Non-interventional study to collect data for the application of lidocaine gel 2% during scaling and root planing and professional mechanical plaque removal

Abstract

Objectives

Evaluation of the safety and efficacy of a topical lidocaine gel 2% (LG) during scaling and root planing (SRP) and professional mechanical plaque removal (PMPR).

Materials and methods

The anesthetic effects as well as unwanted effects of LG prior to or during SRP and PMPR were evaluated in an observational, non-randomized, non-interventional study design. A total of 385 treatments were recorded in 68 study centers all over Germany. Rating of the anesthetic effect of LG by treating personnel and patients using a four-item verbal rating scale (VRS), tolerability, safety (adverse effects), and need for additional local injection anesthesia (ALI).

Results

In SRP as well as in PMPR, application of LG allowed a sufficiently pain-free therapy in more than 90% of the patients as stated on the VRS (SRP: 97.8%, PMPR: 93.75%). Overall, ALI was needed in only 4.23% of the patients treated (SRP: 5.3%, PMPR: 2.62%). One adverse effect occurred within the observation.

Conclusions

Application of LG may offer a safe and effective way to achieve pain-free therapy in periodontal patients.

Clinical relevance

Patient compliance is key to the success of periodontal maintenance therapy. Effective and safe pain control during various kinds of periodontal therapy might increase patient compliance and therefore contribute to the long-term treatment success, among other factors. With regard to the patients observed in this study, 47% had previously received periodontal maintenance therapy and were therefore familiar with the treatment and the associated pain.

https://ift.tt/2HLsRD6

Tropospheric ozone enhancement during post-harvest crop-residue fires at two downwind sites of the Indo-Gangetic Plain

Abstract

In the present study, surface ozone (O₃), nitrogen oxides (NO_x), and carbon monoxide (CO) levels were measured at two sites downwind of fire active region in the Indo-Gangetic Plain (IGP): Agra (27.16° N, 78.08° E) and Delhi (28.37° N, 77.12° E) to study the impact of post-harvest crop-residue fires. The study period was classified into two groups: Pre-harvest period and Post-harvest period. During the post-harvest period, an enhancement of 17.3 and 31.7 ppb in hourly averaged O₃ mixing ratios was observed at Agra and Delhi, respectively, under similar meteorological conditions. The rate of change of O₃ was also higher in the post-harvest period by 56.2% in Agra and 39.5% in Delhi. Relatively higher O₃ episodic days were observed in the post-harvest period. Fire hotspots detected by Moderate Resolution Imaging Spectroradiometer (MODIS) along with backward air-mass trajectory analysis suggested that the enhanced O₃ and CO levels at the study sites during the post-harvest period could be attributed to crop-residue burning over the North-West IGP (NW-IGP). Satellite observations of surface CO mixing ratios and tropospheric formaldehyde (HCHO) column also showed higher levels during the post-harvest period.

Graphical abstract

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Removal of pharmaceutically active compounds from synthetic and real aqueous mixtures and simultaneous disinfection by supported TiO 2 /UV-A, H 2 O 2 /UV-A, and TiO 2 /H 2 O 2 /UV-A processes

Abstract

Pharmaceutically active compounds are carried into aquatic bodies along with domestic sewage, industrial and agricultural wastewater discharges. Psychotropic drugs, which can be toxic to the biota, have been detected in natural waters in different parts of the world. Conventional water treatments, such as activated sludge, do not properly remove these recalcitrant substances, so the development of processes able to eliminate these compounds becomes very important. Advanced oxidation processes are considered clean technologies, capable of achieving high rates of organic compounds degradation, and can be an efficient alternative to conventional treatments. In this study, the degradation of alprazolam, clonazepam, diazepam, lorazepam, and carbamazepine was evaluated through TiO₂/UV-A, H₂O₂/UV-A, and TiO₂/H₂O₂/UV-A, using sunlight and artificial irradiation. While using TiO₂ in suspension, best results were found at [TiO₂] = 0.1 g L⁻¹. H₂O₂/UV-A displayed better results under acidic conditions, achieving from 60 to 80% of removal. When WWTP was used, degradation decreased around 50% for both processes, TiO₂/UV-A and H₂O₂/UV-A, indicating a strong matrix effect. The combination of both processes was shown to be an adequate approach, since removal increased up to 90%. H₂O₂/UV-A was used for disinfecting the aqueous matrices, while mineralization was obtained by TiO₂-photocatalysis.

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Familial alcohol supply, adolescent drinking and early alcohol onset in 45 low and middle income countries

Publication date: September 2018
Source:Addictive Behaviors, Volume 84
Author(s): Gary C.K. Chan, Janni Leung, Adrian B. Kelly, Jason Connor, Stephanie Edward, Wayne Hall, Louisa Degenhardt, Vivian Chiu, George Patton
AimsThis study estimated the extent of familial alcohol supply in 45 low and middle income countries (LMIC), and examined the country-level effects of familial alcohol supply on adolescents' alcohol use.MethodWe used data from 45 LMICs that participated in the Global School-Based Student Health Survey (GSHS) between 2003 and 2013 (n = 139,840). The weighted prevalence of familial alcohol supply in each country was estimated. Multilevel binary and ordinal logistic regression analyses were used to examine the country-level effect of familial alcohol supply on early onset of alcohol use (first alcohol before 12), past 30-day alcohol use, lifetime drunkenness and alcohol-related social problems.ResultsThere were large variations between LMICs in the prevalence of familial alcohol supply and pattern of adolescent alcohol use. The prevalence of familial supply ranged from 0.1% in Tajikistan to 23.8% in St Lucia. It was estimated that a one percentage change in prevalence of familial alcohol supply was associated with 10%, 12% and 12% change in the odds of lifetime drunkenness (OR = 1.10, 95% CI = [1.04, 1.16]), early onset of alcohol use (OR = 1.12, 95% CI = [1.07, 1.08]) and more frequent drinking in the past month (OR = 1.12, 95% CI = [1.04, 1.20]).ConclusionThere were large variations in the prevalence of familial alcohol supply and adolescent alcohol use among LMICs. Adolescents in countries with higher prevalence of familial alcohol supply were more likely to start using alcohol at an earlier age, to have used alcohol in the past 30 days and experience intoxication.



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Electronic cigarette liquid and device parameters and aerosol characteristics: A survey of regular users

Publication date: September 2018
Source:Addictive Behaviors, Volume 84
Author(s): Arit M. Harvanko, Andrea K. McCubbin, Kristin B. Ashford, Thomas H. Kelly
IntroductionElectronic cigarettes are widely variable devices, typically with user definable liquid and device parameters. Yet, little is known about how regular users manipulate these parameters. There is also limited understanding of what factors drive electronic cigarette use and liquid purchasing, and whether two common ingredients, propylene glycol and vegetable glycerin, alter the subjective effects of these devices.MethodsDuring the spring of 2016 522 adults, who reported daily use of electronic cigarettes containing nicotine, completed a survey on electronic cigarettes. Survey questions included an electronic cigarette dependence questionnaire, questions on tobacco and electronic cigarette use, and device and liquid preferences.ResultsFifty-nine percent of respondents reported using another tobacco product, which was positively associated with level of nicotine dependence. On average, devices were set to 28.3 (SD = 24.2) watts. Ability to change device voltage, and level of resistance typically used, was significantly associated with level of nicotine dependence. Amount of liquid consumed, nicotine concentration, and milligrams of nicotine used per week, were positively associated with nicotine dependence. Participants rated 'good taste' as the most important consideration when using and purchasing liquids, and propylene glycol is associated with undesirable effects and vegetable glycerin with desirable effects.ConclusionsThese data indicate that electronic cigarette users utilize a wide range device parameter settings and liquid variables, and that individuals with greater nicotine dependence favor voltage control devices, and lower resistance heating elements. Taste is a key factor for electronic cigarette selection, and concentrations of propylene glycol and vegetable glycerin may have a significant impact on the reinforcing effects of liquids.



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Integrating smoking cessation care into routine service delivery in a medically supervised injecting facility: An acceptability study

Publication date: September 2018
Source:Addictive Behaviors, Volume 84
Author(s): Eliza Skelton, Flora Tzelepis, Anthony Shakeshaft, Ashleigh Guillaumier, William Wood, Marianne Jauncey, Allison M. Salmon, Sam McCrabb, Kerrin Palazzi, Billie Bonevski
BackgroundAmong people who inject drugs (PWIDs) the prevalence of tobacco smoking exceeds 80%; making smoking cessation intervention a priority for this population. This study aims to examine staff and client perspectives from a supervised injecting facility regarding: i) whether an organizational change intervention increased rates of smoking cessation care delivery (pre- to post-intervention); and ii) acceptability of the intervention.MethodsA pre-and-post intervention pilot study in a supervised injecting facility was conducted in Sydney, Australia between July 2014–December 2015. The intervention employed an organizational change approach and included six components. Cross-sectional samples of staff (pre n = 27, post n = 22) and clients (pre n = 202, post n = 202) completed online surveys pre and post intervention.ResultsFrom pre to post-intervention staff reported smoking cessation practices significantly increased for the provision of verbal advice (30% to 82%; p < 0.001), offer of free or subsidized nicotine replacement therapy (30% to 91%; p < 0.001), referral to a general practitioner (19% to 64%; p = 0.001), and follow-up to check on quit smoking progress (18.5% to 64%; p = 0.001). Significantly more clients reported receiving all smoking cessation strategies post-intervention. Over 85% of staff agreed that it was acceptable to address client smoking as part of usual care and 95% of clients agreed that it was acceptable to be asked by staff about their tobacco smoking.ConclusionsIncreasing the provision of smoking cessation care using an organizational change approach is both feasible for staff and acceptable to staff and clients of supervised injecting facilities.



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Role of smoking intention in tobacco use reduction: A mediation analysis of an effective classroom-based prevention/cessation intervention for adolescents

Publication date: September 2018
Source:Addictive Behaviors, Volume 84
Author(s): María T. Gonzálvez, Alexandra Morales, Mireia Orgilés, Steve Sussman, José P. Espada
IntroductionAlthough some school-based tobacco cessation and prevention programs have been proven to be effective, there remains a lack of understanding of how these programs succeed.MethodsThis longitudinal study aimed to test smoking intention as a mediator of Project EX's intervention efficacy to reduce tobacco use. Using a computerized random number generator, six high schools located in the Mediterranean coast were randomly selected to participate in the program condition (Spanish version of Project EX) or the waiting-list control group with baseline, immediate-posttest, and 12-month follow-up assessments. At baseline, 685 adolescents aged 14–20 years (mean age: 14.87; SD = 0.92; 47.4% were females) were evaluated using self-administered tests of tobacco, and smoking intention. A biomarker of smoke inhalation, a measurement of exhaled carbon monoxide (ECM), was used. Mediation analyses were conducted using the PROCESS v2.12 macro for Windows.ResultsProject EX had a significant effect on smoking intention. Indirect effects indicated that Project EX reduced the ECM level, and number of cigarettes used. Conclusions: This is the first Spanish study that explored intention as a mediator of the long-term efficacy of Project EX to reduce tobacco use in adolescents. Results suggested that interventions that reduce consumption intention at short-term are more likely to be successful in decreasing tobacco use in the long-term.



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Laryngopharyngeal Reflux: Current Concepts on Etiology and Pathophysiology and Its Role in Dysphagia

Abstract

Purpose of Review

Laryngopharyngeal reflux (LPR) is one of the most commonly encountered chronic inflammatory conditions of the larynx. The lack of a unifying consensus regarding diagnosis and management makes it difficult to relate laryngeal disorders and dysphagia to this disease entity, particularly for an otolaryngologist. This article reviews diagnosis and management of LPR from an otolaryngological and gastroenterological perspective by reconciling current trends in the literature.

Recent Findings

More sophisticated testing via multichannel pH probes as well as the implementation of pepsin assays has potential in diagnosing LPR. This will hopefully more clearly delineate this disease entity, in the setting of dysphagia.

Summary

Dysphagia and LPR both have significant overlap with numerous disease entities. Though there is little literature to address outcomes in treatment and management of dysphagia in the setting of LPR, few studies show that managing LPR-related dysphagia may improve with surgical intervention if there is no improvement with conservative management.

https://ift.tt/2HH8qHd

Book review—Diagnostic Pathology: Cytopathology, 2nd edition

https://ift.tt/2HFq12b

Cosmetics, Vol. 5, Pages 30: A Critical View of Different Botanical, Molecular, and Chemical Techniques Used in Authentication of Plant Materials for Cosmetic Applications

Cosmetics, Vol. 5, Pages 30: A Critical View of Different Botanical, Molecular, and Chemical Techniques Used in Authentication of Plant Materials for Cosmetic Applications

Cosmetics doi: 10.3390/cosmetics5020030

Authors: Samantha Drouet Laurine Garros Christophe Hano Duangjai Tungmunnithum Sullivan Renouard Daniel Hagège Benoit Maunit Éric Lainé

A number of approaches can be implemented to ensure plant-based material authentication for cosmetic applications. Doing this requires knowledge and data dealing with botany, molecular biology, and analytical chemistry, the main techniques of which are described here. A comprehensive and critical view of the methods is provided with comments as well as examples of their application domains.

https://ift.tt/2HFr3PZ

CD14+ monocytes contribute to inflammation in chronic nonbacterial osteomyelitis (CNO) through increased NLRP3 inflammasome expression

Publication date: Available online 30 April 2018
Source:Clinical Immunology
Author(s): D. Brandt, E. Sohr, J. Pablik, A. Schnabel, F. Kapplusch, K. Mäbert, J.H. Girschick, H. Morbach, F. Thielemann, S.R. Hofmann, C.M. Hedrich
The pathophysiology of chronic nonbacterial osteomyelitis (CNO) remains incompletely understood. Increased NLRP3 inflammasome activation and IL-1β release in monocytes from CNO patients was suggested to contribute to bone inflammation. Here, we dissect immune cell infiltrates and demonstrate the involvement of monocytes across disease stages. Differences in cell density and immune cell composition may help to discriminate between BOM and CNO. However, differences are subtle and infiltrates vary in CNO. In contrast to other cells involved, monocytes are a stable element during all stages of CNO, which makes them a promising candidate in the search for "drivers" of inflammation. Furthermore, we link increased expression of inflammasome components NLRP3 and ASC in monocytes with site-specific DNA hypomethylation around the corresponding genes NLRP3 and PYCARD. Our observations deliver further evidence for the involvement of pro-inflammatory monocytes in the pathophysiology of CNO. Cellular and molecular alterations may serve as disease biomarkers and/or therapeutic targets.



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Frontmatter

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 5
Pages: i-iii

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Review and evaluation of patient-centered psychosocial assessments for children with central precocious puberty or early puberty

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 5
Pages: 485-495

https://ift.tt/2I67WxR

Childhood obesity: how long should we wait to predict weight?

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 5
Pages: 497-501

https://ift.tt/2w2glgP

Glycated hemoglobin A1c as a screening test for detecting type 2 diabetes mellitus in obese children and adolescents

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 5
Pages: 503-506

https://ift.tt/2raRLFB

Effect of a multidisciplinary treatment program on eating behavior in overweight and obese preschool children

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 5
Pages: 507-513

https://ift.tt/2w0hhSY

Body composition and metabolic health of young male adults with childhood-onset multiple pituitary hormone deficiency after cessation of growth hormone treatment

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 5
Pages: 533-537

https://ift.tt/2I2QDxD

Hematuria as an adverse outcome following provocative growth hormone stimulation testing in children

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 5
Pages: 539-543

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Adult height in patients with familial male-limited precocious puberty and the role of an aromatase inhibitor in patient management

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 5
Pages: 551-560

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Association between UCP polymorphisms and adipokines with obesity in Mexican adolescents

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 5
Pages: 561-568

https://ift.tt/2rbn0k8

Impact of childhood type 1 diabetes on maternal work-family relations

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 5
Pages: 569-576

https://ift.tt/2w0GEUP

Graves’ disease following allogenic hematopoietic stem cell transplantation for severe aplastic anemia: case report and literature review

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 5
Pages: 589-593

https://ift.tt/2rdNrph

Abstracts of the 16th Annual Scientific Meeting of the College of Pathologists, Academy of Medicine of Malaysia.

Related Articles

Abstracts of the 16th Annual Scientific Meeting of the College of Pathologists, Academy of Medicine of Malaysia.

Malays J Pathol. 2018 Apr;40(1):83-102

Authors:

Abstract
No abstract available.

PMID: 29704390 [PubMed]

https://ift.tt/2Fwqq55

Recommended parameters for pathology reporting of gastroenteropancreatic neuroendocrine tumours (GEP-NETs).

Related Articles

Recommended parameters for pathology reporting of gastroenteropancreatic neuroendocrine tumours (GEP-NETs).

Malays J Pathol. 2018 Apr;40(1):79-82

Authors:

Abstract
No abstract available.

PMID: 29704389 [PubMed - in process]

https://ift.tt/2KsVPZZ

Autologous mononuclear cells from different sources are seen to improve wound healing in patients with haematological malignancies.

Related Articles

Autologous mononuclear cells from different sources are seen to improve wound healing in patients with haematological malignancies.

Malays J Pathol. 2018 Apr;40(1):61-67

Authors: Wan Jamaludin WF, Mohamad Yusoff F, Ismail NA, Mohd Idris MR, Palaniappan S, Ng CKK, Abdullah N, Zaider SZA, Abdul Wahid SFS

Abstract
INTRODUCTION: Immunosuppressive state due to haematological malignancies and chemotherapy may cause disruption to wound healing despite optimum conventional treatment and standard wound dressing. Non-healing wounds are predisposed to infection whereas chemotherapy dose reductions or interruptions are associated with poor survival.
BACKGROUND: Mononuclear cells contain progenitor cells including haematopoietic and mesenchymal stem cells, endothelial progenitor cells and fibroblasts which facilitate wound healing through cytokines, growth factor secretions, cell-cell interactions and provision of extracellular matrix scaffolding. Clinical applications of autologous mononuclear cells therapy in wound healing in non-malignant patients with critical limb ischaemia have been reported with remarkable outcome.
METHODS: We report three patients with haematological malignancies undergoing chemotherapy, who received autologous mononuclear cells implantation to treat non-healing wound after optimum conventional wound care. The sources of mononuclear cells (MNC) were from bone marrow (BM), peripheral blood (PB) and mobilised PB cells (mPB-MNC) using granulocyte colony stimulating factor (G-CSF). The cells were directly implanted into wound and below epidermis. Wound sizes and adverse effects from implantation were assessed at regular intervals.
RESULTS: All patients achieved wound healing within three months following autologous mononuclear cells implantation. No implantation adverse effects were observed.
CONCLUSIONS: Autologous mononuclear cells therapy is a feasible alternative to conventional wound care to promote complete healing in non-healing wounds compounded by morbid factors such as haematological malignancies, chemotherapy, diabetes mellitus (DM), infections and prolonged immobility.

PMID: 29704386 [PubMed - in process]

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CD10 expression pattern in prostatic adenocarcinoma: Elucidation of differences between Gleason's grades.

Related Articles

CD10 expression pattern in prostatic adenocarcinoma: Elucidation of differences between Gleason's grades.

Malays J Pathol. 2018 Apr;40(1):57-60

Authors: Kaur M, Verma S, Gupta R, Pant L, Singh S

Abstract
CD10, a transmembrane endopeptidase, has been shown to be lost as an early event in prostate cancer. We aimed at evaluating the pattern of expression of CD10 in various Gleason's grades of prostatic adenocarcinoma in comparison with nodular hyperplasia of prostate. This retrospective study included 30 cases of nodular hyperplasia and 30 of prostatic adenocarcinoma of various Gleason's grades. Immunohistochemical staining for CD10 was performed on all cases and positivity evaluated as percentage of cells as well as location (membranous or cytoplasmic or both). Of prostatic adenocarcinomas, grade 3 was seen in 10 foci, grade 4 in 28 and grade 5 in 22 foci. CD10 positivity in carcinoma was lower than in nodular hyperplasia, with the lowest positivity in grade 5. The pattern of expression of CD10 also changed from membranous in grade 3 to cytoplasmic in grade 5. Loss of CD10 expression appears to be associated with increasing tumour grade in carcinoma prostate and this can potentially be useful in stratification of such patients.

PMID: 29704385 [PubMed - in process]

https://ift.tt/2KqkNt3

Epstein-Barr virus infection in B-cell Non-Hodgkin's Lymphomas of the oral and maxillofacial region: Is there any evidence?

Related Articles

Epstein-Barr virus infection in B-cell Non-Hodgkin's Lymphomas of the oral and maxillofacial region: Is there any evidence?

Malays J Pathol. 2018 Apr;40(1):49-56

Authors: Abdelrahim LM, Peh SC, Kallarakkal TG

Abstract
INTRODUCTION: Epstein-Barr virus (EBV) might be an aetiological agent involved in the pathogenesis of certain Non-Hodgkin's Lymphomas (NHLs). EBV infection has been diagnosed by serologic testing within the tumour biopsies of patients with NHL. However, the association between EBV and NHL is inconsistent with a preference for certain anatomic sites, histologic subtypes and immunosuppressed patients. The objective of this study was to characterise the B-cell NHLs of the oral cavity and maxillofacial region using histological and immunophenotypical techniques and to determine its association with EBV infection.
MATERIALS AND METHODS: This was a descriptive cross-sectional study that included 14 cases of B-cell NHLs of the oral cavity and maxillofacial region. The haematopoietic and lymphoid tissue tumours classification of WHO was used to categorize the cases. In-situ hybridisation for EBV-encoded RNA was performed to confirm the EBV infection.
RESULTS: The average age of the patients included in the study was found to be 48.8 ± 23 years with a higher female to male ratio (1.3:1). Our study suggested that diffuse large B-cell lymphomas (DLBCLs) and Burkitt's lymphomas (BLs) constitute the predominant subtypes of lymphomas affecting the oral cavity and maxillofacial regions.
CONCLUSION: The findings from our study support the view that at least a relatively smaller proportion of B-cell NHLs that occur in the oral cavity and maxillofacial region do not have a pathogenic association with EBV.

PMID: 29704384 [PubMed - in process]

https://ift.tt/2Fv2C1J

Study on ABO and RhD blood grouping: Comparison between conventional tile method and a new solid phase method (InTec Blood Grouping Test Kit).

Related Articles

Study on ABO and RhD blood grouping: Comparison between conventional tile method and a new solid phase method (InTec Blood Grouping Test Kit).

Malays J Pathol. 2018 Apr;40(1):27-32

Authors: Yousuf R, Abdul Ghani SA, Abdul Khalid N, Leong CF

Abstract
INTRODUCTION: 'InTec Blood Grouping Test kit' using solid-phase technology is a new method which may be used at outdoor blood donation site or at bed side as an alternative to the conventional tile method in view of its stability at room temperature and fulfilled the criteria as point of care test. This study aimed to compare the efficiency of this solid phase method (InTec Blood Grouping Test Kit) with the conventional tile method in determining the ABO and RhD blood group of healthy donors.
METHODS: A total of 760 voluntary donors who attended the Blood Bank, Penang Hospital or offsite blood donation campaigns from April to May 2014 were recruited. The ABO and RhD blood groups were determined by the conventional tile method and the solid phase method, in which the tube method was used as the gold standard.
RESULTS: For ABO blood grouping, the tile method has shown 100% concordance results with the gold standard tube method, whereas the solid-phase method only showed concordance result for 754/760 samples (99.2%). Therefore, for ABO grouping, tile method has 100% sensitivity and specificity while the solid phase method has slightly lower sensitivity of 97.7% but both with good specificity of 100%. For RhD grouping, both the tile and solid phase methods have grouped one RhD positive specimen as negative each, thus giving the sensitivity and specificity of 99.9% and 100% for both methods respectively.
CONCLUSION: The 'InTec Blood Grouping Test Kit' is suitable for offsite usage because of its simplicity and user friendliness. However, further improvement in adding the internal quality control may increase the test sensitivity and validity of the test results.

PMID: 29704381 [PubMed - in process]

https://ift.tt/2FvBLT2

The spectrum of pathological findings of tonsils in children: A clinicopathological review.

Related Articles

The spectrum of pathological findings of tonsils in children: A clinicopathological review.

Malays J Pathol. 2018 Apr;40(1):11-26

Authors: Tan GC, Stalling M, Al-Rawabdeh S, Kahwash BM, Alkhoury RF, Kahwash SB

Abstract
Tonsillectomy is among the most commonly performed operations in children. Although follicular lymphoid hyperplasia is usually the main and only pathologic finding at microscopic examination, a variety of other rare but important pathologic changes may be encountered. This review aims to provide an inclusive practical resource and reference for both training and practising pathologists. It discusses the spectrum of pathologic findings, including both neoplastic and non-neoplastic conditions and provides illustrative images.

PMID: 29704380 [PubMed - in process]

https://ift.tt/2KpvLiB

Mechanical profiles of murder and murderers: An extensive review.

Related Articles

Mechanical profiles of murder and murderers: An extensive review.

Malays J Pathol. 2018 Apr;40(1):1-10

Authors: Kamaluddin MR, Md Shariff NS, Mat Saat GA

Abstract
INTRODUCTION: Murder is an extreme form of violent crime which occurs across all social, cultural, and ethnic spheres. It is therefore, crucial to understand the nature and the extent of mechanical profiles of murder and murderers. The purpose of this article is to review such critical aspects of murder in a nutshell.
METHODS: An archival research methodology was employed in this study where relevant search for literatures on these mechanical aspects related to murder was made across search engines such as Google Scholar and Elsevier with relevant articles selected for this review.
RESULTS AND DISCUSSION: This review discusses in an in-depth manner, pivotal mechanical profiles which include motives, methods of killing, choice of weapon, settings, targeted body parts, and murder victim concealment. In-depth understanding of each mechanical aspect offers an opportunity to the public at large to expand their knowledge on murder prevention manners which is vital for crime prevention efforts in the future.

PMID: 29704379 [PubMed - in process]

https://ift.tt/2FvB3VS

Feature Highlighting Enhances Learning of a Complex Natural-Science Category.

Author: Miyatsu, Toshiya; Gouravajhala, Reshma; Nosofsky, Robert M.; McDaniel, Mark A.

DOI: 10.1037/xlm0000538

Publication Date: POST AUTHOR CORRECTIONS, 26 April 2018

https://ift.tt/2HLNn6c

Reading Direction Influences Lateral Biases in Letter Processing.

Author: Ransley, Kim; Goodbourn, Patrick T.; Nguyen, Elizabeth H. L.; Moustafa, Ahmed A.; Holcombe, Alex O.

DOI: 10.1037/xlm0000540

Publication Date: POST AUTHOR CORRECTIONS, 26 April 2018

https://ift.tt/2I6MaKj

Children Learn Spurious Associations in Their Math Textbooks: Examples From Fraction Arithmetic.

Author: Braithwaite, David W.; Siegler, Robert S.

DOI: 10.1037/xlm0000546

Publication Date: POST AUTHOR CORRECTIONS, 26 April 2018

https://ift.tt/2HGQGM7

The Variability Puzzle in Human Memory.

Author: Kahana, Michael J.; Aggarwal, Eash V.; Phan, Tung D.

DOI: 10.1037/xlm0000553

Publication Date: POST AUTHOR CORRECTIONS, 26 April 2018

https://ift.tt/2jiuAVC

The Native-Language Benefit for Talker Identification Is Robust in 7.5-Month-Old Infants.

Author: Fecher, Natalie; Johnson, Elizabeth K.

DOI: 10.1037/xlm0000555

Publication Date: POST AUTHOR CORRECTIONS, 26 April 2018

https://ift.tt/2HLCykZ

Lexical Gaps and Morphological Decomposition: Evidence From German.

Author: Schuster, Swetlana; Lahiri, Aditi

DOI: 10.1037/xlm0000560

Publication Date: POST AUTHOR CORRECTIONS, 26 April 2018

https://ift.tt/2I3ZoY4

Effects of Phrase and Word Frequencies in Noun Phrase Production.

Author: Shao, Zeshu; van Paridon, Jeroen; Poletiek, Fenna; Meyer, Antje S.

DOI: 10.1037/xlm0000570

Publication Date: POST AUTHOR CORRECTIONS, 26 April 2018

https://ift.tt/2jhvhyx

Metamemory and Memory for a Wide Range of Font Sizes: What is the Contribution of Perceptual Fluency?.

Author: Undorf, Monika; Zimdahl, Malte F.

DOI: 10.1037/xlm0000571

Publication Date: POST AUTHOR CORRECTIONS, 26 April 2018

https://ift.tt/2HIahLM

Reward-Based Motor Adaptation Can Generalize Across Actions.

Author: van der Kooij, Katinka; Smeets, Jeroen B. J.

DOI: 10.1037/xlm0000573

Publication Date: POST AUTHOR CORRECTIONS, 26 April 2018

https://ift.tt/2jh2dXU

Simulation, False Memories, and the Planning of Future Events.

Author: Dewhurst, Stephen A.; Anderson, Rachel J.; Grace, Lydia; Howe, David

DOI: 10.1037/xlm0000575

Publication Date: POST AUTHOR CORRECTIONS, 26 April 2018

https://ift.tt/2HLdhHC

Sleep Reduces the Testing Effect-But Not After Corrective Feedback and Prolonged Retention Interval.

Author: Abel, Magdalena; Haller, Valerie; Kock, Hanna; Potschke, Sarah; Heib, Dominik; Schabus, Manuel; Bauml, Karl-Heinz T.

DOI: 10.1037/xlm0000576

Publication Date: POST AUTHOR CORRECTIONS, 26 April 2018

https://ift.tt/2jk6lGv

How Does Chunking Help Working Memory?.

Author: Thalmann, Mirko; Souza, Alessandra S.; Oberauer, Klaus

DOI: 10.1037/xlm0000578

Publication Date: POST AUTHOR CORRECTIONS, 26 April 2018

https://ift.tt/2HKBPjF

How the Tracking of Habitual Rate Influences Speech Perception.

Author: Maslowski, Merel; Meyer, Antje S.; Bosker, Hans Rutger

DOI: 10.1037/xlm0000579

Publication Date: POST AUTHOR CORRECTIONS, 26 April 2018

https://ift.tt/2jk69XN

Flexible Egocentricity: Asymmetric Switch Costs on a Perspective-Taking Task.

Author: Samuel, Steven; Roehr-Brackin, Karen; Jelbert, Sarah; Clayton, Nicola S.

DOI: 10.1037/xlm0000582

Publication Date: POST AUTHOR CORRECTIONS, 26 April 2018

https://ift.tt/2HGijop

Cross-Sensory Correspondences in Language: Vowel Sounds Can Symbolize the Felt Heaviness of Objects.

Author: Walker, Peter; Parameswaran, Caroline Regina

DOI: 10.1037/xlm0000583

Publication Date: POST AUTHOR CORRECTIONS, 26 April 2018

https://ift.tt/2I3yyzq

Persistent Structural Priming During Online Second-Language Comprehension.

Author: Wei, Hang; Boland, Julie E.; Cai, Zhenguang G.; Yuan, Fang; Wang, Min

DOI: 10.1037/xlm0000584

Publication Date: POST AUTHOR CORRECTIONS, 26 April 2018

https://ift.tt/2HLd4Ek

Recollection Is Fast and Slow.

Author: Brainerd, C. J.; Nakamura, K.; Lee, W.-F. A.

DOI: 10.1037/xlm0000588

Publication Date: POST AUTHOR CORRECTIONS, 26 April 2018

https://ift.tt/2jht85R

Remembering What Was Said and Done: The Activation and Facilitation of Memory for Gesture as a Consequence of Retrieval.

Author: Overoye, Acacia L.; Storm, Benjamin C.

DOI: 10.1037/xlm0000591

Publication Date: POST AUTHOR CORRECTIONS, 26 April 2018

https://ift.tt/2HIDaHV

Fluorescent characteristic and compositional change of dissolved organic matter and its effect on heavy metal distribution in composting leachates

Abstract

Composting leachates were collected to investigate the fluorescent characteristic and compositional change of dissolved organic matter (DOM) and the effects of the DOM and nutrients on heavy metal distribution during a leachate combination treatment process. Excitation-emission matrix (EEM) fluorescence spectra showed that, with the progress of the treatment units, the content of fulvic-like, humic-like, and protein-like substances gradually decreased. One fulvic-like component (C1), three humic-like components (C2, C3, and C4), and three protein-like components (C5, C6, and C7) were identified in the leachate DOM by parallel factor analysis. Anaerobic-aerobic processes removed a large fraction of the tyrosine-like component (C7) and tryptophan-like component (C6) and a small amount of humic-like component (C2), while the membrane bioreactor showed a good removal effect on protein-like component. The ultra-filtration membrane treatment had a removal effect on fulvic-like and humic-like component and other recalcitrant compounds, while the reverse osmosis treatment had a good removal effect on both humic-like and protein-like components. Correlation analysis indicated that Mn and Cr were primarily associated with protein-like components and nutrients in the composting leachates. Ni and Pb were bound to fulvic-like, humic-like, and protein-like components, Co and Zn interacted with inorganic nitrogen and total phosphorus, and Cd only interacted with inorganic nitrogen.

https://ift.tt/2HD3FCy

Remembering Pathogen Dose: Long-Term Adaptation in Innate Immunity

Publication date: Available online 30 April 2018
Source:Trends in Immunology
Author(s): Michael Bauer, Sebastian Weis, Mihai G. Netea, Reinhard Wetzker
Recent investigations reveal memory-like adaptive responses of the innate immune system to sequential pathogen challenge. Of note, opposing effects that include both sensitization ('training') and desensitization ('tolerance') have been reported. While hitherto the nature of the pathogen was thought to be of prime importance, we propose that pathogen dose plays a key role in determining these opposing effects. Within this concept, training and tolerance of innate immune cells emerge as adaptive responses to increasing pathogen load. Furthermore, environmental stressors significantly impact the pathogen-induced responses of these innate immune cells. Therefore, we hypothesize that pathogens, like other stressors, provoke hormetic responses of the affected cells. This concept could explain the tight interplay of dose-related effects of pathogens and other stressors in infectious diseases.



https://ift.tt/2HL8W7i

The Intestinal Epithelium: Central Coordinator of Mucosal Immunity

Publication date: Available online 30 April 2018
Source:Trends in Immunology
Author(s): Joannie M. Allaire, Shauna M. Crowley, Hong T. Law, Sun-Young Chang, Hyun-Jeong Ko, Bruce A. Vallance
The gastrointestinal (GI) tract represents a unique challenge to the mammalian immune system. It must tolerate the presence of the luminal microbiota and thus not respond to their products, but still protect the intestinal mucosa from potentially harmful dietary antigens and invading pathogens. The intestinal epithelium, composed of a single layer of cells, is crucial for preserving gut homeostasis and acts both as a physical barrier and as a coordinating hub for immune defense and crosstalk between bacteria and immune cells. We highlight here recent findings regarding communication between microbes and intestinal epithelial cells (IECs), as well as the immune mechanisms employed by distinct IEC subsets to promote homeostasis, emphasizing the central and active role that these cells play in host enteric defense.



https://ift.tt/2jiZfC9

Divergent Roles of Antiself Antibodies during Infection

Publication date: Available online 30 April 2018
Source:Trends in Immunology
Author(s): Juan Rivera-Correa, Ana Rodriguez
Antiself antibodies are most commonly associated with autoimmune disorders, but a large body of evidence indicates that they are also present in numerous infectious diseases. These autoimmune antibodies appear transiently during infection with a number of viruses, bacteria, and parasites and in some cases have been associated with the development of autoimmune disorders that develop after infection has been cleared. Traditionally these infection-associated autoantibodies are considered an erroneous byproduct of a legitimate immune response, but their possible role in the clearance of microbes and infected cells or inhibition of host-cell invasion suggests that they may be present because of their beneficial protective role against various infections.



https://ift.tt/2HI32Um

RE: “MODELING RISK-FACTOR TRAJECTORIES WHEN MEASUREMENT TOOLS CHANGE SEQUENTIALLY DURING FOLLOW-UP IN COHORT STUDIES: APPLICATION TO DIETARY HABITS IN PRODROMAL DEMENTIA”

https://ift.tt/2HZeGgS

The impact of environmental pollution on public health expenditure: dynamic panel analysis based on Chinese provincial data

Abstract

In recent years, along with rapid economic growth, China's environmental problems have become increasingly prominent. At the same time, the level of China's pollution has been growing rapidly, which has caused huge damages to the residents' health. In this regard, the public health expenditure ballooned as the environmental quality deteriorated in China. In this study, the effect of environmental pollution on residents' health expenditure is empirically investigated by employing the first-order difference generalized method of moments (GMM) method to control for potential endogeneity. Using a panel data of Chinese provinces for the period of 1998–2015, this study found that the environmental pollution (represented by SO₂ and soot emissions) would indeed lead to the increase in the medical expenses of Chinese residents. At the current stage of economic development, an increase in SO₂ and soot emissions per capita would push up the public health expenditure per capita significantly. The estimation results are quite robust for different types of regression specifications and different combinations of control variables. Some social and economic variables such as public services and education may also have remarkable influences on residential medical expenses through different channels.

https://ift.tt/2FvnR3n

Deletion of fetoplacental Fshr inhibits fetal vessel angiogenesis in the mouse placenta

Publication date: Available online 30 April 2018
Source:Molecular and Cellular Endocrinology
Author(s): Julie A.W. Stilley, Deborah L. Segaloff
It has been shown in both human and mouse placentas that follicle stimulating hormone receptor (FSHR) is expressed in fetal vascular endothelium. There are conflicting reports, however, on the role of FSH to stimulate angiogenesis in vitro in cultured endothelial cells from umbilical veins. Therefore, in this study we undertook an in vivo approach utilizing Fshr null mice to definitively address this question. In the context where all pregnant dams have identical Fshr genotypes, we generated fetuses and associated fetal portions of placenta that were Fshr wt or Fshr null and analyzed angiogenesis within the placental labyrinths. Quantitative morphometric analyses of placentas obtained at mid-gestation revealed that the percentage of the placenta composed of labyrinth is significantly decreased in Fshr null placentas relative to wt placentas. Furthermore, data presented demonstrate that within the Fshr null labyrinths, fetal vessel angiogenesis was significantly reduced relative to wt labyrinths. The results obtained with this combination of in vivo and genetic approaches conclusively demonstrate that signaling through endothelial FSHR does indeed stimulate angiogenesis and that placental Fshr is essential for normal angiogenesis of the fetal placental vasculature.



https://ift.tt/2rb6mQJ

Cross-talk between insulin signalling and LPS responses in mouse macrophages

Publication date: Available online 30 April 2018
Source:Molecular and Cellular Endocrinology
Author(s): Soumojit Pal, Poulomi Nath, Debabrata Das, Sudip Hajra, Sudipta Maitra
The effect of insulin priming on Il-10 expression, regulation of inflammatory cytokines and participation of intra-cellular signalling events, primarily ERK1/2 and PI3K/Akt, has been investigated in high glucose (HG) and/or lipopolysaccharide (LPS)-induced murine macrophages. Our results demonstrate that congruent with sharp increase in ERK1/2 and CREB phosphorylation, insulin stimulation in vitro promotes significant increase in Il-10 expression in mouse peritoneal macrophage and RAW 264.7 cells, both positive for anti-IRβ. Pharmacological inhibition of MEK/MAPK, but not PI3K/Akt cascade, abrogates CREB phosphorylation and Il-10 synthesis indicating functional relevance of insulin action. Conversely, priming with PI3K inhibitor wortmannin prevents insulin attenuation of HG- and/or LPS-induced p38 MAPK and NF-κB activation, Tnf-α, Il-1β expression as well as NO production. Congruent with reduced Il-10 expression, MEK inhibition abrogates insulin action allowing significant increase in Tlr4 expression and LPS response indicating insulin-induced Il-10 might have pivotal influence in regulation of chronic as well as acute inflammatory response.



https://ift.tt/2HCFrZf

Mindfulness-based exposure and response prevention for obsessive compulsive disorder: Findings from a pilot randomised controlled trial

Publication date: Available online 30 April 2018
Source:Journal of Anxiety Disorders
Author(s): Clara Strauss, Laura Lea, Mark Hayward, Elizabeth Forrester, Tamara Leeuwerik, Anna-Marie Jones, Claire Rosten
BackgroundOnly about half of people with obsessive compulsive disorder (OCD) show clinically significant improvement following the recommended therapy, exposure and response prevention (ERP), partly due to poor therapy acceptability. A mindfulness-based approach to ERP (MB-ERP) has the potential to improve acceptability and outcomes.MethodsThis was an internal pilot randomised controlled trial (RCT) of group MB-ERP compared to group ERP. 37 participants meeting DSM-IV OCD criteria were randomly allocated to MB-ERP or ERP.ResultsBoth groups improved in OCD symptom severity. However, MB-ERP did not lead to clinically important improvements in OCD symptom severity at post-intervention compared to ERP − the minimum clinically important difference was not contained in the 95% confidence intervals. There were negligible between-group differences in engagement and MB-ERP did not appear to have broader benefits compared to ERP on depression, wellbeing or OCD-related beliefs. Conversely, MB-ERP led to medium/medium-large improvements in mindfulness compared to ERP.ConclusionsMB-ERP is unlikely to lead to clinically meaningful improvements in OCD symptom severity compared to ERP alone. We underline the importance of adhering to treatment guidelines recommending ERP for OCD. Insufficient attention may have been given to mindfulness practice/discussion in MB-ERP and further research is recommended to explore this possibility.



https://ift.tt/2jlmPyr

Assessing cross-modal target transition effects with a visual-auditory oddball

Publication date: Available online 30 April 2018
Source:International Journal of Psychophysiology
Author(s): John E. Kiat
Prior research has shown contextual manipulations involving temporal and sequence related factors significantly moderate attention-related responses, as indexed by the P3b event-related-potential, towards infrequent (i.e., deviant) target oddball stimuli. However, significantly less research has looked at the influence of cross-modal switching on P3b responding, with the impact of target-to-target cross-modal transitions being virtually unstudied. To address this gap, this study recorded high-density (256 electrodes) EEG data from twenty-five participants as they completed a cross-modal visual-auditory oddball task. This task was comprised of unimodal visual (70% Nontargets: 30% Deviant-targets) and auditory (70% Nontargets: 30% Deviant-targets) oddballs presented in fixed alternating order (i.e., visual-auditory-visual-auditory, etc.) with participants being tasked with detecting deviant-targets in both modalities. Differences in the P3b response towards deviant-targets as a function of preceding deviant-target's presentation modality was analyzed using temporal-spatial PCA decomposition. In line with predictions, the results indicate that the ERP response to auditory deviant-targets preceded by visual deviant-targets exhibits an elevated P3b, relative to the processing of auditory deviant-targets preceded by auditory deviant-targets. However, the processing of visual deviant-targets preceded by auditory deviant-targets exhibited a reduced P3b response, relative to the P3b response towards visual deviant-targets preceded by visual deviant-targets. These findings provide the first demonstration of temporally and perceptually decoupled target-to-target cross-modal transitions moderating P3b responses on the oddball paradigm, generally providing support for the context-updating interpretation of the P3b response.



https://ift.tt/2raGJAk

Utilizing time-frequency amplitude and phase synchrony measure to assess feedback processing in a gambling task

Publication date: Available online 30 April 2018
Source:International Journal of Psychophysiology
Author(s): Adreanna T.M. Watts, Anne V. Tootell, Spencer T. Fix, Selin Aviyente, Edward M. Bernat
The neurophysiological mechanisms involved in the evaluation of performance feedback have been widely studied in the ERP literature over the past twenty years, but understanding has been limited by the use of traditional time-domain amplitude analytic approaches. Gambling outcome valence has been identified as an important factor modulating event-related potential (ERP) components, most notably the feedback negativity (FN). Recent work employing time-frequency analysis has shown that processes indexed by the FN are confounded in the time-domain and can be better represented as separable feedback-related processes in the theta (3–7 Hz) and delta (0–3 Hz) frequency bands. In addition to time-frequency amplitude analysis, phase synchrony measures have begun to further our understanding of performance evaluation by revealing how feedback information is processed within and between various brain regions. The current study aimed to provide an integrative assessment of time-frequency amplitude, inter-trial phase synchrony, and inter-channel phase synchrony changes following monetary feedback in a gambling task. Results revealed that time-frequency amplitude activity explained separable loss and gain processes confounded in the time-domain. Furthermore, phase synchrony measures explained unique variance above and beyond amplitude measures and demonstrated enhanced functional integration between medial prefrontal and bilateral frontal, motor, and occipital regions for loss relative to gain feedback. These findings demonstrate the utility of assessing time-frequency amplitude, inter-trial phase synchrony, and inter-channel phase synchrony together to better elucidate the neurophysiology of feedback processing.



https://ift.tt/2JFedxv

Biotechnological applications of bacteriophages: State of the art

Publication date: Available online 30 April 2018
Source:Microbiological Research
Author(s): Liliam K. Harada, Erica C. Silva, Welida F. Campos, Fernando S. Del Fiol, Marta Vila, Krystyna Dąbrowska, Victor N. Krylov, Victor M. Balcão
Bacteriophage particles are the most abundant biological entities on our planet, infecting specific bacterial hosts in every known environment and being major drivers of bacterial adaptive evolution. The study of bacteriophage particles potentially sheds light on the development of new biotechnology products. Bacteriophage therapy, although not new, makes use of strictly lytic phage particles as an alternative in the antimicrobial treatment of resistant bacterial infections and is being rediscovered as a safe method due to the fact that these biological entities devoid of any metabolic machinery do not have affinity to eukaryotic cells. Furthermore, bacteriophage-based vaccination is emerging as one of the most promising preventive strategies. This review paper discusses the biological nature of bacteriophage particles, their mode(s) of action and potential exploitation in modern biotechnology. Topics covered in detail include the potential of bacteriophage particles in human infections (bacteriophage therapy), nanocages for gene delivery, food biopreservation and safety, biocontrol of plant pathogens, phage display, bacterial biosensing devices, vaccines and vaccine carriers, biofilm and bacterial growth control, surface disinfection, corrosion control, together with structural and functional stabilization issues.



https://ift.tt/2HIULQ6

Evidence for Up and Down Regulation of 450 genes by rpoB12 (rif) Mutation and their Implications in Complexity of Transcription Modulation in Escherichia coli

Publication date: Available online 30 April 2018
Source:Microbiological Research
Author(s): Shanmugaraja Meenakshi, M. Hussain Munavar
Analyses of mutations in rpoB subunit of Escherichia coli that lead to resistance to rifampicin have been invaluable in providing insight into events during transcription continue to be discovered. Earlier we reported that rpoB12 suppresses over-expression of cps genes in Δlon mutant of E.coli, by interfering with the transcription of rcsA. Here we report Microarray based Transcriptome profile of Δlon and Δlon rpoB12 strains. The data analyses clearly reveal that rpoB12 mutation results in the differential expression of ∼450 genes. The transcription profiles of some of the genes namely, rcsA, gadE, csgD, bolA, ypdI, dnaJ, clpP, csrA and hdeA are significantly altered, particularly the genes implicated in virulence. Some of the phenotypic traits namely, biofilm formation, motility, curli synthesis and ability to withstand acidic stress in a lon⁺rpoB12 strain were assessed. The results clearly indicate that rpoB12 up-regulates biofilm formation and curli synthesis while it makes the cells sensitive for growth in acidic medium and inhibits motility almost completely. Furthermore, rpoB12 modulates the expression profile of a significant number of genes involved in stress responses, genes encoding small RNAs. Thus, this study reveals the versatile role of the rpoB12 mutation, especially its impact on the regulation of genes related to virulence and highlights its medical importance.



https://ift.tt/2I5LmFE

Pathogenesis-Related Proteins and Peptides as Promising Tools for Engineering Plants with Multiple Stress Tolerance

Publication date: Available online 30 April 2018
Source:Microbiological Research
Author(s): Sajad Ali, Bashir Ahmad Ganai, Azra N Kamili, Ajaz Ali Bhat, Zahoor Ahmad Mir, Javaid Akhter Bhat, Anshika Tyagi, Sheikh Tajamul Islam, Muntazir Mushtaq, Prashant Yadav, Sandhya Rawat, Anita Grover
Pathogenesis-related (PR) proteins and antimicrobial peptides (AMPs) are a group of diverse molecules that are induced by phytopathogens as well as defense related signaling molecules. They are the key components of plant innate immune system especially systemic acquired resistance (SAR), and are widely used as diagnostic molecular markers of defense signaling pathways. Although, PR proteins and peptides have been isolated much before but their biological function remains largely enigmatic despite the availability of new scientific tools. The earlier studies have demonstrated that PR genes provide enhanced resistance against both biotic and abiotic stresses, which make them one of the most promising candidates for developing multiple stress tolerant crop varieties. In this regard, plant genetic engineering technology is widely accepted as one of the most fascinating approach to develop the disease resistant transgenic crops using different antimicrobial genes like PR genes. Overexpression of PR genes (chitinase, glucanase, thaumatin, defensin and thionin) individually or in combination have greatly uplifted the level of defense response in plants against a wide range of pathogens. However, the detailed knowledge of signalling pathways that regulates the expression of these versatile proteins is critical for improving crop plants to multiple stresses, which is the future theme of plant stress biology. Hence, this review provides an overall overview on the PR proteins like their classification, role in multiple stresses (biotic and abiotic) as well as in various plant defense signaling cascades. We also highlight the success and snags of transgenic plants expressing PR proteins and peptides.



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Use of Neodymium magnetic discs as pressure earrings for ear lobe keloid post-excision

https://ift.tt/2JBiGBp

2 to Z flap for reconstruction of adjacent skin defects

https://ift.tt/2ra1Brg

Split Ear Lobe Repair with Piercing Preservation and Optimal Ear Lobe Aesthetics

https://ift.tt/2FtYdMx

Chemotherapy Plus Bevacizumab as Neoadjuvant or Conversion Treatment in Patients with Colorectal Liver Metastases

Aim: To evaluate the efficacy of chemotherapy plus bevacizumab as neoadjuvant or conversion treatment for colorectal liver metastases (CLM). Patients and Methods: A retrospective chart review was carried out of 74 patients with CLM treated with neoadjuvant or conversion chemotherapy plus bevacizumab. Results: The overall response rate was 63.4%. An optimal morphological response by computed tomography was reported in 35% of patients. The rate of complete resection was 71.6%. Complete or major pathological response (pR) was attained in 58.2%. The median overall survival (OS) was not reached. Median progression-free (PFS) and relapse-free (RFS) survival were 14.6 and 8.7 months. Among patients reaching an optimal pR, median OS was not reached (p=0.08), and a trend towards longer RFS and PFS was seen. Conclusion: Neoadjuvant or conversion chemotherapy with bevacizumab is an active and tolerable option for CLM with minimal post-surgery complications. Optimal pR is associated with a longer OS and a trend for prolonged PFS and RFS.

https://ift.tt/2r9W3wk

Molecular Mechanisms of Breast Cancer Metastasis and Potential Anti-metastatic Compounds

Throughout the world, breast cancer is among the major causes of cancer-related death and is the most common cancer found in women. The development of cancer molecular knowledge has surpassed the novel concept of cancer biology and unraveled principle targets for anticancer drug developments and treatment strategies. Metastatic breast cancer cells acquire their aggressive features through several mechanisms, including augmentation of survival, proliferation, tumorigenicity, and motility-related cellular pathways. Clearly, natural product-derived compounds have since long been recognized as an important source for anticancer drugs, several of which have been shown to have promising anti-metastasis activities by suppressing key molecular features supporting such cell aggressiveness. This review provides the essential details of breast cancer, the molecular-based insights into metastasis, as well as the effects and mechanisms of potential compounds for breast cancer therapeutic approaches. As the abilities of cancer cells to invade and metastasize are addressed as the hallmarks of cancer, compounds possessing anti-metastatic effects, together with their defined molecular drug action could benefit the development of new drugs as well as treatment strategies.

https://ift.tt/2HELQD0

Chromatin Proteins and Transcription Factors as Therapeutic Targets, Volume 107. 1st Edition

https://ift.tt/2r9VPFu

Estimation of Risk of Normal-tissue Toxicity Following Gastric Cancer Radiotherapy with Photon- or Scanned Proton-beams

Background/Aim: Gastric cancer (GC) radiotherapy involves irradiation of large tumour volumes located in the proximities of critical structures. The advantageous dose distributions produced by scanned-proton beams could reduce the irradiated volumes of the organs at risk (OARs). However, treatment-induced side-effects may still appear. The aim of this study was to estimate the normal tissue complication probability (NTCP) following proton therapy of GC, compared to photon radiotherapy. Patients and Methods: Eight GC patients, previously treated with volumetric-modulated arc therapy (VMAT), were retrospectively planned with scanned proton beams carried out with the single-field uniform-dose (SFUD) method. A beam-specific planning target volume was used for spot positioning and a clinical target volume (CTV) based robust optimisation was performed considering setup- and range-uncertainties. The dosimetric and NTCP values obtained with the VMAT and SFUD plans were compared. Results: With SFUD, lower or similar dose-volume values were obtained for OARs, compared to VMAT. NTCP values of 0% were determined with the VMAT and SFUD plans for all OARs (p>0.05), except for the left kidney (p<0.05), for which lower toxicity was estimated with SFUD. Conclusion: The NTCP reduction, determined for the left kidney with SFUD, can be of clinical relevance for preserving renal function after radiotherapy of GC.

https://ift.tt/2HEXCxu

Re-irradiation Using Intensity-modulated Radiotherapy for Recurrent and Second Primary Head and Neck Cancer

Background/Aim: Information on re-irradiation (re-RT) for recurrent and second primary head and neck cancer is limited. Herein, a description of our long-term experience of re-RT for previously irradiated head and neck cancer is provided. Materials and Methods: A retrospective review was performed for 73 consecutive patients re-irradiated for head and neck cancer between 2006 and 2015. Re-RT targets encompassed only the recurrent gross tumor and had tight margins (5-10 mm). Results: Salvage surgery was performed on 28 (38%) patients before re-RT and 53 (73%) patients received chemotherapy concurrent with re-RT. The median interval between initial and re-RT was 31 months and the median cumulative dose of the two irradiations was 126 Gy (biologically equivalent to 2 Gy fractionation). With a median survival of 33 months, locoregional recurrence after re-RT developed in 37 patients (51%; 25 infield, 12 outfield). In multivariate analysis, higher re-RT dose (≥66 Gy), longer time interval (>2 years), and use of concurrent chemotherapy were associated with improved locoregional recurrence-free survival (all p<0.05). Additionally, performance status, additional surgical resection, and longer interval were associated with better overall survival (p=0.006, 0.021, 0.004, respectively). Clinically significant acute and late toxicities occurred in 14% and 22% of evaluable patients, but no grade 5 toxicity was observed. Conclusion: Moderate safety and acceptable toxicity was found after re-RT using tight margins, sufficient radiation dose, and daily image guidance. Encouraging local control and survival were obtained, similar to historical data using 1-2 cm margins.

https://ift.tt/2rdtgH9

Efficacy of Asparaginase Erwinia chrysanthemi With and Without Temozolomide Against Glioma Cells and Intracranial Mouse Medulloblastoma

Background: Anti-metabolites are less-myelosuppressive than DNA-damaging anticancer drugs and may be useful against brain tumors. Materials and Methods: We evaluated the asparagine/glutamine-deaminating agent Erwinaze with/without temozolomide against brain tumor cells and mouse medulloblastomas. Results. Erwinaze treatment of cell lines and neurospheres led to dose-dependent reductions of cells (reversible by L-glutamine), with half maximal inhibitory concentrations (IC₅₀s) of 0.12->10 IU/ml. Erwinaze at <1 IU/ml reduced temozolomide IC₅₀s by 3.6- to 13-fold (300-1,200 μM to 40-330 μM). Seven-week-old SMO/SMO mice treated with Erwinaze (regardless of temozolomide treatment) had better survival 11 weeks post-therapy, compared to those not treated with Erwinaze (81.25% vs. 46.15, p=0.08). Temozolomide-treated mice developed 10% weight loss, impairing survival. All 16 mice treated with temozolomide (regardless of Erwinaze treatment) succumbed by 40-weeks of age, whereas 5/8 animals treated with Erwinaze alone and 2/6 controls survived (p=0.035). Conclusion: Erwinaze enhances cytotoxicity of temozolomide in vitro, and improves survival in SMO/SMO mice, likely by reducing cerebrospinal fluid glutamine. Temozolomide-associated toxicity prevented demonstration of any potential combinatorial advantage with Erwinaze in vivo.

https://ift.tt/2rb3IeL

The Alcohol Dehydrogenase Isoenzyme as a Potential Marker of Pancreatitis

Background/Aim: Human pancreas parenchyma contains various alcohol dehydrogenase (ADH) isoenzymes and also possesses aldehyde dehydrogenase (ALDH) activity. The altered activities of ADH and ALDH in damaged pancreatic tissue in the course of pancreatitis are reflected in the human serum. The aim of this study was to investigate a potential role of ADH and ALDH as markers for acute (AP) and chronic pancreatitis (CP). Patients and Methods: Serum samples were collected for routine biochemical investigations from 75 patients suffering from acute pancreatitis and 70 patients with chronic pancreatitis. Fluorometric methods were used to measure the activity of class I and II ADH and ALDH activity. The total ADH activity and activity of class III and IV isoenzymes were measured by a photometric method. Results: There was a significant increase in the activity of ADH III isoenzyme (15.06 mU/l and 14.62 mU/l vs. 11.82 mU/l; p<0.001) and total ADH activity (764 mU/l and 735 mU/l vs. 568 mU/l) in the sera of patients with acute pancreatitis or chronic pancreatitis compared to the control. The diagnostic sensitivity for ADH III was about 84%, specificity was 92 %, positive and negative predictive values were 93% and 87% respectively in acute pancreatitis. Area under the Receiver Operating Curve (ROC) curve for ADH III in AP and CP was 0.88 and 0.86 respectively. Conclusion: ADH III has a potential role as a marker of acute and chronic pancreatitis.

https://ift.tt/2JGmhhC

Effect of Tissue Factor on Colorectal Cancer Stem Cells

Background/Aim: Tissue factor (TF) expression increases cancer stem cell (CSC) activity in breast and lung cancer. There are ongoing studies focused on targeting CSCs via anti-TF treatment, for breast and lung cancer therapy. Herein, the aim was to determine whether targeting TF could have an anti-CSC therapeutic role in colorectal cancer (CRC). Materials and Methods: Evaluation of colonosphere-forming efficiency (CFE) and aldehyde dehydrogenase (ALDH) expression level was used to quantify CSC activity in two CRC cell lines, after TF knockdown (TFKD) or TF over-expression (TFOE). Results: TFKD resulted in increased levels of ALDH in SW620 (1.31±0.04-fold, p<0.001) and DLD-1 (1.63±0.14-fold, p=0.04) cells. CFE was increased in SW620 (1.21±0.23% vs. 2.03±0.29%, p=0.01) and DLD-1 (0.41±0.12% vs. 0.68±0.9%, p=0.01) cells. Conversely, TFOE decreased ALDH expression (0.72±0.04-fold, p=0.001) and CFE (0.33±0.05% vs. 0.66±0.14%, p=0.006) in DLD-1, but had no impact on SW620 cells. Conclusion: In the examined CRC cell lines, TF expression was inversely related to CSC activity suggesting that anti-TF therapies may not have a role in CRC treatment.

https://ift.tt/2r90Vmm

Image-guided Stereotactic Body Radiotherapy in Metastatic Prostate Cancer

Background/Aim: In the last years, the use of Image Guided Stereotactic Radiotherapy (IG-SBRT) in patients with metastatic prostate cancer has increased. In this study, we aimed to assess the role of IG-SBRT in terms of local control and safety in patients with metastatic prostate cancer. Materials and Methods: Primary and secondary endpoints of this prospective observational study were local control and safety related to IG-SBRT. All lesions were treated with 24 Gy as a single fraction or 27 Gy in 3 fractions. After SBRT, Systemic therapies were administered only after the occurrence of more than three synchronous active lesions in oligometastatic patients (patients with less than 4 active synchronous lesions) or new lesions occurrence in patients with more than 3 synchronous lesions. Results: From April 2011 to June 2017, 78 metastatic lesions (32 bone and 46 node) from 51 patients with prostate cancer were treated. After a median follow-up of 18.5 months (range=3-103 months), only 2 lesions (4%) relapsed inside the radiation field. All local recurrences were located on the bone. Estimated 12 and 24 months local control ratios were 98.7 and 97.4%, respectively. Except for one case, toxicity greater than G2 was not recorded. Conclusion: IG-SBRT is safe and can be considered as a valid therapy in patients with metastatic prostate cancer requiring a long-lasting metastases control.

https://ift.tt/2JIbGT9

Biology and Engineering of Stem Cell Niches. 1st Edition

https://ift.tt/2JIP2KF

Chemerin in a Mouse Model of Non-alcoholic Steatohepatitis and Hepatocarcinogenesis

Background/Aim: Non-alcoholic steatohepatitis (NASH) is a risk factor for hepatocellular carcinoma (HCC). The adipokine chemerin protects from HCC and is reduced in human HCC. In this study, chemerin expression was analyzed in a murine model of NASH-HCC. Materials and Methods: Serum and hepatic chemerin, and ex vivo chemerin receptor activation were monitored in NASH and NASH-HCC in mice fed a low-methionine diet deficient in choline after initiation of tumors by injection of diethylnitrosamine. Results: In non-tumorous liver tissues, the extent of hepatic steatosis, and the levels of proteins regulating hepatic lipids and liver fibrosis were similar in NASH and NASH-associated HCC. Systemic and hepatic chemerin, and chemerin receptor activation were not changed in HCC. Liver tumors only developed in diethylnitrosamine-injected mice and their number was increased in NASH. Chemerin protein was induced in liver in NASH, but was unchanged in HCC tissues. Conclusion: Hepatic and serum chemerin and ex vivo analyzed chemerin receptor activation do not differ in murine NASH-associated HCC when compared to NASH. Hepatic tumors still develop despite high endogenous levels of serum and liver chemerin protein.

https://ift.tt/2rc6Qqs

Sinusoidal Obstruction Syndrome (Veno-occlusive Disease) Following Hematopoietic Stem Cell Transplant: Insights and Therapeutic Advances

Hepatic sinusoidal obstruction syndrome (SOS) is a rare fatal clinical entity seen following hematopoietic stem cell transplant (HSCT). It is more commonly reported to occur following allogeneic HSCT compared to autologous HSCT. Historically, it is known as hepatitis following HSCT. It is thought that endothelial damage to the hepatic venules leading to occlusion of the terminal hepatic venules and hepatic sinusoids is the trigger for the development of SOS. Several risk factors have been associated with this condition. Some of these risk factors are patient related while others are transplant process related. Given the high mortality of this condition, early identification of high-risk patients with severe disease is of utmost importance. The management of SOS varies depending on the severity of the disease. Mild to moderate disease has a good outcome with supportive measures alone, while severe presentation of the disease requires a more aggressive management. Defibrotide is the only Food and Drug Administration-approved therapy and it is reserved for severe cases of SOS. The role of defibrotide as a prophylactic therapy remains under investigation.

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The Expression of Riboflavin Transporters in Human Colorectal Cancer

Background/Aim: Riboflavin transport in enterocytes is mediated by three translocators: RFVT3 located on the apical membrane, and RFVT1 and RFVT2 on the basolateral membrane. The aim of this study was to investigate whether the expression levels of RFVTs are altered in human colorectal cancer (CRC). Materials and Methods: In human colon adenocarcinoma cell lines (CaCo2, DLD-1, HT-29) and in tissues of patients with CRC, gene and protein expression levels were evaluated by real time-polymerase chain reaction and western blotting. Intracellular flavin content was determined by high-performance liquid chromatography. Results: RFVT3 and RFVT2 gene and protein expression levels were higher in DLD-1 and HT-29 compared to Caco2 cells. In HT-29 cells, the RFVT1 protein level was drastically lower. These differences are presumably responsible for the higher total flavin content in DLD-1 and HT-29 cells. In tumor tissues of patients with CRC, RFVT1 content was reduced at both protein and mRNA levels compared to normal mucosa. RFVT3 and RFVT2 gene expression levels were increased, while protein expression was reduced, with a small reduction in riboflavin amount. Conclusion: This study provides first evidence that transcription/translation of RFVTs are profoundly altered in CRC.

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Comparing Image-guided targeted Biopsies to Radical Prostatectomy Specimens for Accurate Characterization of the Index Tumor in Prostate Cancer

Aim: To evaluate the accuracy of multiparametric magnetic resonance–transrectal ultrasound fusion targeted biopsy (TBx) in the characterization of the index tumor, as confirmed by association with radical prostatectomy (RP) specimens. Patients and Methods: A total of 152 patients with TBx-confirmed prostate cancer (PCa) underwent robot-assisted RP. Stained whole-mount histological sections were used as the reference standard. All lesions with a volume >0.5 ml and/or pathological Gleason score (GS) >6 were defined as clinically significant PCa. The index lesion was defined as the largest tumor focus within the prostate gland. Results: The pathological index tumours included: 147 lesions (96.7%) with a volume >0.5 ml and five (3.3%) with a volume ≤0.5 ml, but with a pathological GS ≥7; 135 (88.8%) were located in the peripheral zone. TBx accuracy in the detection of the correct site of the index lesion by reference standard was 82.2%. Sensitivity, specificity, positive and negative predictive value were: 82.3%, 50.4%, 82.8% and 49.7%, respectively. The primary/secondary Gleason grade and GS of the 152 index tumors were properly estimated in 130 (85.5%), 115 (75.6%) and 127 (83.6%) cases, respectively. The concordance of TBx with pathological GS was 83.6%. The rate of up-grading and down-grading of TBx Gleason sum was 12.2% and 4.2%, respectively. Conclusion: TBx has a high sensitivity for characterization of index lesions, with a good concordance for topographic and Gleason grading accuracy between biopsy and surgical specimens.

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Tumor Cell-selective Synergism of TRAIL- and ATRA-induced Cytotoxicity in Breast Cancer Cells

Background/Aim: One of the major problems in breast cancer treatment is pharmacoresistance. Therefore, exploration of treatment alternatives is of clinical relevance. The present work focused on tumor cell-inhibiting effects of a combination of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and all trans retinoic acid (ATRA) in breast cancer cells. Materials and Methods: Breast cancer cell lines (BT-20, BT-474, MDA-MB-231, MDA-MB-436, MDA-MB-453, MCF-7, SKBR3, T47D, ZR-75-1) and the mammary epithelial cell line MCF-10A were treated with TRAIL and ATRA alone and in combination. Cell viability was assessed via 3-(4,5)-dimethylthiahiazo(-z-yl)-3,5-di-phenytetrazoliumromide (MTT) assay, the potential of cell colony formation via clonogenic assay, cell death induction via cell-cycle analysis by fluorescence-activated cell sorting (FACS), terminal deoxynucleotidyltransferase-mediated UTP nick end labeling (TUNEL) assay and Cell death detection ELISA^PLUS, expression of apoptosis and TRAIL pathway proteins via western blot and cell surface expression of TRAIL receptor 1 (DR4) via FACS analysis. Results: TRAIL and ATRA evoked synergistic inhibition of breast cancer cell viability based on cytostatic and cytotoxic mechanisms. This correlated with augmented fragmentation of nuclear DNA, up-regulation of TRAIL receptor, down-regulation of cyclin D1 and enhancement of caspase activity. MCF-10A cells were merely slightly susceptible to TRAIL and ATRA. Conclusion: The cytostatic and cytotoxic effects of the combination of TRAIL and ATRA are tumor cell-selective.

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A Genitourinary Cancer-specific Scoring System for the Prediction of Survival in Patients with Bone Metastasis: A Retrospective Analysis of Prostate Cancer, Renal Cell Carcinoma, and Urothelial Carcinoma

Aim: The aim of this study was to develop a risk scoring system specific to patients with bone metastasis of genitourinary cancer. Materials and Methods: This study included 180 patients with bone metastasis of three major types of genitourinary cancer: prostate cancer (n=111), renal cell carcinoma (n=43,), and urothelial carcinoma (n=26). Clinical factors at diagnosis of bone metastasis were evaluated to identify independent prognostic factors. Results: Multivariate analysis showed that type of primary cancer, poor performance status, the presence of visceral metastases, high Glasgow prognostic score and elevated neutrophil-to-lymphocyte ratio were independently predictive of poor prognosis. Patients were able to be classified by the prognostic risk score into four prognostic groups with low, intermediate, high, and very high risk. Conclusion: This risk scoring system could be useful for predicting survival of patients with bone metastasis of genitourinary cancer and in making decisions on appropriate treatments for them.

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Application of Albumin-embedded Magnetic Nanoheaters for Release of Etoposide in Integrated Chemotherapy and Hyperthermia of U87-MG Glioma Cells

Background/Aim: Malignant gliomas remain refractory to several therapeutic approaches and the requirement for novel treatment modalities is critical to combat this disease. Etoposide is a topoisomerase-II inhibitor, which promotes DNA damage and apoptosis of cancer cells. In this study, we prepared albumin with embedded magnetic nanoparticles and etoposide for in vitro evaluation of combined hyperthermia and chemotherapy. Material and Methods: Magnetic nanoparticles were prepared by a modified co-precipitation method in the presence of human serum albumin and etoposide. A cellular proliferation assay was used to determine the effects of these nanostructures on the viability of U87 glioma cells in an alternating magnetic field. Results: The in vitro experiments showed that cell viability decreased to 59.4% after heat treatment alone and to 53.8% on that with free etoposide, while combined treatment resulted in 7.8% cell viability. Conclusion: Integrating hyperthermia and chemotherapy using albumin co-embedded magnetic nanoheaters and etoposide may represent a promising therapeutic option for glioblastoma.

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Radiotherapy Plus Total Androgen Block Versus Radiotherapy Plus LHRH Analog Monotherapy for Non-metastatic Prostate Cancer

Background/Aim: Patients with locally advanced prostate cancer are generally treated with radiotherapy (RT) which can be combined with hormonal therapy. RT plus monotherapy with luteinizing hormone-releasing hormone (LHRH) analog triptorelin was compared to RT plus total androgen block (TAB). Patients and Methods: A retrospective study was carried out on patients with locally advanced prostate cancer comparing RT plus monotherapy versus RT plus TAB. Results: For overall survival, no differences between patients receiving RT with monotherapy and those treated with TAB were observed. A trend favoring use of TAB was found for progression-free survival. No differences in late gastrointestinal and genitourinary toxicities were reported. Conclusion: This study suggests that monotherapy with LHRH is as effective as TAB, which is important in selecting appropriate treatment considering that TAB can have higher risks of adverse events and reduce the quality of life of patients.

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Potent Antitumour Effects of Novel Pentabromobenzylisothioureas Studied on Human Glial-derived Tumour Cell Lines

Background/Aim: Tumours of astroglial origin are the most common primary brain malignancy characterized by infiltrative growth and resistance to standard antitumour therapy. Glioma progression is thought to be related to various intracellular signal transduction pathways that involve the activation of protein kinases. Protein kinases play important roles in cell differentiation, proliferation, and survival. Recently, novel, specific inhibitors of constitutively active serine/threonine kinases and structurally similar isothiourea derivatives were suggested to induce apoptosis and inhibit proliferation in several types of human cancer cells. Materials and Methods: In this study, we examined the cytotoxic and proapoptotic activities of selected modified pentabromobenzyl isothioureas (ZKKs) in an adult human glioblastoma (T98G) and a subependymal giant cell astrocytoma cell (SEGA) line. We evaluated cell proliferation, viability, and apoptosis. Results: Two pentabromobenzyl isothiourea bromide derivatives, ZKK-13 and N,N,N'-trimethyl-ZKK1 (TRIM), exhibited the most potent cytotoxic and proapoptotic efficacies against human glioma-derived cells, even at a very low concentration (1 μM). ZKK-13 (25-50 μM) inhibited cell growth by approximately 80-90% in 24 and 48 h of treatment. We showed that selected ZKKs exerted antiproliferative activity against astroglial neoplastic cells of both low- and high-grade tumour malignancy classes. No synergistic effects were detected when ZKKs were combined with serine/threonine kinase inhibitors. Conclusion: Our findings indicated that modified ZKKs show promise for the treatment of glioma-derived brain tumours.

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Relationship between exposure to treosulfan and its monoepoxytransformer – An insight from population pharmacokinetic study in pediatric patients before hematopoietic stem cell transplantation

Publication date: 30 July 2018
Source:European Journal of Pharmaceutical Sciences, Volume 120
Author(s): Dorota Danielak, Anna Kasprzyk, Tomasz Wróbel, Jacek Wachowiak, Krzysztof Kałwak, Franciszek Główka
Treosulfan (TREO), a structural analog of busulfan, is currently studied as a myeloablative agent in conditioning regimens before hematopoietic stem cell transplantation in pediatric patients. High exposure to TREO (>1650 mg∗h/mL) might be related to early toxicity, especially skin toxicity and mucositis. The aim of the present study was to investigate a potential relationship between exposure to TREO and its monoepoxytransformer (S,S-EBDM), as well as variability of the pharmacokinetics of these entities by means of a population pharmacokinetic approach with a non-linear mixed-effects analysis.The study included data from 14 children with malignant and non-malignant diseases treated with TREO in daily doses 10–14 g/m². The parent-metabolite population pharmacokinetic model was developed in NONMEM 7.3 software. Upon the constructed model, an extensive simulation was performed to assess the correlation between exposure to TREO and S,S-EBDM.It was found that TREO and S,S-EBDM pharmacokinetics was best described with 2-compartmental and 1-compartmental linear models, respectively. The vast majority (>65%) of TREO was transformed to S,S-EBDM. Overall, a considerable interpatient variability of pharmacokinetic parameters was observed, especially the clearance of S,S-EBDM. A weak correlation was found between the exposure to TREO and S,S-EBDM (r = 0.1681, p < 0.0001). Also, patients with an exposure to TREO above 1650 mg∗h/mL were most likely to have also a high exposure to S,S-EBDM (35.38 μM∗h vs. 43.14 μM∗h, p < 0.0001).In summary, a parent-metabolite population pharmacokinetic model for TREO and S,S-EBDM was developed for the first time. It was shown that there is a weak correlation between exposure to TREO and S,S-EBDM. Therefore therapeutic drug monitoring of not only prodrug but also its active epoxide might be needed.

Graphical abstract

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A comparative study between outbred and inbred rat strains for the use in in vivo IPV potency testing

Publication date: 17 May 2018
Source:Vaccine, Volume 36, Issue 21
Author(s): Viki Bockstal, Barbara Sanders, Rogier Achterberg, Machteld Tiemessen, Lies Bogaert, Marjolein Van der Meer, Hanneke Schuitemaker, Roland Zahn
In vivo potency testing of inactivated poliovirus vaccines (IPV) is generally performed in rats, although no systematic investigation has identified the most appropriate rat strain for anti-poliovirus antibody quantification. We investigated humoral immune responses to IPV in five different rat strains to identify the most suitable strain. Three outbred (Wistar, Wistar Hannover, Sprague-Dawley) and two inbred rat strains (Fisher 344, Wistar Furth) were immunized intramuscularly with a full or one-fifth human dose of commercial IPV. Anti-poliovirus neutralizing antibody (NA) titers were measured using Salk and Sabin virus neutralizing assays. Post-vaccination responses varied between strains; inbred strains showed greater animal-to-animal variation in NA responses than outbred strains. Virus NA titers persisted for 9 weeks with little reduction in the response. The outbred Wistar rat model was identified as the preferred strain for IPV potency testing based on its capacity to produce high, dose-dependent anti-poliovirus NA responses, with low animal-to-animal variation.



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Brucellosis vaccines based on the open reading frames from genomic island 3 of Brucella abortus

Publication date: 17 May 2018
Source:Vaccine, Volume 36, Issue 21
Author(s): Leonardo Gómez, Francisco Alvarez, Daniel Betancur, Angel Oñate
Brucella abortus is the etiological agent of brucellosis, a zoonotic disease affecting cattle and humans. This disease has been partially controlled in cattle by immunization with live attenuated B. abortus S19 and RB51 strains. However, use of these vaccine strains has been associated with safety issues in animals and humans. New vaccines have since emerged in the prevention of brucellosis, particularly DNA vaccines, which have shown effectiveness and a good safety profile. Their protection efficacy in mice is associated with the induction of Th1 type and cytotoxic T cell mediated immune response against structural antigens and virulence factors expressed during B. abortus infection. Some antigenic candidate for vaccine design against brucellosis (mainly DNA vaccines) have been obtained from genomic island 3 (GI-3) of B. abortus, which encodes several open reading frames (ORFs) involved in the intracellular survival and virulence of this pathogen. The immunogenicity and protection conferred by these DNA vaccines in a murine model is reviewed in this article, suggesting that some of them could be safe and effective vaccine candidates against to prevent B. abortus infection.



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VaxArray for hemagglutinin and neuraminidase potency testing of influenza vaccines

Publication date: 17 May 2018
Source:Vaccine, Volume 36, Issue 21
Author(s): Laura R. Kuck, Rose Byrne-Nash, Jacob Gillis, Katie Bueter, Laura K. Couzens, Maryna C. Eichelberger, Kathy L. Rowlen
Practical methods to measure the potency of influenza vaccines are needed as alternatives for the standard single radial immunodiffusion (SRID) assay. VaxArray assays for influenza hemagglutinin (HA) and neuraminidase (NA) have been developed to address this need. In this report, we evaluate the use of these assays to assess the potency of HA and NA of an A/H3N2 subunit vaccine by determining the correlation between the amounts measured by VaxArray and the immunogenicity in mice. The antibody response after one and two doses of five formulations of the vaccine ranging from 5 µg/mL to 80 µg/mL of HA, was measured by hemagglutination inhibition (HAI) and neuraminidase inhibition (NAI) assays. For hemagglutinin, vaccine potency determined by VaxArray was equivalent to potency measured SRID and these amounts were predictive of immunogenicity, with excellent correlation between potency measured by VaxArray and the HAI geometric mean titers (GMT). Likewise, the amount of NA measured by VaxArray was predictive of the NAI GMT. The VaxArray NA assay reported non-detectable levels of intact NA for a sample that had been heat degraded at 56 °C for 20 h, demonstrating that the assay measures the native, active form of NA. Similarly, the HA potency measured by VaxArray in this heat-treated sample was very low when a monoclonal antibody was used to detect the amount of antigen bound. Importantly, the force degraded sample induced low HAI titers and the NAI titers were not measurable, supporting the conclusion that the VaxArray HA and NA assays measure the immunogenic forms of these A/H3N2 antigens. This study indicates that VaxArray assays can be used to assess the potency of HA and NA components in influenza vaccines as a proxy for immunogenicity.



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The influence of incomplete case ascertainment on measures of vaccine efficacy

Publication date: 17 May 2018
Source:Vaccine, Volume 36, Issue 21
Author(s): Yue Wu, Julie A. Marsh, Emma S. McBryde, Thomas L. Snelling
BackgroundMotivated by the unexplained variation in the performance of some vaccines across different settings, we extend previous theoretical work to consider the potential impact of incomplete case ascertainment on measures of vaccine efficacy (VE), which is more likely in subclinical or clinically unimportant infections, such as rotavirus gastroenteritis.MethodsBy simulating the measurement of VE under outbreak conditions using a discrete time stochastic SIR model, we compare three commonly used measures, VERisk, VERate, and VEHazard, calculated respectively based on risk ratio, rate ratio and hazard ratio of disease. We investigate how these measures are influenced by factors such as biological activity, action mechanism of vaccine, proportion of cases ascertained, and underlying force of infection.ResultsUnder plausibly low levels of ascertainment, the group with the most infections, and therefore the most missed cases, has the most falsely inflated denominator, producing similar rates in the control and intervention groups. As a result, VERate and VEHazard will underestimate the true VE compared to high case ascertainment scenarios. Furthermore, the extent of underestimation is greater for leaky vaccine models with lower biological protective effects and under conditions which are conducive to high transmission.ConclusionsThis study demonstrates that a biologically active vaccine may produce a low measured VE under a range of epidemiological, vaccine-related and logistical conditions. Low case ascertainment may partly explain the observed heterogeneity in the performance of rotavirus vaccine across different settings, and should be considered in the design and interpretation of future field trials.



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Editorial Board/Aims and Scope

Publication date: 17 May 2018
Source:Vaccine, Volume 36, Issue 21





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The impact of time since vaccination and study design on validity in parental recall of childhood vaccination status in the All Our Families cohort

Publication date: 17 May 2018
Source:Vaccine, Volume 36, Issue 21
Author(s): Ellen Rafferty, Erin Hetherington, Suzanne Tough, Shyrose Aujla, Deborah McNeil, Vineet Saini, Sheila McDonald, Shannon E. MacDonald
IntroductionParental reporting of childhood vaccination status is often used for policy and program evaluation and research purposes. Many factors can bias parental reporting of childhood vaccination status, however, to our knowledge, no analysis has assessed whether time since vaccination impacts reporting accuracy. Therefore, using the Calgary electronic vaccine registry (PHANTIM) as the gold standard, we aimed to test the accuracy of parental reporting of childhood vaccination status at three different time-points since vaccination.MethodsThe All Our Families (AOF) cohort study asked parents to report their child's 2, 4, 6, 12 and 18 month vaccines (vaccination time-point) on questionnaires given when the child was 1, 2 and 3 years of age (survey time-point). We linked the AOF parental reporting of vaccination status to the PHANTIM registry and calculated the percent agreement and difference in coverage estimates between PHANTIM and AOF at each vaccination and survey time-point combination. Furthermore, we measured the sensitivity and specificity, and negative (NPV) and positive predictive values (PPV) of parental vaccine recall across time.ResultsAOF parent reports of coverage rates were consistently higher than the PHANTIM estimates. While we saw significant differences in percent agreement for certain vaccination time-points, we saw no consistent directional difference by survey time-point, suggesting that parental accuracy did not change with time. We found a uniformly high sensitivity across all vaccination and survey time-points, and no consistent patterns in the specificity, PPV and NPV results.ConclusionTime since vaccination may not be the most important consideration when designing and implementing a vaccination survey. Other factors that may contribute to the bias associated with parental reporting of vaccination status include the complexity of the vaccine schedule, schedule changes over time, and the wording and structure of the questionnaires.



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Effectiveness of inactivated influenza vaccine against laboratory-confirmed influenza pneumonia among adults aged ≥65 years in Japan

Publication date: 17 May 2018
Source:Vaccine, Volume 36, Issue 21
Author(s): Motoi Suzuki, Naoko Katsurada, Minh Nhat Le, Norihiro Kaneko, Makito Yaegashi, Naoto Hosokawa, Yoshihito Otsuka, Masahiro Aoshima, Lay Myint Yoshida, Konosuke Morimoto
BackgroundThe effectiveness of inactivated influenza vaccine (IIV) against laboratory-confirmed influenza pneumonia in older adults remains to be established.MethodsPneumonia patients aged ≥65 years who visited a study hospital in Chiba, Japan, were prospectively enrolled from February 2012 to January 2014. Sputum samples were collected from participants and tested for influenza virus by polymerase chain reaction assays. Influenza vaccine effectiveness (IVE) against laboratory-confirmed influenza pneumonia was estimated by a test-negative design.ResultsAmong a total of 814 pneumonia patients, 42 (5.2%) tested positive for influenza: 40 were positive for influenza A virus, and two were positive for influenza B virus. The IVE against laboratory-confirmed influenza pneumonia was 58.3% (95% confidence interval, 28.8–75.6%). The IVE against influenza pneumonia hospital admission, severe pneumonia, and death was 60.2% (95% CI, 22.8–79.4%), 65.5% (95% CI, 44.3–78.7%), and 71% (95% CI, −62.9% to 94.8%), respectively. In the subgroup analyses, the IVE against influenza pneumonia was higher for patients with immunosuppressive conditions (85.9%; 95% CI, 67.4–93.9%) than for those without (48.7%; 95% CI, 2.7–73%) but did not differ by patients' statin use status.ConclusionIIV effectively reduces the risk of laboratory-confirmed influenza pneumonia in older adults.



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Safety, tolerability and immunogenicity of intramuscular administration of PRP-CRM197 Hib vaccine to healthy Japanese children: An open-label trial

Publication date: 17 May 2018
Source:Vaccine, Volume 36, Issue 21
Author(s): Takehiro Togashi, Nodoka Mitsuya, Shuji Sumino, Yohei Takanami
BackgroundJapan licensed the conjugate Haemophilus influenzae type b vaccine, Vaxem™ Hib, based on clinical studies using subcutaneous injection. The present study was performed to ensure this vaccine is suitable for intramuscular injection in Japanese children.MethodsThirty-one healthy 2–6-month-old infants received three doses of Vaxem™ Hib by intramuscular injection at 4-week intervals and a booster dose 1 year later, concomitant with routine infant (DTaP-IPV and pneumococcal) and toddler (measles–rubella) vaccines. Immunogenicity was assessed before and after the primary series and booster dose by enzyme-linked immunosorbent assay for anti-polyribosyl-ribitol-phosphate (PRP) antibodies. Safety was assessed by medical examination and diary cards completed by the subjects' parents/legal guardians.ResultsThere were no vaccine-related serious adverse events or withdrawals; all children completed the study. Four weeks after the primary series, the geometric mean anti-PRP titer (GMT) was 19.68 μg/mL, and all children had seroprotective titers (≥0.15 μg/mL) that persisted until the booster dose. Proportions of titers indicative of long-term protection (≥1.0 μg/mL) were 100% after the primary series and 77.4% before the booster. Anamnestic responses to the booster had a GMT of 51.33 μg/mL, and 100% had titers ≥1.0 μg/mL. All but one subject reported injection site reactions as resolved within 3 days of vaccination; systemic reactions due to Hib and routine vaccines were also resolved within this period.ConclusionsVaxem™ Hib was generally well tolerated and immunogenic in Japanese children when administered by intramuscular injection in a three-dose primary series and as a booster with concomitant routine vaccines.Clinical trial registry: Registered on Clinical Trials.gov: NCT02074345.



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Immunisation of chickens with live Salmonella vaccines – Role of booster vaccination

Publication date: 17 May 2018
Source:Vaccine, Volume 36, Issue 21
Author(s): U. Methner
It is accepted that booster vaccinations of chickens with live Salmonella vaccines are essential part of vaccinations schemes to induce an effective adaptive immune response. As manufacturer of registered live Salmonella vaccines recommend different times of booster the question raises whether the duration between the first and second immunisation might influence the protective effect against Salmonella exposure. Chickens were immunised with a live Salmonella Enteritidis vaccine on day 1 of age followed by a booster vaccination at different intervals (day 28, 35 or 42 of age) to study the effects on the colonisation and invasion of the Salmonella vaccine strain, the humoral immune response and the efficacy against infection with Salmonella Enteritidis on day 56 of age. Immunisation of all groups resulted in a very effective adaptive immune response and a high degree of protection against severe Salmonella exposure, however, the time of booster had only an unverifiable influence on either the colonisation of the vaccine strain, the development of the humoral immune response or the colonisation of the Salmonella challenge strain. Therefore, the first oral immunisation of the chicks on day 1 of age seems to be of special importance and prerequisite for the development of the effective immune response. A booster immunisation should be carried out, however, the time of booster may vary between week 3 and week 7 of age of the chickens without adversely impact on the efficacy of the adaptive immune response or the protective effects.



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Invasive pneumococcal disease in Northern Alberta, not a Red Queen but a dark horse

Publication date: 17 May 2018
Source:Vaccine, Volume 36, Issue 21
Author(s): Thomas J. Marrie, Gregory J. Tyrrell, Sumit R. Majumdar, Dean T. Eurich
BackgroundThe consequences of the introduction of various pneumococcal protein conjugate vaccines (PCV) for children and adults is poorly understood.ObjectiveWe undertook a population-based cohort study of invasive pneumococcal disease (IPD) in Northern Alberta (Canada) from 2000 to 2014, years spanning pre-and early PCV (2000–2004) vs PCV-7 (2005–2009) vs PCV-13 (2010–2014) time periods.DesignWe collected clinical, laboratory, and Streptococcus pneumoniae serotype information on all patients from 2000 to 2014. We determined changes in presentation, outcomes, serotypes, and incidence in children and adults across time periods.SettingThere were 509 cases of IPD in children, an 80% decrease over time. Rates of empyema (4.0–15.7%, p < 0.001), ICU admission (13.1–20%), and mortality (1.8–8.4%, p < 0.001) increased over time. There were 2417 cases of IPD in adults. Unlike children, incidence of IPD did not change nor did rates of empyema. ICU admissions increased (p = 0.004) and mortality decreased (18.7–16.5%, p = 0.002). The total number of serotypes causing IPD remained stable in children (22 vs 26 vs 20) while they decreased in adults (49 vs 47 vs 42).Conclusions and relevanceFor children, PCV vaccination strategies resulted in decreased overall rates of IPD and we observed increased rates of empyema and mortality; for adults, there was no change in IPD rates although disease severity increased while mortality decreased. On a population-wide basis, our results suggest that current PCV vaccination strategies are associated with an overall decrease in IPD but disease severity seems to be increasing in both children and adults.



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