Inter-vender and test-retest reliabilities of resting-state functional magnetic resonance imaging: Implications for multi-center imaging studies

Publication date: December 2017
Source:Magnetic Resonance Imaging, Volume 44
Author(s): Hyeong Su An, Won-Jin Moon, Jae-Kyun Ryu, Ju Yeon Park, Won Sung Yun, Jin Woo Choi, Geon-Ho Jahng, Jang-Yeon Park
This prospective multi-center study aimed to evaluate the inter-vendor and test-retest reliabilities of resting-state functional magnetic resonance imaging (RS-fMRI) by assessing the temporal signal-to-noise ratio (tSNR) and functional connectivity. Study included 10 healthy subjects and each subject was scanned using three 3T MR scanners (GE Signa HDxt, Siemens Skyra, and Philips Achieva) in two sessions. The tSNR was calculated from the time course data. Inter-vendor and test-retest reliabilities were assessed with intra-class correlation coefficients (ICCs) derived from variant component analysis. Independent component analysis was performed to identify the connectivity of the default-mode network (DMN). In result, the tSNR for the DMN was not significantly different among the GE, Philips, and Siemens scanners (P=0.638). In terms of vendor differences, the inter-vendor reliability was good (ICC=0.774). Regarding the test-retest reliability, the GE scanner showed excellent correlation (ICC=0.961), while the Philips (ICC=0.671) and Siemens (ICC=0.726) scanners showed relatively good correlation. The DMN pattern of the subjects between the two sessions for each scanner and between three scanners showed the identical patterns of functional connectivity. The inter-vendor and test-retest reliabilities of RS-fMRI using different 3T MR scanners are good. Thus, we suggest that RS-fMRI could be used in multicenter imaging studies as a reliable imaging marker.



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Reproducibility and relative stability in magnetic resonance imaging indices of tumor vascular physiology over a period of 24h in a rat 9L gliosarcoma model

Publication date: December 2017
Source:Magnetic Resonance Imaging, Volume 44
Author(s): Tavarekere N. Nagaraja, Rasha Elmghirbi, Stephen L. Brown, Lonni R. Schultz, Ian Y. Lee, Kelly A. Keenan, Swayamprava Panda, Glauber Cabral, Tom Mikkelsen, James R. Ewing
PurposeThe objective was to study temporal changes in tumor vascular physiological indices in a period of 24h in a 9L gliosarcoma rat model.MethodsFischer-344 rats (N=14) were orthotopically implanted with 9L cells. At 2weeks post-implantation, they were imaged twice in a 24h interval using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Data-driven model-selection-based analysis was used to segment tumor regions with varying vascular permeability characteristics. The region with the maximum number of estimable parameters of vascular kinetics was chosen for comparison across the two time points. It provided estimates of three parameters for an MR contrast agent (MRCA): i) plasma volume (vp), ii) forward volumetric transfer constant (K^trans) and interstitial volume fraction (ve, ratio of K^trans to reverse transfer constant, kep). In addition, MRCA extracellular distribution volume (VD) was estimated in the tumor and its borders, along with tumor blood flow (TBF) and peritumoral MRCA flux. Descriptors of parametric distributions were compared between the two times. Tumor extent was examined by hematoxylin and eosin (H&E) staining. Picrosirus red staining of secreted collagen was performed as an additional index for 9L cells.ResultsTest-retest differences between population summaries for any parameter were not significant (paired t and Wilcoxon signed rank tests). Bland-Altman plots showed no apparent trends between the differences and averages of the test-retest measures for all indices. The intraclass correlation coefficients showed moderate to almost perfect reproducibility for all of the parameters, except vp. H&E staining showed tumor infiltration in parenchyma, perivascular space and white matter tracts. Collagen staining was observed along the outer edges of main tumor mass.ConclusionThe data suggest the relative stability of these MR indices of tumor microenvironment over a 24h duration in this gliosarcoma model.



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MRI characteristics of the glia limitans externa: A 7T study

Publication date: December 2017
Source:Magnetic Resonance Imaging, Volume 44
Author(s): Kiyotaka Suzuki, Kenichi Yamada, Kazunori Nakada, Yuji Suzuki, Masaki Watanabe, Ingrid L. Kwee, Tsutomu Nakada
PurposeTo perform a systematic analysis of the intrinsic contrast parameters of the FLAIR hyperintense rim (FHR), a thin layer of high intensity covering the entire surface of the cerebral cortex detected on fluid-attenuated inversion recovery (FLAIR) sequence T2 weighted imaging performed on a 7T system, in an attempt to identify its anatomical correlate.MethodsFast spin echo inversion recovery (FSE-IR) and cardiac-gated fast spin echo (FSE) images were obtained with defined parameters in eight normal volunteers on a 7 T MRI system to determine T2 and proton density, T1 characteristics. K-means clustering analysis of parameter sets was performed using MATLAB version R2015b for the purpose of identifying the cluster reflecting FHR. The results were subsequently confirmed by independent component analysis (ICA) based on T1 behavior on FSE-IR using a MATLAB script of FastICA algorithm.ResultsThe structure giving rise to FHR was found to have a unique combination of intrinsic contrast parameters of low proton density, long T2, and disproportionally short T1. The findings are in strong agreement with the functional and structural specifics of the glia limitans externa (GLE), a structure composed of snuggled endfeet of astrocytes containing abundant aquaporin-4 (AQP-4), the main water channel of the brain.ConclusionIntrinsic contrast parameters of FHR reflect structural and functional specifics of the GLE, and their values are highly dependent on the physiologic functionality of AQP-4. Microscopic imaging on a 7T system and analysis of GLE contrast parameters can be developed into a method for evaluating AQP-4 functionality.



http://ift.tt/2xpNQcZ

Collagen Membrane Over Buccal Fat Pad Versus Buccal Fat Pad in Management of Oral Submucous Fibrosis: A Comparative Prospective Study

Abstract

Objective

The objective of this study was to assess the effectiveness of collagen membrane as biological dressing over buccal fat pad (BFP) during crucial postoperative healing phase in the surgical management of oral submucous fibrosis (OSMF).

Study Design

The study comprised of 40 patients of OSMF of group IVa (Khanna and Andrade). Patients were randomly divided in two groups (20 patients in each group). Group I patients were treated using buccal fat pad only, whereas collagen membrane was used as a covering over harvested BFP in group II patients. Postoperative follow-up was done at 1 week, 3 weeks, 6 months and 1 year.

Result

Mean postoperative mouth opening achieved in both the groups was comparable at every follow-up visit. Infection was evident in four patients of group I at 1-week follow-up, whereas none of the group II patients developed infection. Pain score was lesser in group II patients as compared to group I. Relapse was seen in two patients in group I and one patient in group II. Time taken for epithelialization was 2–3 weeks in both the groups.

Conclusion

Although intraoperative time was increased in group II application of collagen membrane reduced infection when compared with group I. Also, the chances of damage to BFP are reduced during the hygiene maintenance at surgical site and jaw-opening exercise. Reduction in pain scores during postoperative period in group II patients was an additional advantage.

http://ift.tt/2xqz6uc

Perceptual Visual Skills in Delayed Language Developed Children

Publication date: Available online 9 September 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences
Author(s): Eman Mostafa
AimTo evaluate Perceptual visual skills in delayed language developed children.Material and methodsThe relation between visual skills and language has not been rigorously examined in previous investigations. This is a case-control study which comprised of 25 preschool children with Delayed Language Development (DLD) (cases) and 25 typically developed children (control). Exclusion criteria: any neurological or visual impaired disorder. All children had undergone Intelligent Quotient (I.Q) using Stanford Binet (IV edition), Attention Deficit Hyperactivity disorder Test (ADHDT) and Illinois Test of Psycholinguistic Abilities (ITPA). The performance of cases was surprisingly superior to the performance of controls in all visual skills. Moreover, it was significantly different in visual closure (P value=0.027) and visual memory (P value=0.005).ConclusionReading disorders that may develop in children with DLD are more related to language than to visual skills. DLD has some strong perceptual skills such as visual closure and visual memory. This should be taken in consideration while planning a strategy for language therapy.



http://ift.tt/2gVKw2g

20Q: Hearing Loss and Its Comorbidities

From the Desk of Gus MuellerTell me if you've heard this one before.  Your Monday morning patient is in his 50s, has a history of some noise exposure (occasional hunting), and states that over the past few years he is starting to have trou

http://ift.tt/2xpcgmJ

Perceptual Visual Skills in Delayed Language Developed Children

Publication date: Available online 9 September 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences
Author(s): Eman Mostafa
AimTo evaluate Perceptual visual skills in delayed language developed children.Material and methodsThe relation between visual skills and language has not been rigorously examined in previous investigations. This is a case-control study which comprised of 25 preschool children with Delayed Language Development (DLD) (cases) and 25 typically developed children (control). Exclusion criteria: any neurological or visual impaired disorder. All children had undergone Intelligent Quotient (I.Q) using Stanford Binet (IV edition), Attention Deficit Hyperactivity disorder Test (ADHDT) and Illinois Test of Psycholinguistic Abilities (ITPA). The performance of cases was surprisingly superior to the performance of controls in all visual skills. Moreover, it was significantly different in visual closure (P value=0.027) and visual memory (P value=0.005).ConclusionReading disorders that may develop in children with DLD are more related to language than to visual skills. DLD has some strong perceptual skills such as visual closure and visual memory. This should be taken in consideration while planning a strategy for language therapy.



http://ift.tt/2gVKw2g

Issue Information - TOC

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Continuing Professional Development Quiz

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Issue Information - JEB

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The use of mobile health applications in school dental screening

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Continuing Professional Development Calendar

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Personalized/Precision Dentistry – The Future of Dentistry?

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Chromatin: Probing a piRNA paradox

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Harnessing ancient genomes to study the history of human adaptation

Ancient genomes can inform our understanding of the history of human adaptation through the direct tracking of changes in genetic variant frequency across different geographical locations and time periods. The authors review recent ancient DNA analyses of human, archaic hominin, pathogen, and domesticated animal and plant genomes, as well as the insights gained regarding past human evolution and behaviour.

http://ift.tt/2vOGhIl

Leaching variations of heavy metals in chelator-assisted phytoextraction by Zea mays L. exposed to acid rainfall

Abstract

Chelant-enhanced phytoextraction method has been put forward as an effective soil remediation method, whereas the heavy metal leaching could not be ignored. In this study, a cropping-leaching experiment, using soil columns, was applied to study the metal leaching variations during assisted phytoextraction of Cd- and Pb-polluted soils, using seedlings of Zea mays, applying three different chelators (EDTA, EDDS, and rhamnolipid), and artificial rainfall (acid rainfall or normal rainfall). It showed that artificial rainfall, especially artificial acid rain, after chelator application led to the increase of heavy metals in the leaching solution. EDTA increased both Cd and Pb concentrations in the leaching solution, obviously, whereas EDDS and rhamnolipid increased Cd concentration but not Pb. The amount of Cd and Pb decreased as the leaching solution increased, the patterns as well matched LRMs (linear regression models), with R-square (R ²) higher than 90 and 82% for Cd and Pb, respectively. The maximum cumulative Cd and Pb in the leaching solutions were 18.44 and 16.68%, respectively, which was amended by EDTA and acid rainwater (pH 4.5), and followed by EDDS (pH 4.5), EDDS (pH 6.5), rhamnolipid (0.5 g kg⁻¹ soil, pH 4.5), and rhamnolipid (pH 6.5).

http://ift.tt/2vOYyFq

Intralesional excision combined with intralesional cryosurgery for the treatment of oversized and therapy-resistant keloids of the neck and ears

Abstract

This prospective case study presents a new method for the treatment of oversized and therapy-resistant keloids of the neck and ears employing intralesional excision combined with intralesional cryosurgery. The keloids were excised in an intralesional approach, and the remaining base and lateral margins of the scar tissue were frozen using intralesional cryoneedles. After complete thawing of the frozen tissues, the margins of the scar were approximated and sutured. The follow-up period extended over 18–24 months. Over a period of 12 months, the scars gradually flattened with no hypopigmentation. No signs of recurrence of the keloids were seen. Intralesional excision of oversized and therapy-resistant keloids combined with intralesional cryosurgery could well be an additional tool to the plastic surgical armamentarium, for treating this group of patients.

Level of Evidence: Level IV, therapeutic study.

http://ift.tt/2gWwSYY

Acne Scars: How Do We Grade Them?

Abstract

Acne vulgaris is a chronic inflammatory skin disease that can lead to permanent scarring. Although grading scales exist for acne scarring, there are many limitations, and there is still a need for a well validated gold standard scale for use in clinical practice or research trials. An objective measure of scar severity should be a component of global acne severity evaluations. This manuscript reviews currently available acne scar grading modalities: lesion counting; subjective self-assessment; Acne Scar Rating Scale (ASRS); evaluator-based qualitative and quantitative scarring grading systems; Echelle d'Evaluation Clinique des Cicatrices d'acne (ECCA); Global Scale for Acne Scar Severity (SCAR-S); and imaging. Despite the varying tools, most of the currently available scales do not account for scar color, depth, or change over time. A new, validated scale is needed that would allow for a more objective and accurate assessment of scar progression over time to assist with effective treatment and research.

http://ift.tt/2wTMy8t

Helicobacter pylori infection and extragastric diseases in 2017

Abstract

The huge variety of extragastric diseases linked to Helicobacter pylori infection is widely known, and new studies are conducted every year on this topic. Neurological disorders and metabolic syndrome are some of the main issues debated in the most recent literature. Articles on the association of H. pylori with skin diseases, inflammatory bowel diseases, immunologic impairment, kidney dysfunction, allergic asthma, and respiratory diseases have been published as well. In this perspective, eradication therapy for this infection could become a mandatory measure in prevention strategy.

http://ift.tt/2jhdE4D

Genomics of Helicobacter pylori

Abstract

As Helicobacter pylori infects half the world's population and displays an extensive intraspecies diversity, genomics is a powerful tool to understand evolution and disease, to identify factors that confer higher risk of severe sequelae, and to find new approaches for therapy both among bacterial and host targets. In line with these objectives, this review article summarizes the major findings in Helicobacter genomics in papers published between April 2016 and March 2017.

http://ift.tt/2wUaWXR

Gastric cancer: Basic aspects

Abstract

Gastric cancer is one of the most incident and deadliest malignancies in the world. Gastric cancer is a heterogeneous disease and the end point of a long and multistep process, which results from the stepwise accumulation of numerous (epi)genetic alterations, leading to dysregulation of oncogenic and tumor suppressor pathways. Gastric cancer stem cells have emerged as fundamental players in cancer development and as contributors to gastric cancer heterogeneity. For this special issue, we will report last year's update on the gastric cancer molecular classification, and in particular address the gastric cancer groups who could benefit from immune checkpoint therapy. We will also review the latest advances on gastric cancer stem cells, their properties as gastric cancer markers and therapeutic targets, and associated signaling pathways. The understanding of the molecular basis underlying gastric cancer heterogeneity and of the role played by gastric cancer stem cells in cancer development and heterogeneity is of major significance, not only for identifying novel targets for cancer prevention and treatment, but also for clinical management and patient stratification for targeted therapies.

http://ift.tt/2jgRwHz

Other Helicobacters, gastric and gut microbiota

Abstract

The current article is a review of the most important and relevant literature published in 2016 and early 2017 on non-Helicobacter pylori Helicobacter infections in humans and animals, as well as interactions between H. pylori and the microbiota of the stomach and other organs. Some putative new Helicobacter species were identified in sea otters, wild boars, dogs, and mice. Many cases of Helicobacter fennelliae and Helicobacter cinaedi infection have been reported in humans, mostly in immunocompromised patients. Mouse models have been used frequently as a model to investigate human Helicobacter infection, although some studies have investigated the pathogenesis of Helicobacters in their natural host, as was the case for Helicobacter suis infection in pigs. Our understanding of both the gastric and gut microbiome has made progress and, in addition, interactions between H. pylori and the microbiome were demonstrated to go beyond the stomach. Some new approaches of preventing Helicobacter infection or its related pathologies were investigated and, in this respect, the probiotic properties of Saccharomyces, Lactobacillus and Bifidobacterium spp. were confirmed.

http://ift.tt/2wTWOha

Diagnosis of Helicobacter pylori infection

Abstract

Important progress is being made in endoscopic methods which allow clinicians to predict the presence of Helicobacter pylori based on characteristics of gastric mucosa and to obtain targeted biopsies. There are also important developments in molecular methods with various techniques derived from standard PCR, applied both on gastric biopsies and stool specimens. Progress is being made in microfluidic systems to get a reliable diagnosis in a very short time. The interest of the ¹³C urea breath test has been confirmed as well as stool antigen tests. Attempts are being made to find biological markers of premalignant conditions by serology, other than pepsinogens.

http://ift.tt/2jgRAHj

Helicobacter: Inflammation, immunology and vaccines

Abstract

Helicobacter pylori is usually acquired in early childhood and the infection persists lifelong without causing symptoms. In a small of cases, the infection leads to gastric or duodenal ulcer disease, or gastric cancer. Why disease occurs in these individuals remains unclear, however the host response is known to play a very important part. Understanding the mechanisms involved in maintaining control over the immune and inflammatory response is therefore extremely important. Vaccines against H. pylori have remained elusive but are desperately needed for the prevention of gastric carcinogenesis. This review focuses on research findings which may prove useful in the development of prognostic tests for gastric cancer development, therapeutic agents to control immunopathology, and effective vaccines.

http://ift.tt/2wUCOel

Abstracts

http://ift.tt/2jflxrk

Keyword Index

http://ift.tt/2wUgVfg

Pathogenesis of Helicobacter pylori infection

Abstract

Helicobacter pylori is responsible for the most commonly found infection in the world's population. It is the major risk factor for gastric cancer development. Numerous studies published over the last year provide new insights into the strategies employed by H. pylori to adapt to the extreme acidic conditions of the gastric environment, to establish persistent infection and to deregulate host functions, leading to gastric pathogenesis and cancer. In this review, we report recent data on the mechanisms involved in chemotaxis, on the essential role of nickel in acid resistance and gastric colonization, on the importance of adhesins and Hop proteins and on the role of CagPAI-components and CagA. Among the host functions, a special focus has been made on the escape from immune response, the ability of bacteria to induce genetic instability and modulate telomeres, the mechanism of autophagy and the deregulation of micro RNAs.

http://ift.tt/2jeyQYY

Treatment of Helicobacter pylori infection 2017

Abstract

This review summarizes important studies regarding Helicobacter pylori therapy published from April 2016 to April 2017. The main themes that emerge involve studies assessing the efficacy of bismuth and nonbismuth quadruple regimens. While in recent years, much of the emphasis on the use of bismuth has focussed on its utility in a second-line setting, an increasing number of studies this year have shown excellent efficacy in first-line therapy. The efficacy of bismuth as a second-line after sequential and concomitant therapy was particularly noteworthy. Antibiotic resistance was more intensely studied this year than for a long time, and definite trends are presented regarding an increase in resistance, including the fact that clarithromycin resistance in particular is now at a level where the continued use of clarithromycin triple therapy first-line as a mainstream treatment is not recommended. Another exciting trend to emerge this year is the utility of vonoprazan as an alternative to PPI therapy, especially in resistant and difficult-to-treat groups.

http://ift.tt/2wU3c7Z

Epidemiology of Helicobacter pylori infection

Abstract

The study of Helicobacter pylori genetic variability brought us interesting data on the history of mankind. Based on multilocus sequence typing and more recently on whole-genome sequencing, paleomicrobiology still attracts the attention of global researchers in relation to its ancestor roots and coexistence with humans. Three studies determining the prevalence of virulence factors illustrates the controversial results obtained since 30 years by studies trying to associate prevalence of different virulence markers and clinical outcomes of H. pylori infection. Three articles analyzed the prevalence and risk of multiple (genetically distinct isolates) and mixed (susceptible and resistant isolates) infections. A number of studies confirm that H. pylori prevalence is falling worldwide especially in the developed world and in children but that the level of infection is higher in certain ethnic minorities and in Migrants. There is little new in identifying the mode of H. pylori transmission though intrafamilial spread appears to be important. There have, however, been some interesting papers on the presence of the organism in food, water, and the oral cavity.

http://ift.tt/2jf9oTn

Helicobacter pylori, gastric cancer and other gastrointestinal malignancies

Abstract

In a retrospective study performed in California, U.S.A., ca. 3% of patients with gastric intestinal metaplasia (GIM) developed gastric cancer (GC) within a median time period of 4.6 years after diagnosis of GIM. This observation stresses the importance of targeted surveillance even in regions with a low GC prevalence. Patients with alcoholic liver disease as well as survivors of colorectal and lobular breast cancer were found to be at increased risk of secondary GC. A population-based Chinese study confirmed "serologic biopsy" as a useful screening tool for stratifying the individual risk of developing GC. Concerning GC therapy, a post hoc analysis of the MAGIC trial reported that regression of lymph node metastases, but not the tumor regression itself, predicts overall survival. Furthermore, in patients with high microsatellite instable tumors, perioperative chemotherapy leads to an increased risk of mortality. Two studies confirmed that eradication therapy is worthwhile as an initial treatment for gastric mucosa-associated lymphoid tissue (MALT) lymphoma irrespective of the H. pylori infection status and stage. An increased risk of a second primary malignancy including GC was observed in these patients treated with immuno/chemotherapy but not in patients treated solely with an H. pylori eradication treatment. With respect to gastrointestinal malignancies other than GC, discrepant data have been published regarding the association of H. pylori with pancreatic cancer whereas no association has been reported with esophageal squamous cell carcinoma. The majority of published studies still support an association of H. pylori with colon neoplasms.

http://ift.tt/2wTL3Hn

Issue Information

http://ift.tt/2jf9cU9

Helicobacter pylori infection in children

Abstract

Helicobacter pylori infection in children differs from that in adults, from the point of view of epidemiology, host response, clinical features, related diseases, and diagnosis, as well as treatment strategies.

The prevalence of H. pylori infection, in both children and adults, is decreasing in the Western World as well as in some developing countries, which contrasts with the increase in childhood asthma and allergic diseases. Recurrent abdominal pain is not specific during H. pylori infection in children. The role of H. pylori infection and failure to thrive, children's growth, type I diabetes mellitus (T1DM) and celiac disease remains controversial.

The main initial diagnosis is based on upper digestive endoscopy with biopsy-based methods. Nodular gastritis may be a pathognomonic endoscopic finding of childhood H. pylori infection. The infection eradication control is based on validated noninvasive tests.

The main cause of treatment failure of H. pylori infection is its clarithromycin resistance. We recommend standard antibiotic susceptibility testing of H. pylori in pediatric patients prior to the initiation of eradication therapy. H. pylori treatment in children should be based on an evaluation of the rate of eradication in the local population, a systematic use of a treatment adapted to the susceptibility profile and a treatment compliance greater than 90%. The last meta-analysis in children did not show an advantage for sequential therapy when compared to a 14-day triple therapy.

Finally, the high rate of antibiotic resistance responsible for therapy failure in recent years justifies the necessity of a novel vaccine to prevent H. pylori infection in children.

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30th anniversary of the European helicobacter & microbiota study group!

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Author Index

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Helicobacter pylori infection and nonmalignant diseases

Abstract

A substantial decrease in Helicobacter pylori-associated peptic ulcer disease has been observed during the last decades. Drug-related ulcers as well as idiopathic ulcers are becoming predominant and are more refractory to treatment; however, H. pylori infection still plays an important role in ulcer bleeding and recurrence after therapy. The effect of H. pylori eradication upon functional dyspepsia symptoms has been reviewed in this article and generally confirms the results of previous meta-analyses. Additional evidence suggests a lack of impact upon the quality of life, in spite of improvement in symptoms. The association of H. pylori with gastroesophageal reflux disease and Barrett's esophagus remains controversial with a majority of published studies showing a negative association. Furthermore, a strong inverse relationship between the presence of H. pylori and the esophageal eosinophilia was also reported. Several studies and a review addressed the role of H. pylori in autoimmune gastritis and pernicious anemia. The association of the above still remains controversial. Finally, the necessity of routine endoscopy and H. pylori eradication before bariatric surgery is discussed. Several studies suggest the rationale of preoperative upper endoscopy and H. pylori eradication prior to surgery. However, the prevalence of H. pylori infection prior to surgery in these studies generally reflects the overall prevalence of the infection in the particular geographic area. In addition, results on the role of H. pylori in developing postoperative complications remain controversial.

http://ift.tt/2wU3awT

Helicobacter pylori infection and extragastric diseases in 2017

Abstract

The huge variety of extragastric diseases linked to Helicobacter pylori infection is widely known, and new studies are conducted every year on this topic. Neurological disorders and metabolic syndrome are some of the main issues debated in the most recent literature. Articles on the association of H. pylori with skin diseases, inflammatory bowel diseases, immunologic impairment, kidney dysfunction, allergic asthma, and respiratory diseases have been published as well. In this perspective, eradication therapy for this infection could become a mandatory measure in prevention strategy.

http://ift.tt/2jhdE4D

Genomics of Helicobacter pylori

Abstract

As Helicobacter pylori infects half the world's population and displays an extensive intraspecies diversity, genomics is a powerful tool to understand evolution and disease, to identify factors that confer higher risk of severe sequelae, and to find new approaches for therapy both among bacterial and host targets. In line with these objectives, this review article summarizes the major findings in Helicobacter genomics in papers published between April 2016 and March 2017.

http://ift.tt/2wUaWXR

Gastric cancer: Basic aspects

Abstract

Gastric cancer is one of the most incident and deadliest malignancies in the world. Gastric cancer is a heterogeneous disease and the end point of a long and multistep process, which results from the stepwise accumulation of numerous (epi)genetic alterations, leading to dysregulation of oncogenic and tumor suppressor pathways. Gastric cancer stem cells have emerged as fundamental players in cancer development and as contributors to gastric cancer heterogeneity. For this special issue, we will report last year's update on the gastric cancer molecular classification, and in particular address the gastric cancer groups who could benefit from immune checkpoint therapy. We will also review the latest advances on gastric cancer stem cells, their properties as gastric cancer markers and therapeutic targets, and associated signaling pathways. The understanding of the molecular basis underlying gastric cancer heterogeneity and of the role played by gastric cancer stem cells in cancer development and heterogeneity is of major significance, not only for identifying novel targets for cancer prevention and treatment, but also for clinical management and patient stratification for targeted therapies.

http://ift.tt/2jgRwHz

Other Helicobacters, gastric and gut microbiota

Abstract

The current article is a review of the most important and relevant literature published in 2016 and early 2017 on non-Helicobacter pylori Helicobacter infections in humans and animals, as well as interactions between H. pylori and the microbiota of the stomach and other organs. Some putative new Helicobacter species were identified in sea otters, wild boars, dogs, and mice. Many cases of Helicobacter fennelliae and Helicobacter cinaedi infection have been reported in humans, mostly in immunocompromised patients. Mouse models have been used frequently as a model to investigate human Helicobacter infection, although some studies have investigated the pathogenesis of Helicobacters in their natural host, as was the case for Helicobacter suis infection in pigs. Our understanding of both the gastric and gut microbiome has made progress and, in addition, interactions between H. pylori and the microbiome were demonstrated to go beyond the stomach. Some new approaches of preventing Helicobacter infection or its related pathologies were investigated and, in this respect, the probiotic properties of Saccharomyces, Lactobacillus and Bifidobacterium spp. were confirmed.

http://ift.tt/2wTWOha

Diagnosis of Helicobacter pylori infection

Abstract

Important progress is being made in endoscopic methods which allow clinicians to predict the presence of Helicobacter pylori based on characteristics of gastric mucosa and to obtain targeted biopsies. There are also important developments in molecular methods with various techniques derived from standard PCR, applied both on gastric biopsies and stool specimens. Progress is being made in microfluidic systems to get a reliable diagnosis in a very short time. The interest of the ¹³C urea breath test has been confirmed as well as stool antigen tests. Attempts are being made to find biological markers of premalignant conditions by serology, other than pepsinogens.

http://ift.tt/2jgRAHj

Helicobacter: Inflammation, immunology and vaccines

Abstract

Helicobacter pylori is usually acquired in early childhood and the infection persists lifelong without causing symptoms. In a small of cases, the infection leads to gastric or duodenal ulcer disease, or gastric cancer. Why disease occurs in these individuals remains unclear, however the host response is known to play a very important part. Understanding the mechanisms involved in maintaining control over the immune and inflammatory response is therefore extremely important. Vaccines against H. pylori have remained elusive but are desperately needed for the prevention of gastric carcinogenesis. This review focuses on research findings which may prove useful in the development of prognostic tests for gastric cancer development, therapeutic agents to control immunopathology, and effective vaccines.

http://ift.tt/2wUCOel

Abstracts

http://ift.tt/2jflxrk

Keyword Index

http://ift.tt/2wUgVfg

Pathogenesis of Helicobacter pylori infection

Abstract

Helicobacter pylori is responsible for the most commonly found infection in the world's population. It is the major risk factor for gastric cancer development. Numerous studies published over the last year provide new insights into the strategies employed by H. pylori to adapt to the extreme acidic conditions of the gastric environment, to establish persistent infection and to deregulate host functions, leading to gastric pathogenesis and cancer. In this review, we report recent data on the mechanisms involved in chemotaxis, on the essential role of nickel in acid resistance and gastric colonization, on the importance of adhesins and Hop proteins and on the role of CagPAI-components and CagA. Among the host functions, a special focus has been made on the escape from immune response, the ability of bacteria to induce genetic instability and modulate telomeres, the mechanism of autophagy and the deregulation of micro RNAs.

http://ift.tt/2jeyQYY

Treatment of Helicobacter pylori infection 2017

Abstract

This review summarizes important studies regarding Helicobacter pylori therapy published from April 2016 to April 2017. The main themes that emerge involve studies assessing the efficacy of bismuth and nonbismuth quadruple regimens. While in recent years, much of the emphasis on the use of bismuth has focussed on its utility in a second-line setting, an increasing number of studies this year have shown excellent efficacy in first-line therapy. The efficacy of bismuth as a second-line after sequential and concomitant therapy was particularly noteworthy. Antibiotic resistance was more intensely studied this year than for a long time, and definite trends are presented regarding an increase in resistance, including the fact that clarithromycin resistance in particular is now at a level where the continued use of clarithromycin triple therapy first-line as a mainstream treatment is not recommended. Another exciting trend to emerge this year is the utility of vonoprazan as an alternative to PPI therapy, especially in resistant and difficult-to-treat groups.

http://ift.tt/2wU3c7Z

Epidemiology of Helicobacter pylori infection

Abstract

The study of Helicobacter pylori genetic variability brought us interesting data on the history of mankind. Based on multilocus sequence typing and more recently on whole-genome sequencing, paleomicrobiology still attracts the attention of global researchers in relation to its ancestor roots and coexistence with humans. Three studies determining the prevalence of virulence factors illustrates the controversial results obtained since 30 years by studies trying to associate prevalence of different virulence markers and clinical outcomes of H. pylori infection. Three articles analyzed the prevalence and risk of multiple (genetically distinct isolates) and mixed (susceptible and resistant isolates) infections. A number of studies confirm that H. pylori prevalence is falling worldwide especially in the developed world and in children but that the level of infection is higher in certain ethnic minorities and in Migrants. There is little new in identifying the mode of H. pylori transmission though intrafamilial spread appears to be important. There have, however, been some interesting papers on the presence of the organism in food, water, and the oral cavity.

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Helicobacter pylori, gastric cancer and other gastrointestinal malignancies

Abstract

In a retrospective study performed in California, U.S.A., ca. 3% of patients with gastric intestinal metaplasia (GIM) developed gastric cancer (GC) within a median time period of 4.6 years after diagnosis of GIM. This observation stresses the importance of targeted surveillance even in regions with a low GC prevalence. Patients with alcoholic liver disease as well as survivors of colorectal and lobular breast cancer were found to be at increased risk of secondary GC. A population-based Chinese study confirmed "serologic biopsy" as a useful screening tool for stratifying the individual risk of developing GC. Concerning GC therapy, a post hoc analysis of the MAGIC trial reported that regression of lymph node metastases, but not the tumor regression itself, predicts overall survival. Furthermore, in patients with high microsatellite instable tumors, perioperative chemotherapy leads to an increased risk of mortality. Two studies confirmed that eradication therapy is worthwhile as an initial treatment for gastric mucosa-associated lymphoid tissue (MALT) lymphoma irrespective of the H. pylori infection status and stage. An increased risk of a second primary malignancy including GC was observed in these patients treated with immuno/chemotherapy but not in patients treated solely with an H. pylori eradication treatment. With respect to gastrointestinal malignancies other than GC, discrepant data have been published regarding the association of H. pylori with pancreatic cancer whereas no association has been reported with esophageal squamous cell carcinoma. The majority of published studies still support an association of H. pylori with colon neoplasms.

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Issue Information

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Helicobacter pylori infection in children

Abstract

Helicobacter pylori infection in children differs from that in adults, from the point of view of epidemiology, host response, clinical features, related diseases, and diagnosis, as well as treatment strategies.

The prevalence of H. pylori infection, in both children and adults, is decreasing in the Western World as well as in some developing countries, which contrasts with the increase in childhood asthma and allergic diseases. Recurrent abdominal pain is not specific during H. pylori infection in children. The role of H. pylori infection and failure to thrive, children's growth, type I diabetes mellitus (T1DM) and celiac disease remains controversial.

The main initial diagnosis is based on upper digestive endoscopy with biopsy-based methods. Nodular gastritis may be a pathognomonic endoscopic finding of childhood H. pylori infection. The infection eradication control is based on validated noninvasive tests.

The main cause of treatment failure of H. pylori infection is its clarithromycin resistance. We recommend standard antibiotic susceptibility testing of H. pylori in pediatric patients prior to the initiation of eradication therapy. H. pylori treatment in children should be based on an evaluation of the rate of eradication in the local population, a systematic use of a treatment adapted to the susceptibility profile and a treatment compliance greater than 90%. The last meta-analysis in children did not show an advantage for sequential therapy when compared to a 14-day triple therapy.

Finally, the high rate of antibiotic resistance responsible for therapy failure in recent years justifies the necessity of a novel vaccine to prevent H. pylori infection in children.

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30th anniversary of the European helicobacter & microbiota study group!

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Author Index

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Helicobacter pylori infection and nonmalignant diseases

Abstract

A substantial decrease in Helicobacter pylori-associated peptic ulcer disease has been observed during the last decades. Drug-related ulcers as well as idiopathic ulcers are becoming predominant and are more refractory to treatment; however, H. pylori infection still plays an important role in ulcer bleeding and recurrence after therapy. The effect of H. pylori eradication upon functional dyspepsia symptoms has been reviewed in this article and generally confirms the results of previous meta-analyses. Additional evidence suggests a lack of impact upon the quality of life, in spite of improvement in symptoms. The association of H. pylori with gastroesophageal reflux disease and Barrett's esophagus remains controversial with a majority of published studies showing a negative association. Furthermore, a strong inverse relationship between the presence of H. pylori and the esophageal eosinophilia was also reported. Several studies and a review addressed the role of H. pylori in autoimmune gastritis and pernicious anemia. The association of the above still remains controversial. Finally, the necessity of routine endoscopy and H. pylori eradication before bariatric surgery is discussed. Several studies suggest the rationale of preoperative upper endoscopy and H. pylori eradication prior to surgery. However, the prevalence of H. pylori infection prior to surgery in these studies generally reflects the overall prevalence of the infection in the particular geographic area. In addition, results on the role of H. pylori in developing postoperative complications remain controversial.

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Inhibition of hemangioma growth using polymer–lipid hybrid nanoparticles for delivery of rapamycin

Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Haitao Li, Yunfei Teng, Jin Sun, Jianyong Liu
Although infantile hemangiomas is benign, its rapid growth may induce serious complications. However, only one drug Hemangeol™ has been approved by US Food and Drug Administration (FDA) to treat infantile hemangiomas. Thus it is necessary to develop novel alternative drugs to treat infantile hemangiomas. Rapamycin is a well-know potent antiangiogenic agent, whereas the daily oral administration of rapamycin exerts undesired metabolic effects due to its inhibition of mechanistic target of rapamycin (mTOR) which is critical in cell metabolism. We hereby developed rapamycin-loaded polymer–lipid hybrid nanoparticles (Rapamycin-PLNPs) as a local controlled release system to realize local and sustained release of rapamycin, aiming to reduce the side effects and frequency of administration of rapamycin. Rapamycin-PLNPs are of a small size (129.1nm), desired drug encapsulation efficiency (63.7%), and sustained drug release for 5 days. Rapamycin-PLNPs were shown to be able to effectively bind to hemangioma endothelia cells (HemECs), induce significant proliferation inhibition and reduce expression of angiogenesis factors in HemECs. The therapeutic effect of Rapamycin-PLNPs against infantile hemangioma in vivo was superior to rapamycin, as reflected by reduced hemangioma volume, weight and microvessel density. Taken together, Rapamycin-PLNPs represent a very promising local approach in the treatment of infantile hemangiomas.

Graphical abstract

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YAP1-TEAD1-Glut1 axis dictates the oncogenic phenotypes of breast cancer cells by modulating glycolysis

Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Chunli Lin, Xiaofeng Xu
Altered energy metabolism is a universal property of most cancer cells. The Hippo signaling pathway and its principal downstream effector YAP1 are responsible for tissue homeostasis including organ size, cell proliferation, apoptosis, and differentiation. Dysregulation of the Hippo pathway leads to the activation of YAP1 and further culminates in the development of multiple human cancers. In this study, by loss-of-function assay, we demonstrated that YAP1 contributed to the glycolytic phenotype of breast cancer cells. Knockdown of YAP1 inhibited the extracellular acidification rates, glucose consumption, and lactate production of breast cancer cells. Moreover, YAP1 interacted with TEAD1, exerted their transcriptional control of the functional target, glucose transporter 1 (Glut1). Overexpression of Glut1 restored the inhibitory effects of YAP1 knockdown on glycolysis as demonstrated by glucose consumption and lactate production. Suppression of glycolysis by deprivation of glucose largely compromised the oncogenic roles of YAP1 on cell proliferation, apoptosis, and invasive potential. Taken together, our data identify a novel role of YAP1-TEAD1 pathway in cancer energy metabolism.



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Antinociceptive, anti-inflammatory and anxiolytic-like effects of the ethanolic extract, fractions and Hibalactone isolated from Hydrocotyle umbellata L. (Acariçoba) – Araliaceae

Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Thiago Levi Silva Oliveira, Sandra Ribeiro de Morais, Stone de Sá, Matheus Gabriel de Oliveira, Iziara Ferreira Florentino, Dayane Moreira da Silva, Verônica Vale Carvalho, Vinícius Barreto da Silva, Boniek Gontijo Vaz, José Ricardo Sabino, Elson Alves Costa, José Realino de Paula
Hydrocotyle umbellata Linn. (Araliaceae) is specie used in the treatment of inflammatory diseases. Crude extract (E-HU) was prepared from H. umbellata subterraneous parts and fractionated by liquid-liquid partition, resulting hexane fraction (HF-HU), dichloromethane fraction (DF-HU), ethyl acetate fraction (EAF-HU) and aqueous fraction (AF-HU). The hibalactone (HU-1) was isolated from the DF-HU and its structure was elucidated by ¹H NMR and ¹³C NMR Spectroscopy, mass spectrometry and crystallographic x-ray analysis. The formalin-induced nociception was used to evaluate antinociceptive activity; carrageenan-induced edema and pleurisy tests to evaluate anti-inflammatory activity and light-dark box to evaluate anxiolytic-like activity in mice. The acute oral treatments with E-HU (1000mg/kg), DF-HU (150mg/kg), EAF-HU (400mg/kg) and HU-1 (33mg/kg) decreased the licking time in both phases of the formalin test. In the carrageenan-induced inflammation models, the treatment with the same doses of E-HU, DF-HU, EAF-HU and HU-1 reduced the paw edema formation and leukocytes account into pleural cavity. In silico findings suggest that hibalactone present anti-inflammatory activity by interacting with the enzymes 5-lipoxygenase and cyclooxygenase-2. In the light dark box, the treatments with DF-HU, EAF-HU and HU-1 revealed an anxiolytic like effect. Thus, the E-HU and fractions of H. umbellata showed antinociceptive, anti-inflammatory and anxiolytic like activities, as also hibalactone, a possible phytoconstituent responsible for the biological effects of this specie.

Graphical abstract

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Bamboo leaf extract ameliorates cardiac fibrosis possibly via alleviating inflammation, oxidative stress and apoptosis

Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Lili Zhang, Yizhen Mao, Jiajun Pan, Shanshan Wang, Lei Chen, Jie Xiang
Previous studies have shown that inflammatory process contributes to the pathogenesis of cardiac damage induced by diabetes mellitus. However, the underlying mechanisms and strategies to alleviate inflammatory injury in the diabetic heart are not fully elucidated. In this study, we investigated the potential role and related mechanism of bamboo leaf extract (BLE) on diabetes-induced cardiac fibrosis in rats. Diabetes was induced by streptozocin (STZ) in rats, blood glucose and glycosylated hemoglobin A1c (HbAlc) were measured. Super oxide dismutase (SOD) activity and malondialdehyde (MDA) level in rat heart homogenates were tested using special kits. Cardiac function was evaluated by echocardiography, and myocardial histology was detected by hematoxylin eosin (HE) staining and Masson's trichrome staining. Furthermore, expression of transforming growth factor-β1 (TGF-β1), interleukin 6 (IL-6) and Cleaved-cysteinyl aspartate-specific proteinase-3 (Cleaved-caspase-3), and the activity of nuclear factor κB (NF-κB) were examined by western blot analysis. From the data, we found that the BLE treatment inhibits oxidative stress and improved cardiac function in STZ-induced diabetic rats. BLE treatment significantly ameliorated diabetes-induced myocardial morphological changes and cardiac inflammation. Moreover, the protein levels of TGF-β1, IL-6,Cleaved-caspase-3 and the nuclear transcription of NF-κB in the hearts were markedly reduced in diabetic rats result from BLE treatment. In conclusion, this study suggested that BLE ameliorates cardiac fibrosis in streptozotocin-induced diabetic rats, and this protective effect possibly through inhibiting inflammation, oxidative stress and apoptosis. BLE might serve as a potential therapeutic target for the treatment of the cardiac fibrosis in diabetic patients.



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Development and characterization of hyaluronic acid modified PLGA based nanoparticles for improved efficacy of cisplatin in solid tumor

Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Noor Alam, Mytre Koul, Mubashir J. Mintoo, Vaibhav Khare, Rahul Gupta, Neha Rawat, Parduman Raj Sharma, Shashank K. Singh, Dilip M. Mondhe, Prem N. Gupta
Cisplatin is a potent and widely used chemotherapeutic agent to treat a variety of tumors. However, its clinical use is associated with undesirable side effects and acquired resistance to cisplatin. In this study, cisplatin loaded hyaluronic acid (HA) functionalized poly (lactic-co-glycolic acid)–poly (ethylene glycol) nanoparticles (CP-HA-PLGA-PEG-NPs) were fabricated using double emulsion solvent evaporation method to target CD44 receptor expressed on cancerous cells. The developed nanoconstructs were characterized for various in vitro parameters, including size distribution, zeta potential, morphology, drug loading and in vitro release. The HA content on the HA-PLGA-PEG-NPs was quantified by a turbidimetric method. The in vitro anticancer study in human ovarian cancer (SKOV-3) cells showed significantly (p<0.05) higher cytotoxicity of CP-HA-PLGA-PEG NPs as compared to free cisplatin and non-targeted nanoparticles (CP-PLGA-PEG NPs). Further, laser scanning confocal microscopy revealed that there was enhanced cellular uptake of HA-PLGA-PEG NPs in CD44-over expressing ovarian cancer cell line (SKOV-3). The in vivo antitumor activity of CP-HA-PLGA-PEG-NPs was significantly (p<0.05) higher than free cisplatin and CP-PLGA-PEG-NPs in Ehrlich tumor (solid) bearing mice. The results demonstrated the potential of target specific nanoconstruct of cisplatin in the improved cancer chemotherapy.

Graphical abstract

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Mixed micelles for encapsulation of doxorubicin with enhanced in vitro cytotoxicity on breast and ovarian cancer cell lines versus Doxil®

Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Maximiliano Cagel, Ezequiel Bernabeu, Lorena Gonzalez, Eduardo Lagomarsino, Marcela Zubillaga, Marcela A. Moretton, Diego A. Chiappetta
Doxorubicin (DOX) is used as a "first-line" antineoplastic drug in ovarian and metastatic breast cancer. However, serious side effects, such as cardiotoxicity have been reported after DOX intravenous administration. Hence, we investigated different micelle-former biomaterials, as Soluplus^®, Pluronic F127, Tetronic T1107 and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) to develop a potential mixed micellar nanocarrier for DOX delivery. Since DOX hydrochloride is a poor candidate to be encapsulated inside the hydrophobic core of the mixed micelles, we assayed a hydrophobic complex between DOX and sodium deoxycholate (NaDC) as an excellent candidate to be encapsulated within polymeric micelles. The combination of T1107:TPGS (1:3, weight ratio) demonstrated the best physicochemical properties together with a high DL capacity (6.43% w/v). Particularly, DOX in vitro release was higher at acidic tumour microenvironment pH value (5.5) than at physiological counterpart (7.4). The hydrodynamic diameter of the DOX/NaDC-loaded mixed micellar system was 10.7nm (PDI=0.239). The in vitro cytotoxicity of the mixed micellar formulation resulted significantly (p<0.05) higher than Doxil^® against ovarian (SKOV-3) and triple-negative breast cancer cells (MDA-MB- 231). Further, the in vitro cellular uptake assays demonstrated a significant increment (p<0.05) of the DOX intracellular content for the mixed micelles versus Doxil^® for both, SKOV-3 (at 2, 4 and 6h of incubation) and MDA-MB-231 (at 4h of incubation) cells. These findings suggest that T1107:TPGS (1:3) mixed micelles could be employed as a potential nanotechnological platform for drug delivery of DOX.

Graphical abstract

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In vitro, In silico and In vivo Antitumor Activity of Crude Methanolic Extract of Tetilla dactyloidea (Carter, 1869) on DEN Induced HCC in a Rat Model

Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Gowri Shankar Krishnan, Vidhya Rajagopal, Sophy Renilda Antony Joseph, Divya Sebastian, Ignacimuthu Savarimuthu, Karthick Raja Namasivayam Selvaraj, Albin Fleming Thobias
Tetilla dactyloidea (Carter, 1869) is a marine sponge classified under Demospongia and recent studies have demonstrated that active constituents of Demospongia class have exhibited several potential medical applications. However, no preliminary pharmacological studies have been reported so far. The present investigation was carried out to evaluate the zoo-chemical status, antioxidant potential and anticancer activity of Crude Methanolic Extract of Tetilla dactyloidea (CMETD). Hepatocellular Carcinoma (HCC) was induced in the liver of male Sprague Dawley (SD) rats by treating with diethylnitrosamine (DEN). Nodule incidence, body weight, liver marker enzymes, enzymatic and non-enzymatic antioxidant, phase I metabolizing and liver macromolecular damaging enzymes and immuno-histopathological changes were assessed in DEN and DEN+CMETD treated rats. Oral administration of CMETD at a dose of 400mg/kg body weight to DEN treated rats restored the above parameters to near normal levels compared to control. The biochemical results were consistent with histopathological observations suggesting marked hepatoprotective effect of CMETD in a dose dependent manner. The GCMS of CMETD analysis showed the presence of six compounds. In in silico analysis 9-Octadecenoic acid (Z)-, 2-hydroxy-1-(hydroxymethyl) ethyl ester ligand showed an effective binding energy of −7.1kcal/mol against Cox-2 receptor. The compounds showed desirable pharmacokinetic properties and significant molecular interactions with the HCC receptors. To conclude, our results clearly suggested that CMETD treatment prevented liver damage, protected the antioxidant defense system and possessed anti-carcinogenic potential in DEN induced hepatic carcinoma.



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Homoisoflavonoids as potential antiangiogenic agents for retinal neovascularization

Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Sk. Abdul Amin, Nilanjan Adhikari, Shovanlal Gayen, Tarun Jha
A number of people worldwide have been suffering from ocular neovascularization that may be treated by a variety of drugs but these may possess adverse effects. Therefore, small antiangiogenic molecules with higher potency and lower toxic effects are intended. However, homoisoflavonoids of natural origin show the potential antiangiogenic effect in ocular neovascularization. These homoisoflavonoids are judged quantitatively in terms of statistical validation through multi-chemometric modeling approaches for the betterment and refinement of their structures required for higher antiangiogenic activity targeted to ocular neovascularization. These approaches may be utilized to design better antiangiogenic homoisoflavonoids.

Graphical abstract

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The effects of β-caryophyllene oxide and trans-nerolidol on the efficacy of doxorubicin in breast cancer cells and breast tumor-bearing mice

Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Veronika Hanušová, Kateřina Caltová, Hana Svobodová, Martin Ambrož, Adam Skarka, Natálie Murínová, Věra Králová, Pavel Tomšík, Lenka Skálová
BackgroundOne approach to improve effect of chemotherapy is combination of classical cytostatic drugs with natural compounds, e. g. sesquiterpenes. In our previous study, sesquiterpenes β-caryophyllene oxide (CAO) and trans-nerolidol (NER) improved the anti-proliferative effect of doxorubicin (DOX) in intestinal cancer cell lines.PurposeThe present study was designed to evaluate the effect of CAO and NER on DOX efficacy, focusing on cell proliferation, migration, apoptosis and DOX accumulation in breast cancer cells MDA-MB-231 and MCF7 in vitro and in mice bearing solid Ehrlich tumors (EST) in vivo.MethodsThe impact of cytotoxic effect was assessed by the neutral red uptake test. The ability to migrate was tested using real-time measurement in x-CELLigence system. Expressions of molecules were examined using western blot analysis. The accumulation of DOX inside the cells using time lapse microscopy was observed. The mice with inoculated EST cells were treated repeatedly with DOX and DOX+CAO or DOX+NER and the growth of tumors were monitored. DOX concentrations in plasma and tumor were assayed using HPLC.ResultsIn MDA-MB-231, combination of DOX with CAO enhanced anti-proliferative effect and acted strongly synergistic. NER increased accumulation of DOX inside the cells; moreover combination DOX with NER suppressed migration ability in vitro. In vivo, apoptosis was activated especially in group treated with DOX and CAO. However, none of tested sesquiterpenes was able to improve DOX accumulation in tumors and DOX-mediated inhibition of tumor growth.ConclusionIn conclusion, sesquiterpenes CAO and NER increased the efficacy of DOX in breast cancer cells in vitro, but did not improve its effect in vivo, in Ehrlich solid tumor bearing mice.

Graphical abstract

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Diamine derivative anti-Trichomonas vaginalis and anti-Tritrichomonas foetus activities by effect on polyamine metabolism

Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Graziela Vargas Rigo, Márcia Rodrigues Trein, Danielle da Silva Trentin, Alexandre José Macedo, Bruno Assis de Oliveira, Angelina Maria de Almeida, Raquel Brandt Giordani, Mauro Vieira de Almeida, Tiana Tasca
Human and bovine trichomoniasis are sexually transmitted diseases (STD) caused by Trichomonas vaginalis and Tritrichomonas foetus, respectively. Human trichomoniasis is the most common non-viral STD in the world and bovine trichomoniasis causes significant economic losses to breeders. Considering the significant impact of the infections caused by these protozoa and the treatment failures, the search for new therapeutic alternatives becomes crucial. In this study the effect of diamines and amino alcohols in the in vitro viability of trichomonads was evaluated. Screening demonstrated the high activity of diamine 4 against these protozoa. Although cytotoxicity against HMVII cell line and slight hemolysis were observed in vitro, the compound showed no toxic effect on the Galleria mellonella in vivo model. Importantly, diamine 4 was active against both trichomonads species at 6h and 24h of incubation, and these effects was reverted by putrescine, a polyamine, suggesting competition for the same metabolic pathway. These findings indicate that the mechanism of action of diamine 4 is through the polyamine metabolism, a pathway distinct from that presented by metronidazole, the drug usually used to treat trichomoniasis and to which resistance is widely reported. These data demonstrate the importance of diamines as potential novel candidates as anti-T. vaginalis and anti-T. foetus agents.

Graphical abstract

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Molecular estimation of alteration in intestinal microbial composition in Hashimoto’s thyroiditis patients

Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Hafiz Muhammad Ishaq, Imran Shair Mohammad, Hui Guo, Muhammad Shahzad, Yin Jian Hou, Chaofeng Ma, Zahid Naseem, Xiaokang Wu, Peijie Shi, Jiru Xu
The gut microbiota has a crucial effect on human health and physiology. Hypothyroid Hashimoto's thyroiditis (HT) is an autoimmune disorder manifested with environmental and genetic factors. However, it is hypothesized that intestinal microbes might play a vital role in the pathogenesis of HT. The aim of current was to investigate and characterize the gut microbial composition of HT patients both quantitatively and qualitatively. The fecal samples from 29 HT patients and 12 healthy individuals were collected. The PCR-DGGE targeted V3 site of 16S rRNA gene and real time PCR for Bifidobacterium Lactobacillus, Bacteroides vulgatus and Clostridium leptum were performed. Pyrosequencing of 16S rRNA gene with V4 location was performed on 20 randomly selected samples. The comparative analysis of diversity and richness indices revealed diversification of gut microbiota in HT as compared to control. The statistical data elucidate the alterations in phyla of HT patients which was also affirmed at the family level. We observed the declined abundance of Prevotella_9 and Dialister, while elevated genera of the diseased group included Escherichia-Shigella and Parasutterella. The alteration in gut microbial configuration was also monitored at the species level, which showed an increased abundance of E. coli in HT. Therefore, the current study is in agreement with the hypothesis that HT patients have intestinal microbial dysbiosis. The taxa statistics at species-level along with each gut microbial community were modified in HT. Thus, the current study may offer the new insights into the treatment of HT patients, disease pathway, and mechanism.

Graphical abstract

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Dexmedetomidine exerts neuroprotective effect via the activation of the PI3K/Akt/mTOR signaling pathway in rats with traumatic brain injury

Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Min Shen, Shan Wang, Xin Wen, Xin-Rui Han, Yong-Jian Wang, Xiu-Min Zhou, Man-He Zhang, Dong-Mei Wu, Jun Lu, Yuan-Lin Zheng
Objective: This study aims to explore the neuroprotective effects of dexmedetomidine (Dex) in rats suffering from traumatic brain injury (TBI) via the PI3K/Akt/mTOR signaling pathway.MethodsA weight drop model was performed for TBI model establishment. A total of 150 Sprague Dawley rats were selected and assigned into control, sham, TBI, TBI+Dex, TBI+LY294002 (LY) and TBI+Dex+LY groups. Modified Neurological Severity Score (mNSS) was conducted in order to evaluate the neurological injury. The water content in brain tissues was measured. The expressions of PI3K/Akt/mTOR signaling pathway-related proteins, tight junction proteins (ZO-1 and Claudin-5) and autophagy proteins (LC3 I/II and Beclin-1) were detected using Western blot assay. A TUNEL assay was applied for cell apoptosis, immunofluorescence was employed for the detection of the positive expression of LC3, and ELISA was applied for detection of levels of inflammatory factors [tumor necrosis factor-alph (TNF-a), interleukin-1β (IL-1β), interferon-γ (INF-γ) as well as IL-6], respectively.ResultsCompared with the control group, the other four groups exhibited increased mNSS, brain water content, expression of LC3, TNF-a, IL-1β, INF-γ and IL-6, and positive expression of LC3, expression of LC3 I/II and Beclin-1, but decreased expression of pp-PI3K/t-PI3K, p-Akt/t-Akt, p-mTOR/t-mTOR, ZO-1 and Claudin-5. Compared with the TBI group, the TBI+Dex group exhibited reduced mNSS, brain water content, expression of LC3, TNF-a, IL-1β, INF-γ and IL-6, positive expression of LC3, as well as expression of LC3 I/II and Beclin-1 but demonstrated an elevated expression of pp-PI3K/t-PI3K, p-Akt/t-Akt, p-mTOR/t-mTOR, ZO-1 and Claudin-5, while opposite trends were observed in the TBI+LY group. The TBI+Dex group exhibited reduced mNSS, brain water content, expression of LC3, TNF-a, IL-1β, INF-γ and IL-6, positive expression of LC3, as well as expression of LC3 I/II and Beclin-1 but demonstrated an elevated expression of pp-PI3K/t-PI3K, p-Akt/t-Akt, p-mTOR/t-mTOR, ZO-1 and Claudin-5, while opposite trends were observed in the TBI+LY group, as compared with the TBI+Dex+LY group.ConclusionThe data shows that Dex exerts a neuroprotective effect via the activation of the PI3K/Akt/mTOR signaling pathway in rats with TBI.



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Maslinic acid inhibits impairment of endothelial functions induced by high glucose in HAEC cells through improving insulin signaling and oxidative stress

Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Feng Li, Qingxian Li, Xianai Shi, Yanghao Guo
Impaired endothelial functions are closely associated with many chronic vascular-related diseases. Maslinic acid (MA), a natural pentacyclic triterpene compound, has received more and more attentions in recent years due to a variety of bioactivities. In the present study, we investigated the effect of MA on impaired endothelial functions in human aortic endothelial cells (HAEC) induced by high glucose treatment and discussed its possible mechanism. We showed that MA decreased the ROS level, inhibited the inflammatory cytokines expression, facilitated insulin-mediated IRS-1/PI3K/Akt/eNOS signaling and suppressed the cellular apoptosis ratio induced by high glucose. The molecular docking results showed that MA may regulate multiple targets to improve the endothelial dysfunction in HAECs exposed to high glucose. These results revealed potential application of MA in improving endothelia dysfunction.



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Hormonal and genetic factors interact to control aromatase expression in the developing brain

Abstract

The brain expression of the enzyme P450-aromatase has been extensively studied. Since the aromatization hypothesis established brain aromatase as a key factor to convert gonadal testosterone to oestradiol, several studies have investigated the regulation of aromatase during the critical period of brain sexual differentiation. Here, we review previous and recent findings concerning regulation of aromatase. The role of gonadal hormones, sex chromosome genes and neurosteroids is analysed in term of their contribution to aromatase expression and the implications for the organizational effect of steroids during development.

This article is protected by copyright. All rights reserved.

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Adenocarcinoma of the lacrimal gland: a case report

Primary ductal adenocarcinomas of the lacrimal gland are very rare. This neoplasm shares some histological and immunohistochemical similarities with salivary duct carcinoma.

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The changing landscape of dermatology practice: melanoma and pump-probe laser microscopy

Abstract

To present current melanoma diagnosis, staging, prognosis, and treatment algorithms and how recent advances in laser pump-probe microscopy will fill in the gaps in our clinical understanding. Expert opinion and significantly cited articles identified in SCOPUS were used in conjunction with a pubmed database search on Melanoma practice guidelines from the last 10 years. Significant advances in melanoma treatment have been made over the last decade. However, proper treatment algorithm and prognostic information per melanoma stage remain controversial. The next step for providers will involve the identification of patient population(s) that can benefit from recent advances. One method of identifying potential patients is through new laser imaging techniques. Pump-probe laser microscopy has been shown to correctly identify nevi from melanoma and furthermore stratify melanoma by aggressiveness. The recent development of effective adjuvant therapies for melanoma is promising and should be utilized on appropriate patient populations that can potentially be identified using pump-probe laser microscopy.

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Effect of hydrophobicity of pharmaceuticals and personal care products for adsorption on activated carbon: Adsorption isotherms, kinetics and mechanism

Abstract

Adsorption of three pharmaceuticals and personal care products (PPCPs), namely caffeine, ibuprofen and triclosan on commercial powdered activated carbon was examined in aqueous medium. The contaminants were chosen based on their diverse log K_ow (octanol-water partition coefficient) viz. − 0.07 for caffeine, 3.97 for ibuprofen and 4.76 for triclosan to examine the role of hydrophobicity on adsorption process. The adsorbent characterisation was achieved using BET surface area, SEM, pore size distribution studies and FTIR. Influence of mass of PAC, contact time, solution pH and initial concentration on adsorption capacity of PAC was studied. Adsorption isotherms and kinetics were applied to establish the mechanism of adsorption. The kinetics followed pseudo-second order with physisorption occurring through particle diffusion. The Freundlich model fitted best among the isotherm models. The adsorption capacity increased in the order CFN < IBU < TCS which correlates with increasing hydrophobicity (log K_ow), molecular weight and decreasing water solubility, respectively. We conclude that micro-pollutant hydrophobicity contributes towards adsorption on activated carbon.

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Clinicopathological parameters affecting nodal yields in patients with oral squamous cell carcinoma receiving selective neck dissection

Oral squamous cell carcinoma (OSCC) represents one of the most common malignancies worldwide, and 90% of head and neck cancers (Shah and Gil 2009). 263,000 newly diagnosed cases and 128,000 deaths are registered per year (Shah and Gil 2009).

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Hyperirritable stomach as a cause of obstructive symptoms after sleeve gastrectomy: clinical and radiographic findings

Publication date: Available online 10 September 2017
Source:Clinical Imaging
Author(s): Amelia M. Wnorowski, Marc S. Levine, Stephen E. Rubesin, Noel N. Williams, Kristoffel R. Dumon
PurposeTo characterize clinical and radiographic features of a hyperirritable stomach after sleeve gastrectomy.Materials/methodsRadiology reports revealed that 10/76 patients (13%) with obstructive symptoms after sleeve gastrectomy had a hyperirritable stomach.ResultsAll 10 patients presented with nausea, vomiting, and/or regurgitation. All 10 had emesis on barium studies in the absence of gastric outlet obstruction, gastroparesis, or small bowel obstruction/ileus. Five had extraintestinal causes of nausea/vomiting. Eight had improvement/resolution of symptoms on medical treatment.ConclusionIn 13% of patients with nausea/vomiting after sleeve gastrectomy, barium studies revealed a hyperirritable stomach, which likely is multifactorial and self-limited in most patients.



http://ift.tt/2eY10WQ

The new targeted therapy in systemic lupus erythematosus: Is the glass half-full or half-empty?

Publication date: Available online 9 September 2017
Source:Autoimmunity Reviews
Author(s): Andrea Doria, Ricard Cervera, Mariele Gatto, Gamal Chehab, Matthias Schneider
Biologic therapy is still limited in lupus, where chronic steroid exposure and wide-spectrum immunosuppression are major triggers of organ damage.In this viewpoint, the authors summarize their views for a "half-full or half-empty" glass on targeted therapy in SLE.The are several reasons for seeing the glass half-empty and in this section the authors propose a critical reflection on scarceness of novel targeted lupus therapies. They show how hard it is to identify suitable biological and clinical targets and to choose the patients that may best fit those targets, as well as to stratify patients according to disease subtype and response, all contributing to the final outcome.On the other hand, reasons are emerging to see the glass half-full, including the growing evidence that disease activity and damage can both be hindered by the proper use of novel drugs and that promising molecules are upcoming. In this section, the authors contextualize potentials and failures of new drugs, providing a critical reading of disappointing results and underlining the concrete benefits obtainable through a wise use of available treatments.Indeed, combining medications with new therapeutic strategies such as the treat-to-target seems the right approach to add some water to a filling glass.



http://ift.tt/2vZjPAh

Can we withdraw anticoagulation in patients with antiphospholipid syndrome after seroconvertion?

Publication date: Available online 9 September 2017
Source:Autoimmunity Reviews
Author(s): S. Sciascia, E. Coloma-Bazán, M. Radin, M.L. Bertolaccini, C. López-Pedrera, Gerard Espinosa, P.L. Meroni, R. Cervera, M.J. Cuadrado
The current mainstay of treatment in patients with thrombotic antiphospholipid syndrome (APS) is long-term anticoagulation, mainly with Vitamin K antagonist agents. Some recently available studies have created new ground for discussion about the possible discontinuation of anticoagulation therapy in patients with a history of thrombotic APS in whom antiphospholipid antibodies (aPL) are not detected any longer (i.e. aPL seroconversion).We report the main points discussed at the last CORA Meeting regarding the issue whether or not anticoagulation can be stopped after aPL seroconversion. In particular, we systematically reviewed the available evidence investigating the clinical outcome of APS patients with aPL seroconversion in whom anticoagulation was stopped when compared to those in whom therapy was continued regardless the aPL profile. Furthermore, the molecular basis for the aPL pathogenicity, the available evidence of non-criteria aPL and their association with thrombosis are addressed.To date, available evidence is still limited to support the indication to stop oral anticoagulation therapy in patients with a previous diagnosis of thrombotic APS who subsequently developed a negative aPL profile. The identification of the whole risk profile for cardiovascular manifestations and possibly of a second level aPL testing in selected patients with aPL might support the eventual clinical decision but further investigation is warranted.



http://ift.tt/2wTrNIt

Humanistic and cost burden of systemic sclerosis: A review of the literature

Publication date: Available online 9 September 2017
Source:Autoimmunity Reviews
Author(s): Aryeh Fischer, Evelina Zimovetz, Caroline Ling, Dirk Esser, Nils Schoof
BackgroundSystemic sclerosis (SSc), or systemic scleroderma, is a chronic multisystem autoimmune disease characterised by widespread vascular injury and progressive fibrosis of the skin and internal organs. Patients with SSc have decreased survival, with pulmonary involvement as the main cause of death. Current treatments for SSc manage a range of symptoms but not the cause of the disease. Our review describes the humanistic and cost burden of SSc.MethodsA structured review of the literature was conducted, using predefined search strategies to search PubMed, Embase, and the Cochrane Library. Grey literature searches also were conducted.ResultsIn total, 2226 articles were identified in the databases and 52 were included; an additional 10 sources were included from the grey literature. The review identified six studies reporting relevant cost estimates conducted in five different countries and four studies that assessed the humanistic burden of SSc. Total direct annual medical costs per patient for Europe varied from €3544 to €8452. For Canada, these costs were reported to be from Can$5038 to Can$10,673. In the United States, the total direct health care costs were reported to be US$17,365 to US$18,396. Different key drivers of direct costs were reported, including hospitalisations, outpatients, and medication. The total annual costs per patient were reported at Can$18,453 in Canada and varied from €11,074 to €22,459 in Europe. Indirect costs represented the largest component of the total costs. EQ-5D utility scores were lower for patients with SSc than those observed in the general population, with reported mean values of 0.49 and 0.68, respectively. The average value of the Health Assessment Questionnaire for patients with SSc was significantly higher than the control population (0.94), and the average value of the SF-36 was significantly lower than the control population: 49.99 for the physical dimension and 58.42 for the mental dimension.ConclusionsOverall, there is a paucity of information on the burden of SSc. Nonetheless, our review indicates that the quality of life of patients with SSc is considerably lower than that of the general population. In addition, SSc places a considerable economic burden on health care systems and society as a whole.



http://ift.tt/2vYTyCb

Is PET/CT essential in the diagnosis and follow-up of temporal arteritis?

Publication date: Available online 9 September 2017
Source:Autoimmunity Reviews
Author(s): Carlo Salvarani, Alessandra Soriano, Francesco Muratore, Yehuda Shoenfeld, Daniel Blockmans
The increasing availability and improvement of imaging techniques are deeply influencing diagnosis and work-up of patients affected with vasculitis, particularly those with large vessel vasculitis (LVV). Fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET), especially when integrated with computed tomography (CT), is taking hold as a useful diagnostic technique to examine the aorta and the other large vessels in giant cell arteritis (GCA) with concomitant large vessel involvement (LV-GCA). In this paper we examined the progresses performed in this field in the last twenty years and the evidence available so far according to two different points of view ('pros' and 'cons'), in order to give a comprehensive answer to a still open question about the role of PET/CT in the diagnosis and follow-up of GCA.



http://ift.tt/2wSQUer

Neutrophil extracellular traps (NETs) in autoimmune diseases: A comprehensive review

Publication date: Available online 9 September 2017
Source:Autoimmunity Reviews
Author(s): Keum Hwa Lee, Andreas Kronbichler, David Duck-Young Park, YoungMin Park, Hanwool Moon, Hyungdo Kim, Jun Hyug Choi, YoungSeo Choi, Songjoo Shim, Il Suk Lyu, Byung Hwan Yun, Yeonseung Han, Donghee Lee, Sang Yoon Lee, Byung Hun Yoo, Kyung Hwan Lee, Tai Lim Kim, Heonki Kim, Joo Sung Shim, Wonseok Nam, Heesung So, SooYeon Choi, Sangmok Lee, Jae Il Shin
The structures named neutrophil extracellular traps (NETs) are fibrous networks which protrude from the membrane of activated neutrophils. NETs are found in a variety of conditions, such as infection, malignancy, atherosclerosis, and autoimmune diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV), psoriasis, and gout. The impact of NETs on the development mechanisms of autoimmune diseases are proposed to arise from an imbalance between "NETosis" which is a process of NET formation and NET degradation. Neutrophils, interleukin-8, ANCA and other many inflammatory molecules are considered to play a key role in NET formation. In this way, prolonged exposure to these abnormal cascade of NETs affect autoimmunity and increase the chance of systemic organ damage. In this review, we will discuss the specific roles of various inflammatory molecules in relationship to NETs. We will also provide evidence of the importance of NETs in the pathogenesis of autoimmune diseases and furthermore highlight the potential that target therapies may influence NET formation and associated molecules.



http://ift.tt/2vYTfre

Should we treat congenital heart block with fluorinated corticosteroids?

Publication date: Available online 9 September 2017
Source:Autoimmunity Reviews
Author(s): Antonio Brucato, Angela Tincani, Micaela Fredi, Silvia Breda, Veronique Ramoni, Nathalie Morel, Nathalie Costedoat-Chalumeau




http://ift.tt/2wSQO6z

Bone mineral density and vitamin D status in systemic lupus erythematosus (SLE): A systematic review

Publication date: Available online 9 September 2017
Source:Autoimmunity Reviews
Author(s): Tarek Carlos Salman-Monte, Vicenç Torrente-Segarra, Ana Leticia Vega Vidal, Patricia Corzo, F. Castro-Dominguez, F. Ojeda, Jordi Carbonell Abelló
Despite the improvement in the quality of life of patients with SLE due to scientific and technological advances, SLE remains a disease that over the years may produce irreversible damage to patients. Osteoporosis and secondary bone fractures are two of the major causes of irreparable injury in patients with SLE. Vitamin D insufficiency may play a vital role both in reduced Bone Mineral Density (BMD) and in the appearance of fractures, although its mechanisms of action are still unclear. We performed a systematic review of the literature in order to determine the prevalence and predictors of reduced vitamin D plasma levels, bone loss and the presence of fractures in SLE patients. Our review encompassed all English-language publications using Medline and EMBase electronic databases from their inception (1966 and 1980, respectively) to December 2016. We included all intervention studies and observational studies in which vitamin D plasma levels, BMD and bone loss were measured and applied to patients with SLE. Previous studies suggested an increase in bone loss and fracture in patients with SLE compared with general population and although there is a high prevalence of vitamin D insufficiency in the general population, previous studies had demonstrated lower vitamin D levels in patients with SLE compared to age-matched controls. The etiology of reduced bone mass and reduced vitamin D plasma levels in SLE is multifactorial and includes a variety of intrinsic factors related to the disease itself and treatment side effects. SLE patients are at risk for developing these two comorbidities (reduced vitamin D plasma levels and low BMD) and it is therefore essential to study, monitor, prevent and treat bone metabolism disorders in SLE patients.



http://ift.tt/2vZjCgt

Is ACPA positivity the main driver for rheumatoid arthritis treatment? Pros and cons

Publication date: Available online 9 September 2017
Source:Autoimmunity Reviews
Author(s): Stefano Alivernini, Mauro Galeazzi, Hagit Peleg, Barbara Tolusso, Elisa Gremese, Gianfranco Ferraccioli, Yaakov Naparstek
Rheumatoid Arthritis (RA) is an autoimmune chronic disease that is characterized by the positivity of various antibodies, the most specific being autoantibodies against citrullinated antigens (ACPA). Despite ACPA are not arthritogenic by themselves, ACPA positive individuals have high risk of RA development and ACPA positivity is associated with severe erosive phenotype and higher mortality rate compared to seronegative RA. Moreover, ACPA status is associated with favorable response to biologics targeting pathways involving autoantibody producing cells as B lymphocytes. In the current review we have discussed the pros and cons on the available scientific evidences, regarding the diagnostic, prognostic and management implications of ACPAs in RA.



http://ift.tt/2gVmFfl

The new targeted therapy in systemic lupus erythematosus: Is the glass half-full or half-empty?

Publication date: Available online 9 September 2017
Source:Autoimmunity Reviews
Author(s): Andrea Doria, Ricard Cervera, Mariele Gatto, Gamal Chehab, Matthias Schneider
Biologic therapy is still limited in lupus, where chronic steroid exposure and wide-spectrum immunosuppression are major triggers of organ damage.In this viewpoint, the authors summarize their views for a "half-full or half-empty" glass on targeted therapy in SLE.The are several reasons for seeing the glass half-empty and in this section the authors propose a critical reflection on scarceness of novel targeted lupus therapies. They show how hard it is to identify suitable biological and clinical targets and to choose the patients that may best fit those targets, as well as to stratify patients according to disease subtype and response, all contributing to the final outcome.On the other hand, reasons are emerging to see the glass half-full, including the growing evidence that disease activity and damage can both be hindered by the proper use of novel drugs and that promising molecules are upcoming. In this section, the authors contextualize potentials and failures of new drugs, providing a critical reading of disappointing results and underlining the concrete benefits obtainable through a wise use of available treatments.Indeed, combining medications with new therapeutic strategies such as the treat-to-target seems the right approach to add some water to a filling glass.



http://ift.tt/2vZjPAh

Can we withdraw anticoagulation in patients with antiphospholipid syndrome after seroconvertion?

Publication date: Available online 9 September 2017
Source:Autoimmunity Reviews
Author(s): S. Sciascia, E. Coloma-Bazán, M. Radin, M.L. Bertolaccini, C. López-Pedrera, Gerard Espinosa, P.L. Meroni, R. Cervera, M.J. Cuadrado
The current mainstay of treatment in patients with thrombotic antiphospholipid syndrome (APS) is long-term anticoagulation, mainly with Vitamin K antagonist agents. Some recently available studies have created new ground for discussion about the possible discontinuation of anticoagulation therapy in patients with a history of thrombotic APS in whom antiphospholipid antibodies (aPL) are not detected any longer (i.e. aPL seroconversion).We report the main points discussed at the last CORA Meeting regarding the issue whether or not anticoagulation can be stopped after aPL seroconversion. In particular, we systematically reviewed the available evidence investigating the clinical outcome of APS patients with aPL seroconversion in whom anticoagulation was stopped when compared to those in whom therapy was continued regardless the aPL profile. Furthermore, the molecular basis for the aPL pathogenicity, the available evidence of non-criteria aPL and their association with thrombosis are addressed.To date, available evidence is still limited to support the indication to stop oral anticoagulation therapy in patients with a previous diagnosis of thrombotic APS who subsequently developed a negative aPL profile. The identification of the whole risk profile for cardiovascular manifestations and possibly of a second level aPL testing in selected patients with aPL might support the eventual clinical decision but further investigation is warranted.



http://ift.tt/2wTrNIt

Neutrophil extracellular traps (NETs) in autoimmune diseases: A comprehensive review

Publication date: Available online 9 September 2017
Source:Autoimmunity Reviews
Author(s): Keum Hwa Lee, Andreas Kronbichler, David Duck-Young Park, YoungMin Park, Hanwool Moon, Hyungdo Kim, Jun Hyug Choi, YoungSeo Choi, Songjoo Shim, Il Suk Lyu, Byung Hwan Yun, Yeonseung Han, Donghee Lee, Sang Yoon Lee, Byung Hun Yoo, Kyung Hwan Lee, Tai Lim Kim, Heonki Kim, Joo Sung Shim, Wonseok Nam, Heesung So, SooYeon Choi, Sangmok Lee, Jae Il Shin
The structures named neutrophil extracellular traps (NETs) are fibrous networks which protrude from the membrane of activated neutrophils. NETs are found in a variety of conditions, such as infection, malignancy, atherosclerosis, and autoimmune diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV), psoriasis, and gout. The impact of NETs on the development mechanisms of autoimmune diseases are proposed to arise from an imbalance between "NETosis" which is a process of NET formation and NET degradation. Neutrophils, interleukin-8, ANCA and other many inflammatory molecules are considered to play a key role in NET formation. In this way, prolonged exposure to these abnormal cascade of NETs affect autoimmunity and increase the chance of systemic organ damage. In this review, we will discuss the specific roles of various inflammatory molecules in relationship to NETs. We will also provide evidence of the importance of NETs in the pathogenesis of autoimmune diseases and furthermore highlight the potential that target therapies may influence NET formation and associated molecules.



http://ift.tt/2vYTfre

Humanistic and cost burden of systemic sclerosis: A review of the literature

Publication date: Available online 9 September 2017
Source:Autoimmunity Reviews
Author(s): Aryeh Fischer, Evelina Zimovetz, Caroline Ling, Dirk Esser, Nils Schoof
BackgroundSystemic sclerosis (SSc), or systemic scleroderma, is a chronic multisystem autoimmune disease characterised by widespread vascular injury and progressive fibrosis of the skin and internal organs. Patients with SSc have decreased survival, with pulmonary involvement as the main cause of death. Current treatments for SSc manage a range of symptoms but not the cause of the disease. Our review describes the humanistic and cost burden of SSc.MethodsA structured review of the literature was conducted, using predefined search strategies to search PubMed, Embase, and the Cochrane Library. Grey literature searches also were conducted.ResultsIn total, 2226 articles were identified in the databases and 52 were included; an additional 10 sources were included from the grey literature. The review identified six studies reporting relevant cost estimates conducted in five different countries and four studies that assessed the humanistic burden of SSc. Total direct annual medical costs per patient for Europe varied from €3544 to €8452. For Canada, these costs were reported to be from Can$5038 to Can$10,673. In the United States, the total direct health care costs were reported to be US$17,365 to US$18,396. Different key drivers of direct costs were reported, including hospitalisations, outpatients, and medication. The total annual costs per patient were reported at Can$18,453 in Canada and varied from €11,074 to €22,459 in Europe. Indirect costs represented the largest component of the total costs. EQ-5D utility scores were lower for patients with SSc than those observed in the general population, with reported mean values of 0.49 and 0.68, respectively. The average value of the Health Assessment Questionnaire for patients with SSc was significantly higher than the control population (0.94), and the average value of the SF-36 was significantly lower than the control population: 49.99 for the physical dimension and 58.42 for the mental dimension.ConclusionsOverall, there is a paucity of information on the burden of SSc. Nonetheless, our review indicates that the quality of life of patients with SSc is considerably lower than that of the general population. In addition, SSc places a considerable economic burden on health care systems and society as a whole.



http://ift.tt/2vYTyCb

Is PET/CT essential in the diagnosis and follow-up of temporal arteritis?

Publication date: Available online 9 September 2017
Source:Autoimmunity Reviews
Author(s): Carlo Salvarani, Alessandra Soriano, Francesco Muratore, Yehuda Shoenfeld, Daniel Blockmans
The increasing availability and improvement of imaging techniques are deeply influencing diagnosis and work-up of patients affected with vasculitis, particularly those with large vessel vasculitis (LVV). Fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET), especially when integrated with computed tomography (CT), is taking hold as a useful diagnostic technique to examine the aorta and the other large vessels in giant cell arteritis (GCA) with concomitant large vessel involvement (LV-GCA). In this paper we examined the progresses performed in this field in the last twenty years and the evidence available so far according to two different points of view ('pros' and 'cons'), in order to give a comprehensive answer to a still open question about the role of PET/CT in the diagnosis and follow-up of GCA.



http://ift.tt/2wSQUer

Should we treat congenital heart block with fluorinated corticosteroids?

Publication date: Available online 9 September 2017
Source:Autoimmunity Reviews
Author(s): Antonio Brucato, Angela Tincani, Micaela Fredi, Silvia Breda, Veronique Ramoni, Nathalie Morel, Nathalie Costedoat-Chalumeau




http://ift.tt/2wSQO6z

Bone mineral density and vitamin D status in systemic lupus erythematosus (SLE): A systematic review

Publication date: Available online 9 September 2017
Source:Autoimmunity Reviews
Author(s): Tarek Carlos Salman-Monte, Vicenç Torrente-Segarra, Ana Leticia Vega Vidal, Patricia Corzo, F. Castro-Dominguez, F. Ojeda, Jordi Carbonell Abelló
Despite the improvement in the quality of life of patients with SLE due to scientific and technological advances, SLE remains a disease that over the years may produce irreversible damage to patients. Osteoporosis and secondary bone fractures are two of the major causes of irreparable injury in patients with SLE. Vitamin D insufficiency may play a vital role both in reduced Bone Mineral Density (BMD) and in the appearance of fractures, although its mechanisms of action are still unclear. We performed a systematic review of the literature in order to determine the prevalence and predictors of reduced vitamin D plasma levels, bone loss and the presence of fractures in SLE patients. Our review encompassed all English-language publications using Medline and EMBase electronic databases from their inception (1966 and 1980, respectively) to December 2016. We included all intervention studies and observational studies in which vitamin D plasma levels, BMD and bone loss were measured and applied to patients with SLE. Previous studies suggested an increase in bone loss and fracture in patients with SLE compared with general population and although there is a high prevalence of vitamin D insufficiency in the general population, previous studies had demonstrated lower vitamin D levels in patients with SLE compared to age-matched controls. The etiology of reduced bone mass and reduced vitamin D plasma levels in SLE is multifactorial and includes a variety of intrinsic factors related to the disease itself and treatment side effects. SLE patients are at risk for developing these two comorbidities (reduced vitamin D plasma levels and low BMD) and it is therefore essential to study, monitor, prevent and treat bone metabolism disorders in SLE patients.



http://ift.tt/2vZjCgt

Is ACPA positivity the main driver for rheumatoid arthritis treatment? Pros and cons

Publication date: Available online 9 September 2017
Source:Autoimmunity Reviews
Author(s): Stefano Alivernini, Mauro Galeazzi, Hagit Peleg, Barbara Tolusso, Elisa Gremese, Gianfranco Ferraccioli, Yaakov Naparstek
Rheumatoid Arthritis (RA) is an autoimmune chronic disease that is characterized by the positivity of various antibodies, the most specific being autoantibodies against citrullinated antigens (ACPA). Despite ACPA are not arthritogenic by themselves, ACPA positive individuals have high risk of RA development and ACPA positivity is associated with severe erosive phenotype and higher mortality rate compared to seronegative RA. Moreover, ACPA status is associated with favorable response to biologics targeting pathways involving autoantibody producing cells as B lymphocytes. In the current review we have discussed the pros and cons on the available scientific evidences, regarding the diagnostic, prognostic and management implications of ACPAs in RA.



http://ift.tt/2gVmFfl

The role of nuclear NS1 protein in highly pathogenic H5N1 influenza viruses

Publication date: Available online 10 September 2017
Source:Microbes and Infection
Author(s): Bobo Wing-Yee Mok, Honglian Liu, Pin Chen, Siwen Liu, Siu-Ying Lau, Xiaofeng Huang, Yen-Chin Liu, Pui Wang, Kwok-Yung Yuen, Honglin Chen
The non-structural protein (NS1) of influenza A viruses (IAV) performs multiple functions during viral infection. NS1 contains two nuclear localization signals (NLS): NLS1 and NLS2. The NS1 protein is located predominantly in the nucleus during the early stages of infection and subsequently exported to the cytoplasm. A nonsense mutation that results in a large deletion in the carboxy-terminal region of the NS1 protein that contains the NLS2 domain was found in some IAV subtypes, including highly pathogenic avian influenza (HPAI) H7N9 and H5N1 viruses. We introduced different mutations into the NLS domains of NS1 proteins in various strains of IAV, and demonstrated that mutation of the NLS2 region in the NS1 protein of HPAI H5N1 viruses severely affects its nuclear localization pattern. H5N1 viruses expressing NS1 protein that is unable to localize to the nucleus are less potent in antagonizing cellular antiviral responses than viruses expressing wild-type NS1. However, no significant difference was observed with respect to viral replication and pathogenesis. In contrast, the replication and antiviral defenses of H1N1 viruses are greatly attenuated when nuclear localization of the NS1 protein is blocked. Our data reveals a novel functional plasticity for NS1 proteins among different IAV subtypes.



http://ift.tt/2fcDDpE