bone resection depth during TKA?

Methods

This is a prospective case series of 118 patients who underwent TKA using magnetic resonance imaging-based patient-specific cutting guides. Intraoperative bone resection thickness was measured and compared with the preoperative planned bone resections as a primary outcome. Secondary outcomes included the need for additional bone resections, the number of cases for which the PSG technique was abandoned, final component sizes and mechanical alignment.

Results

PSGs could not accurately recreate preoperative plan. PSGs resulted in over-resection in all bone cuts compared with the preoperative surgical resection plan. Secondary osteotomies were required in 37% of patients. PSGs had to be abandoned in 10.5% of cases, mostly due to suboptimal fit of the femoral block. The tibial component size was altered more frequently than the femoral.

Conclusion

Intraoperatively, PSGs could not accurately recreate the preoperative plan. PSGs are marketed as user-friendly tools to simplify TKA but our research demonstrates the need for surgeons to monitor surgical progression and compensate for errors occurring during the use of PSGs.

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Risk factors for multidrug-resistant Gram-negative infection in burn patients

Background

Infection with multidrug-resistant (MDR) Gram-negative organisms leads to poorer outcomes in the critically ill burn patient. The aim of this study was to identify the risk factors for MDR Gram-negative pathogen infection in critically ill burn patients admitted to a major tertiary referral intensive care unit (ICU) in Australia.

Methods

A retrospective case–control study of all adult burn patients admitted over a 7-year period was conducted. Twenty-one cases that cultured an MDR Gram-negative organism were matched with 21 controls of similar age, gender, burn size and ICU stay. Multivariable conditional logistic regression was used to individually assess risk factors after adjusting for Acute Burn Severity Index. Adjusted odds ratios (ORs) were reported. P-values < 0.25 were considered as potentially important risk factors.

Results

Factors increasing the risk of MDR Gram-negative infection included superficial partial thickness burn size (OR: 1.08; 95% confidence interval (CI): 1.01–1.16; P-value: 0.034), prior meropenem exposure (OR: 10.39; 95% CI: 0.96–112.00; P-value: 0.054), Gram-negative colonization on admission (OR: 9.23; 95% CI: 0.65–130.15; P-value: 0.10) and escharotomy (OR: 2.66; 95% CI: 0.52–13.65; P-value: 0.24). For cases, mean age was 41 (SD: 13) years, mean total body surface area burned was 47% (SD: 18) and mean days in ICU until MDR specimen collection was 17 (SD: 10) days.

Conclusion

Prior meropenem exposure, Gram-negative colonization on admission, escharotomy and superficial partial thickness burn size may be potentially important factors for increasing the risk of MDR Gram-negative infection in the critically ill burn patient.

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Evaluation of NxTAG Respiratory Pathogen Panel and Comparison with xTAG Respiratory Viral Panel Fast v2 and Film Array Respiratory Panel for Detecting Respiratory Pathogens in Nasopharyngeal Aspirates and Swine/Avian-Origin Influenza A Subtypes in Culture Isolates

This study evaluated a new multiplex kit, Luminex NxTAG Respiratory Pathogen Panel, for respiratory pathogens and compared it with xTAG RVP Fast v2 and FilmArray Respiratory Panel using nasopharyngeal aspirate specimens and culture isolates of different swine/avian-origin influenza A subtypes (H2N2, H5N1, H7N9, H5N6, and H9N2). NxTAG RPP gave sensitivity of 95.2%, specificity of 99.6%, PPV of 93.5%, and NPV of 99.7%. NxTAG RPP, xTAG RVP, and FilmArray RP had highly concordant performance among each other for the detection of respiratory pathogens. The mean analytic sensitivity (TCID50/ml) of NxTAG RPP, xTAG RVP, and FilmArray RP for detection of swine/avian-origin influenza A subtype isolates was 0.7, 41.8, and 0.8, respectively. All three multiplex assays correctly typed and genotyped the influenza viruses, except for NxTAG RRP that could not distinguish H3N2 from H3N2v. Further investigation should be performed if H3N2v is suspected to be the cause of disease. Sensitive and specific laboratory diagnosis of all influenza A viruses subtypes is especially essential in certain epidemic regions, such as Southeast Asia. The results of this study should help clinical laboratory professionals to be aware of the different performances of commercially available molecular multiplex RT-PCR assays that are commonly adopted in many clinical diagnostic laboratories.

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Encephalopathy caused by novel mutations in the CMP-sialic acid transporter, SLC35A1

Transport of activated nucleotide-sugars into the Golgi is critical for proper glycosylation and mutations in these transporters cause a group of rare genetic disorders termed congenital disorders of glycosylation. We performed exome sequencing on an individual with a profound neurological presentation and identified rare compound heterozygous mutations, p.Thr156Arg and p.Glu196Lys, in the CMP-sialic acid transporter, SLC35A1. Patient primary fibroblasts and serum showed a considerable decrease in the amount of N- and O-glycans terminating in sialic acid. Direct measurement of CMP-sialic acid transport into the Golgi showed a substantial decrease in overall rate of transport. Here we report the identification of the third patient with CMP-sialic acid transporter deficiency, who presented with severe neurological phenotype, but without hematological abnormalities.

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Factors related to home health-care transition in trisomy 13

Trisomy 13 (T13) is accompanied by severe complications, and it can be challenging to achieve long-term survival without aggressive treatment. However, recently, some patients with T13 have been receiving home care. We conducted this study to investigate factors related to home health-care transition for patients with T13.We studied 28 patients with T13 born between January 2000 and December 2014. We retrospectively compared nine home care transition patients (the home care group) and 19 patients that died during hospitalization (the discharge at death group). The median gestational age of the patients was 36.6 weeks, with a median birth weight of 2,047 g. Currently, three patients (11%) have survived, and 25 (89%) have died. The home care group exhibited a significantly longer gestational age (38.9 vs. 36.3 weeks, p = 0.039) and significantly larger occipitofrontal circumference Z score (−0.04 vs. −0.09, p = 0.019). Congenital heart defects (CHD) was more frequent in the discharge at death group, with six patients in the home care group and 18 patients in the discharge at death group (67% vs. 95%, p = 0.047), respectively. Survival time was significantly longer in the home care group than in the discharge at death group (171 vs. 19 days, p = 0.012). This study has shown that gestational age, occipitofrontal circumference Z score at birth, and the presence of CHD are helpful prognostic factors for determining treatment strategy in patients with T13.

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The use of ofatumumab in the treatment of B-cell malignancies

Future Oncology, Ahead of Print.


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A simple and accurate craniofacial midsagittal plane definition

In this article, we aimed to establish an ideal definition for the craniofacial midsagittal plane (MSP) by first finding an optimal "plane of best fit" and then deriving a simple approximation for clinical use that is highly accurate.

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Information for readers

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Genome-wide association study for mandibular prognathism using microsatellite and pooled DNA method

The purpose of this study was to extend an association study from chromosome 1 to the whole genome (genome-wide association study) to find susceptibility loci of mandibular prognathism.

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Editorial Board

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Root resorptions associated with canine retraction treatment

The hypothesis of this study was that multiple factors are dominant in causing external apical root resorption (EARR). The objective of this investigation was to better understand the clinical factors that may lead to EARR.

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Table of Contents

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Fixed-functional appliance treatment combined with growth hormone therapy

The purpose of this study was to illustrate the effects of growth hormone (GH) therapy and fixed functional appliance treatment in a 13-year-old Class II malocclusion patient without GH deficiency. GH has been shown to effectively increase endochondral growth and induce a more prognathic skeletal pattern. Although a major concern in Class II retrognathic patients is chin deficiency, long-term studies have shown that the mandibular growth enhancement effects of functional appliances are clinically insignificant.

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Survival analysis, part 1: Introduction

When time to an event (eg, how long until an event occurs?) is the main outcome of interest in a trial, the relevant data are often called survival data. The survival time for each participant is the interval from a predetermined start point, such as entry into the study, until the occurrence of the event of interest (eg, lingual retainer failure). Participants can have the same survival time, but they may have been enrolled at different calendar times. Survival analysis can be applied to various situations such as time to death from any cause after treatment for cancer, time to finish an orthodontic treatment, time to achieve initial orthodontic alignment, time to bracket failures, time to eruption of impacted canines, and so on.

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Mandibular molar mesialization

We read the study "Apical root resorption due to mandibular first molar mesialization: a split-mouth study" by Winkler et al1 in the April 2017 issue of the AJO-DO. Mandibular molar mesialization is a difficult process because of the cortical nature of mandibular bone and the wide buccolingual roots of the mandibular molars.2 The split-mouth design mentioned by the authors was appropriate, since it nullifies various limiting factors such as the patient's overall periodontal health and the clinician's skill.

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The proof is in the pudding

You've almost lost count of all those educational loans you have accumulated since your college days. All well worth it, you concede, since you've finally accomplished your ultimate goal to become an orthodontist. You have recently combed the area to identify a practice opportunity close to your fiancé who is enrolled at a local law school. Your lifelong dream has been to acquire your own office and treat your patients in a low-volume setting similar to the style in which your own orthodontic care was delivered.

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Three-dimensional assessment of soft tissue changes associated with bone-anchored maxillary protraction protocols

The aim of this study was to assess the 3-dimensional soft tissue changes in growing Class III patients with maxillary deficiency associated with 2 bone-anchored maxillary protraction protocols in relation to an untreated control group of Class III patients.

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Authors' response

Thank you for your comments on our recent article (Meredith L, Farella M, Lowrey S, Cannon RD, Mei L. Atomic force microscopy analysis of enamel nanotopography after interproximal reduction. Am J Orthod Dentofacial Orthop 2017;151:750-7).

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Quantitative analysis of enamel on debonded orthodontic brackets

Iatrogenic damage to the tooth surface in the form of enamel tearouts can occur during removal of fixed orthodontic appliances. The aim of this study was to assess debonded metal and ceramic brackets attached with a variety of bonding materials to determine how frequently this type of damage occurs.

http://ift.tt/2gq66vl

An orthodontic registry: Producing evidence from existing resources

The specialty of orthodontics was recently recognized by U.S. News & World Report as the number 1 profession in the United States.1 The editor of the American Journal of Orthodontics and Dentofacial Orthopedics, Rolf Behrents, gave a thoughtful and provocative commentary of this ranking in the April 2016 issue.2 Perhaps orthodontists have been singled out because each clinician has the ability to deliver excellent care, since each can obtain and analyze diagnostic records.

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Assessment of upper airway size after orthopedic treatment for maxillary protrusion or mandibular retrusion

The aim of this retrospective study was to find out whether different Class II treatments would affect the airway sizes of patients having maxillary protrusion or mandibular retrusion.

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Midpalatal suture density ratio as a predictor of skeletal response to rapid maxillary expansion

We read with great interest the article in the February issue of the AJO-DO entitled "Midpalatal suture density ratio: a novel predictor of skeletal response to rapid maxillary expansion."1 The authors suggested using a qualitative evaluation method of the midpalatal suture to estimate the skeletal response to the rapid maxillary expansion (RME) procedure. This topic is of great interest to orthodontics, because it focuses on a characteristic of the patient that determines the success of the therapy.

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Directory: AAO Officers and Organizations

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Authors' response

We thank Drs Vitral, Fernandes, Fraga, and Campos for their observant comments on our study.1 We agree that, mainly as a consequence of the study design, the research had some limitations. Most of the ones pointed out in the letter, including the influence of growth, the effect of treatment with fixed edgewise appliances, and the use of the variable "prescribed amount of expansion," are discussed in the article. Some of these limitations were unavoidable, since we used a retrospective design; it was not an "experiment" as suggested by the commentators.

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Immunity from what?

The court started its opinion by stating the following.This case presents a matter of first impression: whether the civil and criminal immunity applicable to physicians… under Virginia Code Sec. 32.1-38 is limited to claims arising from the act of reporting health-related confidential information to authorized state and local entities, or whether the statute provides broader immunity to include misconduct described in the reports.

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Atomic force microscopy analysis of enamel nanotopography after interproximal reduction

In the April 2017 issue of the AJO-DO, Meredith et al1 evaluated enamel topography after interproximal reduction under atomic force microscopy (AFM). As discussed in many previous studies, AFM uses several high-resolution scans for assessment of enamel topography and has been strongly recommended for this purpose.2-4 This tool has advantages such as the need for minimal preparation of the samples, taking 2-dimensional and 3-dimensional images simultaneously, and allowing reproducible assessment of samples.

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MET-GRB2 Signaling-Associated Complexes Correlate with Oncogenic MET Signaling and Sensitivity to MET Kinase Inhibitors

Purpose: Targeting MET in cancer is hampered by lack of diagnostics that accurately reflect high MET signaling and dependence. We hypothesized that assays reflecting MET signaling associated protein complexes could redefine tumors dependent on MET and could add additional precision beyond genomic assessments. Experimental Design: We utilized biochemical approaches, cellular viability studies and proximity ligation assays to assess MET dependence. We examined MET signaling complexes in lung cancer patient specimens (N=406) and patient-derived xenograft models of solid tumors (N=308). We evaluated response to crizotinib in a MET-amplified cohort of patient-derived xenografts models of lung cancer (N=6) and provide a case report of a lung cancer patient harboring a exon14 MET splice variant. Results: We found the interaction of MET with the adaptor protein GRB2 is necessary for oncogenic survival signaling by MET. MET:GRB2 complexes were identified only within MET¬¬-amplified patient-derived xenograft (PDX) models and patient specimens but exhibit substantial variability. Lack of MET:GRB2 complexes was associated with lack of response to MET TKI in cell lines and PDX models. Presence of MET:GRB2 complexes can further sub type tumors with exon14 MET splice variants. Presence of these complexes correlated with response to crizotinib in one patient with exon14 MET lacking MET gene amplification. Conclusions: Proximity assays measuring MET:GRB2 signaling complexes provide novel insights into MET-mediated signaling and could complement current clinical genomics-based assay platforms.

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A panel of novel detection and prognostic methylated DNA markers in primary non-small cell lung cancer and serum DNA

Purpose: To establish a novel panel of cancer-specific methylated genes for cancer detection and prognostic stratification of early stage non-small cell lung cancer (NSCLC). Experimental Design: Identification of differentially methylated regions (DMRs) was performed with bumphunter on "The Cancer Genome Atlas (TCGA)" dataset, and clinical utility was assessed using quantitative methylation-specific PCR assay in multiple sets of primary NSCLC and body fluids that included serum, pleural effusion, and ascites samples. Results: A methylation panel of 6 genes (CDO1, HOXA9, AJAP1, PTGDR, UNCX, and MARCH11) was selected from TCGA dataset. Promoter methylation of the gene panel was detected in 92.2% (83/90) of the training cohort with a specificity of 72.0% (18/25) and in 93.0% (40/43) of an independent cohort of stage IA primary NSCLC. In serum samples from the later 43 stage IA subjects and population-matched 42 control subjects, the gene panel yielded a sensitivity of 72.1% (31/41) and specificity of 71.4% (30/42). Similar diagnostic accuracy was observed in pleural effusion and ascites samples. A prognostic risk category based on the methylation status of CDO1, HOXA9, PTGDR, and AJAP1 refined the risk stratification for outcomes as an independent prognostic factor for an early stage disease. Moreover, the paralogue group for HOXA9, predominantly overexpressed in subjects with HOXA9 methylation, showed poor outcomes. Conclusion: Promoter methylation of a panel of 6 genes has potential for use as a biomarker for early cancer detection and to predict prognosis at the time of diagnosis.

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Prognostic role of Epidermal growth factor receptor variant III (EGFRvIII) positivity in EGFR-amplified primary and recurrent glioblastomas

Purpose: Approximately 40% of all glioblastomas have amplified the epidermal growth factor receptor (EGFR) gene and about half of these tumors express the EGFRvIII variant. The prognostic role of EGFRvIII in EGFR-amplified glioblastoma patients and changes in EGFRvIII expression in recurrent versus primary glioblastomas remain controversial, but such data are highly relevant for EGFRvIII-targeted therapies. Experimental design: EGFR-amplified glioblastomas from 106 patients were assessed for EGFRvIII positivity. Changes in EGFR amplification and EGFRvIII status from primary to recurrent glioblastomas were evaluated in 40 patients with EGFR-amplified tumors and 33 patients with EGFR-non-amplified tumors. EGFR single nucleotide variants (SNVs) were assessed in 27 patients. Data were correlated with outcome and validated in 150 glioblastoma patients from The Cancer Genome Atlas (TCGA) consortium. Results: Sixty of 106 EGFR-amplified glioblastomas were EGFRvIII-positive (56.6%). EGFRvIII positivity was not associated with different progression-free or overall survival. EGFRvIII status was unchanged at recurrence in 35 of 40 patients with EGFR-amplified primary tumors (87.5%). Four patients lost and one patient gained EGFRvIII positivity at recurrence. None of 33 EGFR-non-amplified glioblastomas acquired EGFR amplification or EGFRvIII at recurrence. EGFR SNVs were frequent in EGFR-amplified tumors, but were not linked to survival. Conclusions: EGFRvIII and EGFR SNVs are not prognostic in EGFR-amplified glioblastoma patients. EGFR amplification is retained in recurrent glioblastomas. Most EGFRvIII-positive glioblastomas maintain EGFRvIII positivity at recurrence. However, EGFRvIII expression may change in a subset of patients at recurrence, thus repeated biopsy with reassessment of EGFRvIII status is recommended for recurrent glioblastoma patients to receive EGFRvIII-targeting agents.

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Macrophages facilitate resistance to anti-VEGF therapy by altered VEGFR expression

Purpose:VEGF-targeted therapies have modest efficacy in cancer patients, but acquired resistance is common. The mechanisms underlying such resistance are poorly understood. Experimental Design: To evaluate the potential role of immune cells in the development of resistance to VEGF blockade, we first established a preclinical model of adaptive resistance to anti-VEGF therapy. Additional in vitro and in vivo studies were carried out to characterize the role of macrophages in such resistance. Results: Using murine cancer models of adaptive resistance to anti-VEGF antibody (AVA), we found a previously unrecognized role of macrophages in such resistance. Macrophages were actively recruited to the tumor microenvironment and were responsible for the emergence of AVA resistance. Depletion of macrophages following emergence of resistance halted tumor growth and prolonged survival of tumor-bearing mice. In a macrophage-deficient mouse model, resistance to AVA failed to develop, but could be induced by injection of macrophages. Downregulation of macrophage VEGFR-1 and VEGFR-3 expression accompanied upregulation of alternative angiogenic pathways, facilitating escape from anti-VEGF therapy. Conclusions: These findings provide a new understanding of the mechanisms underlying the modest efficacy of current anti-angiogenesis therapies and identify new opportunities for combination approaches for ovarian and other cancers.

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Low-dose cyclophosphamide induces anti-tumor T-cell responses which associate with survival in metastatic colorectal cancer

Purpose: Anti-cancer T-cell responses can control tumors, but immune-suppressive mechanisms in vivo prevent their function. The role of regulatory T-cells (Tregs) in metastatic colorectal cancer (mCRC) is unclear. We have previously shown depletion of Tregs enhances CRC-specific effector T-cell responses. Low dose cyclophosphamide (CPM) targets Tregs in animal models and some human studies, however the effect of CPM in mCRC is unknown. Experimental Design: Fifty-five mCRC patients were enrolled onto a phase I/II trial and randomized to receive two week-long courses of low-dose (50mg twice-a-day) CPM or not. The absolute number, phenotype and anti-tumor function of peripheral blood-derived lymphocyte subsets were monitored throughout treatment, along with 18-month follow-up. Results: Initially CPM reduced proliferation in all lymphocyte subsets, however, a rapid mobilization of effector T-cells overcame this decrease, leading to increased absolute T-cell numbers. In contrast, a reduction in proportional and absolute Treg, B-cell and NK-cell numbers occurred. The expansion and subsequent activation of effector T-cells was focused on tumor-specific T-cells, producing both granzyme B and IFN-gamma. CPM-treated patients demonstrating the most enhanced IFN-gamma+ tumor-specific T-cell responses exhibited a significant delay in tumor progression (HR=0.29, 95% CI 0.12-0.69, P=0.0047), compared to non-responders and no-treatment controls. Conclusions: CPM-induced Treg-depletion is mirrored by a striking boost to anti-tumor immunity. This study provides the first direct evidence of the benefit of naturally primed T-cells in mCRC patients. Our results also support the concept that non-mutated self-antigens can act as useful targets for immunotherapies.

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Non-Hodgkin and Hodgkin lymphomas select for overexpression of BCLW

Purpose: B-cell lymphomas must acquire resistance to apoptosis during their development. We recently discovered BCLW, an anti-apoptotic BCL2 family member thought only to contribute to spermatogenesis, was overexpressed in diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma. To gain insight into the contribution of BCLW to B-cell lymphomas and its potential to confer resistance to BCL2 inhibitors, we investigated the expression of BCLW and the other anti-apoptotic BCL2 family members in six different B-cell lymphomas. Experimental Design: We performed a large-scale gene expression analysis of data sets comprising approximately 2300 lymphoma patient samples, including non-Hodgkin and Hodgkin lymphomas as well as indolent and aggressive lymphomas. Data were validated experimentally with qRT-PCR and immunohistochemistry. Results: We report BCLW is significantly overexpressed in aggressive and indolent lymphomas, including DLBCL, Burkitt, follicular, mantle cell, marginal zone, and Hodgkin lymphomas. Notably, BCLW was preferentially overexpressed over that of BCL2 and negatively correlated with BCL2 in specific lymphomas. Unexpectedly, BCLW was overexpressed as frequently as BCL2 in follicular lymphoma. Evaluation of all five anti-apoptotic BCL2 family members in six types of B-cell lymphoma revealed that BCL2, BCLW, and BCLX were consistently overexpressed, whereas MCL1 and A1 were not. Additionally, individual lymphomas frequently overexpressed more than one anti-apoptotic BCL2 family member. Conclusions: Our comprehensive analysis indicates B-cell lymphomas commonly select for BCLW overexpression in combination with or instead of other anti-apoptotic BCL2 family members. Our results suggest BCLW is likely equally as important in lymphomagenesis as BCL2 and that targeting BCLW in lymphomas should be considered.

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ADC Approval for ALL Likely to Spur More Research [News in Brief]

Inotuzumab ozogamicin could have broader applications, spark work on other antibody–drug conjugates.

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Surrogate Endpoint ID'd for Prostate Cancer Trials [News in Brief]

Metastasis-free survival a robust substitute for overall survival in long-lasting studies.

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Cesarean sections in a secondary level care hospital of Cameroon: an analysis of their six-year trends and adverse neonatal outcomes

The objectives of this study were to determine the trends of CS in a regional hospital in Cameroon and to explore its association with adverse neonatal outcomes.

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Galleria mellonella (greater wax moth) larvae as a model for antibiotic susceptibility testing and acute toxicity trials

Infectivity trials and toxicity testing in rodents are important prerequisites to the use of compounds in man. However, trials in rats and mice are expensive and there are ethical considerations. Galleria mellone...

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The impact of drug resistance on the risk of tuberculosis infection and disease in child household contacts: a cross sectional study

The relative fitness of organisms causing drug-susceptible (DS) and multidrug-resistant (MDR) tuberculosis (TB) is unclear. We compared the risk of TB infection and TB disease in young child household contacts...

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Landscape review of current HIV ‘kick and kill’ cure research - some kicking, not enough killing

Current antiretroviral therapy (ART) used to treat human immunodeficiency virus (HIV) patients is life-long because it only suppresses de novo infections. Recent efforts to eliminate HIV have tested the abilit...

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Precisão e confiabilidade de um teste imuno-cromatográfico rápido NS1 para diagnóstico DENV-1 no ponto de atendimento e no laboratório

Rapid immunochromatographic tests (ICT) for dengue non-structural protein 1 (NS1) have shown good performance for diagnosing acute-phase dengue in serum in laboratory settings, but rarely have been assessed in...

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Discovery of a Novel Stem Rust Resistance Allele in Durum Wheat That Exhibits Differential Reactions to Ug99 Isolates

Wheat stem rust, caused by Puccinia graminis f. sp. tritici Erikss. & E. Henn, can incur yield losses on susceptible cultivars of durum wheat, Triticum turgidum ssp. durum (Desf.) Husnot. Though several durum cultivars possess the stem rust resistance gene Sr13, additional genes in durum wheat effective against emerging virulent races have not been described. Durum line 8155-B1 confers resistance against the P. graminis f. sp. tritici race TTKST, the variant race of the Ug99 race group with additional virulence to wheat stem rust resistance gene Sr24. However, 8155-B1 does not confer resistance to the first-described race in the Ug99 race group: TTKSK. We mapped a single gene conferring resistance in 8155-B1 against race TTKST, Sr8155B1, to chromosome arm 6AS by utilizing Rusty/8155-B1 and Rusty*2/8155-B1 populations and the 90K Infinium iSelect Custom bead chip supplemented by KASP assays. One marker, KASP_6AS_IWB10558, cosegregated with Sr8155B1 in both populations and correctly predicted Sr8155B1 presence or absence in 11 durum cultivars tested. We confirmed the presence of Sr8155B1 in cultivar Mountrail by mapping in the population Choteau/Mountrail. The marker developed in this study could be used to predict the presence of resistance to race TTKST in uncharacterized durum breeding lines and also to combine Sr8155B1 with resistance genes effective to Ug99 such as Sr13. The map location of Sr8155B1 cannot rule out the possibility that this gene is an allele at the Sr8 locus. However, race specificity indicates that Sr8155B1 is different from the known alleles Sr8a and Sr8b.

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Whole Genome Sequencing-Based Mapping and Candidate Identification of Mutations from Fixed Zebrafish Tissue

As forward genetic screens in zebrafish become more common, the number of mutants that cannot be identified by gross morphology or through transgenic approaches, such as many nervous system defects, has also increased. Screening for these difficult to visualize phenotypes demands techniques such as whole-mount in situ hybridization (WISH) or antibody staining, which require tissue fixation. To date, fixed tissue has not been amenable for generating libraries for whole genome sequencing (WGS). Here, we describe a method for utilizing genomic DNA from fixed tissue and a bioinformatics suite for WGS-based mapping of zebrafish mutants. We tested our protocol using two known zebrafish mutant alleles, gpr126^st49 and egr2b^fh227, both of which cause myelin defects. As further proof of concept we mapped a novel mutation, stl64, identified in a zebrafish WISH screen for myelination defects. We linked stl64 to chromosome 1 and identified a candidate nonsense mutation in the F-box and WD repeat domain containing 7 (fbxw7) gene. Importantly, stl64 mutants phenocopy previously described fbxw7^vu56 mutants, and knock-down of fbxw7 in wild-type animals produced similar defects, demonstrating that stl64 disrupts fbxw7. Together, these data show that our mapping protocol can map and identify causative lesions in mutant screens which require tissue fixation for phenotypic analysis.

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A Comparative Analysis of Genetic Ancestry and Admixture in the Colombian Populations of Choco and Medellin

At least twenty percent of Colombians identify as having African ancestry, yielding the second largest population of Afro-descendants in Latin America. To date, there have been relatively few studies focused on the genetic ancestry of Afro-Latino populations. We report a comparative analysis of the genetic ancestry of Chocó, a state located on Colombia's Pacific coast with a population that is >80% Afro-Colombian. We compared genome-wide patterns of genetic ancestry and admixture for Chocó to six other admixed American populations, with an emphasis on a Mestizo population from the nearby Colombian city of Medellín. One hundred sample donors from Chocó were genotyped across 610,545 genomic sites and compared to 94 publicly available whole genome sequences from Medellín. At the continental level, Chocó shows mostly African genetic ancestry (76%) with a nearly even split between European (13%) and Native American (11%) fractions, whereas Medellín has primarily European ancestry (75%), followed by Native American (18%) and African (7%). Sample donors from Chocó self-identify as having more African ancestry, and conversely less European and Native American ancestry, than can be genetically inferred, as opposed to what we previously found for Medellín, where individuals tend to over-estimate levels of European ancestry. We developed a novel approach for subcontinental ancestry assignment, which allowed us to characterize subcontinental source populations for each of the three distinct continental ancestry fractions separately. Despite the clear differences between Chocó and Medellín at the level of continental ancestry, the two populations show overall patterns of subcontinental ancestry that are highly similar. Their African subcontinental ancestries are only slightly different, with Chocó showing more exclusive shared ancestry with the modern Yoruba (Nigerian) population and Medellín having relatively more shared ancestry with West African populations in Sierra Leone and Gambia. Both populations show very similar Spanish ancestry within Europe and virtually identical patterns of Native American ancestry, with main contributions from the Embera and Waunana tribes. When the three subcontinental ancestry components are considered jointly, the populations of Chocó and Medellín are shown to be most closely related, to the exclusion of the other admixed American populations that we analyzed. We consider the implications of the existence of shared subcontinental ancestries for Colombian populations that appear, at first glance, to be clearly distinct with respect to competing notions of national identity that emphasize ethnic mixing (mestizaje) versus group-specific identities (multiculturalism).

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Genetic Dissection of Trabecular Bone Structure with Mouse Inter-subspecific Consomic Strains

Trabecular bone structure has an important influence on bone strength, but little is known about its genetic regulation. To elucidate the genetic factor(s) regulating trabecular bone structure, we compared the trabecular bone structure of two genetically remote mouse strains, C57BL/6J and Japanese wild mouse-derived MSM/Ms. Phenotyping by X-ray micro-CT revealed that MSM/Ms has structurally more fragile trabecular bone than C57BL/6J. Toward identification of genetic determinants for the difference in fragility of trabecular bone between the two mouse strains, we employed phenotype screening of consomic mouse strains in which each C57BL/6J chromosome is substituted by its counterpart from MSM/Ms. The results showed that many chromosomes affect trabecular bone structure, and that the consomic strain B6-Chr15^MSM, carrying MSM/Ms-derived Chromosome 15, has the lowest values for the parameters BV/TV, Tb.N and Conn.D and the highest values for the parameters Tb.Sp and SMI. Subsequent phenotyping of sub-consomic strains for Chromosome 15 (Chr15) mapped four novel trabecular bone structure-related QTLs (Tbsq1-4) on mouse Chr15. These results collectively indicate that genetic regulation of trabecular bone structure is highly complex, and that even in the single Chr15, the combined action of the four Tbsqs controls the fragility of trabecular bone. Given that Tbsq4 is syntenic to Human Chr 12q12-13.3, where several bone-related SNPs are assigned, further study of Tbsq4 should facilitate our understanding of the genetic regulation of bone formation in human.

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NLOS mitigation in indoor localization by marginalized Monte Carlo Gaussian smoothing

One of the main challenges in indoor time-of-arrival (TOA)-based wireless localization systems is to mitigate non-line-of-sight (NLOS) propagation conditions, which degrade the overall positioning performance....

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Immune development and environment: lessons from Amish and Hutterite children

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Transcrestal sinus floor augmentation with immediate implant placement applied in three types of fresh extraction sockets: A clinical prospective study with 1-year follow-up

Abstract

Background

Immediate implant insertion and transcrestal sinus augmentation both can provide a lot of advantages for patients and clinicians.

Objective

This prospective study aims to verify the use of a modified technique for immediate implant insertion simultaneously with sinus augmentation in different types of sockets.

Materials and methods

Thirty-seven patients were recruited for the clinical study and were divided into 3 groups according to the relationship of their maxillary molar roots and sinus floor: group 1 with none of the teeth roots contacts sinus floor; group 2 as at least 1 teeth root contacting sinus floor, but no root is observed penetrating into sinus cavity; group 3 with at least 1 teeth root penetrating into sinus cavity. Implants were inserted after transcrestal sinus floor augmentation and immediately after tooth extraction. The change of mucosa thickness, diagnosis of rhinosinusitis, marginal bone loss (MBL), pocket depth (PD), and sulcus bleeding index were examined through radiographic measurement or clinical monitoring.

Result

During the study period, no implants failed. The relationship of the root of maxillary molars and sinus floor may have an effect on the bone height of the interradicular crest. Sinus mucosa was observed thicker after surgery. After healing period, sinus mucosa returned as thin as presurgery. At the time of 1-year follow-up, MBL was measured on X-ray (group 1: mesial: 0.63 ± 0.20 mm, distal: 0.70 ± 0.14 mm; group 2: mesial: 0.67 ± 0.21, distal: 0.65 ± 0.22 mm; group 3: mesial: 0.70 ± 0.15 mm, distal: 0.73 ± 0.19 mm). No statistical difference was found in MBL and PD as well as bleeding index among 3 groups.

Conclusion

In consideration of the advantages of sinus floor augmentation and immediate implant placement, our clinical result confirms that it is promising to combine the 2 techniques for replacing maxillary molars especially when using residual roots as implant orientation and taking full advantage of the interradicular crest bone.

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Survival rate of titanium-zirconium narrow diameter dental implants versus commercially pure titanium narrow diameter dental implants: A systematic review

Abstract

Background

Despite the existence of several studies validating the use of narrow diameter implants, most of them are based on pure Ti alloys. There is few clinical evidence of the success of TiZr narrow diameter implants (TiZr NDIs) regarding survival rate (SR) and marginal bone loss (MLB).

Purpose

The aim of this review was to systematically assess SR, as well as MBL of TiZr NDIs compared to commercially pure titanium narrow diameter implants (cpTi NDIs).

Material and Methods

The search was conducted in Medline/PubMed, Cochrane, Scopus, and Embase databases (year 2000 to November 2016). Cohort studies and randomized trials were included.

Results

Six clinical studies from the 3453 articles initially identified met the inclusion criteria. There were no statistically significant differences in SR when TiZr NDIs and cpTi NDIs were compared in the 1-year follow up (P = .5), or when comparing TiZr NDIs placed in posterior and anterior regions. There was no difference between groups regarding 1-year SR: −0.01 (95% CI, −0.05-0.03) and MLB: −0.01 mm (95% CI: −0.14-0.12).

Conclusion

It can be concluded that TiZr NDIs present similar success rates and peri-implant bone resorption to cpTi NDIs.

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Long-term evaluation of osteotome sinus floor elevation and simultaneous placement of implants without bone grafts: 10-Year radiographic and clinical follow-up

Abstract

Background

Insertion of an implant in the edentulous posterior maxilla is a challenging procedure because of poor bone quality and increased pneumatization of the maxillary sinus after tooth extraction. To increase the amount of bone, several surgical bone grafting techniques have been used―with considerable morbidity for patients. Osteotome sinus floor elevation (OSFE) is a less invasive technique. The clinical and radiographic outcome of 53 implants placed with this technique without bone graft has been reported previously.

Purpose

Here we report the clinical and radiographic findings after 10 years of implant load bearing.

Material and methods

In a retrospective study, 34 Astra implants in 25 patients were subjected to 10-year follow-up radiologically and clinically. Each patient received 1 or 2 conical Astra implants. The level of the marginal bone and the height of the residual peri-implant alveolar bone (RPAB) for each implant were measured from digital intra-oral radiographs.

Results

Two implants in edentulous patients were lost at the 1-year follow-up, and 1 more at the 3-year examination. There was no loss between 3-year and 10-year follow-up. At 10-year follow-up 36 implants were included. Implants used in single-tooth replacements and in partially edentulous cases had a 100% survival rate. The mean marginal bone loss was 0.6 ± 0.8 mm. The bone height at the time of implant insertion ranged from 1.8 to 6.9 mm, with a mean value of 4.3 ± 1.0 mm. At 10-year follow-up the mean gain in bone at the implant sites for all implants was 2.6 ± 1.2 mm.

Conclusions

The OSFE technique is a reliable method for rehabilitation of patients with atrophied posterior maxilla. However, the success of this method is associated with the amount of the residual bone. In the present study, this surgical approach without bone graft showed reliable long-term results with Astra implants.

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Antiobesity Activities of Methanolic Extracts of Amaranthus dubius, Cucurbita pepo, and Vigna unguiculata in Progesterone-Induced Obese Mice

Amaranthus dubius, Vigna unguiculata, and Cucurbita pepo are traditionally used to manage obesity in Kenya but lack scientific validation to support their use. The aim of this study was to determine the antiobesity activity of methanolic leaf extracts of these plants in progesterone-induced obese mice. The activity of the methanolic leaf extracts was orally bioscreened in progesterone-induced obese mice at 200 mg/kg/bw and 400 mg/kg/bw. Body mass index was calculated once per week for four weeks and blood samples were obtained at the end of the experiment for lipid profile analysis. Antiobesity activities of the extracts were compared with the controls. Leaf extracts of A. dubius, C. pepo, and V. unguiculata, at dose concentrations of 200 mg/kgbw and 400 mg/kgbw, showed significant effects on body mass index (). There was no significant difference between the three extracts on lipid parameter profiles (). The present study showed high food intake in the negative control group as compared with normal control, positive control, and treatment groups. These extracts contained various phytochemicals such as saponins, flavonoids, alkaloids, and steroids and therefore validate use of aforementioned plants in the suppression of obesity and their use for management of obesity is recommended.

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Rate-control with beta-blockers versus calcium-channel blockers in the emergency setting: predictors of medication class choice and associated hospitalization

Abstract

Objectives

Rate-control is an important component of the management of patients with atrial fibrillation (AF). Previous studies of emergency department (ED) rate-control have been limited by relatively small sample sizes. We examined the use of beta-blockers (BB) versus non-dihydropyridine calcium channel blockers (CCB) in ED patients from 24 sites, and the associated hospital admission rates.

Methods

In this pre-planned sub-study, we examined chart data on AF patients who visited one of 24 hospital EDs in Ontario, Canada, between April 2008 and March 2009. We describe the proportion of patients who received either a BB or a CCB, had a heart rate < 110 beats/minute 2 hours later, and any complications. We used hierarchical logistic regression modeling to determine the predictors of BB versus CCB use, and to assess the between-hospital variation in use of BB versus CCB. Solely in patients who had no rhythm control attempts, we examined the difference in the probability of hospital admission after propensity score matching patients by medication class.

Results

Of the 1639 patients who received either a BB (n=429) or a CCB (n=1210), 70.9% of the patients who received a BB had successful rate-control, versus 66.1% for a CCB. Complications were rare (2.4%), and the large majority were hypotension (2.0%). In adjusted analyses, predictors of receiving a BB (compared to a CCB) included already being on a BB, being sent in from a doctor's office, or being seen at a teaching hospital. In contrast, patients with evidence of heart failure, prior use of a CCB, a higher presenting heart rate, a successful pharmacological cardioversion (versus no attempt), or who were seen at the highest AF volume EDs were significantly less likely to receive a BB, compared to a CCB. Systematic between-hospital differences accounted for 8% of the variation in BB versus CCB use. Hospital characteristics accounted for the large majority of that variation: after accounting for patient characteristics the between-hospital variation decreased by a relative 2.8%. By further adjusting for hospital characteristics, it decreased by a relative 74.7%. Among propensity-score matched patients with no rhythm-control attempts, more CCB patients were admitted (51.6%) compared to BB patients (40.0%) (difference of 11.6%; 95% CI, 7.9-16.2).

Conclusions

In this study of 24 EDs, CCBs were used more frequently for rate-control than BBs, and complications were rare and easily managed using both agents. Variation between hospitals in BB versus CCB use was predominantly due to hospital characteristics such as teaching status and AF volumes, rather than different case-mix. Among patients who did not receive attempts at rhythm control, use of a BB for rate control was associated with a lower rate of hospitalization.

This article is protected by copyright. All rights reserved.

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The 2017 Academic Emergency Medicine Consensus Conference: Catalyzing System Change through Healthcare Simulation: Systems, Competency, and Outcomes

Abstract

Over the past decade, emergency medicine took a lead role in healthcare simulation in part due to its demands for successful interprofessional and multidisciplinary collaboration, along with educational needs in a diverse array of cognitive and procedural skills. Simulation-based methodologies have the capacity to support training and research platforms that model micro-, meso- and macro- systems of healthcare. To fully capitalize on the potential of simulation-based research to improve emergency healthcare delivery will require the application of rigorous methods from engineering, social science, and basic science disciplines. The Academic Emergency Medicine (AEM) Consensus Conference, "Catalyzing System Change Through Healthcare Simulation: Systems, Competency, and Outcome" was conceived to foster discussion among experts in emergency medicine, engineering, and social sciences, focusing on key barriers and opportunities in simulation-based research. This executive summary describes the overall rationale for the conference, conference planning, consensus-building approaches, and outlines the focus of the eight breakout sessions. The consensus outcomes from each breakout session are summarized in Proceedings papers published in this issue of Academic Emergency Medicine. Each paper provides an overview of methodological and knowledge gaps in simulation research and identifies future research targets aimed at improving the safety and quality of healthcare.

This article is protected by copyright. All rights reserved.

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Advanced chronic liver disease in the last year of life: a mixed methods study to understand how care in a specialist liver unit could be improved

Objective

To identify the limitations in palliative care provision in the last year of life for people with liver cirrhosis and potential barriers to and enablers of palliative care.

Design

Mixed methods, including a retrospective case note review, qualitative focus groups and individual interviews.

Setting

A tertiary referral liver centre in the south of England (UK).

Participants

Purposively selected case notes of 30 people with cirrhosis who attended the tertiary referral liver centre and died during an 18-month period; a purposive sample of 22 liver health professionals who participated in either focus groups or individual interviews.

Primary and secondary outcomes

Data collected from case notes included hospital admissions, documented discussions of prognosis and palliative care provision. Qualitative methods explored management of people with cirrhosis, and barriers to and enablers of palliative care.

Results

Participants had high rates of hospital admissions and symptom burden. Clinicians rarely discussed prognosis or future care preferences; they lacked the skills and confidence to initiate discussions. Palliative care provision occurred late because clinicians were reluctant to refer due to their perception that reduced liver function is reversible, poor understanding of the potential of a palliative approach; palliative care was perceived negatively by patients and families.

Conclusions

People dying with cirrhosis have unpredictable trajectories, but share a common pathway of frequent admissions and worsening symptoms as death approaches. The use of clinical tools to identify the point of irreversible deterioration and joint working between liver services and palliative care may improve care for people with cirrhosis.

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Thyroid disorders and Mediterranean diet: which way to prevent metabolic complications

L'articolo Thyroid disorders and Mediterranean diet: which way to prevent metabolic complications sembra essere il primo su European Review.

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The First Reported Case of Majocchi’s Granuloma with Malbranchea sp. in an Immunocompetent Patient

Majocchi's granuloma is a rare condition in which a dermatophyte invades the deeper layers of the dermis and subcutaneous tissue and can often be misidentified and treated as eczema. It has a variable presentation ranging from cutaneous lesions to deeper infections in immunocompromised patients. No prior cases have described the formation of Majocchi's granuloma with the deuteromycetes, Malabranchea.

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Computer-Assessed Preference-Based Quality of Life in Patients with Spinal Cord Injury

Objectives. Our aims were to (1) measure quality of life (QoL) in spinal cord injury (SCI) patients using different methods and analyze differences; (2) enable targeted treatments by identifying variables that affect QoL; and (3) provide decision-makers with useful data for cost-utility analyses in SCI population. Methods. Seventy-one participants were enrolled. The computer-based tool UceWeb was used to elicit QoL in terms of utility coefficients, through the standard gamble, time trade-off, and rating scale methods. The SF36 questionnaire was also administered. Statistical analyses were performed to find predictors of QoL among collected variables. Results. Median values for rating scale, time trade-off, and standard gamble were 0.60, 0.82, and 0.85, respectively. All scales were significantly correlated. Rating scale and SF36 provided similar values, significantly lower than the other methods. Impairment level, male gender, older age, living alone, and higher education were correlated with lower QoL but accounted for only 20% of the variation in utility coefficients. Conclusions. Demographic and clinical variables are useful to predict QoL but do not completely capture utility coefficients variability. Therefore, direct preference-based utility elicitation should be strengthened. Finally, this is the first study providing data that can be used as a reference for cost-utility analyses in the Italian SCI population.

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Heterogeneity of Necrotic Changes between Cortical and Cancellous Bone in Mandibular Osteoradionecrosis: A Histopathological Analysis of Resection Margin after Segmental Mandibulectomy

Background. This study aimed to analyze differences in necrotic changes between cortical and cancellous bone in resection margins after segmental mandibulectomy for advanced mandibular osteoradionecrosis. Methods. Anteroposterior bone specimens from eleven patients who underwent segmental mandibulectomy with simultaneous free fibula flap reconstruction for advanced osteoradionecrosis were analyzed histopathologically for the presence of necrotic bone based on the presence of blood vessels within Haversian canals. Results. Ten of eleven (91%) cortices near the inferior border of the mandible at the anterior margins were necrotic. All cancellous bones at the anterior margins were viable. Seven of eleven (64%) cortices near the inferior border of the mandible at the posterior margins were necrotic. Three of eleven (27%) cancellous bones at the posterior margins were necrotic. Conclusion. Necrotic changes are more prevalent in cortices than in cancellous bones in mandibular osteoradionecrosis, probably due to a decrease of periosteal blood supply caused by radiotherapy.

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Recombinant Vaccinia Viruses Coding Transgenes of Apoptosis-Inducing Proteins Enhance Apoptosis But Not Immunogenicity of Infected Tumor Cells

Genetic modifications of the oncolytic vaccinia virus (VV) improve selective tumor cell infection and death, as well as activation of antitumor immunity. We have engineered a double recombinant VV, coding human GM-CSF, and apoptosis-inducing protein apoptin (VV-GMCSF-Apo) for comparing with the earlier constructed double recombinant VV-GMCSF-Lact, coding another apoptosis-inducing protein, lactaptin, which activated different cell death pathways than apoptin. We showed that both these recombinant VVs more considerably activated a set of critical apoptosis markers in infected cells than the recombinant VV coding GM-CSF alone (VV-GMCSF-dGF): these were phosphatidylserine externalization, caspase-3 and caspase-7 activation, DNA fragmentation, and upregulation of proapoptotic protein BAX. However, only VV-GMCSF-Lact efficiently decreased the mitochondrial membrane potential of infected cancer cells. Investigating immunogenic cell death markers in cancer cells infected with recombinant VVs, we demonstrated that all tested recombinant VVs were efficient in calreticulin and HSP70 externalization, decrease of cellular HMGB1, and ATP secretion. The comparison of antitumor activity against advanced MDA-MB-231 tumor revealed that both recombinants VV-GMCSF-Lact and VV-GMCSF-Apo efficiently delay tumor growth. Our results demonstrate that the composition of GM-CSF and apoptosis-inducing proteins in the VV genome is very efficient tool for specific killing of cancer cells and for activation of antitumor immunity.

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Involvement of Semaphorin (Sema4D) in T-Dependent Activation of B Cells

The involvement of endogenous semaphorin (Sema4D) into the key stage of T-dependent differentiation of B cells, formation of plasmoblasts, was demonstrated in vitro in T/B cell co-culture under conditions of polyclonal activation of T cells. The effect of semaphorin was not associated with activation of high-affinity Sema4D receptor plexin B1, but involves lowaffinity receptor CD72. These data indicate that Sema4D-dependent signal regulates not only the initial stage of B-cell activation, proliferative response to the antigen, but also further differentiation of B cells into plasma cells.

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Activation of Microglyocytes in the Anterior Horns of Rat Spinal Cord after Administration of Bacterial Lipopolysaccharide

We studied the reaction of the microglia of the anterior horns of the rat spinal cord to intraperitoneal administration of bacterial LPS. Immunohistochemical analysis showed that acute systemic inflammation leads to activation of more than half of microglial cells as soon as in 24 h after LPS injection, while the total number of microglial cells does not change significantly. It was hypothesized that activated microglial cells are involved in the reorganization of synaptic connections, but do not have a neurotoxic effect.

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Effects of Miramistin and Phosprenil on Microbial Biofilms

Effects of Miramistin and Phosprenil on biofilms of S. pyogenes, S. aureus, E. coli, L. acidophilus, and L. plantarum were studied. Significant differences in the effects of these substances on mature biofilms of microorganisms and the process of their formation were observed. Miramistin had significant inhibiting effects on the forming of biofilms and on the formed biofilms of all studied microorganisms. Treatment with Miramistin inhibited biofilm formation by 2-3 times compared to the control. This effect was found already after using of Miramistin in the low doses (3.12 μg/ml). Inhibition of the growth of a formed biofilm was observed only after treatment with Miramistin in the high doses (25-50 μg/ml). Phosprenil in the high doses (15-30 mg/ml) inhibited the forming of biofilms, especially the biofilms of S. pyogenes and L. plantarum (by 3-4.5 times). Treatment of formed biofilms with the agent in doses of 6.0 and 0.6 mg/ml was associated with pronounced stimulation of its growth in S. pyogenes, S. aureus, and L. acidophilus.

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The level of Hydrogen Peroxide in HeLa Cells in an Ozonated Medium

We studied the role of hydrogen peroxide in the response of tumor cells to treatment with ozonated culture medium. Changes of the level of hydrogen peroxide in tumor cells incubated in ozonated medium were detected by using fluorescence microscopy and genetically-encoded sensor HyPer2. Modifications of fluorescent properties of the sensor reflecting accumulation of hydrogen peroxide in the cell cytoplasm were detected within 70 min from the start of exposure. The concentration of hydrogen peroxide continued to increase until 375 min. The revealed changes support the involvement of hydrogen peroxide in the cell response to ozone treatment.

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Human Umbilical Cord Mesenchymal Stromal Cells Support Viability of Umbilical Cord Blood Hematopoietic Stem Cells but not the “Stemness” of Their Progeny in Co-Culture

Cell—cell interactions and the ability of mesenchymal stromal cells to support the expansion of hematopoietic progenitor cells were studied in co-culture of human umbilical cord tissue-derived mesenchymal stromal cells and nucleated umbilical cord blood cells. It was found that hematopoietic stem cells from the umbilical cord blood are capable to adhere to mesenchymal stromal cells and proliferate during 3-4 weeks in co-culture. However, despite the formation of hematopoietic foci and accumulation of CD34⁺ and CD133⁺ cells in the adherent cell fraction, the ability of newly generated blood cells to form colonies in semi-solid culture medium was appreciably reduced. These findings suggest that human umbilical cord tissue-derived mesenchymal stromal cells display a weak capability to support the "stemness" of hematopoietic stem cell progeny despite long-term maintenance of their viability and proliferation.

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Effect of Pectin Gel Particles on Endotoxemia Induced by Restraint Stress in Mice

We studied the effect of pectin gel particles on endotoxemia in mice induced by restraint stress. It was shown that the concentration of LPS in mouse blood increased during restraint stress, which was associated with memory impairment. Pectin gel particles prevented the development of stress-induced endotoxemia and memory impairment in mice.

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Assessment of Erythroid and Granulocytic Hematopoietic Lineages in Patients with Non-Small-Cell Lung Carcinoma

The toxic effects of combined cisplatin/docetaxel therapy cycles on erythroid and granulocytic hematopoietic lineages as well as their intercycle recovery were examined in patients with stage III-IV non-small-cell lung carcinoma. Responsiveness of the blood system to this therapy remained at a high level. Combined therapy pronouncedly activated the key elements of the erythroid and granulocytic hematopoietic lineages leading to accumulation of immature and mature myelokaryocytes in the bone marrow, enlargement of the medullary pool of mature neutrophils, and increase in the count of medullary erythroid and granulocytic precursor cells under conditions of their accelerated maturation.

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Expression of Signal Molecules in Culture of Human Endothelial Cells in Atherosclerosis and Restenosis

We compared the expression of signal molecules in the culture of human endothelial cells under normal conditions and in atherosclerosis and restenosis. Expression of connexin-37 and sirtuin-1 in atherosclerosis and restenosis surpassed the normal by 2 and 5 times, respectively, and expression of endothelin-1 3-fold surpassed the normal. In restenosis, changes in the expression connexin-37 and endothelin-1 became more pronounced in comparison with atherosclerosis. Connexin-37 and endothelin-1 can serve as predictive markers for prognosis of post-stenting complications in patients with atherosclerosis.

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Selective Cytotoxicity of Manganese Nanoparticles against Human Glioblastoma Cells

Toxicity of different types of manganese nanoparticles against glioblastoma U-87MG and U-251 cells and normal human cells was studied using MTT test. The selectivity of the toxic effect of nanoparticles was evaluated as the ratio of 50% cytotoxic concentration (СС₅₀) for human embryos fibroblasts (FECh-15) to their СС₅₀ for tumor cells. Five of 6 samples of tested nanoparticles demonstrated selective toxic effect in vitro. Manganese oxide nanoparticles were characterized by maximum selectivity (СС₅₀ 6.9 nM and 2.1 nM for U-87MG and U-251 cells, respectively): selectivity index for glioblastoma U-87MG and U-251 cells was 29 and 95.2, respectively. Manganese oxide nanoparticles used for MRI detection of gliomas can be used for designing an oncolytic agent for the treatment of glial tumors in humans.

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Gene—Gene Interactions of Apolipoprotein Gene Polymorphic Variants in Adolescents with Essential Arterial Hypertension and Dyslipidemia

Using MDR bioinformatic analysis we studied gene—gene interactions between apolipoprotein genes in adolescents with essential arterial hypertension and dyslipidemia against the background of essential arterial hypertension. Optimal models of gene—gene interactions were formed. The six-locus model was the most significant: (ApoA1(+83T), ApoA1(-75A), ApoB(Del), ApoC3(S2), ApoE(ε2), ApoE(ε4). The maximum synergism in both adolescent groups were shown for allele variants ApoA1(-75A), ApoB(Del), and ApoE(ε4). The maximum contribution to gene—gene interactions entropy was made by allelic polymorphisms ApoA1(-75A) and ApoE(ε4) and (in the comorbid pathology group) for ApoE(ε4)+ApoB(Del).

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Peculiarities in Interaction of Independent Components of Resting-State fMRI Signal in Patients with Mild Depressions

Some aspects of resting-state fMRI signal can be the key markers of depression. fMRI was recoded over 4 min in evidently healthy persons (N=21) and in patients with mild depression (N=21). The data were separated into the independent spatial components, and the strength of their association with established brain networks was analyzed. The patients with mild depression were characterized with greater correlations between the components representing the ventral and dorsal subdivisions of default mode network (DMN), whereas correlations between the components relating to cerebellum and to the left hemisphere language system were less pronounced. The data revealed a significant role of DMN in the development of affective abnormalities and importance of its functional state as a probable marker of mild depression.

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Proliferation of Peripheral Blood Lymphocytes and Mesenchymal Stromal Cells Derived from Wharton’s Jelly in Mixed and Membrane-Separated Cultures

We studied the effect of mesenchymal stromal cells on proliferation of CFSE-stained T cells in mixed and membrane-separated (Transwell) cultures and in 3D culture of mesenchymal stromal cells from Wharton's jelly. The interaction of mesenchymal stromal cells with mitogen-activated peripheral blood lymphocytes from an allogeneic donor was followed by suppression of T-cell proliferation in a wide range of cell proportions. Culturing in the Transwell system showed the absence of suppression assessed by the fraction of proliferating cells and by the cell cycle analysis. In 3D cultures, contact interaction of mesenchymal stromal cells and lymphocytes was demonstrated that led to accumulation of G2/M phase lymphocytes and G0/G1 phase mesenchymal stromal cells. The suppressive effect of mesenchymal stromal cells from Wharton's jelly is mediated by two mechanisms. The effects are realized within 6 days, which suggests that the therapeutic effects of mesenchymal stromal cells persist until their complete elimination from the body.

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The Influence of Proinflammatory Factors on the Neuroprotective Efficiency of Multipotent Mesenchymal Stromal Cells in Traumatic Brain Injury

We studied the neuroprotective potential of multipotent mesenchymal stromal cells in traumatic brain injury and the effect of inflammatory preconditioning on neuroprotective properties of stem cells under in vitro conditions. To this end, the effects of cell incubation with LPS or their co-culturing with leukocytes on production of cytokines IL-1α, IL-6, TNFα, and MMP-2 and MMP-9 by these cells were evaluated. Culturing under conditions simulating inflammation increased the production of all these factors by multipotent mesenchymal stromal cells. However, acquisition of the inflammatory phenotype by stromal cells did not reduce their therapeutic effectiveness in traumatic brain injury. Moreover, in some variants of inflammatory preconditioning, multipotent mesenchymal stromal cells exhibited more pronounced neuroprotective properties reducing the volume of brain lesion and promoting recovery of neurological functions after traumatic brain injury.

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Changes in the Activity of Proteasomes and Calpains in Metastases of Human Lung Cancer and Breast Cancer

In patients with breast cancer and lung cancer, chymotrypsin-like and caspase-like activities of proteasomes and total activity of calpains in the primary tumor nodes and lymphogenic metastasis are elevated in comparison with the corresponding normal tissues. The development of lymphogenic metastases of breast cancer and lung cancer was associated with opposite change in caspase-like activity of proteasomes. These results can be useful for the development of methods for evaluation of aggressiveness of breast and lung cancer.

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Plasma Level of hsa-miR-619-5p microRNA Is Associated with Prostatic Cancer Dissemination beyond the Capsule

Profiles of circulating microRNA in the plasma of patients with prostate cancer with pathomorphological stages pT2, pT3, and pT4 are analyzed. The level of circulating microRNA hsa-miR-619-5p is elevated in patients with extracapsular spreading of the tumor, increasing significantly from stage pT2 to stage pT4.

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Application of Tetrameric Recombinant Human Butyrylcholinesterase as a Biopharmaceutical for Amelioration of Symptoms of Acute Organophosphate Poisoning

We present a procedure for optimizing the expression of recombinant tetrameric butyrylcholinesterase that enables large-scale production with the yield >30 mg/liter (>90 mg/roller bottle). Intravenous injection of the preparation significantly increased survival and decreased the severity of symptoms of poisoning with paraoxon, an organophosphorus toxin.

http://ift.tt/2iGVpW4

3111T/C Clock Gene Polymorphism in Women with Insomnia

Comparative analysis of the frequency distributions of genotypes and alleles of 3111T/C Clock gene polymorphism was carried out in climacteric Caucasian women with and without insomnia. Genotype TT is more incident in women with insomnia (55.5% vs. 42.6% in the control). Allele T predominated in the control and study group and its frequency is higher in women with insomnia. The OR for the risk of insomnia realization is 1.78 (95%CI 1.16-2.75). No association between genotypes and complaints of patients with insomnia is detected.

http://ift.tt/2xLcnVM

Unitary Properties of AMPA Receptors with Reduced Desensitization

Wild-type AMPA receptors display a characteristic rapidly desensitizing phenotype. Many studies point to the dimer interface between pairs of extracellular ligand binding domains as the key region controlling the rate at which the receptors desensitize. However, mutations at the extracellular end of the pore-forming regions (near the putative ion channel gate) have also been shown to alter desensitization. Here we report the behavior of single GluA4 receptors carrying one of two mutations that greatly reduce desensitization at the level of ensemble currents: the dimer interface mutation L484Y and the Lurcher mutation (A623T, GluA4-Lc) in the extracellular end of M3 (the second true transmembrane helix).

http://ift.tt/2x2areG

Two Pools of Vesicles Associated with Synaptic Ribbons are Molecularly Prepared for Release

Neurons that form ribbon-style synapses are specialized for continuous exocytosis. To this end, their synaptic terminals contain numerous synaptic vesicles, some of which are ribbon associated, that have difference susceptibilities for undergoing Ca2+-dependent exocytosis. In this study, we probed the relationship between previously defined vesicle populations and determined their fusion competency with respect to SNARE complex formation. We found that both the rapidly releasing vesicle pool and the releasable vesicle pool of the retinal bipolar cell are situated at the ribbon-style active zones, where they functionally interact.

http://ift.tt/2vCnakH

Multiple Symptoms in Family Caregivers of Intensive Care Unit Patients

Worldwide, millions of patients are admitted to an intensive care unit (ICU) every year.1 After being critically ill patients face challenges in their lives, including mental, cognitive or physical impairments.2-5 Patients who survive a critical illness are dependent on both professional and nonprofessional caregivers, and family caregivers (FCs) are essential through all phases of the ICU stay and recovery. FCs have been described as having a positive effect on the patient's psychological state 6, 7 and have shown to provide crucial support that may improve patient outcomes.

http://ift.tt/2wmKMeo

Equality in the distribution of health material and human resources in Guangxi: evidence from Southern China

The aim of this study was to assess the equality in the distribution of health material and human resources in Guangxi, and put forward proposal to improve the equality status of the health material and human ...

http://ift.tt/2x2gKz1

Cost-effectiveness of pre- vs post-liver transplant hepatitis C treatment: Robustness of results

http://ift.tt/2wm1SsB

Spontaneous Tear after Insufflation: A Unique Finding of Collagenous Colitis

http://ift.tt/2wHbsJp

Leukemic infiltration of colon in a case of diarrhea post hematopoietic cell transplantation (HCT)

http://ift.tt/2wm20sh

Two Pools of Vesicles Associated with Synaptic Ribbons are Molecularly Prepared for Release

Neurons that form ribbon-style synapses are specialized for continuous exocytosis. To this end, their synaptic terminals contain numerous synaptic vesicles, some of which are ribbon associated, that have difference susceptibilities for undergoing Ca2+-dependent exocytosis. In this study, we probed the relationship between previously defined vesicle populations and determined their fusion competency with respect to SNARE complex formation. We found that both the rapidly releasing vesicle pool and the releasable vesicle pool of the retinal bipolar cell are situated at the ribbon-style active zones, where they functionally interact.

http://ift.tt/2vCnakH

Unitary Properties of AMPA Receptors with Reduced Desensitization

Wild-type AMPA receptors display a characteristic rapidly desensitizing phenotype. Many studies point to the dimer interface between pairs of extracellular ligand binding domains as the key region controlling the rate at which the receptors desensitize. However, mutations at the extracellular end of the pore-forming regions (near the putative ion channel gate) have also been shown to alter desensitization. Here we report the behavior of single GluA4 receptors carrying one of two mutations that greatly reduce desensitization at the level of ensemble currents: the dimer interface mutation L484Y and the Lurcher mutation (A623T, GluA4-Lc) in the extracellular end of M3 (the second true transmembrane helix).

http://ift.tt/2x2areG

Implantable Cardiac Pacemakers by Abbott (formerly St. Jude Medical): Safety Communication - Firmware Update to Address Cybersecurity Vulnerabilities

Audience: Cardiology, Surgery, Family Practice, Patient [Posted 08/29/2017] ISSUE: On August 23, 2017, the FDA approved a firmware update that is now available and is intended as a recall, specifically a corrective action,  to reduce the risk...

http://ift.tt/2wGOUs7

Immunohistochemical staining with non-phospho β-catenin as a diagnostic and prognostic tool of COX-2 inhibitor therapy for patients with extra-peritoneal desmoid-type fibromatosis

Immunohistochemical staining with conventional anti-β-catenin antibody has been applied as a diagnostic tool for desmoid-type fibromatosis (DF). This study aimed to evaluate the diagnostic and prognostic value...

http://ift.tt/2x2eqI4

P378 Quantitative electroencephalographic and psychometric analysis of possible cognitive decline in healthy elderly subjects

Numerous studies have been done to investigate aging and age-related changes (ARCs) which refer to the deterioration in the biologic processes occurring with senescence. We aimed to assess cognitive functions in normal elderly subjects using electrophysiological studies, including power of brain activity and psychometric cognitive assessment scales.

http://ift.tt/2wm7rHN

P377 Inappropriate sexual behavior as an initial clinical feature in progressive supranuclear palsy: Case report

Progressive supranuclear palsy (PSP) is a parkinsonian syndrome that typically affects gait and oculomotor control. Early clinical features of PSP are cognitive impairment and nonspecific affective, behavioral disturbances, personality changes, memory defects, depression, apathy, or euphoria, whereas hypersexuality is rare in PSP. Dopamine agonists are the major risk factor triggering hypersexuality in patients with PSP. In this article, we report a patient presented with hypersexual behavior as an initial symptom before using dopamine agonists as a treatment.

http://ift.tt/2wGXOpr

Implantable Cardiac Pacemakers by Abbott (formerly St. Jude Medical): Safety Communication - Firmware Update to Address Cybersecurity Vulnerabilities

Audience: Cardiology, Surgery, Family Practice, Patient [Posted 08/29/2017] ISSUE: On August 23, 2017, the FDA approved a firmware update that is now available and is intended as a recall, specifically a corrective action,  to reduce the risk...

http://ift.tt/2wGOUs7

CXCL7 is a predictive marker of sunitinib efficacy in clear cell renal cell carcinomas

http://ift.tt/2vH8zU9

Dovitinib in patients with gastrointestinal stromal tumour refractory and/or intolerant to imatinib

http://ift.tt/2vpG9CQ

Identification and characterization of bacterial symbionts in three species of filth fly parasitoids.

Abstract

Facultative bacterial symbionts are widespread among insects and have diverse effects on their biology. Here we focused on bacterial symbionts of three ecologically and economically important filth flies parasitoid species—Spalangia cameroni, S. endius and Muscidifurax raptor. Both Spalangia species harbored a Sodalis bacterium that is closely related to S. praecaptivus (a free-living bacterium) and to Sodalis symbionts of weevils. This is the only case of Sodalis infection in the important order Hymenoptera. We also found, for the first time in this parasitoid guild, a Rickettsia infecting the two Spalangia spp., albeit in much higher prevalence in S. cameroni. Molecular and phylogenetic analyses revealed that it is closely related to R. felis and other Rickettsia species from the 'transitional' group. All three parasitoid species harbored Wolbachia. Using Multi-Locus Sequence Typing, we found that M. raptor harbors a single Wolbachia strain whereas the Spalangia spp. have multiple strains. By controlled crossings we found that Wolbachia infection in S. endius cause incomplete cytoplasmic incompatibility and increased longevity, thereby promoting Wolbachia's spread. In contrast, no effects of Wolbachia on the reproduction and longevity of M. raptor were found. This study underscores the diversity and nature of symbiotic interactions between microbes and insects.

http://ift.tt/2vpS6sa

A preliminary assessment of a new dedicated endodontic software for use with CBCT images to evaluate the canal complexity of mandibular molars

Abstract

Aim

To investigate in vivo the complexity of canals within mesial roots of mandibular molars using 3D Endo^™ software linked to CBCT images.

Methodology

The CBCT images of 100 mandibular first molars were analyzed using the 3D Endo^™ software. The number of canals in the mesial roots, the presence of apical confluences, the canal lengths and the canal configurations using Vertucci's classification were evaluated in bucco-lingual (BL) and mesio-distal (MD) views. The software allowed the visualization of canal trajectories in three-dimension using a coloured outline, which was used to develop a new objective scoring system to provide an overall assessment of canal complexity. Data were analyzed statistically using ANOVA and T-tests with the significance set at p<0.05.

Results

Vertucci type IV canals were found in 44% of the cases, while 54% were type II. The mean distance from the apical foramen to the orifice was 13.15 mm (±1.21) and that between a confluence and the foramen, 2.81 mm (± 1.13). The number of curvatures and the canal complexity scores in the M-D view were significantly higher than in the B-L view (p<0.05). The scores were not directly correlated to the canal (MB vs ML), to the canal length or to the presence of confluences.

Conclusions

3D Endo software features the automatic detection and measurement of several anatomical canal parameters, and is a promising tool for the study of canal complexity in vivo. The unpredictable anatomy of the mesial roots of mandibular molars highlights the value of a three-dimensional pre-operative evaluation of each case. The proposed scoring system aims to provide the clinician with an overall assessment of canal complexity.

This article is protected by copyright. All rights reserved.

http://ift.tt/2wg1QUJ

A new classification system for the restoration of root filled teeth

Abstract

The aim of this paper was to: a) review the current literature on the status of root filled teeth, b) analyse the most important factors in decision-making, c) discuss the current restorative concepts, d) classify both the evidence and clinical practice in a way that seeks to be clear, understandable and helpful for clinicians.

Restoration of root filled teeth represents a challenge for the clinician and remains a controversial subject. The guidelines describe a new classification that is drawn from evidence presented in the literature and also from clinical expertise-based reviews. It describes five categories of teeth.

This article is protected by copyright. All rights reserved.

http://ift.tt/2xvIEkw

Systemic Hypoxia Increases Circulating Concentration of Apelin in Humans

High Altitude Medicine & Biology , Vol. 0, No. 0.


http://ift.tt/2vp2xwk

Fabrication of Ultra-thin Color Films with Highly Absorbing Media Using Oblique Angle Deposition

We present a detailed method for fabricating ultra-thin color films with improved characteristics for optical coatings. The oblique angle deposition technique using an electron beam evaporator allows improved color tunability and purity. Fabricated films of Ge and Au on Si substrates were analyzed by reflectance measurements and color information conversion.

http://ift.tt/2vGTAts

EMCrit Wee – Central Line MicroSkills – Dilation

The next in the microskill series

EMCrit by Scott Weingart.

http://ift.tt/2gnQIQr

How to remove the most common uniform stains

Despite your best efforts, blood stains, food grease and the not-so-fun vomit tinge happen from time to time

http://ift.tt/2vpufsE

Texas Department of Licensing and Regulation for Out-of-State Health-Care Providers Assisting with Disaster Response

In accordance with Section 418.016 of the Texas Government Code, Governor Greg Abbott has temporarily suspended all necessary statutes and rules to allow licensed health-care providers employed by a hospital and who are in good standing in another state to practice in Texas to assist with disaster response operations. 

This suspension is in effect until terminated by the Office of the Governor or until the Hurricane Harvey disaster declaration is lifted or expires.

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Metabolic liver function in humans measured by 2- 18 F-fluoro-2-deoxy-D-galactose PET/CT–reproducibility and clinical potential

Abstract

Background

PET/CT with the radioactively labelled galactose analogue 2-¹⁸F-fluoro-2-deoxy-D-galactose (¹⁸F-FDGal) can be used to quantify the hepatic metabolic function and visualise regional metabolic heterogeneity. We determined the day-to-day variation in humans with and without liver disease. Furthermore, we examined whether the standardised uptake value (SUV) of ¹⁸F-FDGal from static scans can substitute the hepatic systemic clearance of ¹⁸F-FDGal (K _met, mL blood/min/mL liver tissue/) quantified from dynamic scans as measure of metabolic function.

Four patients with cirrhosis and six healthy subjects underwent two ¹⁸F-FDGal PET/CT scans within a median interval of 15 days for determination of day-to-day variation. The correlation between K _met and SUV was examined using scan data and measured arterial blood concentrations of ¹⁸F-FDGal (blood samples) from 14 subjects from previous studies. Regional and whole-liver values of K _met and SUV along with total metabolic liver volume and total metabolic liver function (total SUV, average SUV multiplied by total metabolic liver volume) were calculated.

Results

No significant day-to-day differences were found for K _met or SUV. SUV had higher intraclass correlation coefficients than K _met (0.92–0.97 vs. 0.49–0.78). The relationship between K _met and SUV was linear. Total metabolic liver volume had non-significant day-to-day variation (median difference 50 mL liver tissue; P = 0.6). Mean total SUV in healthy subjects was 23,840 (95% CI, 21,609; 26,070), significantly higher than in the patients (P < 0.001).

Conclusions

The reproducibility of ¹⁸F-FDGal PET/CT was good and SUV can substitute K _met for quantification of hepatic metabolic function. Total SUV of ¹⁸F-FDGal is a promising tool for quantification of metabolic liver function in pre-treatment evaluation of individual patients.

http://ift.tt/2vppFuo

Selective Antagonism of Bcl-xL Potentiates M1 Oncolysis by Enhancing Mitochondrial Apoptosis

Human Gene Therapy , Vol. 0, No. 0.


http://ift.tt/2wQ7Xkb

Tumoral LINE-1 hypomethylation is associated with poor survival of patients with intrahepatic cholangiocarcinoma

Abstract

Background

DNA methylation changes occurring in cancer cells are featured with both promoter CpG island hypermethylation and diffuse genomic hypomethylation. Long interspersed element-1 (LINE-1) is repeated in an interspersed manner with an estimated 500,000 copies per genome. LINE-1 has its CpG sites of the 5′ untranslated region methylated heavily in normal cells and undergoes demethylation in association with cancerization. However, little information is available regarding LINE-1 hypomethylation and its prognostic implication in intrahepatic cholangiocarcinomas.

Methods

A total of 172 cases of intrahepatic cholangiocarcinomas were analyzed for their methylation levels at four CpG sites of LINE-1 using bisulfite pyrosequencing. We examined the relation between tumoral LINE-1 methylation level and clinicopathological features, including survival.

Results

Tumor differentiation, lymphatic invasion, and T stage were associated with a low average methylation level of LINE-1 at the four CpG sites; LINE-1 methylation level tended to be lower in high-grade differentiation, lymphatic emboli, and higher T stage. LINE-1 hypomethylation was significantly linked with lower cancer-specific survival in patients with intrahepatic cholangiocarcinoma and was found to be an independent prognostic parameter.

Conclusions

Our findings suggest that tumoral LINE-1 hypomethylation could be a molecular biomarker heralding poor prognosis of patients with intrahepatic cholangiocarcinoma. Our findings need to be validated in further study.

http://ift.tt/2xKwrYx

Prognosis and treatment of FOLFOX therapy related interstitial pneumonia: a plea for multimodal immune modulating therapy in the respiratory insufficient patient

Abstract

Background

The FOLFOX regimen, i.e., folinic acid (FOL), fluorouracil (F) and oxaliplatin (OX), is a drug cocktail that is used to treat gastric and colorectal cancers. Despite the concomitant improvements in response rate, duration of response and patient survival, reports of serious toxic pulmonary side effects have progressively emerged.

Case presentation

We describe a patient who was treated with FOLFOX as an adjuvant to a rectosigmoidal resection of a rectosigmoidal carcinoma and who developed respiratory insufficiency requiring mechanical ventilation. Computed tomography (CT) imaging and open lung biopsy findings were compatible with interstitial pneumonia (IP). She received multimodal combination treatment (acetylcysteine, corticosteroids, immune globulins and cyclophosphamide) and survived.

We performed a systematic literature search and reviewed all 45 reported cases of FOLFOX-related lung toxicity and/or pulmonary fibrosis for their clinical characteristics and their outcomes related to therapy.

Conclusions

We found that for the 45 cases with available data, the median age was 70 years, and the male–female ratio was 3.5: 1. In the patients exhibiting only mild respiratory symptoms, discontinuation of the culprit drug (oxaliplatin) resulted in a 100% regression of the symptoms. However the prognosis of the respiratory insufficient patient proved to be grim: death occurred in 76.9% of the cases despite conventional treatment with corticosteroids. We therefore urge oncologists and critical care specialists not to limit their interventions to the discontinuation of chemotherapy, artificial ventilation, corticosteroids and glutathione replenishment and to consider the gradual introduction of additional immune-modulating agents whenever life-threatening respiratory symptoms in oxaliplatin-treated patients do not subside; all the more so considering the fact that our analysis showed that every patient who survived intubation and mechanical ventilation experienced a full clinical recovery.

http://ift.tt/2wQokgN

Cancer incidence in eastern Morocco: cancer patterns and incidence trends, 2005–2012

Abstract

Background

Cancer is one of the major health problems worldwide. In this article, we present for the first time the cancer incidence trends, the distribution and the socioeconomic profile of incident cancer cases in Eastern Morocco over a period of eight years.

Methods

Retrospective descriptive study of patients diagnosed with cancer at the Hassan II Regional Oncology Center (ROC) since it was created in October 2005 until December 2012. During the study period, the ROC was the only hospital specialized in cancer care in Eastern Morocco.

Results

A total of 7872 incident cases of cancer were registered in Eastern Morocco. Among these incident cases 5220 cases were women and 2652 were men, with a female to male ratio of 1.97. The mean age at diagnosis was 58 years for males and 52 for females and 94% of the patients aged over 30 years. For both sexes combined and for all cancer sites, breast cancer was the commonest followed by cervix uteri, colon-rectum, lung, nasopharynx, and stomach cancers. The most common cancer in women was breast cancer, followed respectively by cervix uteri cancer, colon-rectum cancer, ovary cancer, and stomach cancer. In men, the lung cancer ranked first, followed respectively by colon-rectum cancer, nasopharynx cancer, prostate cancer, and stomach cancer. For most cancers, crude incidence rates (CR) have increased significantly. The CR for all cancers combined has increased from 56.6 to 80.3 per 100,000 females and from 32.3 to 42.6 per 100,000 males during the study period. Patients profile analysis showed that 79% of cancer patients were from urban areas, 83% were unemployed and 85% had no health insurance.

Conclusions

The distribution of cancers in Eastern Morocco is different from those observed in other regions of Morocco. Unlike most countries, women were much more affected with cancer than men in Eastern Morocco. More importantly, the rates of many cancers are rising. Therefore, our data justify the need to develop effective programs for cancer control and prevention in Eastern Morocco. A better access to cancer care should be a priority of the health policies, given that the majority of cancer patients in Eastern Morocco are unemployed, and do not have medical care coverage.

http://ift.tt/2xKm47e

Population-based colorectal cancer screening programmes using a faecal immunochemical test: should faecal haemoglobin cut-offs differ by age and sex?

Abstract

Background

The Basque Colorectal Cancer Screening Programme has both high participation rate and high compliance rate of colonoscopy after a positive faecal occult blood test (FIT). Although, colorectal cancer (CRC) screening with biannual (FIT) has shown to reduce CRC mortality, the ultimate effectiveness of the screening programmes depends on the accuracy of FIT and post-FIT colonoscopy, and thus, harms related to false results might not be underestimated. Current CRC screening programmes use a single faecal haemoglobin concentration (f-Hb) cut-off for colonoscopy referral for both sexes and all ages. We aimed to determine optimum f-Hb cut-offs by sex and age without compromising neoplasia detection and interval cancer proportion.

Methods

Prospective cohort study using a single-sample faecal immunochemical test (FIT) on 444,582 invited average-risk subjects aged 50–69 years. A result was considered positive at ≥20 μg Hb/g faeces. Outcome measures were analysed by sex and age for a wide range of f-Hb cut-offs.

Results

We analysed 17,387 positive participants in the programme who underwent colonoscopy. Participation rate was 66.5%. Men had a positivity rate for f-Hb of 8.3% and women 4.8% (p < 0.0001). The detection rate for advanced neoplasia (cancer plus advanced adenoma) was 44.0‰ for men and 15.9‰ for women (p < 0.0001). The number of colonoscopies required decreased in both sexes and all age groups through increasing the f-Hb cut-off. However, the loss in CRC detection increased by up to 28.1% in men and 22.9% in women. CRC missed were generally at early stages (Stage I-II: from 70.2% in men to 66.3% in women).

Conclusions

This study provides detailed outcomes in men and women of different ages at a range of f-Hb cut-offs. We found differences in positivity rates, neoplasia detection rate, number needed to screen, and interval cancers in men and women and in younger and older groups. However, there are factors other than sex and age to consider when consideration is given to setting the f-Hb cut-off.

http://ift.tt/2wQbEXi

Chromatin Immunoprecipitation (ChIP) Protocol for Low-abundance Embryonic Samples

Here, we describe a chromatin immunoprecipitation (ChIP) and ChIP-seq library preparation protocol to generate global epigenomic profiles from low-abundance chicken embryonic samples.

http://ift.tt/2iFgnVj

Generation of Escape Variants of Neutralizing Influenza Virus Monoclonal Antibodies

We describe a method by which we identify critical residues required for the binding of human or murine monoclonal antibodies that target the viral hemagglutinin of influenza A viruses. The protocol can be adapted to other virus surface glycoproteins and their corresponding neutralizing antibodies.

http://ift.tt/2xvsG9Z

Diagnostic testing for Legionnaires’ disease

Legionnaires' disease is commonly diagnosed clinically using a urinary antigen test. The urinary antigen test is highly accurate for L. pneumophila serogroup 1, however other diagnostic tests should also be utili...

http://ift.tt/2wPOEHO

Phospholipid Phosphatase 4 promotes proliferation and tumorigenesis, and activates Ca 2+ -permeable Cationic Channel in lung carcinoma cells

Abstract

Background

Phospholipid phosphatase 4 (PPAPDC1A or PLPP4) has been demonstrated to be involved in the malignant process of many cancers. The purpose of this study was to investigate the clinical significance and biological roles of PLPP4 in lung carcinoma.

Methods

PLPP4 expression was examined in 8 paired lung carcinoma tissues by real-time PCR and in 265 lung carcinoma tissues by immunohistochemistry (IHC). Statistical analysis was performed to evaluate the clinical correlation between PLPP4 expression and clinicopathological features and survival in lung carcinoma patients. In vitro and in vivo assays were performed to assess the biological roles of PLPP4 in lung carcinoma. Fluorescence-activated cell sorting, Western blotting and luciferase assays were used to identify the underlying pathway through which PLPP4 silencing mediates biological roles in lung carcinoma.

Results

PLPP4 is differentially elevated in lung adenocarcinoma (ADC) and lung squamous cell carcinoma (SQC) tissues. Statistical analysis demonstrated that high expression of PLPP4 significantly and positively correlated with clinicopathological features, including pathological grade, T category and stage, and poor overall and progression-free survival in lung carcinoma patients. Silencing PLPP4 inhibits proliferation and cell cycle progression in vitro and tumorigenesis in vivo in lung carcinoma cells. Our results further reveal that PLPP4 silencing inhibits Ca²⁺-permeable cationic channel, suggesting that downregulation of PLPP4 inhibits proliferation and tumorigenesis in lung carcinoma cells via reducing the influx of intracellular Ca²⁺.

Conclusion

Our results indicate that PLPP4 may hold promise as a novel marker for the diagnosis of lung carcinoma and as a potential therapeutic target to facilitate the development of novel treatment for lung carcinoma.

http://ift.tt/2wm4x5Q

Exosomal miRNAs and miRNA dysregulation in cancer-associated fibroblasts

Abstract

Purpose

The present review aimed to assess the role of exosomal miRNAs in cancer-associated fibroblasts (CAFs), normal fibroblasts (NFs), and cancer cells. The roles of exosomal miRNAs and miRNA dysregulation in CAF formation and activation were summarized.

Methods

All relevant publications were retrieved from the PubMed database, with key words such as CAFs, CAF, stromal fibroblasts, cancer-associated fibroblasts, miRNA, exosomal, exosome, and similar terms.

Results

Recent studies have revealed that CAFs, NFs, and cancer cells can secrete exosomal miRNAs to affect each other. Dysregulation of miRNAs and exosomal miRNAs influence the formation and activation of CAFs. Furthermore, miRNA dysregulation in CAFs is considered to be associated with a secretory phenotype change, tumor invasion, tumor migration and metastasis, drug resistance, and poor prognosis.

Conclusions

Finding of exosomal miRNA secretion provides novel insights into communication among CAFs, NFs, and cancer cells. MicroRNA dysregulation is also involved in the whole processes of CAF formation and function. Dysregulation of miRNAs in CAFs can affect the secretory phenotype of the latter cells.

http://ift.tt/2wGG3ql

The oncogenic role of the In1-ghrelin splicing variant in prostate cancer aggressiveness

Abstract

Background

The Ghrelin-system is a complex, pleiotropic family composed of several peptides, including native-ghrelin and its In1-ghrelin splicing variant, and receptors (GHSR 1a/b), which are dysregulated in various endocrine-related tumors, where they associate to pathophysiological features, but the presence, functional role, and mechanisms of actions of In1-ghrelin splicing variant in prostate-cancer (PCa), is completely unexplored. Herein, we aimed to determine the presence of key ghrelin-system components (native-ghrelin, In1-ghrelin, GHSR1a/1b) and their potential pathophysiological role in prostate cancer (PCa).

Methods

In1-ghrelin and native-ghrelin expression was evaluated by qPCR in prostate tissues from patients with high PCa-risk (n = 52; fresh-tumoral biopsies), and healthy-prostates (n = 12; from cystoprostatectomies) and correlated with clinical parameters using Spearman-test. In addition, In1-ghrelin and native-ghrelin was measured in plasma from an additional cohort of PCa-patients with different risk levels (n = 30) and control-healthy patients (n = 20). In vivo functional (proliferation/migration) and mechanistic (gene expression/signaling-pathways) assays were performed in PCa-cell lines in response to In1-ghrelin and native-ghrelin treatment, overexpression and/or silencing. Finally, tumor progression was monitored in nude-mice injected with PCa-cells overexpressing In1-ghrelin, native-ghrelin and empty vector (control).

Results

In1-ghrelin, but not native-ghrelin, was overexpressed in high-risk PCa-samples compared to normal-prostate (NP), and this expression correlated with that of PSA. Conversely, GHSR1a/1b expression was virtually absent. Remarkably, plasmatic In1-ghrelin, but not native-ghrelin, levels were also higher in PCa-patients compared to healthy-controls. Furthermore, In1-ghrelin treatment/overexpression, and to a much lesser extent native-ghrelin, increased aggressiveness features (cell-proliferation, migration and PSA secretion) of NP and PCa cells. Consistently, nude-mice injected with PC-3-cells stably-transfected with In1-ghrelin, but not native-ghrelin, presented larger tumors. These effects were likely mediated by ERK1/2-signaling activation and involved altered expression of key oncogenes/tumor suppressor genes. Finally, In1-ghrelin silencing reduced cell-proliferation and PSA secretion from PCa cells.

Conclusions

Altogether, our results indicate that In1-ghrelin levels (in tissue) and circulating levels (in plasma) are increased in PCa where it can regulate key pathophysiological processes, thus suggesting that In1-ghrelin may represent a novel biomarker and a new therapeutic target in PCa.

http://ift.tt/2wmc4S2

Auditory Training Schedules: What Is the Best Strategy?

Are the outcomes of an auditory training (AT) program better if the training is intensive and done close together in time (i.e., massed) or spread apart (i.e., spaced)? Tye-Murray et al (2017) attempted to answer this question.

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Total glycosides of Paeony shows Neuroprotective effects against Semen Strychni -induced neurotoxicity by recovering secretion of hormones and improving brain energy metabolism

Abstract

In this study, we investigated the protective effect of total glycosides of paeony against Semen Strychni-induced neurotoxicity and discussed some probably mechanisms. Levels of estrone, estradiol, estriol and growth hormone in male rats' serum were determined by ELISA, levels of ATP and substances associated with energy metabolism in rats' brain were determined by HPLC and levels of progesterone was determined by a UPLC-MS/MS method. The results showed that neurotoxicity induced by Semen Strychni could cause a significant decrease (p < 0.05, compare to the blank group) in secretion of estrogens and GH and disorder brain energy metabolism at the same time. While, rats with total glycosides of paeony pre-protection (orally administrated with total glycosides of paeony for 15 days before administrating Semen Strychni extract) showed a much better condition in the secretion of hormones and brain energy metabolism, and showed no significant changes in most of those associated substances when comparing to the blank group. Our study indicated that total glycosides of paeony have neuroprotective effects on Semen Strychni-induced neurotoxicity. It could recover the disordered hormone secretion and improve the brain energy metabolism. Total glycosides of paeony is potential to be further used in clinic to protect against neurotoxicity induced by other reasons.

http://ift.tt/2gnAXsL